CN103717225B - 用于减少口腔挥发性硫化合物(vsc)的含有锌盐和异硫氰酸酯的组合物 - Google Patents
用于减少口腔挥发性硫化合物(vsc)的含有锌盐和异硫氰酸酯的组合物 Download PDFInfo
- Publication number
- CN103717225B CN103717225B CN201280037437.1A CN201280037437A CN103717225B CN 103717225 B CN103717225 B CN 103717225B CN 201280037437 A CN201280037437 A CN 201280037437A CN 103717225 B CN103717225 B CN 103717225B
- Authority
- CN
- China
- Prior art keywords
- isothiocyanate
- zinc
- oral cavity
- composition
- compositions
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 96
- 150000002540 isothiocyanates Chemical group 0.000 title claims abstract description 60
- 150000003751 zinc Chemical class 0.000 title claims abstract description 54
- 150000003464 sulfur compounds Chemical class 0.000 title claims abstract description 18
- 210000000214 mouth Anatomy 0.000 claims abstract description 74
- ZOJBYZNEUISWFT-UHFFFAOYSA-N allyl isothiocyanate Chemical compound C=CCN=C=S ZOJBYZNEUISWFT-UHFFFAOYSA-N 0.000 claims description 80
- 235000015218 chewing gum Nutrition 0.000 claims description 66
- 229940112822 chewing gum Drugs 0.000 claims description 66
- CANRESZKMUPMAE-UHFFFAOYSA-L Zinc lactate Chemical compound [Zn+2].CC(O)C([O-])=O.CC(O)C([O-])=O CANRESZKMUPMAE-UHFFFAOYSA-L 0.000 claims description 32
- 239000011576 zinc lactate Substances 0.000 claims description 32
- 235000000193 zinc lactate Nutrition 0.000 claims description 32
- 229940050168 zinc lactate Drugs 0.000 claims description 32
- MDKCFLQDBWCQCV-UHFFFAOYSA-N benzyl isothiocyanate Chemical compound S=C=NCC1=CC=CC=C1 MDKCFLQDBWCQCV-UHFFFAOYSA-N 0.000 claims description 30
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 25
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 25
- -1 isothiocyanic acid norborneol ester Chemical class 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 16
- QAADZYUXQLUXFX-UHFFFAOYSA-N N-phenylmethylthioformamide Natural products S=CNCC1=CC=CC=C1 QAADZYUXQLUXFX-UHFFFAOYSA-N 0.000 claims description 15
- QKGJFQMGPDVOQE-UHFFFAOYSA-N Sulforaphen Natural products CS(=O)C=CCCN=C=S QKGJFQMGPDVOQE-UHFFFAOYSA-N 0.000 claims description 13
- 235000009508 confectionery Nutrition 0.000 claims description 13
- QKGJFQMGPDVOQE-HWKANZROSA-N raphanin Chemical group CS(=O)\C=C\CCN=C=S QKGJFQMGPDVOQE-HWKANZROSA-N 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- IZJDOKYDEWTZSO-UHFFFAOYSA-N phenethyl isothiocyanate Chemical compound S=C=NCCC1=CC=CC=C1 IZJDOKYDEWTZSO-UHFFFAOYSA-N 0.000 claims description 11
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 10
- 239000011670 zinc gluconate Substances 0.000 claims description 10
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical group [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 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 235000011478 zinc gluconate Nutrition 0.000 claims description 9
- 229960000306 zinc gluconate Drugs 0.000 claims description 9
- 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 claims description 8
- 239000011746 zinc citrate Substances 0.000 claims description 8
- 235000006076 zinc citrate Nutrition 0.000 claims description 8
- 229940068475 zinc citrate Drugs 0.000 claims description 8
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 claims description 7
- 239000007937 lozenge Substances 0.000 claims description 7
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 claims description 7
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 6
- 239000004246 zinc acetate Substances 0.000 claims description 6
- 235000013904 zinc acetate Nutrition 0.000 claims description 6
- 244000246386 Mentha pulegium Species 0.000 claims description 5
- 235000016257 Mentha pulegium Nutrition 0.000 claims description 5
- 235000004357 Mentha x piperita Nutrition 0.000 claims description 5
- 235000001050 hortel pimenta Nutrition 0.000 claims description 5
- 239000006188 syrup Substances 0.000 claims description 4
- 235000020357 syrup Nutrition 0.000 claims description 4
- 235000019219 chocolate Nutrition 0.000 claims description 3
- 238000007906 compression Methods 0.000 claims description 3
- 230000006835 compression Effects 0.000 claims description 3
- 235000014510 cooky Nutrition 0.000 claims description 3
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 claims description 3
- 229940117953 phenylisothiocyanate Drugs 0.000 claims description 3
- 229960000314 zinc acetate Drugs 0.000 claims description 3
- 210000003800 pharynx Anatomy 0.000 claims description 2
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims 1
- 210000000867 larynx Anatomy 0.000 claims 1
- 206010006326 Breath odour Diseases 0.000 description 39
- 208000032139 Halitosis Diseases 0.000 description 34
- 150000001875 compounds Chemical class 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 230000001055 chewing effect Effects 0.000 description 15
- 235000019640 taste Nutrition 0.000 description 15
- 239000000047 product Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 11
- 239000000796 flavoring agent Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000011701 zinc Substances 0.000 description 9
- 229910052725 zinc Inorganic materials 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 239000008164 mustard oil Substances 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000035807 sensation Effects 0.000 description 6
- 235000019615 sensations Nutrition 0.000 description 6
- 239000000600 sorbitol Substances 0.000 description 6
- 235000010356 sorbitol Nutrition 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 235000019658 bitter taste Nutrition 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 210000000697 sensory organ Anatomy 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 241000219198 Brassica Species 0.000 description 4
- 235000003351 Brassica cretica Nutrition 0.000 description 4
- 235000003343 Brassica rupestris Nutrition 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 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 4
- 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 4
- NMOJAXCSURVGEY-UHFFFAOYSA-N N#CC#N.[S] Chemical compound N#CC#N.[S] NMOJAXCSURVGEY-UHFFFAOYSA-N 0.000 description 4
- KBVQDUHOYIQWSM-BTVCFUMJSA-N N=C=S.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O Chemical compound N=C=S.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O KBVQDUHOYIQWSM-BTVCFUMJSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 4
- 239000000551 dentifrice Substances 0.000 description 4
- OSVXSBDYLRYLIG-UHFFFAOYSA-N dioxidochlorine(.) Chemical compound O=Cl=O OSVXSBDYLRYLIG-UHFFFAOYSA-N 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- 235000010460 mustard Nutrition 0.000 description 4
- 230000003239 periodontal effect Effects 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 240000007124 Brassica oleracea Species 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 208000005946 Xerostomia Diseases 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 206010013781 dry mouth Diseases 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 229910052738 indium Inorganic materials 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 210000003296 saliva Anatomy 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 239000010409 thin film Substances 0.000 description 3
- 210000005239 tubule Anatomy 0.000 description 3
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 2
- JSDZSLGMRRSAHD-UHFFFAOYSA-N 3-methylbutan-2-ylcyclopropane Chemical compound CC(C)C(C)C1CC1 JSDZSLGMRRSAHD-UHFFFAOYSA-N 0.000 description 2
- 235000011302 Brassica oleracea Nutrition 0.000 description 2
- 239000004155 Chlorine dioxide Substances 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 235000017879 Nasturtium officinale Nutrition 0.000 description 2
- 240000005407 Nasturtium officinale Species 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 239000011805 ball Substances 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 235000015895 biscuits Nutrition 0.000 description 2
- 235000015111 chews Nutrition 0.000 description 2
- 235000019398 chlorine dioxide Nutrition 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 125000001651 cyanato group Chemical group [*]OC#N 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 150000002338 glycosides Chemical class 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- GRHBQAYDJPGGLF-UHFFFAOYSA-N isothiocyanic acid Chemical compound N=C=S GRHBQAYDJPGGLF-UHFFFAOYSA-N 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
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 210000002200 mouth mucosa Anatomy 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 230000035943 smell Effects 0.000 description 2
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 2
- 229960002218 sodium chlorite Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229940034610 toothpaste Drugs 0.000 description 2
- 239000000606 toothpaste Substances 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- 239000012224 working solution Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 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
- LQZFQLVBZRVDLJ-DKWTVANSSA-N (2s)-2-aminobutanedioic acid;zinc Chemical compound [Zn].OC(=O)[C@@H](N)CC(O)=O LQZFQLVBZRVDLJ-DKWTVANSSA-N 0.000 description 1
- GDSOZVZXVXTJMI-SNAWJCMRSA-N (e)-1-methylbut-1-ene-1,2,4-tricarboxylic acid Chemical compound OC(=O)C(/C)=C(C(O)=O)\CCC(O)=O GDSOZVZXVXTJMI-SNAWJCMRSA-N 0.000 description 1
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- BHWMZEPWQUFLLQ-UHFFFAOYSA-N 2-hydroxypropanoic acid;zinc Chemical compound [Zn].CC(O)C(O)=O BHWMZEPWQUFLLQ-UHFFFAOYSA-N 0.000 description 1
- SKIHGKNFJKJXPX-UHFFFAOYSA-N 4-isothiocyanato-1-butene Chemical class C=CCCN=C=S SKIHGKNFJKJXPX-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241001465180 Botrytis Species 0.000 description 1
- 241001475783 Brassica juncea subsp. napiformis Species 0.000 description 1
- 235000014700 Brassica juncea var napiformis Nutrition 0.000 description 1
- 235000011293 Brassica napus Nutrition 0.000 description 1
- 235000011291 Brassica nigra Nutrition 0.000 description 1
- 244000180419 Brassica nigra Species 0.000 description 1
- 235000004221 Brassica oleracea var gemmifera Nutrition 0.000 description 1
- 244000308368 Brassica oleracea var. gemmifera Species 0.000 description 1
- 240000008100 Brassica rapa Species 0.000 description 1
- 235000010149 Brassica rapa subsp chinensis Nutrition 0.000 description 1
- 235000000536 Brassica rapa subsp pekinensis Nutrition 0.000 description 1
- 235000000540 Brassica rapa subsp rapa Nutrition 0.000 description 1
- 241000499436 Brassica rapa subsp. pekinensis Species 0.000 description 1
- ZWIWQYBITZGQMF-UHFFFAOYSA-N C(C1=CC=CC=C1)OC#N.[S] Chemical compound C(C1=CC=CC=C1)OC#N.[S] ZWIWQYBITZGQMF-UHFFFAOYSA-N 0.000 description 1
- 241001249699 Capitata Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 240000002514 Cymbidium ensifolium Species 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 101100381997 Danio rerio tbc1d32 gene Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000390128 Eutrema Species 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000589236 Gluconobacter Species 0.000 description 1
- QQGLQYQXUKHWPX-UHFFFAOYSA-N Glucotropaeolin Natural products OC1C(O)C(O)C(CO)OC1SC(=NOS(O)(=O)=O)CC1=CC=CC=C1 QQGLQYQXUKHWPX-UHFFFAOYSA-N 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 235000014435 Mentha Nutrition 0.000 description 1
- 241001072983 Mentha Species 0.000 description 1
- 101100381999 Mus musculus Tbc1d32 gene Proteins 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 241000212324 Oenanthe <angiosperm> Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical group [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 1
- 239000004902 Softening Agent Substances 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 208000037063 Thinness Diseases 0.000 description 1
- 208000026062 Tissue disease Diseases 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 208000025865 Ulcer Diseases 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
- 235000000760 Wasabia japonica Nutrition 0.000 description 1
- 244000195452 Wasabia japonica Species 0.000 description 1
- 208000027418 Wounds and injury 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
- ZNOZWUKQPJXOIG-XSBHQQIPSA-L [(2r,3s,4r,5r,6s)-6-[[(1r,3s,4r,5r,8s)-3,4-dihydroxy-2,6-dioxabicyclo[3.2.1]octan-8-yl]oxy]-4-[[(1r,3r,4r,5r,8s)-8-[(2s,3r,4r,5r,6r)-3,4-dihydroxy-6-(hydroxymethyl)-5-sulfonatooxyoxan-2-yl]oxy-4-hydroxy-2,6-dioxabicyclo[3.2.1]octan-3-yl]oxy]-5-hydroxy-2-( Chemical compound O[C@@H]1[C@@H](O)[C@@H](OS([O-])(=O)=O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H]2OC[C@H]1O[C@H](O[C@H]1[C@H]([C@@H](CO)O[C@@H](O[C@@H]3[C@@H]4OC[C@H]3O[C@H](O)[C@@H]4O)[C@@H]1O)OS([O-])(=O)=O)[C@@H]2O ZNOZWUKQPJXOIG-XSBHQQIPSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- UXHQMSUJQLPRAW-UHFFFAOYSA-N benzene;isothiocyanic acid Chemical compound N=C=S.C1=CC=CC=C1 UXHQMSUJQLPRAW-UHFFFAOYSA-N 0.000 description 1
- QQGLQYQXUKHWPX-SUYBVFMFSA-N benzyl glucosinolate Natural products S(=O)(=O)(O/N=C(/S[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](CO)O1)\Cc1ccccc1)O QQGLQYQXUKHWPX-SUYBVFMFSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical class COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical compound NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012990 dithiocarbamate Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000002864 food coloring agent Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 125000004383 glucosinolate group Chemical group 0.000 description 1
- QQGLQYQXUKHWPX-RFEZBLSLSA-N glucotropeolin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1S\C(=N/OS(O)(=O)=O)CC1=CC=CC=C1 QQGLQYQXUKHWPX-RFEZBLSLSA-N 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 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
- 244000005700 microbiome Species 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000014569 mints Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000019617 piquancy Nutrition 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000014860 sensory perception of taste Effects 0.000 description 1
- 239000011257 shell material Substances 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000004354 sulfur functional group Chemical group 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 206010048828 underweight Diseases 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 239000005418 vegetable material Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 235000015099 wheat brans Nutrition 0.000 description 1
- 239000000811 xylitol Substances 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
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- GTQFPPIXGLYKCZ-UHFFFAOYSA-L zinc chlorate Chemical compound [Zn+2].[O-]Cl(=O)=O.[O-]Cl(=O)=O GTQFPPIXGLYKCZ-UHFFFAOYSA-L 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G1/00—Cocoa; Cocoa products, e.g. chocolate; Substitutes therefor
- A23G1/30—Cocoa products, e.g. chocolate; Substitutes therefor
- A23G1/32—Cocoa products, e.g. chocolate; Substitutes therefor characterised by the composition containing organic or inorganic compounds
- A23G1/325—Cocoa products, e.g. chocolate; Substitutes therefor characterised by the composition containing organic or inorganic compounds containing inorganic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
- A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
- A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
- A23G3/362—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing inorganic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G4/00—Chewing gum
- A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
- A23G4/064—Chewing gum characterised by the composition containing organic or inorganic compounds containing inorganic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/20—Inorganic substances, e.g. oligoelements
- A23K20/30—Oligoelements
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/26—Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/27—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
- A61K9/0058—Chewing gums
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
Abstract
本发明提供了锌盐和异硫氰酸酯的组合,更具体来说涉及含有这样的组合,可有效地减少挥发性硫化合物(VSC)的消费者可接受的口腔用组合物。
Description
技术领域
本发明涉及锌盐和异硫氰酸酯的有效组合,更具体来说涉及含有这样的组合并表现出对抗挥发性硫化合物(VSC)的提高的口腔护理效果的口腔用组合物。
背景技术
当在本文中使用时,口腔异味或“口臭”涉及由生理(短暂或暂时的)和/或病理状况引起的难闻口气。口臭的生理原因包括:由不良习惯引起的口臭,早晨口气和口腔干燥(口干)。口臭的病理原因包括:与牙龈和牙周疾病相关的继发或口腔组织病症,急性坏死溃疡性牙龈炎,术后残留血液,牙科器械下的残屑,口腔的溃疡性病变,舌苔,口腔干燥,唾液腺疾病和扁桃体结石(扁桃体石)。
口腔异味的产生主要由蛋白质分解成单个氨基酸、某些氨基酸随后进一步分解产生可察觉的臭气造成。口腔为革兰氏阴性厌氧菌提供有利生长环境,所述厌氧菌通过分解来自于压紧的食物粒子和脱落的口腔细胞碎片的蛋白质物质,将蛋白质作为能源进行代谢。通常,炎症使这些细胞以比唾液所能净化的更快的速率脱落。随后细菌的作用是将蛋白质水解成氨基酸,并且含有硫官能团的氨基酸甲硫氨酸和半胱氨酸,起到挥发性硫化合物(VSC)的前体的作用。
这些气态挥发性硫化合物(VSC)造成口腔异味,并主要由硫化氢(H2S)、甲硫醇(CH3SH)和二甲硫醚[(CH3)2S]构成。例如,氨基酸甲硫氨酸和半胱氨酸在硫化氢解酶阳性微生物存在下分别被还原成硫化氢和甲硫醇。已发现,在患有牙周疾病的患者中甲硫醇是舌背表 面异味的主要组分,而在口腔健康的对象中硫化氢占主导地位。
尽管难闻口气主要是难堪或烦恼的来源,但主要造成口臭的VSC也潜在地损伤口腔中的组织,并且可以引起牙周炎(支持牙齿的牙床和韧带的炎症)。具体来说,已发现VSC通过断裂二硫键而损伤结缔组织中的胶原蛋白和蛋白聚糖。这种细胞外基质的解聚集作用,允许微生物透过口腔黏膜。当细菌在牙齿附近形成的囊中进一步积累时,发生牙周病以及口臭。如果牙周疾病显著发展,可能危及整体系统健康;例如,牙周细菌副产物可以进入血流,并且可能引起心脏病、中风和低体重出生婴儿。
为了治疗口腔异味,公众越来越多地求助于可商购的口腔清新产品。由于慢性口腔异味患者经历个人不适和社交难堪,这些产品的市场持续增长。
在各种口腔用组合物中,已使用各种化合物例如二氧化氯、亚氯酸钠和金属盐例如锌和铜盐作为VSC中和剂。目前,这样的化合物作为口腔清洗剂和含漱剂提供并可获得,用于口腔异味的预防和/或治疗。总的来说,许多目前可用的口腔含漱剂被用于口腔异味或口臭的预防和/或治疗,但是对于慢性难闻口气,许多含漱剂提供的帮助很小或没有帮助。
尽管能够有效对抗口腔异味,但诸如二氧化氯、亚氯酸钠和金属盐例如锌和铜盐的化合物提供强烈的令人不快的口味和气味,从而不利地影响味觉并妨碍使用。通常,掺有这些化合物的漱口剂也可以造成对口腔的一些普遍刺激,例如脱皮、溃疡和炎症。此外,掺有这些化合物并在口腔中保留较长时间段的口腔用组合物(除了口腔清洗剂和含漱剂之外)例如口香糖、薄荷糖和糖锭,当使用这些化合物时进一步增强对口腔的刺激。
可供选择地,异硫氰酸酯通过将巯基(SH)转变成水溶性二硫代氨基甲酸酯或通过形成挥发性较低的二硫化物,也起到移除固有和外来VSC两者的试剂的作用。不幸的是,在某些浓度下,异硫氰酸酯具有辛辣或刺激性气味和强烈的苦味。由于令人不快的感官属性,在口腔用组合物中使用异硫氰酸酯是困难的。
鉴于上述挑战,对开发用于由生理和/或病理状况造成的口腔异味的有效治疗,存在着持续不断的需求。因此,牙科学共同体以及普通公众持续不断地寻求有效、商业上可行并且在感官上令人愉悦的口腔用组合物,以减轻各种类型的难闻口气(口臭),包括偶尔的、长期的或在每天特定时间的难闻口气。
因此,提供用于口腔异味的有效、商业上可行并且在感官上令人愉悦的产品解决方案,将是非常有利的。
发明概述
本发明提供了一种口腔用组合物,其含有锌盐与异硫氰酸酯的有效组合,用于减少口腔中的挥发性硫化合物(VSC)。此外,还提供了减少挥发性硫化合物的方法。
发明描述
本发明涉及有效对抗口腔中存在的多种挥发性硫化合物(VSC)的金属盐与异硫氰酸酯的不太可能的组合。此外,在本发明中所描述的相互组合中使用的金属盐和异硫氰酸酯的水平,低于单独使用的每种所述化合物。因此,本申请人的发明提供了有效减少VSC、从而减轻口腔异味的口腔用组合物。
当在本文中使用时,术语“有效”意味着产生或能够产生所需效果。此外,“有效量”是指产生或能够产生所需效果的水平、量、份数或百分数。除非另有指明,否则本文中使用的所有百分率和比率以 组合物的总重量计,并且所有测量在25℃下做出。
锌盐与消费者的口味接受标准不相容,在单独使用时,对减少某些挥发性硫化合物例如甲硫醇(CH3SH)来说仅仅短时间有效或者完全无效。
异硫氰酸酯是挥发性化合物,并且被分类为口或鼻刺激剂或两者。异硫氰酸酯的辛辣感觉可以在整个口腔黏膜组织(包括上呼吸道在内)中被感觉到。
正如在下面更详细描述的,本发明在消费或咀嚼口腔用组合物后提供持续的口气清新。例如,在消费或咀嚼口腔用组合物后,口气清新益处将持续至少约15分钟、通常地至少约30分钟、优选地至少约60分钟。通常,在消费或咀嚼后,口气清新将持续至少约60分钟,维持至少50%的总VSC降低。当在本文中使用时,“总VSC”包括以任何方式组合的两种或更多种下列VSC:硫化氢(H2S),甲硫醇(CH3SH)和二甲硫醚[(CH3)2S]。在其他实施方式中,在消费或咀嚼口腔用组合物之后,口气清新益处将持续到120分钟后并且总VSC减少至少40%,优选地持续到180分钟后并且总VSC减少至少20%。
具体来说,本发明的各种实施方式在口腔用组合物中提供了有效量的乳酸锌、葡萄糖酸锌、抗坏血酸锌或天冬氨酸锌及其混合物,其与异硫氰酸酯组合,在低于0.50重量%的合并浓度下抑制或减少多种挥发性硫化合物。
本发明的口腔用组合物可以采取适合于施用到人、狗、猫或其他动物的口腔表面的任何物理形式,并提供口腔内或源自于口腔的美容学预防和治疗益处。在各种实施方式中,本发明的口腔用组合物可以是洁齿剂例如牙粉或牙膏;可食用薄膜或生物粘附性薄膜;糖食组合物,包括但不限于清新薄荷糖、慢煮糖(low boiled candy)、口香糖、 耐嚼糖、硬糖(hard boiled candy)、包衣糖果、糖锭、糖浆、压缩薄荷糖(pressed mints)、咽喉滴剂和巧克力;宠物食品、咀嚼物或饼干等。在某些实施方式中,口腔用组合物的消费或咀嚼可以定期重复。
本申请人鉴定了在各种口腔用组合物中,用于减少口腔中的多种VSC的锌盐和异硫氰酸酯两者的适合、有效且消费者可接受的水平。
锌盐
正如前面根据本发明的各种实施方式所建议的,可以使用有效量的锌盐来抑制口腔中的挥发性硫化合物,从而减轻口腔异味。用于减少VSC的有机锌盐的实例包括葡萄糖酸锌(平均锌离子含量为12.8%)、乳酸锌(平均锌离子含量为23.2%)、乙酸锌离子(平均锌离子含量为29.8%)和柠檬酸锌(平均锌离子含量为32.2%);尽管根据本申请人的研究(正如在下面更详细地提供的),不是所有锌盐都有效对抗所有类型的VSC。在正常情况下,含有高水平锌离子的锌盐性能优于含有低水平锌离子的锌盐。
在这些配制物中使用的适合的锌盐包括乙酸锌(在水中的摩尔溶解度为1.64摩尔/升)、柠檬酸锌(在水中的摩尔溶解度<0.1摩尔/升)、葡萄糖酸锌(在水中的摩尔溶解度为0.28摩尔/升)和乳酸锌(在水中的摩尔溶解度为0.17摩尔/升)。通常,水溶性更好的锌盐性能优于水溶性差的锌盐。
金属盐例如锌盐具有螯合口腔中存在的VSC并形成不挥发性金属离子-硫化物复合物,从而中和口腔异味的能力。然而,这种中和口腔异味的能力是暂时的。金属盐不改变口腔条件,并且不表现出针对口腔中存在的产臭味细菌的活性。因此,含有锌盐的口腔卫生产品例如氯化锌口腔清洗剂,被认为有些对口臭有效,但许多是无效的或仅仅具有短暂效果。
总的来说,本申请人鉴定到某些锌盐不有效对抗所有VSC例如硫化氢(H2S)、二甲硫醚[(CH3)2S]和甲硫醇(CH3SH),而是可能仅仅有效对抗特定的VSC。
为了评估各种锌盐对抗特定的VSC的效能,本发明人使用装备有硫检测器的顶部空间气相色谱,建立了一种体外方法。因此,制备了在5ml磷酸盐缓冲液(PBS)中的总共200ppm CH3SH。pH被维持在7.4。在试管内加入不同量的乳酸锌或葡萄糖酸锌,并在37℃下混合5分钟。将顶部空间样品注入气相色谱硫化学发光检测器(GC-SCD)。下面的图1示出了试验结果。
图1-在添加乳酸锌或葡萄糖酸锌后顶部空间CH3SH浓度的变化。
如上面的图1中所示,本申请人鉴定到乳酸锌和葡萄糖酸锌两者对于减少顶部空间的甲硫醇(CH3SH)浓度是无效的。事实上,本申请人观察到所测试的锌盐将CH3SH的挥发性提高10-40%。
在另一个实验中,如下面图2所示,通过连续稀释法在22ml顶部空间小瓶中制备含有1mg H2S的5ml PBS溶液。加入不同量的锌盐并在37℃下混合5min。通过GC-SCD分析顶部空间的H2S浓度。图2示出了试验结果。
图2-通过GC-SCD分析的在添加锌盐后顶部空间H2S浓度的变化
如上面的图2中所示,本申请人鉴定到葡萄糖酸锌、乳酸锌、天冬氨酸氢锌和抗坏血酸锌减少由硫化氢(H2S)产生的口腔异味。
更显著的是,在体外,乳酸锌在高于0.25mg的浓度下,并且葡萄糖酸锌、天冬氨酸氢锌和抗坏血酸锌在高于0.5mg的浓度下减少H2S。
因此,本申请人令人吃惊地发现,乳酸锌和葡萄糖酸锌都不降低顶部空间的挥发性硫化合物甲硫醇(CH3SH)的浓度,所述甲硫醇与硫化氢(H2S)相比是更令人不快和敏感的气味剂。
不幸的是,尽管有效对抗某些VSC,但金属阳离子的盐例如硫酸铝和氯酸锌、乳酸锌、乙酸锌等,对于许多消费者来说常常是令人不快或不适口的。由于由含有金属盐的产品造成的这种不受欢迎的效果,并考虑到短暂的口臭中和益处,消费者在口腔异味的治疗中购买并使用含有这些成分的产品的动机低。
异硫氰酸酯
异硫氰酸酯是挥发性化合物,并且被分类为口腔刺激剂或鼻刺激剂或两者。异硫氰酸酯的辛辣感觉可以在整个口腔黏膜组织(包括上呼吸道在内)中感觉到。
异硫氰酸酯作为前体结合在整个植物上,并在植物材料被磨碎时 通过酶的作用被释放。异硫氰酸酯是葡糖异硫氰酸酯的生物活性水解(分解)产物。十字花科植物例如西兰花、花椰菜、芥兰、红萝卜、甘蓝、抱子甘蓝、卷心菜、大头菜、芜菁甘蓝、白菜和青菜含有各种葡糖异硫氰酸酯,其每种在水解时形成不同的异硫氰酸酯,并示出在图3中。
图3
例如,西兰花是萝卜硫素(SFN)的葡糖异硫氰酸酯前体萝卜硫苷和异硫氰酸烯丙酯(AITC)的葡糖异硫氰酸酯前体黑介子苷的良好来源。水田芥是异硫氰酸苯乙基酯(PEITC)的前体水田芥苷的丰富来源,而水芹富含异硫氰酸苄酯(BITC)的前体金莲葡糖硫苷。研究显示,这些化合物造成生的或煮熟的十字花科植物的令人不快的口味。
辣根和芥末具有共同家族的异硫氰酸酯作为辛辣成分。在芥末和辣根两者中存在的异硫氰酸烯丙酯(AITC),是这一家族的最常见成员。棕芥末含有异硫氰酸-3-丁烯基酯。芥属葡糖异硫氰酸酯,或者被称为芥子油苷,倾向于具有苦味。
可用于本发明的天然异硫氰酸酯包括如图3中所示的下列来自于十字花科植物的黑芥子酶催化的葡糖异硫氰酸酯化合物:萝卜硫素(SFN),异硫氰酸烯丙酯(AITC),异硫氰酸苯乙基酯(PEITC), 异硫氰酸苄酯(BITC)。可用于本发明的优选的天然异硫氰酸酯是异硫氰酸烯丙酯,也称为芥子油,通常存在于辣根和山葵中。正如本文中所描述的,术语“天然的”是指由活生物体产生并在自然界中存在的化学化合物或物质,其可能具有在药物发现和药物设计中使用的药理或生物活性。尽管产物通过全合成来制备,但如果组分基本上与自然界中存在的物质一致,则所述产物也可以被当作“天然的”。
合成或非天然的异硫氰酸酯的实例包括异硫氰酸-3-吗啉代丙基酯、异硫氰酸苯酯和异硫氰酸降冰片酯([内-2-乙酰基-外-6-异硫氰酰基降冰片烷、外-2-乙酰基-外-6-异硫氰酰基降冰片烷、外-2-乙酰基-外-5-异硫氰酰基降冰片烷],其可以从萝卜硫素或可商购的2-乙酰基-5-降冰片烯合成)。
本申请人针对挥发性硫化合物硫化氢(H2S)测试了各种异硫氰酸酯。
通过连续稀释在PBS缓冲液(pH7.4)中制备了H2S的储用溶液,其终浓度为200ppm。将异硫氰酸烯丙酯、异硫氰酸苄酯、异硫氰酸乙酯和异硫氰酸-3-甲基硫代丙基酯(都来自于Sigma-Aldrich)溶解在纯乙醇中,以形成各自的1.0%工作溶液。在顶部空间小瓶(22ml容积)中,将含有200ppm H2S的总共5ml PBS缓冲液分别与0.125、0.25、0.5和1mg每种异硫氰酸酯化合物,在37℃下混合5min。将顶部空间样品通过自动进样器注入GC-SCD,进行VSC分析。顶部空间的H2S浓度的降低通过下述公式来计算:
表1-在体外异硫氰酸烯丙酯、异硫氰酸苄酯、异硫氰酸乙酯和异硫氰酸-3-甲基硫代丙基酯引起的硫化氢(H2S)减少
上面的表1表明,所测试的异硫氰酸酯有助于减少硫化氢(H2S)。在50ppm下,异硫氰酸苄酯显示出超过50%的H2S减少。更显著的是,异硫氰酸乙酯在200ppm下将顶部空间的H2S减少68%;异硫氰酸-3-甲基硫代丙基酯在100ppm下将顶部空间H2S减少75%,在200ppm下减少94.5%。具体来说,异硫氰酸烯丙酯(AITC)显示出H2S的强烈减少(在100ppm或更高浓度下超过90%)。
然而,为了在口腔用组合物中提供上面示出的有效水平,这将提供强烈的令人不快的口味,并且在感官上不舒适。
鉴于表1中与异硫氰酸烯丙酯相关的结果,本申请人在体外进一步评估了异硫氰酸烯丙酯对硫化氢(H2S)的VSC消除效果。将含有5ml PBS溶液和200ppm H2S的20ml顶部空间小瓶分别用各种浓度(0.25-1.0mg)的异硫氰酸烯丙酯处理。在标准实验流程中,通过将约0.10g硫化钠溶解在总共10ml磷酸盐缓冲液(PBS)(pH7.4)中,制备硫化氢储用溶液。将它在PBS中进一步稀释以产生在缓冲液中含有200ppm H2S的工作溶液。
表2-通过异硫氰酸烯丙酯(AITC)体外减少硫化氢(H2S)
异硫氰酸烯丙酯 | H2S的减少 |
0mg | 0.0% |
0.25mg | 49.0% |
0.5mg | 98.4% |
1mg | 99.5% |
表2表明,在体外,异硫氰酸烯丙酯(AITC)在高于0.25mg(或50ppm)的浓度下减少与硫化氢(H2S)相关的口腔异味。
根据前面在体外鉴定到的效能(表1和表2),进一步评估了异硫氰酸烯丙酯(AITC)的体内口气清新效果。
在实验室中制备含有100ppm异硫氰酸烯丙酯(AITC)的口香糖,将其卷绕、制片并切割成条,平均重量为2.7g。
进行随机双盲临床研究来评估含有异硫氰酸烯丙酯(AITC)的口香糖。总共15位满足包含和排出标准的对象被召集并完成研究。要求对象克制不要在试验地点进行口腔卫生、进食和饮水。每位对象向气相色谱呼气,以分析基线(处理之前,t=0)VSC。然后对象咀嚼一剂实验口香糖(或对照口香糖)12分钟。在咀嚼后立即以及60、120和180分钟,对象向气相色谱呼气。每个试验重复两次。在处理之间间隔至少两天。
表3-使用含有100ppm异硫氰酸烯丙酯(AITC)的口香糖体内减少H2S
1.来自于以前研究的结果
与基线相比统计学显著
*与对照口香糖相比统计学显著
表3显示,含有100ppm AITC的口香糖与对照口香糖和基线(处理前,t=0)相比,减少与硫化氢(H2S)相关的口腔异味;当与咀嚼后即刻的基线结果相比时,所述结果是显著的(p>0.05)。此外,当与表2中反映的体外硫化氢(H2S)试验相比时,当应用于口香糖组合物时,AITC显得效率较低。
表4-使用含有100ppm异硫氰酸烯丙酯(AITC)的口香糖体内减少CH3SH
1.来自于以前研究的结果
与基线相比统计学显著
*与对照口香糖相比统计学显著
上面表4的数据显示,实验性AITC口香糖与对照口香糖和基线(处理前,t=0)相比,减少与CH3SH相关的口腔异味;当与对照口香糖和咀嚼后即刻的基线两者相比时,以及当与基线结果相比时在60min后,所述结果是显著的(p>0.05)。
鉴于当与体外结果相比时发现的AITC在体内的效能降低,本申请人测试了异硫氰酸烯丙酯从口香糖释放的能力。将含有0.27mg异硫氰酸烯丙酯的一片口香糖(片重量:2.7g)咀嚼20分钟,并通过气相色谱分析残留的口香糖嚼团。将结果与回收率为48.5%的未咀嚼的口香糖的提取率进行比较。发现在咀嚼20分钟,异硫氰酸烯丙酯从口香糖的释放为69.6%。
尽管异硫氰酸酯例如异硫氰酸烯丙酯显示出减少VSC(例如H2S)的能力,但本领域技术人员认识到,异硫氰酸酯即使在低浓度下消费 时,也提供辛辣香气、辣和苦的口味,并且对口腔和黏膜两者具有刺激性。显示出有效的水平将向消费者提供令人不快的口味和其他不利感官性质。应该理解,所证实的异硫氰酸酯的有效浓度,受到提供口腔异味减轻并且对各种口腔用组合物的外观、口味、颜色或质地没有不利影响的要求的限制。
锌盐与异硫氰酸酯的组合
根据本发明,已发现金属盐与异硫氰酸酯的组合有效对抗口腔中存在的多种挥发性硫化合物(VSC)。此外,本文中描述的组合和水平比单独使用时更低,提供消费者可接受的且有效减少VSC、从而减少口腔异味的口腔用组合物。
正如上面确立的,当单独使用时,锌盐或异硫氰酸酯在减少某些挥发性硫化合物(例如甲硫醇(CH3SH))中,可能短时间有效或完全无效。本申请人的两种化合物的组合,长时间提供多种VSC的有效减少,即使在咀嚼或消费后。此外,金属盐和异硫氰酸酯的组合与每种化合物以较高浓度单独使用时相比,产生可以被消费者接受的感官上令人喜爱的口味。
可用于本发明的组合物包含锌盐和从芥子油提取的化合物,例如异硫氰酸烯丙酯(“AITC”)或这样的组分或其化合物的合成或半合成的等同物。AITC通常可以是芥子油的提取物。
锌盐和异硫氰酸酯相对于彼此的组合,提供了本申请人的发明的所需效果。更具体来说,本发明的口腔用组合物中乳酸锌和异硫氰酸烯丙酯的有效浓度,不仅取决于获得对抗挥发性硫化合物的活性增强时的相对浓度,而且取决于提供消费者可接受的口味时的浓度。在本发明的一种情况下,口腔用组合物中锌盐/异硫氰酸酯的增强重量比为至少0.1:1,通常为至少0.5:1,优选为至少1:1。这种重量比可以高达100:1或更高,通常高达1:1,优选地高达10:1。典型的重量比范围在 0.5:1至约50:1之间,优选地在1:1至20:1之间。
在实施方式中,锌盐与异硫氰酸酯的比例在1:1至约20:1之间,其中锌盐是有机锌盐,异硫氰酸酯是异硫氰酸烯丙酯。
在本发明的其他实施方式中,锌盐以约0.001重量%至约0.50重量%的量存在于口腔用组合物中。这样的浓度取决于用于获得针对挥发性硫化合物(VSC)的增强结果的异硫氰酸酯浓度。在一种实施方式中,锌盐以约0.001重量%至约1重量%的量存在于口腔用组合物中。在其他实施方式中,锌盐以低于0.50重量%的量存在,例如,锌盐以约0.01重量%至约0.25重量%的量的浓度存在。在一种优选实施方式中,乳酸锌以约0.10重量%的浓度存在于口腔用组合物中。总的来说,锌盐的浓度低于产生令人讨厌的口味的水平。
锌盐可以是常用的有机锌盐,包括葡萄糖酸锌、乳酸锌、乙酸锌、柠檬酸锌及其组合。
此外,异硫氰酸酯以约0.001重量%至约1重量%的量存在于口腔用组合物中。在其他实施方式中,异硫氰酸酯以低于1重量%的量存在。在一种优选实施方式中,异硫氰酸烯丙酯以约0.01重量%的浓度存在于口腔用组合物中。异硫氰酸烯丙酯可以通过气相色谱-质谱(GC-MS)来测定。异硫氰酸酯可以是天然或非天然的,包括但不限于单独或以任何方式组合的萝卜硫素(SFN)、异硫氰酸烯丙酯(AITC)、异硫氰酸苯乙基酯(PEITC)、异硫氰酸苄酯(BITC)、异硫氰酸-3-吗啉代丙基酯、异硫氰酸苯酯和异硫氰酸降冰片酯([内-2-乙酰基-外-6-异硫氰酰基降冰片烷、外-2-乙酰基-外-6-异硫氰酰基降冰片烷、外-2-乙酰基-外-5-异硫氰酰基降冰片烷],其可以从萝卜硫素或从可商购的2-乙酰基-5-降冰片烯合成)。
可用于本发明的口腔用组合物含有有效减少VSC的量的锌盐和异 硫氰酸酯与适合载体的组合。适合的载体通常是可食用或可接触食品的材料,本发明中使用的锌盐和异硫氰酸酯可以掺入或分散在其中而没有不利效果。典型的适合载体是水溶性固体或可咀嚼固体例如糖食组合物。另一种适合的载体是洁齿剂例如牙膏或牙粉。用于猫、狗和其他动物的其他适合载体包括但不限于咀嚼物、饼干、粗磨(干)和罐装(湿/软)宠物食品。
当在本文中使用时,术语“糖食组合物”包括口香糖和口溶性片剂、球珠和糖锭。唾液溶解糖锭或口香糖产品,并促进与口腔表面的延长接触,使得当使用产品时,采取糖锭、片剂、球珠或口香糖形式的VSC减少剂的递送确保足够剂量的活性成分被递送到口腔表面。或者,糖食组合物可以采取包衣、壳、薄膜、糖浆或悬液的形式。
在实施方式中,口腔用组合物是口香糖组合物,其适合于咀嚼并包含组合物重量的2%或更高的弹性体。一般来说,口香糖组合物被消费者咀嚼,通过这一过程用牙齿将食品磨碎并压碎。这样的口香糖组合物可以采取各种形状和形式,例如球粒、口香糖球、正方形、条等,并且可以用各种材料包括糖、多元醇、巧克力、糖浆、薄膜等,单独或以任何方式组合地包衣。也可以向包衣溶液添加天然或人造色素及其组合、高强度甜味剂和调味剂。对于球粒或包衣口香糖来说,可以将锌盐掺入到包衣或芯中。
可用于本发明的口香糖是含有锌盐和异硫氰酸酯以减少VSC的无糖口香糖。除了口香糖胶基之外,口香糖配制物通常含有一种或多种增塑剂、至少一种甜味剂和至少一种调味剂。
根据一种实施方式,提供了含有约0.002重量%至约2重量%的乳酸锌和0.001重量%至约5重量%的异硫氰酸烯丙酯的口香糖,其中所述口香糖在咀嚼后长达180分钟提供多种VSC的减少。
在本发明的一种情况下,提供了一种口香糖组合物,其中锌盐的浓度为约0.10重量%,异硫氰酸酯的浓度为约0.01重量%。提供的异硫氰酸酯可以包含多种天然或非天然的异硫氰酸酯及其组合。将口香糖咀嚼至少5分钟、至少10分钟或至少15分钟。在咀嚼后立即或至少30分钟、60分钟、通常至少90分钟、优选地至少120分钟内,发生总VSC的减少。
在一种实施方式中,异硫氰酸烯丙酯有至少50%从口香糖释放到使用者的口腔中。
在另一种实施方式中,提供了一种无糖硬糖,其含有少于0.50重量%的锌盐和少于1重量%的异硫氰酸酯。
尽管不受束缚本发明的理论的限制,但一般来说相信,口腔用组合物中锌盐的增强有效的抗挥发性硫化合物(VSC)的最低水平在约100μg/mL(100mg/kg或百万分率(ppm))至约2500μg/mL(2500ppm)之间,异硫氰酸酯的抗VSC浓度在10μg/mL(10ppm)至约1000μg/mL(1000ppm)之间。
在一种实施方式中,口腔用组合物中异硫氰酸烯丙酯的水平低于50ppm。
在优选实施方式中,乳酸锌的抗VSC的有效增强口气清新的水平在100μg/mL至约2000μg/mL之间,并且异硫氰酸酯选自异硫氰酸烯丙酯、异硫氰酸苄酯、异硫氰酸苯乙基酯和萝卜硫素,其中异硫氰酸酯的水平在10μg/mL至约500μg/mL之间。
在本发明的一种情况下,提供了一种口腔用悬液,其中锌盐以约1250μg/mL的量提供,非天然异硫氰酸酯以约1000μg/mL的量提供。
I.数据
a.对抗多种VSC:H2S和CH3SH的乳酸锌与异硫氰酸烯丙酯(AITC)的组合
方法:通过将5份H2S与1份CH3SH在pH7.4的磷酸盐缓冲水溶液(PBS)中混合,来制备硫化氢(H2S)与甲硫醇(CH3SH)的混合物。溶液中H2S和CH3SH的终浓度分别为200ppm和40ppm。试验小管中VSC的终浓度为1.2mg。尽管H2S和CH3SH的顶部空间浓度明显高于在典型的难闻口气中存在的水平(200-500十亿分率),但VSC的总量接近于口腔中存在的量。随后,将5ml VSC混合物在22ml紧密螺旋盖顶部空间小管中在37℃下保持5min。将顶部空间样品注入带有SCD检测器的GC柱中。下面的图4示出了试验结果(对照)。CH3SH的大的峰面积反映出它与H2S相比在顶部空间中的挥发性。
分开地,向每个含有5ml VSC混合物的小管加入1mg乳酸锌、或1mg异硫氰酸烯丙酯(AITC)、或1mg乳酸锌与1mg AITC的组合,并在37℃下平衡5min。通过Combi-Pal自动进样器将每个顶部空间样品注入GC柱。通过Agilent SCD-355化学发光硫化物检测器分析硫的量。
图4
图4证实了异硫氰酸烯丙酯(AITC)和乳酸锌(ZnL或ZL)对 多种VSC(H2S和CH3SH)表现出增强的效果;1mg AITC消除98%的H2S和78%的CH3SH;1mg ZL消除98%的H2S、0%的CH3SH。
b.AITC-ZL口香糖的口味和感觉的专家评估小组评估
为了评估AITC-锌口香糖的感觉和口味可接受性,使用6位内部训练的专家评估小组进行ESA(专家感觉分析)试验。每位评估小组成员咀嚼对照口香糖或实验口香糖6min。如下面表5中所示,对照口香糖不含AITC,实验口香糖含有0.01%(100ppm)的AITC和0.1%(1000ppm)的乳酸锌。评估小组成员在9个点的量表(0-最低强度;9-最高强度)中评估甜味强度、苦味强度和异味感觉。下面的图5-7示出了试验结果:
对于下面的口香糖制备来说,将胶基在口香糖混合机中加热至85℃。向加温的胶基加入乳酸锌、山梨糖醇、高强度甜味剂、甘油和山梨糖醇糖浆。在向口香糖混合机添加之前,向调味剂加入异硫氰酸烯丙酯(AITC)并充分搅拌。在加入剩余的口香糖成分之后,将口香糖团制片并切割成条。每条口香糖重2.7克。下面的表5示出了实验口香糖的配制物:
表5
成分 | 对照口香糖 | 实验口香糖A | 实验口香糖B |
山梨糖醇 | 33.10% | 32.95% | 31.73% |
胶基 | 31.00% | 31.00% | 30.00% |
山梨糖醇糖浆 | 33.40% | 33.40% | 33.00% |
甘油 | 0.90% | 0.90% | 0.90% |
乳酸锌 | --- | 0.10% | 0.10% |
包封的高强度甜味剂 | 0.35% | 0.35% | 1.1% |
高强度甜味剂 | 0.16% | 0.16% | 0.16% |
香蕉调味剂 | 1.00% | 1.00% | --- |
薄荷油 | --- | --- | 3.00% |
AITC(添加到调味油) | --- | 0.01% | 0.01% |
合计 | 100.0% | 100.0% | 100.0% |
图5
图6
图7
结果
图5-7中的数据显示,在实验口香糖A与对照口香糖之间没有观察到异味(包括涩味)和苦味的显著差异。也没有观察到甜味强度的显著差异。
这些结果提供了证据,即本申请人的发明提供了减少与VSC相关的口腔异味的独特、廉价、消费者友好和容易获得的手段。
c.口气清新临床试验
为了评估含有乳酸锌和异硫氰酸烯丙酯(AITC)的口香糖,进行了随机双盲临床研究。总共15位满足包含和排出标准的对象被召集并完成研究。要求对象克制不要在试验地点进行口腔卫生、进食和饮水。每位对象向气相色谱呼气,以分析基线VSC。然后对象咀嚼一剂实验口香糖(或对照口香糖)12分钟。在咀嚼后立即以及60、120和180分钟,对象向气相色谱呼气。每个试验重复两次。在处理之间间隔至少两天。下面的表6示出了临床试验结果。
表6-处理后总VSC的减少(或增加)
(*与基线相比双尾p<0.05;与对照口香糖相比双尾p<0.05)
结果
通过使用气相色谱在60、120和180min测量VSC总浓度,胶基没有显示出统计学显著的口腔异味减少。事实上,胶基在60、120和180分钟分别使VSC增加3%、44%和46%。
单独含有AITC的口香糖在咀嚼后即刻、60、120和180min,分别将口腔异味减少67%、32%、29%和9%。
咀嚼AITC-ZL口香糖在在咀嚼后即刻、60、120和180min,分别将总VSC减少87%、56%、48%和24%的统计学显著的量。
因此,结果显示,将异硫氰酸酯与锌盐组合与单独使用相比减少了每种物质的水平,提供口味良好、感官上舒适的组合物,其有效对抗多种VSC,从而减少口腔异味。此外,这种组合在消费后提供至少60分钟的口气清新益处。
在一种实施方式中,提供了一种口香糖,其含有低于0.2重量%的锌盐和低于0.02重量%的异硫氰酸酯,在个体消费后提供至少约2小时的口气清新益处。
适合用于本发明实践的口香糖胶基材料在本领域中是公知的,并包括天然或合成的胶基或其混合物。胶基可以以约10重量%至约40重量%、优选地约20重量%至约35重量%的浓度掺入到口香糖产品中。
在口香糖组合物中常用的增塑剂/软化剂适合以约0.1重量%至约5重量%的量用于本发明,并包括明胶、蜡及其混合物。在本发明的实践中使用的甜味剂成分可以选自广泛的各种材料,并包括与用于片剂、球珠和糖锭的制备相同的人造和多元醇甜味剂。多元醇甜味剂例如山梨糖醇和麦芽糖醇以约40重量%至约80重量%、优选地约50重量%至约75重量%的量存在于本发明的口香糖组合物中。人造甜味剂以约0.1重量%至约2重量%、优选地约0.3重量%至约1重量%的量存在于本发明的口香糖组合物中。
还可以向本文公开的任何口腔用组合物施加任选的包衣。本领域 技术人员认识到的包衣材料包括但不限于蜡、虫胶、多元醇、羧甲基纤维素、聚乙烯/马来酸酐共聚物或κ-卡拉胶。
在另一种实施方式中,本发明的口腔用组合物还可以包含三叉神经刺激剂或增感剂,包括但不限于薄荷醇和其他凉味化合物例如WS-23和其他凉味羧酰胺化合物,以及辛辣化合物包括但不限于辣椒素类和胡椒碱类。
正如在下面进一步详细示出的,本发明可以提供在各种口腔用组合物中。因此,下面的实施例说明但不限制本发明的各种实施方式:
实施例1
含有异硫氰酸酯和锌盐的口香糖配制物(被称为“组合物E、F和G”)。
实施例2
本发明用含有异硫氰酸烯丙酯和柠檬酸锌的压制片剂配制物(被称为“组合物H”)来说明,但不受其限制:
成分 | 重量% |
山梨糖醇 | 97.14 |
硬脂酸镁 | 1.00 |
薄荷油 | 0.10 |
甜味剂 | 1.00 |
柠檬酸锌 | 0.75 |
异硫氰酸烯基酯(AITC) | 0.01 |
实施例3
本发明用下面的硬糖配制物(被称为“组合物I”)来说明,但不受其限制:
成分 | 重量% |
异麦芽糖醇 | 97.83 |
木糖醇 | 1.05 |
高强度甜味剂 | 0.07 |
调味剂 | 0.04 |
乳酸锌 | 1.00 |
异硫氰酸苯乙基酯 | 0.01 |
实施例4
本发明用狗饼干配制物(被称为“组合物J”)来说明,但不受其限制。所述狗饼干按照常规技术来制备,并包含下列成分:
成分 | 重量% |
小麦粉 | 30.0 |
燕麦和麸皮 | 17.0 |
粗磨粉和种子 | 16.5 |
谷蛋白 | 7.5 |
食糖 | 6.0 |
脂肪 | 5.0 |
香料,调味剂 | 7.5 |
维生素和矿物质 | 9.95 |
乳酸锌 | 0.50 |
异硫氰酸烯基酯(AITC) | 0.05 |
本发明不限于上面的实施方式,并且可以进行各种修改。上面描述的优选实施方式、包括实施例,仅仅是打算使本领域其他技术人员了解本发明、它的原理及其实际应用,以便本领域的其他技术人员可以以可能最适合于特定用途的要求的大量形式来改变和应用本发明。
对于在整个本说明书(包括权利要求书)中使用的单词“包含”来说,除非上下文另有要求,否则该单词在它应该被包含性而不是排他性地解释这一基础和清晰理解上使用,并且本申请人打算在整个本说明书的解释中对每个该单词做出如此解释。
Claims (17)
1.口腔用组合物,其包含有效量的锌盐和异硫氰酸酯,用于对抗挥发性硫化合物,其中所述锌盐选自葡萄糖酸锌、乳酸锌、乙酸锌、柠檬酸锌及其组合,并且所述异硫氰酸酯选自萝卜硫素(SFN)、异硫氰酸烯丙酯(AITC)、异硫氰酸苯乙基酯(PEITC)、异硫氰酸苄酯(BITC)、异硫氰酸-3-吗啉代丙基酯、异硫氰酸苯酯、异硫氰酸降冰片酯及其组合。
2.权利要求1的组合物,其中所述锌盐与异硫氰酸酯的重量比为1:10至100:1。
3.权利要求1的组合物,其中所述口腔用组合物是薄荷糖、慢煮糖、硬糖、糖锭、糖浆、咽喉滴剂和巧克力。
4.权利要求1的组合物,其中所述口腔用组合物是压缩薄荷糖。
5.权利要求1的组合物,其中所述口腔用组合物是口香糖或耐嚼糖。
6.权利要求1的组合物,其中所述口腔用组合物是宠物咀嚼物或饼干。
7.口腔用组合物,其有效地减少硫化氢(H2S)、二甲硫醚[(CH3)2S]、甲硫醇(CH3SH)及其组合,所述组合物包含乳酸锌和异硫氰酸酯的组合,其中所述异硫氰酸酯选自异硫氰酸烯丙酯(AITC)、异硫氰酸苯乙基酯(PEITC)、异硫氰酸苄酯(BITC)及其组合。
8.权利要求7的组合物,其中所述异硫氰酸酯是异硫氰酸烯丙酯。
9.权利要求7的组合物,其中乳酸锌的有效量为0.002重量%至2重量%,以及所述异硫氰酸酯的有效量为0.001重量%至5重量%。
10.权利要求7的组合物,其中所述口腔用组合物是口香糖、耐嚼糖或硬糖。
11.权利要求7的组合物,其中所述口腔用组合物是未包衣的。
12.减少选自硫化氢(H2S)、二甲硫醚[(CH3)2S]和甲硫醇(CH3SH)的挥发性硫化合物的方法,所述方法包含具有有效量的有机锌盐与异硫氰酸酯的组合的口腔用组合物,其中所述有机锌盐选自葡萄糖酸锌、乳酸锌、乙酸锌、柠檬酸锌及其组合,并且所述异硫氰酸酯选自萝卜硫素(SFN)、异硫氰酸烯丙酯(AITC)、异硫氰酸苯乙基酯(PEITC)、异硫氰酸苄酯(BITC)、异硫氰酸-3-吗啉代丙基酯、异硫氰酸苯酯、异硫氰酸降冰片酯及其组合。
13.权利要求12的方法,其中所述甲硫醇(CH3SH)由选自乳酸锌、柠檬酸锌及其组合的有机锌盐与异硫氰酸酯的组合来减少,其中所述异硫氰酸酯包含至少80%的异硫氰酸烯丙酯。
14.权利要求13的方法,其中所述乳酸锌与异硫氰酸烯丙酯的组合比单独使用时更加有效地减少挥发性硫化合物。
15.权利要求13的方法,其中所述口腔用组合物含有有效量的0.002重量%至2重量%的乳酸锌和0.001重量%至5重量%的异硫氰酸烯丙酯。
16.权利要求13的方法,其中乳酸锌与异硫氰酸烯丙酯的比例为1:1至20:1。
17.权利要求12的方法,其中所述异硫氰酸酯是异硫氰酸-3-吗啉代丙基酯或异硫氰酸苯酯。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161511646P | 2011-07-26 | 2011-07-26 | |
US61/511,646 | 2011-07-26 | ||
PCT/US2012/046071 WO2013015979A2 (en) | 2011-07-26 | 2012-07-10 | Compositions containing zinc salts and isothiocyanates for reduction of oral volatile sulfur compounds (vscs) |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103717225A CN103717225A (zh) | 2014-04-09 |
CN103717225B true CN103717225B (zh) | 2016-09-28 |
Family
ID=47601714
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201280037437.1A Active CN103717225B (zh) | 2011-07-26 | 2012-07-10 | 用于减少口腔挥发性硫化合物(vsc)的含有锌盐和异硫氰酸酯的组合物 |
Country Status (9)
Country | Link |
---|---|
US (1) | US10543155B2 (zh) |
EP (1) | EP2736520B1 (zh) |
CN (1) | CN103717225B (zh) |
AU (1) | AU2012287333B2 (zh) |
CA (1) | CA2842745C (zh) |
MX (1) | MX362350B (zh) |
PL (1) | PL2736520T3 (zh) |
RU (1) | RU2573987C2 (zh) |
WO (1) | WO2013015979A2 (zh) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106806886B (zh) * | 2015-12-01 | 2021-07-16 | 华中科技大学 | 一种快速消除口臭的口气清新剂及其医药用途 |
CN108852909B (zh) * | 2018-08-01 | 2021-11-23 | 海南医学院 | 一种防龋齿牙膏及其制备方法 |
US20210060058A1 (en) * | 2019-09-04 | 2021-03-04 | Unm Rainforest Innovations | Compositions and methods for treating hydrogen sulfide-mediated hyperdynamic circulation |
CN112076165B (zh) * | 2020-09-08 | 2022-05-13 | 北京哈三联科技有限责任公司 | 一种能使口气清新的口腔崩解片及其制备方法 |
WO2022216769A1 (en) * | 2021-04-07 | 2022-10-13 | Fontana Biosciences, Inc. | Rapidly disintegrating allyl isothiocyanate tablet |
CN113176359A (zh) * | 2021-06-16 | 2021-07-27 | 山东京博石油化工有限公司 | 一种利用顶空气相色谱评价沥青挥发物中硫化物含量的方法 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3940476A (en) * | 1972-03-20 | 1976-02-24 | General Foods Corporation | Oral preparations for preventing dental plaque |
JP3197873B2 (ja) | 1993-06-30 | 2001-08-13 | 三洋電機株式会社 | 電源回路の設計方法および電源回路 |
JPH11246319A (ja) | 1998-02-27 | 1999-09-14 | Ogawa Koryo Co Ltd | 抗菌抗かび剤 |
AU3765999A (en) * | 1998-06-29 | 2000-01-17 | Warner-Lambert Company | Improved oral compositions for control and prevention of tartar, oral malodor, plaque and gingivitis |
JP2000086414A (ja) | 1998-09-04 | 2000-03-28 | Kinjirushi Wasabi Kk | 制菌、抗菌性に優れた抗菌剤 |
NO990975A (no) * | 1999-03-01 | 2000-02-21 | Orix As | Oralt preparat som er effektivt mot halitose |
US6361812B1 (en) * | 1999-11-18 | 2002-03-26 | The Procter & Gamble Co. | Products comprising an isothiocyanate preservative system and methods of their use |
US8283135B2 (en) * | 2000-06-30 | 2012-10-09 | The Procter & Gamble Company | Oral care compositions containing combinations of anti-bacterial and host-response modulating agents |
US7087255B2 (en) | 2000-12-27 | 2006-08-08 | Wm. Wrigley Jr. Company | Chewing gums that provide breath freshening characteristics |
US6723305B2 (en) * | 2002-03-04 | 2004-04-20 | Colgate Palmolive Company | Anti-microbial breath freshening mouthrinse |
EP1865929A2 (en) * | 2005-03-28 | 2007-12-19 | Bioresponse, L.L.C. | Diindolylmethane-based compositions and methods of use thereof for promoting oral mucosal and bone health |
GB0605634D0 (en) | 2006-03-21 | 2006-05-03 | Biofilm Ltd | Breath deodoriser |
US20080253976A1 (en) * | 2007-04-16 | 2008-10-16 | Douglas Craig Scott | Personal Care Compositions Comprising An Antimicrobial Blend of Essential Oils or Constituents Thereof |
BRPI1005670A8 (pt) * | 2009-01-05 | 2017-12-26 | Epitogenesis Inc | composições adjuvantes e processos de uso. |
JP2010279414A (ja) | 2009-06-02 | 2010-12-16 | Kinjirushi Kk | ω−メチルチオアルキルイソチオシアネートを含有する消臭剤 |
GB0915265D0 (en) * | 2009-09-02 | 2009-10-07 | Cadbury Uk Ltd | Confectionery composition |
-
2012
- 2012-07-10 MX MX2014000904A patent/MX362350B/es active IP Right Grant
- 2012-07-10 CN CN201280037437.1A patent/CN103717225B/zh active Active
- 2012-07-10 PL PL12818073T patent/PL2736520T3/pl unknown
- 2012-07-10 WO PCT/US2012/046071 patent/WO2013015979A2/en active Application Filing
- 2012-07-10 RU RU2014103675/15A patent/RU2573987C2/ru active
- 2012-07-10 CA CA2842745A patent/CA2842745C/en active Active
- 2012-07-10 US US14/234,517 patent/US10543155B2/en active Active
- 2012-07-10 EP EP12818073.4A patent/EP2736520B1/en active Active
- 2012-07-10 AU AU2012287333A patent/AU2012287333B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
AU2012287333A1 (en) | 2013-05-02 |
RU2014103675A (ru) | 2015-09-10 |
EP2736520B1 (en) | 2020-09-09 |
US10543155B2 (en) | 2020-01-28 |
WO2013015979A2 (en) | 2013-01-31 |
AU2012287333B2 (en) | 2016-02-25 |
MX362350B (es) | 2019-01-11 |
RU2573987C2 (ru) | 2016-01-27 |
WO2013015979A3 (en) | 2013-05-10 |
MX2014000904A (es) | 2015-04-10 |
EP2736520A4 (en) | 2015-07-08 |
CN103717225A (zh) | 2014-04-09 |
CA2842745A1 (en) | 2013-01-31 |
US20140294739A1 (en) | 2014-10-02 |
EP2736520A2 (en) | 2014-06-04 |
PL2736520T3 (pl) | 2020-11-30 |
CA2842745C (en) | 2018-01-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103717225B (zh) | 用于减少口腔挥发性硫化合物(vsc)的含有锌盐和异硫氰酸酯的组合物 | |
Brook | Early side effects of radiation treatment for head and neck cancer | |
CN1267079C (zh) | 改善口腔卫生的草本组合物 | |
JP4375664B2 (ja) | 舌苔除去効果を有する食品 | |
WO2005063184A1 (en) | Methods and compositions for oral hygiene | |
CN108135814A (zh) | 木兰树皮提取物和L-精氨酸Nα-月桂酰基乙酯对唾液菌的协同抗菌作用 | |
CN108186384A (zh) | 一种漱口水及其制备方法 | |
JP2004532831A (ja) | 歯科用調剤 | |
EP3290041B1 (en) | Oral care composition | |
KR100513117B1 (ko) | 애완동물의 구강 및 치아 보호용 놀이기구 | |
KR101721145B1 (ko) | L-카르니틴 구연산 마그네슘을 포함하는 배변촉진 겸용 다이어트용 식품 조성물 | |
KR101660467B1 (ko) | 구기자 발효추출물을 함유하는 구강용 조성물 | |
WO2011007552A1 (ja) | 口臭除去剤 | |
KR20190014220A (ko) | 숙취해소용 혼합발효 추출액 조성물 및 이를 유효성분으로 함유하는 숙취해소제 제조방법 | |
JP2009286749A (ja) | 口腔衛生用固形物 | |
DE202021000357U1 (de) | Zahnpflegemittel für die orale Anwendung in Pulverform aus naturbelassenen Inhaltstoffen zur Remineralisierung des Zahnschmelzes, zur Verminderung dentaler Plaque und der Förderung einer positiven Mundflora, sowie dem Zusatz von Methylcobalamin (Vitamin B12 ) zur Verringerung von Müdigkeit und Erschöpfung | |
JP2014094968A (ja) | 口臭除去剤 | |
EP2123167A1 (en) | The product for cleaning the tongue, the method of its production and use of cereal grains and seeds of oil bearing plants | |
KR20230040932A (ko) | 구취 제거 또는 개선용 조성물 | |
PL241360B1 (pl) | Kompozycja do higienizacji jamy ustnej i zastosowanie bakteriobójczego olejku eterycznego i dodatku ściernego do wytwarzania kompozycji | |
KR20100056085A (ko) | 금연 효과가 우수한 혼합정유 조성물과 금연 보조제 | |
EP2127535A1 (en) | Flaxseed product for cleaning the tongue, the method of the production of the product for cleaning the tongue, use of flaxseed for the product |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant |