JP5756614B2 - Autoinducer-2 inhibitor and preventive and / or therapeutic agent for caries disease - Google Patents
Autoinducer-2 inhibitor and preventive and / or therapeutic agent for caries disease Download PDFInfo
- Publication number
- JP5756614B2 JP5756614B2 JP2010246112A JP2010246112A JP5756614B2 JP 5756614 B2 JP5756614 B2 JP 5756614B2 JP 2010246112 A JP2010246112 A JP 2010246112A JP 2010246112 A JP2010246112 A JP 2010246112A JP 5756614 B2 JP5756614 B2 JP 5756614B2
- Authority
- JP
- Japan
- Prior art keywords
- mass
- bacteria
- sodium
- autoinducer
- inhibitor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- BVIYGXUQVXBHQS-IUYQGCFVSA-N (2R,4S)-2-methyltetrahydrofuran-2,3,3,4-tetrol Chemical compound C[C@@]1(O)OC[C@H](O)C1(O)O BVIYGXUQVXBHQS-IUYQGCFVSA-N 0.000 title claims description 84
- 239000003112 inhibitor Substances 0.000 title claims description 26
- 239000003814 drug Substances 0.000 title claims description 20
- 208000002925 dental caries Diseases 0.000 title claims description 19
- 229940124597 therapeutic agent Drugs 0.000 title claims description 16
- 230000003449 preventive effect Effects 0.000 title description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 13
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 35
- 239000004480 active ingredient Substances 0.000 claims description 27
- 229960003624 creatine Drugs 0.000 claims description 18
- 239000006046 creatine Substances 0.000 claims description 18
- 235000013305 food Nutrition 0.000 claims description 17
- 239000002537 cosmetic Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 230000037396 body weight Effects 0.000 claims description 3
- 230000006806 disease prevention Effects 0.000 claims 1
- 241000894006 Bacteria Species 0.000 description 70
- -1 acyl homoserine lactone Chemical compound 0.000 description 56
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 36
- 208000035473 Communicable disease Diseases 0.000 description 32
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 26
- 230000000694 effects Effects 0.000 description 24
- 150000003839 salts Chemical class 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 230000002401 inhibitory effect Effects 0.000 description 19
- 229960003080 taurine Drugs 0.000 description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 239000000606 toothpaste Substances 0.000 description 16
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 15
- 235000014113 dietary fatty acids Nutrition 0.000 description 15
- 239000000194 fatty acid Substances 0.000 description 15
- 229930195729 fatty acid Natural products 0.000 description 15
- 239000002609 medium Substances 0.000 description 15
- 208000015181 infectious disease Diseases 0.000 description 14
- 229940034610 toothpaste Drugs 0.000 description 14
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 13
- GSXOAOHZAIYLCY-UHFFFAOYSA-N D-F6P Natural products OCC(=O)C(O)C(O)C(O)COP(O)(O)=O GSXOAOHZAIYLCY-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- BGWGXPAPYGQALX-ARQDHWQXSA-N beta-D-fructofuranose 6-phosphate Chemical compound OC[C@@]1(O)O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O BGWGXPAPYGQALX-ARQDHWQXSA-N 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 241000607598 Vibrio Species 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 230000018612 quorum sensing Effects 0.000 description 11
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 9
- 239000003205 fragrance Substances 0.000 description 9
- 230000002265 prevention Effects 0.000 description 9
- 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 8
- 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 8
- 241000194019 Streptococcus mutans Species 0.000 description 8
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 8
- 235000011187 glycerol Nutrition 0.000 description 8
- 210000003296 saliva Anatomy 0.000 description 8
- 239000000600 sorbitol Substances 0.000 description 8
- 229960002920 sorbitol Drugs 0.000 description 8
- 235000010356 sorbitol Nutrition 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- 229940085605 saccharin sodium Drugs 0.000 description 7
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 6
- 239000011626 DL-alpha-tocopherylacetate Substances 0.000 description 6
- 235000001809 DL-alpha-tocopherylacetate Nutrition 0.000 description 6
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000002324 mouth wash Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 229940042585 tocopherol acetate Drugs 0.000 description 6
- 239000003053 toxin Substances 0.000 description 6
- 231100000765 toxin Toxicity 0.000 description 6
- 108700012359 toxins Proteins 0.000 description 6
- 241000193830 Bacillus <bacterium> Species 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 5
- 241000588698 Erwinia Species 0.000 description 5
- 241000186660 Lactobacillus Species 0.000 description 5
- 108091005804 Peptidases Proteins 0.000 description 5
- 102000035195 Peptidases Human genes 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 241000194017 Streptococcus Species 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 239000003963 antioxidant agent Substances 0.000 description 5
- 235000006708 antioxidants Nutrition 0.000 description 5
- 244000052616 bacterial pathogen Species 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 description 5
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 5
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229940039696 lactobacillus Drugs 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000011775 sodium fluoride Substances 0.000 description 5
- 235000013024 sodium fluoride Nutrition 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 241000186046 Actinomyces Species 0.000 description 4
- 241000607528 Aeromonas hydrophila Species 0.000 description 4
- 241000193468 Clostridium perfringens Species 0.000 description 4
- 241000606768 Haemophilus influenzae Species 0.000 description 4
- 241000590002 Helicobacter pylori Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 241000607720 Serratia Species 0.000 description 4
- 241000607768 Shigella Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 239000003082 abrasive agent Substances 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229940121363 anti-inflammatory agent Drugs 0.000 description 4
- 239000002260 anti-inflammatory agent Substances 0.000 description 4
- FUWUEFKEXZQKKA-UHFFFAOYSA-N beta-thujaplicin Chemical compound CC(C)C=1C=CC=C(O)C(=O)C=1 FUWUEFKEXZQKKA-UHFFFAOYSA-N 0.000 description 4
- 230000032770 biofilm formation Effects 0.000 description 4
- 230000021615 conjugation Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 229940047650 haemophilus influenzae Drugs 0.000 description 4
- 229940037467 helicobacter pylori Drugs 0.000 description 4
- 238000004020 luminiscence type Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229940051866 mouthwash Drugs 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 241000607620 Aliivibrio fischeri Species 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 241000193738 Bacillus anthracis Species 0.000 description 3
- 241000606125 Bacteroides Species 0.000 description 3
- 241000589968 Borrelia Species 0.000 description 3
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 3
- 241000589876 Campylobacter Species 0.000 description 3
- 208000002064 Dental Plaque Diseases 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 241000605986 Fusobacterium nucleatum Species 0.000 description 3
- 241000589989 Helicobacter Species 0.000 description 3
- 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 3
- 208000016604 Lyme disease Diseases 0.000 description 3
- 241001293415 Mannheimia Species 0.000 description 3
- YRYOXRMDHALAFL-UHFFFAOYSA-N N-(3-oxohexanoyl)homoserine lactone Chemical compound CCCC(=O)CC(=O)NC1CCOC1=O YRYOXRMDHALAFL-UHFFFAOYSA-N 0.000 description 3
- 241000206591 Peptococcus Species 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 241001135221 Prevotella intermedia Species 0.000 description 3
- 241000589516 Pseudomonas Species 0.000 description 3
- 241000607142 Salmonella Species 0.000 description 3
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 3
- 241001134658 Streptococcus mitis Species 0.000 description 3
- 241000194025 Streptococcus oralis Species 0.000 description 3
- 241000193998 Streptococcus pneumoniae Species 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 241000607618 Vibrio harveyi Species 0.000 description 3
- 241000607479 Yersinia pestis Species 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 238000004166 bioassay Methods 0.000 description 3
- 238000005415 bioluminescence Methods 0.000 description 3
- 230000029918 bioluminescence Effects 0.000 description 3
- 230000017531 blood circulation Effects 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
- 239000003086 colorant Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 208000007565 gingivitis Diseases 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 239000002736 nonionic surfactant Substances 0.000 description 3
- 208000028169 periodontal disease Diseases 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920001451 polypropylene glycol Polymers 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000028070 sporulation Effects 0.000 description 3
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 239000011732 tocopherol Substances 0.000 description 3
- 229930003799 tocopherol Natural products 0.000 description 3
- UYTRITJAZOPLCZ-BYPYZUCNSA-N (S)-4,5-dihydroxypentane-2,3-dione Chemical compound CC(=O)C(=O)[C@@H](O)CO UYTRITJAZOPLCZ-BYPYZUCNSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- XGRSAFKZAGGXJV-UHFFFAOYSA-N 3-azaniumyl-3-cyclohexylpropanoate Chemical compound OC(=O)CC(N)C1CCCCC1 XGRSAFKZAGGXJV-UHFFFAOYSA-N 0.000 description 2
- IJALWSVNUBBQRA-UHFFFAOYSA-N 4-Isopropyl-3-methylphenol Chemical compound CC(C)C1=CC=C(O)C=C1C IJALWSVNUBBQRA-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 241000606750 Actinobacillus Species 0.000 description 2
- 241000606749 Aggregatibacter actinomycetemcomitans Species 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
- 241000193755 Bacillus cereus Species 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- 241000606124 Bacteroides fragilis Species 0.000 description 2
- 241000606215 Bacteroides vulgatus Species 0.000 description 2
- 241000589877 Campylobacter coli Species 0.000 description 2
- 241000589996 Campylobacter rectus Species 0.000 description 2
- 235000002566 Capsicum Nutrition 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 206010008631 Cholera Diseases 0.000 description 2
- 241000193163 Clostridioides difficile Species 0.000 description 2
- 241000193403 Clostridium Species 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 208000004232 Enteritis Diseases 0.000 description 2
- 241000194033 Enterococcus Species 0.000 description 2
- 241000194032 Enterococcus faecalis Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- 241000588722 Escherichia Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241001076388 Fimbria Species 0.000 description 2
- 206010016952 Food poisoning Diseases 0.000 description 2
- 208000019331 Foodborne disease Diseases 0.000 description 2
- 241000605909 Fusobacterium Species 0.000 description 2
- 201000000628 Gas Gangrene Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241000606790 Haemophilus Species 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241000588748 Klebsiella Species 0.000 description 2
- 241000588747 Klebsiella pneumoniae Species 0.000 description 2
- 240000001046 Lactobacillus acidophilus Species 0.000 description 2
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 2
- 244000199866 Lactobacillus casei Species 0.000 description 2
- 235000013958 Lactobacillus casei Nutrition 0.000 description 2
- 241000186606 Lactobacillus gasseri Species 0.000 description 2
- 241000186604 Lactobacillus reuteri Species 0.000 description 2
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 2
- 241000186869 Lactobacillus salivarius Species 0.000 description 2
- 239000004166 Lanolin Substances 0.000 description 2
- 241000186781 Listeria Species 0.000 description 2
- 241000186779 Listeria monocytogenes Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 241000186359 Mycobacterium Species 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- 241000588653 Neisseria Species 0.000 description 2
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 2
- 241000588650 Neisseria meningitidis Species 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- ZYEMGPIYFIJGTP-UHFFFAOYSA-N O-methyleugenol Chemical compound COC1=CC=C(CC=C)C=C1OC ZYEMGPIYFIJGTP-UHFFFAOYSA-N 0.000 description 2
- 206010033078 Otitis media Diseases 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- 239000006002 Pepper Substances 0.000 description 2
- 101710124951 Phospholipase C Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 235000016761 Piper aduncum Nutrition 0.000 description 2
- 235000017804 Piper guineense Nutrition 0.000 description 2
- 240000003889 Piper guineense Species 0.000 description 2
- 235000008184 Piper nigrum Nutrition 0.000 description 2
- 241000605862 Porphyromonas gingivalis Species 0.000 description 2
- 241000605861 Prevotella Species 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 241000588769 Proteus <enterobacteria> Species 0.000 description 2
- 241000588770 Proteus mirabilis Species 0.000 description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
- 241000607715 Serratia marcescens Species 0.000 description 2
- 241000191940 Staphylococcus Species 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- 241000194008 Streptococcus anginosus Species 0.000 description 2
- 241000194049 Streptococcus equinus Species 0.000 description 2
- 241000194026 Streptococcus gordonii Species 0.000 description 2
- 241000193996 Streptococcus pyogenes Species 0.000 description 2
- 241000194023 Streptococcus sanguinis Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108010055044 Tetanus Toxin Proteins 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 description 2
- 241000607626 Vibrio cholerae Species 0.000 description 2
- 241000607272 Vibrio parahaemolyticus Species 0.000 description 2
- 241000607734 Yersinia <bacteria> Species 0.000 description 2
- 241000607447 Yersinia enterocolitica Species 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 150000005215 alkyl ethers Chemical class 0.000 description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- TUFYVOCKVJOUIR-UHFFFAOYSA-N alpha-Thujaplicin Natural products CC(C)C=1C=CC=CC(=O)C=1O TUFYVOCKVJOUIR-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000003945 anionic surfactant Substances 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229940065181 bacillus anthracis Drugs 0.000 description 2
- 239000003899 bactericide agent Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 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
- 235000013361 beverage Nutrition 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- 230000001013 cariogenic effect Effects 0.000 description 2
- ULDHMXUKGWMISQ-UHFFFAOYSA-N carvone Chemical compound CC(=C)C1CC=C(C)C(=O)C1 ULDHMXUKGWMISQ-UHFFFAOYSA-N 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000010630 cinnamon oil Substances 0.000 description 2
- QMVPMAAFGQKVCJ-UHFFFAOYSA-N citronellol Chemical compound OCCC(C)CCC=C(C)C QMVPMAAFGQKVCJ-UHFFFAOYSA-N 0.000 description 2
- JOZKFWLRHCDGJA-UHFFFAOYSA-N citronellol acetate Chemical compound CC(=O)OCCC(C)CCC=C(C)C JOZKFWLRHCDGJA-UHFFFAOYSA-N 0.000 description 2
- 239000012459 cleaning agent Substances 0.000 description 2
- 230000006854 communication Effects 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229940032049 enterococcus faecalis Drugs 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 235000013376 functional food Nutrition 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 201000005917 gastric ulcer Diseases 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 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
- 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 2
- 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 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 235000013402 health food Nutrition 0.000 description 2
- 239000000185 hemagglutinin Substances 0.000 description 2
- 108010037896 heparin-binding hemagglutinin Proteins 0.000 description 2
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 208000022760 infectious otitis media Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- NFIDBGJMFKNGGQ-UHFFFAOYSA-N isopropylmethylphenol Natural products CC(C)CC1=CC=CC=C1O NFIDBGJMFKNGGQ-UHFFFAOYSA-N 0.000 description 2
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 2
- 229940017800 lactobacillus casei Drugs 0.000 description 2
- 229940001882 lactobacillus reuteri Drugs 0.000 description 2
- 229940039717 lanolin Drugs 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 2
- CDOSHBSSFJOMGT-UHFFFAOYSA-N linalool Chemical compound CC(C)=CCCC(C)(O)C=C CDOSHBSSFJOMGT-UHFFFAOYSA-N 0.000 description 2
- 235000021056 liquid food Nutrition 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
- 235000010335 lysozyme Nutrition 0.000 description 2
- 229960000274 lysozyme Drugs 0.000 description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 229910000021 magnesium carbonate Inorganic materials 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
- 239000002207 metabolite Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000002453 shampoo Substances 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229960004711 sodium monofluorophosphate Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 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
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- 235000010384 tocopherol Nutrition 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 2
- 229960000401 tranexamic acid Drugs 0.000 description 2
- RUVINXPYWBROJD-ONEGZZNKSA-N trans-anethole Chemical compound COC1=CC=C(\C=C\C)C=C1 RUVINXPYWBROJD-ONEGZZNKSA-N 0.000 description 2
- 229960003500 triclosan Drugs 0.000 description 2
- 229940118696 vibrio cholerae Drugs 0.000 description 2
- 239000000304 virulence factor Substances 0.000 description 2
- 230000007923 virulence factor Effects 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 229940098232 yersinia enterocolitica Drugs 0.000 description 2
- OJYLAHXKWMRDGS-UHFFFAOYSA-N zingerone Chemical compound COC1=CC(CCC(C)=O)=CC=C1O OJYLAHXKWMRDGS-UHFFFAOYSA-N 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
- 229930007845 β-thujaplicin Natural products 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- 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
- 239000001490 (3R)-3,7-dimethylocta-1,6-dien-3-ol Substances 0.000 description 1
- QYIXCDOBOSTCEI-QCYZZNICSA-N (5alpha)-cholestan-3beta-ol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-QCYZZNICSA-N 0.000 description 1
- KRLBLPBPZSSIGH-CSKARUKUSA-N (6e)-3,7-dimethylnona-1,6-dien-3-ol Chemical compound CC\C(C)=C\CCC(C)(O)C=C KRLBLPBPZSSIGH-CSKARUKUSA-N 0.000 description 1
- QMVPMAAFGQKVCJ-SNVBAGLBSA-N (R)-(+)-citronellol Natural products OCC[C@H](C)CCC=C(C)C QMVPMAAFGQKVCJ-SNVBAGLBSA-N 0.000 description 1
- CDOSHBSSFJOMGT-JTQLQIEISA-N (R)-linalool Natural products CC(C)=CCC[C@@](C)(O)C=C CDOSHBSSFJOMGT-JTQLQIEISA-N 0.000 description 1
- WUOACPNHFRMFPN-SECBINFHSA-N (S)-(-)-alpha-terpineol Chemical compound CC1=CC[C@@H](C(C)(C)O)CC1 WUOACPNHFRMFPN-SECBINFHSA-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
