CN101938955A - 牙线 - Google Patents
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- CN101938955A CN101938955A CN2009801049328A CN200980104932A CN101938955A CN 101938955 A CN101938955 A CN 101938955A CN 2009801049328 A CN2009801049328 A CN 2009801049328A CN 200980104932 A CN200980104932 A CN 200980104932A CN 101938955 A CN101938955 A CN 101938955A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C15/00—Devices for cleaning between the teeth
- A61C15/04—Dental floss; Floss holders
- A61C15/041—Dental floss
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- 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
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
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- 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
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
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- 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
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- 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
本发明涉及包含碱性氨基酸或其盐的牙线。
Description
本申请要求2008年2月8日提交的美国专利申请系列号61/027,436的权益,其内容通过引用结合于本文中。
发明背景
使用牙线和其它牙间清洁器是牙齿卫生的重要部分,并用于从牙间和牙龈(gum line)下,如,口腔中牙刷接触不到的地方去除牙菌斑和其它颗粒。这些常常成为龋齿的起动位点,尤其是如果不能定期地清洁时。然而,即使采用常规维护,龋齿和牙龈炎仍然在这些区域发生。因此,对于开发更有效的牙线存在持续的需求。
虽然推荐人们每日至少一次使用牙线清洁其牙齿,但实际情况是很少有人如推荐的那样经常用牙线清洁牙齿。因此,需要更有效的牙线组合物供偶尔使用牙线者使用。
发明简述
已经发现,碱性氨基酸在抑制细菌附着、促进牙齿的再矿化(remineralization)、降低口腔和牙齿超敏性的发生率和抑制有利于精氨酸分解(arginolytic)菌的致龋菌中提供有益作用。
本发明提供与包含碱性氨基酸或其盐,如精氨酸、精氨酸碳酸氢盐、精氨酸盐酸盐或精氨酸磷酸盐的组合物组合或相关(association)的牙线。可将碱性氨基酸或盐涂敷在牙线上,或将牙线浸渍在牙线基质中,或可使用包装分发牙线,其中牙线经由包括含碱性氨基酸的组合物,如,以下组合物1.1-1.15的任一个的容器储存或分发。
因此,本发明包括与组合物(组合物1.0)组合或相关(如,用组合物涂敷或浸渍)的牙线,所述组合物包含碱性氨基酸或其盐,如,与以下任何组合物组合或相关的牙线:
组合物1.0,其中的碱性氨基酸是精氨酸、赖氨酸、瓜氨酸、鸟氨酸、肌氨酸、组氨酸、二氨基丁酸、二氨基丙酸(diaminoproprionic acid)、其盐和/或其组合。
组合物1.0或1.1,其中的碱性氨基酸具有L-构型。
任一种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的。
任一种前述组合物,其中的碱性氨基酸是精氨酸。
任一种前述组合物,其中的碱性氨基酸是L-精氨酸。
包含碱性氨基酸的生理学上可接受的盐的任一种前述组合物。
任一种前述组合物,其中的碱性氨基酸的盐是碳酸盐。
任一种前述组合物,其中的碱性氨基酸的盐是碳酸氢盐。
任一种前述组合物,其中的碱性氨基酸盐是精氨酸碳酸氢盐。
还包含氟化物或氟离子源的任一种前述组合物。
包含选自氟化亚锡、氟化钠、氟化钾、一氟磷酸钠、氟硅酸钠、氟硅酸铵、氟化胺、氟化铵,及其组合的氟离子源的任一种前述组合物。
还包含防腐剂或抗微生物剂的任一种前述组合物。
还包含选自以下的抗菌剂的任一种前述组合物:三氯生、草药提取物和精油(如,迷迭香提取物、茶提取物、木兰花提取物、麝香草酚、薄荷醇、桉油醇、香叶醇、香芹酚、柠檬醛、扁柏酚(hinokitol)、儿茶酚、水杨酸甲酯、表没食子儿茶精没食子酸酯、表没食子儿茶精、没食子酸、miswak提取物、沙棘提取物、蜂胶)、双胍(bisguanide)防腐剂(如,氯己定、阿来西定(alexidine)或奥替尼啶(octenidine))、季铵化合物(如,西吡氯铵(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))、酚防腐剂、海克替啶(hexetidine)、奥替尼啶、血根碱、聚维酮碘、地莫匹醇、5-正辛酰-3′-三氟甲基苯基水杨酰胺(salifluor)、金属离子(如,锌盐,例如,柠檬酸锌、锡盐、铜盐、铁盐)、血根碱、蜂胶和氧化剂(oxygenating agents)(如,过氧化氢、缓冲的过硼酸钠或过氧碳酸钠)、酞酸及其盐、单过氧邻苯二甲酸(monoperthalic acid)及其盐和酯、抗坏血酸硬脂酸酯(ascorbyl stearate)、油酰肌氨酸、烷基硫酸盐、磺基琥珀酸二辛酯、水杨酰苯胺、度米芬、地莫匹醇、辛哌醇和其它哌啶子基衍生物、乳链菌肽(nicin)制剂、亚氯酸盐类;和前述的任何混合物。
还包含选自止痛剂、抗炎剂、促凝药、收敛剂、维生素,及其组合的其它成分的任一种前述组合物。
还包含粘合剂、蜡或载体的任一种前述组合物。
本发明还包括用于储存或分发牙线的包装,该包装包括含碱性氨基酸的容器(chamber),其中在储存或分发期间牙线暴露于碱性氨基酸中,如,其中的容器含有包含碱性氨基酸的组合物,如,依据组合物1.0-1.15的任一组合物。
本发明还包括方法2.0,一种(i)减少或抑制龋齿的形成,(ii)减少、修复或抑制牙釉质的龋前缺损,如,由定量光导(light-induced)荧光(QLF)或龋齿的电学检测(ECM)探测的缺损,(iii)减少或抑制牙齿的去矿化和促进牙齿的再矿化,(iv)减少牙齿的超敏性,(v)减少或抑制牙龈炎,(vi)促进口腔中疮或伤口的愈合,(vii)降低产酸菌的水平,(viii)提高精氨酸分解细菌的相对水平,(ix)抑制口腔中微生物生物膜的形成,(x)提高和/或保持牙菌斑pH为至少pH 5.5的水平,(xi)减少牙菌斑聚积,(xii)清洁牙齿和口腔,(xiii)使牙齿对致龋菌免疫,和/或(xiv)减少侵蚀,(xv)增加全身健康,和/或(xvi)治疗或抑制口干症的方法,该方法包括用与游离的碱性氨基酸或盐形式组合或相关(如,与上文描述的组合物1.0-1.15中任一的组合物组合或相关的)的牙线清洁有此需要的患者的牙齿或口腔的其它表面。
对于本领域技术人员而言,本发明的其它实施方案将是显而易见的。
发明详述
不打算受特定的理论的束缚,认为口腔中的碱性氨基酸被某些类型的细菌,例如血链球菌(S.sanguis)代谢,该细菌为不致龋的并与致龋菌,例如变性链球菌(S.mutans)竞争在牙齿上和口腔中的位置。精氨酸分解细菌可利用精氨酸和其它碱性氨基酸而生成氨,从而提高其环境的pH,而致龋菌代谢糖生成趋于降低牙菌斑pH和使牙齿去矿化,最终生成牙洞的乳酸。认为采用本发明组合物可相对增加精氨酸分解细菌和相对减少致龋菌,产生较高的牙菌斑pH并相应减少牙洞形成(cavitation)过程。
可用于本发明组合物的碱性氨基酸不仅包括天然存在的碱性氨基酸,诸如精氨酸、赖氨酸和组氨酸,还包括在分子中具有羧基和氨基的任何碱性氨基酸。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、肌氨酸、组氨酸、二氨基丁酸、二氨基丙酸、其盐或其组合。在具体的实施方案中,碱性氨基酸选自精氨酸、瓜氨酸和鸟氨酸,优选精氨酸,例如,l-精氨酸。
本发明的组合物用于口腔,按提供的量和浓度针对这类用途而用于本发明的这类盐应该是安全的。合适的盐包括本领域已知是药学上可接受的盐,通常认为按照所提供的量和浓度,其在生理上是可接受的。生理上可接受的盐包括衍生自药学上可接受的无机或有机酸或碱的那些盐,例如由生成生理上可接受的阴离子的酸所形成的酸加成盐,例如,氢氯酸盐或氢溴酸盐,和由生成生理上可接受的阳离子,例如衍生自碱金属诸如钾和钠或碱土金属诸如钙和镁的那些碱所形成的碱加成盐。可采用本领域已知的标准程序,例如,通过使足够碱性化合物,诸如胺与适用的酸反应,得到生理上可接受的阴离子,得到生理上可接受的盐。优选的盐是碳酸氢盐,例如,精氨酸碳酸氢盐。
制造牙线的方法为本领域所熟知。例如,在尼龙盐被聚合且将得到的聚合物泵出或挤出以形成单纤维丝时,可由尼龙生产牙线。使细丝变硬,然后合并形成一股牙线。可由聚四氟乙烯(PTFE或Teflon)、聚丙烯、聚乙烯、苯乙烯丁二烯(butadyene)共聚物、它们的组合生产牙线。将聚合物融化并挤出形成细丝线。也参见美国专利号6,270,890,其内容通过参考结合于本文。
在一个实施方案中,将树脂,如尼龙或PTFE与碱性氨基酸或其盐混合,并挤出以形成细丝(如,在尼龙的情况下),将其捻搓(twisted)形成牙线,或形成牙线的单根丝带(ribbon)(如,在PTFE的情况下)。应该理解的是,一些碱性氨基酸或盐将被布置在牙线表面附近,并且当使用牙线时将被暴露和释放出来。在一个实施方案中,牙线的旦尼尔为约450至约1350。在另一个实施方案中,牙线的旦尼尔(dernier)从约100至约900。
涂敷牙线的方法为本领域所熟知。在本发明的一个实施方案中,在含精氨酸或其药学上可接受的盐的乳剂浴液中处理牙线。该乳剂浴液可任选含一种或多种蜡,其附着于牙线上,并由此使精氨酸附着于牙线上。在另一个实施方案中,包含非-PTFE纤维的牙线经第一次和第二次涂敷,第二次涂敷覆盖在第一次涂层上。第一次涂层是尼龙粘结涂层,而第二次涂层是蜡或聚合物,例如与碱性氨基酸或其盐组合或相关的聚乙烯醇、聚乙酸乙烯酯等。参见,如,美国专利号6,289,904,其通过参考结合于本文。
牙线可为单根丝带(如,Teflon或聚乙烯丝带)的形式。或者,其可为细丝,如尼龙细丝束。细丝的数量将从约2至约300条,如从约2至约200条,其取决于细丝的旦尼尔。将以每英寸约1至5个捻度(twists)捻搓细丝以形成牙线。捻搓提供在线轴(spool)上和在后续处理期间牙线的完整性。然而,在使用时,细丝将展开并斜对着(splay against)齿面。牙线也可形成连锁纤维的形式,如,像Oral-B Ultra牙线TM的情形。在任何情况下,最终的牙线产品优选具有使之适宜牙齿之间的厚度。可用蜡涂敷牙线。在使用多股细丝时,可在捻搓之前或之后,优选在捻搓之后应用涂敷。在蜡涂敷之后,可将其它的添加剂应用于蜡涂敷的牙线。可应用为液体或固体的香料。优选的是使用喷雾干燥的固体。同样地,可应用多种为液体或固体其它的添加剂。当应用为液体的添加剂时,在缠绕在线轴上之前使牙线干燥。可通过辐射干燥或风干进行干燥。干燥后,将牙线缠绕在线轴上。
一般以含10至50米牙线的塑料分配器(dispenser)供应牙线。典型地,该分配器具有小的受保护的刀片,用于在拉出所需要的量的牙线时将其切断。
在本发明的一个实施方案中,提供含放置在容器中并与牙线接触的碱性氨基酸、盐或其溶液的牙线分配器。在储存牙线时或在用户拉出需要量的牙线时,牙线即与碱性氨基酸、盐或其溶液接触,从而涂敷牙线。
已经开发了多种器械帮助用户用牙线清洁其牙齿,特别是当用牙线清洁特定的牙齿时间有困难或使用不便时(awkward)。这样的器械形状像小棒以夹持牙线。本发明预期与这样的器械组合使用碱性氨基酸及其盐。另外,可将不含碱性氨基酸或盐并且保留在这样的小棒上的牙线浸渍在碱性氨基酸、盐或其溶液中,以获取本发明的优点。
在本发明的一个实施方案中,牙线可任选包括氟化物或氟离子源。很多种产生氟离子的原料可被用作本文组合物中的适宜的氟化物源。产生适宜的氟离子的原料的实例,在Briner等的美国专利号3,535,421、Parran,Jr.等的美国专利号4,885,155和Widder等的美国专利号3,678,154中找到,这些文献通过参考结合于本文。代表性的氟离子源包括,但不限于氟化亚锡、氟化钠、氟化钾、一氟磷酸钠、氟硅酸钠、氟硅酸铵、氟化胺、氟化铵,及其组合。在某些实施方案中,氟离子源包括氟化亚锡、氟化钠、一氟磷酸钠及其混合物。
本发明的牙线也可包含磨料微粒,如,氧化铝、小粒硅胶或其它研磨剂或抛光粒子。参见如,美国专利号6,453,912,其通过参考结合于本文。
本发明的牙线也可包含选自以下的防腐剂或抗微生物剂:三氯生、草药提取物和精油(如,迷迭香提取物、麝香草酚、薄荷醇、桉油醇、水杨酸甲酯)、双胍防腐剂(如,氯己定、阿来西定或奥替尼啶)、季铵化合物(如,西吡氯铵)、酚防腐剂、海克替啶、聚维酮碘、地莫匹醇、5-正辛酰-3′-三氟甲基苯基水杨酰胺、金属离子(如,锌盐,例如,柠檬酸锌)、血根碱、蜂胶,及其组合,以进一步促进碱性氨基酸的有益效应。
由于使用牙线,可在使用期间或之后引起不适或出血,可任选包含止痛剂、抗炎剂、促凝药、维生素,及其组合。
Claims (18)
1.一种与碱性氨基酸组合或相关的牙线。
2.权利要求1的牙线,其中的碱性氨基酸是碱性氨基酸的生理学上可接受的盐。
3.权利要求1或2的牙线,其中的碱性氨基酸是精氨酸、赖氨酸、瓜氨酸、鸟氨酸、肌氨酸、组氨酸、二氨基丁酸、二氨基丙酸、其盐和/或其组合。
4.前述权利要求的任一项的牙线,其中的碱性氨基酸具有L-构型。
5.前述权利要求的任一项的牙线,其中的碱性氨基酸是精氨酸。
6.前述权利要求的任一项的牙线,其中的碱性氨基酸是L-精氨酸。
7.前述权利要求的任一项的牙线,其中的碱性氨基酸的盐是碳酸盐。
8.权利要求2-6的任一项的牙线,其中的碱性氨基酸的盐是碳酸氢盐。
9.权利要求2-5和8的任一项的牙线,其中的碱性氨基酸盐是精氨酸碳酸氢盐。
10.前述权利要求的任一项的牙线,其还包含氟离子源。
11.权利要求1-10的任一项的牙线,其还包含防腐剂或抗微生物化合物。
12.权利要求1-11的任一项的牙线,其还包含选自止痛剂、促凝药、抗炎剂、阿片样物质和维生素的其它成分。
13.权利要求1-12的任一项的牙线,其还包含粘合剂、蜡或载体。
14.权利要求1-13的任一项的牙线,其中牙线用碱性氨基酸涂敷或浸渍。
15.一种用于储存或分发牙线的包装,该包装包括含碱性氨基酸的容器,其中在储存或分发期间牙线暴露于碱性氨基酸中。
16.一种制造牙线的方法,该方法包括使碱性氨基酸与单体混合、使单体反应产生聚合体,并使聚合体形成一条或多条细线。
17.通过权利要求16的方法获得的或可获得的牙线。
18.一种(i)减少或抑制龋齿的形成,(ii)减少、修复或抑制牙釉质的龋前缺损,(iii)减少或抑制牙齿的去矿化和促进牙齿的再矿化,(iv)减少牙齿的超敏性,(v)减少或抑制牙龈炎,(vi)促进口腔中疮或伤口的愈合,(vii)降低产酸菌的水平,(viii)提高精氨酸分解细菌的相对水平,(ix)抑制口腔中微生物生物膜的形成,(x)提高和/或保持牙菌斑pH为至少pH 5.5的水平,(xi)减少牙菌斑聚积,(xii)清洁牙齿和口腔,(xiii)使牙齿对致龋菌免疫,和/或(xiv)减少侵蚀,(xv)增加全身健康,和/或(xvi)治疗或抑制口干症的方法,该方法包括用与游离或盐形式的碱性氨基酸组合或相关的牙线清洁有此需要的患者的牙齿或口腔的其它表面。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US2743608P | 2008-02-08 | 2008-02-08 | |
US61/027436 | 2008-02-08 | ||
PCT/US2009/033305 WO2009100276A2 (en) | 2008-02-08 | 2009-02-06 | Dental floss |
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CN101938955A true CN101938955A (zh) | 2011-01-05 |
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CN2009801049328A Pending CN101938955A (zh) | 2008-02-08 | 2009-02-06 | 牙线 |
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US (1) | US9888988B2 (zh) |
EP (1) | EP2252235A4 (zh) |
JP (2) | JP2011511667A (zh) |
CN (1) | CN101938955A (zh) |
AR (1) | AR070696A1 (zh) |
AU (1) | AU2009212332B2 (zh) |
BR (1) | BRPI0906464A2 (zh) |
CA (1) | CA2705519C (zh) |
CO (1) | CO6321207A2 (zh) |
MX (1) | MX2010005190A (zh) |
MY (1) | MY154018A (zh) |
RU (2) | RU2010137326A (zh) |
SG (1) | SG191691A1 (zh) |
TW (1) | TW200946083A (zh) |
WO (1) | WO2009100276A2 (zh) |
ZA (1) | ZA201003683B (zh) |
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- 2009-02-06 US US12/866,775 patent/US9888988B2/en active Active
- 2009-02-06 CN CN2009801049328A patent/CN101938955A/zh active Pending
- 2009-02-06 EP EP09708231.7A patent/EP2252235A4/en not_active Withdrawn
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- 2009-02-06 MX MX2010005190A patent/MX2010005190A/es active IP Right Grant
- 2009-02-06 BR BRPI0906464-8A patent/BRPI0906464A2/pt not_active IP Right Cessation
- 2009-02-06 AR ARP090100443A patent/AR070696A1/es unknown
- 2009-02-06 WO PCT/US2009/033305 patent/WO2009100276A2/en active Application Filing
- 2009-02-06 JP JP2010546023A patent/JP2011511667A/ja active Pending
- 2009-02-06 AU AU2009212332A patent/AU2009212332B2/en not_active Ceased
- 2009-02-06 SG SG2013047675A patent/SG191691A1/en unknown
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2013
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Also Published As
Publication number | Publication date |
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MX2010005190A (es) | 2010-06-03 |
WO2009100276A3 (en) | 2009-10-22 |
WO2009100276A2 (en) | 2009-08-13 |
ZA201003683B (en) | 2014-11-26 |
CA2705519A1 (en) | 2009-08-13 |
JP2011511667A (ja) | 2011-04-14 |
US9888988B2 (en) | 2018-02-13 |
BRPI0906464A2 (pt) | 2015-07-14 |
TW200946083A (en) | 2009-11-16 |
AU2009212332A1 (en) | 2009-08-13 |
AU2009212332B2 (en) | 2012-08-09 |
AR070696A1 (es) | 2010-04-28 |
EP2252235A4 (en) | 2014-08-20 |
RU2010137326A (ru) | 2012-03-20 |
SG191691A1 (en) | 2013-07-31 |
CO6321207A2 (es) | 2011-09-20 |
JP5719901B2 (ja) | 2015-05-20 |
JP2014050728A (ja) | 2014-03-20 |
CA2705519C (en) | 2015-04-28 |
RU2013101564A (ru) | 2014-07-27 |
US20110044916A1 (en) | 2011-02-24 |
EP2252235A2 (en) | 2010-11-24 |
MY154018A (en) | 2015-04-30 |
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