JP2017193538A - Composition containing copper compound, zinc compound, and L-menthol - Google Patents
Composition containing copper compound, zinc compound, and L-menthol Download PDFInfo
- Publication number
- JP2017193538A JP2017193538A JP2017078626A JP2017078626A JP2017193538A JP 2017193538 A JP2017193538 A JP 2017193538A JP 2017078626 A JP2017078626 A JP 2017078626A JP 2017078626 A JP2017078626 A JP 2017078626A JP 2017193538 A JP2017193538 A JP 2017193538A
- Authority
- JP
- Japan
- Prior art keywords
- zinc
- copper
- compound
- menthol
- oral
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 38
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 title claims abstract description 25
- 239000005749 Copper compound Substances 0.000 title claims abstract description 16
- 150000001880 copper compounds Chemical class 0.000 title claims abstract description 16
- 150000003752 zinc compounds Chemical class 0.000 title claims abstract description 16
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 40
- 208000028169 periodontal disease Diseases 0.000 claims description 23
- 206010006326 Breath odour Diseases 0.000 claims description 21
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical compound [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 claims description 20
- 229940108925 copper gluconate Drugs 0.000 claims description 20
- 239000011592 zinc chloride Substances 0.000 claims description 20
- 235000005074 zinc chloride Nutrition 0.000 claims description 20
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 15
- 239000010949 copper Substances 0.000 claims description 15
- 229910052802 copper Inorganic materials 0.000 claims description 15
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 14
- 239000011787 zinc oxide Substances 0.000 claims description 7
- 235000014692 zinc oxide Nutrition 0.000 claims description 6
- GAAKLDANOSASAM-UHFFFAOYSA-N undec-10-enoic acid;zinc Chemical compound [Zn].OC(=O)CCCCCCCCC=C GAAKLDANOSASAM-UHFFFAOYSA-N 0.000 claims description 5
- 229940118257 zinc undecylenate Drugs 0.000 claims description 5
- FMRLDPWIRHBCCC-UHFFFAOYSA-L Zinc carbonate Chemical compound [Zn+2].[O-]C([O-])=O FMRLDPWIRHBCCC-UHFFFAOYSA-L 0.000 claims description 4
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims description 4
- 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 claims description 4
- 229930002875 chlorophyll Natural products 0.000 claims description 4
- 235000019804 chlorophyll Nutrition 0.000 claims description 4
- 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 claims description 4
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 4
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 239000011667 zinc carbonate Substances 0.000 claims description 4
- 235000004416 zinc carbonate Nutrition 0.000 claims description 4
- 229910000010 zinc carbonate Inorganic materials 0.000 claims description 4
- 229940043825 zinc carbonate Drugs 0.000 claims description 4
- 239000011670 zinc gluconate Substances 0.000 claims description 4
- 235000011478 zinc gluconate Nutrition 0.000 claims description 4
- 229960000306 zinc gluconate Drugs 0.000 claims description 4
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 4
- 229960001763 zinc sulfate Drugs 0.000 claims description 4
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 4
- 229960001939 zinc chloride Drugs 0.000 claims description 3
- 229940098697 zinc laurate Drugs 0.000 claims description 3
- 229940105125 zinc myristate Drugs 0.000 claims description 3
- 229960001296 zinc oxide Drugs 0.000 claims description 3
- 229940012185 zinc palmitate Drugs 0.000 claims description 3
- 229940043810 zinc pyrithione Drugs 0.000 claims description 3
- PICXIOQBANWBIZ-UHFFFAOYSA-N zinc;1-oxidopyridine-2-thione Chemical compound [Zn+2].[O-]N1C=CC=CC1=S.[O-]N1C=CC=CC1=S PICXIOQBANWBIZ-UHFFFAOYSA-N 0.000 claims description 3
- ZNVKGUVDRSSWHV-UHFFFAOYSA-L zinc;4-hydroxybenzenesulfonate Chemical compound [Zn+2].OC1=CC=C(S([O-])(=O)=O)C=C1.OC1=CC=C(S([O-])(=O)=O)C=C1 ZNVKGUVDRSSWHV-UHFFFAOYSA-L 0.000 claims description 3
- GPYYEEJOMCKTPR-UHFFFAOYSA-L zinc;dodecanoate Chemical compound [Zn+2].CCCCCCCCCCCC([O-])=O.CCCCCCCCCCCC([O-])=O GPYYEEJOMCKTPR-UHFFFAOYSA-L 0.000 claims description 3
- GJAPSKMAVXDBIU-UHFFFAOYSA-L zinc;hexadecanoate Chemical compound [Zn+2].CCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCC([O-])=O GJAPSKMAVXDBIU-UHFFFAOYSA-L 0.000 claims description 3
- GBFLQPIIIRJQLU-UHFFFAOYSA-L zinc;tetradecanoate Chemical compound [Zn+2].CCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCC([O-])=O GBFLQPIIIRJQLU-UHFFFAOYSA-L 0.000 claims description 3
- 241000894006 Bacteria Species 0.000 abstract description 18
- 201000001245 periodontitis Diseases 0.000 abstract 2
- 238000012360 testing method Methods 0.000 description 17
- 210000000214 mouth Anatomy 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- 239000002609 medium Substances 0.000 description 10
- 239000003814 drug Substances 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 8
- 230000028327 secretion Effects 0.000 description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- -1 fluorine Copper iodide Chemical compound 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 229940034610 toothpaste Drugs 0.000 description 6
- 239000000606 toothpaste Substances 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 239000002537 cosmetic Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 239000003205 fragrance Substances 0.000 description 5
- 239000002324 mouth wash Substances 0.000 description 5
- 229940051866 mouthwash Drugs 0.000 description 5
- 210000003296 saliva Anatomy 0.000 description 5
- 239000011701 zinc Substances 0.000 description 5
- 229910052725 zinc Inorganic materials 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 208000032139 Halitosis Diseases 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 239000000551 dentifrice Substances 0.000 description 4
- 239000007935 oral tablet Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 235000002639 sodium chloride Nutrition 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 235000009161 Espostoa lanata Nutrition 0.000 description 3
- 240000001624 Espostoa lanata Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 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
- 238000007796 conventional method Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
- 229940041616 menthol Drugs 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 235000019645 odor Nutrition 0.000 description 3
- 229940042125 oral ointment Drugs 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- PVXPPJIGRGXGCY-DJHAAKORSA-N 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@](O)(CO)O1 PVXPPJIGRGXGCY-DJHAAKORSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 2
- 235000006679 Mentha X verticillata Nutrition 0.000 description 2
- 235000002899 Mentha suaveolens Nutrition 0.000 description 2
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- BACYUWVYYTXETD-UHFFFAOYSA-N N-Lauroylsarcosine Chemical compound CCCCCCCCCCCC(=O)N(C)CC(O)=O BACYUWVYYTXETD-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 241001135221 Prevotella intermedia Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000589892 Treponema denticola Species 0.000 description 2
- 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 2
- 239000002253 acid Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- YEOCHZFPBYUXMC-UHFFFAOYSA-L copper benzoate Chemical compound [Cu+2].[O-]C(=O)C1=CC=CC=C1.[O-]C(=O)C1=CC=CC=C1 YEOCHZFPBYUXMC-UHFFFAOYSA-L 0.000 description 2
- QYCVHILLJSYYBD-UHFFFAOYSA-L copper;oxalate Chemical compound [Cu+2].[O-]C(=O)C([O-])=O QYCVHILLJSYYBD-UHFFFAOYSA-L 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 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 2
- 238000005259 measurement Methods 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 229940041667 oral paste Drugs 0.000 description 2
- 229940042126 oral powder Drugs 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 235000002949 phytic acid Nutrition 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 108700004121 sarkosyl Proteins 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 150000003464 sulfur compounds Chemical class 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- 125000001755 (-)-menthol group Chemical group 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
- SHVRRGGZMBWAJT-ODZAUARKSA-N (z)-but-2-enedioic acid;copper Chemical compound [Cu].OC(=O)\C=C/C(O)=O SHVRRGGZMBWAJT-ODZAUARKSA-N 0.000 description 1
- PKMTWMDBJHRDBM-ODZAUARKSA-N (z)-but-2-enedioic acid;zinc Chemical compound [Zn].OC(=O)\C=C/C(O)=O PKMTWMDBJHRDBM-ODZAUARKSA-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
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- CLWNPUARORRDFD-UHFFFAOYSA-N 2-hydroxybutanedioic acid;zinc Chemical compound [Zn].OC(=O)C(O)CC(O)=O CLWNPUARORRDFD-UHFFFAOYSA-N 0.000 description 1
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
- JXSRRBVHLUJJFC-UHFFFAOYSA-N 7-amino-2-methylsulfanyl-[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile Chemical compound N1=CC(C#N)=C(N)N2N=C(SC)N=C21 JXSRRBVHLUJJFC-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
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- 239000005711 Benzoic acid Substances 0.000 description 1
- MOZDKDIOPSPTBH-UHFFFAOYSA-N Benzyl parahydroxybenzoate Chemical compound C1=CC(O)=CC=C1C(=O)OCC1=CC=CC=C1 MOZDKDIOPSPTBH-UHFFFAOYSA-N 0.000 description 1
- 241000589996 Campylobacter rectus Species 0.000 description 1
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- 239000005751 Copper oxide Substances 0.000 description 1
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- 239000004287 Dehydroacetic acid 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
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- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- XPJVKCRENWUEJH-UHFFFAOYSA-N Isobutylparaben Chemical compound CC(C)COC(=O)C1=CC=C(O)C=C1 XPJVKCRENWUEJH-UHFFFAOYSA-N 0.000 description 1
- CMHMMKSPYOOVGI-UHFFFAOYSA-N Isopropylparaben Chemical compound CC(C)OC(=O)C1=CC=C(O)C=C1 CMHMMKSPYOOVGI-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
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- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- CCXAYLQLOLXXKE-DWJAGBRCSA-K trisodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4s,5s,6s)-2-[[(3s,4ar,6ar,6bs,8as,11s,12ar,14ar,14bs)-11-carboxylato-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1h-picen-3-yl]oxy]-6-carboxylato-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-t Chemical compound [Na+].[Na+].[Na+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C([O-])=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O CCXAYLQLOLXXKE-DWJAGBRCSA-K 0.000 description 1
- WGIWBXUNRXCYRA-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WGIWBXUNRXCYRA-UHFFFAOYSA-H 0.000 description 1
- BIKXLKXABVUSMH-UHFFFAOYSA-N trizinc;diborate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]B([O-])[O-].[O-]B([O-])[O-] BIKXLKXABVUSMH-UHFFFAOYSA-N 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000004246 zinc acetate Substances 0.000 description 1
- 229940056904 zinc ascorbate Drugs 0.000 description 1
- 229940062776 zinc aspartate Drugs 0.000 description 1
- 239000011746 zinc citrate Substances 0.000 description 1
- 235000006076 zinc citrate Nutrition 0.000 description 1
- 229940068475 zinc citrate Drugs 0.000 description 1
- SRWMQSFFRFWREA-UHFFFAOYSA-M zinc formate Chemical compound [Zn+2].[O-]C=O SRWMQSFFRFWREA-UHFFFAOYSA-M 0.000 description 1
- 239000011576 zinc lactate Substances 0.000 description 1
- 235000000193 zinc lactate Nutrition 0.000 description 1
- 229940050168 zinc lactate Drugs 0.000 description 1
- LRXTYHSAJDENHV-UHFFFAOYSA-H zinc phosphate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O LRXTYHSAJDENHV-UHFFFAOYSA-H 0.000 description 1
- 229910000165 zinc phosphate Inorganic materials 0.000 description 1
- 229940077935 zinc phosphate Drugs 0.000 description 1
- 229940032991 zinc picolinate Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- WWRJFSIRMWUMAE-ZZMNMWMASA-L zinc;(2r)-2-[(1s)-1,2-dihydroxyethyl]-3-hydroxy-5-oxo-2h-furan-4-olate Chemical compound [Zn+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] WWRJFSIRMWUMAE-ZZMNMWMASA-L 0.000 description 1
- VRGNUPCISFMPEM-ZVGUSBNCSA-L zinc;(2r,3r)-2,3-dihydroxybutanedioate Chemical compound [Zn+2].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VRGNUPCISFMPEM-ZVGUSBNCSA-L 0.000 description 1
- NJNDBGREJCHIFG-MDTVQASCSA-L zinc;(2s)-2,6-diaminohexanoate Chemical compound [Zn+2].NCCCC[C@H](N)C([O-])=O.NCCCC[C@H](N)C([O-])=O NJNDBGREJCHIFG-MDTVQASCSA-L 0.000 description 1
- POEVDIARYKIEGF-CEOVSRFSSA-L zinc;(2s)-2-aminobutanedioate;hydron Chemical compound [Zn+2].[O-]C(=O)[C@@H](N)CC(O)=O.[O-]C(=O)[C@@H](N)CC(O)=O POEVDIARYKIEGF-CEOVSRFSSA-L 0.000 description 1
- HJSYJHHRQVHHMQ-TYYBGVCCSA-L zinc;(e)-but-2-enedioate Chemical compound [Zn+2].[O-]C(=O)\C=C\C([O-])=O HJSYJHHRQVHHMQ-TYYBGVCCSA-L 0.000 description 1
- JNPQFTCBVDSMDO-UHFFFAOYSA-L zinc;2,3-dihydroxypropanoate Chemical compound [Zn+2].OCC(O)C([O-])=O.OCC(O)C([O-])=O JNPQFTCBVDSMDO-UHFFFAOYSA-L 0.000 description 1
- UOXSXMSTSYWNMH-UHFFFAOYSA-L zinc;2-aminoacetate Chemical compound [Zn+2].NCC([O-])=O.NCC([O-])=O UOXSXMSTSYWNMH-UHFFFAOYSA-L 0.000 description 1
- GAMIYQSIKAOVTG-UHFFFAOYSA-L zinc;2-aminopentanedioate Chemical compound [Zn+2].[O-]C(=O)C(N)CCC([O-])=O GAMIYQSIKAOVTG-UHFFFAOYSA-L 0.000 description 1
- MCOGTQGPHPAUJN-UHFFFAOYSA-L zinc;2-hydroxyacetate Chemical compound [Zn+2].OCC([O-])=O.OCC([O-])=O MCOGTQGPHPAUJN-UHFFFAOYSA-L 0.000 description 1
- XLMCDAMBOROREP-UHFFFAOYSA-N zinc;3-phosphonooxypropane-1,2-diolate Chemical compound [Zn+2].OP(O)(=O)OCC([O-])C[O-] XLMCDAMBOROREP-UHFFFAOYSA-N 0.000 description 1
- AGFGXVAAIXIOFZ-UHFFFAOYSA-L zinc;butanedioate Chemical compound [Zn+2].[O-]C(=O)CCC([O-])=O AGFGXVAAIXIOFZ-UHFFFAOYSA-L 0.000 description 1
- WDHVIZKSFZNHJB-UHFFFAOYSA-L zinc;butanoate Chemical compound [Zn+2].CCCC([O-])=O.CCCC([O-])=O WDHVIZKSFZNHJB-UHFFFAOYSA-L 0.000 description 1
- JDLYKQWJXAQNNS-UHFFFAOYSA-L zinc;dibenzoate Chemical compound [Zn+2].[O-]C(=O)C1=CC=CC=C1.[O-]C(=O)C1=CC=CC=C1 JDLYKQWJXAQNNS-UHFFFAOYSA-L 0.000 description 1
- MFMKGXZULQONRI-UHFFFAOYSA-L zinc;diiodate Chemical compound [Zn+2].[O-]I(=O)=O.[O-]I(=O)=O MFMKGXZULQONRI-UHFFFAOYSA-L 0.000 description 1
- MQHUBPZUHMDZNT-UHFFFAOYSA-L zinc;methanedisulfonate Chemical compound [Zn+2].[O-]S(=O)(=O)CS([O-])(=O)=O MQHUBPZUHMDZNT-UHFFFAOYSA-L 0.000 description 1
- ZPEJZWGMHAKWNL-UHFFFAOYSA-L zinc;oxalate Chemical compound [Zn+2].[O-]C(=O)C([O-])=O ZPEJZWGMHAKWNL-UHFFFAOYSA-L 0.000 description 1
- XDWXRAYGALQIFG-UHFFFAOYSA-L zinc;propanoate Chemical compound [Zn+2].CCC([O-])=O.CCC([O-])=O XDWXRAYGALQIFG-UHFFFAOYSA-L 0.000 description 1
- NHVUUBRKFZWXRN-UHFFFAOYSA-L zinc;pyridine-2-carboxylate Chemical compound C=1C=CC=NC=1C(=O)O[Zn]OC(=O)C1=CC=CC=N1 NHVUUBRKFZWXRN-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
Description
本発明は、口臭及び歯周病の原因菌に対して有効であり、口臭及び／又は歯周病を、予防又は改善することができる組成物に関する。 The present invention relates to a composition that is effective against bacteria that cause bad breath and periodontal disease and can prevent or ameliorate bad breath and / or periodontal disease.
口腔から発せられる不快な臭いは、周囲の者を不快にさせるため社会的コミュニケーションの障害になる。そのため、口臭を低減することは全身の健康とともに良好な社会的コミュニケーションの維持にも繋がることから、口臭を低減する物質についてさまざまな観点から研究開発が行われてきた。 The unpleasant odor emitted from the oral cavity is an obstacle to social communication because it makes the surrounding people uncomfortable. For this reason, reducing bad breath leads to the maintenance of good social communication as well as general health. Therefore, research and development have been conducted from various viewpoints on substances that reduce bad breath.
歯周病は細菌の感染によって引き起こされる炎症性疾患である。歯周病は歯の喪失につながるばかりでなく、歯周病菌の飲み込みによる消化管への毒素の影響や腸内細菌叢の変化、更には、歯周組織から直接血液循環系に侵入して血管や各臓器に弊害を与えることが判っている。 Periodontal disease is an inflammatory disease caused by bacterial infection. Periodontal disease not only leads to tooth loss, but also the effects of toxins on the gastrointestinal tract due to swallowing of periodontal disease bacteria and changes in the intestinal microflora, and also directly enters the blood circulation system from the periodontal tissue. And it has been found to be harmful to each organ.
口臭の原因が口腔内による場合には、そのほとんどが、メチルメルカプタン、硫化水素、ジメチルサルファイドといった揮発性硫黄化合物（ＶＳＣ）であることがよく知られている。このような揮発性硫黄化合物は、口腔内に棲息する嫌気性細菌の代謝によって産生される。特に、歯周病の病原菌でもある、プレボテラ・インターメディア(Prevotella intermedia)、ポルフィロモナス・ジンジバリス(Porphyromonas gingivalis)、タネレラ・フォーサイセンシス(Tannerella forsythensis)、カンピロバクター・レクタス(Campylobacter rectus)、トレポネーマ・デンティコーラ(Treponema denticola)、フゾバクテリウム・ヌクレアタム(Fusobacterium nucleatum)等の細菌が高いＶＳＣ産生能を有すると言われており、それゆえ歯周病患者の口腔からはとりわけ強い悪臭が発生する。
口臭の原因物質であるＶＳＣは、唾液中のタンパクや脱落上皮細胞あるいは食物残渣に存在するシステインやメチオニンといった成分を基質として口腔内細菌が代謝を行う際に産生されるものであって、口臭を根本的に抑制するには、歯周病と同様に、口腔内細菌の殺菌又は増殖を抑制することが必要不可欠である。
When the cause of bad breath is in the oral cavity, it is well known that most of them are volatile sulfur compounds (VSC) such as methyl mercaptan, hydrogen sulfide, and dimethyl sulfide. Such volatile sulfur compounds are produced by the metabolism of anaerobic bacteria that inhabit the oral cavity. In particular, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythensis, Campylobacter rectus, Treponema denticola, which are pathogens of periodontal disease Bacteria such as (Treponema denticola) and Fusobacterium nucleatum are said to have a high VSC producing ability, and therefore a particularly strong odor is generated from the oral cavity of periodontal disease patients.
VSC, the causative agent of bad breath, is produced when oral bacteria metabolize using cysteine and methionine components in saliva, deciduous epithelial cells or food residues as a substrate. In order to suppress it fundamentally, it is indispensable to suppress sterilization or growth of oral bacteria as in periodontal disease.
銅化合物や亜鉛化合物には殺菌作用を有することが知られ（特許文献１）、グルコン酸銅及び塩化亜鉛に、キサンタンガム又はヒドロキシエチルセルロースを含有した、収斂実感かつ曳糸性が改善された歯磨剤が知られている（特許文献２）。 It is known that a copper compound and a zinc compound have a bactericidal action (Patent Document 1), and a dentifrice containing xanthan gum or hydroxyethyl cellulose in copper gluconate and zinc chloride and having an astringent feeling and improved spinnability. Known (Patent Document 2).
メントールについては、メントールを主成分とするハッカオイルなど、食品用の香料成分等を抗菌剤として使用する技術が開示されている。（特許文献３）。 As for menthol, a technique of using a fragrance ingredient for foods such as mint oil mainly composed of menthol as an antibacterial agent is disclosed. (Patent Document 3).
しかし、これまでに銅化合物、亜鉛化合物、及びＬ−メントールを組合せて使用することで飛躍的に口臭及び歯周病の原因菌の殺菌又は増殖を抑制できるということは知られていない。 However, it has not been known so far that the use of a copper compound, a zinc compound, and L-menthol in combination can drastically suppress the sterilization or proliferation of causal odors and periodontal diseases.
本発明の課題は、口臭及び歯周病の発生原因である細菌について、殺菌又は菌の増殖を抑制することで、口臭及び／又は歯周病を、予防又は改善することができる組成物を提供することである。 An object of the present invention is to provide a composition capable of preventing or improving halitosis and / or periodontal disease by sterilizing or suppressing the growth of bacteria for bacteria that cause halitosis and periodontal disease. It is to be.
本発明者らは、かかる課題を解決するために鋭意研究を行う中で、銅化合物、亜鉛化合物、及びＬ−メントールの組合せが優れた抗菌作用及び唾液分泌作用を示すことを見出し、本発明を完成させた。すなわち、本発明は、銅化合物、亜鉛化合物、及びＬ−メントールを含有する、口臭又は／及び歯周病の、予防又は改善用組成物である。 In order to solve such problems, the present inventors have found that the combination of a copper compound, a zinc compound, and L-menthol exhibits an excellent antibacterial action and salivary secretion action. Completed. That is, the present invention is a composition for preventing or improving bad breath or / and periodontal disease, which contains a copper compound, a zinc compound, and L-menthol.
すなわち、本発明は下記（１）〜（５）に関する。
（１）銅化合物、亜鉛化合物、及びＬ−メントールを含有する、口腔用組成物。
（２）銅化合物が、硫酸銅、グルコン酸銅、銅クロロフィリンナトリウム、及び銅クロロフィルからなる群より選ばれる１種又は２種以上である、（１）に記載の組成物。
（３）亜鉛化合物が、酸化亜鉛、炭酸亜鉛、塩化亜鉛、硫酸亜鉛、グルコン酸亜鉛、ウンデシレン酸亜鉛、低温焼成酸化亜鉛、パラフェノールスルホン酸亜鉛、パルミチン酸亜鉛、ピリチオン亜鉛、ミリスチン酸亜鉛、及びラウリン酸亜鉛からなる群より選ばれる１種又は２種以上である、（１）又は（２）に記載の組成物。
（４）銅化合物がグルコン酸銅であり、亜鉛化合物が塩化亜鉛である（１）に記載の組成物。
（５）口臭及び／又は歯周病の、予防又は改善に用いられる（１）乃至（４）のいずれか１に記載の組成物。
That is, the present invention relates to the following (1) to (5).
(1) The composition for oral cavity containing a copper compound, a zinc compound, and L-menthol.
(2) The composition according to (1), wherein the copper compound is one or more selected from the group consisting of copper sulfate, copper gluconate, copper chlorophyllin sodium, and copper chlorophyll.
(3) the zinc compound is zinc oxide, zinc carbonate, zinc chloride, zinc sulfate, zinc gluconate, zinc undecylenate, low-temperature fired zinc oxide, zinc paraphenolsulfonate, zinc palmitate, zinc pyrithione, zinc myristate, and The composition according to (1) or (2), which is one or more selected from the group consisting of zinc laurate.
(4) The composition according to (1), wherein the copper compound is copper gluconate and the zinc compound is zinc chloride.
(5) The composition according to any one of (1) to (4), which is used for prevention or improvement of bad breath and / or periodontal disease.
本発明によれば、優れた抗菌作用を有する口臭又は／及び歯周病の、予防又は改善用組成物を提供することができる。本発明の組成物により、口腔内の口臭及び歯周病の原因菌が殺菌又はその増殖が抑制されると共に、本発明の組成物による唾液分泌促進作用によって生じた唾液が、上記原因菌を殺菌又はその増殖を抑制する。 According to the present invention, a composition for preventing or improving bad breath or / and periodontal disease having an excellent antibacterial action can be provided. The composition of the present invention sterilizes the oral bad breath and periodontal disease causative bacteria or suppresses their growth, and saliva produced by the salivary secretion promoting action of the composition of the present invention sterilizes the causative bacteria. Or the proliferation is suppressed.
本発明において、「予防」とは、口臭及び歯周病の原因菌を殺菌又は菌の増殖を抑制することにより、口臭又は／及び歯周病の発症を防ぐことを意味する。 In the present invention, “prevention” means prevention of the development of halitosis or / and periodontal disease by sterilizing the causative bacteria of bad breath and periodontal disease or suppressing the growth of the bacteria.
本発明において、「改善」とは、口臭及び歯周病の原因菌を低減することにより、口臭又は／及び歯周病の症状を軽減することを意味する。 In the present invention, “improvement” means that the symptoms of bad breath and / or periodontal disease are reduced by reducing the causative bacteria of bad breath and periodontal disease.
本発明において用いられる「銅化合物」とは、銅の無機塩又は有機塩であり、医薬品・食品・化粧品原料に用いられるものであればよく、例えば、酸化銅、ホウ酸銅、炭酸銅、フッ化銅、ヨウ素酸銅、塩化銅、硫酸銅、硝酸銅、酢酸銅、乳酸銅、酪酸銅、蟻酸銅、クエン酸銅、リン酸銅、グルコン酸銅、アスパラギン酸銅、グルタミン酸銅、プロピオン酸銅、シュウ酸銅、フィチン酸銅、酒石酸銅、リンゴ酸銅、コハク酸銅、マロン酸銅、マレイン酸銅、安息香酸銅、サリチル酸銅、フマル酸銅、グリセリン酸銅、グリセロリン酸銅、グリコール酸銅、ピコリン酸銅、アスコルビン酸銅、ビスグリシン酸銅、リシン酸銅、メチオニン酸銅、ピドロ酸銅、オレイン酸銅、ステアリン酸銅、ラウロイルサルコシン銅、フルオロケイ酸銅、フルオロホウ酸銅、ウンデシレン酸亜鉛、銅クロロフィリンナトリウム、又は銅クロロフィル等が挙げられ、好適には、硫酸銅、グルコン酸銅、銅クロロフィリンナトリウム、又は銅クロロフィルが挙げられ、より好適には、グルコン酸銅が挙げられる。 The “copper compound” used in the present invention is an inorganic salt or organic salt of copper and may be used as a raw material for pharmaceuticals, foods, and cosmetics. For example, copper oxide, copper borate, copper carbonate, fluorine Copper iodide, copper iodate, copper chloride, copper sulfate, copper nitrate, copper acetate, copper lactate, copper butyrate, copper formate, copper citrate, copper phosphate, copper gluconate, copper aspartate, copper glutamate, copper propionate , Copper oxalate, copper phytate, copper tartrate, copper malate, copper succinate, copper malonate, copper maleate, copper benzoate, copper salicylate, copper fumarate, copper glycerate, copper glycerophosphate, copper glycolate , Copper picolinate, copper ascorbate, copper bisglycinate, copper ricinate, copper methionate, copper pudroate, copper oleate, copper stearate, copper lauroyl sarcosine, copper fluorosilicate, fluoro Examples thereof include copper oxalate, zinc undecylenate, copper chlorophyllin sodium, or copper chlorophyll, preferably copper sulfate, copper gluconate, copper chlorophyllin sodium, or copper chlorophyll, and more preferably copper gluconate. Is mentioned.
本発明において用いられる「亜鉛化合物」とは、亜鉛の無機塩又は有機塩であり、医薬品・食品・化粧品原料に用いられるものであればよく、例えば、酸化亜鉛、ホウ酸亜鉛、炭酸亜鉛、フッ化亜鉛、ヨウ素酸亜鉛、塩化亜鉛、硫酸亜鉛、硝酸亜鉛、酢酸亜鉛、乳酸亜鉛、酪酸亜鉛、蟻酸亜鉛、クエン酸亜鉛、リン酸亜鉛、グルコン酸亜鉛、アスパラギン酸亜鉛、グルタミン酸亜鉛、プロピオン酸亜鉛、シュウ酸亜鉛、フィチン酸亜鉛、酒石酸亜鉛、リンゴ酸亜鉛、コハク酸亜鉛、マロン酸亜鉛、マレイン酸亜鉛、安息香酸亜鉛、サリチル酸亜鉛、フマル酸亜鉛、グリセリン酸亜鉛、グリセロリン酸亜鉛、グリコール酸亜鉛、ピコリン酸亜鉛、アスコルビン酸亜鉛、ビスグリシン酸亜鉛、リシン酸亜鉛、メチオニン酸亜鉛、ピドロ酸亜鉛、オレイン酸亜鉛、ステアリン酸亜鉛、ラウロイルサルコシン亜鉛、フルオロケイ酸亜鉛、フルオロホウ酸亜鉛、又はウンデシレン酸亜鉛等が挙げられ、好適には、酸化亜鉛、炭酸亜鉛、塩化亜鉛、硫酸亜鉛、グルコン酸亜鉛、ウンデシレン酸亜鉛、低温焼成酸化亜鉛、パラフェノールスルホン酸亜鉛、パルミチン酸亜鉛、ピリチオン亜鉛、ミリスチン酸亜鉛、又はラウリン酸亜鉛が挙げられ、より好適には、塩化亜鉛が挙げられる。 The “zinc compound” used in the present invention is an inorganic salt or organic salt of zinc and may be used as a raw material for pharmaceuticals, foods and cosmetics. For example, zinc oxide, zinc borate, zinc carbonate, fluorine Zinc iodide, Zinc iodate, Zinc chloride, Zinc sulfate, Zinc nitrate, Zinc acetate, Zinc lactate, Zinc butyrate, Zinc formate, Zinc citrate, Zinc phosphate, Zinc gluconate, Zinc aspartate, Zinc glutamate, Zinc propionate , Zinc oxalate, Zinc phytate, Zinc tartrate, Zinc malate, Zinc succinate, Zinc malonate, Zinc maleate, Zinc benzoate, Zinc salicylate, Zinc fumarate, Zinc glycerate, Zinc glycerophosphate, Zinc glycolate , Zinc picolinate, zinc ascorbate, zinc bisglycinate, zinc lysinate, zinc methionate, zinc pidroate, Zinc innate, zinc stearate, zinc lauroyl sarcosine, zinc fluorosilicate, zinc fluoroborate, zinc undecylenate, etc., preferably zinc oxide, zinc carbonate, zinc chloride, zinc sulfate, zinc gluconate, Examples include zinc undecylenate, low-temperature calcined zinc oxide, zinc paraphenolsulfonate, zinc palmitate, zinc pyrithione, zinc myristate, or zinc laurate, and more preferably zinc chloride.
本発明において用いられる「Ｌ−メントール」は、Ｌ−メントール単剤として用いてもよいし、Ｌ−メントールが含まれる清涼剤又は香料を用いてもよい。
本発明において用いられる上記の「銅化合物」、「亜鉛化合物」及び「Ｌ−メントール」は、医薬部外品、食品又は化粧品原料として市販されており、容易に入手でき、また、公知の方法で製造することもできる。
The “L-menthol” used in the present invention may be used as a single agent of L-menthol, or a refreshing agent or a fragrance containing L-menthol may be used.
The above-mentioned “copper compound”, “zinc compound” and “L-menthol” used in the present invention are commercially available as quasi-drugs, foods or cosmetic raw materials, and can be easily obtained, or by known methods. It can also be manufactured.
本発明は、医薬品、医薬部外品、化粧品等として使用される。 The present invention is used as pharmaceuticals, quasi drugs, cosmetics and the like.
本発明の形態や、口腔への適用方法は特に限定されない。例えば、マウスウォッシュ（洗口剤）、練歯磨、液体歯磨、歯磨粉、ガム剤、トローチ剤、バッカル錠、歯肉付着性テープ製剤、口腔内用ゲル製剤、口腔内用軟膏、口腔内用スプレー剤、口腔内用パスタ剤、口腔内用ペースト剤、口腔用丸剤、口腔内用錠剤、口腔用散剤、口腔内用粉剤、口腔内用液剤、口腔内用懸濁剤、口腔内用乳剤、口腔内用顆粒剤、又は口腔内用カプセル剤などが挙げられる。好ましくは、マウスウォッシュ（洗口剤）、練歯磨、液体歯磨又は歯磨粉である。 The form of this invention and the application method to an oral cavity are not specifically limited. For example, mouthwash, toothpaste, liquid toothpaste, toothpaste, gum, troche, buccal tablets, gingival adhesive tape, oral gel, oral ointment, oral spray , Oral paste, oral paste, oral pill, oral tablet, oral powder, oral powder, oral liquid, oral suspension, oral emulsion, oral cavity Examples thereof include an internal granule or an oral capsule. Mouthwash (mouth wash), toothpaste, liquid toothpaste or toothpaste are preferred.
本発明における、銅化合物の組成物中の配合量は、好ましくは、０．００１〜１０重量％であり、より好ましくは、０．０１〜１重量％である。 In the present invention, the blending amount of the copper compound in the composition is preferably 0.001 to 10% by weight, more preferably 0.01 to 1% by weight.
本発明における、亜鉛化合物の組成物中の濃度は、好ましくは、０．００１〜１重量％であり、より好ましくは０．０１〜０．１重量％である。 In the present invention, the concentration of the zinc compound in the composition is preferably 0.001 to 1% by weight, more preferably 0.01 to 0.1% by weight.
本発明における、Ｌ−メントールの組成物中の配合量は、好ましくは、０．００１〜５重量％であり、より好ましくは０．０１〜１重量％である。 The compounding quantity in the composition of L-menthol in this invention becomes like this. Preferably it is 0.001 to 5 weight%, More preferably, it is 0.01 to 1 weight%.
本発明において、銅化合物、亜鉛化合物、及びＬ−メントールは任意の比率で混合して使用することが出来る。 In this invention, a copper compound, a zinc compound, and L-menthol can be mixed and used for arbitrary ratios.
本発明には、湿潤剤、ｐＨ調節剤、矯味剤、防腐剤、香料、可溶化剤等を適宜添加することができる。 In the present invention, wetting agents, pH adjusting agents, flavoring agents, preservatives, fragrances, solubilizers and the like can be added as appropriate.
湿潤剤としては、医薬品・食品・化粧品原料として市販されているものであればよく、例えば、多価アルコール、さらに具体的にソルビット、グリセリン、濃グリセリン、エチレングリコール、プロピレングリコール、１,３−ブチレングリコール、プロパンジオール(１，３−プロパンジオール)、ポリエチレングリコール、ポリプロピレングリコール、キシリット、マルチット、ラクチット、トレハロース、ヒアルロン酸ナトリウム、加水分解コラーゲン等が挙げられ、これらの１種又は２種以上の組み合わせを適宜選択して、必要に応じて配合することができる。 The wetting agent is not particularly limited as long as it is commercially available as a raw material for pharmaceuticals, foods and cosmetics. For example, polyhydric alcohol, more specifically sorbit, glycerin, concentrated glycerin, ethylene glycol, propylene glycol, 1,3-butylene. Glycol, propanediol (1,3-propanediol), polyethylene glycol, polypropylene glycol, xylit, malt, lactit, trehalose, sodium hyaluronate, hydrolyzed collagen, etc., and one or a combination of two or more of these It can select suitably and can mix | blend as needed.
本発明の歯周病又は口臭用組成物のｐＨは、４．５〜８．０の範囲であるのが好ましい。本発明に使用しうるｐＨ調整剤としては、例えばリン酸、リン酸一水素ナトリウム、リン酸二水素ナトリウム、リン酸一水素カリウム、リン酸二水素カリウム、クエン酸、リンゴ酸、ピロリン酸、酒石酸、酢酸又はこれらの塩、水酸化ナトリウム等が挙げられる。これらの１種又は２種以上の組み合わせを適宜選択して、必要に応じて配合することができる。 The pH of the composition for periodontal disease or bad breath according to the present invention is preferably in the range of 4.5 to 8.0. Examples of the pH adjuster that can be used in the present invention include phosphoric acid, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, potassium dihydrogen phosphate, citric acid, malic acid, pyrophosphoric acid, tartaric acid. , Acetic acid or a salt thereof, sodium hydroxide and the like. These 1 type, or 2 or more types of combinations can be selected suitably, and can be mix | blended as needed.
矯味剤としては、例えば、サッカリン、サッカリンナトリウム、グリチルリチン酸二ナトリウム、グリチルリチン酸三ナトリウム、ショ糖、ブドウ糖、果糖、乳糖、ハチミツ、アスパルテーム、ステビア、スクラロース、キシリトール、イノシトール、Ｄ−ソルビトール、Ｄ−マンニトール、ラフィノース、ラクチュロース、ラクチトール、エリスリトール、還元パラチノース、パラチノース、パラチニット、アセスルファムＫ、マルトース、マルトシルトレハロース又はマルチトールが挙げられる。これらの１種又は２種以上の組み合わせを適宜選択して配合することができる。 Examples of the corrigent include, for example, saccharin, sodium saccharin, disodium glycyrrhizinate, trisodium glycyrrhizinate, sucrose, glucose, fructose, lactose, honey, aspartame, stevia, sucralose, xylitol, inositol, D-sorbitol, D-mannitol, Examples include raffinose, lactulose, lactitol, erythritol, reduced palatinose, palatinose, palatinit, acesulfame K, maltose, maltosyl trehalose or maltitol. These 1 type, or 2 or more types of combinations can be selected suitably, and can be mix | blended.
防腐剤としては、例えば、メチルパラベン、エチルパラベン、イソプロピルパラベン、プロピルパラベン、ブチルパラベン、イソブチルパラベン、ベンジルパラベン等のパラベン（パラオキシ安息香酸エステル）類、フェノキシエタノール、エタノール等のアルコール類、あるいはソルビン酸、安息香酸、デヒドロ酢酸、プロピオン酸又はこれらの塩等が挙げられる。これらの１種又は２種以上の組み合わせを適宜選択して配合することができる。 Examples of the preservative include parabens (paraoxybenzoic acid esters) such as methylparaben, ethylparaben, isopropylparaben, propylparaben, butylparaben, isobutylparaben and benzylparaben, alcohols such as phenoxyethanol and ethanol, or sorbic acid and benzoic acid. Examples thereof include acids, dehydroacetic acid, propionic acid, and salts thereof. These 1 type, or 2 or more types of combinations can be selected suitably, and can be mix | blended.
香料としては、例えば、Ｌ−メントール、ペパーミント、スペアミント又はフルーツ香料、ハッカ油等が挙げられる。香料は、唾液分泌を刺激するという利点も有する。これらの１種又は２種以上の組み合わせを適宜選択して配合することができる。 Examples of the fragrance include L-menthol, peppermint, spearmint or fruit fragrance, mint oil, and the like. The perfume also has the advantage of stimulating salivation. These 1 type, or 2 or more types of combinations can be selected suitably, and can be mix | blended.
可溶化剤は、本発明の主基剤である水への上記添加剤や薬効成分の溶解を促進させるために添加してもよい。そのような可溶化剤の例として、プロピレングリコール、ジプロピレングリコール、ブチレングリコール、ポリエチレングリコール等の多価アルコール類等を挙げることができる。これらの１種又は２種以上の組み合わせを適宜選択して配合することができる。 You may add a solubilizer in order to accelerate | stimulate melt | dissolution of the said additive and medicinal component in the water which is the main base of this invention. Examples of such a solubilizer include polyhydric alcohols such as propylene glycol, dipropylene glycol, butylene glycol, and polyethylene glycol. These 1 type, or 2 or more types of combinations can be selected suitably, and can be mix | blended.
その他、歯磨や軟膏の場合には研磨剤、発泡剤、粘稠剤が適宜使用される。 In addition, in the case of dentifrice and ointment, an abrasive, a foaming agent, and a thickener are appropriately used.
本発明には、さらに抗菌剤、抗炎症剤、フッ化物、ビタミン剤、生薬エキス、歯垢分解酵素等の薬効成分を配合することができる。これらの薬効成分は、医薬品等に使用しうるものであれば特に限定されない。 The present invention may further contain medicinal ingredients such as antibacterial agents, anti-inflammatory agents, fluorides, vitamins, crude drug extracts, plaque degrading enzymes and the like. These medicinal ingredients are not particularly limited as long as they can be used for pharmaceuticals and the like.
以下に、実施例、製剤例を示し、本発明をさらに詳細に説明するが、本発明の範囲はこれらに限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples and Formulation Examples, but the scope of the present invention is not limited thereto.
（実施例１）口臭原因菌の増殖抑制試験
（１）被験物質
グルコン酸銅（以下、GCu）及び塩化亜鉛（以下、ZnCl2）は和光純薬工業製、Ｌ−メントール（以下、Men）は鈴木薄荷製のものを使用した。
（２）試験菌株
本試験には、口臭及び歯周病の原因菌としてよく知られているPrevotella intermedia ATCC 25611を使用した。
（３）試験方法：菌液調製
Prevotella intermediaはアネロコロンビアウサギ血液寒天培地(日本ベクトン・ディッキンソン)で35℃、48〜72時間嫌気培養後、滅菌生理食塩液を用いて懸濁し、約3.0×108 CFU/mLの菌液を調製した。さらにGAM brothを用いて約107 CFU/mLとなるように菌液を調製した。
（４）試験方法：試験液調製
グルコン酸銅、塩化亜鉛、Ｌ−メントールの被験物質を各終濃度となるように培地にて調製し、この9.9 容に対してPrevotella intermediaの菌液を各0.1容添加して試験液を調製した。これを35℃、嫌気条件下で24時間培養を行った後、1mLあたりの生菌数(CFU/mL)を測定した。
（５）試験結果
各被験物質及び対照（菌液のみ）の生菌数測定結果を、それぞれ表１及び図１に示す。
表１及び図１より、グルコン酸銅(GCu)、塩化亜鉛(ZnCl2)及びＬ−メントール(Men)を併用することで口臭及び歯周病の原因菌に対して優れた抗菌作用が飛躍的に発現するという意外な結果が得られた。
(Example 1) growth inhibition test of halitosis causing bacteria (1) test substance copper gluconate (hereinafter, GCU) and zinc chloride (hereinafter, ZnCl 2) is made by Wako Pure Chemical Industries, L- menthol (hereinafter, Men) is The thing made from Suzuki light load was used.
(2) Test strain Prevotella intermedia ATCC 25611, which is well known as a causative bacterium of bad breath and periodontal disease, was used in this test.
(3) Test method: Bacterial solution preparation
Prevotella intermedia was anaerobically cultured on Anero Columbia rabbit blood agar medium (Nippon Becton Dickinson) at 35 ° C for 48-72 hours, and then suspended in sterile physiological saline to prepare approximately 3.0 x 10 8 CFU / mL bacterial solution did. Further, a bacterial solution was prepared using GAM broth so as to be about 10 7 CFU / mL.
(4) Test method: Preparation of test solution Copper gluconate, zinc chloride, and L-menthol test substances were prepared in a medium so as to have final concentrations. The test solution was prepared by volume addition. This was cultured at 35 ° C. under anaerobic conditions for 24 hours, and then the viable cell count (CFU / mL) per mL was measured.
(5) Test results Table 1 and Fig. 1 show the viable count results of each test substance and control (bacteria solution only), respectively.
From Table 1 and Fig. 1, the combination of copper gluconate (GCu), zinc chloride (ZnCl 2 ), and L-menthol (Men) has dramatically improved antibacterial action against bacteria that cause bad breath and periodontal disease. Surprising results were obtained.
（実施例２）唾液分泌促進作用試験
（１）被験物質
グルコン酸銅及び塩化亜鉛は和光純薬工業製、Ｌ−メントールは鈴木薄荷製のものを使用した。
（２）使用動物
Ｓｌｃ：Ｗｉｓｔａｒ雄ラット［日本エスエルシー（株）］６週齢を購入し、検疫・馴化を行った。
（３）試験方法
検疫・馴化期間（７日間）を終了したラットをウレタン（１ｇ／ｋｇ）及びα−クロラロース（２５ｍｇ／ｋｇ）を腹腔内投与し麻酔を行い、気道確保のために気管カニューレを実施し、投与液の胃内流入を防ぐため、食道を縫合糸で結紮した。
次に、グルコン酸銅４ｍｇ／ｍＬ及び塩化亜鉛１０ｍｇ／ｍＬの混合物を媒体（４％カルボキシメチルセルロースナトリウム水溶液：ＣＭＣ水溶液と称す）を用いて調製した被験物質投与液をマイクロピペットで口腔内に１００μＬ投与した。
同様にして、グルコン酸銅４ｍｇ／ｍＬ、塩化亜鉛１０ｍｇ／ｍＬ、及びＬ−メントール１０ｍｇ／ｍＬの混合物を媒体（４％カルボキシメチルセルロースナトリウム水溶液：ＣＭＣ水溶液と称す）を用いて調製した被験物質投与液を、マイクロピペットで口腔内に１００μＬ投与した。
なお、対照として、媒体（４％ＣＭＣ水溶液）を口腔内に、被験物質と同量（１００μＬ）を投与した。
媒体又は被験物質投与１０分後に、風袋重量測定済みの綿球を用いて、口腔内の媒体又は投与液を拭い取った。拭き取り後の重量から風袋と媒体又は被験物質投与液の重量を差し引いて、投与中の唾液分泌量を概算した。
口腔内の媒体又は投与液を拭い取った直後に、口腔内に風袋重量測定済みの綿球を入れた。いずれの群についても、１０分ごとに綿球を交換し、交換後の重量との差し引きで唾液分泌量を測定した。測定は３０分後まで実施した。
（４）試験結果
各被験物質及び対照（媒体）投与から３０分間の総唾液分泌量の測定結果（いずれもｎ＝６）を、それぞれ表２及び図２に示す。
表２及び図２より、グルコン酸銅、塩化亜鉛及びＬ−メントールを併用することで対照と比較して約400倍もの優れた唾液分泌促進作用が発現するという意外な結果が得られた。
(Example 2) Salivary secretion promoting action test (1) Test substances Copper gluconate and zinc chloride were manufactured by Wako Pure Chemical Industries, and L-menthol was manufactured by Suzuki Hikaru.
(2) Animals used Slc: Wistar male rats [Japan SLC Co., Ltd.] 6 weeks old were purchased, quarantined and acclimatized.
(3) Test method Rats that have completed the quarantine / acclimation period (7 days) are given anesthesia with urethane (1 g / kg) and α-chloralose (25 mg / kg) intraperitoneally, and a tracheal cannula is attached to secure the airway. The esophagus was ligated with a suture to prevent the administration solution from flowing into the stomach.
Next, 100 μL of the test substance administration solution prepared by using a medium (4% sodium carboxymethylcellulose aqueous solution: CMC aqueous solution) prepared from a mixture of copper gluconate 4 mg / mL and zinc chloride 10 mg / mL in the oral cavity with a micropipette did.
Similarly, a test substance-administered solution prepared by using a medium (4% sodium carboxymethylcellulose aqueous solution: CMC aqueous solution) as a mixture of copper gluconate 4 mg / mL, zinc chloride 10 mg / mL, and L-menthol 10 mg / mL Was administered into the oral cavity with a micropipette.
As a control, a medium (4% CMC aqueous solution) was administered into the oral cavity in the same amount (100 μL) as the test substance.
Ten minutes after administration of the medium or test substance, the medium or administration liquid in the oral cavity was wiped with a cotton ball having a tare weight measured. The saliva secretion amount during administration was estimated by subtracting the weight of the tare and the medium or the test substance administration liquid from the weight after wiping.
Immediately after wiping off the medium or administration liquid in the oral cavity, a tare weight-measured cotton ball was placed in the oral cavity. In any group, the cotton balls were changed every 10 minutes, and the saliva secretion amount was measured by subtracting the weight after the replacement. The measurement was carried out until 30 minutes later.
(4) Test results Table 2 and Fig. 2 show the measurement results of total salivary secretion for 30 minutes after administration of each test substance and control (vehicle) (both are n = 6), respectively.
From Table 2 and FIG. 2, the unexpected result that the salivary secretion promotion effect about 400 times as compared with the control | contrast was expressed by using copper gluconate, zinc chloride, and L-menthol together was obtained.
（製剤例１，２，３，４，５）歯磨剤
表３の成分及び分量をとり、常法に従ってペースト状の歯磨剤を製造する。
(Formulation Examples 1, 2, 3, 4, 5) Dentifrice The ingredients and amounts shown in Table 3 are used to produce a paste dentifrice according to a conventional method.
（製剤例６，７，８，９，１０）洗口液
表４の成分及び分量をとり、常法に従って洗口液を製造する。
(Formulation Examples 6, 7, 8, 9, 10) Mouthwash The ingredients and amounts shown in Table 4 are taken, and a mouthwash is produced according to a conventional method.
（製剤例１１）口腔内用軟膏
表５の成分及び分量をとり、常法に従って口腔内用軟膏を製造する。
(Formulation Example 11) Oral Ointment The ingredients and amounts shown in Table 5 are taken, and an oral ointment is produced according to a conventional method.
（製剤例１２）トローチ剤
表６の成分及び分量をとり、日局製剤総則「トローチ剤」の項に準じてトローチ剤を製造する。
(Formulation Example 12) Lozenges The ingredients and amounts shown in Table 6 are taken, and lozenges are produced according to the section “General Lozenges” in Japanese Pharmacopoeia.
（製剤例１３）口腔内用錠剤
表７の成分及び分量をとり、日局製剤総則「口腔用錠剤」の項に準じて口腔内用錠剤を製造する。
(Formulation Example 13) Oral Tablets Ingredients and quantities shown in Table 7 are taken, and oral tablets are produced according to the section “General Oral Tablets” in the Japanese Pharmacopoeia.
Claims (5)
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| WO2021255472A1 (en) * | 2020-06-19 | 2021-12-23 | Marvelbiotics Limited | Antimicrobial combinations |
| WO2022137870A1 (en) * | 2020-12-23 | 2022-06-30 | 小林製薬株式会社 | Composition for oral cavity |
| KR20230040932A (en) * | 2021-09-15 | 2023-03-23 | 주식회사 엘지생활건강 | Composition for removing or improving oral malodor |
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| WO2022137870A1 (en) * | 2020-12-23 | 2022-06-30 | 小林製薬株式会社 | Composition for oral cavity |
| KR20230040932A (en) * | 2021-09-15 | 2023-03-23 | 주식회사 엘지생활건강 | Composition for removing or improving oral malodor |
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| JP7382697B2 (en) | 2023-11-17 |
| JP2023080246A (en) | 2023-06-08 |
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