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 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
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- ZBZWVGNHJHDIEH-UHFFFAOYSA-N 3-bromo-2-(4-methoxyphenyl)-2h-furan-5-one Chemical compound C1=CC(OC)=CC=C1C1C(Br)=CC(=O)O1 ZBZWVGNHJHDIEH-UHFFFAOYSA-N 0.000 description 1
- MYGRPRSFUHJZPY-UHFFFAOYSA-N 3-octyl-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(CCCCCCCC)OC(=O)C2=C1 MYGRPRSFUHJZPY-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000186045 Actinomyces naeslundii Species 0.000 description 1
- 108010083528 Adenylate Cyclase Toxin Proteins 0.000 description 1
- 241000607534 Aeromonas Species 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- 240000002234 Allium sativum Species 0.000 description 1
- 241001116389 Aloe Species 0.000 description 1
- 101710092462 Alpha-hemolysin Proteins 0.000 description 1
- 101710197219 Alpha-toxin Proteins 0.000 description 1
- 241001237961 Amanita rubescens Species 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004382 Amylase Substances 0.000 description 1
- 108010065511 Amylases Proteins 0.000 description 1
- 102000013142 Amylases Human genes 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 108091005658 Basic proteases Proteins 0.000 description 1
- 235000018185 Betula X alpestris Nutrition 0.000 description 1
- 235000018212 Betula X uliginosa Nutrition 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 108030001720 Bontoxilysin Proteins 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000589969 Borreliella burgdorferi Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108010059574 C5a peptidase Proteins 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000589875 Campylobacter jejuni Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000190890 Capnocytophaga Species 0.000 description 1
- 241000190882 Capnocytophaga sputigena Species 0.000 description 1
- 240000004160 Capsicum annuum Species 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- 239000005973 Carvone Substances 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- JOZKFWLRHCDGJA-LLVKDONJSA-N Citronellyl acetate Natural products CC(=O)OCC[C@H](C)CCC=C(C)C JOZKFWLRHCDGJA-LLVKDONJSA-N 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 241001112695 Clostridiales Species 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- FBUKMFOXMZRGRB-UHFFFAOYSA-N Coronaric acid Natural products CCCCCC=CCC1OC1CCCCCCCC(O)=O FBUKMFOXMZRGRB-UHFFFAOYSA-N 0.000 description 1
- 241000270722 Crocodylidae Species 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 241000192093 Deinococcus Species 0.000 description 1
- 241000192091 Deinococcus radiodurans Species 0.000 description 1
- 101710121036 Delta-hemolysin Proteins 0.000 description 1
- 108010001682 Dextranase Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 241000588877 Eikenella Species 0.000 description 1
- 241000588878 Eikenella corrodens Species 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 235000009008 Eriobotrya japonica Nutrition 0.000 description 1
- 244000061508 Eriobotrya japonica Species 0.000 description 1
- 241000588694 Erwinia amylovora Species 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- WEEGYLXZBRQIMU-UHFFFAOYSA-N Eucalyptol Chemical compound C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 1
- 239000005770 Eugenol Substances 0.000 description 1
- 101710205374 Extracellular elastase Proteins 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 235000009419 Fagopyrum esculentum Nutrition 0.000 description 1
- 240000008620 Fagopyrum esculentum Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 206010017914 Gastroenteritis salmonella Diseases 0.000 description 1
- 108010026132 Gelatinases Proteins 0.000 description 1
- 102000013382 Gelatinases Human genes 0.000 description 1
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920000569 Gum karaya Polymers 0.000 description 1
- 241000193004 Halobacillus Species 0.000 description 1
- 241001453258 Helicobacter hepaticus Species 0.000 description 1
- 101710179002 Hemolytic toxin Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 241000546188 Hypericum Species 0.000 description 1
- 235000017309 Hypericum perforatum Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- UCUNFLYVYCGDHP-BYPYZUCNSA-N L-methionine sulfone Chemical compound CS(=O)(=O)CC[C@H](N)C(O)=O UCUNFLYVYCGDHP-BYPYZUCNSA-N 0.000 description 1
- 235000019501 Lemon oil Nutrition 0.000 description 1
- 101710170970 Leukotoxin Proteins 0.000 description 1
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 1
- 101710164436 Listeriolysin O Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 244000280244 Luffa acutangula Species 0.000 description 1
- 235000009814 Luffa aegyptiaca Nutrition 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 240000000982 Malva neglecta Species 0.000 description 1
- 235000000060 Malva neglecta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101710085938 Matrix protein Proteins 0.000 description 1
- 101710127721 Membrane protein Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 101000783356 Naja sputatrix Cytotoxin Proteins 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000736199 Paeonia Species 0.000 description 1
- 235000006484 Paeonia officinalis Nutrition 0.000 description 1
- 241000606210 Parabacteroides distasonis Species 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
- 108010056995 Perforin Proteins 0.000 description 1
- 102000004503 Perforin Human genes 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 101000606032 Pomacea maculata Perivitellin-2 31 kDa subunit Proteins 0.000 description 1
- 101000606027 Pomacea maculata Perivitellin-2 67 kDa subunit Proteins 0.000 description 1
- 241000605894 Porphyromonas Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- HDSBZMRLPLPFLQ-UHFFFAOYSA-N Propylene glycol alginate Chemical compound OC1C(O)C(OC)OC(C(O)=O)C1OC1C(O)C(O)C(C)C(C(=O)OCC(C)O)O1 HDSBZMRLPLPFLQ-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241001138501 Salmonella enterica Species 0.000 description 1
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 description 1
- 241001647091 Saxifraga granulata Species 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010079723 Shiga Toxin Proteins 0.000 description 1
- 241000607766 Shigella boydii Species 0.000 description 1
- 241000607762 Shigella flexneri Species 0.000 description 1
- 108090000233 Signal peptidase II Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 241000736131 Sphingomonas Species 0.000 description 1
- 241000191963 Staphylococcus epidermidis Species 0.000 description 1
- 241000191984 Staphylococcus haemolyticus Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000934878 Sterculia Species 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[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 UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 101000815632 Streptococcus suis (strain 05ZYH33) Rqc2 homolog RqcH Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- 108010046334 Urease Proteins 0.000 description 1
- 241001148134 Veillonella Species 0.000 description 1
- 241001148135 Veillonella parvula Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000607594 Vibrio alginolyticus Species 0.000 description 1
- 241000544286 Vibrio anguillarum Species 0.000 description 1
- 241000607253 Vibrio mimicus Species 0.000 description 1
- 241000607265 Vibrio vulnificus Species 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 229910021536 Zeolite Inorganic materials 0.000 description 1
- OKSSKVHGKYJNLL-LJRZAWCWSA-N [(3as,4r,9s,10as)-2,6-diamino-10,10-dihydroxy-9-sulfooxy-3a,4,8,9-tetrahydro-1h-pyrrolo[1,2-c]purin-4-yl]methoxycarbonylsulfamic acid Chemical compound OS(=O)(=O)NC(=O)OC[C@@H]1N=C(N)N2C[C@H](OS(O)(=O)=O)C(O)(O)[C@@]22N=C(N)N[C@H]21 OKSSKVHGKYJNLL-LJRZAWCWSA-N 0.000 description 1
- JVOGSHDZLOJKKR-MXFMKSRJSA-I [Na+].[Na+].[Na+].[Mg++].CCc1c(C)c2cc3[n-]c(c(C)c3C=C)c(C)c3nc(C[C@H]3CCC([O-])=O)c(CC([O-])=O)c3[n-]c(cc1n2)c(C)c3C([O-])=O Chemical compound [Na+].[Na+].[Na+].[Mg++].CCc1c(C)c2cc3[n-]c(c(C)c3C=C)c(C)c3nc(C[C@H]3CCC([O-])=O)c(CC([O-])=O)c3[n-]c(cc1n2)c(C)c3C([O-])=O JVOGSHDZLOJKKR-MXFMKSRJSA-I 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910052891 actinolite Inorganic materials 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- 239000002776 alpha toxin Substances 0.000 description 1
- OVKDFILSBMEKLT-UHFFFAOYSA-N alpha-Terpineol Natural products CC(=C)C1(O)CCC(C)=CC1 OVKDFILSBMEKLT-UHFFFAOYSA-N 0.000 description 1
- QYIXCDOBOSTCEI-UHFFFAOYSA-N alpha-cholestanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 QYIXCDOBOSTCEI-UHFFFAOYSA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 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
- 229940088601 alpha-terpineol Drugs 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910000323 aluminium silicate Inorganic materials 0.000 description 1
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 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 description 1
- 235000019418 amylase Nutrition 0.000 description 1
- 229940011037 anethole Drugs 0.000 description 1
- LNTHITQWFMADLM-UHFFFAOYSA-N anhydrous gallic acid Natural products OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 1
- 239000010617 anise oil Substances 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 229960000271 arbutin Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 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
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 150000001545 azulenes Chemical class 0.000 description 1
- 239000003788 bath preparation Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229950004580 benzyl nicotinate Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- JGQFVRIQXUFPAH-UHFFFAOYSA-N beta-citronellol Natural products OCCC(C)CCCC(C)=C JGQFVRIQXUFPAH-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 229940116229 borneol Drugs 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 229940053031 botulinum toxin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 229940067596 butylparaben Drugs 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- JUNWLZAGQLJVLR-UHFFFAOYSA-J calcium diphosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O JUNWLZAGQLJVLR-UHFFFAOYSA-J 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229940043256 calcium pyrophosphate Drugs 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 238000000738 capillary electrophoresis-mass spectrometry Methods 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 229920003090 carboxymethyl hydroxyethyl cellulose Polymers 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000002340 cardiotoxin Substances 0.000 description 1
- 231100000677 cardiotoxin Toxicity 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 229930007050 cineol Natural products 0.000 description 1
- 229960005233 cineole Drugs 0.000 description 1
- DERZBLKQOCDDDZ-JLHYYAGUSA-N cinnarizine Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C\C=C\C1=CC=CC=C1 DERZBLKQOCDDDZ-JLHYYAGUSA-N 0.000 description 1
- 229960000876 cinnarizine Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 235000000484 citronellol Nutrition 0.000 description 1
- 239000010634 clove oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000013353 coffee beverage Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000002433 cyclopentenyl group Chemical class C1(=CCCC1)* 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 210000004268 dentin Anatomy 0.000 description 1
- LNNWVNGFPYWNQE-GMIGKAJZSA-N desomorphine Chemical compound C1C2=CC=C(O)C3=C2[C@]24CCN(C)[C@H]1[C@@H]2CCC[C@@H]4O3 LNNWVNGFPYWNQE-GMIGKAJZSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 description 1
- 235000019821 dicalcium diphosphate Nutrition 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229960003720 enoxolone Drugs 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
- 239000010642 eucalyptus oil Substances 0.000 description 1
- 229940044949 eucalyptus oil Drugs 0.000 description 1
- 229960002217 eugenol Drugs 0.000 description 1
- 108010000165 exo-1,3-alpha-glucanase Proteins 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 102000036072 fibronectin binding proteins Human genes 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 150000002241 furanones Chemical class 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 235000004515 gallic acid Nutrition 0.000 description 1
- 229940074391 gallic acid Drugs 0.000 description 1
- FODTZLFLDFKIQH-FSVGXZBPSA-N gamma-Oryzanol (TN) Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)O[C@@H]2C([C@@H]3CC[C@H]4[C@]5(C)CC[C@@H]([C@@]5(C)CC[C@@]54C[C@@]53CC2)[C@H](C)CCC=C(C)C)(C)C)=C1 FODTZLFLDFKIQH-FSVGXZBPSA-N 0.000 description 1
- 235000004611 garlic Nutrition 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000034659 glycolysis Effects 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
- 239000001685 glycyrrhizic acid Substances 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
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- 239000003676 hair preparation Substances 0.000 description 1
- 230000003806 hair structure Effects 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229960001545 hydrotalcite Drugs 0.000 description 1
- 229910001701 hydrotalcite Inorganic materials 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- VVIUBCNYACGLLV-UHFFFAOYSA-N hypotaurine Chemical compound [NH3+]CCS([O-])=O VVIUBCNYACGLLV-UHFFFAOYSA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052816 inorganic phosphate Inorganic materials 0.000 description 1
- 229960005436 inositol nicotinate Drugs 0.000 description 1
- 230000006859 interspecies communication Effects 0.000 description 1
- 238000005468 ion implantation Methods 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 235000010494 karaya gum Nutrition 0.000 description 1
- 239000000231 karaya gum Substances 0.000 description 1
- 229940039371 karaya gum Drugs 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 229940094522 laponite Drugs 0.000 description 1
- 239000010501 lemon oil Substances 0.000 description 1
- 235000001510 limonene Nutrition 0.000 description 1
- 229940087305 limonene Drugs 0.000 description 1
- 229930007744 linalool Natural products 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- XCOBTUNSZUJCDH-UHFFFAOYSA-B lithium magnesium sodium silicate Chemical compound [Li+].[Li+].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Na+].[Na+].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3 XCOBTUNSZUJCDH-UHFFFAOYSA-B 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 239000004137 magnesium phosphate Substances 0.000 description 1
- 229960002261 magnesium phosphate Drugs 0.000 description 1
- 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
- 235000010994 magnesium phosphates Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 239000001683 mentha spicata herb oil Substances 0.000 description 1
- 229940041616 menthol Drugs 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
- AHXDSVSZEZHDLV-UHFFFAOYSA-N mesulfen Chemical compound CC1=CC=C2SC3=CC(C)=CC=C3SC2=C1 AHXDSVSZEZHDLV-UHFFFAOYSA-N 0.000 description 1
- 229960005479 mesulfen Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229940116837 methyleugenol Drugs 0.000 description 1
- PRHTXAOWJQTLBO-UHFFFAOYSA-N methyleugenol Natural products COC1=CC=C(C(C)=C)C=C1OC PRHTXAOWJQTLBO-UHFFFAOYSA-N 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- MFZCIDXOLLEMOO-GYSGTQPESA-N myo-inositol hexanicotinate Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](OC(=O)C=2C=NC=CC=2)[C@@H](OC(=O)C=2C=NC=CC=2)[C@@H]1OC(=O)C=1C=NC=CC=1)OC(=O)C=1C=NC=CC=1)OC(=O)C=1C=NC=CC=1)C(=O)C1=CC=CN=C1 MFZCIDXOLLEMOO-GYSGTQPESA-N 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- FBUKVWPVBMHYJY-UHFFFAOYSA-M nonanoate Chemical compound CCCCCCCCC([O-])=O FBUKVWPVBMHYJY-UHFFFAOYSA-M 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 150000007823 ocimene derivatives Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 description 1
- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 description 1
- 235000015927 pasta Nutrition 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 108010007439 proline transporter Proteins 0.000 description 1
- 235000010409 propane-1,2-diol alginate Nutrition 0.000 description 1
- 239000000770 propane-1,2-diol alginate Substances 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
- 235000019419 proteases Nutrition 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 235000011962 puddings Nutrition 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000019685 rice crackers Nutrition 0.000 description 1
- 239000010668 rosemary oil Substances 0.000 description 1
- 229940058206 rosemary oil Drugs 0.000 description 1
- 229940109850 royal jelly Drugs 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 239000010670 sage oil Substances 0.000 description 1
- 229940058287 salicylic acid derivative anticestodals Drugs 0.000 description 1
- 150000003872 salicylic acid derivatives Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229940080237 sodium caseinate Drugs 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- AQMNWCRSESPIJM-UHFFFAOYSA-M sodium metaphosphate Chemical compound [Na+].[O-]P(=O)=O AQMNWCRSESPIJM-UHFFFAOYSA-M 0.000 description 1
- 229950005425 sodium myristyl sulfate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- UPUIQOIQVMNQAP-UHFFFAOYSA-M sodium;tetradecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCOS([O-])(=O)=O UPUIQOIQVMNQAP-UHFFFAOYSA-M 0.000 description 1
- 235000002316 solid fats Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 235000019721 spearmint oil Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940037649 staphylococcus haemolyticus Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- 235000019202 steviosides Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 108010075210 streptolysin O Proteins 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000001913 submandibular gland Anatomy 0.000 description 1
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
- 229960004291 sucralfate Drugs 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 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
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- SHWIJIJNPFXOFS-UHFFFAOYSA-N thiotaurine Chemical compound NCCS(O)(=O)=S SHWIJIJNPFXOFS-UHFFFAOYSA-N 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 150000003601 thymols Chemical class 0.000 description 1
- YUOWTJMRMWQJDA-UHFFFAOYSA-J tin(iv) fluoride Chemical compound [F-].[F-].[F-].[F-].[Sn+4] YUOWTJMRMWQJDA-UHFFFAOYSA-J 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 125000002640 tocopherol group Chemical class 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- XJPBRODHZKDRCB-UHFFFAOYSA-N trans-alpha-ocimene Natural products CC(=C)CCC=C(C)C=C XJPBRODHZKDRCB-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 230000004102 tricarboxylic acid cycle 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
- 238000000108 ultra-filtration Methods 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 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
- 239000009538 yokuinin Substances 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、オートインデューサー−2阻害剤、並びに齲蝕病の予防及び/又は治療剤に関する。 The present invention relates to an autoinducer-2 inhibitor and a preventive and / or therapeutic agent for caries disease.
自然界において、微生物は様々な環境下で生存しなければならない。貧栄養、低温度、高温、pH変化はもちろんのこと、生体内においては貪食細胞又は抗菌性液性因子(補体、抗体、リゾチーム等)が存在する環境での生存を余儀なくされる。このような状況下で、細菌は自らの存在環境の変化を敏感に感知する機構を獲得してきた。そのような機構の1つとして、微生物は特異的な情報伝達物質を介して環境における自らの密度を感知し、その密度に応じて自らの様々な生物活性を巧妙に制御していることが明らかとなっている。このような細胞間の情報伝達機構は、クオラムセンシングシステムと称される。 In nature, microorganisms must survive in various environments. In addition to oligotrophic, low temperature, high temperature, and pH change, living organisms are forced to survive in an environment where phagocytic cells or antibacterial humoral factors (complements, antibodies, lysozyme, etc.) are present. Under these circumstances, bacteria have acquired a mechanism for sensitively sensing changes in their environment. As one of such mechanisms, it is clear that microorganisms sense their own density in the environment through specific signaling substances and skillfully control their various biological activities according to their density. It has become. Such an information transmission mechanism between cells is called a quorum sensing system.
クオラムセンシングは、発光性海洋細菌であるビブリオ・フィシェリ及びビブリオ・ハーベイにおいて最初に報告された。しかし、最近では、多くの細菌における一般的な遺伝子調節機構であると認識されている。この現象により、細菌は、生物発光、スウォーミング、バイオフィルム形成、タンパク質分解酵素の産生、抗生物質の合成、遺伝子受容能の発達、プラスミド接合伝達、病原因子産生及び胞子形成などといった活動を一斉に行うことができる。 Quorum sensing was first reported in the luminescent marine bacteria Vibrio Fischeri and Vibrio Harvey. Recently, however, it has been recognized as a general gene regulatory mechanism in many bacteria. This phenomenon allows bacteria to perform activities such as bioluminescence, warming, biofilm formation, proteolytic enzyme production, antibiotic synthesis, gene acceptability development, plasmid conjugation transfer, virulence factor production and sporulation. Can be done.
クオラムセンシングシステムを有する細菌は、オートインデューサーと呼ばれるシグナル伝達分子を合成し、放出し、そのシグナル伝達分子に応答して、遺伝子発現を細胞密度の関数として制御する。これまで、アシルホモセリンラクトンがオートインデューサー−1として、4,5−ジヒドロキシ−2,3−ペンタンジオンがオートインデューサー−2として同定されている。 Bacteria with a quorum sensing system synthesize and release a signaling molecule called an autoinducer and respond to the signaling molecule to control gene expression as a function of cell density. So far, acyl homoserine lactone has been identified as autoinducer-1, and 4,5-dihydroxy-2,3-pentanedione as autoinducer-2.
ビブリオ属細菌、緑膿菌、セラチア、エンテロバクターなど臨床上重要な細菌がクオラムセンシングにオートインデューサー−1を利用することが報告されている。また、ビブリオ・ハーベイが、種内連絡には種特異性の高いオートインデューサー−1を利用し、種間連絡には種特異性の低いオートインデューサー−2を利用することが知られている。さらに最近の研究では、ある種の病原性細菌がオートインデューサー−2による種間でのクオラムセンシングにより、病原因子の産生を調節していることも示されている。このような病原性細菌としては、齲蝕原性菌であるストレプトコッカス・ミュータンス(Streptococcus mutans)、胃潰瘍及び胃ガンを惹起すると言われているヘリコバクター・ピロリ(Helicobacter pylori)、食中毒、ガス壊疽、出血性腸炎などの原因菌であるウェルシュ菌(Clostridium perfringens)等が挙げられる。従って、オートインデューサー−2を阻害する活性を有する物質が求められていた。 It has been reported that clinically important bacteria such as Vibrio bacteria, Pseudomonas aeruginosa, Serratia and Enterobacter use autoinducer-1 for quorum sensing. In addition, it is known that Vibrio Harvey uses autoinducer-1 with high species specificity for intra-species communication and uses autoinducer-2 with low species specificity for interspecies communication. . More recent studies have also shown that certain pathogenic bacteria regulate the production of virulence factors by quorum sensing between species with autoinducer-2. Such pathogenic bacteria include Streptococcus mutans , a cariogenic bacterium, Helicobacter pylori , which is said to cause gastric ulcer and gastric cancer, food poisoning, gas gangrene, hemorrhagic Examples include Clostridium perfringens, which is a causative bacterium such as enteritis. Therefore, a substance having an activity of inhibiting autoinducer-2 has been demanded.
オートインデューサー−2を阻害する物質としては、これまで、フラノン化合物、シクロペンテン化合物などが報告されている(例えば、特許文献1〜3参照)。 As substances that inhibit autoinducer-2, furanone compounds, cyclopentene compounds, and the like have been reported so far (see, for example, Patent Documents 1 to 3).
本発明は、オートインデューサー−2を阻害する活性を有し、感染症の予防及び治療等に有効な、オートインデューサー−2阻害剤の提供を課題とする。 An object of the present invention is to provide an autoinducer-2 inhibitor which has an activity of inhibiting autoinducer-2 and is effective for prevention and treatment of infectious diseases.
本発明者等は、上記課題に鑑み鋭意検討を行った。その結果、タウリン、フルクトース−6−リン酸、ヒポキサンチン及びクレアチン、並びにこれらの塩がオートインデューサー−2を阻害する活性を有するとともに、感染症に対して有効な化合物であることを見い出した。本発明はこの知見に基づいて完成するに至った。 The present inventors have conducted intensive studies in view of the above problems. As a result, it has been found that taurine, fructose-6-phosphate, hypoxanthine and creatine, and salts thereof have an activity of inhibiting autoinducer-2 and are effective compounds against infectious diseases. The present invention has been completed based on this finding.
本発明は、タウリン、フルクトース−6−リン酸、ヒポキサンチン及びクレアチン、並びにこれらの塩からなる群より選ばれる少なくとも1種を有効成分とするオートインデューサー−2阻害剤に関する。
また、本発明は、前記オートインデューサー−2阻害剤を含有してなる、医薬組成物、食品組成物、口腔用組成物又は化粧料組成物に関する。
また、本発明は、タウリン、フルクトース−6−リン酸、ヒポキサンチン及びクレアチン、並びにこれらの塩からなる群より選ばれる少なくとも1種を有効成分とする齲蝕病の予防及び/又は治療剤に関する。
The present invention relates to an autoinducer-2 inhibitor comprising as an active ingredient at least one selected from the group consisting of taurine, fructose-6-phosphate, hypoxanthine and creatine, and salts thereof.
The present invention also relates to a pharmaceutical composition, food composition, oral composition or cosmetic composition comprising the autoinducer-2 inhibitor.
The present invention also relates to a preventive and / or therapeutic agent for caries diseases comprising at least one selected from the group consisting of taurine, fructose-6-phosphate, hypoxanthine and creatine, and salts thereof as active ingredients.
本発明によれば、オートインデューサー−2を阻害する活性を有し、感染症の予防及び治療等に有効な、オートインデューサー−2阻害剤が提供される。 ADVANTAGE OF THE INVENTION According to this invention, the autoinducer-2 inhibitor which has the activity which inhibits autoinducer-2 and is effective in prevention, treatment, etc. of infectious disease is provided.
本発明に用いるタウリン(2−アミノエタンスルホン酸)、フルクトース−6−リン酸、ヒポキサンチン及びクレアチンは、広く一般に入手することができる。例えば、通常の合成方法により化学的に合成してもよいし、天然物から抽出してもよい。また、本発明では市販のものを用いてもよい。 Taurine (2-aminoethanesulfonic acid), fructose-6-phosphate, hypoxanthine and creatine used in the present invention are widely available. For example, it may be chemically synthesized by a normal synthesis method or extracted from a natural product. In the present invention, a commercially available product may be used.
タウリン、フルクトース−6−リン酸、ヒポキサンチン及びクレアチンの塩としては、薬学的に許容できる塩であれば特に制限されないが、例えば、酸付加塩及び塩基付加塩が挙げられる。酸付加塩としては、塩酸、硫酸、硝酸及びリン酸等の無機酸との塩、酢酸、リンゴ酸、コハク酸、酒石酸及びクエン酸等の有機酸との塩が挙げられる。塩基付加塩としては、ナトリウム及びカリウム等のアルカリ金属との塩、カルシウム及びマグネシウム等のアルカリ土類金属との塩、アンモニウム及びトリエチルアミン等のアミン類との塩が挙げられる。
本発明において、タウリンの塩としては、カリウム塩及び塩酸塩が好ましく、カリウム塩がより好ましい。フルクトース−6−リン酸の塩としては、ナトリウム塩及びカリウム塩が好ましく、ナトリウム塩がより好ましい。ヒポキサンチンの塩としては、ナトリウム塩が好ましい。クレアチンの塩としては、塩酸塩が好ましい。
The salt of taurine, fructose-6-phosphate, hypoxanthine and creatine is not particularly limited as long as it is a pharmaceutically acceptable salt, and examples thereof include acid addition salts and base addition salts. Examples of the acid addition salt include salts with inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid, and salts with organic acids such as acetic acid, malic acid, succinic acid, tartaric acid and citric acid. Base addition salts include salts with alkali metals such as sodium and potassium, salts with alkaline earth metals such as calcium and magnesium, and salts with amines such as ammonium and triethylamine.
In the present invention, as the taurine salt, potassium salt and hydrochloride are preferable, and potassium salt is more preferable. As a salt of fructose-6-phosphate, a sodium salt and a potassium salt are preferable, and a sodium salt is more preferable. As a salt of hypoxanthine, a sodium salt is preferable. The salt of creatine is preferably hydrochloride.
本発明のオートインデューサー−2阻害剤において、有効成分として、タウリン、フルクトース−6−リン酸、ヒポキサンチン及びクレアチン、並びにこれらの塩のうちいずれか1種を用いてもよいし、2種以上を用いてもよい。
さらに、前記有効成分のうち立体異性体(例えば、光学異性体)を有するものについては、立体異性体の混合物として用いてもよい。
In the autoinducer-2 inhibitor of the present invention, any one of taurine, fructose-6-phosphate, hypoxanthine and creatine, and salts thereof may be used as the active ingredient. May be used.
Further, among the active ingredients, those having stereoisomers (for example, optical isomers) may be used as a mixture of stereoisomers.
本発明において、前記有効成分を溶媒に溶解/分散させ、オートインデューサー−2阻害剤、並びに齲蝕病の予防及び/又は治療剤としてもよい。本発明で用いることができる溶媒としては特に制限はないが、水、エタノール、プロピレングリコール、ジメチルスルホキサイド等が挙げられ、水及びエタノールが好ましい。 In the present invention, the active ingredient may be dissolved / dispersed in a solvent to serve as an autoinducer-2 inhibitor and a preventive and / or therapeutic agent for caries disease. Although there is no restriction | limiting in particular as a solvent which can be used by this invention, Water, ethanol, propylene glycol, a dimethyl sulfoxide etc. are mentioned, Water and ethanol are preferable.
本発明におけるオートインデューサー−2(以下、「AI−2」ともいう)としては、細菌が産生するものでAI−2活性を有するものであれば特に制限はない。
本発明におけるAI−2の具体例としては、下記式で表される4,5−ジヒドロキシ−2,3−ペンタンジオン(本明細書において、DPDともいう)、及びDPDが有するAI−2活性と同等のAI−2活性を有する化合物が包含される。
The autoinducer-2 (hereinafter also referred to as “AI-2”) in the present invention is not particularly limited as long as it is produced by bacteria and has AI-2 activity.
Specific examples of AI-2 in the present invention include 4,5-dihydroxy-2,3-pentanedione (also referred to herein as DPD) represented by the following formula, and AI-2 activity possessed by DPD. Compounds having equivalent AI-2 activity are included.
前記DPDは、細菌のAI−2受容体と結合するときにボロンを取り込んで、フラノシルボレートジエステルに変換される。本発明におけるAI−2の別の具体例としては、前記フラノシルボレートジエステルが挙げられる。また、DPDはリン酸化されてリン酸化DPD(Phospho-DPD)となり、AI−2活性を発現することが知られている(例えば、Taga M.et al.,Mol.Microbiol.,42,p.777-793,2001参照)。本発明におけるAI−2は、リン酸化DPDも包含する。
前記フラノシルボレートジエステル及びPhospho-DPDの具体例を以下に示す。しかし、本発明はこれらに制限するものではない。
When DPD binds to the bacterial AI-2 receptor, it incorporates boron and is converted to furanosyl borate diester. Another specific example of AI-2 in the present invention is the furanosyl borate diester. It is also known that DPD is phosphorylated to become phosphorylated DPD (Phospho-DPD) and expresses AI-2 activity (see, for example, Taga M. et al., Mol. Microbiol., 42, p. 777-793, 2001). AI-2 in the present invention includes phosphorylated DPD.
Specific examples of the furanosyl borate diester and Phospho-DPD are shown below. However, the present invention is not limited to these.
本発明においてAI−2を阻害することは、AI−2がクオラムセンシングを介して細菌に及ぼす影響を阻害することをさし、AI−2活性を阻害すること、AI−2分解すること、AI−2のAI−2受容体への結合を阻害することなどが包含される。 Inhibiting AI-2 in the present invention refers to inhibiting the effect of AI-2 on bacteria via quorum sensing, inhibiting AI-2 activity, decomposing AI-2, Inhibiting the binding of AI-2 to the AI-2 receptor is included.
本発明においてAI−2活性は、AI−2がクオラムセンシングシステムを有する細菌に影響を及ぼす活性、すなわち、AI−2を介するクオラムセンシングによりもたらされる細菌の機能を促進する活性をさす。細菌は、AI−2を介するクオラムセンシングにより、発光、スウォーミング、バイオフィルム形成、タンパク質分解酵素の産生、抗生物質の合成、遺伝子受容能の発達、プラスミド接合伝達、病原因子産生及び胞子形成等を行うことが知られている。したがって、AI−2活性は、換言すれば、AI−2を認識する細菌、すなわちAI−2受容体を有する細菌による生物発光、スウォーミング、バイオフィルム形成、タンパク質分解酵素の産生、抗生物質の合成、遺伝子受容能の発達、プラスミド接合伝達、病原因子産生及び/又は胞子形成の活性ということができる。本発明においてAI−2活性は、特に、細菌の病原因子産生活性をさす。 In the present invention, AI-2 activity refers to an activity in which AI-2 affects bacteria having a quorum sensing system, that is, an activity that promotes the function of bacteria brought about by quorum sensing via AI-2. Bacteria can luminescence, warming, biofilm formation, proteolytic enzyme production, antibiotic synthesis, gene acceptability development, plasmid conjugation transfer, pathogenic factor production and spore formation by quorum sensing via AI-2 Etc. are known to perform. Thus, AI-2 activity is, in other words, bioluminescence, warming, biofilm formation, proteolytic enzyme production, antibiotic production by bacteria that recognize AI-2, ie, bacteria having an AI-2 receptor. It can be referred to as activity of synthesis, development of gene acceptability, plasmid conjugation transfer, pathogenic factor production and / or sporulation. In the present invention, AI-2 activity particularly refers to bacterial pathogen production activity.
