CN104394937B - 液体活化系统 - Google Patents
液体活化系统 Download PDFInfo
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- CN104394937B CN104394937B CN201280062891.2A CN201280062891A CN104394937B CN 104394937 B CN104394937 B CN 104394937B CN 201280062891 A CN201280062891 A CN 201280062891A CN 104394937 B CN104394937 B CN 104394937B
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Abstract
本文描述包含未活化的液体、固定化的微溶性酸或碱的组合物,使得在储存期间未活化的液体不与固定化的微溶性酸或碱接触,但是在使用时,未活化的液体接触固定化的微溶性酸或碱,借以改变液体的pH,从而活化液体,提供益处;连同变体和备选设计、制备和使用所述组合物、及其组分的方法。
Description
背景
已提出将精氨酸和其它碱性氨基酸用于口腔护理,并认为其在防止牙洞形成和牙齿敏感方面具有显著益处。组合这些碱性氨基酸与具有口腔护理益处的矿物质例如氟化物或钙以形成漱口剂,呈现了挑战。例如,碱性氨基酸趋于升高pH,但是在较高的pH下,矿物离子比如氟离子和钙趋于形成盐,并且对于递送至牙齿可用度较低。此外,较高的pH具有引起口腔刺激的可能性。然而,在中性pH或酸性pH下,采用精氨酸碳酸氢盐的系统(其技术教导为优选的,并存在于销售的基于精氨酸的口腔护理产品中)可释放二氧化碳,导致容器在储存时鼓胀和破裂。其它制剂赋形剂比如甜菜碱(三甲基甘氨酸)在一些应用中具有口腔护理益处,但是像精氨酸,趋于升高制剂的pH。
对于漱口剂制剂的另一个问题是难以制备包含酶的制剂,因为酶可能为pH敏感的,并且可与制剂赋形剂反应。
包含漂白剂的制剂呈现进一步的困难,因为漂白剂可能在较高的pH下更加稳定,但是在较低的pH下更有效。
因此,通常存在的问题是,具体漱口剂制剂的制剂稳定性的最佳pH完全不同于有益试剂自漱口剂递送的最佳pH。需要稳定的漱口剂产品,其提供稳定的制剂,然而也提供有益试剂比如氟化物、钙和碱性氨基酸以及pH敏感试剂像酶和漂白剂的有效递送。
概述
为了解决这些问题,我们开发了一种系统,其中漱口剂制剂在瓶中具有较高的pH或较低的pH,然后在分配制剂以使用期间,通过分别与微溶的酸或碱接触降低或升高pH,从而达到提高漱口剂中的有益试剂递送的水平。pH的变化也可提供美学益处,例如颜色变化、泡腾或者风味和香味释放。
此外,这个概念不限于漱口剂,而是也可适用于个人护理产品比如液体皂,和家庭护理产品比如表面清洁剂。
因此,在一个实施方案中,本发明提供在容器中包含未活化的液体的pH活化系统,所述容器在分开的部分含有固定化的微溶性酸或碱,使得在储存期间未活化的液体不与固定化的微溶性酸或碱接触,但是在使用时,未活化的液体接触固定化的微溶性酸或碱,借以改变液体的pH,从而活化溶液,例如,其中通过提供以下的一种或多种,pH改变活化液体:漱口剂中的矿物离子例如氟离子的利用度提高、漱口剂中包含碱性氨基酸和矿物离子的复合物的沉积增强、酶的活性提高或酶底物的反应性提高、漂白剂的活性提高、用于皮肤或口腔的pH更可接受、颜色变化、泡腾、风味变化或香味变化。
在另一个实施方案中,本发明提供一种活化液体例如漱口剂、个人护理产品或家庭护理产品的方法,所述方法包括例如在临用前使液体与固定化的微溶性酸或碱接触,以改变液体的pH,从而如前面段落所述活化液体;和牙齿美白或清洁或者治疗口腔病况比如牙龈炎、牙菌斑或口臭,或者降低牙釉质的去矿化作用的方法,所述方法包括将因此活化的漱口剂施用于口腔;和清洁表面的方法,所述方法包括将因此活化的液体表面清洁剂施用于表面;以及清洁皮肤的方法,所述方法包括将因此活化的液体皮肤护理产品施用于皮肤。
本发明其它的适用性领域自下文提供的详述将变得显而易见。应该理解,详述和具体实例,尽管表明本发明的优选实施方案,打算仅用于说明的目的,并且不打算限制本发明的范围。
详述
以下优选实施方案的描述仅为示例性质,并且决不打算限制本发明、其应用或用途。
本发明提供例如一种液体产品(产品1),例如漱口剂产品、皮肤护理产品或家庭护理产品,所述产品包含具有以下的容器
第一隔室,该隔室含有固定化的微溶性酸或碱,例如包含微溶性酸或碱的固体颗粒或基质;及第二隔室,
一个或多个另外的隔室,各含有未活化的液体,任选地不同的未活化液体,其中存在多于一个另外的隔室,并连接到第一隔室,以致在使用时允许未活化的制剂流入第一隔室,并且第一隔室具有用于在与固定化的微溶性酸或碱接触后分配漱口剂制剂的孔口,
使得在储存期间未活化的液体不与固定化的微溶性酸或碱接触,但是在使用时,未活化的液体接触固定化的微溶性酸或碱,借以改变液体的pH,例如,其中pH改变通过提供以下的一种或多种而活化液体:矿物离子例如氟离子的利用度提高、包含碱性氨基酸和矿物离子的复合物在牙齿的沉积增强、酶的活性提高或酶底物的反应性提高、漂白剂的活性提高、用于皮肤或口腔的pH更可接受、颜色变化、泡腾、风味变化或香味变化。
例如,本发明提供
1.1. 产品1,其中至第一隔室的连接包含单向阀,例如瓣阀(flap valve)或球阀,允许液体流入第一隔室,但是限制流回到一个或多个另外的隔室。
1.2. 产品1或1.1,所述产品包含将液体泵送到第一隔室中和离开孔口的泵。
1.3. 产品1或1.1,其中通过经第一隔室倾倒来自一个或多个另外的隔室的液体并离开孔口,分配所述活化的液体。
1.4. 前述权利要求中任何一项的产品,其中在不使用时,例如通过环捻闭合(ring twist closure)密封至第一隔室的连接。
1.5. 前述权利要求中任何一项的产品,其中所述未活化的液体为口腔可接受的漱口剂制剂。
1.6. 前述权利要求中任何一项的产品,其中所述未活化的液体为包含有效量的氟化物的口腔可接受的漱口剂制剂,例如,其中微溶性的
1.7. 前述权利要求中任何一项的产品,其中所述未活化的液体为包含碱性氨基酸,包含例如选自以下的氨基酸的口腔可接受的漱口剂制剂:精氨酸、赖氨酸、瓜氨酸(citrullene)、鸟氨酸、肌酸、组氨酸、二氨基丁酸、二氨基丙酸、其盐和/或其组合,例如游离或盐形式的L-精氨酸,例如精氨酸碳酸氢盐。
1.8. 前述权利要求中任何一项的产品,其中所述未活化的液体为包含一种或多种钙盐的口腔可接受的漱口剂制剂。
1.9. 前述权利要求中任何一项的产品,其中所述未活化的液体包含卤色染料(halochromicdye) (即响应pH变化而改变颜色的染料),例如选自刃天青(Resazurin)、龙胆紫(Gentian violet) (甲基紫10B (Methyl violet 10B))、隐色孔雀石绿(Leucomalachite green)、百里酚蓝(Thymol blue) (第一转变)、甲基黄(Methylyellow)、溴酚蓝(Bromophenol blue)、刚果红(Congo red)、甲基橙(Methyl orange)、溴甲酚绿(Bromocresol green)、甲基红(Methyl red)、石蕊精(Azolitmin)、溴甲酚紫(Bromocresol Purple)、溴百里酚蓝(Bromothymol blue)、酚红(Phenol red)、中性红(Neutral red)、萘酚酞(Naphtholphthalein)、甲酚红(Cresol Red)、酚酞(Phenolphthalein)、绣球花(Hydrangea flowers)、花色素苷(Anthocyanins)和石蕊(Litmus),例如选自酚酞(Phenolphthalein)、绣球花(Hydrangea flowers)、花色素苷(Anthocyanins)和石蕊(Litmus)。
1.10. 前述权利要求中任何一项的产品,其中所述未活化的液体包含在pH变化时转化为香料的香料前体(profragrance),例如在pH变化时快速水解提供香醇的酯或醚化合物,例如,其中香料前体为(2-二甲氧基)乙基-苯,未活化液体的pH为碱性的,而固定化的微溶性酸或碱为酸,使得当未活化液体的pH在使用时降低至中性或酸性pH时,(2-二甲氧基)乙基-苯水解,提供苯乙醇(玫瑰香味)。
1.11. 前述权利要求中任何一项的产品,其中所述未活化的液体包含微粒基质中的调味剂、香料或其它成分,其中所述微粒基质包含在pH变化时崩解的聚合物,例如,其中未活化的液体具有酸性pH,和微粒基质包含在较高的pH下去质子化和崩解的多羧基(polycarboxyl)化合物,例如丙烯酸酯聚合物或共聚物、丙烯酰氯-赖氨酸、醋酸羟丙基甲基纤维素琥珀酸酯(hydroxypropyl methylcellulose acetate succinate),从而释放调味剂、香料或其它成分。
1.12. 前述权利要求中任何一项的产品,其中所述未活化的液体包含选自碳酸盐、碳酸氢盐及其组合的盐,例如碳酸氢钠或精氨酸碳酸氢盐,例如,其中所述固定化的微溶性酸或碱为酸,使得当未活化液体的pH在使用时降低时释放二氧化碳,引起泡腾。
1.13. 前述权利要求中任何一项的产品,其中所述未活化的液体包含酶和酶底物,并且未活化液体的pH在酶对底物具有活性的范围之外。
1.14. 前述产品,其中所述酶为具有小于7的最佳pH范围的葡萄糖氧化酶,底物为葡萄糖,和固定化的微溶性酸或碱为酸,使得当未活化液体的pH在使用时降低时,产生过氧化氢。
1.15. 前述权利要求中任何一项的产品,其中所述未活化的液体包含过氧化氢,例如,其中未活化液体的pH低,例如在对过氧化氢的稳定性最佳的pH,例如小于pH 4下,固定化的微溶性酸或碱为碱,使得制剂的pH增大至在使用时对皮肤较小刺激性的水平。
1.16. 前述权利要求中任何一项的产品,其中所述固定化的微溶性酸或碱为固体形式的酸。
1.17. 前述权利要求中任何一项的产品,其中所述固定化的微溶性酸或碱为甲酸。
1.18. 前述权利要求中任何一项的产品,其中所述固定化的微溶性酸或碱为固体形式的碱。
1.19. 前述权利要求中任何一项的产品,其中所述未活化的液体包含一种或多种选自以下的试剂:氟化物、抗菌剂(例如三氯生或西吡氯铵)、精氨酸、甜菜碱、钾盐(例如硝酸钾)、调味剂、染料、湿润剂、聚合物和表面活性剂。
1.20. 前述权利要求中任何一项的产品,其中所述固定化的微溶性酸或碱包含不溶性的液体渗透基质中的固体颗粒。
在一些实施方案中,微溶性酸为有机微溶性酸。在其它的实施方案中,微溶性酸为酸性磷酸盐。在一些实施方案中,微溶性酸为酸性焦磷酸钠(sodium acidpyrophosphate)、磷酸铝钠、磷酸二氢钾或其混合物。在一些实施方案中,微溶性酸选自:富马酸、丙酸、戊酸及其两种或更多种的组合。在一些实施方案中,微溶性酸为富马酸。
在另一个实施方案中,本发明提供一种活化液体例如漱口剂、个人护理产品或家庭护理产品的方法,所述方法包括例如在临用前使液体与固定化的微溶性酸或碱接触,以改变液体的pH,从而如前面段落所述活化液体。
在另一个实施方案中,本发明提供一种牙齿美白或清洁或者治疗口腔病况比如牙龈炎、牙菌斑或口臭,或者降低牙釉质的去矿化作用的方法,所述方法包括例如通过用活化的漱口剂将口腔清洗15秒-1分钟的时间段,然后吐出漱口剂,将按照前面段落活化的漱口剂施用于口腔。
在另一个实施方案中,本发明提供一种清洁表面的方法,所述方法包括将上述活化的液体表面清洁剂施用于表面。
在另一个实施方案中,本发明提供清洁皮肤的方法,所述方法包括将上述活化的液体皮肤护理产品施用于皮肤。
在另一个实施方案中,本发明提供一种用于口腔护理、个人护理或家庭护理产品pH活化系统,包含在容器中的未活化液体,所述容器在分开的部分中含有固定化的微溶性酸或碱,使得在储存期间未活化的液体不与固定化的微溶性酸或碱接触,但是在使用时,未活化的液体接触固定化的微溶性酸或碱,借以改变液体的pH,从而活化溶液,例如,其中pH改变通过提供以下的一种或多种而活化液体:漱口剂中的矿物离子例如氟离子的利用度提高、漱口剂中包含碱性氨基酸和矿物离子的复合物的沉积增强、酶的活性提高或酶底物的反应性提高、漂白剂的活性提高、用于皮肤或口腔的pH更可接受、颜色变化、泡腾、风味变化或香味变化。
本发明的一些实施方案提供一种包含第一组分和第二组分的口腔护理组合物,所述第一组分包含固定化的酶,和所述第二组分包含含有反应物的可流动液体,使得在储存期间可流动液体不与固定化的酶接触,但是在使用时,可流动液体接触固定化的酶,并且酶催化可流动液体中涉及反应物的反应,产生增白剂。
在一些实施方案中,将固定化的酶吸附到不溶性材料上,捕集在不溶性珠粒中,通过化学反应共价键合于不溶性材料,通过对不溶性材料具有亲和性的肽的结合结构域而连接,或者捕集在不溶性基质中。
在其它的实施方案中,酶包含多组氨酸标签,和不溶性材料包含多组氨酸标签结合的金属例如镍或钴,或用其涂布。在一些实施方案中,不溶性材料为组氨酸亲和性介质,比如Ni Sepharose (Ni琼脂糖)、NTA-agarose (NTA-琼脂糖)、His60 Ni、HisPur树脂或TALON树脂。在一些实施方案中,不溶性材料为包含镍的钢丝绒。
在一些实施方案中,酶包含结合于羟磷灰石的序列,和不溶性材料包含羟磷灰石。在一些实施方案中,一种或多种酶包含过水解酶(perhydrolase)。在一些实施方案中,一种或多种酶包含过水解酶而可流动液体包含过氧化物源和羧基供体,例如羧酸或酰基化合物,例如,使得当可流动液体接触过水解酶时,过水解酶催化过氧化物和羧基供体之间的反应,形成过酸。
在一些实施方案中,可流动液体包含选自以下的羧基供体:(i) 一种或多种C2-18羧酸,例如C2-6羧酸(例如乙酸),包括任选地用羟基和/或C1-4烷氧基取代的低级线性或分支的烷基羧酸;(ii) 其一种或多种可水解和可接受的酯(例如单-、二-和三-甘油酯及酰化糖类)和(iii) 其混合物。在一些实施方案中,可流动液体包含选自以下的羧基供体:1,2,3-三乙酰氧基丙烷(本文有时称为三醋精或甘油三乙酸酯)和酰化糖类,例如乙酰化糖类。
在一些实施方案中,可流动液体包含羧基供体,所述羧基供体在过水解酶的存在下与过氧化物反应,提供过酸,并且所述羧基供体包括在25℃下具有至少5 ppm的水中溶解度的酯化合物。
在一些实施方案中,一种或多种酶包含过水解酶而可流动液体包含过氧化氢和三醋精,例如,使得当可流动液体接触过水解酶时,过水解酶催化过氧化物和三醋精之间的反应,产生过乙酸。在一些实施方案中,一种或多种酶包含葡萄糖氧化酶而可流动液体包含葡萄糖,例如,使得当可流动液体接触氧化酶时,氧化酶催化葡萄糖氧化为过氧化氢和D-葡萄糖酸-δ-内酯。
在其它的实施方案中,一种或多种酶包含过水解酶和葡萄糖氧化酶,而可流动液体包含葡萄糖和三醋精,例如,使得当可流动液体接触氧化酶时,氧化酶催化葡萄糖氧化为过氧化氢和D-葡萄糖酸-δ-内酯,而过水解酶催化过氧化物和三醋精之间的反应,产生过乙酸。
在一些实施方案中,一种或多种酶包含过水解酶而可流动液体包含过氧化氢、三醋精和甲基乙基酮,例如,使得当可流动液体接触过水解酶时,过水解酶催化过氧化物和三醋精之间的反应,产生过乙酸,并且过乙酸使酮转化为相应的双环氧乙烷。
在一些实施方案中,可流动液体包含一种或多种选自以下的试剂:氟化物、抗菌剂(例如三氯生或西吡氯铵)、精氨酸、甜菜碱、钾盐(例如硝酸钾)、调味剂、染料、湿润剂、聚合物和表面活性剂。在其它的实施方案中,可流动液体包含在口腔可接受的载体中的过氧化物源和酰基化合物以及任选地包含酮。
在一些实施方案中,可流动液体包含过氧化氢。在一些实施方案中,可流动液体包含三醋精。在一些实施方案中,可流动液体进一步包含氟化物。
在仍然其它的实施方案中,可流动液体进一步包含例如有效量,例如0.001-1%,例如0.01-0.5%的例如选自以下的抗菌剂:三氯生(5-氯-2-(2,4-二氯苯氧基)苯酚)、锌或亚锡离子源、季铵化合物比如西吡氯铵(CPC)、双胍(bisguanide)比如氯己定和苯扎氯铵,例如三氯生或西吡氯铵。
在一些实施方案中,可流动液体进一步包含碱性氨基酸和/或铵酸化合物,例如选自游离或盐形式的精氨酸和三甲基甘氨酸及其组合。
一些实施方案提供口腔组合物,其中可流动液体进一步包含调味剂,例如植物精油,例如薄荷醇。而其它的实施方案提供组合物,其中可流动液体进一步包含钾盐,例如柠檬酸钾、氯化钾、酒石酸钾、碳酸氢钾、草酸钾、硝酸钾;锶盐;或其混合物。
在一些实施方案中,可流动液体进一步包含例如选自以下的湿润剂:甘油、丙二醇和山梨醇。在其它的实施方案中,可流动液体进一步包含缓冲剂,例如磷酸盐缓冲剂。在一些实施方案中,可流动液体进一步包含一种或多种聚合物。
在一些实施方案中,可流动液体进一步包含一种或多种表面活性剂。在一些实施方案中,可流动液体进一步包含口腔可接受的酮,例如甲基乙基酮。
在其它的实施方案中,第一和第二组分的成分以在可流动液体与一种或多种酶接触时足以提供以有效美白牙齿的量和浓度的增白剂的量存在。
一些实施方案提供一种生产液体口腔护理制剂中的增白剂的方法,所述方法包括使液体与固定化的酶接触,其中酶与液体中的一种或多种组分反应,提供漂白剂,并使所得的包含增白剂的液体与酶分离。其它的实施方案提供一种美白牙齿或者治疗牙龈炎、牙菌斑或口臭的方法,所述方法包括按照本文描述的实施方案制备包含增白剂的液体,并例如通过用液体将口腔清洗15秒-1分钟的时间段,然后吐出液体,将液体给予口腔。
口腔可接受的:用于口腔护理例如本文描述的漱口剂、制剂的所有成分,应为口腔可接受的。当该术语用于本文时,“口腔可接受的”意思是指存在于所描述的制剂中的成分以不使制剂不安全、不可口或者另外不适用于口腔的量和形式存在。
局部可接受的:用于如本文描述的个人护理制剂例如液体皂或清洁剂的所有成分,应为局部可接受的。当该术语用于本文时,“局部可接受的”意思是指存在于所描述的制剂中的成分以不使制剂不安全或者另外不适用于皮肤的量和形式存在。
活性剂:本文使用的活性成分的有效浓度取决于所使用的具体试剂和递送系统。活性剂,当存在于本发明的组合物中时,以有效量提供。精氨酸,当存在于漱口剂中时,可以约0.1-约3 wt%的水平存在(表示为游离碱的重量)。氟化物,当存在于漱口剂中时,可以例如约25-约250 ppm的水平存在。漱口剂中抗菌剂的水平将类似地变化,例如在一些实施方案中,抗菌剂以按重量计约0.001-约1%的浓度存在,例如其中抗菌剂为例如按重量计约0.05%的浓度的西吡氯铵,或者其中抗菌剂为例如按重量计约0.03%的浓度的三氯生。
氟离子源:口腔护理组合物可进一步包含一种或多种氟离子源,例如可溶性氟化物盐。广泛种类的产生氟离子的材料可用作本组合物中的可溶性氟化物的来源。合适的产生氟离子的材料的实例见于Briner等的美国专利第3535421号、Parran, Jr.等的美国专利第4885155号和Widder等的美国专利第3678154号,其通过引用结合到本文中。代表性的氟离子源非限制性地包括氟化亚锡、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、单氟磷酸钠及其混合物。在某些实施方案中,本发明的口腔护理组合物因此可以足以供给约25-约250 ppm氟化物的量含有氟离子源或提供氟的成分。提供合适水平的氟离子的氟化物盐的重量显然基于盐中反离子的重量而变化。
本文描述的口腔或个人护理产品可包含湿润剂。本文有用的湿润剂包括多元醇比如甘油、山梨醇、木糖醇或低分子量PEGs、亚烷基二醇比如聚乙二醇或丙二醇。在多种实施方案中湿润剂也起甜味剂作用。在一些实施方案中,湿润剂各自以按重量计约1-约40%的量存在。在一些实施方案中,湿润剂为山梨醇。在一些实施方案中,山梨醇以按重量计约5-约25%的浓度存在。在一些实施方案中,山梨醇以按重量计约5-约15%的浓度存在。在一些实施方案中,山梨醇以按重量计约10%的浓度存在。本文提及山梨醇指的是一般地以70%水溶液可市售得到的材料。在一些实施方案中,总的湿润剂浓度为按重量计约1-约60%。在一些实施方案中,湿润剂为甘油。在一些实施方案中,甘油以按重量计约5-约15%的浓度存在。在一些实施方案中,甘油以按重量计约7.5%的浓度存在。在一些实施方案中,湿润剂为丙二醇。在一些实施方案中,丙二醇以按重量计约5-约15%的浓度存在。在一些实施方案中,丙二醇以按重量计约7%的浓度存在。
前述实施方案中的未活化液体可任选地包含着色剂。着色剂比如染料可为目前以Food Drug & Cosmetic Act认证用于食物和摄入药物的食品着色添加剂,包括染料比如FD&C Red No.3 (四碘荧光素的钠盐)、Food Red 17 (6-羟基-5-{(2-甲氧基-5-甲基-4-磺基苯基)偶氮}-2-萘磺酸的二钠盐)、Food Yellow 13 (喹酞酮(quinophtalone)或2-(2-喹啉基)茚满二酮的单和二磺酸的混合物的钠盐)、FD&C Yellow No.5 (4-对-磺基苯基偶氮-1-对-磺基苯基-5-羟基吡唑-3-甲酸的钠盐)、FD&C Yellow No.6 (对-磺基苯基偶氮-B-萘酚-6-单磺酸酯的钠盐)、FD&C Green No.3 (4-{[4-(N-乙基-对-磺基苄基氨基)-苯基]-(4-羟基-2-硫鎓(sulfonium)苯基)-亚甲基}-[1-(N-乙基-N-对-磺基苄基)-δ-3,5-环己二烯亚胺(cyclohexadienimine)]的二钠盐)、FD&C Blue No.1 (二苄基二乙基-二氨基-三苯基甲醇三磺酸的二钠盐无水石膏)、FD&C Blue No.2 (靛蓝的二磺酸的钠盐)及其以各种比例的混合物。一般地,着色剂(如果包含的话)以非常小的量存在。
前述口腔护理实施方案中的未活化液体可任选地包含调味剂。调味剂为已知的,比如天然和人工调味剂。这些调味剂可选自合成的调味油和调味香料和/或油类、油性树脂以及源于植物、叶子、花、果实等的提取物,及其组合。代表性的调味油包括:留兰香油、肉桂油、薄荷油、丁香油、月桂油、百里香油、雪松叶油、肉豆蔻油、鼠尾草油和苦杏仁油。这些调味剂可单个或以混合使用。常用的调味剂包括薄荷比如胡椒薄荷、人工香草精、肉桂衍生物和各种果实调味剂,无论单个还是以混合使用。通常,可使用任何调味剂或食品添加剂,比如在用于食品加工的化学品(Chemicals Used in Food Processing),国家科学院(theNational Academy of Sciences)的出版物1274,第63-258页中描述的那些调味剂或食品添加剂。一般地,调味剂(如果包含的话)以按重量计0.01-1%存在。在一些实施方案中,调味剂可以按重量计约0.2%存在。
前述口腔护理实施方案中的未活化液体可任选地包含甜味剂。甜味剂包括天然和人工甜味剂两者。合适的甜味剂包括水溶性甜味剂比如单糖、二糖和多糖类,比如木糖、核糖、葡萄糖(右旋糖)、甘露糖、半乳糖、果糖(左旋糖)、蔗糖(糖)、麦芽糖;水溶性人工甜味剂比如可溶性的糖精盐,即糖精钠或钙盐、基于环己基氨基磺酸盐二肽的甜味剂,比如L-天冬氨酸衍生的甜味剂,比如L-天冬氨酰-L-苯丙氨酸甲酯(阿斯巴甜)。通常,有效量的甜味剂用于提供对具体组合物期望的甜味水平,并随着所选择的甜味剂而变化。该量通常为按组合物的重量计约0.001%-约5%。在一些实施方案中,甜味剂为糖精钠,并以按组合物的重量计约0.01%存在。
前述口腔护理实施方案中的未活化液体可任选地包含口气清新剂。可提供任选的口气清新剂。可使用任何口腔可接受的口气清新剂,非限制性地包括锌盐比如葡萄糖酸锌、柠檬酸锌和亚氯酸锌、α-紫罗兰酮及其混合物。一种或多种口气清新剂任选地以口气清新有效的总量存在。
前述口腔护理实施方案中的未活化液体可包含牙垢控制(抗牙垢)剂。本文有用的那些当中的牙垢控制剂包括磷酸盐和多磷酸盐(例如焦磷酸盐)、聚氨基丙磺酸(AMPS)、聚烯烃磺酸盐、聚烯烃磷酸盐;二膦酸盐,比如氮杂环烷烃-2,2-二膦酸盐(例如氮杂环庚烷-2,2-二膦酸)、N-甲基氮杂环戊烷2,3-二膦酸、乙烷-1-羟基-1,1-二膦酸(EHDP)和乙烷-1-氨基-1,1-二膦酸盐;膦烷烃(phosphonoalkane)羧酸和这些试剂中任何一种的盐,例如其碱金属和铵盐。有用的无机磷酸盐和多磷酸盐包括磷酸二氢钠、磷酸氢二钠和磷酸钠、三聚磷酸钠、四聚磷酸盐、焦磷酸一钠、焦磷酸二钠、焦磷酸三钠和焦磷酸四钠、三偏磷酸钠、六偏磷酸钠及其混合物,其中钠可任选地被钾或铵替代。其它有用的抗牙垢剂包括聚羧酸盐聚合物和聚乙烯甲醚/马来酸酐(PVME/MA)共聚物,比如可以Gantrez™商标得自ISP,Wayne, N.J的那些聚合物。
在一些实施方案中,牙垢控制剂以按重量计约0.01-10%的浓度存在。在一些实施方案中,牙垢控制剂以按重量计约1%的浓度存在。在一些实施方案中,牙垢控制剂也起缓冲剂作用。例如,在磷酸盐缓冲剂系统中,磷酸二氢钠以按重量计约0.01-约5%的浓度存在,和磷酸二钠以按重量计约0.01-约5%的浓度存在,精确比率取决于制剂中的其它赋形剂和期望的pH。
其它任选的添加剂包括抗微生物(例如抗菌)剂。可使用任何口腔可接受的抗菌剂,包括三氯生(5-氯-2-(2,4-二氯苯氧基)苯酚)、锌和亚锡离子源、季铵化合物比如西吡氯铵(CPC)、双胍类比如氯己定以及苯扎氯铵。在Gaffar等的美国专利第5776435号中提供了有用的抗菌剂的其它说明性列表。在一些实施方案中,抗菌剂以按重量计约0.001-约1%的浓度存在。在一些实施方案中,抗菌剂为西吡氯铵。在一些实施方案中,西吡氯铵以按重量计约0.05%的浓度存在。
抗氧化剂为另一类任选的添加剂。可使用任何口腔可接受的抗氧化剂,包括丁羟茴香醚(BHA)、丁羟甲苯(BHT)、维生素A、类胡萝卜素、维生素E、类黄酮、多酚类、抗坏血酸、草本抗氧化剂、叶绿素、褪黑激素及其混合物。
在口腔护理实施方案中还可包含可用于例如改善口干的任选的唾液刺激剂。可使用任何口腔可接受的唾液刺激剂,非限制性地包括食品酸,比如柠檬酸、乳酸、苹果酸、琥珀酸、抗坏血酸、己二酸、富马酸和酒石酸及其混合物。一种或多种唾液刺激剂任选地以唾液刺激有效的总量存在。
任选地,在口腔护理实施方案中可包含抗菌斑(例如菌斑破坏)剂。可使用任何口腔可接受的抗菌斑剂,非限制性地包括亚锡、铜、镁和锶盐;二甲硅油共聚醇,比如十六烷基二甲硅油共聚醇;木瓜蛋白酶、葡糖淀粉酶、葡萄糖氧化酶、尿素、乳酸钙、甘油磷酸钙、聚丙烯酸锶及其混合物。
口腔护理实施方案中的任选的脱敏剂包括柠檬酸钾、氯化钾、酒石酸钾、碳酸氢钾、草酸钾、硝酸钾、锶盐及其混合物。在一些实施方案中,可使用局部或全身性镇痛剂比如阿司匹林、可待因、对乙酰氨基酚、水杨酸钠或水杨酸三乙醇胺盐。
在一些实施方案中,方法包括上述的用漱口剂组合物清洗口腔的步骤。在一些实施方案中,含漱5 ml或更多的组合物。在一些实施方案中,使用10 ml或者更多。在一些实施方案中,使用10-50 ml。在一些实施方案中,使用15-25 ml或者更多。在一些实施方案中,使用15 ml或者更多。在一些实施方案中,个体每天用组合物含漱多次。在一些实施方案中,个体用组合物含漱多天。在一些实施方案中,个体每天每4-6小时用组合物含漱最多6次。
从始至终使用的范围用作用于描述在该范围内的每个和每一个值的简写。可选择在该范围内的任何值作为范围的端点。此外,本文引用的所有参参考文献通过引用而全文结合到本文中。在本公开中的定义与引用的参考文献冲突的情况下,以本公开为准。
除非另外说明,否则本文和在说明书的其它地方表述的所有百分数和量应理解为指重量百分数。给出的量基于材料的活性重量。
实施例
实施例1:按需的(On Demand)漱口剂递送
将约0.3 g富马酸加入到具有25 mm滤嘴(5 μm膜)的3 ml注射器中。制备10 μg/ml刃天青的去离子水溶液。溶液的颜色为紫色,pH为约7。向注射器中加入2 ml紫色刃天青溶液,通过滤器分配并收集。所分配的溶液颜色为橙色,pH为约2.3。加载另外2 ml刃天青溶液,并通过相同的注射器分配。对于同一注射器将此重复第三次。用3种加载不同富马酸的注射器将整个实验重复3次。结果概述在下表中。
该实验显示,固定化的微溶性酸(在此为富马酸)可反复地降低液体的pH,从而活化液体,用卤色染料(刃天青)提供颜色变化。
Claims (27)
1.一种口腔护理、皮肤护理或家庭护理产品,所述产品包含具有以下的容器:
第一隔室,所述隔室含有包含固定化的微溶性酸的固体颗粒或基质,所述固定化的微溶性酸为富马酸,及第二隔室,
和任选地一个或多个另外的隔室,各含有未活化的液体,
使得在储存期间未活化的液体不与固定化的微溶性酸接触,并且使得从第二隔室分配液体需要将液体通过第一隔室,使得未活化的液体接触固定化的微溶性酸,借以改变液体的pH,从而活化液体,和
其中所述pH改变通过提供以下益处中的一种或多种而活化液体:矿物离子的利用度提高、包含碱性氨基酸和矿物离子的复合物在牙齿的沉积增强、酶的活性提高或酶底物的反应性提高、漂白剂的活性提高、用于口腔的pH更可接受、颜色变化、泡腾、风味变化或香味变化,其中所述未活化的液体为口腔可接受的漱口剂制剂。
2.前述权利要求中的任何一项的产品,其中所述未活化液体为包含有效量的氟化物的口腔可接受的漱口剂制剂。
3.权利要求1-2中任何一项的产品,其中所述未活化的液体为包含碱性氨基酸的口腔可接受的漱口剂制剂。
4.权利要求1-2中任何一项的产品,其中所述未活化的液体为包含选自以下的氨基酸的口腔可接受的漱口剂制剂: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、其盐和/或其组合。
5.权利要求1-2中任何一项的产品,其中所述未活化的液体为包含选自游离或盐形式的L-精氨酸的口腔可接受的漱口剂制剂。
6.权利要求3的产品,其中所述未活化的液体为包含选自精氨酸碳酸氢盐的碱性氨基酸的口腔可接受的漱口剂制剂。
7.权利要求1-2中任何一项的产品,其中所述未活化的液体为包含一种或多种钙盐的口腔可接受的漱口剂制剂。
8.权利要求1-2中任何一项的产品,其中所述未活化的液体包含响应pH变化而改变颜色的卤色染料。
9.权利要求8的产品,其中所述卤色染料选自刃天青、龙胆紫、隐色孔雀石绿、百里酚蓝、甲基黄、溴酚蓝、刚果红、甲基橙、溴甲酚绿、甲基红、石蕊精、溴甲酚紫、溴百里酚蓝、酚红、中性红、萘酚酞、甲酚红、酚酞、绣球花、花色素苷和石蕊。
10.权利要求1-2中任何一项的产品,其中所述未活化的液体包含在pH变化时转化为香料的香料前体,未活化液体的pH为碱性,使得当未活化液体的pH在使用时降低至中性或酸性pH时,(2,2-二甲氧基)乙基苯水解,提供苯乙醇。
11.权利要求10的产品,其中所述香料前体为在pH变化时快速水解提供香醇的酯或醚化合物。
12.权利要求10的产品,其中香料前体为(2,2-二甲氧基)乙基苯。
13.权利要求1-2中任何一项的产品,其中所述未活化的液体包含微粒基质中的调味剂、香料或其它成分,其中所述微粒基质包含在pH变化时崩解的聚合物。
14.权利要求1-2中任何一项的产品,其中所述未活化的液体包含微粒基质中的调味剂、香料或其它成分,其中所述微粒基质包含在pH变化时崩解的聚合物,其中未活化的液体具有酸性pH,和微粒基质包含在较高的pH下去质子化和崩解的多羧基化合物,从而释放调味剂、香料或其它成分。
15.权利要求14的产品,其中所述多羧基化合物选自丙烯酸酯聚合物或共聚物、丙烯酰氯-赖氨酸、醋酸羟丙基甲基纤维素琥珀酸酯。
16.权利要求1-2中任何一项的产品,其中所述未活化的液体包含选自碳酸盐、碳酸氢盐及其组合的盐,使得当未活化液体的pH在使用时降低时释放二氧化碳,引起泡腾。
17.权利要求1-2中任何一项的产品,其中所述未活化的液体包含选自碳酸氢钠或精氨酸碳酸氢盐的盐。
18.权利要求1-2中任何一项的产品,其中所述未活化的液体包含酶和酶底物,并且未活化液体的pH在酶对底物具有活性的范围之外。
19.权利要求1-2中任何一项的产品,其中所述酶为具有小于7的最佳pH范围的葡萄糖氧化酶,底物为葡萄糖,使得当未活化液体的pH在使用时降低时,产生过氧化氢。
20.权利要求1-2中任何一项的产品,其中所述固定化的微溶性酸为固体形式的酸。
21.权利要求1-2中任何一项的产品,其中所述未活化的液体包含一种或多种选自以下的试剂:氟化物、抗菌剂、精氨酸、甜菜碱、钾盐、调味剂、染料、湿润剂、聚合物和表面活性剂。
22.权利要求21的产品,其中所述抗菌剂选自三氯生或西吡氯铵;所述钾盐选自硝酸钾。
23.权利要求1-2中任何一项的产品,其中所述固定化的微溶性酸包含不溶性的液体渗透基质中的固体颗粒。
24.一种活化漱口剂的方法,所述方法包括在临用前使漱口剂与固定化的微溶性酸接触,以改变漱口剂的pH,从而活化漱口剂,所述固定化的微溶性酸为富马酸,
其中所述pH改变通过提供以下益处中的一种或多种而活化漱口剂:矿物离子的利用度提高、包含碱性氨基酸和矿物离子的复合物在牙齿的沉积增强、酶的活性提高或酶底物的反应性提高、漂白剂的活性提高、用于皮肤或口腔的pH更可接受、颜色变化、泡腾、风味变化或香味变化。
25.按照权利要求24活化的漱口剂在制备用于牙齿美白或清洁的产品中的用途,包括任选通过用活化的漱口剂将口腔清洗15秒-1分钟的时间段,然后吐出漱口剂,将按照权利要求24活化的漱口剂施用于口腔。
26.按照权利要求24活化的漱口剂在制备用于治疗口腔病况或者降低牙釉质的去矿化作用的药物中的用途,包括任选通过用活化的漱口剂将口腔清洗15秒-1分钟的时间段,然后吐出漱口剂,将按照权利要求24活化的漱口剂施用于口腔。
27.按照权利要求24活化的漱口剂在制备用于治疗牙龈炎、牙菌斑或口臭的药物中的用途,包括任选通过用活化的漱口剂将口腔清洗15秒-1分钟的时间段,然后吐出漱口剂,将按照权利要求24活化的漱口剂施用于口腔。
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US201161577555P | 2011-12-19 | 2011-12-19 | |
US61/577555 | 2011-12-19 | ||
PCT/US2012/070572 WO2013096425A2 (en) | 2011-12-19 | 2012-12-19 | Liquid activation system |
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CA (1) | CA2858257A1 (zh) |
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WO2014067933A1 (en) * | 2012-10-31 | 2014-05-08 | C-Lecta Gmbh | Bioactive carrier preparation for enhanced safety in care products and food |
EP3383357B1 (en) * | 2015-12-17 | 2021-07-21 | Colgate-Palmolive Company | Hydrogen peroxide booster system for enhanced teeth whitening |
JP7127524B2 (ja) * | 2018-12-18 | 2022-08-30 | ライオン株式会社 | 口腔用製品 |
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HK1201773A1 (zh) | 2015-09-11 |
CO6990715A2 (es) | 2014-07-10 |
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EP2790791B1 (en) | 2017-04-19 |
MX2014007340A (es) | 2014-09-15 |
CA2858257A1 (en) | 2013-06-27 |
US10238590B2 (en) | 2019-03-26 |
EP2790791A2 (en) | 2014-10-22 |
BR112014014811A2 (pt) | 2017-06-13 |
AU2012359083A1 (en) | 2014-06-19 |
TW201338791A (zh) | 2013-10-01 |
WO2013096425A2 (en) | 2013-06-27 |
JP2015500348A (ja) | 2015-01-05 |
MX346904B (es) | 2017-04-05 |
AU2012359083B2 (en) | 2015-11-26 |
PH12014501307A1 (en) | 2014-09-15 |
SG11201402538SA (en) | 2014-10-30 |
RU2014129870A (ru) | 2016-02-10 |
AR089312A1 (es) | 2014-08-13 |
US20150086487A1 (en) | 2015-03-26 |
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