• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
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  • 优先权
    • 专利摘要:
    a composition for oral hygiene comprising zinc phosphate, stannous fluoride, arginine or lysine and an organic acid buffer system, as well as methods of using it.
    公开号:BR112019012356B1
    申请号:R112019012356-3
    申请日:2017-08-10
    公开日:2021-03-23
    发明作者:Aarti Rege；Michael Prencipe；Marc ESTRIPLET
    申请人:Colgate-Palmolive Company；
    IPC主号:
    专利说明:

    [0001] [1] This order claims priority for U.S. Provisional Order No. 62 / 437,085, filed on December 21, 2016, the content of which is incorporated into this document by reference. FIELD OF THE INVENTION
    [0002] [2] The present invention relates to a composition for oral care for use in the treatment or prevention of erosive demineralization of the tooth, gingivitis, plaque and dental caries. This oral care composition includes zinc phosphate, stannous fluoride, arginine or lysine and an organic acid buffer system. BACKGROUND OF THE INVENTION
    [0003] [3] Dental erosion involves demineralization and damage to the tooth structure due to acid attack from non-bacterial sources. Erosion is found initially in the enamel and, if left unchecked, can progress to the underlying dentin. Dental erosion can be caused or exacerbated by acidic foods and drinks, exposure to chlorinated pool water and regurgitation of gastric acids.
    [0004] [4] Dental plaque is a biofilm or an adherent bacterial mass that is usually found between the teeth, along the gum line, and below the margins of the gum line. Dental plaque can cause tooth decay and periodontal problems such as gingivitis and periodontitis. Deterioration of the tooth caused by caries or demineralization of the tooth caused by the acid produced from the bacterial degradation of fermentable sugar
    [0005] [5] Compositions for oral care that contain sources of stannous ion exhibit excellent clinical benefits, in particular in reducing gingivitis and in preventing or treating erosive tooth demineralization. Stannous fluoride is well known for use in clinical dentistry, with a history of therapeutic benefits of more than forty years. However, until recently, its popularity has been limited by its instability in aqueous solutions. The instability of stannous fluoride in water is primarily due to the reactivity of stannous ion (Sn2 +). Stannous salts hydrolyze easily above pH 4, resulting in precipitation of the solution, with a consequent loss of therapeutic properties.
    [0006] [6] One way to overcome stability problems with stannous ions is to limit the amount of water in the composition to very low levels, or to use a two-phase system. Both of these solutions to the stannous ion problem have drawbacks. Compositions for oral care with low water content can be difficult to formulate with desired rheological properties, and biphasic compositions are considerably more expensive to manufacture and package.
    [0007] [7] Soluble zinc salts, such as zinc citrate, have been used in toothpaste compositions, but have several disadvantages. The zinc ions in the solution give an unpleasant and astringent feeling in the mouth, so formulations that provide effective levels of zinc and that also have acceptable organoleptic properties were difficult to obtain. In addition, free zinc ions can react with fluoride ions to produce zinc fluoride, which is insoluble and thus reduces the availability of zinc and fluoride. Finally, zinc ions will react with anionic surfactants, such as sodium lauryl sulfate, thus interfering with foaming and cleaning.
    [0008] [8] Zinc phosphate (Zn3 (PO4) 2) is insoluble in water, although it is soluble in acidic or basic solutions, for example, solutions of mineral acids, acetic acid, ammonia or alkaline hydroxides. See, for example, Merck Index, 13th Ed. (2001) p. 1812, monograph number 10205. In part, because it is seen in the art as a generally inert material, zinc phosphate is commonly used in dental cement, for example, in cementation of encrustations, crowns, bridges and orthodontic appliances, which are intended to last in your mouth for many years. Dental zinc phosphate cements are generally prepared by mixing zinc oxide and magnesium oxide powders with a liquid that consists mainly of phosphoric acid, water and buffers, thus, the cement comprising zinc phosphate is formed in situ by reaction with phosphoric acid.
    [0009] [9] Arginine-based toothpastes available on the market, for example, contain arginine bicarbonate and precipitated calcium carbonate, but do not contain fluoride. The carbonate ion is believed to have cariostatic properties, and calcium is believed to form in complex with arginine to provide a protective effect.
    [0010] [10] The formulation of certain oral care compositions presents special challenges. For example, oral care compositions comprising arginine or basic amino acids can have a basic pH, increasing the potential for microbial contamination compared to acidic formulations. In addition, not all condoms are active at high pH. Some condoms negatively affect the taste and aesthetics of the product. While certain condoms, such as ethanol or parabens, are known to have an effect over a pH range, these condoms are not suitable for all products or all markets.
    [0011] [11] Therefore, there is also a need to provide products containing enhanced tin ions to treat or prevent tooth enamel erosion with antimicrobial efficacy, reducing plaque or treating or controlling gingivitis. There is also a desire for new antimicrobial compositions that are stable in water and easy to manufacture. BRIEF SUMMARY
    [0012] [12] Oral care compositions comprising zinc phosphate, stannous fluoride, arginine or lysine and an organic acid buffer system are disclosed in this document. The methods and uses for this composition are also described throughout the document. The compositions disclosed herein in this document provide enhanced protection against demineralization and potentiation of stannous stability compared to the state of the art and certain market formulations, while also being able to offer benefits derived from arginine or lysine. In some embodiments, zinc phosphate is added to the toothpaste as a preformed salt. In some embodiments, the organic acid buffer system is a citric acid / citrate buffer system. In some embodiments, the oral care composition is a composition of toothpaste or a mouth gel.
    [0013] [13] Additional areas of applicability of this disclosure will become evident from the detailed description provided below. It should be understood that the detailed description and specific examples, while indicating the preferred mode of disclosure, are intended for purposes of illustration only and are not intended to limit the scope of the disclosure. DETAILED DESCRIPTION
    [0014] [14] The following description of the preferred mode (s) is merely exemplary in nature and is in no way intended to limit disclosure, its application or uses.
    [0015] [15] As used throughout the document, ranges are used as an abbreviation to describe each and every value that falls within the range. Any value within the range can be selected as the end of the range. In addition, all references cited in this document are incorporated in their entirety in this document by reference. In the event of a conflict in a definition in this disclosure and that cited as a reference, the definition of this disclosure will prevail.
    [0016] [16] Unless otherwise specified, all percentages and quantities expressed in this document and elsewhere in the specification should be understood as referring to the weight percentages of the total composition. The quantities supplied are based on the active weight of the material.
    [0017] [17] It has surprisingly been found that a high water content oral care composition comprising zinc phosphate, stannous fluoride, and an organic acid buffer system, selected in certain concentrations and quantities, is unexpectedly more effective in enhancing anti-erosive and antimicrobial properties of a formulation containing stannous ions when compared to formulations according to the prior art.
    [0018] [18] As used in this document, the term “high water content” refers to a composition for oral hygiene, such as a toothpaste or an oral gel, comprising 10% to 99% water, by weight of the composition . For example, the composition may comprise at least 10%, 15%, 20%, 25%, 30%, 35% or 40% water, up to a maximum, for example, 60%, of 70%, 80%, 90%, 95% or 99% water, by weight of the composition. As used in this document, the amounts of water refer to the water added directly to the composition, as well as the water added as part of the ingredients or components that are added as aqueous solutions. In some embodiments, the composition comprises 10-60% water, or 10-50% water, or 10-40% water, or 10-30% water, or 15-30% water, or 20-30 % water, or approximately 25% water, by weight of the composition.
    [0019] [19] As used in this document, the term “preformed salt” - when used in reference to zinc phosphate - means that zinc phosphate is not formed in situ in the oral hygiene composition, for example, through the reaction of phosphoric acid and another zinc salt.
    [0020] 1.1 Composição 1, em que o fosfato de zinco é um sal de fosfato de zinco pré-formado (por exemplo, hidrato de fosfato de zinco). 1.2 Composição 1 ou 1.2, em que o fosfato de zinco está presente em uma quantidade suficiente de modo que o fluoreto estanoso se dissocia para fornecer uma quantidade terapeuticamente eficaz de íons estanosos em solução aquosa. 1.3 Qualquer composição precedente, em que a quantidade de fosfato de zinco é de 0,05 a 10% em peso, relativa ao peso da composição para higiene bucal, por exemplo, de 0,1 a 8% em peso, ou de 0,5 a 5% em peso, ou de 0,5 a 4% em peso, ou de 1 a 4% em peso, ou de 1 a 3% em peso, ou de 2 a 3% em peso, ou cerca de 1%, ou cerca de 2%, ou cerca de 2,25%, ou cerca de 2,5% em peso. 1.4 Qualquer composição precedente, em que a quantidade de fluoreto estanoso é de 0,01% a 5% em peso, relativa ao peso da composição para higiene bucal, por exemplo, de 0,05 a 4% em peso, ou de 0,1% a 3% em peso, ou de 0,2 a 2% em peso, ou de 0,3 a 1% em peso, ou de 0,4 a 0,8% em peso, ou de 0,4 a 0,6% em peso, ou de 0,4 a 0,5% em peso, ou cerca de 0,45% em peso (por exemplo, 0,454% em peso). 1.5 Qualquer composição precedente, em que a quantidade de água é 10% em peso ou mais, em relação ao peso da composição para higiene bucal, por exemplo, 10-90%, ou 10- 80%, ou 10-70%, ou 10-60%, ou 10-50%, ou 10-40%, ou 10- 30%, ou 15-30% ou 20-30% ou cerca de 18 ou cerca de 25% em peso da composição. 1.6 Qualquer composição precedente, em que o sistema de tampão orgânico compreende um ácido carboxílico e um ou mais sais de base conjugados do mesmo, por exemplo, sais metálicos alcalinos do mesmo. 1.7 Composição 1.6, em que o ácido é selecionado dentre ácido cítrico, ácido lático, ácido málico, ácido maleico, ácido fumárico, ácido acético, ácido succínico, e ácido tartárico. 1.8 Composição 1.6 ou 1.7, em que o um ou mais sais de base conjugados são selecionados dentre sais de sódio e de potássio, ou combinações dos mesmos. 1.9 Composição 1.6, 1.7 ou 1.8 em que o ácido é ácido cítrico, e o um ou mais sais de base conjugados compreende citrato monossódico (monobásico), o citrato dissódico (dibásico), citrato trissódico (tribásico), e combinações dos mesmos. 1.10 Qualquer composição precedente, em que a composição compreende o sistema tampão de ácido orgânico em uma quantidade de 0,1 a 5,0% em peso da composição, medido como as quantidades combinadas de ácido orgânico e quaisquer sais de base conjugada; por exemplo, de 0,5 a 4,0%, ou de 1,0 a 3,0%, ou de 1,5 a 3,0%, ou de 1,0 a 2,4%, ou de 1,0% a 2,0% em peso da composição. 1.11 Qualquer composição precedente, em que o sistema de tampão consiste de um ácido orgânico e um sal de base conjugado do mesmo, por exemplo, em uma razão de 1:1 a 1:10, por exemplo, de 1:2 a 1:8, ou de 1:3 a 1:6, ou de 1:4 a 1:6, ou de 1:5 a 1:6, ou cerca de 1:5, em peso dos componentes. 1.12 Qualquer composição precedente, em que o sistema de tampão compreende por ácido cítrico e um sal de citrato de sódio (por exemplo, citrato trissódico, citrato dissódico ou citrato monossódico), em uma razão de 1:3 a 1:6 ou 1:4 a 1:6, ou cerca de 1:5 (por exemplo, cerca de 1:5,7), em peso. 1.13 Qualquer composição anterior, em que a composição para cuidado oral compreende, adicionalmente, um abrasivo, por exemplo, abrasivos de sílica, abrasivos de cálcio e outros abrasivos conforme divulgados neste documento. 1.14 Qualquer composição precedente que compreende ainda um ou mais umectantes, conforme descrito neste documento, por exemplo, selecionados dentre sorbitol, glicerol, xilitol e propilenoglicol, ou combinações dos mesmos. 1.15 Qualquer composição precedente que compreende ainda um ou mais surfactantes, conforme descrito neste documento, por exemplo, lauril sulfato de sódio, lauriléter sulfato de sódio, ou cocamidopropil betaína, ou combinações dos mesmos. 1.16 Qualquer composição anterior, compreendendo, adicionalmente, uma quantidade eficaz de um ou mais sais de fosfato alcalino, por exemplo, ortofosfatos, pirofosfatos, tripolifosfatos, tetrafosfatos ou polifosfatos maiores. 1.17 Composição 1.16, em que os sais de fosfato alcalinos compreendem pirofosfato tetrassódico ou pirofosfato tetrapotássico, por exemplo, em uma quantidade de 0,5 a 5% em peso da composição, por exemplo, 1-3% ou 1-2% ou cerca de 2% em peso. 1.18 Composição 1.16 ou 1.17, em que os sais de fosfato alcalinos compreendem tripolifosfato de sódio ou tripolifosfato de potássio, por exemplo, em uma quantidade de 0.5 a 6% em peso da composição, por exemplo, 1-4%, ou 2-3%, ou cerca de 3% em peso. 1.19 Qualquer uma das composições anteriores, compreendendo, adicionalmente, um agente clareador. 1.20 Qualquer composição anterior, compreendendo, adicionalmente, uma ou mais fontes de íons de zinco além do fosfato de zinco, por exemplo, um sal de zinco selecionado dentre citrato de zinco, óxido de zinco, lactato de zinco, pirofosfato de zinco, sulfato de zinco ou cloreto de zinco. 1.21 Qualquer composição precedente, compreendendo ainda uma ou mais fontes de fluoreto além da fonte de fluoreto estanoso, por exemplo, uma fonte de íon fluoreto selecionadas dentre: fluoreto de sódio, fluoreto de potássio, monofluorofosfato de sódio, fluorossilicato de sódio, fluorossilicato de amônio, fluoreto de amina e fluoreto de amônio e uma combinação dos mesmos. 1.22 Qualquer composição anterior, em que a composição para cuidado oral é um dentifrício, por exemplo, um creme dental ou gel para higiene bucal. 1.23 Qualquer composição precedente, em que o pH da composição é de 6 a 9, como de 6,5 a 8, ou de 6,5 a 7,5 ou cerca de 7,0. 1.24 Qualquer composição anterior, em que a composição é uma composição monofásica (por exemplo, não é uma composição bifásica). 1.25 Qualquer composição anterior, em que a composição não compreende um ou mais dentre óxido de zinco, citrato de zinco ou lactato de zinco. 1.26 Qualquer composição anterior, em que o fosfato de zinco é a única fonte de íons de zinco. 1.27 Qualquer composição precedente, em que a composição é essencialmente livre ou livre de fosfatos de mais de quatro grupos fosfato. 1.28 Qualquer composição precedente, em que a composição é essencialmente livre ou livre de fosfatos de mais de três grupos fosfato. 1.29 Qualquer composição precedente, em que a composição é essencialmente livre ou livre de sais do hexametafosfato (por exemplo, hexametafosfato de sódio). 1.30 Qualquer composição precedente, em que a composição é livre de copolímero metil vinil éter anidrido maleio. 1.31 Qualquer uma das composições anteriores, em que a composição é livre de polímero aniônico. 1.32 Qualquer uma das composições anteriores, em que a composição é eficaz mediante aplicação à cavidade oral, por exemplo, por meio de enxágue, opcionalmente em conjunto com escovação para (i) reduzir ou inibir a formação de cáries dentárias, (ii) reduzir, reparar ou inibir lesões pré-cariais no esmalte, por exemplo, como detectado pela fluorescência quantitativa induzida por luz (QLF) ou medição elétrica de cáries (ECM), (iii) reduzir ou inibir a desmineralização e promover a remineralização dos dentes, (iv) reduzir a hipersensibilidade dos dentes, (v) reduzir ou inibir a gengivite, (vi) promover a cicatrização de feridas ou cortes na boca, (v) reduzir os níveis de bactérias produtoras de ácido, (viii) aumentar os níveis relativos de bactérias arginolíticas, (ix) inibir a formação de biofilme microbiano na cavidade oral, (x) aumentar e/ou manter o pH das placas em níveis de pelo menos pH 5,5, seguido de exposição ao açúcar, (xi) reduzir acúmulo de placa, (xii) tratar, aliviar ou reduzir a boca seca, (xiii) limpar os dentes e a cavidade oral, (xiv) reduzir a erosão, (xv) prevenir manchas e/ou clarear os dentes, (xvi) imunizar os dentes contra bactérias cariogênicas; e/ou (xvii) promover a saúde sistêmica, incluindo a saúde cardiovascular, por exemplo, por meio da redução do potencial de infecção sistêmica através dos tecidos orais. 1.33 Qualquer uma das composições anteriores, em que a arginina ou lisina tem a configuração L (por exemplo, L-arginina). 1.34 Qualquer uma das composições anteriores que compreendem arginina na forma livre. 1.35 Qualquer uma das composições anteriores, em que a arginina ou lisina é fornecida na forma de um di ou tripeptídeo compreendendo arginina ou seus sais. 1.36 Qualquer das composições anteriores onde o aminoácido básico é arginina e em que a arginina está presente em uma quantidade correspondente a 1% para 15%, por exemplo, 3% a 10% em peso da composição, cerca de por exemplo, 1,5%, 4%, 5% ou 8%, onde o peso do aminoácido básico é calculado como forma livre. 1.37 Qualquer uma das composições anteriores, em que o aminoácido é arginina de 0,1% em peso - 6,0% em peso (por exemplo, cerca de 1,5% em peso). 1.38 Qualquer uma das composições anteriores, em que o aminoácido é arginina de cerca de 1,5% em peso. 1.39 Qualquer uma das composições anteriores que compreendem lisina na forma livre. 1.40 Qualquer uma das composições anteriores, em que o aminoácido básico é lisina e em que a lisina está presente em uma quantidade correspondente a 1% a 15%, por exemplo, 3% a 10% em peso da composição, cerca de por exemplo, 1,5%, 4%, 5% ou 8%, onde o peso do aminoácido básico é calculado como forma livre. 1.41 Qualquer uma das composições anteriores, em que o aminoácido é a lisina de 0,1% em peso - 6,0% em peso (por exemplo, cerca de 1,5% em peso). 1.42 Qualquer uma das composições anteriores, em que o aminoácido é a lisina de cerca de 1,5% em peso. [20] In one aspect, the present disclosure provides a high water content oral care composition (Composition 1) comprising an orally acceptable carrier, zinc phosphate and stannous fluoride, arginine or lysine and an organic acid buffer system. In other forms of this aspect, the present disclosure provides: 1.1 Composition 1, wherein zinc phosphate is a preformed zinc phosphate salt (for example, zinc phosphate hydrate). 1.2 Composition 1 or 1.2, in which the zinc phosphate is present in an amount sufficient so that the stannous fluoride dissociates to provide a therapeutically effective amount of stannous ions in aqueous solution. 1.3 Any preceding composition, in which the amount of zinc phosphate is 0.05 to 10% by weight, relative to the weight of the oral hygiene composition, for example, from 0.1 to 8% by weight, or from 0, 5 to 5% by weight, or from 0.5 to 4% by weight, or from 1 to 4% by weight, or from 1 to 3% by weight, or from 2 to 3% by weight, or about 1% , or about 2%, or about 2.25%, or about 2.5% by weight. 1.4 Any preceding composition, in which the amount of stannous fluoride is 0.01% to 5% by weight, relative to the weight of the oral hygiene composition, for example, 0.05 to 4% by weight, or 0, 1% to 3% by weight, or from 0.2 to 2% by weight, or from 0.3 to 1% by weight, or from 0.4 to 0.8% by weight, or from 0.4 to 0 , 6 wt%, or 0.4 to 0.5 wt%, or about 0.45 wt% (for example, 0.454 wt%). 1.5 Any preceding composition, in which the amount of water is 10% by weight or more, relative to the weight of the oral hygiene composition, for example, 10-90%, or 10-80%, or 10-70%, or 10-60%, or 10-50%, or 10-40%, or 10-30%, or 15-30% or 20-30% or about 18 or about 25% by weight of the composition. 1.6 Any preceding composition, in which the organic buffer system comprises a carboxylic acid and one or more conjugated base salts thereof, for example, alkali metal salts thereof. 1.7 Composition 1.6, in which the acid is selected from citric acid, lactic acid, malic acid, maleic acid, fumaric acid, acetic acid, succinic acid, and tartaric acid. 1.8 Composition 1.6 or 1.7, in which the one or more conjugated base salts are selected from sodium and potassium salts, or combinations thereof. 1.9 Composition 1.6, 1.7 or 1.8 in which the acid is citric acid, and the one or more conjugated base salts comprise monosodium citrate (monobasic), disodium citrate (dibasic), trisodium citrate (tribasic), and combinations thereof. 1.10 Any preceding composition, wherein the composition comprises the organic acid buffer system in an amount of 0.1 to 5.0% by weight of the composition, measured as the combined amounts of organic acid and any conjugated base salts; for example, from 0.5 to 4.0%, or from 1.0 to 3.0%, or from 1.5 to 3.0%, or from 1.0 to 2.4%, or from 1, 0% to 2.0% by weight of the composition. 1.11 Any preceding composition, in which the buffer system consists of an organic acid and a conjugated base salt thereof, for example, in a ratio of 1: 1 to 1:10, for example, from 1: 2 to 1: 8, or from 1: 3 to 1: 6, or from 1: 4 to 1: 6, or from 1: 5 to 1: 6, or about 1: 5, by weight of the components. 1.12 Any preceding composition, in which the buffer system comprises citric acid and a sodium citrate salt (for example, trisodium citrate, disodium citrate or monosodium citrate), in a ratio of 1: 3 to 1: 6 or 1: 4 to 1: 6, or about 1: 5 (e.g., about 1: 5.7), by weight. 1.13 Any prior composition, wherein the oral care composition further comprises an abrasive, for example, silica abrasives, calcium abrasives and other abrasives as disclosed in this document. 1.14 Any preceding composition that further comprises one or more humectants, as described in this document, for example, selected from sorbitol, glycerol, xylitol and propylene glycol, or combinations thereof. 1.15 Any preceding composition that further comprises one or more surfactants, as described in this document, for example, sodium lauryl sulfate, sodium lauryl ether sulfate, or cocamidopropyl betaine, or combinations thereof. 1.16 Any prior composition, additionally comprising an effective amount of one or more alkaline phosphate salts, for example, orthophosphates, pyrophosphates, tripolyphosphates, tetraphosphates or larger polyphosphates. 1.17 Composition 1.16, wherein the alkaline phosphate salts comprise tetrasodium pyrophosphate or tetrapotassium pyrophosphate, for example, in an amount of 0.5 to 5% by weight of the composition, for example, 1-3% or 1-2% or about 2% by weight. 1.18 Composition 1.16 or 1.17, wherein the alkaline phosphate salts comprise sodium tripolyphosphate or potassium tripolyphosphate, for example, in an amount of 0.5 to 6% by weight of the composition, for example, 1-4%, or 2-3 %, or about 3% by weight. 1.19 Any of the foregoing compositions, additionally comprising a bleaching agent. 1.20 Any prior composition, additionally comprising one or more sources of zinc ions in addition to zinc phosphate, for example, a zinc salt selected from zinc citrate, zinc oxide, zinc lactate, zinc pyrophosphate, zinc sulfate zinc or zinc chloride. 1.21 Any preceding composition, further comprising one or more fluoride sources in addition to the stannous fluoride source, for example, a fluoride ion source selected from: sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, sodium fluorosilicate , amine fluoride and ammonium fluoride and a combination thereof. 1.22 Any previous composition, where the oral care composition is a toothpaste, for example, a toothpaste or gel for oral hygiene. 1.23 Any preceding composition, where the pH of the composition is 6 to 9, such as 6.5 to 8, or 6.5 to 7.5 or about 7.0. 1.24 Any previous composition, where the composition is a monophasic composition (for example, it is not a biphasic composition). 1.25 Any prior composition, in which the composition does not comprise one or more of zinc oxide, zinc citrate or zinc lactate. 1.26 Any previous composition, in which zinc phosphate is the only source of zinc ions. 1.27 Any preceding composition, in which the composition is essentially free or free of phosphates from more than four phosphate groups. 1.28 Any preceding composition, in which the composition is essentially free or free of phosphates from more than three phosphate groups. 1.29 Any preceding composition, where the composition is essentially free or free of hexametaphosphate salts (for example, sodium hexametaphosphate). 1.30 Any preceding composition, in which the composition is free of copolymer methyl vinyl ether maleic anhydride. 1.31 Any of the above compositions, in which the composition is free of anionic polymer. 1.32 Any of the above compositions, in which the composition is effective upon application to the oral cavity, for example, by rinsing, optionally in conjunction with brushing to (i) reduce or inhibit the formation of dental caries, (ii) reduce, repair or inhibit pre-carious lesions on the enamel, for example, as detected by quantitative light-induced fluorescence (QLF) or electrical measurement of caries (ECM), (iii) reduce or inhibit demineralization and promote tooth remineralization, (iv ) reduce tooth hypersensitivity, (v) reduce or inhibit gingivitis, (vi) promote healing of wounds or cuts in the mouth, (v) reduce the levels of acid-producing bacteria, (viii) increase the relative levels of bacteria arginolytic, (ix) inhibit the formation of microbial biofilm in the oral cavity, (x) increase and / or maintain the pH of the plates at levels of at least pH 5.5, followed by exposure to sugar, (xi) reduce plaque accumulation , (xii) treat, relieve or reduce dry mouth, (xiii) cleaning teeth and oral cavity, (xiv) reducing erosion, (xv) preventing stains and / or whitening teeth, (xvi) immunizing teeth against cariogenic bacteria; and / or (xvii) promote systemic health, including cardiovascular health, for example, by reducing the potential for systemic infection through oral tissues. 1.33 Any of the above compositions, in which arginine or lysine has the L configuration (for example, L-arginine). 1.34 Any of the above compositions that comprise free form arginine. 1.35 Any of the foregoing compositions, wherein arginine or lysine is provided in the form of a di or tripeptide comprising arginine or its salts. 1.36 Any of the previous compositions where the basic amino acid is arginine and in which arginine is present in an amount corresponding to 1% to 15%, for example, 3% to 10% by weight of the composition, about for example, 1.5 %, 4%, 5% or 8%, where the weight of the basic amino acid is calculated as a free form. 1.37 Any of the foregoing compositions, wherein the amino acid is arginine of 0.1% by weight - 6.0% by weight (for example, about 1.5% by weight). 1.38 Any of the above compositions, in which the amino acid is arginine of about 1.5% by weight. 1.39 Any of the above compositions which comprise free form lysine. 1.40 Any of the above compositions, in which the basic amino acid is lysine and in which the lysine is present in an amount corresponding to 1% to 15%, for example, 3% to 10% by weight of the composition, about for example, 1.5%, 4%, 5% or 8%, where the weight of the basic amino acid is calculated as a free form. 1.41 Any of the above compositions, where the amino acid is lysine of 0.1% by weight - 6.0% by weight (for example, about 1.5% by weight). 1.42 Any of the above compositions, where the amino acid is lysine of about 1.5% by weight.
    [0021] [21] Any amount of zinc phosphate that is effective to protect against enamel erosion and / or provide any other benefits described in this document can be employed. Examples of suitable amounts of zinc phosphate can vary from 0.05 to 5% by weight, such as from 0.1 to 4% by weight, or from 0.5 to 3% by weight, or from 0.5 to 2 % by weight, or from 0.8 to 1.5% by weight, or from 0.9 to 1.1% by weight, or about 1% by weight relative to the weight of the oral hygiene composition.
    [0022] [22] Although zinc phosphate is considered insoluble (for example, poor solubility) in water, when placed in the formulation, for example, at acidic or basic pH, zinc phosphate can dissolve sufficiently after use to provide an effective concentration of zinc ions in relation to the enamel, thus protecting against erosion, reducing bacterial colonization and the development of biofilm and providing more shine to the teeth. It was also found that zinc phosphate in a formulation with a second phosphate source intensifies the phosphate deposit. As explained in WO2014 / 088573, whose disclosure is incorporated by reference in its entirety by reference in its entirety, due to the low solubility of zinc phosphate, and the view recognized by the technique that it is substantially inert in the conditions of the oral cavity, as evidenced by its widespread use in dental cement. At the same time, formulations containing zinc phosphate do not have a bad taste and feel in the mouth, low fluoride distribution and little foam and poor cleaning in combination with conventional zinc-based oral care products, which use more soluble zinc salts .
    [0023] [23] An amount of stannous fluoride, preferably an effective amount, is used in combination with zinc phosphate in the compositions of the present disclosure. For example, stannous fluoride can be used in an amount that is effective to provide antimicrobial benefits, such as anti-cavity protection and / or anti-gingivitis protection and / or anti-erosion benefits for the protection of tooth enamel. Examples of suitable amounts of stannous fluoride range from 0.01% to 5% by weight, relative to the weight of the oral hygiene composition, for example, from 0.05 to 4% by weight, or from 0.1% to 3% by weight, or from 0.2 to 2% by weight, or from 0.3 to 1% by weight, or from 0.4 to 0.8% by weight, or from 0.4 to 0.6% by weight , or 0.4 to 0.5% by weight, or about 0.45% by weight (e.g. 0.454%), relative to the total weight of the toothpaste composition. The formulations can include stannous levels, provided by stannous fluoride, varying, for example, from 3,000 ppm to 15,000 ppm (mass fraction) of stannous ions in the total composition. In embodiments, the soluble stannous content can vary from 0.1% by weight to 0.5% by weight or more, such as from 0.15% by weight to 0.32% by weight, based on the total weight of the composition .
    [0024] [24] The combination of zinc and stannous ions provides one or more of the following benefits: improved antimicrobial benefits compared to zinc ions alone; improved control of plaque and / or gingivitis; improved protection against tooth enamel erosion.
    [0025] [25] In compositions that comprise significant amounts of water, zinc phosphate acts as a stabilizing agent for stannous fluoride, so that stannous fluoride remains in solution in water. As discussed above, stannous fluoride is generally considered unstable in water due to the hydrolytic and oxidative loss of stannous ions in the typical pH ranges used in oral hygiene compositions. Consequently, stannous fluoride is generally used in compositions that contain no water or little water, or with a chelating agent. Tedious procedures are employed to provide stable solutions in which the tendency of the stannous ion to be oxidized or hydrolyzed is inhibited. Depositors have surprisingly found that zinc phosphate and stannous fluoride can be combined in a single-phase formulation and stabilized by the presence of an appropriate organic acid buffer system. The organic acid buffer system helps to solubilize zinc phosphate and helps to stabilize soluble stannous ions.
    [0026] [26] The compositions may optionally comprise additional ingredients suitable for use in oral hygiene compositions. Examples of such ingredients include active agents, such as a source of fluoride and / or a source of phosphate, in addition to zinc phosphate. The compositions can be formulated on a suitable toothpaste base, for example, comprising abrasives, for example, silica abrasives, surfactants, foaming agents, vitamins, polymers, enzymes, humectants, thickeners, additional antimicrobial agents, preservatives, flavorings, dyes and / or combinations of these. Examples of suitable toothpaste bases are known in the art. Alternatively, the compositions can be formulated as a gel (for example, for use in a tray), chewing gum, lozenge or lozenge against bad breath. Examples of suitable additional ingredients that can be employed in the compositions of the present disclosure are discussed in more detail below.
    [0027] [27] Active Agents: The compositions of the disclosure may comprise several other agents that are active to protect and enhance the strength and integrity of the enamel and tooth structure and / or reduce bacteria and associated tooth decay and / or gum disease or provide other desired benefits. The effective concentration of the active ingredients used in this document will depend on the specific agent and the distribution system used. The concentration will also depend on the exact salt or polymer selected. For example, when the active agent is provided in the form of salt, the counterion will affect the weight of the salt, so that if the counterion is heavier, more salt by weight will be required to provide the same concentration of active ion. in the final product.
    [0028] [28] Compositions of the disclosure may contain from 0.1 to 1% by weight of an antibacterial agent, such as about 0.3% by weight. Any suitable antimicrobial assets can be employed.
    [0029] [29] Basic Amino Acids
    [0030] [30] Basic amino acids can be used in compositions and methods of the invention that include not only naturally occurring basic amino acids such as arginine, lysine and histidine, but also some basic amino acids that have a carboxyl group and an amino group in the molecule which are water-soluble and provide an aqueous solution with a pH of approximately 7 or greater.
    [0031] [31] For example, basic amino acids may include, but are not limited to, arginine, lysine, citrulline, ornithine, creatine, histidine, diaminobutanoic acid, diaminopropionic acid, salts thereof and combinations thereof. In a specific embodiment, the basic amino acids are selected from arginine, lysine and histidine.
    [0032] [32] In certain embodiments, the basic amino acid is arginine or lysine, for example, L-arginine or salts thereof.
    [0033] [33] The compositions of the invention are intended for topical use in the mouth just as the salts for use in the present invention must be safe for such use, in the quantities and concentrations provided. Suitable salts include salts known in the art to be pharmaceutically acceptable salts are generally considered to be physiologically acceptable in the amounts and concentrations provided. Physiologically acceptable salts include those derived from pharmaceutically acceptable organic or inorganic acids or bases, for example, acid addition salts formed by acids that form a physiologically acceptable anion, for example, hydrochloride or bromide salt and basic addition salts formed by bases that they form a physiologically acceptable cation, for example, those derived from alkali metals like potassium and sodium or alkaline earth metals like calcium and magnesium. Physiologically acceptable salts can be obtained using standard procedures known in the art, for example, by reacting a sufficiently basic compound such as an amine with a suitable acid, generating a physiologically acceptable anion.
    [0034] [34] Fluoride Ion Source: Oral care compositions may include one or more additional fluoride ion sources, for example, soluble fluoride salts. A wide variety of fluoride ion generating materials can be used as sources of soluble fluoride in the present compositions. Examples of suitable fluoride ion generating materials are found in U.S. Pat. No. 3,535,421, by Briner et al .; Pat. No. 4,885,155, by Parran, Jr. et al. and Pat. No. 3,678,154, by Widder et al., The disclosures of which are incorporated herein by reference in their entirety. Representative fluoride ion sources include, but are not limited to, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride and combinations thereof. In certain embodiments, the fluoride ion source includes sodium fluoride, sodium monofluorophosphate as well as mixtures thereof. In certain embodiments, the oral care composition of the disclosure may contain stannous fluoride and any additional sources of fluoride ions or fluoride-providing agents in sufficient quantities to provide a total of about 25 ppm to about 25,000 ppm (mass fraction) of fluoride ions, generally at least 500 ppm, for example, from 500 to 2000 ppm, for example, from 1000 to 1600 ppm, for example, about 1450 ppm. The appropriate level of fluoride will depend on the particular application. A toothpaste for use by the general consumer would typically range from 1000 to about 1500 ppm, with pediatric toothpaste having slightly less. A professional toothpaste or coating could contain up to 5,000 or even about 25,000 ppm of fluoride. Fluoride ion sources can be added to the compositions of the disclosure at a level of about 0.01% by weight to 10% by weight in one embodiment or about 0.03% by weight to 5% by weight and in another embodiment from about 0.1% by weight to 1% by weight of the composition. As discussed above, the weights of the fluoride salts to provide the appropriate level of fluoride ion will vary based on the weight of the counterion in the salt.
    [0035] [35] Abrasives: The compositions of the disclosure may include abrasives. Examples of suitable abrasives include silica abrasives, such as standard cleaning silicas, high cleaning silicas and / or any other suitable abrasive silicas. Additional examples of abrasives that can be used in addition to or in place of silica abrasives include, for example, a calcium phosphate abrasive, for example, tricalcium phosphate (Ca3 (PO4) 2), hydroxyapatite (Ca10 (PO4) 6 (OH ) 2), or dihydrated dicalcium phosphate (CaHPO4 • 2H2O, also occasionally referred to in this document as DiCal) or calcium pyrophosphate; calcium carbonate abrasive; or abrasives, such as sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, bentonite or other siliceous materials, or combinations thereof.
    [0036] [36] The silica abrasive polishing materials useful in this document, as well as other abrasives, generally have an average particle size ranging between 0.1 and 30 microns, such as between 5 and 15 microns. The silica abrasives can be precipitated silica or silica gels, such as the silica xerogels described in U.S. Patent No. 3,538,230, to Pader et al. and U.S. Patent No. 3,862,307, to Digiulio, the disclosures of which are incorporated herein by reference in their entirety. Particulate silica xerogels are marketed under the trade name Syloid® by W. R. Grace & Co., Davison Chemical Division. Precipitated silica materials include those marketed by J. M. Huber Corp. under the trade name of Zeodent®, including silica with the designation Zeodent 115 and 119. Such silica abrasives are described in U.S. Pat. No. 4,340,583, by Watson, the disclosure of which is incorporated herein by reference in its entirety. In certain embodiments, abrasive materials useful in the practice of oral hygiene compositions, according to the disclosure, include silica gels and precipitated amorphous silica, with an oil absorption value of less than 100 cm³ / 100 g of silica, such as 45 cm³ / 100 g to 70 cm³ / 100 g of silica. Oil absorption values are measured using the ASTA Rub-Out D281 method. In certain embodiments, silicas are colloidal particles with an average particle size of 3 microns to 12 microns, and 5 to 10 microns. Examples of low oil absorption silica abrasives useful in the practice of disclosure are marketed under the trade name Sylodent XWA® by Davison Chemical Division of W.R. Grace & Co., Baltimore, Md. 21203. Sylodent 650 XWA®, a silica hydrogel composed of colloidal silica particles with a water content of 29% by weight, on average 7 to 10 microns in diameter, and an absorption of oil less than 70 cm³ / 100 g of silica is an example of a silica abrasive with low oil absorption useful in the practice of the present disclosure.
    [0037] [37] Any suitable amount of silica abrasive can be used. Examples of suitable amounts include 10% by weight or more dry weight of silica particles, such as 15% by weight to 30% by weight or 15% by weight to 25% by weight based on the total weight of the composition.
    [0038] [38] Foaming agents: The oral care compositions of the disclosure may also include an agent to increase the amount of foam that is produced when the oral cavity is brushed. Illustrative examples of agents that increase the amount of foam include, but are not limited to, polyoxyethylene and certain polymers including, but not limited to alginate polymers. Polyoxyethylene can increase the amount of foam and the foam thickness generated by the oral care compositions of the present disclosure. Polyoxyethylene is also commonly known as polyethylene glycol ("PEG") or polyethylene oxide. Polyoxyethylene suitable for compositions of the present disclosure can have a molecular weight of 200,000 to 7,000,000. In one embodiment, the molecular weight can be from 600,000 to 2,000,000 and in another modality from 800,000 to 1,000,000. Polyox® is the trade name for the high molecular weight polyoxyethylene produced by Union Carbide. The foaming agent (eg polyoxyethylene) can be present in an amount of 0, 1% to 50%, in a mode of 0.5% to 20% and, in another mode, from 1% to 10%, or from 2% to 5% by weight of the oral care compositions of the present disclosure.
    [0039] i. sais solúveis em água de monossulfatos de monoglicerídeo de ácido graxo superiores, tais como o sal de sódio do monoglicerídeo monossulfatado de ácidos graxos de óleo de coco hidrogenado, tais como N-metil N-cocoil taurato de sódio, cocomonoglicerídeo sulfato de sódio, ii. alquil sulfatos superiores, tais como lauril sulfato de sódio, iii. alquil éter sulfatos superiores, por exemplo, de fórmula CH3(CH2)mCH2(OCH2CH2)nOSO3X, em que m é 6-16, por exemplo, 10, n é 1-6, por exemplo, 2, 3 ou 4, e X é Na ou K, por exemplo, lauril éter2 sulfato de sódio (CH3(CH2)10CH2(OCH2CH2)2OSO3Na), iv. alquil aril sulfonatos superiores, tais como dodecil benzeno sulfonato de sódio (lauril benzeno sulfonato de sódio), v. alquil sulfoacetatos superiores, tais como lauril sulfoacetato de sódio (dodecil sulfoacetato de sódio), ésteres de ácido graxo superiores de 1,2-di-hidroxi propano sulfonato, sulfocolaurato (N-2-etil laurato sulfoacetamida de potássio) e lauril sarcosinato de sódio. [39] Surfactants: Compositions useful in the compositions of the present disclosure may contain anionic surfactants, for example: i. water-soluble salts of higher fatty acid monoglyceride monosulfates, such as the sodium salt of the monoglyceride monoglyceride of hydrogenated coconut oil fatty acids, such as sodium N-methyl N-cocoyl taurate, sodium sulfate cocomonoglyceride, ii. higher alkyl sulfates, such as sodium lauryl sulfate, iii. higher alkyl ether sulfates, for example, of the formula CH3 (CH2) mCH2 (OCH2CH2) nOSO3X, where m is 6-16, for example, 10, n is 1-6, for example, 2, 3 or 4, and X is Na or K, for example, sodium lauryl ether 2 sulfate (CH3 (CH2) 10CH2 (OCH2CH2) 2OSO3Na), iv. higher alkyl aryl sulfonates, such as sodium dodecyl benzene sulfonate (sodium lauryl benzene sulfonate), v. higher alkyl sulfoacetates, such as sodium lauryl sulfoacetate (sodium dodecyl sulfoacetate), higher fatty acid esters of 1,2-dihydroxy propane sulfonate, sulfocolaurate (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl sarcosinate .
    [0040] [40] "Upper alkyl" means, for example, C6-30 alkyl. In certain embodiments, the anionic surfactants useful in this document include the water-soluble salts of alkyl sulfates with 10 to 18 carbon atoms in the alkyl radical and the water-soluble salts of sulfonated monoglycerides of fatty acids with 10 to 18 carbon atoms. Sodium lauryl sulfate, sodium lauroyl sarcosinate and coconut monoglyceride sodium sulfonates are examples of such anionic surfactants. In particular modalities, the anionic surfactant is selected from sodium lauryl sulfate and sodium lauryl ether sulfate. In one embodiment, the compositions of the disclosure comprise sodium lauryl sulfate. The anionic surfactant can be present in an amount that is effective, for example, ˃0.01% by weight of the formulation, but not in a concentration that would irritate the oral tissue, for example, ˂10%, and ideal concentrations depend on the formulation and the particular surfactant. In one embodiment, the anionic surfactant is present in a toothpaste from 0.3% to 4.5% by weight, for example, about 1.5%. The compositions of the disclosure may optionally contain mixtures of surfactants, for example, comprising anionic surfactants and other surfactants which may be anionic, cationic, zwitterionic or non-ionic. In general, suitable surfactants are those that are reasonably stable over a wide pH range. Surfactants are more fully described, for example, in U.S. Pat. No. 3,959,458, by Agricola et al .; Pat. No. 3,937,807, to Haefele; and Pat. No. 4,051,234, by Gieske et al, the disclosures of which are incorporated herein by reference in their entirety.
    [0041] [41] The surfactant or mixtures of compatible surfactants that are included in addition to anionic surfactants may be present in the compositions of the present disclosure from 0.1% to 5.0%, in another modality from 0.3% to 3.0% and, in another modality, from 0.5% to 2.0% by weight of the total composition. These variations do not include the amounts of anionic surfactant.
    [0042] [42] In some embodiments, the compositions of the present disclosure include a zwitterionic surfactant, for example a betaine surfactant, for example cocamidopropyl betaine, for example, in an amount of 0.1% to 4.5% by weight, for example, 0.5 to 2% by weight of cocamidopropyl betaine.
    [0043] [43] Tartar control agents: In various embodiments of the present disclosure, the compositions comprise an anti-calculating agent (tartar control). Suitable anticalculating agents include, without limitation, phosphates and polyphosphates (e.g., pyrophosphates and tripolyphosphates), polyaminopropanesulfonic acid (AMPS), hexametaphosphate salts, zinc citrate trihydrate, polypeptides, polyolefin sulfates, polyolefin phosphates and polyolefin phosphates and polyolefin phosphates. The compositions of the disclosure can thus comprise phosphate salts, in addition to zinc phosphate. In particular embodiments, these salts are alkaline phosphate salts, for example, alkali metal hydroxide salts or alkaline earth hydroxides, for example, sodium, potassium or calcium salts. "Phosphate" as used in this document covers orally acceptable mono- and polyphosphates, for example, P1-6 phosphates, for example, monomeric phosphates, such as monobasic, dibasic or tribasic phosphate; and dimeric phosphates, such as pyrophosphates; and multimeric phosphates; , such as tripolyphosphates, tetraphosphates, hexaphosphates and hexametaphosphates (eg sodium hexametaphosphate). In particular examples, the selected phosphate is selected from dibasic alkaline phosphate and alkaline pyrophosphate salts, eg selected from dibasic sodium phosphate, phosphate dibasic potassium, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate and mixtures of any two or more of these. 0.5 to 5% by weight, for example, 1-3%, or 1-2% or about 2% by weight of the composition. In another embodiment, the compositions may comprise a mixture of tetrasodium pyrophosphate (TSPP) and sodium tripolyphosphate (STPP), for example, in TSPP ratios of 0.5 to 5% by weight, such as 1 to 2% by weight and STPP from 0.5% to 6% by weight, such as from 1 to 4%, or from 2 to 3% by weight of the composition. Such phosphates are supplied in an effective amount to reduce enamel erosion, to assist in cleaning teeth and / or to reduce the accumulation of tartar on teeth, for example, in an amount of 0.2 to 20% by weight, for example. example, from 1 to 15% by weight of the total composition.
    [0044] [44] Flavorings: The oral care compositions of the disclosure may also include a flavoring. Flavorings that are used in the practice of the present disclosure include, but are not limited to, essential oils, as well as various aldehydes, esters, flavoring alcohols and similar materials. Examples of essential oils include common mint, peppermint, gualtéria, sassafras, clover, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit and orange oils. Chemicals such as menthol, carvone and anethole are also useful. Certain modalities use peppermint and common mint oils. Flavorings can be incorporated into the oral composition in a concentration of 0.1 to 5% by weight, for example, from 0.5 to 1.5% by weight.
    [0045] [45] Polymers: The oral care compositions of the disclosure may also include additional polymers to adjust the viscosity of the formulation or to enhance the solubility of other ingredients. Such additional polymers include polyethylene glycols, polysaccharides (for example cellulose derivatives, for example, carboxymethyl cellulose, hydroxymethyl cellulose, ethyl cellulose, microcrystalline cellulose or polysaccharide gums, for example, xanthan gum, guar gum or carrageenan gum). Acid polymers, for example, polyacrylate gels, can be provided in the form of their free acids, or partially soluble or totally neutralized water-soluble alkali metal (eg, potassium and sodium) or ammonium salts. In one embodiment, the oral care composition may contain PVP. In general, PVP refers to a polymer that contains vinylpyrrolidone (also referred to as N-vinylpyrrolidone, N-vinyl-2-pyrrolidone and N-vinyl-2-pyrrolidone) as a monomeric unit. The monomeric unit consists of a polar imide group, four non-polar methylene groups and a non-polar methane group.
    [0046] [46] In some embodiments, the compositions of the description comprise one or more polyethylene glycols, for example, polyethylene glycols in a molecular weight range of 200 to 800. For example, the compositions may comprise one or more of polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, or polyethylene glycol 800.
    [0047] [47] Silica thickeners, which form polymeric structures or gels in aqueous media, may be present. Note that these silica thickeners are physically and functionally distinct from the particulate silica abrasives, also present in the compositions, since the silica thickeners are divided very finely and provide little or no abrasive action. Other thickening agents are polymers of carboxyvinyl, carrageenan, hydroxyethyl cellulose and water soluble salts of cellulose ethers, such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums, such as karaya, gum arabic and tragacanth gum, can also be incorporated. Colloidal aluminum and magnesium silicate can also be used as a component of the thickener composition to further improve the texture of the composition. In certain embodiments, thickening agents in an amount of 0.5% to 5.0% by weight of the total composition are used.
    [0048] [48] In some embodiments, the compositions of the disclosure may include an anionic polymer, for example, in an amount of 0.05 to 5%. Examples of such agents, in general, known for use in dentifrice are disclosed in U.S. Pat. U.S. 5,188,821 and 5,192,531, both of which are incorporated herein by reference in their entirety; and include synthetic anionic polymeric polycarboxylates, such as 1: 4 to 4: 1 copolymers of maleic anhydride or acid with another polymerisable ethylenically unsaturated monomer, preferably methyl vinyl ether / maleic anhydride with a molecular weight (MW) of 30,000 to 1,000. 000, such as 300,000 to 800,000. These copolymers are available, for example, as Gantrez, for example, AN 139 (MW 500,000), AN 119 (MW 250,000) and, preferably, Pharmaceutical Grade S-97 (MW 700,000) available from ISP Technologies, Inc., Bound Brook , NJ 08805. Potentiating agents, when present, are present in amounts ranging from 0.05 to 3% by weight. Other operational polymers include those, such as 1: 1 maleic anhydride copolymers with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or ethylene, the latter being available, for example, as Monsanto EMA no. 1103, M.W. 10,000 and EMA Grade 61, and 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone. Generally suitable, are olefinically or ethylenically polymerized unsaturated carboxylic acids containing an activated carbon-to-carbon olefinic double bond and at least one carboxyl group, that is, an acid containing an olefinic double bond that readily works in polymerization due to its presence in the polymerization molecule. monomer, in the alpha-beta position in relation to a carboxyl group or as part of a terminal methylene group. Illustrative of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic, alpha-chlorosorbic, cinnamic, beta-styrylacrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, alphaacrylic, acacitic, alpha-chloric, phenacrylic, alpha-chloroacetic, alpha-chloroacetic. , 2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbilic, fumaric, maleic acids and anhydrides. Other olefinic monomers other than copolymerizable, with such carboxylic monomers, include vinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymers contain sufficient carboxylic salt groups for solubility in water. An additional class of polymeric agents includes a composition containing substituted acrylamide homopolymers and / or unsaturated sulfonic acid homopolymers and salts thereof, in particular where the polymers are based on unsaturated sulfonic acids selected from acrylamidoalkane sulfonic acids, such as 2-acrylamide, acid Sulfonic 2-methylpropane, with a molecular weight of 1,000 to 2,000,000. Another useful class of polymeric agents includes polyamino acids containing proportions of anionic surfactant amino acids, such as aspartic acid, glutamic acid and phosphoserine, for example, as disclosed in Pat. No. 4,866,161, issued to Sikes et al., Which is incorporated herein by reference in its entirety.
    [0049] [49] In some embodiments, there are no anionic polymers present in the composition. In other embodiments, anionic polymers may be present, but these do not include copolymers of methyl vinyl ether and maleic acid or anhydride.
    [0050] [50] Humectants: Within certain modalities of oral compositions, it is also desirable to incorporate a humectant to prevent the composition from hardening after exposure to air. Certain humectants can also impart desirable sweetness or flavor to toothpaste compositions. Suitable humectants include edible polyhydric alcohols, such as glycerin, sorbitol, xylitol, propylene glycol, as well as other polyols and mixtures of these humectants. In a disclosure modality, the main humectant is one of glycerin, sorbitol or a combination of these. The humectant can be present at levels greater than 15% by weight, such as from 15% by weight to 55% by weight or from 20% by weight to 50% by weight or from 20% by weight to 40% by weight or about 20%, or about 30%, or about 40%, based on the total weight of the composition.
    [0051] [51] Other Optional Ingredients: In addition to the components described above, the modalities of this disclosure may contain a variety of optional oral care ingredients, some of which are described below. Optional ingredients include, for example, but are not limited to adhesives, foaming agents, flavorings, sweetening agents, such as sodium saccharin, additional anti-plaque, abrasive, aesthetic agents, such as TiO2-coated mica or other coloring agents, such as dyes and / or pigments.
    [0052] [52] In some embodiments, the compositions of the present disclosure may have any pH suitable for a product for use in oral hygiene. Examples of suitable pH ranges range from 6 to 9, such as 6.5 to 8, or 6.5 to 7.5, or about 7.0.
    [0053] [53] In some embodiments, the oral care compositions of the present disclosure are essentially free of, are free of, or do not include any sodium hexametaphosphate. In some embodiments, the oral care compositions of the present disclosure are essentially free of, are free of, or do not include any halogenated diphenyl ethers (e.g., triclosan).
    [0054] [54] By "essentially free" are compositions that have no more than 0.01% by weight of these compounds.
    [0055] [55] In some embodiments, the compositions of the present disclosure are essentially free of, are free of, or do not include any complexing agents to improve the solubility of zinc phosphate and / or keep the stannous fluoride in solution. Examples of known complexing agents that can be excluded from the compositions of the present disclosure include the chelating agents taught in U.S. Patent Application No. 2007/0025928, the disclosure of which is incorporated by reference in this document in its entirety. Such chelating agents include mineral surfactants, including mineral surfactants which are polymeric and / or polyelectrolytes and which are selected from phosphorylated polymers, where, if the phosphorylated polymer is a polyphosphate, the polyphosphate has an average chain length of 3.5 or more, such as 4 or more; polyphosphonates; polycarboxylates; polymers replaced by carboxy; monomer copolymers containing phosphate or phosphonate, or polymers with ethylenically unsaturated monomers, amino acids, proteins, polypeptides, polysaccharides, poly (acrylate), poly (acrylamide), poly (methacrylate), poly (ethacrylate), poly (hydroxyalkyl) methacrylate vinyl alcohol), poly (maleic anhydride), poly (maleate) poly (amide), poly (ethyleneamine), poly (ethylene glycol), poly (propylene glycol), poly (vinyl acetate) and poly (benzyl vinyl chloride); and mixtures of these. Other known complexing agents that may be excluded from the present disclosure include those taught in CA 2634758, the disclosure of which is incorporated by reference in this document in its entirety. Examples include polyphosphorylated inositol compounds, such as phytic acid, myo-inositol pentaquis (dihydrogen phosphate); myo-inositol tetrakis (dihydrogen phosphate), myo-inositol trichis (dihydrogen phosphate) and alkali metal, alkaline earth metal or ammonium salts of any of the above inositol compounds. Phytic acid is also known as myo-inositol 1,2,3,4,5,6-hexakis (dihydrogen phosphate) or inositol hexaphosphoric acid.
    [0056] [56] In another aspect, the present disclosure provides a method of treating or preventing erosive demineralization of the tooth, gingivitis, plaque, and / or dental caries, the method comprising application to a person's oral cavity in a such a need for a composition according to the invention (for example, Composition 1.0 et seq), for example, by brushing, for example, one or more times a day.
    [0057] [57] In another aspect, the current disclosure provides a method for using the compositions described in this document (for example, any of Compositions 1.0 et seq) to increase zinc levels in the enamel and to treat, reduce or control the incidence of enamel erosion. The methods comprise applying any of the compositions as described in this document to the teeth, for example, by brushing or otherwise administering the compositions to the oral cavity of a subject who needs them. The compositions can be administered regularly, such as, for example, one or more times a day. In various embodiments, administering the compositions of the present disclosure to a patient can provide one or more of the following benefits: (i) to reduce tooth hypersensitivity, (ii) to reduce plaque buildup, (iii) to reduce or inhibit tooth decay. demineralization and promote remineralization of teeth, (iv) inhibit the formation of microbial biofilm in the oral cavity, (v) reduce or inhibit gingivitis, (vi) promote healing of wounds or cuts in the mouth, (vii) reduce levels of bacteria acid-producing, (viii) increase the relative levels of non-cariogenic and / or non-plaque forming bacteria, (ix) reduce or inhibit the formation of dental caries, (x) reduce, repair or inhibit enamel lesions prior to caries, for example, as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM), (xi) treating, relieving or reducing dry mouth, (xii) cleaning teeth and oral cavity, (xiii) reducing erosion, (xiv) whitening teeth; (xv) reduce the accumulation of tartar and / or (xvi) promote systemic health, including cardiovascular health, for example, reducing the potential for systemic infection through oral tissues. The disclosure further provides compositions for use in any of the above methods. Other modalities provide methods in which at least one tooth is remineralized after administration of the composition as described in that document.
    [0058] [58] The present application further discloses a method for making any of the compositions of the present disclosure. The method comprises combining zinc phosphate and stannous fluoride in water to form an aqueous mixture of zinc phosphate. In some embodiments, zinc phosphate is added to the toothpaste composition as a preformed salt and remains essentially insoluble in the aqueous mixture. The amount of water used in the mixture can be any of the amounts quoted in this document for the compositions of the present disclosure. All standard mixing techniques can be employed to combine the ingredients and form a stable composition without the need for additional complexing agents to solubilize stannous fluoride, such as any of the complexing agents or chelating agents disclosed above, or the use of anhydrous mixing techniques, such as dissolving stannous fluoride in an anhydrous material, such as glycerin. EXAMPLES
    [0059] [59] Examples 1 and 2 below look at the amount of zinc and water soluble tin using flame atomic absorption spectrophotometry (FAAS) spectrophotometry. All samples (F, Sn and Zn) are diluted with water, initially and then subjected to accelerated aging over the course of 13 weeks, at 25 ° C or 40 ° C. This method is based on the principle that water-soluble Zn can be measured in oral care products by FAAS after diluting the sample in water. Regarding Sn, a portion of the oral care product is digested with an acidic mixture (tin soluble in acid) or dispersed with water (tin soluble in water). The solutions are transferred to a volumetric flask, diluted to volume with water and centrifuged. Tin is detected in the supernatant by atomic absorption spectroscopy and quantified by comparing the absorbance of the sample solution with the absorbances of external calibration standards of known tin concentration.
    [0060] [60] In addition, Examples 1 and 2 below use ion chromatograph and gradient elution, incorporating conductivity detection to the test fluorine. The samples are prepared as aqueous pastes followed by centrifugation and dilution. The working solutions are analyzed by gradient ion chromatography with detection of suppressed conductivity. Analyte concentrations are determined by relating the peak areas of the component to the areas of the corresponding external calibration standards. Example 1: Stannous Stability with Arginine and Citrate Buffer (* ZnP denotes Zinc Phosphate throughout the specification and examples)
    [0061] [61] The citrate buffer has been tested for its ability to stabilize stannous ions in combination with arginine. The ionic concentration was measured over 13 weeks. Formulations with the organic acid buffer system retained a higher percentage of stannous ions than a comparative formulation that does not comprise the organic acid buffer system. The buffer use of organic acid described above in Compositions A - C contains trisodium citrate dihydrate and citric acid in combination with arginine. Buffer amounts are listed as a percentage by weight of the composition.
    [0062] [62] SnZp and arginine formulations (without any citrate buffer) retained only about 36% of the original stannous ion concentration until week 13. Corresponding formulations containing SnZp, Arginine and Buffer (1.2%, 2, 4%, and 3.6%) managed to retain much more of the original tin concentration at room temperature ((25 C)): about 61% (in 1.2% buffer), about 65% (in buffer at 2.4%) and about 65% (in 3.6% buffer). Example 2: Stannous Stability with Lysine and Citrate Buffer
    [0063] [63] The citrate buffer has been tested for its ability to stabilize stannous ions in combination with lysine. The ionic concentration was measured over 13 weeks. The buffer use of organic acid described above in Compositions D - F contains trisodium citrate dihydrate and citric acid in combination with arginine. Buffer amounts are listed as a percentage by weight of the composition. Example 3: Absorption of Zinc in Tests with Bovine Teeth
    [0064] [64] The three toothpaste compositions shown above have been compared in experiments with absorption of stannous ions and zinc using bovine enamel.
    [0065] [65] The absorption of metal ions is measured using the ESCA technique (X-ray photoelectron spectroscopy). Samples of bovine enamel are used to prepare 3mm wide bovine enamel discs in which the entire enamel surface, minus the exposed surface, is protected with acrylic resin. Each enamel sample is eroded with 1M perchloric acid solution, and is then washed. 2 ml of fresh human saliva is then added, and the samples are incubated at 37 ° C for 2 hours in order to cause the formation of a film. After removing the saliva and washing, the samples are treated with 2 mL of a paste with 1: 2 of the test composition in distilled water for 2 minutes at 37 ° C with stirring. A sample is treated with water as a negative control to determine the reference metal ion content. After rinsing the samples with water, they are sent for analysis by ESCA. The reference metal ion levels measured in the negative control are subtracted from the other test measurements to determine the absorption of metal ions from the toothpaste compositions. The results are shown in Table 3 below.
    [0066] • Formulação de Teste A: SnF + ZnP a 2,35%, Lisina a 1,5%, Tampão a 1,2% • Formulação de Teste B: SnF + ZnP a 2,35%, Lisina a 1,5%, Tampão a 2,4% • Formulação de Teste C: SnF + ZnP a 2,35%, Lisina a 1,5%, Tampão a 3,6% • As Formulações Controle contêm: SnF a 0,454% e lactato de zinco a 2,5%. [66] Test Formulations with Toothpaste Formulation: • Test Formulation A: 2.35% SnF + ZnP, 1.5% Lysine, 1.2% Buffer • Test Formulation B: 2.35% SnF + ZnP, 1.5% Lysine, 2.4% Buffer • Test Formulation C: 2.35% SnF + ZnP, 1.5% Lysine, 3.6% Buffer • Control Formulations contain: 0.454% SnF and 2.5% zinc lactate.
    [0067] [67] The results demonstrate better deposition of zinc metals in in vitro tests compared to control formulations containing 0.454% SnF and 2.5% zinc lactate, but which do not contain zinc phosphate: Table 3 Relative Increase in Metal Deposit: Zinc (ppm) *
    [0068] [68] Table 4 demonstrates the buffering composition used in Examples 1-3 above.
    [0069] [69] The water concentration of the above formulations is between 17.0% to 21.0% by weight. These are considered "high water" formulations. Therefore, Depositors addressed the instability of stannous ions without having to resort to: a.) Formulations with a low water content; or b.) biphasic compositions.
    [0070] [70] The experimental toothpaste compositions used to observe the stability of the stannous ion are prepared based on the formulation shown in Tables 5 and 6. Each dentifrice comprises 0.454% stannous fluoride and 2.35% hydrated zinc phosphate and arginine at 1.5%, but varies in the concentration of citric acid and trisodium citrate dihydrate present - these concentrations are detailed in Table 2 above.
    [0071] [71] The Ingredients of Representative Formulas in Tables 5 and 6 are listed by weight of the composition.
    [0072] [72] Although the present invention has been described with reference to the modalities, it should be understood by those skilled in the art that various modifications and variations can be made to it without departing from the scope of the present invention, as defined by the appended claims.
    权利要求:
    Claims (12)
    [0001]
    Composition for oral care, characterized by the fact that it comprises an orally acceptable carrier comprising 15% by weight or more of water, from 0.05% to 10% by weight of zinc phosphate, 0.01% to 5% by weight of stannous fluoride, from 0.1% to 6% by weight of arginine, and from 0.1% to 5.0% by weight of an organic acid buffer system, wherein the organic acid buffer system comprises citric acid and a sodium citrate salt.
    [0002]
    Composition according to claim 1, characterized by the fact that the acid is citric acid, and the sodium citrate salt is selected from: monosodium citrate (monobasic), disodium citrate (dibasic), trisodium citrate (tribasic), and combinations thereof.
    [0003]
    Composition according to claim 1 or 2, characterized in that the buffer system comprises citric acid and a sodium citrate salt, in a ratio of 1: 3 to 1: 6.
    [0004]
    Composition according to any one of claims 1 to 3, characterized in that the composition comprises arginine in 1.5% by weight.
    [0005]
    Composition according to any one of claims 1 to 4, characterized in that the composition comprises arginine.
    [0006]
    Composition according to any one of claims 1 to 5, characterized by the fact that it still comprises one or more humectants.
    [0007]
    Composition according to any one of claims 1 to 5, characterized by the fact that it still comprises one or more surfactants.
    [0008]
    Composition according to claim 1, characterized by the fact that it further comprises one or more alkaline phosphate salts, wherein the alkaline phosphate salts comprise tetrasodium pyrophosphate or tetrapotassium pyrophosphate, optionally in an amount of 0.5 to 5% in weight of the composition.
    [0009]
    Composition according to claim 8, characterized in that the alkaline phosphate salts comprise sodium tripolyphosphate or potassium tripolyphosphate, optionally, in an amount of 0.5 to 6% by weight of the composition.
    [0010]
    Composition according to any one of claims 1 to 9, characterized in that it further comprises one or more sources of zinc ions in addition to zinc phosphate, for example, a zinc salt selected from zinc citrate, zinc oxide , zinc lactate, zinc pyrophosphate, zinc sulfate, or zinc chloride.
    [0011]
    Composition according to any one of claims 1 to 10, characterized in that the oral care composition is a toothpaste.
    [0012]
    Composition according to any one of claims 1 to 11, characterized by the fact that it is used in a method for treating or preventing erosive demineralization of the tooth, gingivitis, plaque and / or dental caries, in which the composition will be applied in the cavity oral.
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    BE539808A|1953-07-08|
    US3538230A|1966-12-05|1970-11-03|Lever Brothers Ltd|Oral compositions containing silica xerogels as cleaning and polishing agents|
    US3678154A|1968-07-01|1972-07-18|Procter & Gamble|Oral compositions for calculus retardation|
    US3535421A|1968-07-11|1970-10-20|Procter & Gamble|Oral compositions for calculus retardation|
    US3959458A|1973-02-09|1976-05-25|The Procter & Gamble Company|Oral compositions for calculus retardation|
    US3937807A|1973-03-06|1976-02-10|The Procter & Gamble Company|Oral compositions for plaque, caries, and calculus retardation with reduced staining tendencies|
    US3862307A|1973-04-09|1975-01-21|Procter & Gamble|Dentifrices containing a cationic therapeutic agent and improved silica abrasive|
    US4051234A|1975-06-06|1977-09-27|The Procter & Gamble Company|Oral compositions for plaque, caries, and calculus retardation with reduced staining tendencies|
    US4340583A|1979-05-23|1982-07-20|J. M. Huber Corporation|High fluoride compatibility dentifrice abrasives and compositions|
    US4885155A|1982-06-22|1989-12-05|The Procter & Gamble Company|Anticalculus compositions using pyrophosphate salt|
    US5188821A|1987-01-30|1993-02-23|Colgate-Palmolive Company|Antibacterial antiplaque oral composition mouthwash or liquid dentifrice|
    US5192531A|1988-12-29|1993-03-09|Colgate-Palmolive Company|Antibacterial antiplaque oral composition|
    US4866161A|1987-08-24|1989-09-12|University Of South Alabama|Inhibition of tartar deposition by polyanionic/hydrophobic peptides and derivatives thereof which have a clustered block copolymer structure|
    US5188820A|1989-10-05|1993-02-23|Chesebrough-Pond's Usa Co., Dividion Of Conopco, Inc.|Method of inhibiting plaque on teeth by applying an oral composition|
    US4961924A|1989-11-15|1990-10-09|Gillette Canada Inc.|Stabilized stannous fluoride toothpaste|
    ID20480A|1997-10-02|1998-12-24|Lg Chemical Ltd|COMPOSITION TO PREVENT OR TREAT PERIODONTAL DISEASE CONSIST OF EXTRACT FROM ACHYRANTHIS RADIX OR ULMUS CORTEX|
    US20070025928A1|1999-11-12|2007-02-01|The Procter & Gamble Company|Stannous oral care compositions|
    US6685920B2|1999-11-12|2004-02-03|The Procter & Gamble Company|Method of protecting teeth against erosion|
    DE60236611D1|2001-11-28|2010-07-15|Procter & Gamble|DENTAL CARE COMPOSITIONS|
    EP1962787A2|2005-12-20|2008-09-03|The Procter and Gamble Company|Oral care compositions comprising zinc and phytate|
    WO2009060385A2|2007-11-09|2009-05-14|The Procter & Gamble Company|Oral stannous compositions|
    CA2705298C|2008-02-08|2013-10-01|Rajnish Kohli|Oral care product and methods of use thereof|
    WO2009130319A1|2008-04-24|2009-10-29|Gaba International Ag|Oral care composition comprising dissolved tin and fluoride|
    JP4783934B2|2009-06-10|2011-09-28|株式会社丸ヱム製作所|Metal glass fastening screw|
    MY159488A|2009-10-29|2017-01-13|Colgate Palmolive Co|Dentifrice comprising stannous fluoride plus zinc citrate and low levels of water|
    BR112012022935A2|2010-03-31|2021-06-01|Colgate-Palmolive Company|oral hygiene composition.|
    GB201013126D0|2010-08-04|2010-09-22|Flexlife Ltd|Corrosion protection|
    RU2552348C2|2010-10-27|2015-06-10|Колгейт-Палмолив Компани|Composition for oral cavity care, containing arginine and calcium carbonate|
    AU2012396295B2|2012-12-05|2015-08-20|Colgate-Palmolive Company|Zinc phosphate containing compositions|
    BR112015012918B1|2012-12-05|2018-10-30|Colgate Palmolive Co|oral care composition, use of a basic amino acid and use of a zinc ion source, a fluoride ion source and a basic amino acid|
    US10154948B2|2014-06-20|2018-12-18|Colgate-Palmolive Company|Oral compositions containing zinc, stannous and fluoride ion sources|
    US10278906B2|2016-06-24|2019-05-07|Colgate-Palmolive Company|Oral care compositions|MX368518B|2014-08-08|2019-10-07|Colgate Palmolive Co|Dental stain removal and prevention.|
    EP3659674A1|2015-10-08|2020-06-03|Colgate-Palmolive Company|Oral care compositions and methods of using the compositions|
    US20190289874A1|2016-05-31|2019-09-26|Wm. Wrigley Jr. Company|Stain prevention formulations|
    AU2017281775B2|2016-06-24|2019-08-15|Colgate-Palmolive Company|Oral care compositions|
    US10278906B2|2016-06-24|2019-05-07|Colgate-Palmolive Company|Oral care compositions|
    EP3541350A1|2016-12-21|2019-09-25|Colgate-Palmolive Company|Oral care compositions|
    RU2727658C1|2016-12-21|2020-07-22|Колгейт-Палмолив Компани|Oral care compositions and methods for use thereof|
    BR112020017909B1|2018-03-29|2021-08-24|The Procter & Gamble Company|COMPOSITIONS FOR ORAL TREATMENT TO PROMOTE GINGIVAS HEALTH|
    CN111989081A|2018-03-29|2020-11-24|宝洁公司|Oral care composition for promoting gum health|
    CA3095054A1|2018-03-29|2019-10-03|The Procter & Gamble Company|Oral care compositions for promoting gum health|
    CA3123017A1|2018-12-21|2020-06-25|Colgate-Palmolive Company|Stable stannous oral care product|
    WO2020139669A1|2018-12-26|2020-07-02|Colgate-Palmolive Company|Oral care compositions|
    US20210059914A1|2019-08-27|2021-03-04|Colgate-Palmolive Company|Zinc Phosphate Containing Compositions|
    法律状态:
    2020-09-15| B07A| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]|
    2021-01-12| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-03-23| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 10/08/2017, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    US201662437085P| true| 2016-12-21|2016-12-21|
    US62/437,085|2016-12-21|
    PCT/US2017/046287|WO2018118138A1|2016-12-21|2017-08-10|Oral care compositions|
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