KR20210112980A - Pharmaceutical composition for prevention or treatment of cancer comprising Leuconostoc sp. as active ingredient - Google Patents
Pharmaceutical composition for prevention or treatment of cancer comprising Leuconostoc sp. as active ingredient Download PDFInfo
- Publication number
- KR20210112980A KR20210112980A KR1020200063684A KR20200063684A KR20210112980A KR 20210112980 A KR20210112980 A KR 20210112980A KR 1020200063684 A KR1020200063684 A KR 1020200063684A KR 20200063684 A KR20200063684 A KR 20200063684A KR 20210112980 A KR20210112980 A KR 20210112980A
- Authority
- KR
- South Korea
- Prior art keywords
- cancer
- leuconostoc
- leuconostoc mesenteroides
- strain
- composition
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 44
- 201000011510 cancer Diseases 0.000 title claims abstract description 35
- 239000004480 active ingredient Substances 0.000 title claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 15
- 230000002265 prevention Effects 0.000 title claims description 15
- 241001627205 Leuconostoc sp. Species 0.000 title claims description 7
- 239000000203 mixture Substances 0.000 claims abstract description 55
- 241000192132 Leuconostoc Species 0.000 claims abstract description 10
- 235000021109 kimchi Nutrition 0.000 claims abstract description 8
- 241000192130 Leuconostoc mesenteroides Species 0.000 claims description 63
- 206010009944 Colon cancer Diseases 0.000 claims description 24
- 239000003674 animal food additive Substances 0.000 claims description 16
- 235000013305 food Nutrition 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 12
- 206010005003 Bladder cancer Diseases 0.000 claims description 8
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 8
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 8
- 235000013373 food additive Nutrition 0.000 claims description 8
- 239000002778 food additive Substances 0.000 claims description 8
- 230000036541 health Effects 0.000 claims description 8
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 8
- 201000001441 melanoma Diseases 0.000 claims description 8
- 201000002528 pancreatic cancer Diseases 0.000 claims description 8
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 8
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 8
- 208000029742 colonic neoplasm Diseases 0.000 claims description 7
- 235000013336 milk Nutrition 0.000 claims description 7
- 239000008267 milk Substances 0.000 claims description 7
- 210000004080 milk Anatomy 0.000 claims description 7
- 235000013361 beverage Nutrition 0.000 claims description 6
- 230000006872 improvement Effects 0.000 claims description 6
- 244000144972 livestock Species 0.000 claims description 6
- 235000015243 ice cream Nutrition 0.000 claims description 5
- 238000010253 intravenous injection Methods 0.000 claims description 5
- 235000010469 Glycine max Nutrition 0.000 claims description 4
- 241000192003 Leuconostoc carnosum Species 0.000 claims description 4
- 241001468192 Leuconostoc citreum Species 0.000 claims description 4
- 241000286209 Phasianidae Species 0.000 claims description 4
- 235000015071 dressings Nutrition 0.000 claims description 4
- 235000013376 functional food Nutrition 0.000 claims description 4
- 235000013622 meat product Nutrition 0.000 claims description 4
- 241000251468 Actinopterygii Species 0.000 claims description 3
- 244000068988 Glycine max Species 0.000 claims description 3
- 240000007594 Oryza sativa Species 0.000 claims description 3
- 235000007164 Oryza sativa Nutrition 0.000 claims description 3
- 235000009508 confectionery Nutrition 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 3
- 235000009566 rice Nutrition 0.000 claims description 3
- 235000013555 soy sauce Nutrition 0.000 claims description 3
- 241000272525 Anas platyrhynchos Species 0.000 claims description 2
- 241000283690 Bos taurus Species 0.000 claims description 2
- 241000283707 Capra Species 0.000 claims description 2
- 241001609213 Carassius carassius Species 0.000 claims description 2
- 241000699800 Cricetinae Species 0.000 claims description 2
- 241000252233 Cyprinus carpio Species 0.000 claims description 2
- 241000282326 Felis catus Species 0.000 claims description 2
- 241000287828 Gallus gallus Species 0.000 claims description 2
- 241000192129 Leuconostoc lactis Species 0.000 claims description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 2
- 241001494479 Pecora Species 0.000 claims description 2
- 241000700159 Rattus Species 0.000 claims description 2
- 241000277331 Salmonidae Species 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 244000299461 Theobroma cacao Species 0.000 claims description 2
- 235000008429 bread Nutrition 0.000 claims description 2
- 235000012970 cakes Nutrition 0.000 claims description 2
- 235000013351 cheese Nutrition 0.000 claims description 2
- 235000019219 chocolate Nutrition 0.000 claims description 2
- 235000015140 cultured milk Nutrition 0.000 claims description 2
- 235000021438 curry Nutrition 0.000 claims description 2
- 230000003511 endothelial effect Effects 0.000 claims description 2
- 238000010255 intramuscular injection Methods 0.000 claims description 2
- 239000007927 intramuscular injection Substances 0.000 claims description 2
- 239000007928 intraperitoneal injection Substances 0.000 claims description 2
- 235000008960 ketchup Nutrition 0.000 claims description 2
- 235000020991 processed meat Nutrition 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 238000010254 subcutaneous injection Methods 0.000 claims description 2
- 239000007929 subcutaneous injection Substances 0.000 claims description 2
- 238000011200 topical administration Methods 0.000 claims description 2
- 239000000052 vinegar Substances 0.000 claims description 2
- 235000021419 vinegar Nutrition 0.000 claims description 2
- 241000272814 Anser sp. Species 0.000 claims 1
- 240000004160 Capsicum annuum Species 0.000 claims 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 claims 1
- 235000007862 Capsicum baccatum Nutrition 0.000 claims 1
- 241000700199 Cavia porcellus Species 0.000 claims 1
- 241000283073 Equus caballus Species 0.000 claims 1
- 241000009328 Perro Species 0.000 claims 1
- 241000282898 Sus scrofa Species 0.000 claims 1
- 239000001728 capsicum frutescens Substances 0.000 claims 1
- 230000001093 anti-cancer Effects 0.000 abstract description 13
- 241001465754 Metazoa Species 0.000 abstract description 11
- 210000004027 cell Anatomy 0.000 description 64
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 17
- 230000010261 cell growth Effects 0.000 description 16
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 16
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 10
- 239000002953 phosphate buffered saline Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- 241000894006 Bacteria Species 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 238000003570 cell viability assay Methods 0.000 description 8
- 239000004310 lactic acid Substances 0.000 description 8
- 235000014655 lactic acid Nutrition 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 206010027476 Metastases Diseases 0.000 description 7
- 230000009401 metastasis Effects 0.000 description 7
- 244000005700 microbiome Species 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 235000013355 food flavoring agent Nutrition 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- -1 etc. Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 235000012149 noodles Nutrition 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 230000037311 normal skin Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000006041 probiotic Substances 0.000 description 4
- 235000018291 probiotics Nutrition 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 108020004465 16S ribosomal RNA Proteins 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000002775 capsule 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
- 239000000306 component Substances 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000010232 migration assay Methods 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 210000004927 skin cell Anatomy 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 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
- 238000011725 BALB/c mouse Methods 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000186660 Lactobacillus Species 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 229920000388 Polyphosphate Polymers 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000005862 Whey Substances 0.000 description 2
- 102000007544 Whey Proteins Human genes 0.000 description 2
- 108010046377 Whey Proteins Proteins 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000002869 basic local alignment search tool Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 235000014171 carbonated beverage Nutrition 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 238000012136 culture method Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 235000013332 fish product Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 229940039696 lactobacillus Drugs 0.000 description 2
- 229940069445 licorice extract Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000001205 polyphosphate Substances 0.000 description 2
- 235000011176 polyphosphates Nutrition 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 235000013594 poultry meat Nutrition 0.000 description 2
- 235000008476 powdered milk Nutrition 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 230000000529 probiotic effect Effects 0.000 description 2
- 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 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 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
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 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
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- QJZYHAIUNVAGQP-UHFFFAOYSA-N 3-nitrobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid Chemical compound C1C2C=CC1C(C(=O)O)C2(C(O)=O)[N+]([O-])=O QJZYHAIUNVAGQP-UHFFFAOYSA-N 0.000 description 1
- UZOVYGYOLBIAJR-UHFFFAOYSA-N 4-isocyanato-4'-methyldiphenylmethane Chemical compound C1=CC(C)=CC=C1CC1=CC=C(N=C=O)C=C1 UZOVYGYOLBIAJR-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000272517 Anseriformes Species 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 235000007319 Avena orientalis Nutrition 0.000 description 1
- 244000075850 Avena orientalis Species 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- 239000005996 Blood meal Substances 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 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
- 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
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 235000019733 Fish meal Nutrition 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
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 244000020551 Helianthus annuus Species 0.000 description 1
- 235000003222 Helianthus annuus Nutrition 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010043515 Throat cancer Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 206010062129 Tongue neoplasm Diseases 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 238000003915 air pollution Methods 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229940087168 alpha tocopherol Drugs 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
- 230000003698 anagen phase Effects 0.000 description 1
- 239000006053 animal diet Substances 0.000 description 1
- 235000021120 animal protein Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000015241 bacon Nutrition 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229940036811 bone meal Drugs 0.000 description 1
- 239000002374 bone meal Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000015155 buttermilk Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- 229950001002 cianidanol Drugs 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000035614 depigmentation Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 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
- 239000002270 dispersing agent Substances 0.000 description 1
- 235000011869 dried fruits Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 235000021107 fermented food Nutrition 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000010610 frozen noodles Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 235000020251 goat milk Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000020688 green tea extract Nutrition 0.000 description 1
- 229940094952 green tea extract Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000007952 growth promoter Substances 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 230000007366 host health Effects 0.000 description 1
- 239000004021 humic acid Substances 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003871 intestinal function Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 235000020121 low-fat milk Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 208000026045 malignant tumor of parathyroid gland Diseases 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 235000013310 margarine Nutrition 0.000 description 1
- 239000003264 margarine Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000012533 medium component Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 235000019462 natural additive Nutrition 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 235000015927 pasta Nutrition 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000000467 phytic acid Substances 0.000 description 1
- 235000002949 phytic acid Nutrition 0.000 description 1
- 229940068041 phytic acid Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 235000014059 processed cheese Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229940092258 rosemary extract Drugs 0.000 description 1
- 235000020748 rosemary extract Nutrition 0.000 description 1
- 239000001233 rosmarinus officinalis l. extract Substances 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000015067 sauces Nutrition 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000013322 soy milk Nutrition 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 239000011269 tar Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 201000006134 tongue cancer Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
- A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
Abstract
Description
본 발명은 김치로부터 분리된 류코노스톡(Leuconostoc) 속 균주, 구체적으로는 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주 또는 이의 배양물을 유효성분으로 포함하는 암의 예방 또는 치료용 조성물에 관한 것이다.The present invention is a leuconostoc strain isolated from kimchi, specifically, a Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain or a culture thereof as an active ingredient. It relates to a therapeutic composition.
암은 세계적으로 높은 사망률을 보이며, 서구 사회에서는 심혈관 질환 다음으로 가장 일반적인 사망 원인이다. 특히, 식생활이 서구화되어 고지방식의 섭취가 일반화되고, 환경 오염 물질의 급격한 증가, 음주량의 증가 등으로 대장암, 유방암, 전립선암 등이 지속적으로 증가하는 추세에 있으며, 인구의 고령화와 더불어 흡연 인구의 증가 및 대기 오염으로 인해 폐암이 증가하고 있는 실정이다. 이러한 실정에서 암의 조기 예방 및 치료를 가능하게 하여 인간 건강의 증진, 건강한 삶의 질 향상 및 인류 보건 증진에 기여할 수 있는 항암 물질의 창출이 절실히 요구되고 있다.Cancer has the highest mortality rate worldwide and is the second most common cause of death in Western societies after cardiovascular disease. In particular, the consumption of high-fat diets has become common due to the westernization of diets, and the incidence of colorectal cancer, breast cancer, and prostate cancer continues to increase due to the rapid increase in environmental pollutants and the increase in alcohol consumption. Lung cancer is increasing due to the increase in the number of cancer cells and air pollution. In this situation, there is an urgent need for the creation of anticancer substances that can contribute to the promotion of human health, the improvement of the quality of healthy life, and the promotion of human health by enabling the early prevention and treatment of cancer.
한편, 유산균은 인간과 동물의 구강, 장, 질, 분변, 그리고 김치와 같은 발효식품 등에 널리 분포하면서 사람과 동물의 건강과 밀접한 관련을 맺고 있다. 유산균은 정장작용, 유해균 억제, 면역조절, 혈중 콜레스테롤 저하, 항암 등 다양한 건강증진 효과를 나타내고 있다.On the other hand, lactic acid bacteria are widely distributed in the oral cavity, intestine, vagina, feces, and fermented foods such as kimchi of humans and animals, and are closely related to the health of humans and animals. Lactobacillus has various health-promoting effects such as intestinal function, suppression of harmful bacteria, immune regulation, lowering blood cholesterol, and anti-cancer.
현재, 한국공개특허 제10-2010-0013184호에서는 류코노스톡 메센테로이데스 균주의 항암 활성을 개시하고 있으나, 대장암에 대한 예방 또는 치료 효과에 대해서만 구체적 실시예를 기재하고 있을 뿐, 이 외의 암종에 대해서는 구체적인 실험예나 실시예가 기재된 바 없다.Currently, Korean Patent Application Laid-Open No. 10-2010-0013184 discloses the anticancer activity of the Leukonostok mecenteroides strain, but only describes specific examples for the prevention or treatment effect on colorectal cancer, and other carcinomas. No specific experimental examples or examples have been described.
본 발명의 목적은 류코노스톡 속 균주를 유효성분으로 포함하는 암의 예방 또는 치료용 약학 조성물을 제공하기 위한 것이다.It is an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of cancer comprising a leuconostok sp. strain as an active ingredient.
또한 본 발명의 다른 목적은 류코노스톡 속 균주를 유효성분으로 포함하는 암의 예방 또는 개선용 식품 조성물 또는 식품 첨가제 조성물을 제공하기 위한 것이다.Another object of the present invention is to provide a food composition or food additive composition for the prevention or improvement of cancer comprising the leuconostok sp. strain as an active ingredient.
또한 본 발명의 또 다른 목적은 류코노스톡 속 균주를 유효성분으로 포함하는 암의 예방 또는 개선용 사료 조성물 또는 사료 첨가제 조성물을 제공하기 위한 것이다.Another object of the present invention is to provide a feed composition or feed additive composition for preventing or improving cancer comprising a leuconostok sp. strain as an active ingredient.
이에, 본 발명자들은 김치로부터 암의 예방 및 치료 효과를 나타내는 유산균 균주를 찾고자 노력한 결과, 여러 암종에 항암 활성을 갖는 신규한 류코노스톡(Leuconostoc) 속 균주를 분리, 동정하여 본 발명을 완성하게 되었다. Accordingly, the present inventors have tried to find a lactic acid bacteria strain exhibiting the preventive and therapeutic effect of cancer from kimchi, and as a result, a novel Leuconostoc genus strain having anticancer activity in various carcinomas was isolated and identified, and the present invention was completed. .
상기 목적을 달성하기 위하여, 류코노스톡 속 균주 또는 이의 배양물을 유효성분으로 포함하는 암의 예방 또는 치료용 약학 조성물을 제공한다.In order to achieve the above object, there is provided a pharmaceutical composition for the prevention or treatment of cancer comprising a Leukonostok sp. strain or a culture thereof as an active ingredient.
또한, 본 발명은 류코노스톡 속 균주 또는 이의 배양물을 유효성분으로 포함하는 암의 예방 또는 개선용 식품 조성물 또는 식품 첨가제 조성물을 제공한다.In addition, the present invention provides a food composition or food additive composition for the prevention or improvement of cancer comprising a leuconostok sp. strain or a culture thereof as an active ingredient.
또한, 본 발명은 류코노스톡 속 균주 또는 이의 배양물을 유효성분으로 포함하는 가축의 암 예방 또는 개선용 사료 조성물 또는 사료 첨가제 조성물을 제공한다.In addition, the present invention provides a feed composition or feed additive composition for preventing or improving cancer of livestock comprising a leuconostok sp. strain or a culture thereof as an active ingredient.
본 발명에 따른 류코노스톡 속 균주 또는 이의 배양물은 여러 암종에 대해 우수한 항암 활성을 나타내므로, 사람 또는 동물의 암의 치료, 예방 또는 개선 등의 용도를 위한 조성물로서 유용하게 이용될 수 있다.Since the Leukonostok sp. strain or a culture thereof according to the present invention exhibits excellent anticancer activity against various carcinomas, it can be usefully used as a composition for use such as treatment, prevention or improvement of cancer in humans or animals.
도 1은 본 발명에 따른 조성물을 대장암 CT26 세포 이식 마우스에 1회 정맥 주사한 후 시간 경과에 따라 종양의 크기가 변화하는 것을 관찰한 종양의 사진을 나타낸 도이다.
도 2는 본 발명에 따른 조성물을 대장암 CT26 세포 이식 마우스에 1회 정맥 주사한 후 시간 경과에 따라 종양 성장률을 측정한 그래프를 나타낸 도이다.
도 3은 대장암 CT26, SW620 및 HCT116 세포주에 본 발명에 따른 조성물을 처리하고 세포 성장률(cell viability assay)을 측정한 그래프를 나타낸 도이다.
도 4는 췌장암 AsPC-1 세포주에 본 발명에 따른 조성물을 처리하고 세포 성장률(cell viability assay)을 측정한 그래프를 나타낸 도이다.
도 5는 방광암 T24 세포주에 본 발명에 따른 조성물을 처리하고 세포 성장률(cell viability assay)을 측정한 그래프를 나타낸 도이다.
도 6은 흑색종 B16-F10 세포주에 본 발명에 따른 조성물을 처리하고 세포 성장률(cell viability assay)을 측정한 그래프를 나타낸 도이다.
도 7은 정상 CCD986-sk 세포주에 본 발명에 따른 조성물을 처리하고 세포 성장률(cell viability assay)을 측정한 그래프를 나타낸 도이다.
도 8은 대장암 MC38 세포주에 본 발명에 따른 조성물을 처리하고 세포 전이(migration assay) 후 이미지를 촬영한 사진을 나타낸 도이다.
도 9는 대장암 MC38 세포주에 본 발명에 따른 조성물을 처리하고 세포 전이(migration assay) 억제능을 측정한 그래프를 나타낸 도이다. 1 is a view showing a photograph of a tumor observed to change the size of the tumor over time after intravenous injection of a composition according to the present invention to a colorectal cancer CT26 cell transplanted mouse once.
2 is a diagram showing a graph measuring the tumor growth rate over time after intravenous injection of a composition according to the present invention to a colorectal cancer CT26 cell transplanted mouse once.
Figure 3 is a diagram showing a graph measuring the cell growth rate (cell viability assay) by treating the composition according to the present invention in colorectal cancer CT26, SW620 and HCT116 cell lines.
4 is a diagram illustrating a graph obtained by treating a pancreatic cancer AsPC-1 cell line with the composition according to the present invention and measuring the cell growth rate (cell viability assay).
5 is a diagram illustrating a graph measuring bladder cancer T24 cell line by treating the composition according to the present invention and measuring the cell growth rate (cell viability assay).
6 is a view showing a graph of melanoma B16-F10 cell line treated with the composition according to the present invention and measuring the cell growth rate (cell viability assay).
7 is a diagram showing a graph of normal CCD986-sk cell line treated with the composition according to the present invention and cell growth rate (cell viability assay) was measured.
8 is a view showing a photograph taken after the treatment of the composition according to the present invention to the colorectal cancer MC38 cell line and cell metastasis (migration assay).
9 is a diagram illustrating a graph measuring colon cancer MC38 cell line by treating the composition according to the present invention and measuring the cell metastasis (migration assay) inhibitory ability.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
본 발명의 류코노스톡(Leuconostoc) 속 균주 또는 이의 배양물을 유효성분으로 포함하는 조성물은 암의 예방 또는 치료 효과를 가지며, 약제학적 조성물로 이용될 수 있다.The composition comprising the Leuconostoc sp. strain or a culture thereof of the present invention as an active ingredient has a preventive or therapeutic effect on cancer, and can be used as a pharmaceutical composition.
본 발명의 류코노스톡(Leuconostoc) 속 균주는 유산균 균주이다. 상기 류코노스톡 속 균주는 프로바이오틱스로서, 유산균의 일반적인 정장 효과 및 면역 증강 효과를 갖는다. 류코노스톡 속의 유산균이 정장 효과 면역 증강 효과를 갖는 것은 잘 알려진 사실이다.Leuconostoc sp. strain of the present invention is a lactic acid bacteria strain. The Leukonostok sp. strain is a probiotic, and has a general intestinal effect and immune enhancing effect of lactic acid bacteria. It is a well-known fact that lactic acid bacteria of the genus Leukonostok have an effect on the intestine and immunity enhancement.
상기 류코노스톡 속 균주는 류코노스톡 메센테로이데스(Leuconostoc mesenteroides), 류코노스톡 카노섬(Leuconostoc carnosum), 류코노스톡 시트리움(Leuconostoc citreum), 류코노스톡 홀잡펠리(Leuconostoc holzapfelli) 또는 류코노스톡 락티스(Leuconostoc lactis) 중 하나일 수 있다.The leuconostoc sp. strain is leuconostoc mesenteroides (Leuconostoc mesenteroides), leuconostoc carnosum (Leuconostoc carnosum), leuconostoc citreum (Leuconostoc citreum), leuconostoc holjapelli (Leuconostoc holzapfelli) or leucono stock lactis (Leuconostoc lactis).
본 발명의 실시예를 통해 김치로부터 분리된 류코노스톡 메센테로이데스 균주는 미생물의 동정 및 분류를 위한 16S rRNA 염기서열 분석 결과, 서열번호 1(SEQ ID NO: 1)의 핵산서열을 갖는 것으로 나타났다.As a result of 16S rRNA sequencing analysis for the identification and classification of microorganisms, the Leukonostok mecenteroides strain isolated from kimchi through the Examples of the present invention showed that it has the nucleic acid sequence of SEQ ID NO: 1 (SEQ ID NO: 1). .
따라서, 서열번호 1(SEQ ID NO: 1)의 16S rRNA 염기서열을 갖는 본 발명의 미생물을 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1)로 명명하였으며, 한국미생물보존센터에 2020년 04월 24일자로 기탁하였다(기탁번호 KCCM12701P).Therefore, the microorganism of the present invention having the 16S rRNA base sequence of SEQ ID NO: 1 (SEQ ID NO: 1) was named Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1), and 2020 to the Korea Microorganism Conservation Center. It was deposited on April 24, 2014 (Accession No. KCCM12701P).
상기 류코노스톡 균주는 MRS 액체배지에 0.1 내지 10% 접종하여 25 내지 37℃에서 4시간 내지 48시간 동안 배양하여 이용할 수 있다. The leucono stock strain can be used by inoculating 0.1 to 10% in MRS broth and culturing at 25 to 37° C. for 4 to 48 hours.
상기 배양의 방법은 정치배양 방법이 바람직하나, 이에 한정되지 않는다. The culture method is preferably a stationary culture method, but is not limited thereto.
본 발명에 있어서, '프로바이오틱스(probiotics)'는 사람을 포함한 동물의 위장관 내에서 숙주의 장내 미생물 환경을 개선하여 숙주의 건강에 유익한 영향을 주는 살아있는 미생물'이라는 의미로 이해된다. 프로바이오틱스는 프로바이오틱 활성을 갖는 살아있는 미생물로 단일 또는 복합균주 형태로 사람이나 동물에 건조된 세포 형태나 발효산물 형태로 급여될 경우, 숙주의 장내 균총에 유익한 영향을 미칠 수 있다.In the present invention, 'probiotics' is understood to mean 'living microorganisms that have a beneficial effect on the health of the host by improving the intestinal microbial environment of the host in the gastrointestinal tract of animals including humans'. Probiotics are living microorganisms with probiotic activity. When fed to humans or animals in the form of single or complex strains, in the form of dried cells or fermentation products, probiotics can have a beneficial effect on the intestinal flora of the host.
상기 암은 방광암, 유방암, 흑색종양, 갑상선암, 부갑상선암, 인후암, 후두암, 식도암, 췌장암, 위암, 설암, 피부암, 뇌종양, 자궁암, 두담낭암, 구강암, 신장암, 간암, 폐암, 결장암, 직장암 및 대장암으로 이루어지는 군으로부터 선택되는 어느 하나의 암일 수 있으며, 이에 한정되지 않는다.The cancer is bladder cancer, breast cancer, melanoma, thyroid cancer, parathyroid cancer, throat cancer, laryngeal cancer, esophageal cancer, pancreatic cancer, stomach cancer, tongue cancer, skin cancer, brain tumor, uterine cancer, gallbladder cancer, oral cancer, kidney cancer, liver cancer, lung cancer, colon cancer, rectal cancer and colon cancer It may be any one cancer selected from the group consisting of cancer, but is not limited thereto.
본 발명에 따른 조성물에 포함되는 류코노스톡 속 균주는 생균체 또는 사균체로서 존재할 수 있으며, 또한 건조 또는 동결건조된 형태로 존재할 수도 있다. 또한, 류코노스톡 속 균주의 배양물이 유효성분일 수 있으며, 상기 배양물에는 생균 배양액 또는 사균 상등액이 포함될 수 있다. 다양한 조성물 내에 포함시키기 적합한 유산균의 형태 및 제제화 방법은 당업자에게 잘 알려져 있다.The leuconostok sp. strain included in the composition according to the present invention may exist as a live cell or a dead cell, and may also exist in a dried or lyophilized form. In addition, the culture of the leuconostok sp. strain may be an active ingredient, and the culture may include a live cell culture medium or a dead cell supernatant. Forms of lactic acid bacteria suitable for inclusion in various compositions and methods of formulation are well known to those skilled in the art.
상기 조성물은 경구 또는 비경구로 투여할 수 있다. 비경구 투여인 경우에는 정맥 내 주입, 피하 주입, 근육 주입, 복강 주입, 내피 투여, 국소 투여, 비내 투여, 폐 내 투여 및 직장 내 투여 등으로 투여할 수 있으며, 바람직하게는 정맥 내 주입방법으로 투여할 수 있으나, 이에 한정되지 않는다.The composition may be administered orally or parenterally. In the case of parenteral administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endothelial administration, topical administration, intranasal administration, intrapulmonary administration and rectal administration, etc. may be administered, preferably by intravenous injection. may be administered, but is not limited thereto.
상기 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여시간, 투여경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다.A suitable dosage of the composition may be variously prescribed according to factors such as formulation method, administration method, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity of the patient.
본 발명의 조성물이 약제학적 조성물로 활용될 경우, 본 발명의 약제학적 조성물은 상기 유효성분 이외에 약제학적으로 적합하고 생리학적으로 허용되는 보조제를 사용하여 제조될 수 있으며, 상기 보조제로는 부형제, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제 또는 향미제 등을 사용할 수 있다.When the composition of the present invention is used as a pharmaceutical composition, the pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant includes an excipient, bog Release, sweetener, binder, coating agent, swelling agent, lubricant, lubricant or flavoring agent and the like can be used.
상기 약제학적 조성물은 투여를 위해서 상기 기재한 유효성분 이외에 추가로 약제학적으로 허용가능한 담체를 1종 이상 포함하여 약제학적 조성물로 바람직하게 제제화할 수 있다.The pharmaceutical composition may be preferably formulated as a pharmaceutical composition by including one or more pharmaceutically acceptable carriers in addition to the active ingredients described above for administration.
예를 들어, 정제 또는 캡슐제의 형태로의 제제화를 위해, 유효성분은 에탄올, 글리세롤, 물 등과 같은 경구, 무독성의 약제학적으로 허용가능한 불활성 담체와 결합될 수 있다. 또한, 원하거나 필요한 경우, 적합한 결합제, 윤활제, 붕해제 및 발색제 또한 혼합물로 포함될 수 있다. 적합한 결합제는 이에 제한되는 것은 아니나, 녹말, 젤라틴, 글루코스 또는 베타-락토오스와 같은 천연당, 옥수수감미제, 아카시아, 트래커캔스 또는 소듐올레이트와 같은 천연 및 합성검, 소듐 스테아레이트, 마그네슘 스테아레이트, 소듐 벤조에이트, 소듐아세테이트, 소듐클로라이드 등을 포함한다. 붕해제는 이에 제한되는 것은 아니나, 녹말, 메틸셀룰로스, 아가, 벤토니트, 잔탄검 등을 포함한다. 액상 용액으로 제제화되는 조성물에 있어서 허용가능한 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충식염수, 알부민 주사 용액, 덱스트로즈 용액, 말토덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.For example, for formulation in the form of a tablet or capsule, the active ingredient may be combined with an orally, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or required, suitable binders, lubricants, disintegrants and color-developers may also be included in the mixture. Suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate. ate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methylcellulose, agar, bentonite, xanthan gum, and the like. In the composition formulated as a liquid solution, acceptable pharmaceutical carriers include sterile and biocompatible, saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostats may be added as needed. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to form an injectable formulation such as an aqueous solution, suspension, emulsion, etc., pills, capsules, granules or tablets.
나아가 해당 분야의 적절한 방법으로 Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.Furthermore, by using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA by an appropriate method in the field, it can be preferably formulated according to each disease or component.
본 발명의 류코노스톡 속(Leuconostoc) 균주 또는 이의 배양물을 유효성분으로 포함하는 조성물은 암의 예방 또는 개선용 식품 조성물 또는 식품 첨가제 조성물로 이용될 수 있다.The composition comprising the Leuconostoc strain or a culture thereof of the present invention as an active ingredient may be used as a food composition or food additive composition for preventing or improving cancer.
상기 식품 조성물은 건강기능식품의 형태일 수 있다.The food composition may be in the form of a health functional food.
상기 "건강기능식품"은 건강기능식품에 관한 법률에 따라 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미(제3조 제1호)하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻는 것(동조 제2호)을 의미한다.The above "health functional food" means food manufactured and processed using raw materials or ingredients useful for the human body in accordance with the Health Functional Food Act (Article 3, No. 1), and "functionality" means Controlling nutrients for the structure and function of the human body or obtaining useful effects for health purposes such as physiological action (Article 2).
상기 식품 조성물은 식품 첨가물을 추가로 포함할 수 있으며, "식품첨가물"로서의 적합여부는 다른 규정이 없는 한 식품의약품안정청에 승인된 식품첨가물공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.The food composition may additionally contain food additives, and the suitability as a "food additive" is determined according to the general rules and general test methods of the Food Additives Code approved by the Food and Drug Administration, unless otherwise specified. It is judged according to the standard.
상기 "식품첨가물공전"에 수재된 품목으로 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성품, 감색소, 감초추출물, 결정셀롤로오스, 구아검 등의 천연첨가물, L-글루타민산나트륨제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합 제제류 들을 들 수 있다.Items listed in the "Food Additives Code", for example, chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as depigmentation, licorice extract, crystalline cellulose, and guar gum, L- Mixed preparations such as sodium glutamate preparation, noodle-added alkali agent, preservative agent, and tar color agent can be mentioned.
본 발명의 유효성분이 포함된 식품으로는 빵, 떡류, 건과류, 캔디류, 초콜릿류, 츄잉껌, 쨈류와 같은 과자류 아이스크림류, 빙과류, 아이스크림 분말류와 같은 아이스크림 제품류 우유류, 저지방 우유류, 유당분해 우유, 가공유류, 산양유, 발효유류, 버터유류, 농축유류, 유크림류, 버터유, 자연치즈, 가공치즈, 분유류, 유청류와 같은 유가공품류 식육가공품, 알가공품, 햄버거와 같은 식육제품류 어묵, 햄, 소세지, 베이컨 등의 어육가공품과 같은 어육제품류 라면류, 건면류, 생면류, 유탕면류, 호화건먼류, 개량숙면류, 냉동면류, 파스타류와 같은 면류 과실음료, 채소류음료, 탄산음료, 두유류, 요구르트 등의 유산균음료, 혼합음료와 같은 음료 간장, 된장, 고추장, 춘장, 청국장, 혼합장, 식초, 소스류, 토마토케첩, 카레, 드레싱과 같은 조미식품 마가린, 쇼트닝 및 피자를 들 수 있으나, 이에 한정되는 것은 아니다.Foods containing the active ingredient of the present invention include bread, rice cakes, dried fruits, candies, chocolates, chewing gum, confectionery products such as jams, ice cream products, ice cream products, ice cream products such as ice cream powder milk, low-fat milk, lactose-decomposed milk, Processed milk, goat milk, fermented milk, buttermilk, concentrated milk, milk cream, butter oil, natural cheese, processed cheese, milk powder, milk products such as whey Processed meat products, processed eggs, meat products such as hamburgers Fish cakes, ham, Fish and meat products such as sausages, bacon, etc. Fish and meat products Ramen, dried noodles, raw noodles, fried noodles, luxurious dried noodles, improved soft noodles, frozen noodles, pastas, etc. Fruit drinks, vegetable drinks, carbonated drinks, soy milk, Lactobacillus drinks such as yogurt, beverages such as mixed drinks Soy sauce, soybean paste, gochujang, chunjang, cheonggukjang, mixed soy sauce, vinegar, sauces, tomato ketchup, curry and seasonings such as dressings, margarine, shortening and pizza, but limited to this it's not going to be
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 포함할 수 있다. 그 밖에 본 발명의 조성물은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 포함할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, It may include a carbonation agent used in carbonated beverages, and the like. In addition, the composition of the present invention may contain the pulp for the production of natural fruit juice, fruit juice beverage, and vegetable beverage. These components may be used independently or in combination.
본 발명의 유효성분을 포함한 음료 조성물은 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가성분으로 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, (예를 들어, 포도당, 과당 등); 디사카라이드, (예를 들어 말토스, 슈크로스 등); 및 폴리사카라이드, (예를 들어 덱스트린, 시클로덱스트린 등)과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다.The beverage composition including the active ingredient of the present invention is not particularly limited in other ingredients, and may contain various flavoring agents or natural carbohydrates as additional ingredients like a conventional beverage. Examples of the aforementioned natural carbohydrates include monosaccharides (eg, glucose, fructose, etc.); disaccharides, (eg maltose, sucrose, etc.); and conventional sugars such as polysaccharides (eg, dextrin, cyclodextrin, etc.), and sugar alcohols such as xylitol, sorbitol, erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. .
또한, 본 발명의 류코노스톡 속(Leuconostoc) 균주 또는 이의 배양물을 유효성분으로 포함하는 조성물은 가축의 암 예방 또는 개선용 사료 조성물 또는 사료 첨가제 조성물로 이용될 수 있다.In addition, the composition comprising the Leuconostoc strain or a culture thereof of the present invention as an active ingredient may be used as a feed composition or feed additive composition for preventing or improving cancer in livestock.
상기 조성물이 사료 첨가제로서 제조될 경우, 상기 조성물은 20 내지 90% 고농축액이거나 분말 또는 과립 형태로 제조될 수 있다. 상기 사료 첨가제는 구연산, 후말산, 아디픽산, 젖산, 사과산등의 유기산이나 인산 나트륨, 인산 칼륨, 산성 피로인산염, 폴리인산염(중합인산염) 등의 인산염이나, 폴리페놀, 카테킨, 알파-토코페롤, 로즈마리 추출물, 비타민 C, 녹차 추출물, 감초 추출물, 키토산, 탄닌산, 피틴산 등의 천연 항산화제 중 어느 하나 또는 하나 이상을 추가로 포함할 수 있다. 사료로서 제조될 경우, 상기 조성물은 통상의 사료 형태로 제제화될 수 있으며, 통상의 사료 성분을 함께 포함할 수 있다.When the composition is prepared as a feed additive, the composition may be 20 to 90% highly concentrated or may be prepared in powder or granular form. The feed additives include organic acids such as citric acid, humic acid, adipic acid, lactic acid, and malic acid, or phosphates such as sodium phosphate, potassium phosphate, acid pyrophosphate, polyphosphate (polyphosphate), polyphenol, catechin, alpha-tocopherol, rosemary Extract, vitamin C, green tea extract, licorice extract, chitosan, tannic acid, any one or more of natural antioxidants such as phytic acid may be further included. When prepared as a feed, the composition may be formulated in the form of a conventional feed, and may include common feed ingredients together.
상기 사료 및 사료 첨가제는 곡물, 예를 들면 분쇄 또는 파쇄된 밀, 귀리, 보리, 옥수수 및 쌀; 식물성 단백질 사료, 예를 들면 평지, 콩, 및 해바라기를 주성분으로 하는 사료; 동물성 단백질 사료, 예를 들면 혈분, 육분, 골분 및 생선분; 당분 및 유제품, 예를 들면 각종 분유 및 유장 분말로 이루어지는 건조성분 등을 더 포함할 수 있으며, 이외에도 영양보충제, 소화 및 흡수향상제, 성장촉진제 등을 더 포함할 수 있다.The feed and feed additives include grains such as milled or crushed wheat, oats, barley, corn and rice; plant protein feeds, such as feeds based on rape, soybean, and sunflower; animal protein feeds such as blood meal, meat meal, bone meal and fish meal; Sugar and dairy products, for example, may further include dry ingredients made of various powdered milk and whey powder, and may further include nutritional supplements, digestion and absorption enhancers, growth promoters, and the like.
상기 사료 첨가제는 동물에게 단독으로 투여하거나 식용 담체 중에서 다른 사료 첨가제와 조합하여 투여할 수도 있다. 또한, 상기 사료 첨가제는 탑드레싱으로서 또는 이들을 동물사료에 직접 혼합하거나 또는 사료와 별도의 경구제형으로 용이하게 동물에게 투여할 수 있다. 상기 사료 첨가제를 동물사료와 별도로 투여할 경우, 당해 기술분야에 잘 알려진 바와 같이 약제학적으로 허용 가능한 식용 담체와 조합하여, 즉시 방출 또는 서방성 제형으로 제조할 수 있다. 이러한 식용 담체는 고체 또는 액체, 예를 들어 옥수수전분, 락토오스, 수크로오스, 콩플레이크, 땅콩유, 올리브유, 참깨유 및 프로필렌글리콜일 수 있다. 고체 담체가 사용될 경우, 사료 첨가제는 정제, 캡슐제, 산제, 트로키제 또는 함당정제 또는 미분산성 형태의 탑 드레싱일 수 있다. 액체 담체가 사용될 경우, 사료 첨가제는 젤라틴 연질 캡슐제, 또는 시럽제나 현탁액, 에멀젼제, 또는 용액제의 제형일 수 있다.The feed additive may be administered to the animal alone or in combination with other feed additives in an edible carrier. In addition, the feed additive can be easily administered to the animal as a top dressing, directly mixing them with animal feed, or as an oral formulation separate from the feed. When the feed additive is administered separately from the animal feed, it may be combined with a pharmaceutically acceptable edible carrier as well known in the art to prepare an immediate release or sustained release formulation. Such edible carriers may be solid or liquid, for example cornstarch, lactose, sucrose, soy flakes, peanut oil, olive oil, sesame oil and propylene glycol. When a solid carrier is used, the feed additive may be a tablet, capsule, powder, troche or sugar-containing tablet or top dressing in microdispersed form. When a liquid carrier is used, the feed additive may be in the form of a gelatin soft capsule, or a syrup or suspension, emulsion, or solution.
또한, 상기 사료 및 사료 첨가제는 보조제, 예를 들어 보존제, 안정화제, 습윤제 또는 유화제, 용액 촉진제 등을 함유할 수 있다. 상기 사료 첨가제는 침주, 분무 또는 혼합하여 동물의 사료에 첨가하여 이용될 수 있다.In addition, the feed and feed additives may contain adjuvants, for example, preservatives, stabilizers, wetting or emulsifying agents, solution accelerators, and the like. The feed additive may be used by being added to animal feed by immersion, spraying, or mixing.
본 발명의 사료 또는 사료 첨가제는 포유류, 가금 및 어류를 포함하는 다수의 동물 식이에 적용할 수 있다.The feed or feed additive of the present invention can be applied to a number of animal diets including mammals, poultry and fish.
상기 포유류로서 돼지, 소, 말, 양, 토끼, 염소, 설치동물 및 실험용 설치동물인 쥐, 햄스터, 기니피그 뿐만 아니라, 애완동물(예: 개, 고양이) 등에게 사용할 수 있으며, 상기 가금류로서 닭, 칠면조, 오리, 거위, 꿩, 및 메추라기 등에도 사용할 수 있고, 상기 어류로서 잉어, 붕어 및 송어 등에 이용될 수 있으나, 이에 한정되는 것은 아니다.Pigs, cows, horses, sheep, rabbits, goats, rodents and experimental rodents as the mammals can be used not only for rats, hamsters, and guinea pigs, but also for pets (eg, dogs, cats), etc., and chickens as the poultry, It can be used for turkey, duck, geese, pheasant, and quail, and the like, and can be used as the fish, such as carp, crucian carp and trout, but is not limited thereto.
실시예 1. 균주의 분리 및 동정Example 1. Isolation and identification of strains
여러 종류의 김치 시료를 파쇄한 후, 김치액을 PBS(phosphate buffered saline)로 연속희석(serial dilution, 103~108)하여 1차 젖산균 선택 배지인 MRS에 도말한 후 30℃ 또는 37℃에서 각각 24시간 배양한다. 형성된 콜로니를 단일 콜로니로 분리한 뒤, 류코노스톡 선택 배지인 Phenylethyl alcohol sucrose agar 배지에 선상 도말하여 20℃에서 24시간 배양하였다. 배양 후, 형성된 단일 콜로니를 수거하여 MRS 액체배지에 넣고 배양하였다. 24시간 배양한 배양액으로부터 genomic DNA를 추출하였다. 16S rDNA 염기서열을 확인하기 위해, 얻어진 genomic DNA 산물은 마크로젠에 분석 의뢰하였다. 확인한 염기서열을 National Center for Biotechnology information (NCBI, www.ncbi.nlm.nih.gov)의 Basic Local Alignment Search Tool (BLAST)을 이용하여 유사도 분석하였고, 이 결과를 통해 최종적으로 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주로 명명하고, 한국미생물 보존센터에 2020년 4월 24일자로 기탁하였다.After crushing various types of kimchi samples, serial dilution (10 3 ~ 10 8 ) of the kimchi solution with PBS (phosphate buffered saline) is applied to MRS, the primary lactic acid bacteria selection medium, and then at 30°C or 37°C. Incubate for 24 hours each. After the formed colonies were separated into single colonies, they were streaked on a Phenylethyl alcohol sucrose agar medium, which is a leuconostok selective medium, and cultured at 20° C. for 24 hours. After culturing, the formed single colonies were collected and cultured in MRS broth. Genomic DNA was extracted from the culture medium cultured for 24 hours. In order to confirm the 16S rDNA base sequence, the obtained genomic DNA product was requested for analysis by Macrogen. The confirmed nucleotide sequence was analyzed for similarity using the Basic Local Alignment Search Tool (BLAST) of the National Center for Biotechnology information (NCBI, www.ncbi.nlm.nih.gov). Named as LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain, it was deposited at the Korea Microorganism Conservation Center on April 24, 2020.
실시예 2. 균주의 배양Example 2. Culture of the strain
분리한 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 MRS 액체배지 30ml에 1% 접종하여 37℃에서 6시간 동안 정치배양 하였다. 배양 후, 3500 rpm에서 10분 동안 원심분리하여 배양액은 제거하고 균체는 PBS(phosphate buffered saline) 용액으로 3회 세척하여 남아 있는 배지 성분을 제거하였다. The isolated Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain was inoculated with 1% in 30 ml of MRS broth, and cultured at 37° C. for 6 hours. After incubation, the culture medium was removed by centrifugation at 3500 rpm for 10 minutes, and the cells were washed three times with a phosphate buffered saline (PBS) solution to remove the remaining medium components.
실시예Example 3. 실험동물(마우스)의 조건 3. Conditions of experimental animals (mouse)
실험에 사용된 실험동물은 수컷 5주령의 BALB/c 마우스(오리엔트바이오, 한국)를 공급받았고, 실내 온도 20±2℃ 습도 55±15%가 유지되는 SPF 환경의 동물 사육실에서 1주일의 안정화 기간을 거쳐 실험기간 동안 사육하였다. 사료는 항생제가 첨가되지 않은 일반적인 팰렛 사료를 공급하였고, 물은 수시로 섭취할 수 있게 하였다. 종양 크기 변화의 관찰은 3.14 x (길이 x 높이 x 넓이)/6의 식을 사용하여 종양의 부피(mm3)를 측정하여 진행하였다. The experimental animals used in the experiment were supplied with male 5-week-old BALB/c mice (Orient Bio, Korea), and a stabilization period of 1 week in an SPF environment where
실시예Example 4. 대장암 CT26 세포 이식 마우스 모델에서의 항종양 효과 분석 4. Analysis of antitumor effect in colorectal cancer CT26 cell transplantation mouse model
4-1. 세포 배양4-1. cell culture
CT26 대장암 세포는 한국세포주은행에서 구입하였고, DMEM 배지에 10% FBS(fetal bovine serum)와 1% 항생제(penicillin/streptomycin)를 첨가하여 5% CO2, 37℃ 조건에서 배양하였다. CT26 colorectal cancer cells were purchased from Korea Cell Line Bank, and 10% FBS (fetal bovine serum) and 1% antibiotics (penicillin/streptomycin) were added to DMEM medium and cultured at 5% CO 2 and 37°C conditions.
4-2. CT26 세포 이식 암 동물모델 제작4-2. CT26 cell transplantation cancer animal model production
CT26 세포 이식 동물모델 제작을 위해서 6주령 BALB/c 마우스(18-21g)를 실험에 이용하였다. 배양한 대장암 세포 CT26은 1x105 cell을 수확(harvest)한 후, 50㎕의 PBS에서 재부유하여 마우스의 오른쪽 대퇴부 피하에 주입하였다. 6-week-old BALB/c mice (18-21 g) were used in the experiment for the CT26 cell transplantation animal model production. Cultured colorectal cancer cells CT26 were harvested (harvest) of 1x10 5 cells, resuspended in 50 μl PBS, and injected subcutaneously into the right thigh of the mouse.
4-3. 항종양 효과 분석4-3. Anti-tumor effect analysis
종양이 약 80~100mm3의 부피로 형성된 CT26 세포 이식 마우스의 꼬리에 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1)을 정맥 내 주사하였다. PBS에 준비한 류코노스톡 메센테로이데스 LB-LM1 0.1ml(1x109 CFU)을 정맥 주사하였고, 대조군에는 PBS를 투여하였다. 시간 경과에 따라 CT26 세포 이식 마우스의 종양 크기의 변화를 육안으로 확인한 결과를 도 1에 나타내었다. Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) was intravenously injected into the tail of a CT26 cell-transplanted mouse in which the tumor was formed in a volume of about 80-100 mm 3 . 0.1ml (1x10 9 CFU) of Leukonostok mecenteroides LB-LM1 prepared in PBS was intravenously injected, and PBS was administered to the control group. The results of visually confirming the change in the tumor size of the CT26 cell transplanted mice over time are shown in FIG. 1 .
도 1에 나타난 바와 같이, 대조군(PBS)에 비해 류코노스톡 메센테로이데스 LB-LM1을 투여한 그룹이 14일이 지난 후에 종양의 크기가 현저하게 줄어든 것을 관찰하였다. As shown in Figure 1, compared to the control group (PBS), it was observed that the size of the tumor was significantly reduced after 14 days in the group administered with Leukonostok mecenteroides LB-LM1.
또한, 시간 경과에 따른 CT26 세포 이식 마우스에서 종양의 부피 변화를 측정한 결과를 도 2에 나타내었다. In addition, the result of measuring the volume change of the tumor in the CT26 cell transplanted mouse over time is shown in FIG. 2 .
도 2에 나타난 바와 같이, CT26세포 이식 마우스의 종양 크기가 대조군과 비교하였을 때 류코노스톡 메센테로이데스 LB-LM1을 투여한 그룹에서 약 80% 정도 감소한 것을 확인하였다. As shown in FIG. 2 , it was confirmed that the tumor size of the CT26 cell transplanted mice was reduced by about 80% in the group administered with Leukonostok mecenteroides LB-LM1 compared to the control group.
실시예Example 5. In vitro 항암 활성 효능 분석 5. In vitro anticancer activity analysis
5-1. 세포주의 준비5-1. Preparation of cell lines
분리한 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주의 항암 활성 효과를 관찰하기 위해 Cell counting Kit-8을 이용하여 세포 성장률(cell viability assay)을 측정하였다. 항암 활성 효능실험에 사용된 세포는 대장암 CT26, SW620, HCT116 세포주, 췌장암 AsPC-1 세포주, 방광암 T24 세포주, 흑색종 B16-F10 세포주, 그리고 정상 피부 세포주인 CCD-986sk이다.In order to observe the anticancer activity of the isolated Leuconostoc mesenteroides LB-LM1 strain, cell growth rate (cell viability assay) was measured using Cell Counting Kit-8. The cells used in the anticancer activity efficacy experiment were colon cancer CT26, SW620, HCT116 cell line, pancreatic cancer AsPC-1 cell line, bladder cancer T24 cell line, melanoma B16-F10 cell line, and normal skin cell line CCD-986sk.
SW620, H1650, AsPC-1, T24 세포주는 RPMI 배지에, CT26, HCT116, B16-F10 세포주는 DMEM 배지에, CCD-986sk 세포주는 IMDM 배지에 10% FBS(fetal bovine serum)와 1% 항생제(penicillin/streptomycin)를 첨가하여 5% CO2, 37℃ 조건에서 계대배양하여 성장기의 세포를 사용하여 실험하였다. 배양된 세포는 0.25% trypsin-EDTA를 37℃ 배양기에서 3분간 처리하여 세포를 탈착한 다음 DPBS로 2회 세척하였고, 각 세포가 96-well plate의 한 well당 80% 합류(confluency)가 되도록 준비하였다. SW620, H1650, AsPC-1, T24 cell lines in RPMI medium, CT26, HCT116, B16-F10 cell lines in DMEM medium, and CCD-986sk cell lines in IMDM medium with 10% FBS (fetal bovine serum) and 1% antibiotic (penicillin) /streptomycin) was added and subcultured at 5% CO 2 and 37° C. conditions, and experiments were performed using cells in the growth phase. The cultured cells were treated with 0.25% trypsin-EDTA in an incubator at 37°C for 3 minutes to detach the cells, and then washed twice with DPBS, and each cell was prepared to 80% confluency per well of a 96-well plate. did.
5-2. 세포 성장률(cell viability assay) 측정 결과5-2. Cell viability assay measurement result
본 발명은 대장암(3종), 췌장암(1종), 방광암(1종), 흑색종(1종) 세포 및 정상 피부 세포(1종)를 배양한 후 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리하여 세포 성장(cell viability)을 측정하였다. In the present invention, after culturing colon cancer (3 types), pancreatic cancer (1 type), bladder cancer (1 type), melanoma (1 type) cells and normal skin cells (1 type), Leukonostok mecenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain was treated to measure cell viability.
세포 성장률(cell viability assay)은 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 각 세포에 MOI 1로 처리한 다음 72시간 동안 배양하였고, 배양 후 Cell counting Kit-8 시약을 처리하여 흡광도(OD 450nm)를 측정하였다. 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리하지 않은 세포들의 흡광도를 100% 기준으로, 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리한 세포의 성장률을 계산하였으며, 실험 결과를 하기에 기재하였다.Cell growth rate (cell viability assay) was treated with Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain in each cell, followed by incubation for 72 hours. After treatment, absorbance (OD 450 nm) was measured. Based on 100% absorbance of cells not treated with Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain, Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) The growth rate of the cells was calculated, and the experimental results are described below.
대장암 CT26, SW620 및 HCT116 세포주에 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리하여 세포 성장률을 측정한 결과를 도 3에 나타내었다.Colorectal cancer CT26, SW620 and HCT116 cell lines treated with Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain to measure the cell growth rate is shown in FIG. 3 .
도 3에 나타난 바와 같이, 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리한 CT26, SW620, HCT116 대장암 세포주의 세포 성장률이 각각 31.2%, 30.9%, 22.7% 감소하는 것을 확인함에 따라 류코노스톡 메센테로이데스 LB-LM1 균주가 대장암에 대해 우수한 항암 활성 효능을 가짐을 확인할 수 있다.As shown in Figure 3, the cell growth rate of CT26, SW620, and HCT116 colon cancer cell lines treated with Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strains decreased by 31.2%, 30.9%, and 22.7%, respectively. As a result, it can be confirmed that the Leukonostok mecenteroides LB-LM1 strain has excellent anticancer activity against colorectal cancer.
또한, 췌장암 AsPC-1 세포주에 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리하여 세포 성장률을 측정한 결과를 도 4에 나타내었다.In addition, the result of measuring the cell growth rate by treating the pancreatic cancer AsPC-1 cell line with Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain is shown in FIG. 4 .
도 4에 나타낸 바와 같이, 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리한 AsPC-1 췌장암 세포주의 세포 성장률이 58.1% 감소하는 것을 확인함에 따라 류코노스톡 메센테로이데스 LB-LM1 균주가 췌장암에 대해 우수한 항암 활성 효능을 가짐을 확인할 수 있다.As shown in FIG. 4, as it was confirmed that the cell growth rate of the AsPC-1 pancreatic cancer cell line treated with the Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain was reduced by 58.1%, Leuconostoc mesenteroides LB-LM1 It can be confirmed that the LB-LM1 strain has excellent anticancer activity against pancreatic cancer.
또한, 방광암 T24 세포주에 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리하여 세포 성장률을 측정한 결과를 도 5에 나타내었다.In addition, the result of measuring the cell growth rate by treating the bladder cancer T24 cell line with Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain is shown in FIG. 5 .
도 5에 나타난 바와 같이, 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리한 T24 방광암 세포주의 세포 성장률이 29.8% 감소하는 것을 확인함에 따라 류코노스톡 메센테로이데스 LB-LM1 균주가 방광암에 대해 우수한 항암 활성 효능을 가짐을 확인할 수 있다.As shown in FIG. 5 , as it was confirmed that the cell growth rate of the T24 bladder cancer cell line treated with the Leuconostoc mesenteroides LB-LM1 strain was reduced by 29.8%, the Leuconostoc mesenteroides LB- It can be confirmed that the LM1 strain has excellent anticancer activity against bladder cancer.
또한, 흑색종 B16-F10 세포주에 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리하여 세포 성장률을 측정한 결과를 도 6에 나타내었다.In addition, the result of measuring the cell growth rate by treating the melanoma B16-F10 cell line with the Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain is shown in FIG. 6 .
도 6에 나타난 바와 같이, 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리한 B16-F10 흑색종 세포주의 세포 성장률이 23.9% 감소하는 것을 확인함에 따라 류코노스톡 메센테로이데스 LB-LM1 균주가 흑색종에 대해 우수한 항암 활성 효능을 가짐을 확인할 수 있다.As shown in FIG. 6, as it was confirmed that the cell growth rate of the B16-F10 melanoma cell line treated with the Leuconostoc mesenteroides LB-LM1 strain was reduced by 23.9%, It can be confirmed that the des LB-LM1 strain has excellent anticancer activity against melanoma.
상기 실험과 대비하여 정상 피부 CCD-986sk 세포주에 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리하여 세포 성장률을 측정한 결과를 도 7에 나타내었다.In contrast to the above experiment, normal skin CCD-986sk cell line was treated with Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain to measure the cell growth rate is shown in FIG. 7 .
도 7에 나타난 바와 같이, 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주는 CCD-986sk 정상 피부 세포주에 대해서는 독성을 보이지 않음을 확인할 수 있다.As shown in Figure 7, it can be confirmed that the Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain does not show toxicity to the CCD-986sk normal skin cell line.
실시예Example 6. In vitro 전이 (migration assay) 억제 능력 확인 6. Confirmation of the ability to inhibit in vitro migration (migration assay)
6-1. 세포주의 준비6-1. Preparation of cell lines
분리한 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주의 전이 억제 능력을 확인하기 위해 대장암 세포주인 MC38을 이용하였다. 100mm 배양 접시에 MC38 세포가 2x106 cell이 되도록 준비한 후, 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 MOI 1로 처리하여, 5% CO2, 37℃ 조건에서 24시간 배양하였다. 배양 후, PBS로 2번 세척하고 0.25% trypsin-EDTA를 처리하여 세포를 탈착하였다. Trans-well chamber membrane 바깥쪽을 10ug/ml fibronectin으로 미리 코팅하고, 탈착한 세포는 챔버(chamber) 안쪽에 넣어서 5% CO2, 37℃ 조건에서 24시간 배양하였다. 배양 후, PBS로 2회 세척하고 Diff Quik 용액으로 염색하였다. 충분히 건조를 한 후에 현미경으로 이미지를 촬영하여 세포수를 측정하여 전이율 결과를 산출하였다.In order to confirm the metastasis inhibiting ability of the isolated Leuconostoc mesenteroides LB-LM1 strain, MC38, a colorectal cancer cell line, was used. After preparing MC38 cells to become 2x10 6 cells in a 100 mm culture dish, the Leuconostoc mesenteroides LB-LM1 strain was treated with
류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리한 후 대장암 MC38 세포가 전이된 후의 이미지를 촬영한 사진을 도 8에 나타내었다.8 shows a photograph taken after the colorectal cancer MC38 cells metastasized after treatment with Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain.
도 8에 나타난 바와 같이, 류코노스톡 메센테로이데스 LB- LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리한 MC38 대장암 세포주가 대조군에 비해 챔버(chamber)를 통과하여 이동한 세포의 수가 감소되어있는 것을 확인하였다. As shown in Figure 8, the MC38 colorectal cancer cell line treated with the Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain has decreased in the number of cells that have passed through the chamber compared to the control. confirmed that.
또한, 대장암 MC38 세포주에 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리하여 계산한 전이율을 도 9에 나타내었다. In addition, the metastasis rate calculated by treating the colorectal cancer MC38 cell line with Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1) strain is shown in FIG. 9 .
도 9에 나타난 바와 같이, 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1) 균주를 처리한 MC38 대장암 세포주의 전이율이 27.5% 감소하는 것을 확인함에 따라 류코노스톡 메센테로이데스 LB-LM1 균주가 대장암의 전이를 억제하는 효능이 우수함을 확인하였다.As shown in FIG. 9, as it was confirmed that the metastasis rate of the MC38 colorectal cancer cell line treated with the Leuconostoc mesenteroides LB-LM1 strain was reduced by 27.5%, the Leuconostoc mesenteroides LB-LM1 It was confirmed that the -LM1 strain had excellent efficacy in inhibiting metastasis of colorectal cancer.
<110> LISCure Biosciences Inc. <120> Pharmaceutical composition for prevention or treatment of cancer comprising Leuconostoc sp. as active ingredient <130> KP20-0013-1 <150> KR 1020200027655 <151> 2020-03-05 <160> 1 <170> KoPatentIn 3.0 <210> 1 <211> 1487 <212> DNA <213> Leuconostoc mesenteroides <400> 1 tctgtcagga tgaacgctgg cggcgtgcct aatacatgca agtcgaacgc acagcgaaag 60 gtgcttgcac ctttcaagtg agtggcgaac gggtgagtaa cacgtggaca acctgcctca 120 aggctgggga taacatttgg aaacagatgc taataccgaa taaaacttag tgtcgcatga 180 cacaaagtta aaaggcgctt cggcgtcacc tagagatgga tccgcggtgc attagttagt 240 tggtggggta aaggcctacc aagacaatga tgcatagccg agttgagaga ctgatcggcc 300 acattgggac tgagacacgg cccaaactcc tacgggaggc tgcagtaggg aatcttccac 360 aatgggcgaa agcctgatgg agcaacgccg cgtgtgtgat gaaggctttc gggtcgtaaa 420 gcactgttgt atgggaagaa cagctagaat aggaaatgat tttagtttga cggtaccata 480 ccagaaaggg acggctaaat acgtgccagc agccgcggta atacgtatgt cccgagcgtt 540 atccggattt attgggcgta aagcgagcgc agacggttta ttaagtctga tgtgaaagcc 600 cggagctcaa ctccggaatg gcattggaaa ctggttaact tgagtgcagt agaggtaagt 660 ggaactccat gtgtagcggt ggaatgcgta gatatatgga agaacaccag tggcgaaggc 720 ggcttactgg actgcaactg acgttgaggc tcgaaagtgt gggtagcaaa caggattaga 780 taccctggta gtccacaccg taaacgatga acactaggtg ttaggaggtt tccgcctctt 840 agtgccgaag ctaacgcatt aagtgttccg cctggggagt acgaccgcaa ggttgaaact 900 caaaggaatt gacggggacc cgcacaagcg gtggagcatg tggtttaatt cgaagcaacg 960 cgaagaacct taccaggtct tgacatcctt tgaagctttt agagatagaa gtgttctctt 1020 cggagacaaa gtgacaggtg gtgcatggtc gtcgtcagct cgtgtcgtga gatgttgggt 1080 taagtcccgc aacgagcgca acccttattg ttagttgcca gcattcagat gggcactcta 1140 gcgagactgc cggtgacaaa ccggaggaag gcggggacga cgtcagatca tcatgcccct 1200 tatgacctgg gctacacacg tgctacaatg gcgtatacaa cgagttgcca gcccgcgagg 1260 gtgagctaat ctcttaaagt acgtctcagt tcggattgta gtctgcaact cgactacatg 1320 aagtcggaat cgctagtaat cgcggatcag cacgccgcgg tgaatacgtt cccgggtctt 1380 gtacacaccg cccgtcacac catgggagtt tgtaatgccc aaagccggtg gcctaacctt 1440 ttaggaagga gccgtctaag gcaggacaga tgactggggt gaagtct 1487 <110> LISCure Biosciences Inc. <120> Pharmaceutical composition for prevention or treatment of cancer comprising Leuconostoc sp. as active ingredient <130> KP20-0013-1 <150> KR 1020200027655 <151> 2020-03-05 <160> 1 <170> KoPatentIn 3.0 <210> 1 <211> 1487 <212> DNA <213> Leuconostoc mesenteroides <400> 1 tctgtcagga tgaacgctgg cggcgtgcct aatacatgca agtcgaacgc acagcgaaag 60 gtgcttgcac ctttcaagtg agtggcgaac gggtgagtaa cacgtggaca acctgcctca 120 aggctgggga taacatttgg aaacagatgc taataccgaa taaaacttag tgtcgcatga 180 cacaaagtta aaaggcgctt cggcgtcacc tagagatgga tccgcggtgc attagttagt 240 tggtggggta aaggcctacc aagacaatga tgcatagccg agttgagaga ctgatcggcc 300 acattgggac tgagacacgg cccaaactcc tacgggaggc tgcagtaggg aatcttccac 360 aatgggcgaa agcctgatgg agcaacgccg cgtgtgtgat gaaggctttc gggtcgtaaa 420 gcactgttgt atgggaagaa cagctagaat aggaaatgat tttagtttga cggtaccata 480 ccagaaaggg acggctaaat acgtgccagc agccgcggta atacgtatgt cccgagcgtt 540 atccggattt attgggcgta aagcgagcgc agacggttta ttaagtctga tgtgaaagcc 600 cggagctcaa ctccggaatg gcattggaaa ctggttaact tgagtgcagt agaggtaagt 660 ggaactccat gtgtagcggt ggaatgcgta gatatatgga agaacaccag tggcgaaggc 720 ggcttactgg actgcaactg acgttgaggc tcgaaagtgt gggtagcaaa caggattaga 780 taccctggta gtccacaccg taaacgatga acactaggtg ttaggaggtt tccgcctctt 840 agtgccgaag ctaacgcatt aagtgttccg cctggggagt acgaccgcaa ggttgaaact 900 caaaggaatt gacggggacc cgcacaagcg gtggagcatg tggtttaatt cgaagcaacg 960 cgaagaacct taccaggtct tgacatcctt tgaagctttt agagatagaa gtgttctctt 1020 cggagacaaa gtgacaggtg gtgcatggtc gtcgtcagct cgtgtcgtga gatgttgggt 1080 taagtcccgc aacgagcgca acccttattg ttagttgcca gcattcagat gggcactcta 1140 gcgagactgc cggtgacaaa ccggaggaag gcggggacga cgtcagatca tcatgcccct 1200 tatgacctgg gctacacacg tgctacaatg gcgtatacaa cgagttgcca gcccgcgagg 1260 gtgagctaat ctcttaaagt acgtctcagt tcggattgta gtctgcaact cgactacatg 1320 aagtcggaat cgctagtaat cgcggatcag cacgccgcgg tgaatacgtt cccgggtctt 1380 gtacacaccg cccgtcacac catgggagtt tgtaatgccc aaagccggtg gcctaacctt 1440 ttaggaagga gccgtctaag gcaggacaga tgactggggt gaagtct 1487
Claims (13)
상기 류코노스톡 속 균주는 류코노스톡 메센테로이데스(Leuconostoc mesenteroides), 류코노스톡 카노섬(Leuconostoc carnosum), 류코노스톡 시트리움(Leuconostoc citreum), 류코노스톡 홀잡펠리(Leuconostoc holzapfelli) 또는 류코노스톡 락티스 (Leuconostoc lactis)인 것을 특징으로 하는 암의 예방 또는 치료용 약학 조성물.According to claim 1,
The leuconostoc sp. strain is leuconostoc mesenteroides (Leuconostoc mesenteroides), leuconostoc carnosum (Leuconostoc carnosum), leuconostoc citreum (Leuconostoc citreum), leuconostoc holjapelli (Leuconostoc holzapfelli) or leucono A pharmaceutical composition for the prevention or treatment of cancer, characterized in that the stock lactis (Leuconostoc lactis).
상기 류코노스톡 메센테로이데스 균주는 류코노스톡 메센테로이데스 LB-LM1(Leuconostoc mesenteroides LB-LM1, 기탁번호 KCCM12701P)인 것을 특징으로 하는 암의 예방 또는 치료용 약학 조성물.3. The method of claim 2,
The Leuconostoc mesenteroides strain is Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1, accession number KCCM12701P), characterized in that the pharmaceutical composition for the prevention or treatment of cancer.
상기 암은 대장암, 췌장암, 방광암, 피부암 또는 흑색종양의 예방 또는 치료용 약학 조성물.According to claim 1,
The cancer is colon cancer, pancreatic cancer, bladder cancer, skin cancer or a pharmaceutical composition for the prevention or treatment of melanoma.
상기 조성물은 경구 투여 또는 비경구 투여의 방법으로 투여 가능한 것을 특징으로 하는 암의 예방 또는 치료용 약학 조성물.According to claim 1,
The composition is a pharmaceutical composition for preventing or treating cancer, characterized in that it can be administered by oral administration or parenteral administration.
상기 비경구 투여의 방법은 정맥 내 주입, 피하 주입, 근육 주입, 복강 주입, 내피 투여, 국소 투여, 비내 투여, 폐 내 투여 또는 직장 내 투여인 것인, 암의 예방 또는 치료용 약학 조성물.6. The method of claim 5,
The method of parenteral administration is intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endothelial administration, topical administration, intranasal administration, intrapulmonary administration or rectal administration, the pharmaceutical composition for the prevention or treatment of cancer.
상기 식품은 건강기능식품인, 암의 예방 또는 개선용 식품 조성물.8. The method of claim 7,
The food is a health functional food, a food composition for the prevention or improvement of cancer.
상기 식품은 빵, 떡, 캔디, 초콜릿, 껌, 아이스크림, 우유, 치즈, 식육가공품, 어육가공품, 김치, 간장, 된장, 고추장, 춘장, 청국장, 식초, 케첩, 카레, 드레싱, 음료 및 발효유로 이루어지는 군으로부터 선택되는 어느 하나의 식품인 것을 특징으로 하는 암의 예방 또는 개선용 식품 조성물.8. The method of claim 7,
The food includes bread, rice cake, candy, chocolate, gum, ice cream, milk, cheese, processed meat products, processed fish meat products, kimchi, soy sauce, soybean paste, red pepper paste, chunjang, cheonggukjang, vinegar, ketchup, curry, dressing, beverage and fermented milk. Food composition for the prevention or improvement of cancer, characterized in that any one food selected from the group.
상기 가축은 돼지, 소, 말, 양, 토끼, 염소, 쥐, 햄스터, 기니피그, 개, 고양이, 닭, 칠면조, 오리, 거위, 꿩, 메추라기, 잉어, 붕어 및 송어로 이루어지는 군으로부터 선택되는 어느 하나인 것인, 가축의 암 예방 또는 개선용 사료 조성물.12. The method of claim 11,
The livestock is any one selected from the group consisting of pig, cow, horse, sheep, rabbit, goat, rat, hamster, guinea pig, dog, cat, chicken, turkey, duck, goose, pheasant, quail, carp, crucian carp and trout A feed composition for preventing or improving cancer in livestock.
Leuconostoc mesenteroides LB-LM1 (Leuconostoc mesenteroides LB-LM1, accession number KCCM12701P) or a feed additive composition for preventing or improving livestock cancer comprising a culture thereof as an active ingredient.
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA3169371A CA3169371A1 (en) | 2020-03-05 | 2021-01-27 | Pharmaceutical composition for prevention or treatment of cancer comprising leuconostoc sp. as active ingredient |
| BR112022017706A BR112022017706A2 (en) | 2020-03-05 | 2021-01-27 | PHARMACEUTICAL COMPOSITION FOR PREVENTION OR TREATMENT OF CANCER COMPRISING LEUCONOSTOC SP. AS ACTIVE INGREDIENT |
| EP21765170.2A EP4134089A1 (en) | 2020-03-05 | 2021-01-27 | Pharmaceutical composition comprising genus leuconostoc strain as active ingredient for prevention or treatment of cancer |
| PCT/KR2021/001060 WO2021177600A1 (en) | 2020-03-05 | 2021-01-27 | Pharmaceutical composition comprising genus leuconostoc strain as active ingredient for prevention or treatment of cancer |
| CN202180018050.0A CN115551523A (en) | 2020-05-27 | 2021-01-27 | Pharmaceutical composition for preventing or treating cancer comprising leuconostoc strain as active ingredient |
| JP2022552893A JP2023517869A (en) | 2020-03-05 | 2021-01-27 | Pharmaceutical composition for prevention or treatment of cancer containing Leuconostoc as an active ingredient |
| US17/909,167 US20230120406A1 (en) | 2020-03-05 | 2021-01-27 | Pharmaceutical composition for prevention or treatment of cancer comprising leuconostoc sp. as active ingredient |
| AU2021231055A AU2021231055A1 (en) | 2020-03-05 | 2021-01-27 | Pharmaceutical composition comprising genus leuconostoc strain as active ingredient for prevention or treatment of cancer |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20200027655 | 2020-03-05 | ||
| KR1020200027655 | 2020-03-05 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20210112980A true KR20210112980A (en) | 2021-09-15 |
| KR102511221B1 KR102511221B1 (en) | 2023-03-17 |
Family
ID=77793451
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020200063684A KR102511221B1 (en) | 2020-03-05 | 2020-05-27 | Pharmaceutical composition for prevention or treatment of cancer comprising Leuconostoc sp. as active ingredient |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR102511221B1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022177409A1 (en) * | 2021-02-22 | 2022-08-25 | 주식회사 리스큐어바이오사이언시스 | Pharmaceutical composition containing leuconostoc mesenteroides strain-derived nanovesicles as active ingredient for preventing or treating cancer |
| WO2023090903A1 (en) * | 2021-11-17 | 2023-05-25 | 씨제이바이오사이언스 주식회사 | Composition for preventing or treating cancer or inflammation comprising novel leuconostoc mesenteroides strain, and method for preventing or treating cancer or inflammation using same |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20100013184A (en) | 2008-07-30 | 2010-02-09 | 한국식품연구원 | Leuconostoc mesenteroides 6-2 bacteria having anti-cancer activity and kimchi comprising thereof |
| KR20140098708A (en) * | 2013-01-31 | 2014-08-08 | 부산대학교 산학협력단 | Novel starter strain and method functional fermentation foods containing kimchi use thereof |
-
2020
- 2020-05-27 KR KR1020200063684A patent/KR102511221B1/en active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20100013184A (en) | 2008-07-30 | 2010-02-09 | 한국식품연구원 | Leuconostoc mesenteroides 6-2 bacteria having anti-cancer activity and kimchi comprising thereof |
| KR20140098708A (en) * | 2013-01-31 | 2014-08-08 | 부산대학교 산학협력단 | Novel starter strain and method functional fermentation foods containing kimchi use thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022177409A1 (en) * | 2021-02-22 | 2022-08-25 | 주식회사 리스큐어바이오사이언시스 | Pharmaceutical composition containing leuconostoc mesenteroides strain-derived nanovesicles as active ingredient for preventing or treating cancer |
| WO2023090903A1 (en) * | 2021-11-17 | 2023-05-25 | 씨제이바이오사이언스 주식회사 | Composition for preventing or treating cancer or inflammation comprising novel leuconostoc mesenteroides strain, and method for preventing or treating cancer or inflammation using same |
Also Published As
| Publication number | Publication date |
|---|---|
| KR102511221B1 (en) | 2023-03-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102009742B1 (en) | Pharmaceutical composition for prevention or treatment of cancer comprising Weissella cibaria WIKIM28 as active ingredient | |
| KR101995328B1 (en) | Lactobacillus fermentum WiKim0102 having anti-cancer activity and composition for comprising the same | |
| KR102511221B1 (en) | Pharmaceutical composition for prevention or treatment of cancer comprising Leuconostoc sp. as active ingredient | |
| KR102136772B1 (en) | Pharmaceutical composition for prevention or treatment of cancer comprising Lactobacillus sakei WIKIM30 as active ingredient | |
| KR102390755B1 (en) | Composition for prevention or treatment of cancer comprising Weissella paramesenteroides WiKim0137 as active ingredient | |
| KR102069622B1 (en) | Pharmaceutical composition for prevention or treatment of cancer comprising Lactobacillus fermentum WiKim0102 as active ingredient | |
| KR102339314B1 (en) | Pharmaceutical composition for prevention or treatment of cancer comprising Weissella cibaria WIKIM28 as active ingredient | |
| EP4134089A1 (en) | Pharmaceutical composition comprising genus leuconostoc strain as active ingredient for prevention or treatment of cancer | |
| KR102390775B1 (en) | Composition for prevention or treatment of cancer comprising Leuconostoc pseudomesenteroides WiKim0138 as active ingredient | |
| RU2792300C2 (en) | Pharmaceutical composition for prevention or treatment of cancer containing weissella cibaria wikim28 as an active ingredient | |
| EP4098271A1 (en) | Pharmaceutical composition for preventing or treating cancer, comprising weissella cibaria wikim28 as active ingredient | |
| US20240091281A1 (en) | Pharmaceutical composition for preventing or treating intestinal damage comprising leuconostoc citreum strain as active ingredient | |
| KR20220114490A (en) | Pharmaceutical composition for prevention or treatment of intestinal damage comprising Leuconostoc citreum as active ingredient | |
| KR20240014859A (en) | Pharmaceutical composition for prevention or treatment of cancer comprising Leuconostoc mesenteroides as active ingredient | |
| KR20220094155A (en) | Pharmaceutical composition for the prevention or treatment of cancer containing nanovesicles derived from the strains of Lactobacillus Sakei as an active ingredient | |
| KR20220120502A (en) | Pharmaceutical composition for prevention or treatment of cancer comprising Weissella cibaria LBML2 as active ingredient | |
| KR20220120498A (en) | Pharmaceutical composition for the prevention or treatment of cancer containing nanovesicles derived from the strains of Leuconostoc mesenteroides as an active ingredient | |
| KR20220094154A (en) | Pharmaceutical composition for the prevention or treatment of cancer containing nanovesicles derived from the strains of Lactobacillus Fermentum as an active ingredient | |
| KR20220120503A (en) | Pharmaceutical composition for the prevention or treatment of cancer containing nanovesicles derived from the strains of Weissella cibaria as an active ingredient | |
| KR20220094153A (en) | Pharmaceutical composition for the prevention or treatment of cancer containing nanovesicles derived from the strains of Weisella sibaria as an active ingredient | |
| US20220118033A1 (en) | Lactobacillus fermentum wikim0102 having anticancer activity and composition comprising same as active ingredient | |
| KR20220114489A (en) | Pharmaceutical composition for prevention or treatment of fibrosis comprising Leuconostoc citreum as active ingredient |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E902 | Notification of reason for refusal | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant |