CN104644468A - 口腔护理产品及其使用方法 - Google Patents
口腔护理产品及其使用方法 Download PDFInfo
- Publication number
- CN104644468A CN104644468A CN201510086892.6A CN201510086892A CN104644468A CN 104644468 A CN104644468 A CN 104644468A CN 201510086892 A CN201510086892 A CN 201510086892A CN 104644468 A CN104644468 A CN 104644468A
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- CN
- China
- Prior art keywords
- weight
- oral care
- anionic surfactant
- fluoride
- acid
- 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.)
- Pending
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- 238000000034 method Methods 0.000 title claims abstract description 30
- 239000000203 mixture Substances 0.000 claims abstract description 162
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims abstract description 35
- 150000003839 salts Chemical group 0.000 claims abstract description 34
- 210000000214 mouth Anatomy 0.000 claims description 43
- 229940091249 fluoride supplement Drugs 0.000 claims description 37
- 239000003945 anionic surfactant Substances 0.000 claims description 30
- 239000004475 Arginine Substances 0.000 claims description 27
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 27
- 208000002925 dental caries Diseases 0.000 claims description 22
- 230000000844 anti-bacterial effect Effects 0.000 claims description 21
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 claims description 20
- 229960003500 triclosan Drugs 0.000 claims description 20
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 16
- 230000036541 health Effects 0.000 claims description 16
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 16
- 230000006378 damage Effects 0.000 claims description 15
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 14
- 241000894006 Bacteria Species 0.000 claims description 13
- 208000002064 Dental Plaque Diseases 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 208000027418 Wounds and injury Diseases 0.000 claims description 10
- 229920001577 copolymer Polymers 0.000 claims description 10
- 238000005115 demineralization Methods 0.000 claims description 9
- 230000002328 demineralizing effect Effects 0.000 claims description 9
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims description 8
- 229920006318 anionic polymer Polymers 0.000 claims description 7
- 230000036996 cardiovascular health Effects 0.000 claims description 7
- 239000011775 sodium fluoride Substances 0.000 claims description 7
- 235000013024 sodium fluoride Nutrition 0.000 claims description 7
- 229960000414 sodium fluoride Drugs 0.000 claims description 7
- XGRSAFKZAGGXJV-UHFFFAOYSA-N 3-azaniumyl-3-cyclohexylpropanoate Chemical compound OC(=O)CC(N)C1CCCCC1 XGRSAFKZAGGXJV-UHFFFAOYSA-N 0.000 claims description 6
- XJRBAMWJDBPFIM-UHFFFAOYSA-N methyl vinyl ether Chemical compound COC=C XJRBAMWJDBPFIM-UHFFFAOYSA-N 0.000 claims description 6
- 229960004711 sodium monofluorophosphate Drugs 0.000 claims description 6
- RYJDNPSQBGFFSF-WCCKRBBISA-N (2s)-2-amino-5-(diaminomethylideneamino)pentanoic acid;carbonic acid Chemical compound OC(O)=O.OC(=O)[C@@H](N)CCCNC(N)=N RYJDNPSQBGFFSF-WCCKRBBISA-N 0.000 claims description 5
- 241000697872 Bactria Species 0.000 claims description 5
- 230000002053 acidogenic effect Effects 0.000 claims description 5
- 238000004140 cleaning Methods 0.000 claims description 5
- 208000007565 gingivitis Diseases 0.000 claims description 5
- 230000036039 immunity Effects 0.000 claims description 5
- 208000014674 injury Diseases 0.000 claims description 5
- 230000000813 microbial effect Effects 0.000 claims description 5
- 230000007406 plaque accumulation Effects 0.000 claims description 5
- 230000008439 repair process Effects 0.000 claims description 5
- 230000002087 whitening effect Effects 0.000 claims description 5
- KWTQSFXGGICVPE-WCCKRBBISA-N Arginine hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCCN=C(N)N KWTQSFXGGICVPE-WCCKRBBISA-N 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 206010013781 dry mouth Diseases 0.000 claims description 4
- 230000003628 erosive effect Effects 0.000 claims description 4
- 230000006872 improvement Effects 0.000 claims description 3
- CCTIOCVIZPCTGO-BYPYZUCNSA-N phosphoarginine Chemical class OC(=O)[C@@H](N)CCCNC(=N)NP(O)(O)=O CCTIOCVIZPCTGO-BYPYZUCNSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 229940057950 sodium laureth sulfate Drugs 0.000 claims 3
- SXHLENDCVBIJFO-UHFFFAOYSA-M sodium;2-[2-(2-dodecoxyethoxy)ethoxy]ethyl sulfate Chemical compound [Na+].CCCCCCCCCCCCOCCOCCOCCOS([O-])(=O)=O SXHLENDCVBIJFO-UHFFFAOYSA-M 0.000 claims 3
- 150000001413 amino acids Chemical class 0.000 abstract description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 46
- 229940024606 amino acid Drugs 0.000 description 46
- 235000001014 amino acid Nutrition 0.000 description 46
- -1 DAB Chemical compound 0.000 description 44
- 239000003795 chemical substances by application Substances 0.000 description 30
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 23
- 235000009697 arginine Nutrition 0.000 description 23
- 229960003121 arginine Drugs 0.000 description 23
- 239000002253 acid Substances 0.000 description 22
- 239000000463 material Substances 0.000 description 22
- 239000000606 toothpaste Substances 0.000 description 22
- 238000000227 grinding Methods 0.000 description 21
- 239000000377 silicon dioxide Substances 0.000 description 21
- 229940034610 toothpaste Drugs 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 239000004094 surface-active agent Substances 0.000 description 18
- 150000004673 fluoride salts Chemical class 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 229920000642 polymer Polymers 0.000 description 11
- 239000000080 wetting agent Substances 0.000 description 11
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 235000012239 silicon dioxide Nutrition 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 229940088598 enzyme Drugs 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 235000011180 diphosphates Nutrition 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 239000008187 granular material Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-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
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 6
- 239000003513 alkali Substances 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 239000001506 calcium phosphate Substances 0.000 description 6
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 6
- 125000002091 cationic group Chemical group 0.000 description 6
- 239000004567 concrete Substances 0.000 description 6
- 239000000551 dentifrice Substances 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical class OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 5
- 150000001340 alkali metals Chemical class 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 230000000845 anti-microbial effect Effects 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 229960005069 calcium Drugs 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 5
- 239000000811 xylitol Substances 0.000 description 5
- 235000010447 xylitol Nutrition 0.000 description 5
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 5
- 229960002675 xylitol Drugs 0.000 description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 244000060011 Cocos nucifera Species 0.000 description 4
- 235000013162 Cocos nucifera Nutrition 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
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- INVGWHRKADIJHF-UHFFFAOYSA-N Sanguinarin Chemical compound C1=C2OCOC2=CC2=C3[N+](C)=CC4=C(OCO5)C5=CC=C4C3=CC=C21 INVGWHRKADIJHF-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 150000008051 alkyl sulfates Chemical class 0.000 description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 description 4
- 235000011010 calcium phosphates Nutrition 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 4
- 210000004268 dentin Anatomy 0.000 description 4
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 4
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
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- 150000004804 polysaccharides Chemical class 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
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- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 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 3
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- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 3
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- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
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- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 3
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- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
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- MPPQGYCZBNURDG-UHFFFAOYSA-N 2-propionyl-6-dimethylaminonaphthalene Chemical compound C1=C(N(C)C)C=CC2=CC(C(=O)CC)=CC=C21 MPPQGYCZBNURDG-UHFFFAOYSA-N 0.000 description 2
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-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
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- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
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Abstract
本发明涉及包含有效量的游离形式或盐形式的碱性氨基酸和低剂量的氟化物的口腔护理组合物,并涉及使用这种组合物的方法。
Description
本申请是申请日为2009年2月6日、申请号为200980104886.1、发明名称为“口腔护理产品及其使用方法”的发明专利申请的分案申请。
本申请要求2008年2月9日提交的美国专利申请序列号61/027,441的权利,还要求2008年2月9日提交的美国专利申请序列号61/027,442以及2008年2月8日提交的美国专利申请序列号61/027,432、61/027,431、61/027,420和61/027,435的权利,这些专利申请的内容都通过引用并入本文。
发明领域
本发明涉及包含游离形式或盐形式的碱性氨基酸和低剂量的氟化物的口腔护理组合物,并涉及使用这些组合物的方法。
发明背景
精氨酸和其他碱性氨基酸已被提出用于口腔护理,且据信在抵抗蛀洞形成和牙齿敏感上具有显著的好处。但是,要将这些碱性氨基酸与具有口腔护理好处的矿物质(如氟和钙)组合形成具有可接受的长期稳定性的口腔护理产品,已证明是极具挑战性的。具体地讲,碱性氨基酸可提高pH和促进钙离子的解离,而钙离子可与氟离子反应形成不溶性沉淀物。此外,较高的pH具有造成刺激的潜在可能。但是,在中性pH或酸性pH下,利用精氨酸碳酸氢盐(本领域教导说其是优选的)的系统可释放二氧化碳,导致容器膨胀和暴裂。此外,可预期的是,将pH降低到中性或酸性条件会降低配方的功效,因为精氨酸可形成对牙齿表面亲和力较差的不溶性精氨酸-钙复合物,而且降低pH会减少配方可能具有的任何缓冲口腔中龋齿乳酸的作用。部分上由于这些未得到解决的配方困难,部分上由于精氨酸在本领域中一般已被认为是氟化物的潜在替代物而不是共活性物,因此一直以来制造同时包含精氨酸和氟化物的口腔护理产品的动机很弱。另外的困难由抗微生物剂的添加所潜在造成。例如,市售的基于精氨酸的牙膏如和含有精氨酸碳酸氢盐和碳酸钙,但不含氟化物,也不含任何抗微生物剂。
同时,抗微生物剂如三氯生在牙膏中的价值已得到许多牙科医生的认可。但是,要将这些抗微生物剂以有效量递送到牙齿和齿龈是有挑战性的,而且它们的溶解性、递送和在牙齿上的保持是依赖于配方的。例如,三氯生(5-氯-2-(2,4-二氯苯氧基)苯酚)仅微溶于水。
氟化物在口腔护理中的好处已得到确认,特别是通过在牙齿中形成对酸溶解(去矿化)更具抗性的氟磷灰石而提供好处。但是,年纪小的儿童过度暴露于氟化物(例如通过吞咽大量的氟化牙膏)会受伤害,导致发育中的牙齿出现牙氟中毒,而且虽然牙膏中所用的氟化物具有出色的安全记录,不过有一些人还是宁愿氟化物的量对于有效性而言是绝对极小值。
因此,需要能提供碱性氨基酸和有益氟化物的稳定的口腔护理产品,所述有益氟化物剂量低,同时能提供有效的氟化物活性。
发明概述
现出乎意料地发现,碱性氨基酸如精氨酸与一定量的氟化物(如果没有碱性氨基酸的话,该氟化物量将属低剂量)相组合,却能使口腔护理好处增强,因此可促进口腔健康和/或全身健康(包括心血管健康),例如通过降低经由口腔组织发生的全身性感染的潜在可能来促进全身健康。
不想受限于具体的理论,但还是猜测精氨酸有利作用的一个显著因素是,精氨酸和其他碱性氨基酸能被某些类型的细菌如血链球菌(S.sanguis)代谢,这些类型的细菌不会造成龋齿,且能与龋齿细菌如变形链球菌(S.mutans)在牙齿上和口腔中竞争位置。分解精氨酸的细菌能利用精氨酸和其他碱性氨基酸来产氨,从而提高它们的环境pH,而龋齿细菌则会代谢糖而产乳酸,这趋向于降低牙菌斑pH和使牙齿去矿化,最终导致蛀洞。据信,日常使用本发明的组合物,会随着时间的推移导致分解精氨酸的细菌相对增加而龋齿细菌相对减少,从而导致更高的牙菌斑pH,实际上使牙齿免疫而能抵抗龋齿细菌和它们的有害作用。据信这个pH提高作用可与氟促进再矿化和加强牙釉质的作用从理论上区别开来且与氟的所述作用互补。
但是,不论确切的机制如何,的确出乎意料地发现,氟化物和碱性氨基酸(例如精氨酸)在根据本发明的口腔护理产品中的组合能在促进再矿化、修复龋前损伤和增强口腔健康方面产生意想不到的好处,这些意想不到的好处超出且在定性上不同于使用包含有效量的任一单独化合物的组合物所能观察到的好处。此外,对于在碱性氨基酸不存在下将不会在治疗上有效的氟化物水平,仍见到有益的作用。
另外发现,加入小颗粒研磨剂可进一步增强这个作用,小颗粒研磨剂可有助于填充牙釉质中的微裂缝和牙质中的微管。还出乎意料地发现,碱性氨基酸与阴离子型表面活性剂组合在一起存在,能降低细菌对牙齿表面的附着。最后,碱性氨基酸与阴离子型表面活性剂一起能大大增强溶解性差的活性剂例如抗微生物剂(如三氯生)的溶解、释放、递送、沉积和有效性。
本发明因此进一步涵括用于以下用途的方法:(i)减少或抑制牙龋的形成,(ii)减少、修复或抑制早期牙釉质损伤,所述损伤例如通过定量光导荧光(QLF)或电龋测量(ECM)检测到,(iii)减少或抑制牙齿的去矿化和促进再矿化,(iv)减少牙齿的超敏,(v)减少或抑制齿龈炎,(vi)促进口中伤口或切口的康复,(vii)降低产酸细菌的水平,(viii)提高分解精氨酸的细菌的相对水平,(ix)抑制口腔中微生物膜的形成,(x)在糖攻击(sugar challenge)后提高和/或维持牙菌斑pH在至少pH 5.5的水平,(xi)减少牙菌斑积累,(xii)治疗干口症,(xiii)例如通过降低经由口腔组织发生的全身性感染的潜在可能来增强全身健康,包括心血管健康,(xiv)减少牙齿的侵蚀,(xv)使牙齿对龋齿细菌具有免疫力,和/或(xvi)清洁牙齿和口腔,所述方法包括将本发明的组合物施用于口腔,例如通过将本发明的组合物施用于有需要的患者的口腔来进行。
发明详述
本发明因此包含洁齿剂(组合物1.0),其包含:
i.有效量的游离形式或盐形式的碱性氨基酸,例如精氨酸;
氟化物源,例如可溶性氟化物盐,例如小于0.1%氟化物盐,例如
提供小于约1000ppm氟化物,例如小于约700ppm,例如约200
至约600ppm氟化物。
本发明还提供:
1.0.1.组合物1.0,其中碱性氨基酸是精氨酸、赖氨酸、瓜氨酸、鸟氨酸、肌酸、组氨酸、二氨基丁酸、二氨基丙酸、它们的盐和/或它们的组合。
1.0.2.组合物1.0或1.0.1,其中碱性氨基酸具有L-构型。
1.0.3.任何前述组合物是以包含碱性氨基酸的二肽或三肽的盐的形式提供。
1.0.4.任何前述组合物,其中碱性氨基酸是精氨酸。
1.0.5.任何前述组合物,其中碱性氨基酸是L-精氨酸。
1.0.6.任何前述组合物,其中碱性氨基酸部分或全部为盐形式。
1.0.7.组合物1.0.6,其中碱性氨基酸是精氨酸磷酸盐。
1.0.8.组合物1.0.6,其中碱性氨基酸为精氨酸盐酸盐的形式。
1.0.9.组合物1.0.6,其中碱性氨基酸是精氨酸硫酸盐。
1.0.10.组合物1.0.6,其中碱性氨基酸是精氨酸碳酸氢盐。
1.0.11.任何前述组合物,其中碱性氨基酸的盐是通过用酸或酸的盐中和碱性氨基酸而在配方中原位形成。
1.0.12.任何前述组合物,其中碱性氨基酸的盐是通过中和碱性氨基酸以形成预混合物,然后与氟化物盐相组合而形成。
1.0.13.任何前述组合物,其中碱性氨基酸的存在量占总组合物重量的约0.1至约20%、例如约1重量%至约10重量%,其中碱性氨基酸的重量是以游离碱形式计算。
1.0.14.组合物1.0.11,其中碱性氨基酸的存在量占总组合物重量的约7.5重量%。
1.0.15.组合物1.0.11,其中碱性氨基酸的存在量占总组合物重量的约5重量%。
1.0.16.组合物1.0.11,其中碱性氨基酸的存在量占总组合物重量的约3.75重量%。
1.0.17.组合物1.0.11,其中碱性氨基酸的存在量占总组合物重量的约1.5重量%。
1.0.18.任何前述组合物,其中氟化物盐选自氟化亚锡、氟化钠、氟化钾、单氟磷酸钠、氟硅酸钠、氟硅酸铵、氟化胺(例如N'-十八烷基三亚甲基二胺-N,N,N'-三(2-乙醇)-二氢氟化物)、氟化铵、氟化钛、六氟硫酸盐以及它们的组合。
1.0.19.任何前述组合物,其中氟化物盐为氟磷酸盐。
1.0.20.任何前述组合物,其中氟化物盐为单氟磷酸钠。
1.0.21.任何前述组合物,其中氟化物盐为氟化钠。
1.0.22.任何前述组合物,其中氟化物盐的存在量占总组合物重量的约0.01重量%至约0.1重量%。
1.0.23.任何前述组合物,其中氟化物盐提供的氟离子量占总组合物重量的约0.05至约0.1重量%。
1.0.24.任何前述组合物,其中可溶性氟化物盐提供的氟离子量为约50至约600ppm。
1.0.25.任何前述组合物,其为具有约50至约250ppm可利用氟离子的漱口剂。
1.0.26.任何前述组合物,其为具有约100至约500ppm可利用氟离子的洁齿剂。
1.0.27.任何前述组合物,其中pH为约6至约9,例如约6.5至约7.4或约7.5至约9。
1.0.28.任何前述组合物,其中pH为约6.5至约7.4。
1.0.29.任何前述组合物,其中pH为约6.8至约7.2。
1.0.30.任何前述组合物,其中pH大约为中性。
1.0.31.任何前述组合物,其还包含研磨剂或微粒。
1.0.32.刚刚所述的组合物,其中研磨剂或微粒选自碳酸氢钠、磷酸钙(例如二水磷酸二钙)、硫酸钙、沉淀碳酸钙、二氧化硅(例如水合二氧化硅)、氧化铁、氧化铝、珍珠岩、塑料颗粒(例如聚乙烯)以及它们的组合。
1.0.33.刚刚所述的组合物,其中研磨剂或微粒选自磷酸钙(例如二水磷酸二钙)、硫酸钙、沉淀碳酸钙、二氧化硅(例如水合二氧化硅)以及它们的组合。
1.0.34.任何前述组合物,其还包含数量占总组合物重量的约15重量%至约70重量%的研磨剂。
1.0.35.任何前述组合物,其还包含数量占至少约5%、具有小于5微米的d50的小颗粒研磨剂部分。
1.0.36.任何前述组合物,其RDA小于约150,例如约40至约140。
1.0.37.任何前述组合物,其中阴离子型表面活性剂选自:
a.水溶性的高级脂肪酸单甘油酯单硫酸盐(例如氢化椰子油脂肪酸的单硫酸化单甘油酯的钠盐,如N-甲基N-椰油基牛磺酸钠、椰油单甘油酯硫酸钠),
b.高级烷基硫酸盐,例如月桂基硫酸钠,
c.高级烷基醚硫酸盐,例如式CH3(CH2)mCH2(OCH2CH2)nOSO3X的高级烷基醚硫酸盐,其中m为6-16,例如10,n为1-6,例如2、3或4,X为Na或K(例如月桂基聚氧乙烯醚(2)硫酸钠(CH3(CH2)10CH2(OCH2CH2)2OSO3Na)),
d.高级烷基芳基磺酸盐(如十二烷基苯磺酸钠(月桂基苯磺酸钠)),
e.高级烷基磺基乙酸盐(如月桂基磺基乙酸钠(十二烷基磺基乙酸钠)、1,2二羟基丙磺酸的高级脂肪酸酯、sulfocolaurate(N-2-乙基月桂酸钾磺基乙酰胺)和月桂基肌氨酸钠),
f.它们的混合物。
所谓“高级烷基”是指例如C6-30烷基。在具体的实施方案中,阴离子型表面活性剂选自月桂基硫酸钠和醚月桂基硫酸钠。
1.0.38.任何前述组合物,其中阴离子型表面活性剂选自月桂基硫酸钠、醚月桂基硫酸钠和它们的混合物。
1.0.39.任何前述组合物,其中阴离子型表面活性剂的存在量为约0.3%至约4.5重量%。
1.0.40.任何前述组合物,其另外包含选自阴离子型表面活性剂、两性离子型表面活性剂和非离子型表面活性剂以及它们的混合物的表面活性剂。
1.0.41.任何前述组合物,其还包含至少一种湿润剂。
1.0.42.任何前述组合物,其还包含至少一种选自甘油、山梨糖醇、木糖醇和它们的组合的湿润剂。
1.0.43.任何前述组合物,其还包含木糖醇、对羟基苯甲酸乙酯或壳聚糖。
1.0.44.任何前述组合物,其还包含至少一种聚合物。
1.0.45.任何前述组合物,其还包含至少一种选自聚乙二醇、聚乙烯基甲基醚马来酸共聚物、多糖(例如纤维素衍生物如羧甲基纤维素,或多糖树胶如黄原胶或卡拉胶)以及它们的组合的聚合物。
1.0.46.任何前述组合物,其还包含树胶条或树胶碎片。
1.0.47.任何前述组合物,其还包含矫味剂、香料和/或着色剂。
1.0.48.任何前述组合物,其还包含水。
1.0.49.任何前述组合物,其还包含选自以下的抗菌剂:卤化二苯醚(例如三氯生)、草本提取物和香精油(例如迷迭香提取物、茶叶提取物、木兰提取物、百里香酚、薄荷醇、桉叶脑、香叶醇、香芹酚、柠檬醛、日柏酚、儿茶酚、水杨酸甲酯、表没食子儿茶素没食子酸酯、表没食子儿茶素、没食子酸、miswak提取物、沙棘提取物)、双胍防腐剂(例如氯己定、阿来西定或奥替尼啶)、季铵化合物(例如十六烷基氯化吡啶鎓(CPC)、苯扎氯铵、十四烷基氯化吡啶(TPC)、N-十四烷基-4-乙基氯化吡啶(TDEPC))、酚类防腐剂、海克替啶、奥替尼啶、血根碱、聚维酮碘、地莫匹醇、salifluor、金属离子(例如锌盐如柠檬酸锌、亚锡、铜盐、铁盐)、血根碱、蜂胶和加氧剂(例如过氧化氢、缓冲过氧硼酸钠或过氧碳酸钠)、邻苯二甲酸及其盐、单过氧邻苯二甲酸及其盐和酯、抗坏血酸硬脂酸酯、油酰肌氨酸、烷基硫酸盐、二辛基磺基琥珀酸盐、水杨酰替苯胺、度米芬、地莫匹醇、辛哌醇和其他哌啶子基衍生物、nicin制品、亚氯酸盐;以及任何上述物质的混合物。
1.0.50.任何前述组合物,其还包含抗炎化合物,例如至少一种选自以下的宿主促炎因子的抑制剂:基质金属蛋白酶(MMP)、环加氧酶(COX)、PGE2、白细胞介素1(IL-1)、IL-1β转换酶(ICE)、转化生长因子β1(TGF-β1)、诱导型氧化氮合酶(iNOS)、透明质酸酶、组织蛋白酶、核因子κB(NF-κB)和IL-1受体相关激酶(IRAK),所述抑制剂例如选自阿司匹林、酮咯酸、氟比洛芬、布洛芬、萘普生、吲哚美辛、阿司匹林、酮洛芬、吡罗昔康、甲氯芬那酸、去甲二氢化愈创木酸以及它们的混合物。
1.0.51.任何前述组合物,其还包含抗氧化剂,例如选自辅酶Q10、PQQ、维生素C、维生素E、维生素A、茴香脑-dithiothione以及它们的混合物。
1.0.52.任何前述组合物,其中抗菌剂的可溶性差。
1.0.53.任何前述组合物,其还包含三氯生。
1.0.54.任何前述组合物,其包含三氯生和Zn2+离子源,例如柠檬酸锌。
1.0.55.任何前述组合物,其还包含三氯生和木糖醇。
1.0.56.任何前述组合物,其还包含三氯生、木糖醇和沉淀碳酸钙。
1.0.57.任何前述组合物,其还包含抗牙垢剂。
1.0.58.任何前述组合物,其还包含抗牙垢剂,所述抗牙垢剂为聚磷酸盐,例如焦磷酸盐、三聚磷酸盐或六偏磷酸盐,例如为钠盐形式。
1.0.59.任何前述组合物,其还包含数量占总组合物重量的约0.01至约5重量%的抗菌剂。
1.0.60.任何前述组合物,其还包含数量占总组合物重量的约0.01至约1重量%的三氯生。
1.0.61.任何前述组合物,其还包含数量占总组合物重量的约0.3%的三氯生。
1.0.62.任何前述组合物,其还包含增白剂。
1.0.63.任何前述组合物,其还包含选自增白活性物质的增白剂,所述增白活性物质选自过氧化物、金属亚氯酸盐、过硼酸盐、过碳酸盐、过氧酸、次氯酸盐以及它们的组合。
1.0.64.任何前述组合物,其还包含过氧化氢或过氧化氢源,例如过氧化脲或过氧化物盐或复合物(例如过氧磷酸盐、过氧碳酸盐、过硼酸盐、过氧硅酸盐或过硫酸盐;例如过氧磷酸钙、过硼酸钠、碳酸钠过氧化物、过氧磷酸钠和过硫酸钾),或过氧化氢聚合物复合物如过氧化氢-聚乙烯吡咯烷酮聚合物复合物。
1.0.65.任何前述组合物,其还包含干扰或防止细菌附着的物质,例如对羟基苯甲酸乙酯或壳聚糖。
1.0.66.任何前述组合物,其还包含选自以下的钙和磷酸盐来源:(i)钙-玻璃复合物,例如磷硅酸钠钙,和(ii)钙-蛋白质复合物,例如酪蛋白磷酸肽-无定形磷酸钙。
1.0.67.任何前述组合物,其还包含可溶性钙盐,例如选自硫酸钙、氯化钙、硝酸钙、乙酸钙、乳酸钙以及它们的组合。
1.0.68.任何前述组合物,其还包含生理上可接受的钾盐,例如硝酸钾或氯化钾,其数量能有效降低牙本质敏感。
1.0.69.任何前述组合物,其还包含约0.1%至约7.5%的生理上可接受的钾盐,例如硝酸钾和/或氯化钾。
1.0.70.任何前述组合物,其为牙膏,其中包含精氨酸盐如精氨酸盐酸盐、精氨酸磷酸盐或精氨酸碳酸氢盐;三氯生;阴离子型表面活性剂如月桂基硫酸钠;和可溶性氟化物盐如单氟磷酸钠或氟化钠。
1.0.71.任何前述组合物,其在例如通过擦刷施用于口腔时能有效地(i)减少或抑制牙龋的形成,(ii)减少、修复或抑制早期牙釉质损伤,所述损伤例如通过定量光导荧光(QLF)或电龋测量(ECM)检测到,(iii)减少或抑制牙齿的去矿化和促进再矿化,(iv)减少牙齿的超敏,(v)减少或抑制齿龈炎,(vi)促进口中伤口或切口的康复,(vii)降低产酸细菌的水平,(viii)提高分解精氨酸的细菌的相对水平,(ix)抑制口腔中微生物膜的形成,(x)在糖攻击后提高和/或维持牙菌斑pH在至少pH 5.5的水平,(xi)减少牙菌斑积累,(xii)治疗、减轻或减少干口症,(xiii)例如通过降低经由口腔组织发生的全身性感染的潜在可能来增强全身健康,包括心血管健康,(xiv)增白牙齿,(xv)减少牙齿的侵蚀,(xvi)使牙齿对龋齿细菌具有免疫力,和/或(xvii)清洁牙齿和口腔。
1.0.72.通过将任何前述组合物中所提到的成分组合在一起获得的或者可获得的组合物。
1.0.73.任何前述组合物,其为选自漱口剂、牙膏、牙凝胶、牙粉、非磨擦性凝胶、摩丝、泡沫、喷口剂、锭剂、口腔片剂、牙科工具和宠物护理产品的形式。
1.0.74.任何前述组合物,其中所述组合物是牙膏。
1.0.75.任何前述组合物,其中所述组合物是任选还包含水、研磨剂、表面活性剂、发泡剂、维生素、聚合物、酶、湿润剂、增稠剂、抗微生物剂、防腐剂、矫味剂、着色剂和/或它们的组合中的一种或多种的牙膏。
1.0.76.任何前述组合物1.0–1.0.72,其中所述组合物是漱口剂。
1.0.77.任何前述组合物,其还包含口气清新剂、香料或矫味剂。
在另一个实施方案中,本发明涵括本发明组合物(组合物1.1),例如根据任何前述组合物1.0–1.0.77,其包含:
i.有效量的碱性氨基酸盐;
ii.有效量的可溶性氟化物盐;
iii.阴离子型表面活性剂,例如月桂基硫酸钠;
iv.阴离子型聚合物,例如甲基乙烯基醚和马来酸酐的共聚物;和
v.抗菌剂,例如三氯生。
在另一个实施方案中,本发明涵括本发明组合物(组合物1.2),例如根据任何前述组合物1.0–1.0.77,其包含:
i.有效量的碱性氨基酸盐。
ii.抗菌剂,例如三氯生;
iii.有效量的可溶性氟化物盐;和
iv.小颗粒研磨剂,使得组合物的RDA小于约160,例如约40至约140,例如包含至少约5%、例如至少约20%的d50小于约5微米的研磨剂,例如d50为约3至约4微米的二氧化硅。
在另一个实施方案中,本发明涵括用以改善口腔健康的方法(方法2),所述方法包括将“组合物1.0、1.1或1.2”项下任何实施方案的有效量的口腔组合物施用于受试者的口腔,例如用于以下用途的方法:
i.减少或抑制牙龋的形成,
ii.减少、修复或抑制早期牙釉质损伤,所述损伤例如通过定
量光导荧光(QLF)或电龋测量(ECM)检测到,
iii.减少或抑制牙齿的去矿化和促进再矿化,
iv.减少牙齿的超敏,
v.减少或抑制齿龈炎,
vi.促进口中伤口或切口的康复,
vii.降低产酸细菌的水平,
viii.提高分解精氨酸的细菌的相对水平,
ix.抑制口腔中微生物膜的形成,
x.在糖攻击后提高和/或维持牙菌斑pH在至少pH 5.5的水平,
xi.减少牙菌斑积累,
xii.治疗干口症,
xiii.例如通过降低经由口腔组织发生的全身性感染的潜在可能
来增强全身健康,包括心血管健康,
xiv.增白牙齿,
xv.使牙齿对龋齿细菌具有免疫力,
xvi.减少牙齿的侵蚀,和/或
xvii.清洁牙齿和口腔。
本发明进一步包括精氨酸用于制造例如供用于方法2中提出的任何适应症的本发明组合物。
碱性氨基酸
可用于本发明组合物和方法的碱性氨基酸不仅包括天然的碱性氨基酸如精氨酸、赖氨酸和组氨酸,而且包括任何在分子中具有羧基和氨基、能溶于水和能提供pH约7或以上的水溶液的碱性氨基酸。
因此,碱性氨基酸包括但不限于精氨酸、赖氨酸、瓜氨酸、鸟氨酸、肌酸、组氨酸、二氨基丁酸、二氨基丙酸、它们的盐或者它们的组合。在一个具体的实施方案中,碱性氨基酸选自精氨酸、瓜氨酸和鸟氨酸。
在某些实施方案中,碱性氨基酸是精氨酸,例如L-精氨酸,或其盐。
本发明的组合物旨在局部用于口中,因此用于本发明的盐在所提供的数量和浓度下应该对这种用途是安全的。合适的盐包括本领域已知为药物可接受盐的盐,在所提供的数量和浓度下通常认为是生理上可接受的。生理上可接受的盐包括那些衍自药物可接受的无机或有机酸或碱的盐,例如由可形成生理上可接受的阴离子的酸所形成的酸加成盐(例如盐酸盐和溴化物盐),和由可形成生理上可接受的阳离子的碱所形成的碱加成盐,例如那些衍自碱金属(如钾和钠)或碱土金属(如钙和镁)的盐。生理上可接受的盐可用本领域公知的标准方法获得,例如通过使足够碱性的化合物(如胺)与合适的能提供生理上可接受的阴离子的酸反应来获得。
在各个实施方案中碱性氨基酸的存在量占总组合物重量的约0.5重量%至约20重量%,占总组合物重量的约1重量%至约10重量%,例如占总组合物重量的约1.5重量%、约3.75重量%、约5重量%或约7.5重量%。
RDA:RDA是放射性牙质磨损(radioactive dentin abrasion)的英文缩写,放射性牙质磨损是研磨度的相对度量。通常,将拔出的人牙或牛牙在中子通量中照射,所述牙安在甲基丙烯酸甲酯(骨胶)中,剥去釉质,插入到刷牙机中,按美国牙医协会(ADA)标准(参考牙刷,150g压力,1500次擦刷,4:1的水-牙膏浆液)刷牙。然后测量并记录清洗水的放射性。对于试验对照,用由焦磷酸钙制成的ADA参考牙膏重复试验,此测量结果赋值100以校正相对标度。
氟离子源:口腔护理组合物还可包括一种或多种氟离子源,例如可溶性氟化物盐。有很多种能产生氟离子的材料可在本发明组合物中用作可溶性氟化物的来源。合适的能产生氟离子的材料的实例见于Briner等人的美国专利第3,535,421号、Parran,Jr.等人的美国专利第4,885,155号和Widder等人的美国专利第3,678,154号,这些专利通过引用并入本文。
代表性的氟离子源包括但不限于氟化亚锡、氟化钠、氟化钾、单氟磷酸钠、氟硅酸钠、氟硅酸铵、氟化胺、氟化铵和它们的组合。在某些实施方案中,氟离子源包括氟化亚锡、氟化钠、单氟磷酸钠以及它们的混合物。
在某些实施方案中,本发明的口腔护理组合物还可含有其量足以提供约25ppm至600ppm、通常不超过约500ppm、例如约50至约500ppm、例如约100至约450ppm、例如约400ppm的氟离子的氟离子源或供氟成分。氟化物的适当水平将取决于具体的应用。例如,漱口剂通常将具有约25至约150ppm氟化物。一般消费者用的牙膏通常将具有约300至约600ppm,而儿科用牙膏含量稍低。
氟离子源在本发明组合物中的添加水平,以组合物的重量计,在一个实施方案中可为约0.01重量%至约0.1重量%,或者在另一个实施方案中可为约0.03重量%至约0.1重量%,或者在又另一个实施方案中可为约0.05重量%至约0.1重量%。据以提供适当水平的氟离子的氟化物盐的重量,显然将根据盐中的反荷离子的重量而变。
研磨剂
本发明的组合物可包含磷酸钙研磨剂,例如磷酸三钙(Ca3(PO4)2)、羟基磷灰石(Ca10(PO4)6(OH)2)、二水合磷酸二钙(CaHPO4·2H2O,在本文中有时也称DiCal)或焦磷酸钙。
组合物可包括一种或多种另外的研磨剂,例如二氧化硅研磨剂,如平均粒度最多为约20微米的沉淀二氧化硅,如J.M.Huber所出售的Zeodent其他有用的研磨剂还包括偏磷酸钠、偏磷酸钾、硅酸铝、煅烧氧化铝、膨润土或其他含硅材料或者它们的组合。
可用于本发明的二氧化硅研磨抛光材料,以及其他的研磨剂,通常具有约0.1至约30微米、约5至约15微米的平均粒度。二氧化硅研磨剂可来自沉淀二氧化硅或硅胶,如Pader等人的美国专利第3,538,230号和Digiulio的美国专利第3,862,307号中描述的二氧化硅干凝胶,该两个专利通过引用并入本文。具体的二氧化硅干凝胶由W.R.Grace&Co.,Davison Chemical Division以商品名出售。沉淀二氧化硅材料包括由J.M.Huber Corp.以商品名出售的那些沉淀二氧化硅材料,其中包括标识为Zeodent 115和119的二氧化硅。这些二氧化硅研磨剂在Wason的美国专利第4,340,583号中有描述,该专利通过引用并入本文。
在某些实施方案中,可用于根据本发明的口腔护理组合物的实施的研磨材料包括吸油值为约小于约100cc/100g二氧化硅、在约45cc/100g至约70cc/100g二氧化硅范围内的硅胶和沉淀无定形二氧化硅。吸油值是用ASTM Rub-Out Method D281的方法测量的。在某些实施方案中,二氧化硅是平均粒度为约3微米至约12微米、约5至约10微米的胶体颗粒。
在具体的实施方案中,研磨材料包含很大一部分的极小的颗粒,例如d50小于约5微米,例如d50为约3至约4微米的小颗粒二氧化硅(SPS),例如Sorbosil(Ineos)。这种小颗粒在旨在减少超敏性的配方中特别有用。小颗粒成分可以与另一更大颗粒研磨剂组合在一起而存在。例如在某些实施方案中,配方包含约3至约8%的SPS和约25至约45%的常规研磨剂。
在本发明的实施中特别有用的低吸油二氧化硅研磨剂由DavisonChemical Division ofW.R.Grace&Co.(美国马里兰州巴尔的摩,21203)以商品名Sylodent出售。Sylodent 650是可用于本发明的实施的低吸油二氧化硅研磨剂的一个实例,其是一种由胶态二氧化硅的颗粒组成的二氧化硅水凝胶,含水量为约29重量%,直径为约7至约10微米,吸油量小于约70cc/100g二氧化硅。研磨剂在本发明的口腔护理组合物中的存在浓度为约10至约60重量%,在其他实施方案中为约20至约45重量%,在另一实施方案中为约30至约50重量%。
增加发泡量的物质
本发明的口腔护理组合物还可包括能增加刷口腔时所产生的泡沫量的物质。
能增加泡沫量的物质的示例性实例包括但不限于聚氧乙烯和某些聚合物,包括但不限于海藻酸聚合物。
聚氧乙烯可增加本发明的口腔护理载体成分所产生的泡沫的量和厚度。聚氧乙烯通常也称聚乙二醇("PEG")或聚环氧乙烷。适合于本发明的聚氧乙烯将具有约200,000至约7,000,000的分子量。在一个实施方案中,分子量将为约600,000至约2,000,000,在另一个实施方案中为约800,000至约1,000,000。是Union Carbide公司生产的高分子量聚氧乙烯的商品名。
聚氧乙烯的存在量可占本发明口腔护理组合物的口腔护理载体成分的约1%至约90%,在一个实施方案中为约5%至约50%,在另一个实施方案中为约10%至约20重量%。发泡剂在口腔护理组合物中的剂量(即单剂量)为约0.01至约0.9重量%,约0.05至约0.5重量%,在另一个实施方案中为约0.1至约0.2重量%。
表面活性剂
本发明含有阴离子型表面活性剂,例如:
i.水溶性的高级脂肪酸单甘油酯单硫酸盐,例如氢化椰子油脂
肪酸的单硫酸化单甘油酯的钠盐,如N-甲基N-椰油基牛磺
酸钠、椰油单甘油酯硫酸钠,
ii.高级烷基硫酸盐,例如月桂基硫酸钠,
iii.高级烷基醚硫酸盐,例如式
CH3(CH2)mCH2(OCH2CH2)nOSO3X的高级烷基醚硫酸盐,其
中m为6-16,例如10,n为1-6,例如2、3或4,X为Na
或K,例如月桂基聚氧乙烯醚(2)硫酸钠
(CH3(CH2)10CH2(OCH2CH2)2OSO3Na),
iv.高级烷基芳基磺酸盐,如十二烷基苯磺酸钠(月桂基苯磺酸
钠),
v.高级烷基磺基乙酸盐,如月桂基磺基乙酸钠(十二烷基磺基乙
酸钠)、1,2二羟基丙磺酸的高级脂肪酸酯、sulfocolaurate(N-2-
乙基月桂酸钾磺基乙酰胺)和月桂基肌氨酸钠。
所谓“高级烷基”是指例如C6-30烷基。在具体的实施方案中,阴离子型表面活性剂选自月桂基硫酸钠和醚月桂基硫酸钠。
阴离子型表面活性剂以有效的量存在,例如占配方重量的约0.01%以上,但其浓度不会对口腔造成刺激,例如小于约10%,且最佳浓度取决于具体的配方和具体的表面活性剂。例如,用于漱口剂的浓度通常是用于牙膏的浓度的十分之一左右。在一个实施方案中,阴离子型表面活性剂在牙膏中以约0.3重量%至约4.5重量%、例如约1.5重量%的浓度存在。
本发明组合物可任选含有包含阴离子型表面活性剂和其他表面活性剂的表面活性剂混合物,所述其他表面活性剂可以是阴离子型表面活性剂、阳离子型表面活性剂,两性离子型表面活性剂或非离子型表面活性剂。一般而言,表面活性剂是那些在很大pH范围内相当稳定的表面活性剂。表面活性剂在例如Agricola等人的美国专利第3,959,458号、Haefele的美国专利第3,937,807号和Gieske等人的美国专利第4,051,234号中有更充分的描述,这些专利通过引用并入本文。
在某些实施方案中,可用于本发明的阴离子型表面活性剂包括在烷基中具有约10至约18个碳原子的烷基硫酸盐的水溶性盐,和具有约10至约18个碳原子的脂肪酸的磺化单甘油酯的水溶性盐。月桂基硫酸钠、月桂酰肌氨酸钠和椰油酸单甘油酯磺酸钠是这个类型的阴离子型表面活性剂的实例。也可采用阴离子型表面活性剂的混合物。
在另一个实施方案中,可用于本发明的阳离子型表面活性剂可广义定义为具有一个含约8至约18个碳原子的长烷基链的脂族季铵化合物的衍生物,如月桂基三甲基氯化铵、氯化十六烷基吡啶十六烷基三甲基溴化铵、二异丁基苯氧基乙基二甲基苄基氯化铵、椰油基烷基三甲基亚硝酸铵、氟化十六烷基吡啶以及它们的混合物。
示例性的阳离子型表面活性剂是Briner等人的美国专利第3,535,421号中所述的氟化季铵盐,该专利通过引用并入本文。某些阳离子型表面活性剂也可在组合物中充当杀菌剂。
可用于本发明组合物的示例性非离子型表面活性剂可广义定义为由环氧烷基团(本质上为亲水性)与有机疏水化合物(本质上可为脂族的或烷基芳族的)缩合产生的化合物。合适的非离子型表面活性剂的实例包括但不限于Pluronics、烷基酚的聚环氧乙烷缩合物、由环氧乙烷与环氧丙烷和乙二胺的反应产物缩合产生的产物、脂族醇的环氧乙烷缩合物、长链氧化叔胺、长链氧化叔膦、长链二烷基亚砜以及这些物质的混合物。
在某些实施方案中,可用于本发明的两性离子型合成表面活性剂可广义描述为脂族季铵、磷和硫化合物的衍生物,其中脂族基团可以是直链基团或带支链基团,且其中脂族取代基之一含有约8至约18个碳原子,一个含有阴离子型水增溶性基团,例如羧基、磺酸根、硫酸根、磷酸根或膦酸根。适合包括在组合物中的表面活性剂的示例性实例包括但不限于烷基硫酸钠、月桂酰肌氨酸钠、椰油酰胺丙基甜菜碱和聚山梨醇酯20以及它们的组合。
在一个具体的实施方案中,本发明的组合物包含月桂基硫酸钠。
该表面活性剂或者几种相容的表面活性剂的混合物在本发明组合物中的存在量可占总组合物重量的约0.1%至约5%,在另一个实施方案中为约0.3%至约3%,在又另一个实施方案中为约0.5%至约2%。
矫味剂
本发明的口腔护理组合物还可包括矫味剂。可用于本发明的实施的矫味剂包括但不限于香精油以及各种风味醛、酯、醇以及类似的材料。香精油的实例包括以下植物的油:留兰香、胡椒薄荷、冬青、黄樟、丁香、鼠尾草、桉树、甘牛至;马郁兰、肉桂、柠檬、莱母酸橙、葡萄柚和橙。诸如薄荷醇、香芹酮和茴香脑的化学物质也有用。某些实施方案采用胡椒薄荷和留兰香的油。
矫味剂掺入在口腔组合物中的浓度为约0.1至约5重量%、约0.5至约1.5重量%。矫味剂在单个口腔护理组合物剂量(即单剂量)中的剂量为约0.001至约0.05重量%,在另一个实施方案中为约0.005至0.015重量%。
螯合剂
本发明的口腔护理组合物还可任选包括一种或多种能够络合细菌细胞壁中存在的钙的螯合剂。对这个钙的结合能削弱细菌细胞壁,增大细菌裂解。
另一类在本发明中适合用作螯合剂的物质是可溶性焦磷酸盐。用于本发明组合物的焦磷酸盐可以是任何碱金属焦磷酸盐。在某些实施方案中,盐包括四碱金属焦磷酸盐、二碱金属二酸焦磷酸盐、三碱金属一酸焦磷酸盐以及它们的混合物,其中碱金属为钠或钾。盐既可以以其水合形式使用,也可以以其非水合形式使用。可用于本发明组合物的焦磷酸盐的有效量通常足以提供至少约1重量%、约1.5重量%至约6重量%、约3.5重量%至约6重量%的焦磷酸根离子。
聚合物
本发明的口腔护理组合物还可任选包括一种或多种聚合物,如聚乙二醇、聚乙烯基甲基醚马来酸共聚物、多糖(例如纤维素衍生物,如羧甲基纤维素或多糖树胶,如黄原胶或卡拉胶)。酸性聚合物如聚丙烯酸凝胶,可以以其游离酸形式或者部分或完全中性化水溶性碱金属(例如钾和钠)盐或铵盐的形式提供。
特别是当任何洁齿剂成分中包括非阳离子型抗菌剂或抗菌剂如三氯生时,还优选包括约0.05至约5%的、能增强所述抗菌剂向口腔表面的递送和保持以及所述抗菌剂在口腔表面上的保持的物质。可用于本发明的这种物质在美国专利第5,188,821号和第5,192,531号中有公开;包括合成的阴离子型聚合聚碳酸盐,如马来酸酐或马来酸与另一可聚合的多烯键式不饱和单体的约1:4至约4:1共聚物,优选分子量为约30,000至约1,000,000、最优选约30,000至约800,000的甲基乙烯基醚/马来酸酐。这些共聚物可获自ISP Technologies,Inc.(BoundBrook,N.J.08805)的Gantrez,例如AN 139(分子量500,000)、AN 119(分子量250,000)和优选S-97药物级(分子量70,000)。当存在增强剂时,其存在量在约0.05至约3重量%的范围。
其他的有效的聚合物包括例如马来酸酐与丙烯酸乙酯、甲基丙烯酸羟乙酯、N-乙烯基-2-吡咯烷酮或乙烯的1:1共聚物,后者可获自例如Monsanto EMANo.1103(分子量10,000)和EMA Grade 61,和丙烯酸与甲基丙烯酸甲酯或羟乙酯、丙烯酸甲酯或乙酯、异丁基乙烯基醚或N-乙烯基-2-吡咯烷酮的1:1共聚物。
通常合适的是含有活化碳-碳烯烃双键和至少一个羧基的聚合烯烃式或烯键式不饱和羧酸,即含有烯烃双键的酸,所述双键由于在单体分子中相对于羧基在α-β位置存在或者作为末端亚甲基的一部分存在,容易在聚合中起作用。这种酸的示例性实例是丙烯酸、甲基丙烯酸、乙基丙烯酸、α-氯丙烯酸、巴豆酸、β-丙烯酰氧基丙酸、山梨酸、α-氯山梨酸、肉桂酸、β-苯乙烯基丙烯酸、黏康酸、衣康酸、柠康酸、中康酸、戊烯二酸、乌头酸、α-苯基丙烯酸、2-苄基丙烯酸、2-环已基丙烯酸、当归酸、伞形酸、富马酸、马来酸以及这些酸的酸酐。其他不同的可与这些羧酸单体共聚的烯烃单体包括乙酸乙烯酯、氯乙烯、马来酸二甲酯等。共聚物含有足够的羧酸盐基团,从而具有水溶性。
又一类聚合物质包括含有被取代的丙烯酰胺的均聚物和/或不饱和的磺酸及其盐的均聚物的组合物,特别是其中聚合物基于选自分子量为约1,000至约2,000,000的丙烯酰胺基烷磺酸(acrylamidoalykanesulfonic acid)(如2-丙烯酰胺2甲基丙烷磺酸)的不饱和磺酸,如Zahid的美国专利第4,842,847号(1989年6月27日),该专利通过引用并入本文。
另一类有用的聚合物质包括聚氨基酸,特别是那些含有部分阴离子型表面活性氨基酸(如天冬氨酸、谷氨酸和磷酸丝氨酸)的聚氨基酸,如Sikes等人的美国专利第4,866,161号中所公开,该专利通过引用并入本文。
在制备口腔护理组合物时,有时有必要加入一些增稠材料,以提供需要的稠度或者稳定或提高配方性能。在某些实施方案中,增稠剂是羧基乙烯基聚合物、卡拉胶、羟乙基纤维素以及纤维素醚的水溶性盐,如羧甲基纤维素钠和羧甲基羟乙基纤维素钠。还可掺入天然树胶如刺梧桐胶、阿拉伯树胶和黄蓍胶。胶态硅酸镁铝或微细二氧化硅可用作增稠组合物的成分,以进一步改进组合物的质构。在某些实施方案中,增稠剂的用量占总组合物的约0.5%至约5重量%。
酶
本发明的口腔护理组合物还可任选包括一种或多种酶。有用的酶包括任何可利用的蛋白酶、葡聚糖水解酶、内切糖苷酶、淀粉酶、变聚糖酶、脂肪酶和黏蛋白酶或者它们的相容混合物。在某些实施方案中,酶是蛋白酶、葡聚糖、内切糖苷酶和变聚糖酶。在另一个实施方案中,酶是木瓜蛋白酶、内切糖苷酶或者是葡聚糖和变聚糖酶的混合物。另外的适用于本发明的酶在美国专利第5,000,939号(Dring等人)、美国专利第4,992,420号、美国专利第4,355,022号、美国专利第4,154,815号、美国专利第4,058,595号、美国专利第3,991,177号和美国专利第3,696,191号中公开,所有这些专利都通过引用并入本文。在本发明中,某种酶或者几种相容性酶的混合物在一个实施方案中占约0.002%至约2%,或者在另一个实施方案中占约0.05%至约1.5%,或者在又另一个实施方案中占约0.1%至约0.5%。
水
本发明的口腔组合物中还可存在水。用于制备商用口腔组合物的水应经过去离子处理且不含有机杂质。水通常构成组合物的其余部分,占口腔组合物重量的约10%至约90%、约20%至约60%或约10%至约30%。这个水量包括所加入的游离水以及随其他材料(如随山梨糖醇或本发明的任何成分)引入的水量。
湿润剂
在口腔组合物的某些实施方案中,还合乎需要的是掺入湿润剂,以防止组合物在暴露于空气时发生硬化。某些湿润剂还可给洁齿剂组合物赋予所需的甜度或风味。以纯湿润剂计,一般来讲湿润剂在一个实施方案中占洁齿剂组合物重量的约15%至约70%,在另一个实施方案中占约30%至约65%。
合适的湿润剂包括可食用多元醇如甘油、山梨糖醇、木糖醇、丙二醇和其他多元醇,以及这些湿润剂的混合物。甘油和山梨糖醇的混合物在某些实施方案中可用作本发明牙膏组合物的湿润剂成分。
除了上述成分外,本发明的实施方案还可含有多种任选的洁齿成分,其中一些在下文描述。任选的成分包括例如但不限于粘合剂、起泡剂、矫味剂、增甜剂、另外的防牙菌斑剂、研磨剂和着色剂。这些和其他的任选成分在Majeti的美国专利第5,004,597号、Agricola等人的美国专利第3,959,458号和Haefele的美国专利第3,937,807号中有更多的描述,所有这些专利都通过引用并入本文。
制造方法
本发明组合物可用口腔产品领域通用的方法来制备。
在一个示例性的实施方案中,通过用酸例如磷酸、盐酸或碳酸在凝胶相中中和或部分中和精氨酸并混合形成预混合料1,来制备口腔护理组合物。
将活性物质例如维生素、CPC、氟化物、研磨剂和任何其他所需的活性成分加到预混合料1,混合形成预混合料2。
将牙膏基料例如磷酸二钙或二氧化硅加到预混合料2并混合。将最终浆料成形为口腔护理产品。
组合物用途
本发明在其方法方面涉及到将安全和有效量的本文所述组合物施用于口腔。
根据本发明的组合物和方法可用于通过促进修复和再矿化而保护牙齿,特别是减少或抑制龋齿的形成,减少或抑制牙齿去矿化和促进牙齿再矿化,减少牙齿超敏,以及减少、修复或抑制早期牙釉质损伤,所述损伤例如通过定量光导荧光(QLF)或电龋测量(ECM)检测到。
定量光导荧光是一种可见光荧光,可以检测早期损伤和纵向监测进展或衰退情况。正常牙齿在可见光中发荧光;去矿化的牙齿不会发荧光或者发荧光程度较低。可定量去矿化的面积并监测其进展。用蓝色激光使牙齿自动发荧光。失去了矿物质的区域与完好牙齿表面相比具有较低的荧光,看起来较暗。用软件定量来自白点和/或与损伤有关的面积/体积的荧光。一般地,将具有现有的白点损伤的受试者募集作为组员。测量是在体内用真实牙齿进行。损伤面积/体积在临床试验开始时测量。在使用产品六个月结束时测量损伤面积/体积的减少(改善)。数据一般以相对于基线值的改善百分数报告。
电龋监测是一种基于电阻用来测量牙齿的矿物质含量的技术。电导测量利用到这个事实:牙釉质发生去矿化和侵蚀时所暴露的充满流体的小管能导电。随着牙齿失去矿物质,由于孔隙率增加,它对电流的阻力变低。因此,患者牙齿的电导增加可表明发生去矿化。一般地,对具有现有的损伤的根面进行研究。测量是在体内用真实牙齿进行。在六个月治疗前后电阻发生变化。另外,用触觉探头作出根面的经典龋评分。硬度以如下三点尺度进行分类:硬、坚韧或软。在这个类型的研究中,通常将结果以ECM测量的电阻(数值越高越好)和基于触觉探头评分的损伤硬度改善来报道。
本发明的组合物因此可用于减少牙釉质的早期损伤(由QLF或ECM测量)的方法中,所述减少是相对于缺乏有效量的氟和/或精氨酸的组合物而言。
本发明的组合物还适用于减少口腔中的有害细菌的方法中,例如用于以下用途的方法:减少或抑制齿龈炎的方法,降低产酸细菌的水平,提高分解精氨酸的细菌的相对水平,抑制口腔中的微生物膜形成,在糖攻击后提高和/或维持牙菌斑pH在至少pH约5.5的水平,减少牙菌斑积累,和/或清洁牙齿和口腔。
最后,通过提高口中的pH和抑制致病细菌,本发明的组合物可用于促进口中伤口或切口的康复。
本发明的组合物和方法可结合到口腔和牙齿护理用的口腔组合物,如牙膏、透明糊(transparentpaste)、凝胶、漱口剂、喷雾剂和香口胶。
各活性成分的水平将根据递送系统和具体活性成分的性质而变。例如,碱性氨基酸的存在量可例如为约0.1至约20wt%(以游离碱的重量表示),例如对于漱口剂约0.1至约3wt%,对于消费者用牙膏为约1至约10wt%,或者对于专业或处方用治疗产品为约7至约20wt%。氟化物的存在量可例如为约25至约10,000ppm,例如对于漱口剂为约25至约250ppm,对于消费者用牙膏为约750至约2,000ppm,或者对于专业或处方用治疗产品为约2,000至约10,000ppm。抗菌剂的水平同样可变,用于牙膏的水平例如比用于漱口剂的量高约5至约15倍。例如,三氯生漱口剂可含有例如约0.03wt%三氯生,而三氯生牙膏可含有约0.3wt%三氯生。
提高口腔健康也能在全身健康方面提供好处,因为口腔组织可以成为全身性感染的通道。良好的口腔健康与全身健康相关,包括心血管健康。本发明的组合物和方法能提供特别的好处,因为碱性氨基酸特别是精氨酸作为氮源能供应NO合成途径,从而增强口腔组织中的微循环。使口腔环境酸度较低也有助于减少胃部不适,并产生对与胃溃疡有关的螺旋杆菌(Heliobacter)不太有利的环境。具体地讲,精氨酸为特异性免疫细胞受体(例如T细胞受体)的高表达所必需,因此精氨酸能增强有效的免疫应答。本发明的组合物和方法因此可用于增强全身健康,包括心血管健康。
本文通篇所用的数值范围,是作为描述该范围内的每个数值的简便方法而使用。该范围内的任何数值都可选择作为该范围的端值。另外,本文引述的所有参考文献都通过引用整体并入本文。如本公开说明书中的定义与所引述的参考文献中的定义有冲突,以本公开内容的为准。应理解,当描述配方时,它们可以如本领域通常的做法根据它们的成分进行描述,尽管这些成分在实际配方制备、保藏和使用时可在配方中相互发生反应,这类产品也意在被所描述的配方所覆盖。
以下实施例进一步描述和说明落入本发明范围之内的示例性实施方案。实施例仅出于说明的目的给出,不能解释为限制本发明,因为在不背离本发明精神和范围的情况下,可以有多种变化方案。除了本文显示和描述的那些方案之外,还有本发明的各种修改方案应当为本领域技术人员所显而易见,这些修改方案意在落入所附权利要求书的范围内。
实施例
实施例1–氟化物在精氨酸配方中的有效性和递送
用商用牙膏制备配方,所述牙膏中包含有0.3重量%的三氯生、0.075重量%的氟化钠、月桂基硫酸钠以及甲基乙烯基醚和马来酸酐的共聚物(PVM/MA),各配方中分别加入0、1%、3%和5%L-精氨酸盐酸盐(pH 7.0)。
在商用配方中掺入L-精氨酸提高了可从配方得到的可溶性氟化物的量。这个提高了的递送直接导致配方的氟化物作用的递送的提高。
Claims (8)
1.一种口腔护理组合物,其包含:
a. 有效量的游离形式或盐形式的精氨酸;和
b. 一定量的氟化物源,其中所述氟化物不超过所述组合物重量的0.1%;
其中,pH为6.5至7.4,
其中所述口腔护理组合物还包含阴离子型表面活性剂,所述阴离子型表面活性剂选自月桂基硫酸钠和月桂基聚氧乙烯醚硫酸钠以及它们的混合物,其中所述阴离子型表面活性剂的存在量占总组合物重量的约0.01至约10重量%,任选其中所述阴离子型表面活性剂的存在量占总组合物重量的约0.3至约4.5重量%,
其中所述口腔护理组合物还包含阴离子型聚合物,任选其中所述阴离子型聚合物是甲基乙烯基醚和马来酸酐的共聚物。
2.一种口腔护理组合物,其包含:
a. 有效量的游离形式或盐形式的精氨酸;和
b. 提供不超过约600 ppm的氟离子的氟化物源;
其中,pH为6.5至7.4,
其中所述口腔护理组合物还包含阴离子型表面活性剂,所述阴离子型表面活性剂选自月桂基硫酸钠和月桂基聚氧乙烯醚硫酸钠以及它们的混合物,其中所述阴离子型表面活性剂的存在量占总组合物重量的约0.01至约10重量%,任选其中所述阴离子型表面活性剂的存在量占总组合物重量的约0.3至约4.5重量%,
其中所述口腔护理组合物还包含阴离子型聚合物,任选其中所述阴离子型聚合物是甲基乙烯基醚和马来酸酐的共聚物。
3.权利要求1或2的组合物,其中所述精氨酸为盐形式,选自精氨酸磷酸盐、精氨酸碳酸氢盐和精氨酸盐酸盐。
4.权利要求1或2的组合物,其包含选自氟化钠和单氟磷酸钠的氟化物源。
5.权利要求1或2的组合物,其还包含抗菌剂,任选其中所述抗菌剂是三氯生。
6.口腔护理组合物在用于制备改善需要低氟化物剂量的受试者的口腔健康的产品中的用途,所述组合物包含:
a.有效量的游离形式或盐形式的精氨酸;和
b.提供不超过约600 ppm的氟离子的氟化物源;
其中,所述组合物的pH为6.5至7.4,
其中所述口腔护理组合物还包含阴离子型表面活性剂,所述阴离子型表面活性剂选自月桂基硫酸钠和月桂基聚氧乙烯醚硫酸钠以及它们的混合物,其中所述阴离子型表面活性剂的存在量占总组合物重量的约0.01至约10重量%,任选其中所述阴离子型表面活性剂的存在量占总组合物重量的约0.3至约4.5重量%,
其中所述口腔护理组合物还包含阴离子型聚合物,任选其中所述阴离子型聚合物是甲基乙烯基醚和马来酸酐的共聚物。
7.权利要求6的用途,其中所述受试者需要所述产品以:
a. 减少或抑制牙龋的形成,
b. 减少、修复或抑制早期牙釉质损伤,
c. 减少或抑制牙齿的去矿化和促进再矿化,
d. 减少牙齿的超敏,
e. 减少或抑制齿龈炎,
f. 促进口中伤口或切口的康复,
g. 减少产酸细菌的水平,
h. 增加分解精氨酸的细菌的相对水平,
i. 抑制口腔中微生物膜的形成,
j. 在糖攻击后提高和/或维持牙菌斑pH在至少pH 5.5的水平,
k. 减少牙菌斑积累,
l. 治疗、减轻或减少干口症,
m. 增白牙齿,
n. 增强全身健康,包括心血管健康,
o. 使牙齿对龋齿细菌具有免疫力,
p. 减少牙齿的侵蚀,和/或
q. 清洁牙齿和口腔。
8.权利要求1-5中任一项的口腔护理组合物,用于改善需要低氟化物剂量的受试者的口腔健康的方法中,所述方法包括给予所述受试者所述口腔护理组合物。
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AU2009212320B2 (en) | 2012-12-13 |
AU2009212320A1 (en) | 2009-08-13 |
TW200946134A (en) | 2009-11-16 |
EP2249783B1 (en) | 2021-04-07 |
WO2009100264A3 (en) | 2009-11-05 |
BRPI0907107A2 (pt) | 2018-09-11 |
WO2009100264A2 (en) | 2009-08-13 |
RU2010137325A (ru) | 2012-03-20 |
JP2014221781A (ja) | 2014-11-27 |
EP2249783A4 (en) | 2014-01-08 |
CA2705298C (en) | 2013-10-01 |
RU2012135284A (ru) | 2014-02-27 |
CA2705298A1 (en) | 2009-08-13 |
AR070356A1 (es) | 2010-03-31 |
CO6290628A2 (es) | 2011-06-20 |
BRPI0907107B8 (pt) | 2019-08-20 |
RU2469701C2 (ru) | 2012-12-20 |
CN101938983A (zh) | 2011-01-05 |
EP2249783A2 (en) | 2010-11-17 |
US20100316580A1 (en) | 2010-12-16 |
MX2010004647A (es) | 2010-06-07 |
ZA201003682B (en) | 2015-04-29 |
JP2011511093A (ja) | 2011-04-07 |
MY157021A (en) | 2016-04-15 |
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