TWI605853B - 含有磷酸鋅的組成物 - Google Patents
含有磷酸鋅的組成物 Download PDFInfo
- Publication number
- TWI605853B TWI605853B TW102141979A TW102141979A TWI605853B TW I605853 B TWI605853 B TW I605853B TW 102141979 A TW102141979 A TW 102141979A TW 102141979 A TW102141979 A TW 102141979A TW I605853 B TWI605853 B TW I605853B
- Authority
- TW
- Taiwan
- Prior art keywords
- dentifrice
- zinc
- phosphate
- mouthwash
- zinc phosphate
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims description 156
- 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 title claims description 61
- 229910000165 zinc phosphate Inorganic materials 0.000 title claims description 61
- 239000000551 dentifrice Substances 0.000 claims description 47
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 29
- 239000002324 mouth wash Substances 0.000 claims description 29
- 229940051866 mouthwash Drugs 0.000 claims description 28
- 229910019142 PO4 Inorganic materials 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 27
- 235000021317 phosphate Nutrition 0.000 claims description 26
- 239000004475 Arginine Substances 0.000 claims description 23
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 21
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 19
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 18
- 239000010452 phosphate Substances 0.000 claims description 16
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 15
- 239000004094 surface-active agent Substances 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 239000000796 flavoring agent Substances 0.000 claims description 11
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 10
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 claims description 10
- 235000019818 tetrasodium diphosphate Nutrition 0.000 claims description 10
- 235000013355 food flavoring agent Nutrition 0.000 claims description 9
- 239000003906 humectant Substances 0.000 claims description 9
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims description 7
- 230000002378 acidificating effect Effects 0.000 claims description 7
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 7
- 235000019832 sodium triphosphate Nutrition 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- JUNWLZAGQLJVLR-UHFFFAOYSA-J calcium diphosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O JUNWLZAGQLJVLR-UHFFFAOYSA-J 0.000 claims description 6
- 229940043256 calcium pyrophosphate Drugs 0.000 claims description 6
- 235000019821 dicalcium diphosphate Nutrition 0.000 claims description 6
- 235000011187 glycerol Nutrition 0.000 claims description 6
- 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 claims description 5
- 229960001927 cetylpyridinium chloride Drugs 0.000 claims description 5
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 claims description 5
- 201000005581 enamel erosion Diseases 0.000 claims description 5
- 239000000600 sorbitol Substances 0.000 claims description 5
- 230000002087 whitening effect Effects 0.000 claims description 5
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 claims description 4
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- RYCLIXPGLDDLTM-UHFFFAOYSA-J tetrapotassium;phosphonato phosphate Chemical compound [K+].[K+].[K+].[K+].[O-]P([O-])(=O)OP([O-])([O-])=O RYCLIXPGLDDLTM-UHFFFAOYSA-J 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 3
- 239000004599 antimicrobial Substances 0.000 claims description 3
- 235000003599 food sweetener Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000003765 sweetening agent Substances 0.000 claims description 3
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 2
- 229910052684 Cerium Inorganic materials 0.000 claims description 2
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000004302 potassium sorbate Substances 0.000 claims description 2
- 235000010241 potassium sorbate Nutrition 0.000 claims description 2
- 229940069338 potassium sorbate Drugs 0.000 claims description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 1
- MRUAUOIMASANKQ-UHFFFAOYSA-N cocamidopropyl betaine Chemical compound CCCCCCCCCCCC(=O)NCCC[N+](C)(C)CC([O-])=O MRUAUOIMASANKQ-UHFFFAOYSA-N 0.000 claims 1
- 239000011701 zinc Substances 0.000 description 48
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 40
- 210000003298 dental enamel Anatomy 0.000 description 40
- 229910052725 zinc Inorganic materials 0.000 description 40
- -1 fluoride ions Chemical class 0.000 description 29
- 239000000606 toothpaste Substances 0.000 description 29
- 229940034610 toothpaste Drugs 0.000 description 27
- 229940091249 fluoride supplement Drugs 0.000 description 26
- 238000009472 formulation Methods 0.000 description 24
- 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 22
- 239000011746 zinc citrate Substances 0.000 description 22
- 235000006076 zinc citrate Nutrition 0.000 description 22
- 229940068475 zinc citrate Drugs 0.000 description 22
- 150000001413 amino acids Chemical class 0.000 description 21
- 235000001014 amino acid Nutrition 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 235000009697 arginine Nutrition 0.000 description 16
- 239000011575 calcium Substances 0.000 description 15
- 239000011734 sodium Substances 0.000 description 14
- 238000000034 method Methods 0.000 description 11
- 239000002585 base Substances 0.000 description 10
- 210000000214 mouth Anatomy 0.000 description 10
- 229920000642 polymer Polymers 0.000 description 10
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 9
- 239000003945 anionic surfactant Substances 0.000 description 9
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 8
- 238000004833 X-ray photoelectron spectroscopy Methods 0.000 description 8
- KFVPJMZRRXCXAO-UHFFFAOYSA-N [He].[O] Chemical compound [He].[O] KFVPJMZRRXCXAO-UHFFFAOYSA-N 0.000 description 8
- 239000003082 abrasive agent Substances 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 208000002925 dental caries Diseases 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 7
- 229920001577 copolymer Polymers 0.000 description 7
- 235000011180 diphosphates Nutrition 0.000 description 7
- 230000036541 health Effects 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000002562 thickening agent Substances 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 6
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical group O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 229940083542 sodium Drugs 0.000 description 6
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 229920006318 anionic polymer Polymers 0.000 description 5
- 230000003628 erosive effect Effects 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000011775 sodium fluoride Substances 0.000 description 5
- 235000013024 sodium fluoride Nutrition 0.000 description 5
- 229960000414 sodium fluoride Drugs 0.000 description 5
- 229920001864 tannin Polymers 0.000 description 5
- 239000001648 tannin Substances 0.000 description 5
- 235000018553 tannin Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 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
- 208000006558 Dental Calculus Diseases 0.000 description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 description 4
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 125000000129 anionic group Chemical group 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000005115 demineralization Methods 0.000 description 4
- 230000002328 demineralizing effect Effects 0.000 description 4
- 230000008021 deposition Effects 0.000 description 4
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 239000004088 foaming agent Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 235000018977 lysine Nutrition 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 238000005498 polishing Methods 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- 229960003500 triclosan Drugs 0.000 description 4
- 150000003751 zinc Chemical class 0.000 description 4
- XGRSAFKZAGGXJV-UHFFFAOYSA-N 3-azaniumyl-3-cyclohexylpropanoate Chemical compound OC(=O)CC(N)C1CCCCC1 XGRSAFKZAGGXJV-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 3
- 244000060011 Cocos nucifera Species 0.000 description 3
- 235000013162 Cocos nucifera Nutrition 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 229920000388 Polyphosphate Polymers 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003929 acidic solution Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 150000008051 alkyl sulfates Chemical class 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 229960003237 betaine Drugs 0.000 description 3
- 230000032770 biofilm formation Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 3
- 229910001424 calcium ion Inorganic materials 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 159000000007 calcium salts Chemical class 0.000 description 3
- MRUAUOIMASANKQ-UHFFFAOYSA-O carboxymethyl-[3-(dodecanoylamino)propyl]-dimethylazanium Chemical compound CCCCCCCCCCCC(=O)NCCC[N+](C)(C)CC(O)=O MRUAUOIMASANKQ-UHFFFAOYSA-O 0.000 description 3
- 235000010418 carrageenan Nutrition 0.000 description 3
- 239000000679 carrageenan Substances 0.000 description 3
- 229920001525 carrageenan Polymers 0.000 description 3
- 229940113118 carrageenan Drugs 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 238000005260 corrosion Methods 0.000 description 3
- 239000003479 dental cement Substances 0.000 description 3
- 210000004268 dentin Anatomy 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000005530 etching Methods 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 208000007565 gingivitis Diseases 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
- 239000001307 helium Substances 0.000 description 3
- 229910052734 helium Inorganic materials 0.000 description 3
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 229960001774 octenidine Drugs 0.000 description 3
- SMGTYJPMKXNQFY-UHFFFAOYSA-N octenidine dihydrochloride Chemical compound Cl.Cl.C1=CC(=NCCCCCCCC)C=CN1CCCCCCCCCCN1C=CC(=NCCCCCCCC)C=C1 SMGTYJPMKXNQFY-UHFFFAOYSA-N 0.000 description 3
- 239000001205 polyphosphate Substances 0.000 description 3
- 235000011176 polyphosphates Nutrition 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 235000013772 propylene glycol Nutrition 0.000 description 3
- 210000003296 saliva Anatomy 0.000 description 3
- 229960004711 sodium monofluorophosphate Drugs 0.000 description 3
- ANOBYBYXJXCGBS-UHFFFAOYSA-L stannous fluoride Chemical compound F[Sn]F ANOBYBYXJXCGBS-UHFFFAOYSA-L 0.000 description 3
- 229960002799 stannous fluoride Drugs 0.000 description 3
- 239000000341 volatile oil Substances 0.000 description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 2
- YFVBASFBIJFBAI-UHFFFAOYSA-M 1-tetradecylpyridin-1-ium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+]1=CC=CC=C1 YFVBASFBIJFBAI-UHFFFAOYSA-M 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- ANAAMBRRWOGKGU-UHFFFAOYSA-M 4-ethyl-1-tetradecylpyridin-1-ium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+]1=CC=C(CC)C=C1 ANAAMBRRWOGKGU-UHFFFAOYSA-M 0.000 description 2
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 2
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Description
本發明係提供包括磷酸鋅之口腔保健組成物,例如潔牙劑或漱口水,其中磷酸鋅係加入潔牙劑或漱口水中作為預形成鹽(preformed salt);以及製造和使用彼等之方法。
牙齒蛀蝕係涉及去礦化作用以及由於非細菌性來源之酸侵襲所致之牙齒結構的傷害。蛀蝕最初係在琺瑯質中發現,若未受遏止可能進行至下方的牙本質。牙齒蛀蝕可能經由酸性食物和飲料、暴露於經氯消毒的泳池水及胃酸逆流所造成或更加劇。牙齒琺瑯質為一負電荷表面,其本質上傾向吸引正電荷離子例如氫和鈣離子,同時阻抗負電荷離子例如氟化物離子。依照週圍唾液之相對pH,牙齒琺瑯質會失去或得到正電荷離子例如鈣離子。一般而言,唾液具有介於7.2至7.4之pH。當pH降低及氫離子濃度變得相當高時,氫離子將會置換琺瑯質中的鈣離子,形成磷酸氫(磷酸),其會傷害琺瑯質並造成多孔性、類海綿之粗糙表面。若唾液長時間仍為酸性,則再礦化作用可能不會發生且牙齒將持續流失礦物質,造成牙齒弱化及最後結構流失。
對於治療和降低腐蝕之改良性產品有其需求。
重金屬離子例如鋅對於酸侵襲具有阻抗性。在電位序次上鋅排在氫之上,所以當鋅進入溶液,金屬鋅在酸性溶液中將會與游離的氫氣
反應,形成二-陽離子Zn2+。在牙菌斑和齲齒研究中鋅已顯示具有抗細菌性質。
可溶性鋅鹽例如檸檬酸鋅,已用於潔牙劑組成物中,但有數個缺點。在溶液中鋅離子給予一種不愉悅、澀的口感,所以提供有效量以及具有可接受感官感知性質的鋅之組成物,難以達成。再者,游離的鋅離子可能與氟化物離子作用產生氟化鋅,其為不可溶的並因而降低了鋅和氟化物二者之可利用性。最後,鋅離子會與陰離子界面活性劑例如月桂基硫酸鈉反應,因而妨礙起泡性和清潔性。
磷酸鋅(Zn3(PO4)2)雖然可溶於酸性或鹼性溶液,例如無機酸、乙酸、氨或鹼金屬氫氧化物之溶液,但不溶於水。參見例如,Merck Index,13th Ed.(2001)p.1812,專刊編號10205。部分係因為其一般在本項技術中被視為惰性物質,通常用於牙科黏固劑,例如鑲嵌、牙冠、牙橋和矯正裝置之膠結,希望可在口中耐用多年。磷酸鋅牙科黏固劑一般係藉由將氧化鋅和氧化鎂粉末與一主要由磷酸、水和緩衝劑組成的液體相混合所製備,所以該包括磷酸鋅之黏固劑係藉由與磷酸反應於原位所形成。
目前已發現當磷酸鋅至於調配物中,例如於酸性或鹼性pH,可因使用而充分溶解用以提供有效的鋅離子濃度給琺瑯質,藉此防止蛀蝕,降低細菌定植和生物膜生成並增進牙齒閃亮。在某些實施例中,此調配物係包括一胺基酸,例如鹼性胺基酸,例如精胺酸或離胺酸,其可賦予此調配物鹼性的pH。亦發現,磷酸鋅在帶有第二磷酸鹽來源之調配物中會促進磷酸鹽沉積。此項完全為意料之外的,有鑒於磷酸鋅之溶解性差以及技術所理解的觀點其在口腔條件中實質上為惰性的,可從其廣泛地用於牙科黏固劑可證明。同時,含有磷酸鋅之調配物不會出現味道和口感差,氟化物
遞送不足以及與習用鋅-基底的口腔保健產品(其係使用易溶解鋅鹽)有關的起泡性和清潔性差。
本發明因此係提供包含磷酸鋅之口腔保健組成物,例如潔牙劑。在某些實施例中,磷酸鋅係加到潔牙劑中作為預形成鹽。在一實施例中此組成物係進一步包括一胺基酸,例如鹼性胺基酸。此組成物可視需要進一步包括氟化物來源及/或另外的磷酸鹽來源。組成物可調配於習用的潔牙劑或漱口水基底中,例如包括研磨劑,例如矽氧研磨劑、界面活性劑、起泡劑、維生素、聚合物、酵素、保濕劑、增稠劑、抗微生物劑、防腐劑、調味劑、調色劑及/或其組合物。例如,在一實施例中,本發明係提供於矽氧研磨劑潔牙劑基底中包括約2%磷酸鋅、約5%精胺酸、約5%鹼金屬磷酸鹽及約1450ppm氟化物之潔牙劑。
本發明進一步係提供使用本發明組成物用以降低和抑制琺瑯質蛀蝕、清潔牙齒、降低細菌產生的生物膜和牙菌斑、降低牙齦炎、抑制牙齒蛀蝕和蛀洞形成,以及降低牙齒過敏之方法,其包括以本發明組成物刷洗牙齒。
由下文所提供的詳細說明,本發明進一步的適用領域將變得顯而易見。應了解,詳細說明和特定實例,當指出本發明之較佳實施例時,係希望僅供說明之目的而不希望限制本發明之範圍。
下列較佳實施例之說明本質上僅為示例性而不希望在任何方面限制本發明、其應用或用途。
如文中所用,術語「預形成鹽」-當用於有關磷酸鋅時-係指磷酸鋅並非在潔牙劑或漱口水中原位形成,例如經由磷酸和鋅鹽之反應。
本發明因此,在第一實施例中係提供一包括磷酸鋅供間歇使用,例如每天使用,例如潔牙或漱口水形式之口腔保健組成物(組成物1),例如
1.1. 組成物1,於潔牙劑基底中包括磷酸鋅之潔牙劑形式,例如其中該磷酸鋅係以一有效量存在於潔牙劑基底中,例如0.5至4%重量比之量,例如約1至3%重量比。
1.2. 組成物1.1,其中潔牙劑基底係包括一研磨劑,例如一有效量之矽氧研磨劑,例如10-30%,例如約20%。
1.3. 組成物1,於漱口水基底中包括磷酸鋅之漱口水形式,例如0.005-0.05%重量比之量,例如約0.01-0.03%重量比。
1.4. 任何前述組成物,其進一步包括一有效量之氟化物離子來源,例如提供500至3000ppm氟化物。
1.5. 任何前述組成物,其進一步包括一有效量之氟化物,例如其中氟化物為選自氟化亞錫、氟化鈉、氟化鉀、單氟磷酸鈉、氟矽酸鈉、氟矽酸銨、氟化胺(N'-十八基三伸甲基二胺-N,N,N'-叁(2-乙醇)-二氫氟化物)、氟化銨、氟化鈦、六氟硫酸鹽及其組合物。
1.6. 任何前述組成物,其包括有效量之胺基酸以增進磷酸鋅之溶解度,例如總組成物重量之約0.5重量%至約20重量%,總組成物重量之約0.5重量%至約10重量%,例如就潔牙劑的情況為總組成物重量之約1.5重量%,約3.75重量%,約5重量%或約7.5重量%,或例如就漱口水的情況約0.5-2重量%,例如約1%。
1.7. 任何前述組成物,其係包括一鹼性胺基酸,例如精胺酸或離胺酸或其組合物,例如1-精胺酸,例如以一有效量,例如以一有效量與磷酸鋅組合用以降低腐蝕、牙齒過敏及/或牙菌斑堆積,例如就潔牙劑的情況約總組成物重量之1-10%之量,或例如就漱口水的情況約0.5-2重量%,例如約1%。
1.8. 任何前述組成物,其係包括一足以將調配物的pH提高至大於pH 8,例如至pH 8.5-10之量的鹼性胺基酸,例如精胺酸。
1.9. 任何前述組成物,其進一步包括另外的鋅離子來源,例如選自檸檬酸鋅、硫酸鋅、矽酸鋅、乳酸鋅、氧化鋅及其組合物;例如在一實施例中,潔牙劑係包括1%磷酸鋅和1%檸檬酸鋅。
1.10. 任何前述組成物,其係包括一有效量之一或多種鹼性磷酸鹽,例如鈉、鉀或鈣鹽,例如選自鹼性磷酸氫鹽和鹼性焦磷酸鹽,例如選自磷酸氫二鈉、磷酸氫二鉀、磷酸二鈣二水合物、焦磷酸鈣、焦磷酸四鈉、焦磷酸四鉀、三聚磷酸鈉之鹼性磷酸鹽類及任何二或多種此等之混合物,例如以組成物的重量計1-20%,例如2-8%,例如約5%之量。
1.11. 任何前述組成物,其係包括緩衝劑,例如磷酸鈉緩衝劑(例如磷酸二氫鈉和磷酸二鈉)。
1.12. 任何前述組成物,其係包括保濕劑,例如選自甘油、山梨醇、丙二醇、聚乙二醇、木糖醇及其混合物,例如包括至少20%,例如20-40%,例如25-35%甘油。
1.13. 任何前述組成物,其係包括一或多種例如選自陰離子、陽離子、兩性離子和非離子及其混合物之界面活性劑,例如係包括一陰離子界面活性劑,例如選自月桂基硫酸鈉、月桂基醚硫酸鈉及其混合物之界面活性劑,例如從約0.3%至約4.5%重量比之量,例如1-2%的月桂基硫酸鈉(SLS);及/或兩性離子界面活性劑,例如甜菜鹼界面活性劑,例如椰油醯胺丙基甜菜鹼,例如從約0.1%至約4.5%重量比之量,例如0.5-2%椰油醯胺丙基甜菜鹼。
1.14. 任何前述組成物,其進一步包括黏度調變量之一或多種的多糖膠,例如三仙膠或鹿角菜膠、矽氧增稠劑及其組合物。
1.15. 任何前述組成物,其係包括膠條或膠片。
1.16. 任何前述組成物,其進一步包括調味劑、香料及/或調色劑。
1.17. 任何前述組成物,其係包括一有效量之一或多種抗菌劑,例如包括由下列選出之抗菌劑:鹵素化二苯基醚(例如三氯沙)、香草萃取物和精油(例如迷迭香萃取物、茶萃取物、木蘭萃取物、百里醇、薄荷醇、桉油醇、香葉醇、香芹酚、檸檬醛、扁柏酚、兒茶酚、水楊酸甲酯、表沒食子兒茶素沒食子酸酯(epigallocatechin gallate)、表沒食子兒茶素(epigallocatechin)、沒食子酸、美斯瓦克(miswak)萃取物、沙棘萃取物)、雙胍類抗菌劑(例如氯己定(chlorhexidine)、阿來西定(alexidine)或奧替尼啶(octenidine))、四級銨化合物(例如十六烷基氯化吡啶鎓(CPC)、苯紮氯銨(benzalkonium chloride)、十四烷基氯化吡啶(TPC)、N-十四烷基-4-乙基氯化吡啶(TDEPC))、酚系殺菌劑、海克替啶(hexetidine)、奧替尼啶(octenidine)、血根鹼(sanguinarine)、聚維酮碘(povidone iodine)、地莫匹醇(delmopinol)、5-正辛醯-3'-三氟甲基苯基水楊醯胺(salifluor)、金屬離子(如鋅鹽,如檸檬酸鋅,亞錫鹽、銅鹽、鐵鹽)、血根鹼、蜂膠和氧化劑(如過氧化氫、緩衝的過氧硼酸鈉或過氧碳酸鹽)、酞酸及其鹽類、單酞酸(monoperthalicacid)及其鹽類和酯類、抗壞血酸硬脂酸酯、油醯肌胺酸、硫酸烷基酯、磺基琥珀酸二辛酯、水楊醯苯胺、溴化度米芬(domiphen bromide)、地莫匹醇、辛哌醇(octapinol)和其他哌啶基衍生物、nicin製備物、亞氯酸鹽類;以及任何前述之混合物;例如包括三氯沙或十六烷基氯化吡啶鎓。
1.18. 任何前述組成物,其係包括抗細菌上有效量之三氯沙,例如0.1-0.5%,例如約0.3%。
1.19. 任何前述組成物,其進一步包括,例如由下列組成之群中選出之增白劑:過氧化物、金屬亞氯酸鹽、過硼酸鹽、過碳酸鹽、過氧酸、次氯酸鹽及其組合物。
1.20. 任何前述組成物,其進一步包括過氧化氫或過氧化氫來源,例如尿素過氧化物或過氧化物鹽或複合物(例如過氧磷酸鹽、過氧碳酸鹽、過硼酸鹽、過氧矽酸鹽或過硫酸鹽;例如過氧磷酸鈣、過硼酸鈉、過氧碳酸鈉、過氧磷酸鈉和過硫酸鉀);
1.21. 任何前述組成物,其進一步係包括干擾或防止細菌黏附之試劑,例如尼泊金丙酯(solbrol)或幾丁聚醣。
1.22. 任何前述組成物,其進一步係包括選自(i)鈣-玻璃複合物,例如磷矽酸鈉鈣,及(ii)鈣-蛋白複合物,例如酪蛋白磷酸肽-非晶磷酸鈣之鈣和磷酸來源
1.23. 任何前述組成物,其進一步係包括可溶性鈣鹽,例如選自硫酸鈣、氯化鈣、硝酸鈣、乙酸鈣、乳酸鈣及其組合物。
1.24. 任何前述組成物,其進一步係包括有效降低牙本質敏感量之生理上或口腔上可接受的鉀鹽,例如硝酸鉀或氯化鉀。
1.25. 任何前述組成物,其進一步包括陰離子聚合物,例如合成的陰離子聚合性聚羧酸鹽,例如其中該陰離子聚合物係選自馬來酸酐或酸與另外的可聚合乙烯化不飽和單體之1:4至4:1的共聚物,例如其中該陰離子聚合物為具有約30,000至約1,000,000,例如約300,000至約800,000平均分子量(M.W.)之甲基乙烯基醚/馬來酸酐(PVM/MA)共聚物,例如其中該陰離子聚合物為組成物重量的約1-5%,例如約2%。
1.26. 任何前述組成物,其進一步包括一呼吸清新劑、香料或調味劑。
1.27. 任何前述組成物,其中組成物的pH為酸性或鹼性,例如從pH 4至pH 5.5,或從pH 8至pH 10。
1.28. 任何前述組成物,其為一潔牙劑,其中該組成物係於矽氧研磨劑潔牙劑基底中包括:1-3%,例如約2%磷酸鋅;
2-8%,例如約5% L-精胺酸(游離鹼);2-8%,例如約5%鹼性磷酸鹽,例如選自磷酸氫二鈉、磷酸氫二鉀、磷酸二鈣二水合物、焦磷酸鈣、焦磷酸四鈉、焦磷酸四鉀、三聚磷酸鈉之鹼性磷酸鹽類及任何二或多種此等之混合物;700-2000ppm,例如約1450ppm氟化物,例如0.3-0.4%,例如約0.32%氟化鈉。
1.29. 任何前述組成物,其為一漱口水,其中該組成物係於漱口水基底中包括:5-10%,例如約7.5%甘油;3-7%,例如約5.5%山梨醇;5-10%,例如約7%丙二醇;0-0.1% TSPP;0.01-1%甜味劑,例如約0.02%糖精;0.01-1%,例如約0.05%檸檬酸;0-0.1%三仙膠;0.005-0.05%,例如約0.028%磷酸鋅;0-0.01%十六烷基氯化吡啶鎓;0.01-0.1%,例如約0.05%山梨酸鉀;0.05-1%,例如約0.1-0.2%調味劑;0.1-2%,例如約1%椰油醯胺丙基甜菜鹼;水(視需要與任何另外的成份共同)補足餘量,例如約70-85%,例如約80%水。
1.30. 任何前述組成物,其實質上係包括與下文實例1或實例4中之試驗調配物相同的成份。
1.31. 任何前述組成物,例如以刷洗施用於口腔後,可有效(i)降低牙齒過敏,(ii)降低牙菌斑堆積,(iii)降低或抑制去礦化作用並促
進牙齒再礦化,(iv)抑制口腔中微生物生物膜形成,(v)降低或抑制牙齦炎,(vi)促進口中傷口或割傷之癒合,(vii)降低產酸菌的量,(viii)增加非致齲性及/或非牙菌斑形成細菌之相對量,(ix)降低或抑制齲齒形成,(x)降低、修復或抑制琺瑯質之齲前病灶,例如藉由定量光學螢光(QLF)或電子齲蝕監測器(ECM)偵測,(xi)治療、舒緩或降低口乾,(xii)清潔牙齒和口腔,(xiii)降低蛀蝕,(xiv)牙齒增白;及/或(xv)促進全身健康,包括心血管健康,例如藉由降低經由口腔組織之全身性感染的潛在性。
1.32. 一種組成物,其係藉由將任何前述組成物中所述的成份組合而獲得或製得。
本發明進一步係提供磷酸鋅於製造口腔保健組成物,例如潔牙劑中,及於增進琺瑯質中鋅量之方法中的用途。在某些實施例中,此磷酸鋅係加入潔牙劑中作為預形成鹽。
本發明進一步係提供使用本發明組成物,用以增加琺瑯質中鋅量及用以治療、降低或控制琺瑯質蛀蝕發生之方法,其係包括將如上述之組成物,例如任何組成物1及以下的組成物,施用於牙齒,例如藉由刷洗。在各種實施例中,本發明係提供(i)降低牙齒過敏,(ii)降低牙菌斑堆積,(iii)降低或抑制去礦化作用並促進牙齒再礦化,(iv)抑制口腔中微生物生物膜形成,(v)降低或抑制牙齦炎,(vi)促進口中傷口或割傷之癒合,(vii)降低產酸菌的量,(viii)增加非致齲性及/或非牙菌斑形成細菌之相對量,(ix)降低或抑制齲齒形成,(x)降低、修復或抑制琺瑯質之齲前病灶,例如藉由定量光學螢光(QLF)或電子齲蝕監測器(ECM)偵測,(xi)治療、舒緩或降低口乾,(xii)清潔牙齒和口腔,(xiii)降低蛀蝕,(xiv)牙齒增白;(xv)降低酒石形成,及/或(xvi)促進全身健康,包括心血管健康,例如藉由降低經由口腔組織之全身性感染的潛在性,其係包括將如上述之任何組成物1及以下的組成物施用於有此需要之個人的牙齒,例如藉由以任何組成物1及以下的組成物
每天刷洗牙齒一或多次。本發明進一步係提供組成物1及以下的組成物供用於任何這些方法中。
活性劑:本發明之組成物可包括各種對於保護和增進琺瑯質以及牙齒結構之強度和完整性及/或降低細菌和相關牙齒蛀蝕及/或牙齦疾病有效之試劑。用於文中之活性成份的有效濃度將依所用的特定試劑和遞送系統而定。請了解,例如牙膏典型地於使用時會以水稀釋,漱口水典型地則否。因此,牙膏中活性劑的有效濃度一般將比漱口水所要求高5-15倍。濃度亦將依確切的鹽或所選的聚合物而定。例如,當活性劑係以鹽形式提供時,相對離子將會影響鹽的重量,所以若相對離子越重將需要更高重量比的鹽,以提供最終產物中相同的活性離子濃度。精胺酸,若存在時,可以從例如約0.1至約20重量%(以游離鹼的重量表示)之量存在,例如就消費者牙膏約1至約10重量%,或就專業或處方治療產品約7至約20重量%。氟化物,若存在時,可以例如約25至約25,000ppm之量存在,例如就消費者牙膏為750至2,000ppm,或就專業或處方治療產品為2,000至25,000ppm。抗菌劑之量同樣地可不同,就用於牙膏中的量比用於漱口水中的量多例如約5至約15倍。例如三氯沙牙膏可含有0.3%重量比的三氯沙。
氟化物離子來源:口腔保健組成物可進一步包括一或多種氟化物離子來源,例如可溶性氟化物鹽類。可使用廣泛各種產生氟化物離子之物質作為本組合物中之可溶性氟化物。適合的產生氟化物離子之物質的實例係描述於Briner等人之美國專利第3,535,421號、Parran,Jr.等人之美國專利第4,885,155號及Widder等人之美國專利第3,678,154號。代表性的氟化物離子來源包括(但不限於)氟化亞錫、氟化鈉、氟化鉀、單氟磷酸鈉、氟矽酸鈉、氟矽酸銨、氟化胺、氟化銨及其組合物。在特定的實施例中,氟化物離子來源包括氟化亞錫、氟化鈉、單氟磷酸鈉以及其混合物。在特定的實施例中,本發明之口腔保健組成物亦含有足以供應約25ppm至5,000ppm氟化物離子之量的氟化物離子或氟提供成份,一般至少約500ppm,例
如約500至約2000ppm,例如約1000至約1600ppm,例如1450ppm。適當的氟化物之量將依特定的施用而定。供一般消費者使用的牙膏典型地可具有約1000至約1500ppm,而兒童牙膏可具有較少一些。供專業用途之潔牙劑或塗料可具有約5,000或甚至約25,000ppm的氟化物。氟化物離子來源可以組合物之重量計約0.01%至約10%之量加至組成物中,在一實施例中約0.03至約5%,而在另外的實施例中約0.1%至約1%。提供適量氟化物離子之氟化物鹽類的重量明顯地將以鹽中相對離子的重量為基準而變。
胺基酸:在某些實施例中,本發明之組成物係包括一胺基酸。在特定的實施例中,胺基酸可為鹼性胺基酸。「鹼性胺基酸」係指天然生成的鹼性胺基酸,例如精胺酸、離胺酸和組胺酸,以及在分子中具有羧基基團和胺基基團之任何鹼性胺基酸,其為水溶性並提供帶有約7或更高之pH的水溶液。因此,鹼性胺基酸包括(但不限於)精胺酸、離胺酸、瓜胺酸、鳥胺酸、肌胺酸、組胺酸、二胺基丁酸、二胺基丙酸、其鹽類或其組合物。在特定的實施例中,此鹼性胺基酸係選自精胺酸、瓜胺酸和鳥胺酸。在特定的實施例中,此鹼性胺基酸為精胺酸,例如1-精胺酸或其鹽。在其他的實施例中,此胺基酸係經四級化,亦即胺基酸另外係經取代形成四級銨基團,其可與羧基形成內鹽,例如甜菜鹼(N,N,N-三甲基甘胺酸)。
在各種實施例中,胺基酸係以總組成物重量之約0.5重量%至約20重量%,總組成物重量之約1重量%至約10重量%之量存在,例如就潔牙劑的情況約總組成物重量之1.5重量%,約3.75重量%,約5重量%或約7.5重量%,或例如就漱口水的情況約0.5-2重量%,例如約1%。
研磨劑:本發明之組成物,例如組成物1以及以下組成物,係包括矽氧研磨劑,並可包括另外的研磨劑,例如磷酸鈣研磨劑,例如磷酸三鈣(Ca3(PO4)2)、羥磷灰石(Ca10(PO4)6(OH)2)或磷酸氫鈣二水合物(CaHPO4.2H2O,文中有時亦稱DiCal)或焦磷酸鈣;碳酸鈣研磨劑;或例如
偏磷酸鈉、偏磷酸鉀、矽酸鋁、煅燒氧化鋁、膨潤土或其他矽質物質或其組合物之研磨劑。
可用於本文之其他矽氧研磨拋光物質以及其他研磨劑,一般係具有範圍介於約0.1至約30微米,介於約5至約15微米之平均粒子大小。矽氧研磨劑可為沉澱矽氧或矽氧凝膠,例如,Pader等人之美國專利第3,538,230號及Digiulio之美國專利第3,862,307號中所描述的矽氧乾凝膠(silica xerogel)。特定的矽氧乾凝膠有W.R.Grace & Co.,Davison Chemical Division所販售的商品名Syloid®。沉澱矽氧物質包括J.M.Huber公司所販售的商品名Zeodent®,包括名稱Zeodent 115和119之矽氧。這些矽氧研磨劑係描述於Wason之美國專利第4,340,583號中。在特定的實施例中,可用於施行本發明之口腔保健組成物之有用的研磨物質包括具有低於約100毫升/100克矽氧及約45毫升/100克至約70毫升/100克矽氧範圍內吸油值之矽氧凝膠及沉澱非晶矽氧。吸油值係使用ASTA Rub-Out Method D281所測量。在特定的實施例中,矽氧為具有約3微米至約12微米及約5至約10微米之平均粒子大小的膠體粒子。特別可用於本發明施行中之低吸油矽氧研磨劑為Davison Chemical Division of W.R.Grace & Co.,Baltimore,Md.21203所販售的商品名Sylodent XWA®。Sylodent 650 XWA®,一種由膠狀矽氧粒子所組成的矽氧水凝膠,具有約29%重量比之水含量,平均直徑約7至約10微米,及低於約70cc/100g矽氧之吸油性,為可用於本發明施行中之低吸油矽氧研磨劑的實例。
起泡劑:本發明之口腔保健組成物亦可包括當刷洗口腔時增加所產生的泡沫量之試劑。增加泡沫量試劑之說明性實例包括(但不限於)聚氧乙烯及特定的聚合物,包括(但不限於)藻酸鹽聚合物。聚氧乙烯可增加泡沫的量及由口腔保健載劑組份所產生之泡沫的厚度。聚氧乙烯一般亦稱為聚乙二醇("PEG")或聚環氧乙烷。適用於本發明之聚氧乙烯係具有約200,000至約7,000,000之分子量。在一實施例中,分子量係為約600,000至
約2,000,000,及在另一實施例中為約800,000至約1,000,000。Polyox®為由聯合碳化物公司(Union Carbide)所生產的高分子量聚氧乙烯之商品名稱。聚氧乙烯,以本發明口腔保健組成物之口腔保健載劑組份的重量計,可以約1%至約90%之量存在,在一實施例中為約5%至約50%,而在另一實施例中為約10%至約20%。若存在時,口腔保健組成物中起泡劑的量(亦即單一劑量)為約0.01至約0.9%重量比,約0.05至約0.5%重量比,及在另外的實施例中為約0.1至約0.2%重量比。
界面活性劑:可用於本發明之組成物可含有陰離子界面活性劑,例如:i.高脂肪酸單甘油酯單硫酸鹽之水溶性鹽類,例如氫化椰油脂肪酸之單硫酸單甘油酯,例如N-甲基N-椰油醯基牛磺酸鈉、椰單甘油酯硫酸鈉,ii.高烷基硫酸鹽,例如月桂基硫酸鈉,iii.高烷基-醚硫酸鹽,例如式CH3(CH2)mCH2(OCH2CH2)nOSO3X之高烷基-醚硫酸鹽,其中m為6-16例如10,n為1-6例如2、3或4,及X為Na或K,例如月桂醇聚醚-2硫酸鈉(CH3(CH2)10CH2(OCH2CH2)2OSO3Na),iv.高烷基芳基磺酸鹽,例如十二烷基苯磺酸鈉(月桂基苯磺酸鈉),v.高烷基磺基乙酸鹽,例如月桂基磺乙酸鈉(十二烷基磺乙酸鈉)、1,2二羥基丙磺酸之高脂肪酸酯、磺基月桂酸鹽(N-2-乙基月桂酸鉀磺基乙醯胺)及月桂基肌胺酸鈉。
「高烷基」係指例如C6-30烷基。在特定的實施例中,陰離子界面活性劑係選自月桂基硫酸鈉及月桂基醚硫酸鈉。陰離子界面活性劑可以調配物的重量計例如>0.01%之有效量存在,但不可為刺激口腔組織之濃度,例如<10%,且最適濃度係依照特定的調配物及特定的界面活性劑而定。例如,所用的濃度或漱口水典型地為用於牙膏的將近十分之一。在一實施例中,陰離子界面活性劑係以從約0.3至約4.5%重量比,例如約1.5%存在於牙膏中。本發明組成物可視需要含有界面活性劑之混合物,例如係
包含陰離子界面活性劑及其他可為陰離子、陽離子、兩性離子或非離子之界面活性劑。一般而言,界面活性劑為該等在整個廣泛pH範圍中相當穩定之界面活性劑。界面活性劑係更充分地描述於,例如Agricola等人之美國專利第3,959,458號;Haefele之美國專利第3,937,807號及Gieske等人之美國專利第4,051,234號中。在特定實施例中,可用於本文之陰離子界面活性劑包括在烷基上具有約10至約18個碳原子之烷基硫酸鹽的水溶性鹽類,及具有約10至約18個碳原子之脂肪酸的磺酸化單甘油酯之水溶性鹽類。月桂基硫酸鈉、月桂醯肌胺酸鈉及椰子單甘油酯磺酸鈉為此類陰離子界面活性劑之實例。在特定的實施例中,本發明組成物,例如組成物1及以下者,係包括月桂基硫酸鈉。
界面活性劑或相容的界面活性劑之混合物,可以總組成物的重量計約0.1%至約5.0%存在於本發明組成物中;在另一實施例中為約0.3%至約3.0%重量比,及在另一實施例中為約0.5%至約2.0%重量比。
酒石控制劑:在本發明各種實施例中,組合物係包括一抗結石(酒石控制)劑。適合的抗結石劑包括(不限於)磷酸鹽和聚磷酸鹽(例如焦磷酸鹽)、聚胺基丙磺酸(AMPS)、六偏磷酸鹽、檸檬酸鋅三水合物、多肽、聚烯烴磺酸鹽、聚烯烴磷酸鹽、二磷酸鹽。本發明因此可包括除了磷酸鋅外之磷酸鹽類。在特定的實施例中,這些鹽類為鹼性磷酸鹽,亦即鹼金屬氫氧化物或鹼土金屬氫氧化物之鹽類,例如鈉鹽、鉀鹽或鈣鹽。「磷酸鹽」如文中所用係涵蓋口腔可接受的單-或聚磷酸鹽,例如P1-6磷酸鹽,例如單體磷酸鹽例如磷酸二氫鹽、磷酸氫鹽或磷酸鹽;二聚磷酸鹽例如焦磷酸鹽;及多聚磷酸鹽,例如六偏磷酸鈉。在特定的實施例中,所選的磷酸鹽係選自鹼性磷酸氫鹽和鹼性焦磷酸鹽,例如選自磷酸氫二鈉、磷酸氫二鉀、磷酸二鈣二水合物、焦磷酸鈣、焦磷酸四鈉、焦磷酸四鉀、三聚磷酸鈉及任何二或多種此等之混合物。在特定的實施例中,例如此組成物係包括焦磷酸四鈉(Na4P2O7)、焦磷酸鈣(Ca2P2O7)和磷酸氫二鈉(Na2HPO4)之混合物,例
如約3-4%之量的磷酸氫二鈉和約0.2-1%之各焦磷酸鹽。在另外的實施例中,組成物係包括焦磷酸四鈉(TSPP)和三聚磷酸鈉(STPP)(Na5P3O10)之混合物,例如TSPP為約1-2%及STPP為約7%至約10%之比例。此等磷酸鹽係以有效降低琺瑯質蛀蝕、幫助清潔牙齒及/降低酒石累積在牙齒上之量來提供,例如以組成物之重量計2-20%,例如約5-15%之量。
調味劑:本發明之口腔保健組成物亦可包括調味劑。可用於本發明施行中之調味劑包括(但不限於)精油以及各種調味醛類、酯類、醇類及類似物質。精油之實例包括綠薄荷油、椒薄荷油、冬青油、黄樟油、丁香油、鼠尾草油、尤加利油、馬鬱蘭油、肉桂油、檸檬油、萊姆油、葡萄柚油及柳橙油。亦可使用此等化合物如薄荷醇、香芹酮(carvone)及茴香腦(anethole)。特定實施例係使用椒薄荷油及綠薄荷油。調味劑係以約0.1至約5%重量比,例如約0.5至約1.5%重量比之濃度併入口腔組成物中。
聚合物:本發明之口腔保健組成物亦可包括用以調整調配物黏度或增進其他成份溶解度之另外的聚合物。此等另外的聚合物包括聚乙二醇、多糖類(例如纖維素衍生物,例如羧甲基纖維素,或多糖膠,例如三仙膠或鹿角菜膠)。酸聚合物,例如聚丙烯酸凝膠,可以其游離酸或部分或完全中和的水溶性鹼金屬(例如鉀或鈉)或銨鹽形式來提供。
在水性媒劑中形成聚合結構或凝膠之矽氧增稠劑亦可存在。請注意,這些矽氧增稠劑在物理上和功能上與同樣存在組成物中的顆粒矽氧研磨劑不同,因為矽氧增稠劑為非常細的細粉狀且提供極小或並無研磨作用。其他的增稠劑有羧乙烯基聚合物、鹿角菜膠、羥乙基纖維素及纖維素醚類之水溶性鹽類,例如羧甲基纖維素及羧甲基羥乙基纖維素鈉。亦可併入天然膠例如卡拉膠(karaya)、***膠及黄蓍膠。膠體矽酸鎂鋁亦可用作增稠組成物之組份,進一步增進組合物之質地。在特定的實施例中,係使用以總組合物之重量計約0.5%至約5.0%之量的增稠劑。
本發明之組成物可包括,例如從約0.05至約5%之量的陰離子聚合物。可用於本發明中之此等試劑,雖然並非針對此項之特別應用,但一般已知係用於潔牙劑中,係揭示於美國專利第5,188,821號及第5,192,531號中;並包括合成的陰離子聚合性聚羧酸,例如馬來酸酐或酸與另外可聚合的乙烯化不飽和單體之1:4至4:1共聚物,較佳地具有約30,000至約1,000,000,最佳地約30,000至約800,000分子量(M.W.)之甲基乙烯醚/馬來酸酐。這些共聚物可取得的有例如來自ISP Technologies公司(Bound Brook,N.J.08805)之Gantrez如AN 139(M.W.500,000)、AN 119(M.W.250,000)及較佳地S-97醫藥等級(M.W.70,000)。當促進劑存在時,其係以範圍從約0.05至約3%重量比之量存在。其他可施用的聚合物包括該等例如馬來酸酐與丙烯酸乙酯、甲基丙烯酸羥乙基酯、N-乙烯基-2-吡咯酮或乙烯(後者可取得有例如孟山都(Monsanto)EMA編號1103,M.W.10,000及EMA等級61)之1:1共聚物,以及丙烯酸與甲基丙烯酸甲酯或羥乙基酯、丙烯酸甲酯或乙酯、異丁基乙烯醚或N-乙烯基-2-吡咯酮之1:1共聚物。一般適合的為含有一活化碳-碳烯烴雙鍵和至少一羧基基團之聚合烯烴化或乙烯化不飽和羧酸,亦即含有在聚合作用中容易作用之烯烴雙鍵的酸,因為其係以相對於羧基基團之α-β位置或為末端伸甲基基團之部分存在於單體分子中。此等酸之示例有丙烯酸、甲基丙烯酸、乙基丙烯酸、α-氯丙烯酸、巴豆酸、β-丙烯醯氧基丙酸、山梨酸、α-氯山梨酸、肉桂酸、β-苯乙烯基丙烯酸、黏康酸(muconic)、衣康酸(itaconic)、檸康酸(citraconic)、中康酸(mesaconic)、戊烯二酸、烏頭酸、α-苯基丙烯酸、2-苯甲基丙烯酸、2-環己基丙烯酸、當歸酸、傘形酸、延胡索酸、馬來酸及酸酐。可與此等羧酸單體共聚化之其他不同的烯烴單體包括乙烯基乙酸、氯化乙烯、馬來酸二甲酯及其類似物。共聚物含有可溶於水之足夠的羧酸鹽基團。另一類的聚合劑包括含有經取代丙烯醯胺均聚物及/或不飽和磺酸及其鹽類均聚物之組成物,特別是其中聚合物係以選自丙烯醯胺基烷磺酸之不飽和磺酸為主,例如描述於Zahid
之1989年6月27日美國專利第4,842,847號中,具有約1,000至約2,000,000分子量之2-丙烯醯胺2甲基丙磺酸。另外有用的聚合劑種類別包括聚胺基酸,例如Sikes等人之美國專利第4,866,161號所揭示之含陰離子表面活化胺基酸部分,如天門冬胺酸、麩胺酸及磷絲胺酸之聚胺基酸。
水:口腔組成物可包括大量的水。用於製備市售口腔組成物的水應去離子化且無有機雜質。組成物中的水量係包括添加的游離水加上隨其他物質例如隨山梨醇或任何本發明組份共同導入的水量。
保濕劑:在特定的口腔組成物之實施例中,亦希望併入一保濕劑以防止組成物因暴露於空氣中而硬化。特定的保濕劑亦可能給予潔牙組成物所欲的甜味或風味。適合的保濕劑包括可食用之多元醇,例如甘油、山梨醇、木糖醇、丙二醇以及其他多醇類與這些保濕劑之混合物。在本發明一實施例中,主要的保濕劑為甘油,其可以大於25%,例如25-35%,約30%之量存在,帶有5%或更少的其他保濕劑。
其他視需要之成份:除了上述組份,本發明之實施例可含有各種某些下述之視需要的潔牙劑成份。視需要的成份包括,例如(但不限於)黏著劑、泡沫劑、調味劑、甜味劑、另外的抗菌斑劑、研磨劑及調色劑。這些及其他視需要組份係進一步描述於Majeti之美國專利第5,004,597號;Agricola等人之美國專利第3,959,458號;Haefele之美國專利第3,937,807號中,其全部係以引用的方式併入本文中。
如全文所用,範圍係用於速記供描述在此範圍內的各個和每個值。在此範圍內的任何值皆可選作此範圍的最終值。此外,所有文中所引述的參考文獻其全文係以引用的方式併入本文中。在本揭示文與所引述的參考文獻的定義有衝突時,則以本揭示文為主。
除非另有說明否則文中和說明書之他處所表示的所有百分比和量,應了解係指重量百分比。所給予的量係以物質之有效重量為基準。
製備包括2%磷酸鋅與5%精胺酸、1450ppm氟化物和磷酸鹽組合之試驗潔牙劑。此潔牙劑具有9.13之pH,符合相當高精胺酸含量。亦根據下列配方製備包括2%檸檬酸鋅,1%檸檬酸鋅,1%檸檬酸鋅+1%磷酸鋅,無鋅或無精胺酸之潔牙劑(成份以組成物的重量計):
相較於包括1%檸檬酸鋅之對照潔牙劑,含有2%磷酸鋅與精胺酸和氟化物之實例1潔牙劑對酸挑戰顯現優越的效力。
使用活體外方法測定實例1調配物原型之琺瑯質保護活性。藉由將牛門牙嵌入甲基丙烯酸為主的樹脂中並以600和1200粒度之磨砂紙連續拋光,製備琺瑯質基質(N=6/8每格)。在將琺瑯質拋光至鏡面拋光度的同時,小心不要穿透牙本質層。在試驗前,所有的琺瑯質基質係以5%的檸檬酸預浸蝕30秒。各基質的半側係以抗酸膠帶遮蔽以保護表面做為對照表面。用於評估產品之模型根據T-C-C-C-C-T之每日順序以1-分鐘產品治療期與2-分鐘酸暴露期交替(T=產品治療,C=酸挑戰)。酸挑戰係以經NaOH調整至pH=3.8的1%檸檬酸水溶液(未緩衝)來進行。當未進行治療或挑戰時,所有的琺瑯質基質係置於37℃無菌人造唾液溶液中。此療程進行總計五天,在結束時使用顯微硬度分析來定量因蛀蝕而於各琺瑯質基質上受保護的和暴露的表面所流失的琺瑯質之量。計算硬度的百分比變化。無治療的,係使用去離子水取代試驗潔牙劑,其硬度的百分比變化非常高,約80%,依照特定的基質,各個實驗有些微的變化。
在此處設計用來評估早期琺瑯質溶離之保護效用的活體外pH-循環模型中,含有2%磷酸鋅之配方對於對抗去礦化作用為有效的,其在重複的酸挑戰後硬度僅降低24.3%,比1%檸檬酸鋅調配物中所觀察到的硬度下降比26.3%更少。一個別的實驗顯示,將調配物中檸檬酸鋅的量從1%增加至2%並不會增加對抗酸挑戰之效用。在1%時已達到最大效用。因此,在此分析中磷酸鋅調配物之效用係優於,或至少與使用檸檬酸鋅調配
物所達到的最大效用同樣良好,其就本項技術中咸信磷酸鋅在口腔中為相當不活潑之觀點而言,實令人驚訝。
進行另外的實驗評估包含磷酸鋅(ZnP)有和無精胺酸之調配物,以及包括1%磷酸鋅和檸檬酸鋅之調配物。將包括氟化鈉和硝酸鉀之市售琺瑯質-保護牙膏(市售品1)納入作為正性對照。(NB:各實驗組係使用由不同人類牙齒所製造的製備物,所以實驗組之間可能會有一些變異):
在此系列的實驗中,含精胺酸之磷酸鋅至少與正性對照同樣良好,且出乎預期的,比磷酸鋅和檸檬酸鋅之組合明顯更佳。
化學分析之電子能譜(ESCA,亦稱為x-射線光電子能譜或XPS)為一種用於得到有關固體物質表面之化學資訊的表面分析技術。物質的定性方法係利用x-光束激發固體樣本造成光電子發射。這些光電子的能量分析係提供有關樣本表面之元素和化學鍵結資訊二者。以相當低的光電子動能給予ESCA大約30Å之取樣深度。在如前面實例描述所製備和治療之經拋光和浸蝕的琺瑯質基質上,於使用試驗與對照潔牙劑之前和之後,使用ESCA分析琺瑯質的礦物質含量,確認鋅係遞送至琺瑯質表面且即使在酸挑戰後鋅仍留在表面上,以及確認有效的遞送氟化物。
經各種實例1之Zn/精胺酸/磷酸鹽抗-腐蝕牙膏治療過之琺瑯質樣本的ESCA數據係如表3(下表)中所示,其係說明所偵測到的元素及其個別的原子濃度。所有的樣本係於各自拋光、浸蝕和治療步驟後進行分析。為了簡單起見,就所有的樣本僅顯示拋光和浸蝕表面之平均組成。在
所有的案例中係分析各樣本之三至四個個別區域。就治療過的樣本,係顯示個別區域的組成以及各樣本之平均組成。
在經拋光和浸蝕的樣本上從表面有機物偵測到C和N。從琺瑯質的羥磷灰石偵測到Ca和P,具有典型的琺瑯質表面之P/Ca比率。浸蝕表面之平均P/Ca比率略低於拋光表面,其顯示在浸蝕後,發生相對於Ca之表面磷酸鹽減少。拋光表面偵測到低量的Zn,其係經由浸蝕移除了。在拋光和浸蝕過的表面亦偵測到低量的氟化物。亦觀察到低量的Na。整體而言,拋光和浸蝕過的琺瑯質表面之組成為典型的牛琺瑯質。
在所有經治療的樣本上從表面有機物偵測到C和N。由於殘餘的有機物存在,所有樣本的C量皆高於浸蝕表面,很可能係來自牙膏。相對於浸蝕過的表面,經治療的樣本之N量亦較高。
在樣本的表面亦偵測到Ca和P,來自法瑯質的HAP。經治療的樣本之P/Ca比率係高於浸蝕過的表面,其顯示相對於Ca之過量的磷酸鹽。就所有的樣本,Na濃度亦明顯高於浸蝕過的琺瑯質。經治療的樣本上較高的磷酸鹽和Na量顯示來自牙膏的磷酸鈉已沉積在琺瑯質表面上。由於來自牙膏的殘餘矽氧,在經治療的琺瑯質上亦偵測到低量的Si。
對於經含有檸檬酸鋅或磷酸鋅之牙膏治療過的琺瑯質樣本,亦在表面上觀察到升高量的鋅。就之前的研究,Zn/Ca比率係提供琺瑯質表面上鋅吸收比較之最佳方法。經磷酸鋅牙膏治療的琺瑯質之Zn/Ca比率大於檸檬酸鋅牙膏。此顯示磷酸鋅牙膏比檸檬酸鋅產品沉積較多的鋅在琺瑯質上。以莫耳濃度為基準,磷酸鋅比同重的檸檬酸鋅含更多的鋅。此項可能造成在經磷酸鋅牙膏治療的琺瑯質上偵測到較多的鋅,但很清楚的磷酸鋅在遞送鋅至琺瑯質表面上為有效的。總言之,樣本中所觀察到的Zn/Ca比率在本研究中為約之前提出的pH循環研究的琺瑯質樣本的二倍。
ESCA鋅高峰位置可提供琺瑯質表面上鋅之化學狀態的資訊。對所有經含鋅牙膏治療的樣本,鋅高峰位置為相同的。此項顯示,存
在所有樣本中的鋅為類似的化學形式。此外,經鋅牙膏治療的樣本之鋅高峰位置係與拋光過的琺瑯質表面上的背景鋅相同。原本存在琺瑯質中的背景鋅可能為HAP鋅形式。因此,此數據顯示經治療的琺瑯質上的鋅可能亦為HAP鋅形式。
在所有經牙膏治療的琺瑯質樣本之表面上偵測到氟化物形式的F。樣本間相對的氟化物吸收最好亦使用F/Ca比率來偵測。此數據顯示,經1%和2%檸檬酸鋅牙膏治療的琺瑯質具有類似的F/Ca比率,其顯示類似的F吸收。經無精胺酸和Zn3(PO4)2之檸檬酸鋅牙膏治療的樣本比其它樣本具有稍低的F/Ca比率。然而,對於後二種治療之較低的氟化物吸收係為此類研究之正常變異。
ESCA結果顯示,經含檸檬酸鋅或磷酸鋅牙膏治療的琺瑯質發生鋅沉積。相較於檸檬酸鋅牙膏,含磷酸鋅的牙膏鋅沉積較多。此數據亦顯示,鋅可以鋅-HAP之形式存在表面上。所有經牙膏治療的樣本亦觀察到升高量的氟化物。
此分析之詳細結果係如表3(下表)所示。
如該數據所示,使用磷酸鋅調配物將鋅遞送至琺瑯質(平均0.58)實際上比使用任何檸檬酸鋅遞送鋅更多。將鋅併入至琺瑯質,可能經由鋅-羥磷灰石物質,就鋅在控制蛀蝕及降低細菌生物膜沉積上之有益效應而言為有利的。與磷酸鋅調配物一起遞送的氟化物亦在可接受的範圍,其相較於對照組顯示明顯的氟化物沉積,與包括檸檬酸鋅無精胺酸之調配物相類似。
雖然磷酸鋅不溶於水,但發現可溶於酸性溶液。包括例如2%乳酸(約pH 2.4),或甚至少如0.05%檸檬酸(約pH 4)之調配物,其中磷酸鋅為0.01-0.03%並不會出現沉澱。已發現,在包括胺基酸及/或甜菜鹼界面活性劑之調配物中可增進磷酸鋅之溶解度。安定的漱口水調配物係提供如下:
Claims (21)
- 一種包括磷酸鋅之潔牙劑,其中該磷酸鋅係以1至5%重量比之量加入該潔牙劑中作為預形成鹽(preformed salt),該潔牙劑進一步係包括1至8%精胺酸及一或多種保濕劑以及一或多種界面活性劑。
- 如申請專利範圍第1項之潔牙劑,其中該磷酸鋅之量為1至3%重量比。
- 如申請專利範圍第1項之潔牙劑,其進一步係包括一有效量之氟化物離子來源。
- 如申請專利範圍第1項之潔牙劑,其進一步係包括一有效量之一或多種鹼性磷酸鹽。
- 如申請專利範圍第1項之潔牙劑,其進一步係包括一有效量之一或多種抗菌劑。
- 如申請專利範圍第1項之潔牙劑,其進一步係包括一增白劑。
- 如申請專利範圍第1項之潔牙劑,其除了磷酸鋅外,係進一步包括一或多種鋅離子來源。
- 如申請專利範圍第1項之潔牙劑,其中該組成物之pH為酸性。
- 如申請專利範圍第1項之潔牙劑,其中該組成物之pH為鹼性。
- 如申請專利範圍第1項之潔牙劑,更包含一矽氧研磨劑潔牙劑基底,其包括1至3%磷酸鋅;1至8%精胺酸;2至8%鹼性磷酸鹽類、其選自由磷酸氫二鈉、磷酸氫二鉀、磷酸二鈣二水合物、焦磷酸四鈉、焦磷酸四鉀、焦磷酸鈣、三聚磷酸鈉,其及任何二或多種此等之混合物;及700至2000ppm氟化物。
- 一種包括磷酸鋅及精胺酸之漱口水,其中該磷酸鋅係以0.01至0.03%重量比之量加入漱口水中作為預形成鹽。
- 如申請專利範圍第11項之漱口水,其進一步係包括一有效量之氟化物離子來源。
- 如申請專利範圍第11項之漱口水,其進一步係包括一有效量之一或多種鹼性磷酸鹽。
- 如申請專利範圍第11項之漱口水,其進一步係包括一有效量之一或多種抗菌劑。
- 如申請專利範圍第11項之漱口水,其進一步係包括一增白劑。
- 如申請專利範圍第11項之漱口水,其除了磷酸鋅外,係進一步包括一或多種鋅離子來源。
- 如申請專利範圍第11項之漱口水,其中該組成物之pH為酸性。
- 如申請專利範圍第11項之漱口水,其中該組成物之pH為鹼性。
- 如申請專利範圍第11項之漱口水,其中該精胺酸以0.5至2%的量存在,該組成物更包括5至10%甘油;3至7%山梨醇;5至10%丙二醇;0至0.1% TSPP;0.01至1%甜味劑;0.01至1%檸檬酸;0至0.1%三仙膠;0至0.01%十六烷基氯化吡啶鎓;0.01至0.1%山梨酸鉀;0.05至1%調味劑;及0.1至2%椰油醯胺丙基甜菜鹼。
- 一種磷酸鋅及精胺酸用於製造供治療或降低牙齒琺瑯質蛀蝕之申請專利範圍第1項之潔牙劑的用途,其中該磷酸鋅係加入該潔牙劑中作為預形成鹽。
- 一種磷酸鋅及精胺酸用於製造供治療或降低牙齒琺瑯質蛀蝕之申請專利範圍第11項之漱口水的用途,其中該磷酸鋅係加入該漱口水中作為預形成鹽。
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