KR20240036878A - Composition for inhibiting formation of Staphylococcus aureus biofilm comprising tetramethylbutylhydroquinone as an active ingredient - Google Patents
Composition for inhibiting formation of Staphylococcus aureus biofilm comprising tetramethylbutylhydroquinone as an active ingredient Download PDFInfo
- Publication number
- KR20240036878A KR20240036878A KR1020220115457A KR20220115457A KR20240036878A KR 20240036878 A KR20240036878 A KR 20240036878A KR 1020220115457 A KR1020220115457 A KR 1020220115457A KR 20220115457 A KR20220115457 A KR 20220115457A KR 20240036878 A KR20240036878 A KR 20240036878A
- Authority
- KR
- South Korea
- Prior art keywords
- staphylococcus aureus
- composition
- tetramethylbutylhydroquinone
- biofilm formation
- inhibiting
- Prior art date
Links
- 241000191967 Staphylococcus aureus Species 0.000 title claims abstract description 72
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 44
- 239000000203 mixture Substances 0.000 title claims abstract description 43
- AIVHOTJVVRFULE-UHFFFAOYSA-N CC1=C(C(=C(C(=C1O)CCCC)C)OC)C Chemical compound CC1=C(C(=C(C(=C1O)CCCC)C)OC)C AIVHOTJVVRFULE-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 239000004480 active ingredient Substances 0.000 title claims abstract description 19
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 7
- 230000032770 biofilm formation Effects 0.000 claims abstract description 47
- 208000015181 infectious disease Diseases 0.000 claims abstract description 17
- 239000000304 virulence factor Substances 0.000 claims abstract description 13
- 230000007923 virulence factor Effects 0.000 claims abstract description 13
- 239000004367 Lipase Substances 0.000 claims abstract description 11
- 102000004882 Lipase Human genes 0.000 claims abstract description 11
- 108090001060 Lipase Proteins 0.000 claims abstract description 11
- 235000019421 lipase Nutrition 0.000 claims abstract description 11
- 108010006464 Hemolysin Proteins Proteins 0.000 claims abstract description 9
- 239000003228 hemolysin Substances 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 235000013305 food Nutrition 0.000 claims description 11
- 230000036541 health Effects 0.000 claims description 11
- 235000013376 functional food Nutrition 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 claims description 8
- 229960003085 meticillin Drugs 0.000 claims description 8
- 230000003115 biocidal effect Effects 0.000 claims description 7
- 239000008199 coating composition Substances 0.000 claims description 7
- 206010035664 Pneumonia Diseases 0.000 claims description 5
- 108010059993 Vancomycin Proteins 0.000 claims description 5
- 229960003165 vancomycin Drugs 0.000 claims description 5
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 claims description 5
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 claims description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims 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 claims description 4
- 208000031729 Bacteremia Diseases 0.000 claims description 3
- 206010016952 Food poisoning Diseases 0.000 claims description 3
- 208000019331 Foodborne disease Diseases 0.000 claims description 3
- 206010031252 Osteomyelitis Diseases 0.000 claims description 3
- 206010033078 Otitis media Diseases 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 206010014665 endocarditis Diseases 0.000 claims description 3
- PDOUICUKTQRPHO-MENSNCDRSA-N staphyloxanthin Chemical compound CCC(C)CCCCCCCCCCC(=O)OC[C@H]1O[C@@H](OC(=O)C(\C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C)[C@H](O)[C@@H](O)[C@@H]1O PDOUICUKTQRPHO-MENSNCDRSA-N 0.000 claims description 3
- 206010069918 Bacterial prostatitis Diseases 0.000 claims description 2
- 206010061695 Biliary tract infection Diseases 0.000 claims description 2
- 206010011409 Cross infection Diseases 0.000 claims description 2
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 2
- 201000004624 Dermatitis Diseases 0.000 claims description 2
- 208000004232 Enteritis Diseases 0.000 claims description 2
- 206010021531 Impetigo Diseases 0.000 claims description 2
- 206010028885 Necrotising fasciitis Diseases 0.000 claims description 2
- 206010029803 Nosocomial infection Diseases 0.000 claims description 2
- 239000004100 Oxytetracycline Substances 0.000 claims description 2
- 206010040047 Sepsis Diseases 0.000 claims description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 2
- 229960000723 ampicillin Drugs 0.000 claims description 2
- 208000003167 cholangitis Diseases 0.000 claims description 2
- 201000003146 cystitis Diseases 0.000 claims description 2
- 208000002925 dental caries Diseases 0.000 claims description 2
- 239000007943 implant Substances 0.000 claims description 2
- 208000004396 mastitis Diseases 0.000 claims description 2
- 239000012567 medical material Substances 0.000 claims description 2
- 201000007970 necrotizing fasciitis Diseases 0.000 claims description 2
- 229960000625 oxytetracycline Drugs 0.000 claims description 2
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 claims description 2
- 235000019366 oxytetracycline Nutrition 0.000 claims description 2
- 238000004806 packaging method and process Methods 0.000 claims description 2
- 201000001245 periodontitis Diseases 0.000 claims description 2
- 206010034674 peritonitis Diseases 0.000 claims description 2
- 229960005322 streptomycin Drugs 0.000 claims description 2
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 claims description 2
- 230000002485 urinary effect Effects 0.000 claims description 2
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 11
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000001717 pathogenic effect Effects 0.000 abstract description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 94
- 238000004458 analytical method Methods 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 241000244206 Nematoda Species 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 240000007124 Brassica oleracea Species 0.000 description 5
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 5
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 5
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 239000004677 Nylon Substances 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000010261 cell growth Effects 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 229920001778 nylon Polymers 0.000 description 5
- 239000000654 additive Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 235000013373 food additive Nutrition 0.000 description 4
- 239000002778 food additive Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000007226 seed germination Effects 0.000 description 4
- XRCRJFOGPCJKPF-UHFFFAOYSA-N 2-butylbenzene-1,4-diol Chemical compound CCCCC1=CC(O)=CC=C1O XRCRJFOGPCJKPF-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- -1 carbapenems Chemical class 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 238000004624 confocal microscopy Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 229940014259 gelatin Drugs 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000007902 hard capsule Substances 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007901 soft capsule Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 239000004250 tert-Butylhydroquinone Substances 0.000 description 3
- 235000019281 tert-butylhydroquinone Nutrition 0.000 description 3
- JZODKRWQWUWGCD-UHFFFAOYSA-N 2,5-di-tert-butylbenzene-1,4-diol Chemical compound CC(C)(C)C1=CC(O)=C(C(C)(C)C)C=C1O JZODKRWQWUWGCD-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010018910 Haemolysis Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 206010041925 Staphylococcal infections Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- ZXJXZNDDNMQXFV-UHFFFAOYSA-M crystal violet Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1[C+](C=1C=CC(=CC=1)N(C)C)C1=CC=C(N(C)C)C=C1 ZXJXZNDDNMQXFV-UHFFFAOYSA-M 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 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 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000008588 hemolysis Effects 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- MLFHJEHSLIIPHL-UHFFFAOYSA-N isoamyl acetate Chemical compound CC(C)CCOC(C)=O MLFHJEHSLIIPHL-UHFFFAOYSA-N 0.000 description 2
- 235000019626 lipase activity Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 150000002960 penicillins Chemical class 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000008635 plant growth Effects 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 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
- 206010053555 Arthritis bacterial Diseases 0.000 description 1
- 235000011331 Brassica Nutrition 0.000 description 1
- 241000219198 Brassica Species 0.000 description 1
- 235000010149 Brassica rapa subsp chinensis Nutrition 0.000 description 1
- 235000000536 Brassica rapa subsp pekinensis Nutrition 0.000 description 1
- 241000499436 Brassica rapa subsp. pekinensis Species 0.000 description 1
- 241000244203 Caenorhabditis elegans Species 0.000 description 1
- 101100502609 Caenorhabditis elegans fem-1 gene Proteins 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 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
- 208000035473 Communicable disease Diseases 0.000 description 1
- 101100334582 Drosophila melanogaster Fem-1 gene Proteins 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010036410 Postoperative wound infection Diseases 0.000 description 1
- 241001506137 Rapa Species 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 241000750300 Staphylococcus aureus MW2 Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000031650 Surgical Wound Infection Diseases 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 229960003340 calcium silicate Drugs 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 229940041011 carbapenems Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 231100000676 disease causative agent Toxicity 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
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000009036 growth inhibition Effects 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
- 230000008821 health effect Effects 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 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
- 229940117955 isoamyl acetate Drugs 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 238000010859 live-cell imaging Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-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
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 235000019462 natural additive Nutrition 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 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
- 229940069328 povidone Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000015339 staphylococcus aureus infection Diseases 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 238000000352 supercritical drying Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
- A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
- A01N31/16—Oxygen or sulfur directly attached to an aromatic ring system with two or more oxygen or sulfur atoms directly attached to the same aromatic ring system
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- 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
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/03—Organic compounds
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
- C09D5/14—Paints containing biocides, e.g. fungicides, insecticides or pesticides
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D7/00—Features of coating compositions, not provided for in group C09D5/00; Processes for incorporating ingredients in coating compositions
- C09D7/40—Additives
- C09D7/60—Additives non-macromolecular
- C09D7/63—Additives non-macromolecular organic
-
- 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
Abstract
본 발명은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름 형성 억제용 조성물에 관한 것으로, 테트라메틸부틸하이드로퀴논이 병원성 황색포도상구균에 대한 항균 및 바이오필름 형성 억제 활성을 나타내고, 주요 독성인자인 용혈소(hemolysin) 및 리파아제(lipase) 생산을 억제하는 것을 확인함으로써, 황색포도상구균 바이오필름 형성 억제용 조성물이나 황색포도상구균 바이오필름에 의해 유발되는 감염증 예방, 치료 또는 개선용 조성물로서 유용하게 활용될 수 있다.The present invention relates to a composition for inhibiting Staphylococcus aureus biofilm formation containing tetramethylbutylhydroquinone as an active ingredient. Tetramethylbutylhydroquinone has antibacterial and biofilm formation inhibitory activities against pathogenic Staphylococcus aureus. A composition for inhibiting the formation of Staphylococcus aureus biofilm or a composition for preventing, treating or improving infections caused by Staphylococcus aureus biofilm by confirming that it inhibits the production of hemolysin and lipase, which are major virulence factors. It can be usefully utilized.
Description
본 발명은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름 형성 억제용 조성물에 관한 것이다.The present invention relates to a composition for inhibiting Staphylococcus aureus biofilm formation containing tetramethylbutylhydroquinone as an active ingredient.
황색포도상구균(또는 황색포도알균, Staphylococcus aureus)은 자연계에 널리 분포되어 있는 세균 중 하나로, 건강한 사람의 30% 이상의 비강, 인후두, 피부, 털 등에 집락된 채로 보균되어 있는 균이다. 그러나 이 균은 연부 조직 감염(봉와직염, 화농성 근육염), 화농성 관절염, 화농성 골수염, 중이염, 폐렴, 수술 후 창상 감염, 균혈증, 심내막염, 식중독 등을 일으키는 원인균이다.Staphylococcus aureus (or Staphylococcus aureus ) is one of the bacteria widely distributed in nature, and is colonized in the nasal cavity, throat, skin, and hair of more than 30% of healthy people. However, this bacteria is the causative agent of soft tissue infections (cellulitis, purulent myositis), purulent arthritis, purulent osteomyelitis, otitis media, pneumonia, postoperative wound infection, bacteremia, endocarditis, and food poisoning.
특히, 황색포도상구균 감염은 지역사회 및 병원 환경에서 흔하며 생명을 위협하는 다양한 독성 인자, 예를 들어 엔테로톡신(enterotoxin), 스타필로잔틴(staphyloxanthin), 리파아제(lipase), 용혈소(hemolysin), 바이오필름(biofilm) 등을 생성한다. 황색포도상구균 감염시 사용하는 항생제는 페니실린계, 카르바페넴계, 세팔로스포린계 및 베타 락탐계열인데, 항생제의 남용으로 페니실린에 내성이 생긴 것은 이미 오래전 일이고, 메티실린 내성 황색포도상구균(MRSA)과 반코마이신 내성 황색포도상구균(VRSA)의 증가가 세계적인 문제이며, MRSA 또는 VRSA에 감염 시, 항생제 처방이 유효하지 않아 생명을 크게 위협하고 있다.In particular, Staphylococcus aureus infections are common in community and hospital settings and contain a variety of life-threatening virulence factors, such as enterotoxin, staphyloxanthin, lipase, hemolysin, and biofilm. (biofilm) etc. are created. Antibiotics used for Staphylococcus aureus infection include penicillins, carbapenems, cephalosporins, and beta-lactams. Resistance to penicillins has developed a long time ago due to overuse of antibiotics, and methicillin-resistant Staphylococcus aureus (MRSA) The increase in vancomycin-resistant Staphylococcus aureus (VRSA) is a global problem, and when infected with MRSA or VRSA, antibiotic prescriptions are not effective, greatly threatening life.
따라서, 상기 문제를 해결하기 위하여 황색포도상구균의 항균 및 바이오필름 형성 억제제의 개발이 필요한 실정이다.Therefore, in order to solve the above problems, there is a need to develop antibacterial and biofilm formation inhibitors for Staphylococcus aureus.
본 발명의 목적은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름 형성 억제용 조성물을 제공하는 것이다.The purpose of the present invention is to provide a composition for inhibiting Staphylococcus aureus biofilm formation containing tetramethylbutylhydroquinone as an active ingredient.
본 발명의 다른 목적은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름에 의해서 유발되는 감염증 예방 또는 치료용 약학 조성물을 제공하는 것이다.Another object of the present invention is to provide a pharmaceutical composition for preventing or treating infections caused by Staphylococcus aureus biofilm containing tetramethylbutylhydroquinone as an active ingredient.
본 발명의 또 다른 목적은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름에 의해 유발되는 감염증 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health functional food composition for preventing or improving infections caused by Staphylococcus aureus biofilm containing tetramethylbutylhydroquinone as an active ingredient.
본 발명의 또 다른 목적은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름 형성 억제용 코팅 조성물을 제공하는 것이다.Another object of the present invention is to provide a coating composition for inhibiting Staphylococcus aureus biofilm formation containing tetramethylbutylhydroquinone as an active ingredient.
상기 목적을 달성하기 위해, 본 발명은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름 형성 억제용 조성물을 제공한다.To achieve the above object, the present invention provides a composition for inhibiting Staphylococcus aureus biofilm formation containing tetramethylbutylhydroquinone as an active ingredient.
또한, 본 발명은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름에 의해서 유발되는 감염증 예방 또는 치료용 약학 조성물을 제공한다.Additionally, the present invention provides a pharmaceutical composition for preventing or treating infections caused by Staphylococcus aureus biofilm containing tetramethylbutylhydroquinone as an active ingredient.
또한, 본 발명은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름에 의해 유발되는 감염증 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving infections caused by Staphylococcus aureus biofilm containing tetramethylbutylhydroquinone as an active ingredient.
또한, 본 발명은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름 형성 억제용 코팅 조성물을 제공한다.Additionally, the present invention provides a coating composition for inhibiting Staphylococcus aureus biofilm formation containing tetramethylbutylhydroquinone as an active ingredient.
본 발명에 따르면, 테트라메틸부틸하이드로퀴논이 병원성 황색포도상구균에 대한 항균 및 바이오필름 형성 억제 활성을 나타내고, 주요 독성인자인 용혈소(hemolysin) 및 리파아제(lipase) 생산을 억제하는 것을 확인함으로써, 황색포도상구균 바이오필름 형성 억제용 조성물이나 황색포도상구균 바이오필름에 의해 유발되는 감염증 예방, 치료 또는 개선용 조성물로서 유용하게 활용될 수 있다.According to the present invention, it was confirmed that tetramethylbutylhydroquinone exhibits antibacterial and biofilm formation inhibitory activity against pathogenic Staphylococcus aureus and inhibits the production of hemolysin and lipase, which are major virulence factors. It can be usefully used as a composition for inhibiting the formation of a bacterial biofilm or as a composition for preventing, treating, or improving infections caused by Staphylococcus aureus biofilm.
도 1A는 하이드로퀴논 및 그 유도체를 첨가하고 24시간 배양한 후 황색포도상구균 균주(ATCC 6538)의 바이오필름 형성 억제 활성을 분석한 결과이다.
도 1B, 1C, 1D 및 1E는 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone; TBHQ)의 메티실린 민감성 황색포도상구균(S. aureus ATCC 6538; MSSA 6538 및 S. aureus ATCC 25923; MSSA 25923) 및 메티실린 내성 황색포도상구균(S. aureus MW2; MRSA MW2 및 S. aureus ATCC 33591; MRSA 33591)의 바이오필름 형성 억제 활성을 분석한 결과이다.
도 1F 및 1G는 하이드로퀴논(HQ) 및 테트라메틸부틸하이드로퀴논(TBHQ) 처리 시의 황색포도상구균(MSSA 6538) 세포 성장 변화를 분석한 결과이다.
도 2는 하이드로퀴논(HQ) 및 테트라메틸부틸하이드로퀴논(TBHQ)의 황색포도상구균 바이오필름 형성 억제 활성을 분석한 결과이다. 구체적으로, 도 2A는 바이오필름을 iRiS™ 디지털 세포 이미징 시스템을 통해 2D 및 3D로 분석한 이미지이다. 도 2B는 공초점레이저현미경(CLSM)를 이용한 바이오필름 이미지이고, 도 2C는 상기 도 2B의 결과를 바이오필름 정량측정 소프트웨어 COMSTAT으로 분석한 결과이다. 도 2D는 나일론표면에 테트라메틸부틸하이드로퀴논(TBHQ)의 황색포도상구균 바이오필름 형성 억제 활성을 전자현미경(SEM)으로 분석한 결과이다.
도 3은 하이드로퀴논(HQ) 및 테트라메틸부틸하이드로퀴논(TBHQ)의 황색포도상구균 독성인자인 용혈소(hemolysin) 및 리파아제(lipase) 억제 활성을 분석한 결과이다.
도 4는 식물(배추) 발아 및 선충 모델에서 하이드로퀴논(HQ) 및 테트라메틸부틸하이드로퀴논(TBHQ)의 세포 독성을 분석한 결과이다. Figure 1A shows the results of analyzing the biofilm formation inhibitory activity of a Staphylococcus aureus strain (ATCC 6538) after adding hydroquinone and its derivatives and culturing for 24 hours.
Figures 1B, 1C, 1D, and 1E show the use of tetramethylbutylhydroquinone (TBHQ) against methicillin-susceptible Staphylococcus aureus ( S. aureus ATCC 6538; MSSA 6538, and S. aureus ATCC 25923; MSSA 25923) and methicillin-resistant Staphylococcus aureus ( S. aureus MW2; MRSA MW2 and S. aureus ATCC 33591; This is the result of analyzing the biofilm formation inhibitory activity of MRSA 33591).
Figures 1F and 1G show the results of analysis of changes in Staphylococcus aureus (MSSA 6538) cell growth upon treatment with hydroquinone (HQ) and tetramethylbutylhydroquinone (TBHQ).
Figure 2 shows the results of analyzing the inhibitory activity of Staphylococcus aureus biofilm formation of hydroquinone (HQ) and tetramethylbutylhydroquinone (TBHQ). Specifically, Figure 2A is an image of a biofilm analyzed in 2D and 3D using the iRiS™ digital cell imaging system. Figure 2B is a biofilm image using confocal laser microscopy (CLSM), and Figure 2C is the result of analyzing the results of Figure 2B using biofilm quantitative measurement software COMSTAT. Figure 2D shows the results of analyzing the inhibitory activity of tetramethylbutylhydroquinone (TBHQ) on Staphylococcus aureus biofilm formation on a nylon surface using an electron microscope (SEM).
Figure 3 shows the results of analyzing the inhibitory activities of hemolysin and lipase, which are Staphylococcus aureus virulence factors, of hydroquinone (HQ) and tetramethylbutylhydroquinone (TBHQ).
Figure 4 shows the results of analyzing the cytotoxicity of hydroquinone (HQ) and tetramethylbutylhydroquinone (TBHQ) in plant (Chinese cabbage) germination and nematode models.
이하, 본 발명을 보다 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명자들은 특정 부틸하이드로퀴논을 이용한 항균 및 바이오필름 형성 억제용 조성물을 연구하던 중, 다른 부틸하이드로퀴논과 비교해서 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)이 약제내성 황색포도상구균에 대한 우수한 항균 및 바이오필름 형성 억제 활성을 나타내고, 주요 독성인자인 용혈소(hemolysin) 및 리파아제(lipase) 생산을 억제하는 것을 확인함으로써, 본 발명을 완성하였다.While researching a composition for antibacterial and biofilm formation inhibition using a specific butylhydroquinone, the present inventors found that, compared to other butylhydroquinone, tetramethylbutylhydroquinone showed excellent antibacterial and biofilm properties against drug-resistant Staphylococcus aureus. The present invention was completed by confirming that it exhibits formation inhibitory activity and inhibits the production of hemolysin and lipase, which are major toxicity factors.
본 발명은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름 형성 억제용 조성물을 제공한다.The present invention provides a composition for inhibiting Staphylococcus aureus biofilm formation containing tetramethylbutylhydroquinone as an active ingredient.
상기 황색포도상구균은 메티실린 민감성 황색포도상구균(MSSA), 메티실린 내성 황색포도상구균(MRSA) 및 반코마이신 내성 황색포도상구균(VRSA)으로 이루어진 군에서 선택된 하나 이상일 수 있으나, 이에 한정되는 것은 아니다.The Staphylococcus aureus may be one or more selected from the group consisting of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Staphylococcus aureus (VRSA), but is not limited thereto.
상기 조성물은 항생제 내성 황색포도상구균 바이오필름 형성을 억제할 수 있다.The composition can inhibit the formation of antibiotic-resistant Staphylococcus aureus biofilm.
또한, 상기 조성물은 황색포도상구균의 독성인자를 억제할 수 있고, 상기 독성인자는 스타필로잔틴(staphyloxanthin), 용혈소(hemolysin) 및 리파아제(lipase)로 이루어진 군에서 선택된 하나 이상일 수 있으나, 이에 한정되는 것은 아니다.In addition, the composition can inhibit the virulence factor of Staphylococcus aureus, and the virulence factor may be one or more selected from the group consisting of staphyloxanthin, hemolysin, and lipase, but is limited thereto. That is not the case.
또한, 상기 조성물은 항생제를 추가로 포함할 수 있고, 상기 항생제는 반코마이신(vancomycin), 스트렙토마이신(streptomycin), 암피실린(ampicillin) 및 옥시테트라사이클린(oxytetracycline)으로 이루어진 군에서 선택된 하나 이상일 수 있으나, 이에 한정되는 것은 아니다.In addition, the composition may further include an antibiotic, and the antibiotic may be one or more selected from the group consisting of vancomycin, streptomycin, ampicillin, and oxytetracycline. It is not limited.
또한, 본 발명은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름에 의해서 유발되는 감염증 예방 또는 치료용 약학 조성물을 제공하는 것이다.In addition, the present invention provides a pharmaceutical composition for preventing or treating infections caused by Staphylococcus aureus biofilm containing tetramethylbutylhydroquinone as an active ingredient.
상기 감염증은 충치, 치주염, 중이염, 근골계 감염, 괴사성 근막염, 담관계 감염, 골수염, 세균성 전립선염, 유방염, 피부염, 패혈증, 화농성 질환, 식중독, 농가진, 균혈증, 심내막염, 장염, 낭포성 섬유증 폐렴, 멜로이도시스(meloidosis), 병원내 감염(nosocomial infection), ICU 폐렴, 요로 카테터 방광염(urinary catheter cystitis), 복막 투석(CAPD) 복막염 및 담도 배액관 폐쇄(biliary stent blockage)로 이루어진 군에서 선택된 하나 이상일 수 있으나, 이에 한정되는 것은 아니다.The above infections include tooth decay, periodontitis, otitis media, musculoskeletal infection, necrotizing fasciitis, biliary tract infection, osteomyelitis, bacterial prostatitis, mastitis, dermatitis, sepsis, purulent disease, food poisoning, impetigo, bacteremia, endocarditis, enteritis, and cystic fibrosis pneumonia. , one or more days selected from the group consisting of meloidosis, nosocomial infection, ICU pneumonia, urinary catheter cystitis, CAPD peritonitis, and biliary stent blockage. However, it is not limited to this.
본 발명의 약학 조성물은 당해 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약제학적으로 허용되는 담체를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다.The pharmaceutical composition of the present invention is prepared in unit dose form or in a multi-dose container by formulating it using a pharmaceutically acceptable carrier according to a method that can be easily performed by a person skilled in the art. It can be manufactured by internalizing it.
상기 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸 히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘, 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약학 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다.The pharmaceutically acceptable carriers are those commonly used in preparation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Includes, but is not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, etc. In addition to the above components, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc.
본 발명에 있어서, 상기 약학 조성물에 포함되는 첨가제의 함량은 특별히 한정되는 것은 아니며 통상의 제제화에 사용되는 함량 범위 내에서 적절하게 조절될 수 있다.In the present invention, the content of additives included in the pharmaceutical composition is not particularly limited and can be appropriately adjusted within the content range used in conventional formulations.
상기 약학 조성물은 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립, 정제, 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 및 카타플라스마제로 이루어진 군에서 선택된 하나 이상의 피부 외용제 형태로 제형화될 수 있으나, 이에 한정되는 것은 아니다.The pharmaceutical compositions include injectable formulations such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, tablets, creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, paste agents, and cataplasmase agents. It may be formulated in the form of one or more external skin preparations selected from the group consisting of, but is not limited to this.
본 발명의 약학 조성물은 제형화를 위해 추가로 있는 약학적으로 허용 가능한 담체 및 희석제를 포함할 수 있다. 상기 약학적으로 허용 가능한 담체 및 희석제는 전분, 당 및 만니톨과 같은 부형제, 칼슘 포스페이트 등과 같은 충전제 및 증량제, 카르복시메틸셀룰로오스, 히드록시프로필셀룰로오스 등과 같은 셀룰로오스 유도체, 젤라틴, 알긴산염, 폴리비닐 피롤리돈 등과 같은 결합제, 활석, 스테아린산 칼슘, 수소화 피마자유 및 폴리에틸렌글리콜과 같은 윤활제, 포비돈 및 크로스포비돈과 같은 붕해제, 폴리소르베이트, 세틸알코올, 글리세롤 등과 같은 계면활성제를 포함하나, 이에 한정되지 않는다. 상기 약학적으로 허용 가능한 담체 및 희석제는 대상체에게 생물학적 및 생리학적으로 친화적인 것일 수 있다. 희석제의 예로는 염수, 수용성 완충액, 용매 및/또는 분산제(dispersion media)를 들 수 있으나, 이에 제한되는 것은 아니다.The pharmaceutical composition of the present invention may additionally contain pharmaceutically acceptable carriers and diluents for formulation. The pharmaceutically acceptable carriers and diluents include excipients such as starch, sugar and mannitol, fillers and extenders such as calcium phosphate, cellulose derivatives such as carboxymethylcellulose, hydroxypropylcellulose, gelatin, alginate, polyvinyl pyrrolidone. It includes, but is not limited to, binders such as talc, calcium stearate, lubricants such as hydrogenated castor oil and polyethylene glycol, disintegrants such as povidone and crospovidone, and surfactants such as polysorbate, cetyl alcohol, glycerol, etc. The pharmaceutically acceptable carrier and diluent may be biologically and physiologically friendly to the subject. Examples of diluents include, but are not limited to, saline, aqueous buffers, solvents, and/or dispersion media.
본 발명의 약학 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있다. 경구 투여일 경우, 정제, 트로키제(troches), 로젠지(lozenge), 수용성 현탁액, 유성 현탁액, 조제 분말, 과립, 에멀젼, 하드 캡슐, 소프트 캡슐, 시럽, 엘릭시르제 등으로 제형화될 수 있다. 비경구 투여일 경우, 주사액, 좌제, 호흡기 흡입용 분말, 스프레이용 에어로졸제, 연고, 도포용 파우더, 오일, 크림 등으로 제형화 될 수 있다.The pharmaceutical composition of the present invention can be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally, or topically) depending on the desired method. For oral administration, it can be formulated as tablets, troches, lozenges, aqueous suspensions, oily suspensions, powders, granules, emulsions, hard capsules, soft capsules, syrups, elixirs, etc. In the case of parenteral administration, it can be formulated as an injection, suppository, powder for respiratory inhalation, aerosol for spray, ointment, powder for application, oil, cream, etc.
본 발명의 약학 조성물의 투여량은 환자의 상태, 체중, 연령, 성별, 건강상태, 식이 체질 특이성, 제제의 성질, 질병의 정도, 조성물의 투여시간, 투여방법, 투여기간 또는 간격, 배설율 및 약물 형태에 따라 그 범위가 다양할 수 있으며, 이 분야 통상의 기술자에 의해 적절하게 선택될 수 있다. 예컨대, 약 0.1 내지 10,000mg/kg의 범위일 수 있으나 이제 제한되지 않으며, 하루 일회 내지 수회에 나누어 투여될 수 있다.The dosage of the pharmaceutical composition of the present invention is determined by the patient's condition, weight, age, gender, health, dietary constitution specificity, nature of the preparation, degree of disease, administration time of the composition, administration method, administration period or interval, excretion rate, and The range may vary depending on the drug form and can be appropriately selected by a person skilled in the art. For example, it may range from about 0.1 to 10,000 mg/kg, but is not limited and may be administered once to several times a day.
상기 약학 조성물은 목적하는 방법에 따라 경구 투여되거나 비경구 투여(예를 들면, 정맥 내, 피하 내, 복강 내 또는 국소에 적용)될 수 있다. 본 발명의 약학 조성물의 약학적 유효량 및 유효 투여량은 약학 조성물의 제제화 방법, 투여 방식, 투여 시간, 투여 경로 등에 의해 다양해질 수 있으며, 당해 기술 분야에서 통상의 지식을 가진 자는 목적하는 치료에 효과적인 투여량을 용이하게 결정하고 처방할 수 있다. 본 발명의 약학 조성물의 투여는 하루에 1회 투여될 수 있고, 수회에 나누어 투여될 수도 있다.The pharmaceutical composition may be administered orally or parenterally (eg, intravenously, subcutaneously, intraperitoneally, or topically applied) depending on the desired method. The pharmaceutically effective amount and effective dosage of the pharmaceutical composition of the present invention may vary depending on the formulation method, administration method, administration time, administration route, etc. of the pharmaceutical composition, and those skilled in the art will know that it is effective for the desired treatment. Dosage can be easily determined and prescribed. The pharmaceutical composition of the present invention may be administered once a day, or may be administered in several divided doses.
또한, 본 발명은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름에 의해 유발되는 감염증 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving infections caused by Staphylococcus aureus biofilm containing tetramethylbutylhydroquinone as an active ingredient.
본 발명은 통상적으로 이용되는 식품으로써 일반적으로 사용될 수 있다.The present invention can be generally used with commonly used foods.
본 발명의 식품 조성물은 건강기능식품으로서 사용될 수 있다. 상기“건강기능식품”이라 함은 건강기능 식품에 관한 법률에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, “기능성”이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The food composition of the present invention can be used as a health functional food. The term “health functional food” refers to food manufactured and processed using raw materials or ingredients with functionality useful to the human body in accordance with the Health Functional Food Act, and “functionality” refers to food that is related to the structure and function of the human body. It means ingestion for the purpose of controlling nutrients or obtaining useful health effects such as physiological effects.
상기 건강기능식품 조성물은 통상의 식품 첨가물을 포함할 수 있으며, 상기 “식품 첨가물”로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안전처에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.The health functional food composition may contain common food additives, and its suitability as a “food additive” is determined in accordance with the general provisions and general test methods of the food additive code approved by the Ministry of Food and Drug Safety, unless otherwise specified. The decision is made based on the specifications and standards for the item.
상기 “식품 첨가물 공전”에 수재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성물, 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물, L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합제제류들을 들 수 있다.Items listed in the “Food Additives Code” include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; natural additives such as subchromic pigment, licorice extract, crystalline cellulose, high-liquid pigment, and guar gum; Examples include mixed preparations such as sodium L-glutamate preparations, noodle additive alkaline preparations, preservative preparations, and tar coloring preparations.
본 발명의 식품 조성물은 정제, 캡슐, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공할 수 있다. 예를 들어, 캡슐 형태의 건강기능 식품 중 경질 캡슐제는 통상의 경질 캡슐에 본 발명에 따른 조성물을 부형제 등의 첨가제와 혼합 및 충진 하여 제조할 수 있으며, 연질 캡슐제는 본 발명에 따른 조성물을 부형제 등의 첨가제와 혼합하고 젤라틴 등 캡슐기제에 충진하여 제조할 수 있다. 상기 연질 캡슐제 는 필요에 따라 글리세린 또는 소르비톨 등의 가소제, 착색제, 보존제 등을 함유할 수 있다.The food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. For example, among health functional foods in the form of capsules, hard capsules can be manufactured by mixing and filling the composition according to the present invention with additives such as excipients in a regular hard capsule, and soft capsules can be manufactured by mixing and filling the composition according to the present invention. It can be manufactured by mixing with additives such as excipients and filling it with a capsule base such as gelatin. The soft capsule may contain plasticizers such as glycerin or sorbitol, colorants, preservatives, etc., if necessary.
상기 부형제, 결합제, 붕해제, 활택제, 교미제, 착향제 등에 대한 용어 정의는 당업계에 공지된 문헌에 기재된 것으로 그 기능 등이 동일 내지 유사한 것들을 포함한다. 상기 식품의 종류에는 특별한 제한이 없으며, 통상적인 의미에서의 건강 기능식품을 모두 포함한다.Definitions of terms such as excipients, binders, disintegrants, lubricants, coagulants, flavoring agents, etc. are those described in literature known in the art and include those with the same or similar functions. There is no particular limitation on the type of food, and it includes all health functional foods in the conventional sense.
본 발명에서 용어 “예방”은 본 발명에 따른 조성물의 투여로 상기 감염증을 억제 또는 지연시키는 모든 행위를 말한다. In the present invention, the term “prevention” refers to all actions that suppress or delay the infection by administering the composition according to the present invention.
본 발명에서 용어 “치료”는 본 발명에 따른 조성물의 투여로 상기 감염증을 호전시키거나 이롭게 변경하는 모든 행위를 말한다. In the present invention, the term “treatment” refers to all actions that improve or beneficially change the infection by administering the composition according to the present invention.
본 발명에서 용어 “개선”은 본 발명에 따른 조성물의 투여로 상기 감염증의 나쁜 상태를 좋게 하는 모든 행위를 말한다.In the present invention, the term “improvement” refers to all actions that improve the bad condition of the above infectious disease by administering the composition according to the present invention.
또한, 본 발명은 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone)을 유효성분으로 포함하는 황색포도상구균 바이오필름 형성 억제용 코팅 조성물을 제공한다.Additionally, the present invention provides a coating composition for inhibiting Staphylococcus aureus biofilm formation containing tetramethylbutylhydroquinone as an active ingredient.
상기 코팅 조성물은 식품제조기, 식품포장용기, 의료기기, 의료용 재료 또는 의료용 이식물에 코팅될 수 있으나, 이에 한정되는 것은 아니다.The coating composition may be coated on food processors, food packaging containers, medical devices, medical materials, or medical implants, but is not limited thereto.
이하, 본 발명의 이해를 돕기 위하여 실시예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예는 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다. 본 발명의 실시예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, the present invention will be described in detail through examples to aid understanding. However, the following examples only illustrate the content of the present invention and the scope of the present invention is not limited to the following examples. Examples of the present invention are provided to more completely explain the present invention to those skilled in the art.
[실험예 1] 균주, 화합물 및 배양 재료 준비[Experimental Example 1] Preparation of strains, compounds, and culture materials
메티실린 민감성 황색포도상구균(methicillin-sensitive S. aureus strains ATCC 25923 및 ATCC 6538; 이하 MSSA 25923 및 MSSA 6538이라 함) 및 메티실린 내성 황색포도상구균(methicillin-resistant S. aureus strain MW2 및 ATCC 33591; 이하 MRSA MW2 및 MRSA 33591이라 함)을 사용하였다. MSSA 균주는 37℃에서 LB 배지로 배양하였고, MRSA 균주는 0.2% 글루코스(glucose)를 포함하는 LB 배지로 배양하였다.Methicillin-sensitive S. aureus strains ATCC 25923 and ATCC 6538; hereinafter referred to as MSSA 25923 and MSSA 6538) and methicillin-resistant S. aureus strain MW2 and ATCC 33591; hereinafter referred to as MRSA MW2 and MRSA 33591) were used. MSSA strains were cultured in LB medium at 37°C, and MRSA strains were cultured in LB medium containing 0.2% glucose.
4종의 하이드로퀴논 및 그 유도체인 하이드로퀴논(hydroquinone; 이하 HQ라 함), 테트라메틸부틸하이드로퀴논(tetramethylbutylhydroquinone; 이하 TBHQ라 함), 다이터트부틸하이드로퀴논(2,5-Di-tert-butylhydroquinone; 이하 2,5-Di-tert-butylHQ라 함) 및 터트부틸하이드로퀴논(tert-butylhydroquinone; 이하 tert-butylHQ라 함)은 Sigma-Aldrich에서 구매하여 사용하였고, 용해시키는 용매로 DMSO를 사용하였다. DMSO(0.1% v/v)를 음성 대조군으로 사용하였고, DMSO 0.1% 이하는 세균 성장 또는 바이오필름 형성에 영향을 미치지 않았다.Four types of hydroquinone and their derivatives: hydroquinone (hereinafter referred to as HQ), tetramethylbutylhydroquinone (hereinafter referred to as TBHQ), and 2,5-Di-tert-butylhydroquinone (hereinafter referred to as TBHQ). Hereinafter referred to as 2,5-Di-tert-butylHQ) and tert-butylhydroquinone (hereinafter referred to as tert-butylHQ) were purchased from Sigma-Aldrich, and DMSO was used as a dissolving solvent. DMSO (0.1% v/v) was used as a negative control, and DMSO below 0.1% had no effect on bacterial growth or biofilm formation.
[실험예 2] HQ 및 그 유도체의 항균 활성 분석[Experimental Example 2] Analysis of antibacterial activity of HQ and its derivatives
HQ 및 그 유도체의 황색포도상구균에 대한 항균 활성을 확인하기 위해, 황색포도상구균을 HQ 및 그 유도체 존재 유무에 따라 37℃에서 24시간 동안 250ml 플라스크에서 배양한 후, 분광 광도계(Optizen 2120 UV; Mecasys Co. Ltd., 대전, 대한민국)를 사용하여 600nm에서 배양 탁도를 측정하였다. 초기 세포 농도에 비해 세포성장이 없는 경우, 화합물의 최소성장저해농도(MIC)로 하였다. 모든 실험은 최소 2개의 독립적인 배양을 통해 수행하였다.To confirm the antibacterial activity of HQ and its derivatives against Staphylococcus aureus, Staphylococcus aureus was cultured in a 250 ml flask at 37°C for 24 hours in the presence or absence of HQ and its derivatives, and then analyzed with a spectrophotometer (Optizen 2120 UV; Mecasys). Co. Ltd., Daejeon, Korea) was used to measure culture turbidity at 600 nm. If there was no cell growth compared to the initial cell concentration, the minimum growth inhibition concentration (MIC) of the compound was determined. All experiments were performed in at least two independent cultures.
[[ 실험예Experiment example 3] 3] HQHQ 및 그 유도체의 바이오필름 형성 억제 활성 분석 and analysis of biofilm formation inhibition activity of its derivatives.
3-1. 크리스탈 바이올렛(crystal violet) 분석3-1. Crystal violet analysis
HQ 및 그 유도체의 황색포도상구균 바이오필름 형성 억제 활성을 확인하기 위해, 크리스탈 바이올렛 분석을 통해 바이오필름 형성을 정량하였다. 4종류의 균주(MSSA 6538, MSSA 25923, MRSA MW2 및 MRSA 33591) 바이오필름 형성 분석은 96-웰 폴리스티렌 플레이트(SPL Life Sciences, Korea)에서 수행하였다.To confirm the inhibitory activity of HQ and its derivatives on Staphylococcus aureus biofilm formation, biofilm formation was quantified through crystal violet analysis. Biofilm formation analysis of four strains (MSSA 6538, MSSA 25923, MRSA MW2, and MRSA 33591) was performed in 96-well polystyrene plates (SPL Life Sciences, Korea).
초기 세포농도 1 x 107 CFU/ml의 황색포도상구균을 신선한 LB 배지에 접종하고 37℃에서 교반 없이 24시간 동안 HQ 및 그 유도체(0, 0.2, 0.5, 1, 2 및 5μg/mL)와 함께 배양하였다. 부유세포를 제거하기 위해, 증류수를 사용하여 플레이트를 3회 세척한 후 바이오필름 형성을 정량화하였다. 바이오필름은 0.1% 크리스탈-바이올렛과 함께 20분 동안 인큐베이션하고, 증류수를 사용하여 3회 세척한 다음 95% 에탄올을 사용하여 바이오필름 세포에 부착된 크리스탈-바이올렛을 추출하였다. 바이오필름 형성 측정을 위한 흡광도는 570nm에서 Multiskan EX 마이크로플레이트 판독기를 사용하여 측정하였으며, 실험은 최소 6회 이상 반복수행하였다.Staphylococcus aureus at an initial cell concentration of 1 Cultured. To remove floating cells, the plate was washed three times using distilled water and biofilm formation was quantified. The biofilm was incubated with 0.1% crystal-violet for 20 minutes, washed three times with distilled water, and then the crystal-violet attached to the biofilm cells was extracted using 95% ethanol. Absorbance for measuring biofilm formation was measured using a Multiskan EX microplate reader at 570 nm, and the experiment was repeated at least six times.
3-2. 광학현미경을 통한 분석3-2. Analysis through light microscope
바이오필름 형성 억제 활성을 확인하기 위해, 상기 실험예 2-1과 같이 37℃에서 24시간 동안 바이오필름을 생성하고 부유세포를 증류수로 3회 부드럽게 세척하여 제거하고 바이오필름을 iRiS™ 디지털 세포 이미징 시스템(Logos BioSystems)을 사용하여 라이브 이미징 현미경으로 관찰하였다. 바이오필름 이미지는 ImageJ를 사용하여 색상으로 구분된 2D 및 3D 사진으로 생성하였다.In order to confirm the activity of inhibiting biofilm formation, a biofilm was generated at 37°C for 24 hours as in Experimental Example 2-1, the floating cells were removed by gently washing with distilled water three times, and the biofilm was removed using the iRiS™ digital cell imaging system. Observation was made using a live imaging microscope (Logos BioSystems). Biofilm images were generated as color-coded 2D and 3D photographs using ImageJ.
3-3. 공초점현미경을 통한 분석3-3. Analysis through confocal microscopy
바이오필름 형성 억제 활성을 확인하기 위해, 공초점 레이저 현미경을 사용하였다. 황색포도상구균을 HQ 및 그 유도체의 존재 유무에 따라 교반 없이 96-웰 폴리스티렌 플레이트(SPL Life Sciences)에서 배양하였다. 이후 멸균 PBS(phosphate-buffered saline)로 3회 세척하여 부유세포를 제거하였다. 플레이트 바닥의 바이오필름은 20x 대물렌즈가 장착된 공초점 레이저 현미경(Nikon Eclipse Ti, Tokyo, Japan, 488nm)의 Ar 레이저(방출 파장 500~550nm)를 사용하여 시각화하였다. 공초점 이미지는 NIS-Elements C 버전 3.2(Nikon eclipse)를 사용하여 구성하였다. 실험당 최소 12개의 무작위 위치를 분석하였다. To confirm biofilm formation inhibitory activity, confocal laser microscopy was used. Staphylococcus aureus was cultured in 96-well polystyrene plates (SPL Life Sciences) without agitation in the presence or absence of HQ and its derivatives. Afterwards, floating cells were removed by washing three times with sterile PBS (phosphate-buffered saline). The biofilm on the bottom of the plate was visualized using an Ar laser (emission wavelength 500–550 nm) in a confocal laser microscope (Nikon Eclipse Ti, Tokyo, Japan, 488 nm) equipped with a 20× objective. Confocal images were constructed using NIS-Elements C version 3.2 (Nikon eclipse). A minimum of 12 random locations were analyzed per experiment.
3-4. 전자현미경을 통한 분석3-4. Analysis through electron microscope
구체적인 바이오필름 형성 억제 활성을 확인하기 위해, 나일론 막에 형성된 황색포도상구균 바이오필름 세포를 전자현미경(SEM)으로 관찰하였다. 나일론 막을 0.4 x 0.4cm 크기로 자르고, HQ 및 그 유도체(0, 0.5, 1 및 2μg/mL)을 첨가하거나 첨가하지 않은 상태에서 황색포도상구균을 37℃에서 24시간 동안 나일론 막을 첨가하여 배양하였다. 나일론 막에 부착된 세포는 2.5% 글루타르알데하이드(glutaraldehyde) 및 2% 포름알데히드(formaldehyde)로 고정하고, 사산화 오스뮴(OsO4)을 사용하여 전처리하고, 에탄올 계열(50%, 70%, 80%, 90%, 95% 및 100%) 및 이소아밀 아세테이트(isoamyl acetate)를 사용하여 탈수화하였다. 임계점 건조 후, 세포는 팔라듐/금으로 스퍼터 코팅하고, 15kV에서 S-4800 스캐닝 전자 현미경(Hitachi, Tokyo, Japan)으로 관찰하였다.To confirm specific biofilm formation inhibitory activity, Staphylococcus aureus biofilm cells formed on the nylon membrane were observed using an electron microscope (SEM). The nylon membrane was cut into pieces of 0.4 x 0.4 cm, and Staphylococcus aureus was cultured on the nylon membrane for 24 hours at 37°C with or without HQ and its derivatives (0, 0.5, 1, and 2 μg/mL). Cells attached to the nylon membrane were fixed with 2.5% glutaraldehyde and 2% formaldehyde, pretreated with osmium tetroxide (OsO 4 ), and incubated with ethanol series (50%, 70%, 80% %, 90%, 95% and 100%) and was dehydrated using isoamyl acetate. After critical point drying, cells were sputter-coated with palladium/gold and observed with an S-4800 scanning electron microscope (Hitachi, Tokyo, Japan) at 15 kV.
[실험예 4] HQ 및 그 유도체의 황색포도상구균 독성인자 억제 활성 분석[Experimental Example 4] Analysis of Staphylococcus aureus virulence factor inhibition activity of HQ and its derivatives
황색포도상구균은 용혈소(hemolysins) 및 리파아제(lipase)와 같은 여러 독성 인자를 생산한다. 따라서, HQ 및 그 유도체의 황색포도상구균 독성인자 억제 활성을 확인하기 위해, 용혈소 및 리파아제 억제 활성을 분석하였다. Staphylococcus aureus produces several virulence factors such as hemolysins and lipase. Therefore, to confirm the inhibitory activity of HQ and its derivatives against Staphylococcus aureus virulence factors, the hemolysin and lipase inhibitory activities were analyzed.
용혈(hemolysis) 분석은 신선한 양혈액을 MBcell에서 구입하여 사용하였다. 양혈액을 3000 x g로 5분간 원심분리하여 적혈구를 분리하고, PBS로 3회 세척(330 μL의 적혈구 세포/10ml의 PBS 버퍼)하였다. 초기 세포농도 1 x 107 CFU/ml 황색포도상구균에 신선한 LB 배지 2mL와 HQ 및 그 유도체(0, 0.2, 0.5, 1 및 2μg/mL)를 넣고 250rpm에서 교반하면서 37℃에서 배양하였다. 세포 배양물을 희석된 적혈구 세포에 첨가하고 용혈성을 결정하기 위해 혈액과 황색포도상구균(세포 배양액 200μL)의 혼합물을 37℃에서 3시간 동안 250rpm으로 반응하였다. 배양물을 16,600 x g로 10분간 원심분리하여 상등액을 분리하였고, 543nm에서 광학 밀도를 측정하였다.For the hemolysis analysis, fresh sheep blood was purchased from MBcell. Sheep blood was centrifuged at 3000 2 mL of fresh LB medium and HQ and its derivatives (0, 0.2, 0.5, 1 and 2 μg/mL) were added to Staphylococcus aureus with an initial cell concentration of 1 Cell culture was added to diluted red blood cells and to determine hemolysis, a mixture of blood and Staphylococcus aureus (200 μL of cell culture) was reacted at 250 rpm for 3 hours at 37°C. The culture was centrifuged at 16,600 xg for 10 minutes to separate the supernatant, and the optical density was measured at 543 nm.
리파아제(lipase) 억제 활성을 확인하기 위해, 초기 세포농도 1 x 107 CFU/ml 황색포도상구균에 LB 배지 2mL와 HQ 및 그 유도체(0, 0.2, 0.5, 1 및 2μg/mL)를 추가하고 37℃에서 24시간 동안 250rpm에서 교반하면서 배양하였다. 그 후, 상층액을 8,000 x g에서 10분간 원심분리하여 수집하고, 상등액 분취량(0.1mL)과 기질 완충액[0.9mL 완충액 A의 10%(vol/vol) 이소프로필 알코올 중 p-니트로페닐 팔미테이트 3mg/mL 및 1mg/mL 검아리빅과 완충액 B 90%(vol/vol) Na2PO4 완충액(50mM, pH 8.0)]과 혼합하였다. 혼합액을 암실에서 40℃로 30분 가열하고, 1M 탄산나트륨(Na2CO3)을 첨가하여 리파아제 반응을 중단하고 혼합물을 10분 동안 10,000 x g으로 원심분리 후 상등액의 흡광도를 405nm에서 측정하였다.To confirm lipase inhibitory activity, 2 mL of LB medium and HQ and its derivatives (0, 0.2, 0.5, 1, and 2 μg/mL) were added to Staphylococcus aureus at an initial cell concentration of 1 x 10 7 CFU/ml. 37 Cultured at ℃ for 24 hours with stirring at 250 rpm. The supernatant was then collected by centrifugation at 8,000 3mg/mL and 1mg/mL gumarivik and buffer B 90% (vol/vol) Na 2 PO 4 buffer (50mM, pH 8.0)] were mixed. The mixture was heated at 40°C in the dark for 30 minutes, 1M sodium carbonate (Na 2 CO 3 ) was added to stop the lipase reaction, and the mixture was centrifuged at 10,000 xg for 10 minutes, and the absorbance of the supernatant was measured at 405 nm.
[실험예 5] HQ 및 그 유도체의 세포 독성 분석[Experimental Example 5] Cytotoxicity analysis of HQ and its derivatives
HQ 및 그 유도체의 세포 독성을 확인하기 위해, 배추종자 발아 모델 시스템 및 선충 모델(C. elegans)을 사용하였다. To confirm the cytotoxicity of HQ and its derivatives, a cabbage seed germination model system and a nematode model ( C. elegans ) were used.
먼저, 배추(Brassica rapa)의 발아 및 성장에 미치는 영향을 확인하기 위해, 배추 종자를 멸균 증류수에 16시간 동안 담그고 증류수로 3회 헹구었다. 종자 표면을 살균하기 위해 종자를 실온에서 15분 동안 95% 에탄올 및 3% 차아염소산나트륨에서 순차적으로 배양하고 증류수로 3회 헹구었다. 플레이트당 10개의 종자를 0.7% 한천 및 0.86g/l Murashige-Skoog(MS)로 구성된 부드러운 한천 Murashige-Skoog 플레이트에 놓고 실온(24℃)에서 4일 동안 배양하였다. 매일 같은 시간에 종자 발아율 및 식물성장의 길이를 측정하였다. HQ 및 그 유도체(10, 50 및 200μg/mL) 각 농도에 대해 4번의 독립적인 실험을 수행하였다.First, cabbage ( Brassica) rapa ), cabbage seeds were soaked in sterile distilled water for 16 hours and rinsed three times with distilled water. To sterilize the seed surface, seeds were sequentially incubated in 95% ethanol and 3% sodium hypochlorite for 15 min at room temperature and rinsed three times with distilled water. Ten seeds per plate were placed on soft agar Murashige-Skoog plates consisting of 0.7% agar and 0.86 g/l Murashige-Skoog (MS) and incubated at room temperature (24°C) for 4 days. Seed germination rate and plant growth length were measured at the same time every day. Four independent experiments were performed for each concentration of HQ and its derivatives (10, 50, and 200 μg/mL).
또한, 예쁜꼬마선충[C. albicans 균주 fer-15(b26); fem-1(hc17)]을 M9 완충액[3g/l 인산칼륨(KH2PO4), 6g/l 제2인산나트륨(Na2HPO4), 5g/l 염화나트륨(NaCl) 및 1mM 황산마그네슘(MgSO4)]으로 2회 세척한 후, 약 40마리의 선충을 HQ 및 그 유도체(5, 10, 20 및 50μg/mL)가 포함된 M9 완충액(200μl)을 96 웰 플레이트에 넣었다. 그 후, 플레이트를 교반 없이 25℃에서 4일 동안 배양하였다. 4개의 독립적인 실험을 3회 수행하였다. 선충의 생존 결과는 인큐베이션 후 iRiS™ 디지털 세포 이미징 시스템(Logos Bio Systems)을 사용하여 20~30초 동안 LED 조명에 대한 반응을 통해 결정하였다.Additionally, Caenorhabditis elegans [ C. albicans strain fer-15(b26); fem-1(hc17)] in M9 buffer [3 g/l potassium phosphate (KH 2 PO 4 ), 6 g/l sodium phosphate dibasic (Na 2 HPO 4 ), 5 g/l sodium chloride (NaCl) and 1 mM magnesium sulfate (MgSO 4 )], approximately 40 nematodes were placed in M9 buffer (200 μl) containing HQ and its derivatives (5, 10, 20, and 50 μg/mL) in a 96-well plate. Afterwards, the plates were incubated at 25°C for 4 days without agitation. Four independent experiments were performed in triplicate. The survival outcome of the nematodes was determined after incubation through the response to LED lighting for 20 to 30 seconds using the iRiS™ digital cell imaging system (Logos Bio Systems).
[실험예 6] 통계 분석[Experimental Example 6] Statistical analysis
모든 실험예의 결과는 평균±표준편차로 나타내었고, SPSS version 23(SPSS Inc., Chicago, IL, USA) Dunnett 테스트에 따른 one-way ANOVA을 이용한 통계분석을 수행하였으며, p 값이 <0.05 일 때 유의한 것으로 간주하였다.The results of all experimental examples were expressed as mean ± standard deviation, and statistical analysis was performed using one-way ANOVA according to the Dunnett test in SPSS version 23 (SPSS Inc., Chicago, IL, USA). When the p value was <0.05, It was considered significant.
[[ 실시예Example 1] One] HQHQ 및 그 유도체의 항균 활성 분석 and analysis of antibacterial activity of its derivatives
상기 실험예 2에 따라, HQ 및 그 유도체의 황색포도상구균(MSSA 6538)에 대한 항균 활성을 분석한 결과, 표 1에 나타난 바와 같이, TBHQ은 5μg/mL, tert-butylHQ은 200μg/mL, HQ 및 2,5-Di-tert-butylHQ은 400μg/mL 이상으로 나타나, TBHQ의 MIC가 가장 낮은 것을 확인하였다. 또한, 도 1F 및 1G에 나타난 바와 같이, TBHQ 5μg/mL 농도에서 황색포도상구균의 세포성장이 억제됨을 확인하였다. 이는 상기 실험예에서 사용한 화합물 중 TBHQ의 황색포도상구균에 대한 항균 활성이 가장 우수한 것을 의미한다.According to Experimental Example 2, the antibacterial activity of HQ and its derivatives against Staphylococcus aureus (MSSA 6538) was analyzed. As shown in Table 1, TBHQ was 5 μg/mL, tert-butylHQ was 200 μg/mL, and HQ and 2,5-Di-tert-butylHQ were found to be more than 400 μg/mL, confirming that the MIC of TBHQ was the lowest. In addition, as shown in Figures 1F and 1G, it was confirmed that the cell growth of Staphylococcus aureus was inhibited at a concentration of 5 μg/mL of TBHQ. This means that TBHQ has the best antibacterial activity against Staphylococcus aureus among the compounds used in the above experimental example.
(10μg/mL)Cell growth(%)
(10μg/mL)
(50μg/mL)Cell growth(%)
(50μg/mL)
(μg/mL)MIC
(μg/mL)
(Hydroquinone; HQ)hydroquinone
(Hydroquinone; HQ )
(tetramethylbutylhydroquinone; TBHQ)Tetramethylbutylhydroquinone
(tetramethylbutylhydroquinone; TBHQ )
(2,5-Di-tert-butylhydroquinone; 2,5-Di-tert-butylHQ)Dietary Butylhydroquinone
(2,5-Di-tert-butylhydroquinone; 2,5-Di-tert-butylHQ )
(tert-butylhydroquinone; tert-butylHQ)Tertbutylhydroquinone
(tert-butylhydroquinone; tert-butylHQ )
[[ 실시예Example 2] 2] HQHQ 및 그 유도체의 바이오필름 형성 억제 활성 분석 and analysis of biofilm formation inhibition activity of its derivatives.
2-1. 2-1. 크리스탈crystal 바이올렛 분석 violet analysis
상기 실험예 3-1에 따라, HQ 및 그 유도체의 황색포도상구균(MSSA 6538)에 대한 바이오필름 형성 억제 활성을 분석한 결과, 도 1A에 나타난 바와 같이, TBHQ, 2,5-Di-tert-butylHQ 및 tert-butylHQ은 50μg/mL 농도에서 유의미한 바이오필름 형성 억제 활성을 나타냈고, 특히 TBHQ은 10μg/mL 농도에서도 바이오필름 형성을 95% 이상 억제하는 반면, HQ은 바이오필름 형성을 억제시키지 않는 것을 확인하였다. 이는 상기 실험예에서 사용한 화합물 중 TBHQ이 황색포도상구균 바이오필름 억제 활성이 가장 우수하다는 것을 의미한다.According to Experimental Example 3-1, the biofilm formation inhibitory activity of HQ and its derivatives against Staphylococcus aureus (MSSA 6538) was analyzed. As shown in Figure 1A, TBHQ, 2,5-Di-tert- butylHQ and tert-butylHQ showed significant biofilm formation inhibitory activity at a concentration of 50 μg/mL. In particular, TBHQ inhibited biofilm formation by more than 95% even at a concentration of 10 μg/mL, while HQ did not inhibit biofilm formation. Confirmed. This means that TBHQ has the best Staphylococcus aureus biofilm inhibitory activity among the compounds used in the above experimental example.
또한, TBHQ의 황색포도상구균에 대한 바이오필름 형성 억제 활성을 구체적으로 확인하기 위해, TBHQ을 4종의 황색포도상구균(MSSA 25923, MSSA 6538, MRSA MW2 및 MRSA 33591)을 처리한 후 바이오필름 활성도를 분석한 결과, 도 1B, 1C, 1D 및 1E에 나타난 바와 같이, TBHQ이 상기 4종의 균주 모두에서 용량 의존적으로 바이오필름 형성을 억제하였고, 구체적으로 1μg/mL의 TBHQ이 상기 4종의 균주 모두의 바이오필름 형성을 85% 이상 감소시키는 것을 확인하였다.In addition, to specifically confirm the biofilm formation inhibitory activity of TBHQ against Staphylococcus aureus, four types of Staphylococcus aureus (MSSA 25923, MSSA 6538, MRSA MW2, and MRSA 33591) were treated with TBHQ and the biofilm activity was measured. As a result of the analysis, as shown in Figures 1B, 1C, 1D, and 1E, TBHQ inhibited biofilm formation in a dose-dependent manner in all four strains, and specifically, 1 μg/mL of TBHQ inhibited all four strains. It was confirmed that biofilm formation was reduced by more than 85%.
이에, 가장 우수한 항균 및 바이오필름 형성 억제 활성을 나타내는 TBHQ에 대해 추가적인 실험을 수행하기로 결정하였다.Therefore, it was decided to conduct additional experiments on TBHQ, which showed the best antibacterial and biofilm formation inhibitory activities.
2-1. 현미경을 통한 분석2-1. Analysis through microscope
상기 실험예 3-2, 3-3 및 3-4에 따라, 광학현미경, 공초점현미경 및 주사전자현미경을 통해 HQ 및 그 유도체의 황색포도상구균에 대한 바이오필름 형성 억제 활성을 분석한 결과, 도 2B, 2C 및 2D에 나타난 바와 같이, TBHQ이 용량 의존적으로 바이오필름 형성을 감소시키는 반면, HQ은 바이오필름 억제 활성을 나타내지 않는 것을 확인하였다. 특히 공초점현미경에서 관찰한 바이오필름 형성 억제를 COMSTAT 소프트웨어 분석으로 정량화한 결과, 도 2C에 나타난 바와 같이, 1μg/mL의 TBHQ이 바이오필름 양, 표면커버리지 및 바이오필름 두께를 70% 이상 감소시키는 것을 확인하였다. According to Experimental Examples 3-2, 3-3, and 3-4, the results of analyzing the biofilm formation inhibitory activity of HQ and its derivatives against Staphylococcus aureus through optical microscopy, confocal microscopy, and scanning electron microscopy were as follows. As shown in 2B, 2C and 2D, it was confirmed that TBHQ reduced biofilm formation in a dose-dependent manner, while HQ did not exhibit biofilm inhibitory activity. In particular, the inhibition of biofilm formation observed in confocal microscopy was quantified using COMSTAT software analysis, and as shown in Figure 2C, 1 μg/mL of TBHQ reduced biofilm amount, surface coverage, and biofilm thickness by more than 70%. Confirmed.
[실시예 3] HQ 및 그 유도체의 황색포도상구균 독성인자 억제 활성 분석[Example 3] Analysis of Staphylococcus aureus virulence factor inhibition activity of HQ and its derivatives
상기 실험예 4에 따라, HQ 및 그 유도체의 황색포도상구균 독성인자 억제 활성을 분석한 결과, 도 3에 나타난 바와 같이, TBHQ(0.5, 1 및 2μg/mL)은 용혈 활성 및 리파아제 활성을 용량 의존적으로 감소시키는 것을 확인하였다. 구체적으로, TBHQ 1μg/mL 처리 시, 용혈 활성은 70% 이상, 리파아제 활성은 75% 이상 감소하는 것을 확인하였다. According to Experimental Example 4, the Staphylococcus aureus virulence factor inhibitory activity of HQ and its derivatives was analyzed. As shown in Figure 3, TBHQ (0.5, 1, and 2 μg/mL) showed hemolytic activity and lipase activity in a dose-dependent manner. It was confirmed that it was reduced to . Specifically, when treated with TBHQ 1 μg/mL, it was confirmed that hemolytic activity was reduced by more than 70% and lipase activity was reduced by more than 75%.
[실시예 4] HQ 및 그 유도체의 세포 독성 분석[Example 4] Cytotoxicity analysis of HQ and its derivatives
상기 실험예 5에 따라, 배추종자 발아 모델을 사용하여 HQ 및 그 유도체의 세포 독성을 분석한 결과, 도 4A, 4B 및 4C에 나타난 바와 같이, 종자 발아율은 시험 농도(10, 50 및 200μg/mL)에서 TBHQ 및 HQ의 큰 영향을 받지 않았고, 식물 성장 길이는 4일 동안 TBHQ 및 HQ 처리군 모두에서 큰 변화가 나타나지 않는 것을 확인하였다.According to Experimental Example 5, the cytotoxicity of HQ and its derivatives was analyzed using the cabbage seed germination model. As shown in Figures 4A, 4B, and 4C, the seed germination rate was determined at the test concentrations (10, 50, and 200 μg/mL). ) was not significantly affected by TBHQ and HQ, and plant growth length was confirmed to show no significant change in both the TBHQ and HQ treatment groups for 4 days.
또한, 선충 모델을 사용하여 HQ 및 그 유도체의 세포 독성을 분석한 결과, 도 4D에서 나타난 바와 같이, TBHQ은 HQ보다 C. elegans에 대해 독성이 낮게 나타나는 것을 확인하였다. 구체적으로, 대부분의 선충은 TBHQ 50μg/mL를 4일 동안 처리 시 생존한 반면, HQ 50μg/mL 처리 시 선충의 44%가 사망한 것을 확인하였다. 이는 바이오필름 형성 억제 활성 농도(1∼5μg/mL)의 TBHQ이 배추성장 및 선충에 대한 독성이 없음을 의미한다.In addition, as a result of analyzing the cytotoxicity of HQ and its derivatives using a nematode model, it was confirmed that TBHQ had lower toxicity to C. elegans than HQ, as shown in Figure 4D. Specifically, most nematodes survived when treated with TBHQ 50 μg/mL for 4 days, while 44% of nematodes died when treated with HQ 50 μg/mL. This means that TBHQ at the concentration of biofilm formation inhibitory activity (1∼5μg/mL) is not toxic to cabbage growth and nematodes.
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 즉, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다.As the specific parts of the present invention have been described in detail above, it is clear to those skilled in the art that these specific techniques are merely preferred embodiments and do not limit the scope of the present invention. do. That is, the practical scope of the present invention is defined by the appended claims and their equivalents.
Claims (12)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020220115457A KR20240036878A (en) | 2022-09-14 | 2022-09-14 | Composition for inhibiting formation of Staphylococcus aureus biofilm comprising tetramethylbutylhydroquinone as an active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020220115457A KR20240036878A (en) | 2022-09-14 | 2022-09-14 | Composition for inhibiting formation of Staphylococcus aureus biofilm comprising tetramethylbutylhydroquinone as an active ingredient |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20240036878A true KR20240036878A (en) | 2024-03-21 |
Family
ID=90472470
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020220115457A KR20240036878A (en) | 2022-09-14 | 2022-09-14 | Composition for inhibiting formation of Staphylococcus aureus biofilm comprising tetramethylbutylhydroquinone as an active ingredient |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR20240036878A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220117977A (en) | 2021-02-18 | 2022-08-25 | 중앙대학교 산학협력단 | Antifungal agents containing trifluoromethylated hydroquinone derivatives |
-
2022
- 2022-09-14 KR KR1020220115457A patent/KR20240036878A/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220117977A (en) | 2021-02-18 | 2022-08-25 | 중앙대학교 산학협력단 | Antifungal agents containing trifluoromethylated hydroquinone derivatives |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2756773C2 (en) | Compositions based on cannabidiol and their use methods | |
| JP2893035B2 (en) | Enhanced antimicrobial composition | |
| EP2437737B1 (en) | Composition including at least one trans-cinnamaldehyde and the use thereof in the treatment of bacterial infections, specifically in the treatment of nosocomial infections | |
| Karunanidhi et al. | Antibacterial and antibiofilm activities of nonpolar extracts of Allium stipitatum Regel. against multidrug resistant bacteria | |
| Safii et al. | Periodontal application of manuka honey: Antimicrobial and demineralising effects in vitro | |
| US20230355573A1 (en) | Antibiotic cannabinoid-terpene formulations | |
| KR20240036878A (en) | Composition for inhibiting formation of Staphylococcus aureus biofilm comprising tetramethylbutylhydroquinone as an active ingredient | |
| US11369628B2 (en) | Cranberry-derived compositions for potentiating antibiotic efficacy against bacterial persistence | |
| KR102248812B1 (en) | Composition for Inhibiting Biofilm Formation Comprising Glycyrrhizin and Glycyrrhetic Acid Having Synergistic Effect, and Composition for Preventing, Improving or Treating Dental Disease | |
| EP3268002B1 (en) | Antibacterial compositions and methods | |
| CN110179967A (en) | The composition and its application of polymyxins parent nucleus and a kind of antibiotic | |
| KR20240056096A (en) | Composition for inhibiting formation of Staphylococcus aureus biofilm comprising Barnardia japonica extract or fraction thereof as an active ingredient | |
| KR20240020468A (en) | A composition for inhibiting the formation of a biofilm of Staphylococcus aureus containing petrocelic acid as an active ingredient | |
| KR102441377B1 (en) | Composition comprising pectolinarin for inhibiting the formation of biofilm | |
| KR20200030863A (en) | An antimicrobial composition comprising sophoraflavanone g as an active ingredient | |
| KR102430080B1 (en) | Antibacterial composition comprising methyl gallate and tylosin | |
| KR102450964B1 (en) | Composition comprising acetanisol for inhibiting the formation of biofilm | |
| KR102342160B1 (en) | Composition comprising taxifolin for inhibiting the formation of biofilm | |
| KR102275801B1 (en) | Composition comprising cis-jasmone for inhibiting the formation of biofilm | |
| CN106673989A (en) | Pharmaceutical composition as well as preparation method and application thereof | |
| JP6655771B1 (en) | Combination of lysobactin and aminoglycosides for diseases caused by Gram-positive and Gram-negative bacteria in non-human animals | |
| KR20240036881A (en) | Composition for inhibiting formation of vibriobacterial biofilm comprising dimethylhydroquinone as an active ingredient | |
| EP3429579B1 (en) | Enhanced tulathromycin | |
| EP1313500B1 (en) | Combinations of dalfopristine/quinupristine with cefpirome | |
| KR20240018763A (en) | Composition for inhibiting antifungal and biofilm formation of pathogenic fungi containing hydroquinone derivative as an active ingredient |