前記病原因子としては、例えば、エンテロトキシン、アデニル酸シクラーゼ毒素、アドヘシン、アルカリプロテアーゼ、溶血毒、炭疽毒素、APX毒素、α毒素、β毒素、δ毒素、C2毒素、C3毒素、ボツリヌス毒素、束状線毛構造サブユニット、C5Aペプチダーゼ、心臓毒、走化性、コレラ毒素、毛様体毒素、クロストリジウム細胞毒、クロストリジウム神経毒、コラーゲン接着遺伝子、細胞溶解素、嘔吐毒素、内毒素、表皮剥脱毒素、外毒素、細胞外エラスターゼ、フィブリノゲン、フィブロネクチン結合タンパク質、線維状赤血球凝集素、フィンブリア、ゼラチナーゼ、赤血球凝集素、ロイコトキシン、リポタンパク質シグナルペプチダーゼ、リステリオリシンO、Mタンパク質、神経毒、非フィンブリアアドヘシン類、浮腫因子、透過酵素、百日咳毒素、ホスホリパーゼ、線毛、孔形成毒素、プロリンパーミアーゼ、セリンプロテアーゼ、志賀毒素、破傷風毒素、チオール活性化細胞溶解素、気管細胞溶解素、ウレアーゼなどが挙げられるが、本発明はこれらに制限されない。 Examples of the pathogenic factor include enterotoxin, adenylate cyclase toxin, adhesin, alkaline protease, hemolytic toxin, anthrax toxin, APX toxin, α toxin, β toxin, δ toxin, C2 toxin, C3 toxin, botulinum toxin, bundled line Hair structure subunit, C5A peptidase, cardiotoxin, chemotaxis, cholera toxin, ciliary toxin, clostridial cytotoxin, clostridial neurotoxin, collagen adhesion gene, cytolysin, vomiting toxin, endotoxin, exfoliating toxin, external Toxin, extracellular elastase, fibrinogen, fibronectin binding protein, fibrillar hemagglutinin, fimbria, gelatinase, hemagglutinin, leukotoxin, lipoprotein signal peptidase, listeriolysin O, M protein, neurotoxin, non-fimbria adhesin Edema factor, Examples include hyperenzyme, pertussis toxin, phospholipase, pili, pore forming toxin, proline permease, serine protease, Shiga toxin, tetanus toxin, thiol activated cytolysin, tracheal cell lysin, urease, etc. It is not limited to these.
本発明のAI−2阻害剤の有効成分で影響を及ぼすことができる細菌、換言すれば、本発明のAI−2阻害剤の有効成分で増殖・生育を抑制できる細菌は、AI−2によりその機能、例えば、生物発光、スウォーミング、バイオフィルム形成、タンパク質分解酵素の産生、抗生物質の合成、遺伝子受容能の発達、プラスミド接合伝達、病原因子産生及び胞子形成などが促進される細菌である。例えば、AI−2受容体を有する細菌、好ましくはAI−2受容体を有し、AI−2を産生する細菌を対象とすることができる。 Bacteria that can be affected by the active ingredient of the AI-2 inhibitor of the present invention, in other words, bacteria that can suppress the growth and growth of the active ingredient of the AI-2 inhibitor of the present invention are expressed by AI-2. Bacteria whose functions are promoted such as bioluminescence, warming, biofilm formation, proteolytic enzyme production, antibiotic synthesis, gene acceptability development, plasmid conjugation transfer, pathogenic factor production and sporulation . For example, a bacterium having an AI-2 receptor, preferably a bacterium having an AI-2 receptor and producing AI-2 can be used.
AI−2活性は、AI−2を認識することにより発光するレポーター細菌、好ましくはAI−2受容体及びルシフェラーゼを有する細菌を用いるバイオアッセイにより測定することができる(例えば、Keersmaecker S.C.J.et al.,J.Biol.Chem.,280(20),p.19563-19568,2005参照)。具体的には、ビブリオ・ハーベイ(Vibrio harveyi)BB170株をレポーター細菌とし、被検化合物の存在下で培養し、培養後の発光強度をケミルミネッセンス計などで測定することにより、AI−2活性を測定することができる。 AI-2 activity can be measured by a bioassay using a reporter bacterium that emits light by recognizing AI-2, preferably a bacterium having an AI-2 receptor and luciferase (eg, Keersmaecker S.C.J. Et al., J. Biol. Chem., 280 (20), p. 19563-19568, 2005). Specifically, Vibrio harveyi BB170 strain is used as a reporter bacterium, cultured in the presence of a test compound, and the luminescence intensity after the culture is measured with a chemiluminescence meter, etc. Can be measured.
AI−2を阻害することにより影響を及ぼす、又は増殖・生育を抑制することができる細菌としては、例えば、ビブリオ(Vibrio)属細菌、シュードモナス(Pseudomonas)属細菌、ポルフィロモナス(Porphyromonas)属細菌、エルシニア(Yersinia)属細菌、エシェリキア(Escherichia)属細菌、サルモネラ(Salmonella)属細菌、ヘモフィルス(Haemophilus)属細菌、ヘリコバクター(Helicobacter)属細菌、バシルス(Bacillus)属細菌、ボレリア(Borrelia)属細菌、ナイセリア(Neisseria)属細菌、カンピロバクター(Campylobacter)属細菌、デイノコックス(Deinococcus)属細菌、ミコバクテリウム(Mycobacterium)属細菌、エンテロコッカス(Enterococcus)属細菌、ストレプトコッカス(Streptococcus)属細菌、シゲラ(Shigella)属細菌、エロモナス(Aeromonas)属細菌、エイケネラ(Eikenella)属細菌、クロストリジウム(Clostridium)属細菌、スタフィロコッカス(Staphylococcus)属細菌、ラクトバチルス(Lactobacillus)属細菌、アクチノバチルス(Actinobacillus)属細菌、アクチノマイセス(Actinomyces)属細菌、バクテロイデス(Bacteroides)属細菌、カプノサイトファガ(Capnocytophaga)属細菌、クレブシエラ(Klebsiella)属細菌、ハロバチルス(Halobacillus)属細菌、フゾバクテリウム(Fusobacterium)属細菌、エルウィニア(Erwinia)属細菌、エルベネラ(Elbenella)属細菌、ラクトバチルス(Lactobacillus)属細菌、リステリア(Listeria)属細菌、マンヘイミア(Mannheimia)属細菌、ペプトコッカス(Peptococcus)属細菌、プレボテラ(Prevotella)属細菌、プロテウス(Proteus)属細菌、セラチア(Serratia)属細菌及びベイロネラ(Veillonella)属細菌などが挙げられる。より具体的には、ビブリオ・ハーベイ(Vibrio harveyi)、ビブリオ・フィシェリ(Vibrio fischeri)、コレラ菌(Vibrio cholerae)、腸炎ビブリオ(Vibrio parahaemolyticus)、ビブリオ・アルギノリチカス(Vibrio alginolyticus)、シュードモナス・ホスホレウム(Pseudomonas phosphoreum)、ポリフィロモナス・ジンジバリス(Porphyromonas gingivalis)、エルシニア・エンテロコリチカ(Yersinia enterocolitica)、大腸菌(Escherichia coli)、ネズミチフス菌(Salmonella typhimurium)、インフルエンザ菌(Haemophilus influenzae)、ヘリコバクター・ピロリ(Helicobacter pylori)、枯草菌(Bacillus subtilis)、ボレリア・ブルグドルフェリ(Borrelia burgfdorferi)、髄膜炎菌(Neisseria meningitidis)、淋菌(Neisseria gonorrhoeae)、ペスト菌(Yersinia pestis)、カンピロバクター・ジェジュニ(Campylobacter jejuni)、デイノコックス・ラジオデュランス(Deinococcus radiodurans)、結核菌(Mycobacterium tuberculosis)、エンテロコッカス・フェカリス(Enterococcus faecalis)、肺炎レンサ球菌(Streptococcus pneumoniae)、化膿レンサ球菌(Streptococcus pyogenes)、ストレプトコッカス・ミュータンス(Streptococcus mutans)、黄色ブドウ球菌(Staphylococcus aureus)、箕田赤痢菌(Shigella flexneri)、シゲラ・ボイデイ(Shigella boydii)、セレウス菌(Bacillus cereus)、バチルス・クブチリス(Bacillus cubtilis)、エロモナス・ハイドロフィラ(Aeromonas hydrophila)、チフス菌(Salmonella enterica)、エイケネラ・コロデンス(Eikenella corrodens)、ヘリコバクター・ヘパティカス(Helicobacter hepaticus)、ウェルシュ菌(Clostridium perfringens)、スタフィロコッカス・ハエモリティカス(Staphylococcus haemolyticus)、ラクトバチルス・ガセリ(Lactobacillus gasseri)、ラクトバチルス アシドフィラス(Lactobacillus acidophilus)、ラクトバチルス・ロイテリ(Lactobacillus reuteri)、ラクトバチルス・サリバリウス(Lactobacillus salivarius)、ラクトバチルス・カゼイ(Lactobacillus casei)、ストレプトコッカス・サンギニス(Streptococcus sanguinis)、ストレプトコッカス・アンギノーサス(Streptococcus anginosus)、ストレプトコッカス・オラリス(Streptococcus oralis)、ストレプトコッカス・ボビス(Streptococcus bovis)、ストレプトコッカス・ゴルドニ(Streptococcus gordonii)、ストレプトコッカス・ミティス(Streptococcus mitis)、アクチノバチルス・アクチノマイセテムコミタンス(Actinobacillus actinomycetemcomitans)、ビブリオ・ブルニフィカス(Vivrio vulnificus)、ビブリオ・ミミクス(Vibrio mimicus)、ビブリオ・アングイラルム(Vibrio anguillarum)、ラクトバチルス・ラムノサス(Lactobacillus rhamnosus)、エルウィニア・アミロボラ(Erwinia amylovora)、エルウィニア・カロトバラ(Erwinia carotovara)、ハロバチルス・ハロフィラス(Halabacilus halophilus)、セラチア・ピムチカ(Serratia pymuthica)、セラチア・マルセセンス(Serratia marcescens)、バクテロイデス・フラジリス(Bacteroides fragilis)、バクテロイデス・ブルガタス(Bacteroides vulgatus)、バクテロイデス・ディスタソニス(Bacteroides distasonis)、リステリア・モノサイトジェネス(Listeria monocytogenes)、スタフィロコッカス・エピデルミディス(Staphylococcus epidermidis)、クロストリジウム・ディフィシル(Clostridium difficile)、アエロモナス・ハイドロフィリア(Aeromonas hydrophilia)、マンヘイミア・ハエモライティカ(Mannhemia haemolytica)、クレブシエラ・ニューモニアエ(Klebsiella pneumoniae)、バチルス・アンスラシス(Bacillus anthracis)、カンピロバクター・コリ(Campylobacter coli)、カンピロバクター・レクタス(Campylobacter rectus)、プロテウス・ミラビリス(Proteus mirabilis)、アクチノマイセス・ナエスランディ(Actinomyces naeslundii)、ペプトコッカス・アナエロビウス(Peptococcus anaerobius)、フゾバクテリウム・ヌクレアタム(Fusobacterium nucleatum)、ベイロネラ・パルラ(Veillonella parvula)、カプノサイトファガ・スプティゲナ(Capnocytophaga sputigena)及びプレボテラ・インタメディア(Prevotella intermedia)などが挙げられる。 Examples of bacteria that can be affected by inhibiting AI-2 or that can suppress proliferation and growth include bacteria belonging to the genus Vibrio, bacteria belonging to the genus Pseudomonas, bacteria belonging to the genus Porphyromonas. , Yersinia (Yersinia) bacteria, Escherichia (Escherichia) bacteria, Salmonella (Salmonella) bacteria, Haemophilus (Haemophilus) bacteria, Helicobacter (Helicobacter) bacteria, Bacillus (Bacillus) bacteria, Borrelia (Borrelia) bacteria, Neisseria (Neisseria) bacteria belonging to the genus Campylobacter (Campylobacter) bacteria belonging to the genus, Day Roh Cox (Deinococcus) bacteria belonging to the genus Mycobacterium (Mycobacterium) bacteria belonging to the genus Enterococcus (Enterococcus) bacteria belonging to the genus Streptococcus (Streptococcus) bacteria belonging to the genus Shigella (Shigella) genus Bacteria, Aeromonas ( Ae romonas) bacteria belonging to the genus, Eikenera (Eikenella) bacteria belonging to the genus Clostridium (Clostridium) bacteria, Staphylococcus (Staphylococcus) bacteria belonging to the genus Lactobacillus (Lactobacillus) bacteria belonging to the genus Actinobacillus (Actinobacillus) bacteria belonging to the genus Actinomyces (Actinomyces) bacteria belonging to the genus Bacteroides (Bacteroides) bacteria belonging to the genus, Cap Roh site file moth (Capnocytophaga) bacteria belonging to the genus Klebsiella (Klebsiella) bacteria belonging to the genus, Harobachirusu (Halobacillus) bacteria, Fusobacterium (Fusobacterium) bacteria belonging to the genus Erwinia (Erwinia) bacteria belonging to the genus, Erubenera (Elbenella) bacteria belonging to the genus Lactobacillus (Lactobacillus) bacteria belonging to the genus Listeria (Listeria) bacteria belonging to the genus Mannheimia (Mannheimia) bacteria belonging to the genus, Peputokokkasu (Peptococcus) bacteria belonging to the genus Prevotella (Prevotella) bacteria belonging to the genus, Proteus (Proteus) bacteria belonging to the genus, Serachi Examples include bacteria of the genus Serratia and bacteria of the genus Veillonella. More specifically, Vibrio harveyi (Vibrio harveyi), Vibrio fischeri (Vibrio fischeri), cholera (Vibrio cholerae), Vibrio parahaemolyticus (Vibrio parahaemolyticus), Vibrio Aruginorichikasu (Vibrio alginolyticus), Pseudomonas Hosuhoreumu (Pseudomonas phosphoreum ), poly Philo Sphingomonas gingivalis (Porphyromonas gingivalis), Yersinia enterocolitica (Yersinia enterocolitica), E. (Escherichia coli), Salmonella typhimurium (Salmonella typhimurium), Haemophilus influenzae (Haemophilus influenzae), Helicobacter pylori (Helicobacter pylori), Bacillus subtilis (Bacillus subtilis), Borrelia burgdorferi (Borrelia burgfdorferi), meningococcal (Neisseria meningitidis), Neisseria gonorrhoeae (Neisseria gonorrhoeae), Yersinia pestis (Yersinia pestis), Campylobacter Jeji Two (Campylobacter jejuni), Day Roh Cox radiodurans (Deinococcus radiodurans), Mycobacterium tuberculosis (Mycobacterium tuberculosis), Enterococcus faecalis (Enterococcus faecalis), Streptococcus pneumoniae (Streptococcus pneumoniae), Streptococcus pyogenes (Streptococcus pyogenes), Streptococcus mu chest (Streptococcus mutans), Staphylococcus aureus (Staphylococcus aureus), Mita Shigella (Shigella flexneri), Shigella Boidei (Shigella boydii), Bacillus cereus (Bacillus cereus), Bacillus Kubuchirisu (Bacillus cubtilis), Aeromonas hydrophila ( Aeromonas hydrophila), Salmonella typhi (Salmonella enterica), Eikenera-Korodensu (Eikenella corrodens), Helicobacter Hepatikasu (Helicobacter hepaticus), Clostridium perfringens (Clostridium perfringens), staphylococcal · Haemoritikasu (Staphylococcus haemolyticus), Lactobacillus gasseri (Lactobacillus gasseri), Lactobacillus acidophilus (Lactobacillus acidophilus), Lactobacillus reuteri (Lactobacillus reuteri), Lactobacillus salivarius (Lactobacillus salivarius), Lactobacillus casei (Lactobacillus casei) , Streptococcus Sanginisu (Streptococcus sanguinis), Streptococcus anginosus (Streptococcus anginosus), Streptococcus oralis (Streptococcus oralis), Streptococcus bovis (Streptococcus bovis), Streptococcus Gorudoni (Streptococcus gordonii), Streptococcus mitis (Streptococcus mitis), actinolite Bacillus actinomycetemcomitans (Actinobacillus actinomycetemcomitans), Vibrio Vulnificus (Vivrio vulnificus), Vibrio Mimikusu (Vibrio mimicus), Vibrio Anguirarumu (Vibrio anguillarum), Lactobacillus rhamnosus (Lactobacillus rhamnosus), Erwinia Amirobora (Erwinia amylovora), Erwinia Karotobara (Erwinia carotovara), Harobachirusu-halophilus (Halabacilus halophilus), Serratia Pimuchika (Serratia pymuthica), Serratia marcescens (Serratia marcescens), Bacteroides fragilis (Bacteroides fragilis), Bacteroides vulgatus (Bacteroides vulgatus), Bacteroides Disutasonisu (Bacteroides distasonis), Listeria monocytogenes ( Listeria monocytogenes ), Staphylococcus epidermidis , Clostridium difficile ( Clo stridium difficile), Aeromonas hydrophila Philia (Aeromonas hydrophilia), Mannheimia Haemoraitika (Mannhemia haemolytica), Klebsiella pneumoniae (Klebsiella pneumoniae), Bacillus anthracis (Bacillus anthracis), Campylobacter coli (Campylobacter coli), Campylobacter rectus (Campylobacter rectus), Proteus mirabilis (Proteus mirabilis), Actinomyces Naesurandi (Actinomyces naeslundii), Peputokokkasu-Anaerobiusu (Peptococcus anaerobius), Fusobacterium nucleatum (Fusobacterium nucleatum), Beironera-Parla (Veillonella parvula), Cap Roh site file like moth-Suputigena (Capnocytophaga sputigena) and Prevotella inter media (Prevotella intermedia).
本発明のAI−2阻害剤の有効成分は、ストレプトコッカス・ミュータンス、ポリフィロモナス・ジンジバリス、ストレプトコッカス・オラリス、ストレプトコッカス・ゴルドニ、ストレプトコッカス・サングイニス、ストレプトコッカス・ミティス、アクチノマイセス・ナエスランディ、ペプトコッカス・アナエロビウス、アクチノバチルス・アクチノマイセテムコミタンス、フゾバクテリウム・ヌクレアタム、ベイロネラ・パルラ、カプノサイトファガ・スプティゲナ、プレボテラ・インタメディア及びラクトバチルス・サリバリウスなどに対するAI−2の阻害に対し、特に好ましく用いられる。 The active ingredients of the AI-2 inhibitor of the present invention include Streptococcus mutans, Polyphyromonas gingivalis, Streptococcus oralis, Streptococcus gordonii, Streptococcus sanguinis, Streptococcus mitis, Actinomyces naeslandi, Peptococcus anaerodia In particular, it is preferably used for the inhibition of AI-2 against Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Beironella parla, Capnocytofaga sputigena, Prevotella intermedia, Lactobacillus salivaius and the like.
生体内において、AI−2量とある種の感染症の症状とが相関関係を有し、本発明のAI−2阻害剤の有効成分を投与することにより齲蝕病等の感染症の症状を低減できる。したがって、一実施形態において本発明は、タウリン、フルクトース−6−リン酸、ヒポキサンチン及びクレアチン、並びにこれらの塩からなる群より選ばれる少なくとも1種を有効成分とする、齲蝕病の予防及び/又は治療剤に関する。さらに、本発明のAI−2阻害剤は、齲蝕病等の感染症の予防及び/又は治療剤として用いることができる。さらには、本発明のAI−2阻害剤は、齲蝕病等の感染症の予防及び/又は治療剤などに含有させることができる。 In vivo, the amount of AI-2 is correlated with the symptoms of certain infectious diseases, and by administering the active ingredient of the AI-2 inhibitor of the present invention, the symptoms of infectious diseases such as caries disease are reduced. it can. Therefore, in one embodiment, the present invention relates to the prevention and / or caries disease comprising, as an active ingredient, at least one selected from the group consisting of taurine, fructose-6-phosphate, hypoxanthine and creatine, and salts thereof. It relates to a therapeutic agent. Furthermore, the AI-2 inhibitor of the present invention can be used as a preventive and / or therapeutic agent for infectious diseases such as caries diseases. Furthermore, the AI-2 inhibitor of the present invention can be contained in a preventive and / or therapeutic agent for infectious diseases such as caries diseases.
本発明のAI−2阻害剤の有効成分を投与することにより予防及び/又は治療することができる感染症は、AI−2を阻害することにより予防及び/又は治療することができる感染症であり、換言すれば、AI−2を利用するクオラムセンシングシステムを有する細菌、具体的にはAI−2を阻害することにより影響を及ぼすことができる上記のような細菌に関連する感染症である。 The infectious disease that can be prevented and / or treated by administering the active ingredient of the AI-2 inhibitor of the present invention is an infectious disease that can be prevented and / or treated by inhibiting AI-2. In other words, it is a bacterium having a quorum sensing system utilizing AI-2, specifically an infectious disease related to the above-mentioned bacterium that can be affected by inhibiting AI-2.
前記有効成分を投与することにより予防及び/又は治療することができる感染症の具体例として、口腔、皮膚、膣、消化(GI)管、食道及び気道等における感染症が挙げられる。より具体的には、ストレプトコッカス・ミュータンス等により引き起こされる齲蝕病;ポルフィロモナス・ジンジバリス等により引き起こされる歯肉炎、歯骨炎等の歯周病;日和見生物により引き起こされる日和見感染症;肺炎レンサ球菌及びインフルエンザ菌等により引き起こされる急性中耳炎(AOM)及び滲出性中耳炎(OME);インフルエンザ菌により引き起こされるインフルエンザ;ヘリコバクター・ピロリにより引き起こされる十二指腸潰瘍、胃ガン及び胃潰瘍;コレラ菌により引き起こされるコレラ;ペスト菌により引き起こされるペスト;髄膜炎菌により引き起こされる髄膜炎;ネズミチフス菌などのサルモネラ属細菌により引き起こされるサルモネラ中毒;ウェルシュ菌により引き起こされる食中毒、ガス壊疽及び出血性腸炎;及び大腸菌等により引き起こされる下痢症などが挙げられる(後述の実施例、並びに特開2009−114120号公報;Yoshida A.et al.,Appl.Environ.Microbiol.,71(5),p.2372-2380,2005;Wen Z.T.et al.,J.Bacteriol.,189(9),p.2682-2691,2004;Osaki T. et al.,J.Med.Microbiol.,55(Pt11),p.1477-1485,2006;及びOhtani K.et al.,Mol.Microbiol.,44(1),p.171-179,2002等参照)。 Specific examples of infectious diseases that can be prevented and / or treated by administering the active ingredient include infectious diseases in the oral cavity, skin, vagina, digestive (GI) tract, esophagus and respiratory tract. More specifically, caries caused by Streptococcus mutans, etc .; periodontal diseases such as gingivitis and gingivitis caused by Porphyromonas gingivalis, etc .; opportunistic infections caused by opportunistic organisms; Streptococcus pneumoniae Acute otitis media (AOM) and exudative otitis media (OME) caused by Haemophilus influenzae, etc .; influenza caused by Haemophilus influenzae; duodenal ulcer, gastric cancer and gastric ulcer caused by Helicobacter pylori; cholera caused by Vibrio cholerae; Plague caused by Neisseria meningitidis; Salmonella poisoning caused by Salmonella bacteria such as Salmonella typhimurium; Food poisoning, gas gangrene and bleeding caused by Clostridium perfringens Enteritis; and diarrhea caused by Escherichia coli and the like (Examples described later, and JP 2009-114120 A; Yoshida A. et al., Appl. Environ. Microbiol., 71 (5), p. Wen Z. T. et al., J. Bacteriol., 189 (9), p. 2682-2691, 2004; Osaki T. et al., J. Med. Microbiol., 55 (Pt11 ), P. 1477-1485, 2006; and Ohtani K. et al., Mol., Microbiol., 44 (1), p. 171-179, 2002, etc.).
本明細書において感染症の予防には、感染症の発症を抑えること及び遅延させることが含まれ、感染症になる前の予防だけではなく、治療後の感染症の再発に対する予防も含まれる。本明細書において感染症の治療には、感染症を治癒すること、症状を改善すること及び症状の進行を抑えることが包含される。 In the present specification, prevention of infectious diseases includes suppressing and delaying the onset of infectious diseases, and includes not only prevention before infectious diseases but also prevention of recurrence of infectious diseases after treatment. In the present specification, treatment of an infectious disease includes curing an infectious disease, ameliorating symptoms, and suppressing progression of symptoms.
本発明のAI−2阻害剤、並びに前記感染症の予防及び/又は治療剤の投与対象は、好ましくは哺乳動物である。本明細書において哺乳動物は、温血脊椎動物をさし、例えば、ヒト及びサルなどの霊長類、マウス、ラット及びウサギなどの齧歯類、イヌ及びネコなどの愛玩動物、並びにウシ、ウマ及びブタなどの家畜が挙げられる。本発明のAI−2阻害剤、並びに前記感染症の予防及び/又は治療剤は、霊長類、特にヒトへの投与に好適である。感染症に罹患しているヒト、感染症と診断されているヒト、感染症に罹患する可能性があるヒト、感染症を予防する必要があるヒトに投与することが特に好ましい。 The subject of administration of the AI-2 inhibitor of the present invention and the preventive and / or therapeutic agent for the infectious disease is preferably a mammal. As used herein, mammals refer to warm-blooded vertebrates, such as primates such as humans and monkeys, rodents such as mice, rats and rabbits, companion animals such as dogs and cats, and cattle, horses and Examples include livestock such as pigs. The AI-2 inhibitor of the present invention and the preventive and / or therapeutic agent for the infectious disease are suitable for administration to primates, particularly humans. It is particularly preferred to administer to a human suffering from an infectious disease, a human being diagnosed with an infectious disease, a human being likely to suffer from an infectious disease, or a human in need of preventing the infectious disease.
本発明のAI−2阻害剤、並びに前記感染症の予防及び/又は治療剤の形態は特に制限されないが、例えば、医薬組成物、食品組成物、口腔用組成物若しくは化粧料組成物とするか、又はこれらに含有させることができる。 The form of the AI-2 inhibitor of the present invention and the preventive and / or therapeutic agent for the infectious disease is not particularly limited. For example, is it a pharmaceutical composition, a food composition, an oral composition, or a cosmetic composition? Or can be contained in these.
医薬組成物を調製する場合は、通常、前記有効成分と好ましくは薬学的に許容される担体を含む製剤として調製する。薬学的に許容される担体とは、一般的に、前記有効成分とは反応しない、不活性の、無毒の、固体又は液体の、増量剤、希釈剤又はカプセル化材料等をいい、例えば、水、エタノール、ポリオール(例えば、グリセロール、プロピレングリコール、液体ポリエチレングリコールなど)、適切なそれらの混合物、植物性油などの溶媒又は分散媒体などが挙げられる。 When preparing a pharmaceutical composition, it is usually prepared as a preparation containing the active ingredient and preferably a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier generally refers to an inert, non-toxic, solid or liquid, bulking agent, diluent or encapsulating material that does not react with the active ingredient, eg, water. , Ethanol, polyol (eg, glycerol, propylene glycol, liquid polyethylene glycol, etc.), suitable mixtures thereof, solvents or dispersion media such as vegetable oils, and the like.
医薬組成物は、経口により、非経口により、例えば、皮膚に、皮下に、粘膜に、静脈内に、動脈内に、筋肉内に、腹腔内に、膣内に、肺に、脳内に、眼に、及び鼻腔内に投与される。経口投与製剤としては、錠剤、顆粒剤、細粒剤、散剤、カプセル剤、チュアブル剤、ペレット剤、シロップ剤、液剤、懸濁剤及び吸入剤などが挙げられる。非経口投与製剤としては、坐剤、保持型浣腸剤、点滴剤、点眼剤、点鼻剤、ペッサリー剤、注射剤、口腔洗浄剤並びに軟膏、クリーム剤、ゲル剤、制御放出パッチ剤及び貼付剤などの皮膚外用剤などが挙げられる。本発明の医薬組成物は、徐放性皮下インプラントの形態で、又は標的送達系(例えば、モノクローナル抗体、ベクター送達、イオン注入、ポリマーマトリックス、リポソーム及びミクロスフェア)の形態で、非経口で投与してもよい。 The pharmaceutical composition can be administered orally, parenterally, e.g., into the skin, subcutaneously, mucosal, intravenously, intraarterially, intramuscularly, intraperitoneally, intravaginally, into the lungs, into the brain, Administered to the eye and intranasally. Examples of the preparation for oral administration include tablets, granules, fine granules, powders, capsules, chewables, pellets, syrups, solutions, suspensions and inhalants. As parenteral preparations, suppositories, retention enemas, drops, eye drops, nasal drops, pessaries, injections, mouth washes, ointments, creams, gels, controlled release patches and patches Skin external preparations, and the like. The pharmaceutical compositions of the invention are administered parenterally in the form of sustained-release subcutaneous implants or in the form of targeted delivery systems (eg, monoclonal antibodies, vector delivery, ion implantation, polymer matrices, liposomes and microspheres). May be.
医薬組成物はさらに医薬分野において慣用の添加剤を含んでいてもよい。そのような添加剤には、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、抗酸化剤、着色剤、矯味剤などがあり、必要に応じて使用できる。長時間作用できるように徐放化するためには、既知の遅延剤等でコーティングすることもできる。賦形剤としては、例えば、カルボキシメチルセルロースナトリウム、寒天、軽質無水ケイ酸、ゼラチン、結晶セルロース、ソルビトール、タルク、デキストリン、デンプン、乳糖、白糖、ブドウ糖、マンニトール、メタ珪酸アルミン酸マグネシウム、リン酸水素カルシウム等が使用できる。結合剤としては、例えば、アラビアゴム、アルギン酸ナトリウム、エタノール、エチルセルロース、カゼインナトリウム、カルボキシメチルセルロースナトリウム、寒天、精製水、ゼラチン、デンプン、トラガント、乳糖、ヒドロキシセルロース、ヒドロキシメチルセルロース、ヒドロキシプロピルセルロース、ポリビニルピロリドン等が挙げられる。崩壊剤としては、例えば、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、カルボキシメチルセルロースカルシウム、結晶セルロース、デンプン、ヒドロキシプロピルスターチ等が挙げられる。滑沢剤としては、例えば、ステアリン酸、ステアリン酸カルシウム、ステアリン酸マグネシウム、タルク、硬化油、ショ糖脂肪酸エステル、ロウ類等が挙げられる。抗酸化剤としては、トコフェロール、没食子酸エステル、ジブチルヒドロキシトルエン(BHT)、ブチルヒドロキシアニソール(BHA)、アスコルビン酸等が挙げられる。必要に応じてその他の添加剤や薬剤、例えば制酸剤(炭酸水素ナトリウム、炭酸マグネシウム、沈降炭酸カルシウム、合成ヒドロタルサイト等)、胃粘膜保護剤(合成ケイ酸アルミニウム、スクラルファート、銅クロロフィリンナトリウム等)を加えてもよい。 The pharmaceutical composition may further contain additives conventionally used in the pharmaceutical field. Such additives include, for example, excipients, binders, disintegrants, lubricants, antioxidants, colorants, flavoring agents, and the like, and can be used as necessary. In order to achieve sustained release so that it can act for a long time, it can also be coated with a known retarder or the like. Examples of excipients include sodium carboxymethylcellulose, agar, light anhydrous silicic acid, gelatin, crystalline cellulose, sorbitol, talc, dextrin, starch, lactose, sucrose, glucose, mannitol, magnesium aluminate metasilicate, calcium hydrogen phosphate Etc. can be used. Examples of the binder include gum arabic, sodium alginate, ethanol, ethyl cellulose, sodium caseinate, sodium carboxymethyl cellulose, agar, purified water, gelatin, starch, tragacanth, lactose, hydroxycellulose, hydroxymethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, etc. Is mentioned. Examples of the disintegrant include carboxymethyl cellulose, carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, crystalline cellulose, starch, hydroxypropyl starch and the like. Examples of the lubricant include stearic acid, calcium stearate, magnesium stearate, talc, hydrogenated oil, sucrose fatty acid ester, waxes and the like. Examples of the antioxidant include tocopherol, gallic acid ester, dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), ascorbic acid and the like. Other additives and drugs as required, such as antacids (sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate, synthetic hydrotalcite, etc.), gastric mucosa protective agents (synthetic aluminum silicate, sucralfate, copper chlorophyllin sodium, etc.) ) May be added.
口腔用組成物には、前記有効成分のほか、その形態に応じて種々の成分を配合することができる。配合可能な成分として、例えば研磨剤、湿潤剤、粘結剤、歯質強化剤、殺菌剤、pH調整剤、酵素類、抗炎症剤・血行促進剤、甘味剤、防腐剤、着色剤・色素類、香料等を適宜使用することができる。
口腔用組成物に配合することができる成分としては、具体的に、第2リン酸カルシウム、第3リン酸カルシウム、ピロリン酸カルシウム、リン酸マグネシウム、不溶性メタリン酸ナトリウム、無水ケイ酸、水酸化アルミニウム、アルミナ、ハイドロキシアパタイト、炭酸カルシウム、炭酸マグネシウム、硫酸カルシウム、ゼオライト、合成アルミノケイ酸塩、ベンガラ等の研磨剤;前記の研磨剤を結合剤を用いて造粒した顆粒状研磨剤;グリセリン、プロピレングリコール、1,3−ブチレングリコール、エチレングリコール、ポリエチレングリコール、ポリプロピレングリコール、エリスリトール、キシリトール、ソルビトール、マルチトール等の湿潤剤;カルボキシメチルセルロース及びその塩類、メチルセルロース、ヒドロキシエチルセルロース、カラギーナン、ポリアクリル酸ナトリウム、ヒドロキシプロピルセルロース、カルボキシメチルヒドロキシエチルセルロースナトリウム、アルギン酸ナトリウム、アルギン酸プロピレングリコールエステル、キサンタンガム、トラガカントガム、カラヤガム、アラビヤガム、ポリビニルアルコール、ポリビニルピロリドン、ビーガム、ラポナイト等の粘結剤;モノフルオルリン酸ナトリウム、フッ化スズ、フッ化ナトリウム等の歯質強化剤;クロルヘキシジン及びその塩類、トリクロサン、塩化セチルピリジニウム、チモール類、塩化ベンザルコニウム等の殺菌剤;リン酸ナトリウム等のpH調整剤;デキストラナーゼ、アミラーゼ、プロテアーゼ、リゾチーム、ムタナーゼ等の酵素類;塩化ナトリウム、ヒノキチオール、ε−アミノカプロン酸、トラネキサム酸、アラントイン類、トコフェロール類、オクチルフタリド、ニコチン酸エステル類、ジヒドロコレステロール、グリチルレチン酸、グリチルリチン酸及びその塩類、グリセロホスフェート、クロロフィル、水溶性無機リン酸化合物、アズレン類、カミツレ、センブリ、当帰、センキュウ、生薬類等の抗炎症剤・血行促進剤;サッカリンナトリウム、ステビオサイド、タウマチン、アスパラチルフェニルアラニンメチルエステル等の甘味剤;p−ヒドロキシ安息香酸、p−ヒドロキシ安息香酸エチル、p−ヒドロキシ安息香酸プロピル、p−ヒドロキシ安息香酸ブチル、安息香酸ナトリウム等の防腐剤;二酸化チタン等の着色剤・色素類;ペパーミント油、スペアミント油、メントール、カルボン、アネトール、オイゲノール、サリチル酸メチル、リモネン、オシメン、n−デシルアルコール、シトロネロール、α−テルピネオール、メチルアセテート、シトロネリルアセテート、メチルオイゲノール、シネオール、リナロール、エチルリナロール、ワニリン、チモール、アニス油、レモン油、オレンジ油、セージ油、ローズマリー油、桂皮油、ピメント油、桂葉油、冬緑油、丁子油、ユーカリ油等の香料等が挙げられる。
In addition to the active ingredient, various components can be blended in the oral composition depending on the form. Ingredients that can be incorporated include, for example, abrasives, wetting agents, binders, dentin enhancers, bactericides, pH adjusters, enzymes, anti-inflammatory agents / blood circulation promoters, sweeteners, preservatives, colorants / pigments , Fragrances and the like can be used as appropriate.
Specific components that can be blended in the oral composition include dicalcium phosphate, tricalcium phosphate, calcium pyrophosphate, magnesium phosphate, insoluble sodium metaphosphate, anhydrous silicic acid, aluminum hydroxide, alumina, hydroxyapatite Abrasives such as calcium carbonate, magnesium carbonate, calcium sulfate, zeolite, synthetic aluminosilicate, bengara, etc .; granular abrasives granulated from the above abrasives using a binder; glycerin, propylene glycol, 1,3- Wetting agents such as butylene glycol, ethylene glycol, polyethylene glycol, polypropylene glycol, erythritol, xylitol, sorbitol, maltitol; carboxymethylcellulose and its salts, methylcellulose, hydroxyethyl Binders such as roulose, carrageenan, sodium polyacrylate, hydroxypropylcellulose, sodium carboxymethylhydroxyethylcellulose, sodium alginate, propylene glycol alginate, xanthan gum, tragacanth gum, karaya gum, arabic gum, polyvinyl alcohol, polyvinyl pyrrolidone, bee gum, laponite; Dental strengthening agents such as sodium monofluorophosphate, tin fluoride, sodium fluoride; bactericides such as chlorhexidine and its salts, triclosan, cetylpyridinium chloride, thymols, benzalkonium chloride; pH of sodium phosphate, etc. Modifier: Enzymes such as dextranase, amylase, protease, lysozyme, mutanase; sodium chloride, hinokitiol, ε-a Minocaproic acid, tranexamic acid, allantoins, tocopherols, octylphthalide, nicotinic acid esters, dihydrocholesterol, glycyrrhetinic acid, glycyrrhizic acid and its salts, glycerophosphate, chlorophyll, water-soluble inorganic phosphate compounds, azulenes, camomile, Anti-inflammatory agents / blood circulation promoters such as assembly, Toki, Senkyu, herbal medicines; sweeteners such as saccharin sodium, stevioside, thaumatin, aspartylphenylalanine methyl ester; p-hydroxybenzoic acid, ethyl p-hydroxybenzoate, p- Preservatives such as propyl hydroxybenzoate, butyl p-hydroxybenzoate and sodium benzoate; colorants and pigments such as titanium dioxide; peppermint oil, spearmint oil, menthol, carvone, anethole Eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronellyl acetate, methyl eugenol, cineol, linalool, ethyl linalool, crocodile, thymol, anise oil, lemon oil, orange oil, Examples include sage oil, rosemary oil, cinnamon oil, pimento oil, cinnamon oil, winter green oil, clove oil, eucalyptus oil, and the like.
口腔用組成物には、本発明の効果を損なわない限り、界面活性剤を配合することもできる。界面活性剤としては特に制限はないが、アニオン系界面活性剤及びノニオン系界面活性剤を好ましく用いることができる。アニオン系界面活性剤としては、ラウリル硫酸ナトリウム、ミリスチル硫酸ナトリウム等のアルキル硫酸エステル塩;ラウロイルサルコシンナトリウム等のN−アシルアミノ酸塩;ラウロイルメチルタウリンナトリウム等のアシルタウリン塩;ヤシ油脂肪酸エチルエステルスルホン酸ナトリウム塩等の脂肪酸エステルスルホン酸塩等が挙げられる。ノニオン系界面活性剤としては、ポリオキシエチレン硬化ヒマシ油、ショ糖脂肪酸エステル、ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレンソルビット脂肪酸エステル、ポリオキシエチレングリセリン脂肪酸エステル、ポリエチレングリコール脂肪酸エステル等の脂肪酸エステル類、ポリオキシエチレンフィトステロール、ポリオキシエチレンフィトスタノール、ポリオキシエチレンラノリン、ポリオキシエチレンラノリンアルコール、ポリオキシエチレンアルキルアミン、ポリオキシエチレン脂肪酸アミド、ポリオキシエチレンアルキルフェニルホルムアルデヒド縮合物、ポリオキシエチレンアルキルエーテル、ポリオキシエチレンポリオキシプロピレンアルキルエーテル、ポリオキシエチレンポリオキシプロピレン共重合体、ポリオキシエチレンアルキルフェニルエーテル、ポリオキシエチレン脂肪酸エタノールアミドなどが挙げられる。 As long as the effects of the present invention are not impaired, a surfactant may be added to the oral composition. Although there is no restriction | limiting in particular as surfactant, Anionic surfactant and a nonionic surfactant can be used preferably. Examples of anionic surfactants include alkyl sulfate salts such as sodium lauryl sulfate and sodium myristyl sulfate; N-acyl amino acid salts such as sodium lauroyl sarcosine; acyl taurine salts such as sodium lauroyl methyl taurine; coconut oil fatty acid ethyl ester sulfonic acid Examples include fatty acid ester sulfonates such as sodium salts. Nonionic surfactants include polyoxyethylene hydrogenated castor oil, sucrose fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyoxyethylene Fatty acid esters such as glycerin fatty acid ester and polyethylene glycol fatty acid ester, polyoxyethylene phytosterol, polyoxyethylene phytostanol, polyoxyethylene lanolin, polyoxyethylene lanolin alcohol, polyoxyethylene alkylamine, polyoxyethylene fatty acid amide, polyoxy Ethylene alkyl phenyl formaldehyde condensate, polyoxyethylene alkyl ether, polyoxye Ren polyoxypropylene alkyl ethers, polyoxyethylene polyoxypropylene copolymers, polyoxyethylene alkyl phenyl ethers, polyoxyethylene fatty acid ethanol amides.
口腔用組成物は、前記有効成分を配合し、常法により製造することができる。口腔用組成物の形態は特に制限されず、粉歯磨、液状歯磨、練歯磨、潤製歯磨、口腔パスタ等のペースト状洗浄剤、洗口液、マウスウォッシュ等の液状洗浄剤、うがい用錠剤、歯肉マッサージクリーム、チューインガム、トローチ、キャンディ等の食品等の形態とすることができる。 The composition for oral cavity can be manufactured by a conventional method by blending the active ingredients. The form of the composition for oral cavity is not particularly limited, and is a powdery toothpaste, a liquid toothpaste, a toothpaste, a toothpaste, a paste-like cleaning agent such as oral pasta, a mouthwash, a liquid cleaning agent such as mouthwash, a gargle tablet, It can be in the form of food such as gingival massage cream, chewing gum, troche and candy.
食品組成物を調製する場合、その形態は特に制限されず、飲料も包含される。一般食品の他に、感染症(具体的には歯骨炎などの歯周病等)の予防・改善等をコンセプトとしてその旨を表示した飲食品、すなわち、健康食品、機能性食品、病者用食品及び特定保健用食品なども包含される。健康食品、機能性食品、病者用食品及び特定保健用食品は、具体的には、細粒剤、錠剤、顆粒剤、散剤、カプセル剤、シロップ剤、液剤、流動食等の各種製剤形態として使用することができ、これら製剤のために使用することができる。製剤形態の食品組成物は、医薬製剤と同様に製造することができ、前記有効成分と、食品として許容できる担体、例えば適当な賦形剤(例えば、でん粉、加工でん粉、乳糖、ブドウ糖、水等)等とを混合した後、慣用の手段を用いて製造することができる。さらに、食品組成物は、スープ類、ジュース類、乳飲料、茶飲料、コーヒー飲料、ココア飲料、ゼリー状飲料などの液状食品組成物、プリン、ヨーグルトなどの半固形食品組成物、パン類、うどんなどの麺類、クッキー、チョコレート、キャンディ、ガム、せんべいなどの菓子類、ふりかけ、バター、ジャムなどのスプレッド類等の形態もとりうる。また、食品には、飼料も含まれる。 When preparing a food composition, the form in particular is not restrict | limited, A drink is also included. In addition to general foods, foods and drinks that indicate the concept of prevention / improvement of infectious diseases (specifically periodontal diseases such as gingivitis), that is, health foods, functional foods, sick people Foods for specified use and foods for specified health use are also included. Health foods, functional foods, foods for patients and foods for specified health use are specifically formulated in various forms such as fine granules, tablets, granules, powders, capsules, syrups, liquids, and liquid foods. Can be used for these formulations. A food composition in the form of a preparation can be produced in the same manner as a pharmaceutical preparation. The active ingredient and a carrier acceptable as a food, for example, an appropriate excipient (eg, starch, processed starch, lactose, glucose, water, etc.) ) And the like, and then can be produced using conventional means. In addition, food compositions include soups, juices, milk beverages, tea beverages, coffee beverages, cocoa beverages, jelly-like beverages and other liquid food compositions, pudding, yogurt and other semi-solid food compositions, breads, udon Such as noodles such as cookies, chocolate, candy, gum, rice crackers and the like, spreads such as sprinkles, butter, jam and the like. The food also includes feed.
食品組成物には、種々の食品添加物、例えば、酸化防止剤、香料、各種エステル類、有機酸類、有機酸塩類、無機酸類、無機酸塩類、無機塩類、色素類、乳化剤、保存料、調味料、甘味料、酸味料、果汁エキス類、野菜エキス類、花蜜エキス類、pH調整剤、品質安定剤などの添加剤を単独、あるいは併用して配合してもよい。 Food compositions include various food additives such as antioxidants, fragrances, various esters, organic acids, organic acid salts, inorganic acids, inorganic acid salts, inorganic salts, pigments, emulsifiers, preservatives, seasonings Additives such as additives, sweeteners, acidulants, fruit juice extracts, vegetable extracts, nectar extracts, pH adjusters, and quality stabilizers may be used alone or in combination.
化粧料組成物を調製する場合、その形態は特に制限されず、溶液、乳液、粉末、水−油二層系、水−油−粉末三層系、ゲル、エアゾール、ミスト及びカプセル等任意の形態とすることができる。また、化粧料組成物の製品形態も任意であり、例えば、マッサージ剤及びフットスプレー等のボディー化粧料、化粧水、乳液、クリーム及びパック等のフェーシャル化粧料、ファンデーション、おしろい、頬紅、口紅、アイシャドー、アイライナー、マスカラ及びサンスクリーン等のメーキャップ化粧料、メーク落とし、洗顔料及びボディーシャンプー等の皮膚洗浄料、ヘアーリンス及びシャンプー等の毛髪化粧料、浴用剤、軟膏、医薬部外品、あぶら取り紙、芳香化粧料等が挙げられる。 When preparing a cosmetic composition, the form is not particularly limited, and any form such as a solution, emulsion, powder, water-oil two-layer system, water-oil-powder three-layer system, gel, aerosol, mist, capsule, etc. It can be. The product form of the cosmetic composition is also arbitrary, for example, body cosmetics such as massage agents and foot sprays, facial cosmetics such as lotions, emulsions, creams and packs, foundations, funny, blushers, lipsticks, eye Makeup cosmetics such as shadows, eyeliners, mascaras and sunscreens, makeup removers, skin cleansers such as face wash and body shampoo, hair cosmetics such as hair rinses and shampoos, bath preparations, ointments, quasi drugs, oil Examples include papers and aromatic cosmetics.
化粧料組成物は、化粧品、医薬部外品及び医薬品等に慣用される他の成分、例えば、粉末成分、液体油脂、固体油脂、ロウ、炭化水素、高級脂肪酸、高級アルコール、エステル、シリコーン、アニオン界面活性剤、カチオン界面活性剤、両性界面活性剤、非イオン界面活性剤、保湿剤、水溶性高分子、増粘剤、皮膜剤、紫外線吸収剤、金属イオン封鎖剤、低級アルコール、多価アルコール、糖、アミノ酸、有機アミン、高分子エマルジョン、pH調整剤、皮膚栄養剤、ビタミン、酸化防止剤、酸化防止助剤、香料、水等を必要に応じて配合し、常法により製造することができる。 The cosmetic composition includes other components commonly used in cosmetics, quasi drugs and pharmaceuticals, such as powder components, liquid fats and oils, solid fats and oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicones, anions. Surfactant, cationic surfactant, amphoteric surfactant, nonionic surfactant, humectant, water-soluble polymer, thickener, film agent, UV absorber, sequestering agent, lower alcohol, polyhydric alcohol , Sugar, amino acids, organic amines, polymer emulsions, pH adjusters, skin nutrients, vitamins, antioxidants, antioxidant auxiliaries, fragrances, water, etc. may be blended as necessary and manufactured by conventional methods. it can.
その他の化粧料組成物に配合可能な成分としては、例えば、防腐剤(エチルパラベン、ブチルパラベン等)、消炎剤(例えば、グリチルリチン酸誘導体、グリチルレチン酸誘導体、サリチル酸誘導体、ヒノキチオール、酸化亜鉛、アラントイン等)、美白剤(例えば、胎盤抽出物、ユキノシタ抽出物、アルブチン等)、各種抽出物(例えば、オウバク、オウレン、シコン、シャクヤク、センブリ、バーチ、セージ、ビワ、ニンジン、アロエ、ゼニアオイ、アイリス、ブドウ、ヨクイニン、ヘチマ、ユリ、サフラン、センキュウ、ショウキュウ、オトギリソウ、オノニス、ニンニク、トウガラシ、チンピ、トウキ、海藻等)、賦活剤(例えば、ローヤルゼリー、感光素、コレステロール誘導体等)、血行促進剤(例えば、ノニル酸ワレニルアミド、ニコチン酸ベンジルエステル、ニコチン酸β−ブトキシエチルエステル、カプサイシン、ジンゲロン、カンタリスチンキ、イクタモール、タンニン酸、α−ボルネオール、ニコチン酸トコフェロール、イノシトールヘキサニコチネート、シクランデレート、シンナリジン、トラゾリン、アセチルコリン、ベラパミル、セファランチン、γ−オリザノール等)、抗脂漏剤(例えば、硫黄、チアントール等)、抗炎症剤(例えば、トラネキサム酸、チオタウリン、ヒポタウリン等)等が挙げられる。 Examples of other components that can be incorporated into the cosmetic composition include preservatives (ethyl paraben, butyl paraben, etc.), anti-inflammatory agents (eg, glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin, etc. ), Whitening agents (for example, placenta extract, saxifrage extract, arbutin, etc.), various extracts (for example, buckwheat, auren, shikon, peonies, assembly, birch, sage, loquat, carrot, aloe, mallow, iris, grape , Yokuinin, Loofah, Lily, Saffron, Senkyu, Pepper, Hypericum, Onionis, Garlic, Pepper, Chimpi, Toki, Seaweed, etc.), Activator (for example, Royal Jelly, Photosensitizer, Cholesterol Derivative, etc.), Blood circulation promoter (for example, , Wallenylami nonylate Nicotinic acid benzyl ester, nicotinic acid β-butoxyethyl ester, capsaicin, zingerone, cantalis tincture, ictamol, tannic acid, α-borneol, nicotinic tocopherol, inositol hexanicotinate, cyclandrate, cinnarizine, trazoline, acetylcholine, And verapamil, cephalanthin, γ-oryzanol, etc.), antiseborrheic agents (eg, sulfur, thianthol, etc.), anti-inflammatory agents (eg, tranexamic acid, thiotaurine, hypotaurine, etc.).
本発明のAI−2阻害剤、並びに前記感染症の予防及び/又は治療剤における前記有効成分の投与量は、AI−2を阻害しうる量、又は感染症を予防及び/又は治療しうる量であればよく、投与方法、年齢、症状等により適宜決定することができる。例えば、前記有効成分の質量に基づき、1日あたり、体重1kgあたり、経口投与で通常0.001〜100mg、好ましくは0.01〜10mgである。 The dose of the active ingredient in the AI-2 inhibitor of the present invention and the preventive and / or therapeutic agent for infectious diseases is an amount capable of inhibiting AI-2, or an amount capable of preventing and / or treating infectious diseases. And can be appropriately determined depending on the administration method, age, symptoms and the like. For example, based on the mass of the active ingredient, the daily dose is usually 0.001 to 100 mg, preferably 0.01 to 10 mg per kg body weight per day.
本発明のAI−2阻害剤、並びに前記感染症の予防及び/又は治療剤における前記有効成分の含有量は、上記投与量を達成するように適宜決定できる。例えば、本発明のAI−2阻害剤、並びに前記感染症の予防及び/又は治療剤において、前記有効成分の含有量は0.0001〜5質量%が好ましく、0.01〜1質量%がより好ましい。 The content of the active ingredient in the AI-2 inhibitor of the present invention and the preventive and / or therapeutic agent for infectious diseases can be appropriately determined so as to achieve the above dose. For example, in the AI-2 inhibitor of the present invention and the preventive and / or therapeutic agent for infectious diseases, the content of the active ingredient is preferably 0.0001 to 5% by mass, more preferably 0.01 to 1% by mass.
前記有効成分を投与することにより、AI−2を阻害することができ、ひいては、感染症を予防及び/又は治療することができる。 By administering the active ingredient, AI-2 can be inhibited, and thus infection can be prevented and / or treated.
従来、感染症の予防及び治療には抗生物質の投与が行われてきた。しかし細菌が薬剤耐性を獲得するため、抗生物質の効果が減弱してしまう。一方、AI−2を阻害すれば、細菌が本来持つクオラムセンシングシステムを制御し、その病原性を制御することが可能となるため。したがって、本発明のAI−2阻害剤、並びに前記感染症の予防及び/又は治療剤は、薬剤耐性を持っている細菌にも効果が期待できる。 Conventionally, antibiotics have been administered for the prevention and treatment of infectious diseases. However, since bacteria acquire drug resistance, the effectiveness of antibiotics is diminished. On the other hand, if AI-2 is inhibited, it becomes possible to control the quorum sensing system inherent in bacteria and control its pathogenicity. Therefore, the AI-2 inhibitor of the present invention and the preventive and / or therapeutic agent for infectious diseases can be expected to have an effect on bacteria having drug resistance.
以下、本発明を実施例に基づきさらに詳細に説明するが、本発明はこれに限定されるものではない。 EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited to this.
試験例1 AI−2活性の測定
20〜30代の健常男性6名の舌・顎下腺開口部に採取器具を装着し、舌背上舌尖を市販のレモン果汁で刺激することで唾液を採取した。採取後速やかに、カットオフ分子量が10万のスピンカラム(ミリポア社製)を用いて限外濾過し、分子量が10万以上の分子量画分を除去した。その後、カットオフ値1000のスピンカラム(ポール社製)を用いて、分子量1000以下の画分を得た。
Test Example 1 Measurement of AI-2 Activity Saliva was collected by attaching a sampling device to the opening of the tongue and submandibular gland of 6 healthy men in their 20s and 30s and stimulating the upper tongue of the back of the tongue with commercially available lemon juice did. Immediately after collection, ultrafiltration was performed using a spin column (Millipore) having a cutoff molecular weight of 100,000 to remove a molecular weight fraction having a molecular weight of 100,000 or more. Thereafter, a fraction having a molecular weight of 1000 or less was obtained using a spin column (manufactured by Pall) having a cutoff value of 1000.
AI−2バイオアッセイ系のためのレポーター菌株としてのビブリオ・ハーベイBB170株(ATCC BAA−1117)をMarine Agar 2216培地(商品名、Difco社製)で30℃、好気条件下で培養した。このように培養したビブリオ・ハーベイBB170株の一白金耳をMarine Broth 2216培地(商品名、Difco社製)に植菌し、好気条件下8時間、30℃、200rpmで振盪培養を行った。前記菌液200μLをAB(Autoinducer Bioassay)培地に植菌し、好気条件下16時間、30℃、200rpmで振盪培養を行った。この菌液をAB培地で5000倍に希釈し、レポーター菌液とした。
なお、AB培地は、Mol.Microbiol.,9(4),p.773-786,1993を参照して以下の通り調製した。0.2%Vitamin-free casamino acids(Difco社製)、0.3M NaCl(和光純薬社製)、0.05M MgSO4・7H2O(和光純薬社製)の溶液を任意の濃度のKOH溶液(和光純薬社製)でpH7.5に調整し、オートクレーブ後室温で保存した。この溶液1Lに対し、1Mリン酸カリウムバッファー(1M KH2PO4 21.1mL+1M K2HPO4 28.9mL)10mL、0.1M L−アルギニン(free-base、和光純薬社製)10mL、1mg/ml thiamine HCl(和光純薬社製)1mL、10μg/mL リボフラビン(和光純薬社製)1mL及びグリセロール(和光純薬社製)20mLをよく混和後、濾過滅菌したもの42mLを添加し、AB培地を調製した。
Vibrio Harvey BB170 strain (ATCC BAA-1117) as a reporter strain for the AI-2 bioassay system was cultured in Marine Agar 2216 medium (trade name, manufactured by Difco) at 30 ° C. under aerobic conditions. One platinum loop of Vibrio Harvey BB170 strain cultured as described above was inoculated into Marine Broth 2216 medium (trade name, manufactured by Difco), and cultured with shaking at 30 ° C. and 200 rpm for 8 hours under aerobic conditions. 200 μL of the bacterial solution was inoculated on AB (Autoinducer Bioassay) medium, and cultured with shaking at 30 ° C. and 200 rpm for 16 hours under aerobic conditions. This bacterial solution was diluted 5000 times with AB medium to obtain a reporter bacterial solution.
Note that AB medium is obtained from Mol. Microbiol., 9 (4), p. Prepared as follows with reference to 773-786,1993. 0.2% Vitamin-free casamino acids (manufactured by Difco), 0.3M NaCl (manufactured by Wako Pure Chemical Industries, Ltd.), 0.05M MgSO 4 · 7H 2 O (manufactured by Wako Pure Chemical Industries, Ltd.) The pH was adjusted to 7.5 with Kojun Pure Chemicals, and the mixture was stored at room temperature after autoclaving. To 1 L of this solution, 1 M potassium phosphate buffer (1 M KH 2 PO 4 21.1 mL + 1 M K 2 HPO 4 28.9 mL) 10 mL, 0.1 M L-arginine (free-base, manufactured by Wako Pure Chemical Industries) 10 mL, 1 mg / Ml thiamine HCl (Wako Pure Chemical Industries, Ltd.) 1mL, 10μg / mL Riboflavin (Wako Pure Chemical Industries, Ltd.) 1mL and glycerol (Wako Pure Chemical Industries, Ltd.) 20mL are mixed well, then filtered and sterilized 42mL is added. A medium was prepared.
前記レポーター菌液と、未分画唾液又は分子量1000以下の唾液画分とを9:1の割合で混和し、室温で10分プレインキュベートした。次いで、DPD(OMM Scientificに合成検討を依頼し、同社で合成したものを購入した)を終濃度が10μMとなるように添加し、30℃にて好気振盪培養し、4時間後の発光強度をケミルミネッセンス計(ベルトールド社製、Mitharas LB940(商品名))で測定し、AI−2阻害活性を測定した。なお、AI−2阻害活性は、10μMのDPDが惹起する発光を完全に抑制するときのAI−2阻害活性を100とした場合の相対値で示した。さらに、ポジティブコントロールとして、AI−2阻害化合物として既知化合物(4−ブロモ−5−(4−メトキシフェニル)−2(5H)−フラノン、Sigma社製)を用い、同様にAI−2阻害活性を測定した。 The reporter bacterial solution and the unfractionated saliva or the saliva fraction having a molecular weight of 1000 or less were mixed at a ratio of 9: 1 and pre-incubated at room temperature for 10 minutes. Next, DPD (OMM Scientific requested synthesis study and purchased the product synthesized by the company) was added to a final concentration of 10 μM, aerobic shaking culture at 30 ° C., and luminescence intensity after 4 hours Was measured with a chemiluminescence meter (Mitharas LB940 (trade name), manufactured by Bertoold Co., Ltd.) to measure AI-2 inhibitory activity. The AI-2 inhibitory activity was expressed as a relative value when the AI-2 inhibitory activity when the luminescence caused by 10 μM DPD was completely suppressed was taken as 100. Further, as a positive control, a known compound (4-bromo-5- (4-methoxyphenyl) -2 (5H) -furanone, manufactured by Sigma) was used as an AI-2 inhibitory compound, and AI-2 inhibitory activity was similarly observed. It was measured.
次に、分子量1000以下の唾液検体のキャピラリー電気泳動−質量分析(CE/TOF-MS)をSoga T.et al.,J.Biol.Chem.,281,p.16768-16776,2006に記載の方法に準じて行った。なお、検体は、採取した唾液を5倍濃縮して測定に供した。
まずアミノ酸、解糖系、TCA回路、ペントースリン酸回路に含まれる主要なイオン性代謝産物約100種を標準物質として唾液成分からの検索を行い、同定・定量を行った。また、前記イオン性代謝産物以外の副生成物約400種についても同様に検索・同定を行った(内部標準物として、カチオン成分の測定モードではMethionine sulfoneを、アニオン測定モードではD-Camphol-10-sulfonic acidを用いて、これらの質量を1とした時の相対値を測定した)。
Next, capillary electrophoresis-mass spectrometry (CE / TOF-MS) of a saliva sample having a molecular weight of 1000 or less was analyzed by Soga T. et al. et al., J. et al. Biol. Chem., 281, p. This was carried out according to the method described in 16768-16776, 2006. The sample was subjected to measurement after the collected saliva was concentrated 5 times.
First, identification and quantification were performed by searching from saliva components using about 100 major ionic metabolites contained in amino acids, glycolysis, TCA cycle, and pentose phosphate cycle as standard substances. In addition, about 400 kinds of by-products other than the ionic metabolites were similarly searched and identified (as an internal standard, Methionine sulfone was used in the cation component measurement mode, and D-Camphol-10 was used in the anion measurement mode. Using -sulfonic acid, the relative value when these masses were taken as 1 was measured).
以上の結果に基づき、唾液のAI−2阻害活性と、CE/TOF-MS定量値又は相対値との相関係数が0.6以上で、かつ有意傾向以上の統計学的な関連性を示した化合物の中から、タウリン、フルクトース−6−リン酸、ヒポキサンチン及びクレアチンを選択した。 Based on the above results, the correlation coefficient between the salivary AI-2 inhibitory activity and the CE / TOF-MS quantitative value or relative value is 0.6 or more, and a statistical correlation more than a significant tendency is shown. From these compounds, taurine, fructose-6-phosphate, hypoxanthine and creatine were selected.
次に、未分画唾液又は分子量1000以下の唾液画分の代わりに、タウリン(Sigma社より購入)、フルクトース−6−リン酸(Sigma社より購入)、ヒポキサンチン(Sigma社より購入)、又はクレアチン(和光純薬より購入)を用いたこと以外は、前記方法と同様の方法により、タウリン、フルクトース−6−リン酸、ヒポキサンチン及びクレアチンのAI−2阻害活性を測定した。その結果を表1に示す。なお、タウリン、フルクトース−6−リン酸、ヒポキサンチン及びクレアチンの使用量は、前記化合物の終濃度が表1に示す濃度となるようにした。 Next, instead of unfractionated saliva or saliva fraction having a molecular weight of 1000 or less, taurine (purchased from Sigma), fructose-6-phosphate (purchased from Sigma), hypoxanthine (purchased from Sigma), or Except that creatine (purchased from Wako Pure Chemical Industries) was used, the AI-2 inhibitory activity of taurine, fructose-6-phosphate, hypoxanthine and creatine was measured by the same method as described above. The results are shown in Table 1. The amount of taurine, fructose-6-phosphate, hypoxanthine and creatine used was such that the final concentration of the compound was the concentration shown in Table 1.
表1の結果から明らかなように、本発明のAI−2阻害剤は、AI−2阻害活性を有することが示された。 As is clear from the results in Table 1, the AI-2 inhibitor of the present invention was shown to have AI-2 inhibitory activity.
試験例2 歯垢中AI−2量と齲蝕病との関係
ビブリオ・ハーベイBB152株(ATCC BAA−1119)をMarine Agar2216培地で30℃、好気条件下で培養した。このように培養したビブリオ・ハーベイBB152株の一白金耳をMarine Broth2216培地に植菌し、好気条件下8時間、30℃、200rpmで振盪培養を行った。
上記菌液をAB培地に植菌し、さらに好気条件下16時間、30℃、200rpmで振盪培養を行った。遠心分離(8000rpm、15分、4℃)後の上清を取り出し、カットオフ値1Kのスピンカラム(ポール社製)を用いて分子量1000以下の画分を得、AI−2溶液とした(AI−2濃度:約0.1μM)。
Test Example 2 Relationship between the amount of AI-2 in dental plaque and caries disease Vibrio Harvey BB152 strain (ATCC BAA-1119) was cultured in Marine Agar 2216 medium at 30 ° C. under aerobic conditions. One platinum loop of Vibrio Harvey BB152 strain cultured in this way was inoculated into Marine Broth 2216 medium, followed by shaking culture at 30 ° C. and 200 rpm for 8 hours under aerobic conditions.
The above bacterial solution was inoculated into AB medium, and further cultured with shaking at 30 ° C. and 200 rpm for 16 hours under aerobic conditions. The supernatant after centrifugation (8000 rpm, 15 minutes, 4 ° C.) was taken out, and a fraction having a molecular weight of 1000 or less was obtained using a spin column (manufactured by Pall) with a cut-off value of 1K to obtain an AI-2 solution (AI -2 concentration: about 0.1 μM).
齲蝕原性細菌であるストレプトコッカス・ミュータンスJCM5705株をBHI寒天培地(Difco社製)に播種・培養(嫌気条件下で37℃、1日)した。このようにして培養した、ストレプトコッカス・ミュータンスJCM5705株の一白金耳をBHI液体培地(Difco社製)に植菌し、嫌気条件下で37℃、16時間培養した。PBSにて洗浄後、2×1010個/mLになるように菌液を調製した。 Streptococcus mutans JCM5705 strain, which is a cariogenic bacterium, was seeded and cultured (37 ° C., 1 day under anaerobic condition) on BHI agar medium (manufactured by Difco). One platinum loop of the Streptococcus mutans JCM5705 strain thus cultured was inoculated into a BHI liquid medium (manufactured by Difco) and cultured at 37 ° C. for 16 hours under anaerobic conditions. After washing with PBS, a bacterial solution was prepared at 2 × 10 10 cells / mL.
抗生物質水溶液(アンピシリン、カナマイシン各2mg/mL)をSDラット(雄性、3週齢)に5日間自由飲水させた後、ストレプトコッカス・ミュータンス菌液をラットの左右下顎臼歯部に各50μL、1回/日で5日間滴下した。食餌は齲蝕誘導食であるDiet2000(商品名、オリエンタルバイオサービス社製)を与えた。その後、AI−2溶液又はAB培地(コントロール)を2回/日、1回当たり200μLを臼歯部に1ヶ月間滴下した(各群N=5)。また、ストレプトコッカス・ミュータンス菌液を滴下しない群も設定した(N=5)。 An antibiotic aqueous solution (ampicillin and kanamycin 2 mg / mL each) was allowed to freely drink in SD rats (male, 3 weeks old) for 5 days, and then Streptococcus mutans bacteria solution was applied to the left and right lower molars of rats 50 μL each time. Per day for 5 days. Diet was Diet2000 (trade name, manufactured by Oriental Bioservice) which is a caries induction diet. Thereafter, AI-2 solution or AB medium (control) was dropped twice a day at 200 μL per dose to the molar part for 1 month (each group N = 5). In addition, a group in which Streptococcus mutans solution was not dropped was also set (N = 5).
各群のSDラットの齲蝕の程度を示す齲蝕スコアを、Keyes P.H.et al.,J.Dent.Res.,37,6,p.1958に記載の方法に準じて測定した。その結果を表2に示す。 The caries score indicating the degree of caries in each group of SD rats was measured by Keyes P.M. H. et al., J. et al. Dent. Res., 37, 6, p. Measurement was performed according to the method described in 1958. The results are shown in Table 2.
表2の結果から、歯垢中AI−2量と齲蝕病とが相関関係を有し、従って、歯垢中のAI−2が齲蝕亢進に関与し、AI−2活性の阻害が齲蝕病の予防・改善に有効であることが示された。 From the results in Table 2, there is a correlation between the amount of AI-2 in dental plaque and caries disease. Therefore, AI-2 in dental plaque is involved in caries enhancement, and inhibition of AI-2 activity is a cause of caries disease. It was shown to be effective for prevention and improvement.
試験例3 抗菌試験
試験例1と同様に調製したレポーター菌液を5000倍に希釈し、タウリン又はクレアチンの水溶液を9:1の割合(体積比)で混和し、好気条件下で30℃、4時間インキュベートした(各剤の終濃度は100μM)。さらに、培養菌液をAB培地で100〜10000倍に任意に希釈しMarine Agar 2216培地(商品名、Difco社製)に播種し、30℃で1日培養後、コロニー数をカウントし生菌数を算出した。なお、対象試験として、被験品水溶液の代わりにAB培地を用いた以外は同様にして生菌数を算出した。その結果を表3に示す。
Test Example 3 Antibacterial Test The reporter bacterial solution prepared in the same manner as in Test Example 1 was diluted 5000 times, an aqueous solution of taurine or creatine was mixed at a ratio (volume ratio) of 9: 1, and 30 ° C under aerobic conditions Incubated for 4 hours (final concentration of each agent was 100 μM). Further, the culture solution is arbitrarily diluted 100 to 10,000 times with AB medium and seeded on Marine Agar 2216 medium (trade name, manufactured by Difco). After culturing at 30 ° C. for 1 day, the number of colonies is counted and the number of viable bacteria is counted. Was calculated. In addition, the viable cell count was calculated in the same manner except that AB medium was used instead of the aqueous test product solution as the target test. The results are shown in Table 3.
表3に示すように、タウリン、クレアチンのレポーター菌に対する抗菌作用は認められなかった。したがって、本発明のAI−2阻害剤の有効成分は、歯周病、齲蝕病の原因菌等の病原性細菌に対する殺菌能を示すものではなく、病原性細菌の種間連絡に利用されるAI−2の活性を阻害するものであることを示すものである。 As shown in Table 3, the antibacterial action of taurine and creatine on the reporter bacteria was not observed. Therefore, the active ingredient of the AI-2 inhibitor of the present invention does not show bactericidal activity against pathogenic bacteria such as periodontal disease and caries disease, but AI used for interspecific communication of pathogenic bacteria. -2 activity is inhibited.
(処方例)
本発明の齲蝕病の予防及び/又は治療剤として、下記に示す組成のチューブ入り練歯磨、練歯磨及び樹脂製容器入りマウスウォッシュを常法により各々調製した。
(Prescription example)
As a preventive and / or therapeutic agent for caries diseases of the present invention, tube toothpastes, toothpastes and resin-washed mouthwashes having the compositions shown below were prepared by conventional methods.
処方例1 チューブ入り練歯磨の調製
ソルビトール 35質量%
無水ケイ酸 20質量%
濃グリセリン 5質量%
クレアチン 1質量%
カルボキシメチルセルロースナトリウム 1質量%
歯磨き用香料 1質量%
フッ化ナトリウム 0.2質量%
サッカリンナトリウム 0.2質量%
酢酸dl−α−トコフェロール 0.1質量%
精製水 残余
計100質量%
Formulation Example 1 Preparation of toothpaste with tube Sorbitol 35% by mass
Silica anhydride 20% by mass
Concentrated glycerin 5% by mass
Creatine 1% by mass
Carboxymethylcellulose sodium 1% by mass
Toothpaste fragrance 1% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Dl-α-tocopherol acetate 0.1% by mass
Purified water residue
100% by mass in total
処方例2 チューブ入り練歯磨の調製
炭酸カルシウム 30質量%
ソルビトール 28質量%
無水ケイ酸 8質量%
濃グリセリン 5質量%
ラウリル硫酸ナトリウム 1.2質量%
カルボキシメチルセルロースナトリウム 1質量%
歯磨き用香料 1質量%
クレアチン 1質量%
酢酸dl−α−トコフェロール 0.2質量%
フッ化ナトリウム 0.2質量%
サッカリンナトリウム 0.2質量%
イソプロピルメチルフェノール 0.1質量%
精製水 残余
計100質量%
Formulation Example 2 Preparation of toothpaste with tube Calcium carbonate 30% by mass
Sorbitol 28% by mass
Silica anhydride 8% by mass
Concentrated glycerin 5% by mass
Sodium lauryl sulfate 1.2% by mass
Carboxymethylcellulose sodium 1% by mass
Toothpaste fragrance 1% by mass
Creatine 1% by mass
Dl-α-Tocopherol acetate 0.2% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Isopropyl methylphenol 0.1% by mass
Purified water residue
100% by mass in total
処方例3 練歯磨の調製
ソルビトール 25質量%
無水ケイ酸 20質量%
プロピレングリコール 6質量%
ラクチトール 5質量%
カルボキシメチルセルロースナトリウム 1質量%
歯磨き用香料 1質量%
タウリン 1質量%
フッ化ナトリウム 0.2質量%
サッカリンナトリウム 0.2質量%
酢酸dl−α−トコフェロール 0.1質量%
精製水 残余
計100質量%
Formulation Example 3 Preparation of Toothpaste Sorbitol 25% by mass
Silica anhydride 20% by mass
Propylene glycol 6% by mass
Lactitol 5% by mass
Carboxymethylcellulose sodium 1% by mass
Toothpaste fragrance 1% by mass
Taurine 1% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Dl-α-tocopherol acetate 0.1% by mass
Purified water residue
100% by mass in total
処方例4 練歯磨の調製
ソルビトール 28質量%
ポリオキシエチレン(200)ポリオキシプロピレン(40)共重合体 16質量%
無水ケイ酸 12質量%
パラチニット 10質量%
濃グリセリン 8質量%
ラウリル硫酸ナトリウム 1.2質量%
カルボキシメチルセルロースナトリウム 1.5質量%
歯磨き用香料 1質量%
タウリン 1質量%
モノフルオロリン酸ナトリウム 0.7質量%
サッカリンナトリウム 0.2質量%
酢酸dl−α−トコフェロール 0.1質量%
精製水 残余
計100質量%
Formulation Example 4 Preparation of toothpaste sorbitol 28% by mass
16% by mass of polyoxyethylene (200) polyoxypropylene (40) copolymer
Silica anhydride 12% by mass
Palatinit 10% by mass
Concentrated glycerin 8% by mass
Sodium lauryl sulfate 1.2% by mass
Sodium carboxymethylcellulose 1.5% by mass
Toothpaste fragrance 1% by mass
Taurine 1% by mass
Sodium monofluorophosphate 0.7% by mass
Saccharin sodium 0.2% by mass
Dl-α-tocopherol acetate 0.1% by mass
Purified water residue
100% by mass in total
処方例5 練歯磨の調製
ソルビトール 28質量%
無水ケイ酸 15質量%
ポリエチレングリコール400 8質量%
エリスリトール 5質量%
ラウリル硫酸ナトリウム 1.2質量%
カルボキシメチルセルロースナトリウム 1質量%
歯磨き用香料 1質量%
タウリン 1質量%
酢酸dl−α−トコフェロール 0.2質量%
フッ化ナトリウム 0.2質量%
サッカリンナトリウム 0.2質量%
イソプロピルメチルフェノール 0.1質量%
精製水 残余
計100質量%
Formulation Example 5 Preparation of toothpaste Sorbitol 28% by mass
Silica anhydride 15% by mass
Polyethylene glycol 400 8% by mass
Erythritol 5% by mass
Sodium lauryl sulfate 1.2% by mass
Carboxymethylcellulose sodium 1% by mass
Toothpaste fragrance 1% by mass
Taurine 1% by mass
Dl-α-Tocopherol acetate 0.2% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Isopropyl methylphenol 0.1% by mass
Purified water residue
100% by mass in total
処方例6 樹脂製容器入りマウスウォッシュの調製
エタノール 15質量%
ソルビトール 7質量%
ポリオキシエチレン硬化ヒマシ油 2質量%
サッカリンナトリウム 0.5質量%
ヒポキサンチン 1質量%
洗口剤用香料 0.2質量%
安息香酸ナトリウム 0.1質量%
酢酸dl−α−トコフェロール 0.05質量%
トリクロサン 0.02質量%
精製水 残余
計100質量%
Formulation Example 6 Preparation of mouthwash in resin container Ethanol 15% by mass
Sorbitol 7% by mass
Polyoxyethylene hydrogenated castor oil 2% by mass
Saccharin sodium 0.5% by mass
Hypoxanthine 1% by mass
Fragrance for mouthwash 0.2% by mass
Sodium benzoate 0.1% by mass
Dl-α-tocopherol acetate 0.05% by mass
Triclosan 0.02% by mass
Purified water residue
100% by mass in total
Claims (3)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010246112A JP5756614B2 (en) | 2010-11-02 | 2010-11-02 | Autoinducer-2 inhibitor and preventive and / or therapeutic agent for caries disease |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010246112A JP5756614B2 (en) | 2010-11-02 | 2010-11-02 | Autoinducer-2 inhibitor and preventive and / or therapeutic agent for caries disease |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2012097034A JP2012097034A (en) | 2012-05-24 |
JP2012097034A5 JP2012097034A5 (en) | 2013-10-31 |
JP5756614B2 true JP5756614B2 (en) | 2015-07-29 |
Family
ID=46389377
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010246112A Active JP5756614B2 (en) | 2010-11-02 | 2010-11-02 | Autoinducer-2 inhibitor and preventive and / or therapeutic agent for caries disease |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP5756614B2 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2593618T3 (en) * | 2012-12-18 | 2016-12-12 | Sunstar Suisse Sa | Topical oral composition to relieve the symptoms of dry mouth and for the treatment of canker sores |
ES2911516T3 (en) | 2016-01-19 | 2022-05-19 | Achromaz Pte Ltd | A cosmetic composition and the use thereof for regulating skin quality |
CN108042384B (en) * | 2018-01-08 | 2020-07-10 | 弘美制药(中国)有限公司 | A composition with oral cleaning and treating effects |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2338712C (en) * | 1998-07-28 | 2012-10-09 | Synergen Ag | Use of creatine compounds for treatment of bone or cartilage cells and tissues |
DE19841385A1 (en) * | 1998-09-10 | 2000-03-16 | Sueddeutsche Kalkstickstoff | Use of creatine and/or creatine derivatives as moisturizers in cosmetic compositions |
JP2010159219A (en) * | 2009-01-07 | 2010-07-22 | Kao Corp | Ai-2 inhibitor |
-
2010
- 2010-11-02 JP JP2010246112A patent/JP5756614B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
JP2012097034A (en) | 2012-05-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Li et al. | Tea polyphenols: application in the control of oral microorganism infectious diseases | |
JP5852007B2 (en) | Chalcones as enhancers of antimicrobial agents | |
JP5756615B2 (en) | Autoinducer-2 inhibitor and preventive and / or therapeutic agent for periodontal disease or caries disease | |
JP5210598B2 (en) | Autoinducer-2 inhibitor and preventive and / or therapeutic agent for infectious diseases | |
JP5756614B2 (en) | Autoinducer-2 inhibitor and preventive and / or therapeutic agent for caries disease | |
JP5881287B2 (en) | Autoinducer-2 inhibitor | |
US20190224222A1 (en) | Method of inhibiting quorum sensing using d-galactose | |
JP5718614B2 (en) | Autoinducer-2 inhibitor and preventive and / or therapeutic agent for periodontal disease or caries disease | |
JP2012116791A (en) | Autoinducer-2 inhibitor | |
JP2012097037A (en) | Autoinducer-2 inhibitor, and preventing and/or therapeutic agent of tooth osteitis or caries disease | |
JP5749915B2 (en) | Autoinducer-2 inhibitor | |
JP2012116827A (en) | Autoinducer-2 inhibitor and prevention and/or therapeutic agent for periodontal disease and tooth caries disease | |
JP5946608B2 (en) | Autoinducer-2 inhibitor | |
JP2013245167A (en) | Autoinducer-2 inhibitor | |
JP2013245164A (en) | Autoinducer-2 inhibitor | |
JP7333751B2 (en) | human antimicrobial peptide production promoter | |
JP2012097035A (en) | Autoinducer-2 inhibitor, and preventing and/or therapeutic agent of periodontal disease | |
JP2012097033A (en) | Autoinducer-2 inhibitor | |
JP2012116792A (en) | Agent for preventing and/or treating periodontal disease or dental caries disease | |
JP2013245165A (en) | Autoinducer-2 inhibitor | |
JP2013245166A (en) | Autoinducer-2 inhibitor | |
JP2012246235A (en) | Autoinducer-2 inhibitor | |
JP2019094269A (en) | Compositions for inhibiting periodontal bacterial growth | |
JP2022079216A (en) | Lactobacillus-containing compositions | |
Tua-Ngam et al. | Evaluation of Newly Formulated Chlorhexidine Mouthwash |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130913 Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130913 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130913 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20141007 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141202 Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20141202 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150512 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150601 |
|
R151 | Written notification of patent or utility model registration |
Ref document number: 5756614 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R151 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |