Dentifrice compositions for treating dental biofilm

Abstract

A dentifrice composition is provided comprising zinc ions, glycine and a fluoride ion source, particularly in the absence of a stannous ion source, for treating dental plaque biofilm.

Description

Technical Field

[0001] The present invention relates to dentifrice compositions having improved efficacy in helping to inhibit biofilm formation or helping to disrupt biofilm. Background Art

[0002] Dental plaque (also known as dental biofilm) is a sticky, colorless bacterial deposit that continuously forms on the surface of teeth. Dental plaque is generally composed of bacteria and extracellular polymeric substances (so-called "EPS"). EPS is a biopolymer from microorganisms in which biofilm microorganisms are embedded. J. Bacteriol. 2007, 189 (22): 7945. Saliva, food and fluids combine to produce these deposits, which accumulate at the point where the teeth and gums meet. Plaque accumulation is a major factor in poor oral health, which can lead to caries and periodontal (gum) diseases, including gingivitis. One way that dentifrice compositions help prevent and control dental plaque is by utilizing antimicrobial agents such as zinc ion sources. However, a disadvantage or formulation challenge is the unexpected reactivity of the antimicrobial agent with the formulation ingredients and the environment of the dentifrice matrix. This can include oxidative degradation, hydrolysis, adsorption or precipitation of oxy-hydroxide substances, any of which can affect the bioavailability of the antimicrobial agent. Another problem in formulating zinc-containing dentifrices is astringency, an organoleptically unpleasant effect of zinc ions. Therefore, there is a continuing need to provide a dentifrice formulation that helps prevent plaque formation on teeth and at the same time has a reduced astringent taste. Summary of the invention

[0003] The present invention is based on the surprising discovery that the combination of a zinc ion source and glycine in a dentifrice composition helps disrupt and destabilize the biofilm EPS framework. To this end, it has also been surprisingly found that when used in combination with glycine, the penetration depth and / or penetration rate of zinc ions into the biofilm can be increased. In addition, the use of glycine improves the sensory experience, thereby reducing the associated astringency and metallic taste of zinc, which will ensure product compliance and usage habits to deliver oral health benefits.

[0004] One advantage of the present invention resides in a dentifrice composition, particularly containing zinc ions and glycine in the absence of stannous, that is designed to destabilize and disrupt the biofilm EPS framework to aid in active delivery and penetration into the biofilm to optimize efficacy.

[0005] Another advantage of the present invention is that due to the destabilized dental biofilm (reduced thickness, biovolume and increased porosity), it results in improved delivery of fluoride ions to the tooth surface to aid in the enamel remineralization cycle.

[0006] Another advantage of the present invention is that the dentifrice composition can provide reduced astringency to provide a better sensory experience.

[0007] Another advantage of the present invention resides in a phase stable formulation.

[0008] One aspect of the present invention provides a dentifrice composition comprising: a) 0.1% to 0.5% zinc ions by weight of the composition; b) 0.1% to 6.0% glycine or a salt thereof, or a combination thereof, by weight of the composition; and c) 500 ppm to 1500 ppm fluoride ions by weight of the composition. Preferably, the dentifrice composition is substantially free of a stannous ion source.

[0009] Another aspect of the present invention provides a method for treating dental biofilm, the method comprising the step of brushing teeth with the composition of the present invention.

[0010] Another aspect of the present invention provides a method for reducing biofilm thickness and preventing or alleviating plaque formation on tooth enamel, the method comprising the step of brushing teeth with the dentifrice composition of the present invention.

[0011] These and other features, aspects and advantages of the present invention will become apparent to those skilled in the art from the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] While the present invention is particularly pointed out and distinctly claimed by the claims at the end of the specification, it is believed that the present invention will be better understood from the following description of the drawings.

[0013] Figure 1 is a perspective view of a mouth splint with a hydroxyapatite ("HA") disk attached.

[0014] Figure 2 is a perspective view of a HA disk having grooves therein.

[0015] Figure 3 is a schematic cross-sectional view of a groove with a biofilm therein. DETAILED DESCRIPTION

[0016] definition

[0017] As used herein, the articles including "a" and "an" when used in a claim should be understood to mean one or more of what is claimed or described.

[0018] As used herein, the term "comprising" means that steps and ingredients other than those specifically mentioned may be added. The term encompasses the terms "consisting of" and "consisting essentially of." The compositions of the present invention may comprise, consist of, and consist essentially of the essential elements and limitations of the present invention described herein, as well as any additional or optional ingredients, components, steps, or limitations described herein.

[0019] As used herein, the words "preferred", "preferred" and their variations refer to embodiments of the present invention that provide particular benefits under particular circumstances. However, other embodiments may also be preferred under the same or other circumstances. In addition, the description of one or more preferred embodiments does not mean that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the present invention.

[0020] As used herein, the term "substantially free" means that no intentional amount of the material is added to the composition, or the amount of the material is less than 0.05%, 0.01% or 0.001% of the composition. As used herein, the term "substantially free" means that the indicated material is not intentionally added to the composition, or preferably is not present at an analytically detectable level. This refers to compositions including compositions in which the indicated material is present only as an impurity in one of the other intentionally added materials. As used herein, the term "free" means that no reasonably detectable amount of the material is present in the composition.

[0021] As used herein, unless otherwise indicated, the term "dentifrice" means a paste, gel, powder, tablet, or liquid formulation for cleaning oral surfaces. Preferably, the dentifrice composition of the present invention is a single-phase composition. An example of a dentifrice is toothpaste (for brushing teeth). As used herein, the term "tooth" refers to natural teeth as well as artificial teeth or dentures.

[0022] Unless otherwise specified, all percentages, parts and ratios are based on the total weight of the compositions of the present invention. Unless otherwise specified, all such weights relating to listed ingredients are based on the active level, and therefore do not include solvents or by-products that may be included in commercially available materials.

[0023] Unless otherwise specified, all measurements referred to herein were performed at 25° C. (ie, room temperature).

[0024] Dentifrice composition

[0025] It has been surprisingly found that the combination of zinc ions (i.e., antibacterial agents) and glycine (neutral amino acid) in a dentifrice composition is particularly useful for treating dental biofilms. Specifically, it has been surprisingly found that when combined with glycine, the thickness of the biofilm has been significantly reduced, and thus the penetration of zinc ions into the biofilm has been significantly improved. Without being bound by theory, neutral amino acids contain carboxyl and amine groups. It is believed that zinc ions can strongly bind to these chemical moieties on the amino acid to actively influence the penetration of zinc ions into the biofilm.

[0026] It has also been surprisingly discovered that the penetration depth and / or penetration rate of zinc ions into biofilms can be increased or significantly increased when formulated with glycine. In short, the presence of glycine in combination with a zinc ion source in a dentifrice composition aids in the efficacy of the composition in mediating the deleterious effects of bacteria in biofilms on the gums.

[0027] In one aspect, the present invention is directed to a dentifrice composition comprising: a) 0.1% to 0.5% zinc ions, by weight of the composition; b) 0.1% to 6.0% glycine or a salt thereof, or a combination thereof, by weight of the composition; and c) 500 ppm to 1500 ppm fluoride ions, by weight of the composition.

[0028] Preferably, the dentifrice compositions of the present invention are substantially free of stannous ion sources, more preferably essentially free, and still more preferably free of stannous ion sources.

[0029] Zinc ion source

[0030] Herein, the dentifrice composition of the present invention comprises 0.1% to 1% zinc ions by weight of the composition. That is, the dentifrice composition comprises a zinc ion source sufficient to provide 0.1% to 1% zinc ions by weight of the composition. Preferably, the zinc ions are present in an amount of about 0.1% to 0.5% by weight of the composition. For example, the dentifrice composition may comprise about 1000ppm, or about 1500ppm, or about 2000ppm, or about 2500ppm, or about 3000ppm, or about 3500ppm, or about 4000ppm of soluble zinc ions by weight of the composition.

[0031] Insoluble or slightly soluble zinc compounds such as zinc oxide or zinc carbonate can be used as zinc sources. However, preferred zinc sources are soluble zinc sources, such as zinc chloride or zinc sulfate. More preferred zinc sources are those in which the zinc has been combined with a suitable chelating agent in the form of a salt or other complex, such as zinc citrate, zinc gluconate, zinc lactate and zinc glycinate. Particularly preferred zinc ion sources are zinc citrate, zinc gluconate, zinc lactate, and combinations thereof.

[0032] The dentifrice composition of the present invention comprises a chelating agent, wherein the chelating agent is selected from citrate, gluconate, lactate, and combinations thereof. The source of the chelating agent may be a transition metal salt, an alkali metal salt, or an alkaline earth metal salt thereof.

[0033] Preferably, the molar ratio between zinc ion and chelating agent is 1.5: 1 or less, preferably 1.5: 1 to 0.2: 1. For example, the molar ratio between zinc ion and chelating agent in the dentifrice composition may be about 1.5: 1, or about 1.4: 1, or about 1.3: 1, or about 1.2: 1, or about 1.1: 1, or about 1: 1, or about 0.9: 1, or about 0.8: 1, or about 0.7: 1, or about 0.6: 1, or about 0.5: 1, or about 0.4: 1, or about 0.3: 1, or about 0.2: 1.

[0034] In some examples, the zinc ion source is selected from zinc citrate, zinc chloride, zinc sulfate, zinc gluconate, zinc lactate, zinc phosphate, zinc oxide, zinc carbonate, and combinations thereof. In some preferred examples, the dentifrice composition may include a zinc ion source and a chelating agent selected from zinc citrate, zinc gluconate, zinc lactate, and combinations thereof.

[0035] Glycine

[0036] The dentifrice composition of the present invention comprises glycine. Glycine may be present in its free form or in the form of a suitable salt. Suitable salts include those known in the art that are considered pharmaceutically acceptable salts provided in physiologically acceptable amounts and concentrations.

[0037] Preferably, glycine is present in an amount of about 0.1% to about 6% by weight of the composition.Preferably, glycine is present in an amount of about 0.5% to about 5%, more preferably about 0.8% to about 4% by weight of the composition.

[0038] It has been surprisingly found that the presence of glycine in zinc-containing formulations helps increase the penetration depth and / or penetration rate of zinc ions into biofilms. Furthermore, the use of glycine improves the sensory experience by reducing the astringency and metallic taste associated with zinc, which will ensure product compliance and usage habits to deliver oral health benefits. Furthermore, without wishing to be bound by theory, the presence of glycine may also result in improved delivery of a fluoride ion source to the tooth surface due to destabilized dental biofilm, which may also aid in the enamel remineralization cycle.

[0039] Fluoride ion

[0040] Preferably, the dentifrice composition comprises a fluoride ion source as an anti-caries agent. Suitable examples of fluoride ions can be selected from sources including sodium fluoride, potassium fluoride, sodium monofluorophosphate ("MFP"), indium fluoride, amine fluoride, zinc fluoride, and mixtures thereof. Preferably, the fluoride ion source is selected from sodium fluoride, stannous fluoride, MFP, or a combination thereof. The fluoride ion source can be present in an amount of 0.0025% to 5%, or 0.05% to 4%, or 0.1% to 2%, or preferably 0.2% to 1.5% by weight of the composition to provide an anti-caries effect. In some examples, the fluoride ion source can be present in an amount sufficient to provide the following horizontal fluoride ion concentration in the composition: 25ppm to 1500ppm, typically at least 500ppm to 1500ppm, such as 1100ppm or 1450ppm. Appropriate fluoride levels will depend on specific applications. Toothpaste for ordinary users will typically have about 1000ppm to 1500ppm, and children's toothpaste has slightly less.

[0041] Other active agents

[0042] The dentifrice composition of the present invention may also optionally contain other antimicrobial agents, preferably present in an amount of 0.035% or more, 0.05% to 2%, 0.1% to 1% by weight of the composition. Examples of these other antimicrobial agents may include non-cationic antimicrobial agents such as, for example, halogenated diphenyl ethers, phenolic compounds (including phenol and its homologues), monoalkyl and polyalkyl halogenated phenols and aromatic halogenated phenols, resorcinol and its derivatives, xylitol, bisphenol compounds and halogenated N-salicylanilides, benzoates and halogenated N-carbanilides. Other useful antimicrobial agents are enzymes, including endoglycosidases, papains, glucanases, mutant enzymes, and combinations thereof.

[0043] pH

[0044] The pH of the dentifrice composition of the present invention may be pH 5.0 to 10.5, preferably 5.5 to 8.0, more preferably 6.0 to 7.8. In some preferred examples, the pH of the dentifrice composition may be pH 5.5 to 8.5. Alternatively, the dentifrice composition may have a pH of 6 to 9, or 6.5 to 8. In some examples, the pH is 5.5 to 7.8, alternatively pH 6.0 to pH 7.5, for example, pH 7.7, or pH 7.6, or pH 7.5, or pH 7.4, or pH 7.3, or pH 7.2, or pH 7.1, or pH 7.0, or pH 6.9, or pH 6.8, or pH 6.7, or pH 6.6, or pH 6.5, or pH 6.4, or pH 6.3, or pH 6.2, or pH 6.1, or pH 6.0, or pH 5.9, or pH 5.8, or pH 5.7, or pH 5.6, or pH 5.5.

[0045] pH is typically measured using a 1:3 paste:water ratio, whereby 1 gram of a dentifrice composition (e.g., toothpaste) is mixed into 3 grams of deionized water, and then the pH is assessed using an industry-accepted pH probe calibrated at ambient conditions. pH is measured by a pH meter with an automatic temperature compensation (ATC) probe. For purposes of clarity, although the analytical method describes testing the dentifrice composition when freshly prepared, for the purposes of the present invention, pH may be obtained at any time during the reasonable life of the product, including but not limited to the time the product is purchased from a store and brought to the user's home.

[0046] After each use, the electrode should be washed with water to be free of sample solution. Any excess water is removed by wiping with a tissue such as Kimwipes or equivalent. When the electrode is not in use, keep the electrode tip immersed in pH 7 buffer solution or electrode storage solution. Equipment details are as follows:

[0047] pH meter: A measuring instrument capable of reading to 0.01 or 0.001 pH units.

[0048] Electrodes: Orion Ross Sure-Flow combination: Glass body - VWR#34104-834 / Orion#8172BN or VWR#10010-772 / Orion#8172BNWP.

[0049] Epoxy Body - VWR#34104-830 / Orion#8165BN or VWR#10010-770 / Orion#8165BNWP.

[0050] Semi-micro epoxy body - VWR#34104-837 / Orion#8175BN or VWR#10010-774 / Orion#3175BNWP.

[0051] Orion PerpHect combination: VWR#34104-843 / Orion#8203BN semi-micro glass blank.

[0052] ATC probe: Fisher Scientific, Cat. #13-620-16.

[0053] pH Adjusters

[0054] The dentifrice composition herein may optionally include an effective amount of a pH adjusting agent, alternatively wherein the pH adjusting agent is a pH buffer. As used herein, a pH adjusting agent refers to an agent that can be used to adjust the pH of the dentifrice composition to within the pH range determined above. pH adjusting agents include hydrochloric acid, alkali metal hydroxides, ammonium hydroxide, organic ammonium compounds, carbonates, sesquicarbonates, borates, silicates, phosphates, imidazoles, and mixtures thereof.

[0055] Specific pH adjusters include monosodium phosphate (sodium dihydrogen phosphate), trisodium phosphate (trisodium phosphate dodecahydrate or TSP), sodium benzoate, benzoic acid, sodium hydroxide, potassium hydroxide, alkali metal carbonates, sodium carbonate, imidazole, pyrophosphates, linear and cyclic forms of polyphosphates, sodium gluconate, lactic acid, sodium lactate, citric acid, sodium citrate, phosphoric acid.

[0056] Thickener

[0057] The dentifrice composition of the present invention may comprise a thickener. Preferably, the dentifrice composition comprises from 0.1% to 5%, preferably from 0.8% to 3.5%, more preferably from 1% to 3%, still more preferably from 1.3% to 2.6% thickener by weight of the composition.

[0058] Preferably, the thickener comprises a thickening polymer, a thickening silica, or a combination thereof. Still more preferably, when the thickener comprises a thickening polymer, the thickening polymer is selected from charged carboxymethyl cellulose, nonionic cellulose derivatives, linear sulfated polysaccharides, natural gums, polymers comprising at least a polycarboxylated ethylene backbone, and combinations thereof.

[0059] In one example, thickened silica is obtained from a sodium silicate solution by destabilization with acid to obtain very fine particles. A commercially available example is Siloxane from Huber Engineered Materials. Brand silica (such as 103, 124, 113, 115, 163, 165, 167).

[0060] Preferably the linear sulfated polysaccharide is carrageenan (also known as carrageenan). Examples of carrageenan include kappa-carrageenan, iota-carrageenan, lambda-carrageenan, and combinations thereof.

[0061] In one example, CMC is prepared from cellulose by treatment with alkali and monochloroacetic acid or its sodium salt. The different commercial types are characterized by viscosity. A commercially available example is Aqualon TM Brand CMC, available from Ashland Special Ingredients (e.g. Aqualon TM 7H3SF; Aqualon TM 9M3SF Aqualon TM TM9A; Aqualon TM TM12A).

[0062] Preferably, the natural gum is selected from gum karaya, gum arabic (also known as gum arabic), gum tragacanth, xanthan gum, and combinations thereof. More preferably, the natural gum is xanthan gum. Xanthan gum is a polysaccharide secreted by the bacterium Xanthomonas camestris. Generally, xanthan gum is composed of pentose repeating units, each of which contains glucose, mannose and glucuronic acid in a molar ratio of 2:2:1. The chemical formula (monomeric) is C 35 H 49 O 29 In one example, xanthan gum was obtained from CP Kelco Inc (Okmulgee, US).

[0063] Preferably, the nonionic cellulose or its derivative has an average molecular weight in the range of 50,000 to 1,300,000 Daltons, and preferably an average degree of polymerization of 300 to 4,800. More preferably, the nonionic cellulose or its derivative is hydroxyethyl cellulose ("HEC").

[0064] Preferably, the polymer comprising at least a polycarboxylated vinyl backbone is selected from: copolymers of maleic anhydride and methyl vinyl ether having a molecular weight of 30,000 to 1,000,000 Daltons; homopolymers of acrylic acid; and copolymers of maleic acid and acrylic acid or methacrylic acid.

[0065] The copolymer of maleic anhydride and methyl vinyl ether is at least one of: Gantrez AN139 (MW 500,000 Daltons), Gantrez AN119 (MW 250,000 Daltons), or S-97 pharmaceutical grade (MW 70,000 Daltons); and the homopolymer of acrylic acid and the copolymer of maleic acid and acrylic acid or methacrylic acid is at least one of: Acusol 445, Acusol 445N, Accusol 531, Acusol 463, Acusol 448, Acusol 460, Acusol465, Acusol 490, Sokalan CP5, Sokalan CP7, Sokalan CP45 or Sokalan CP12S; and (v) combinations thereof.

[0066] In the example, GANTREZ TM The GANTREZ ® series polymers are copolymers of maleic anhydride and methyl vinyl ether having a molecular weight (MW) of 30,000 to 1,000,000 Daltons. These copolymers can be, for example, GANTREZ TM AN139 (MW 500,000 Daltons), AN119 (MW 250,000 Daltons) and S-97 pharmaceutical grade (MW 70,000 Daltons) were purchased from Ashland Chemicals (Kentucky, USA).

[0067] In another example, ACUSOL TM The SOKALAN series of polymers include homopolymers of acrylic acid and copolymers of maleic acid and acrylic acid or methacrylic acid. Examples are copolymers of maleic acid and acrylic acid in a ratio of 0:1000 to 1000:0 with a molecular weight (MW) of about 2,000 to about 1,000,000. These copolymers can be ACUSOL TM 445 and 445N, ACUSOL TM 531、ACUSOL TM 463、ACUSOL TM 448、ACUSOL TM 460、ACUSOL TM 465、ACUSOL TM 497、ACUSOL TM 490 was commercially available from Dow Chemicals (Michigan, USA), and CP 5, CP 7, CP45 and CP 12S was commercially available from BASF (New Jersey, USA).

[0068] In another example, cross-linked polyacrylic acid (PAA) polymers are a generic term for synthetic high molecular weight polymers of acrylic acid. These can be homopolymers of acrylic acid cross-linked with the allyl ether pentaerythritol, allyl ether of sucrose, or allyl ether of propylene. Moreover, in aqueous solution at neutral pH, PAA is an anionic polymer, i.e., many side chains of PAA will lose their protons and acquire a negative charge. Type polymers such as and It is an acrylic acid polymer crosslinked with polyalkenyl ether or divinyl glycol. Carbomer commercial code is for example 940 TM Indicates the molecular weight and specific composition of the polymer.

[0069] Wetting agent

[0070] The dentifrice composition herein may include a wetting agent, which is present in an amount of 0% to 70% or 15% to 55% by weight of the composition. Wetting agents prevent the dentifrice composition from hardening due to exposure to air, and some wetting agents may also impart the desired sweet flavor to the dentifrice composition. Suitable examples of wetting agents may include glycerol, sorbitol, polyethylene glycol, propylene glycol, xylitol, trimethylglycine, and mixtures thereof. Other examples may include other edible polyols. In some examples, the wetting agent is selected from sorbitol, glycerol, and combinations thereof. In a preferred example, the wetting agent is sorbitol. In another preferred example, the wetting agent is glycerol. In one example, the composition includes 10% to 66%, or 30% to 55% wetting agent by weight of the composition.

[0071] water

[0072] Water is often used as a carrier material in dentifrice compositions for its many beneficial effects. For example, water can be used as a processing aid, is mild to the mouth, and helps the toothpaste foam quickly. Water can be added as an ingredient in its own appropriate manner, or it can be present as a carrier in other common raw materials such as sorbitol and sodium lauryl sulfate.

[0073] In some examples, the dentifrice composition herein may contain a total water content of 10% to 70%, or preferably 15% to 30%, by weight of the composition. As used herein, the term "total water content" refers to the total amount of water present in the dentifrice composition, whether added alone or as a solvent or carrier for other raw materials, but excluding the crystal water present in certain inorganic salts. Preferably, the water is USP water.

[0074] Alternatively, in other examples, the dentifrice compositions herein may comprise a total water content of 0% to 5% by weight of the composition.For example, the dentifrice composition may be substantially free of water, preferably free of water.

[0075] Surfactants

[0076] Optionally but preferably, the dentifrice composition comprises a surfactant. The surfactant may be selected from an anionic surfactant, a nonionic surfactant, an amphoteric surfactant, a zwitterionic surfactant, a cationic surfactant, or a combination thereof, preferably the surfactant is an anionic surfactant, more preferably the anionic surfactant is sodium lauryl sulfate (SLS). An example of a zwitterionic surfactant is cocamidopropyl betaine. The dentifrice composition may comprise one, two, or more surfactants. The composition may comprise a surfactant at a level of 0.1% to 20%, preferably 1% to 10%, by weight of the total composition.

[0077] Abrasive

[0078] The dentifrice composition comprises an effective amount of an abrasive. Examples of abrasives include calcium-containing abrasives, silica, or combinations thereof. If calcium-containing abrasives are included, the calcium-containing abrasive is preferably selected from calcium carbonate, dicalcium phosphate, tricalcium phosphate, calcium orthophosphate, calcium metaphosphate, calcium polyphosphate, calcium oxyapatite, sodium carbonate, sodium bicarbonate, and combinations thereof. If silica, preferably, the silica is precipitated silica (e.g., a sodium silicate solution obtained by destabilizing with an acid to obtain very fine particles), such as available from Huber Engineered Materials. Series (e.g. 103, 124, 113, 115, 163, 165, 167). It is recognized that some of these silicas (e.g., synthetic amorphous silica) can perform both abrasive and thickening functions, but for the purposes of the present invention are included herein by the term "abrasive". Preferably, the dentifrice composition comprises from 1% to 35%, more preferably from 5% to 25%, of an abrasive by weight of the composition.

[0079] Flavoring

[0080] The dentifrice composition herein may include 0.01% to 5%, preferably 0.1% to 2%, of flavoring agents by weight of the composition. Examples of suitable flavoring agents that can be used in dentifrice compositions include those described in U.S. Pat. No. 8,691,190; Haught, JC, column 7, line 61 to column 8, line 21. In some examples, the flavoring agent may be selected from methyl salicylate, menthol, eugenol, and eucalyptol. In some examples, the dentifrice composition may include a flavoring agent mixture that is free of or substantially free of methyl salicylate, menthol, eugenol, and eucalyptol.

[0081] Sweeteners

[0082] The dentifrice composition herein may include a sweetener. The sweetener is typically present in the dentifrice composition at a level of 0.005% to 5% by weight of the composition. Suitable examples of sweeteners include saccharin, dextrose, sucrose, lactose, xylitol, maltose, fructose, aspartame, sodium cyclamate, D-tryptophan, dihydrochalcone, acesulfame, sucralose, neotame, and mixtures thereof. Other suitable examples of sweeteners are described in U.S. Patent No. 8,691,190; Haught, JC, in column 9, line 18 to column 10, line 18.

[0083] Colorants

[0084] The dentifrice composition herein may include a colorant, which is present in an amount of 0.001% to 0.01% by weight of the composition. The colorant may be in the form of an aqueous solution, preferably an aqueous solution of 1% colorant. Suitable examples of colorants may include pigments, stripping agents, filler powders, talc, mica, magnesium carbonate, calcium carbonate, bismuth oxychloride, zinc oxide, and other materials that can change the visual appearance of the dentifrice composition. Other suitable examples may include titanium dioxide (TiO2). Titanium dioxide is a white powder that increases opacity for the composition and is typically present in the dentifrice composition at a level of 0.25% to 5% by weight of the composition.

[0085] Other ingredients

[0086] The dentifrice composition of the present invention may contain common and conventional auxiliary components known to those skilled in the art. Optional ingredients include, for example, but not limited to, anti-plaque agents, anti-allergic agents, whitening and oxidizing agents, anti-inflammatory agents, anticalculus agents, chelating agents, tooth affinity agents, analgesics and anesthetics. It should be understood that the selected dentifrice composition components must be chemically and physically compatible with each other.

[0087] Example

[0088] The following examples and descriptions further illustrate embodiments within the scope of the present invention. These examples are given for illustrative purposes only and should not be construed as limitations of the present invention, as many changes may be made thereto without departing from the spirit and scope of the present invention.

[0089] Embodiment A: Embodiment 1 to 5

[0090] Example 1 is a reference to a phosphate buffer solution, while Examples 2 to 5 are dentifrice compositions. They can be suitably prepared by conventional methods selected by the formulator. Examples 2 and 4 are comparative preparations, while Examples 3 and 5 are inventive preparations according to the present invention. Examples 3 and 5 are made with a fluoride ion source, a zinc ion source (zinc citrate or zinc lactate) and glycine, respectively. In parallel, comparative preparations Examples 2 and 4 are prepared without glycine. All compositions are prepared from mixtures of the components in Table 1 in the ratios shown.

[0091] Table 1: Examples 1 to 5

[0092]

[0093] Example B: Assays for measuring biofilm architecture, penetration of antimicrobial agents, and neutralization of endotoxin in biofilms

[0094] For the dentifrice compositions of the present invention and controls, the following assays were used for in situ dental plaque biofilms to: (1) assess biofilm EPS matrix destabilization and dental biofilm thickness by measuring fluorescence emitted from labeled EPS biofilms; and (2) assess zinc ion penetration efficiency to bacteria by measuring percent colocalization.

[0095] The details of the assay are described below.

[0096] (a) Substrates for biofilm growth

[0097] Hydroxyapatite ("HA") discs were used for in situ growth of biofilms. HA discs were designed with three parallel grooves in each disc (i.e., 200 μm wide for the two side grooves; 200 μm deep; and 500 μm wide and 500 μm deep for the middle groove). When attaching the disc to the subject's mouth, keep these grooves vertical to mimic the interproximal spaces between teeth, which are difficult-to-clean areas where plaque often tends to accumulate. This model allows undisturbed plaque to be collected from the grooves. HA discs are manufactured by Shanghai Bei'erkang biomedicine limited company in Shanghai, China.

[0098] (b) Wearing a splint

[0099] Human subjects wore the splint. Each subject wore up to 12 HA disks on the splint to ensure that at least 9 HA disks were available after 48 hours. Figure 1 Non-limiting examples of such splints and HA discs are shown in FIG. Figure 1 , the device (1) holds a plurality of HA disks (2a to 2d). In a specific example, and referring to Figure 2 , the HA disk (201) has three parallel grooves (203) (the grooves (203a and 203c) on both sides are 300μm wide and 300μm deep; and the middle groove (203b) (between the grooves on both sides) is 500μm wide and 500μm deep). The middle groove is designed to be wider and deeper than the grooves on both sides, so that the HA disk can be more easily divided into two identical half disks for head-to-head comparison purposes. Figure 3 is a schematic cross-sectional view of a groove (2003) having a biofilm (2005) therein. Additional details of HA discs are described in US2017 / 0056531 (e.g., paragraphs

[0019] to

[0020] ).

[0100] Although not in Figure 3 , but the disc could be positioned so that the setback is in the interdental space between the teeth (as this location is prone to plaque (given the difficulty of cleaning, etc.)). The subjects removed the splint only during mealtimes (the splint was stored in an opaque container under moist conditions) and performed an oral hygiene routine. Immediately thereafter, the splint was worn again. The subjects were asked to use a straw when drinking.

[0101] (c) Release of in situ biofilm from HA table

[0102] All HA discs were removed from the clamps by tweezers at 48 hours. Tweezers were used to hold the edges of the HA chip and transfer the HA discs to a 2 mL centrifuge tube containing PBS (phosphate buffered saline) solution. Tweezers were thoroughly cleaned (water; 75% alcohol; and then deionized water) before each disc transfer.

[0103] (d) Preparation of toothpaste supernatant

[0104] 15 grams of deionized water was added to 5 grams of toothpaste (any one of Examples 1 to 5 was used). After thorough stirring, the mixture was centrifuged at 12,000 RPM for 20 minutes. The supernatant was prepared one day before use and stored at 4°C.

[0105] (e) Confocal laser scanning microscopy

[0106] After removing the HA disc from the splint. The HA disc was used for in vitro treatment with different compositions of the present invention and comparative compositions. After treatment with the subject supernatant and labeling with a microbial fluorescent probe and a stannous fluorescent probe (such as described in US2018 / 0072944A1; Shi et al.), the biofilm in the groove was measured by confocal laser scanning microscopy ("CLSM") (described below).

[0107] (f) Disk preparation

[0108] The HA discs were rinsed in a PBS solution, and each HA disc was divided into two halves by tweezers. Thereafter, each half disc was statically placed in a 500 μL to 1000 μL PBS solution for 1 minute. Each disc was treated with a PBS solution or toothpaste supernatant for 2 minutes. Each disc was washed by holding each disc with tweezers, shaking back and forth ten times in a 1 mL PBS solution, and then repeating the washing cycle. Each disc was then statically immersed in a 500 μL to 1000 μL PBS solution for 5 minutes.

[0109] After treatment with PBS and / or oral care composition (eg, toothpaste) supernatant and labeling with specific fluorescent probes, the biofilm in the grooves was measured by confocal laser scanning microscopy (CLSM).

[0110] (g) Fluorescent probe staining and microscopy

[0111] "Ion fluorescent probe" refers to a fluorescent probe that specifically binds to an ion and emits fluorescence at a certain wavelength. In recent years, due to its potential applications in biochemistry and environmental research, people have attached great importance to the development of new highly selective ion fluorescent probes. A variety of signal mechanisms have been proposed and used for optical detection of ions, including photoinduced electron / energy transfer (PET), intramolecular charge transfer (ICT), fluorescence resonance energy transfer (FRET), etc. Some of these fluorescent probes can also be applied to fluorescent bioimaging, which causes almost no cell damage and is highly sensitive to high-speed spatial analysis of living cells. Specifically, FRET imaging that simultaneously records two emission intensities at different wavelengths in the presence and absence of analytes provides a simple method for visualizing complex biological processes at the molecular level. This technology seems to be suitable for the study of the physiological functions or pathogenesis of ions in biological membranes and the human body.

[0112] The zinc penetration efficiency of zinc ions to bacteria is measured by measuring the colocalization percentage. Non-limiting examples of zinc fluorescent probes suitable for labeling biofilms may include any of the following compounds:

[0113] 2-(2(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3',6'-diaminospiro[isoindolin-1,9'-xanthene]-3-one); (b) 2-(2(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3',6'-bis(ethylamino)-2',7'-dimethylspiro[isoindolin-1,9'-xanthene]-3-one); (c) 2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3',6'-bis(diethylamino)spiro[isoindolin-1,9'-xanthene]-3-one; (d) 2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3',6'-bis(ethylamino)-2',7'-dimethylspiro[isoindolin-1,9'-xanthene]-3-one (diethylamino)spiro[isoindolin-1,9'-xanthene]-3-one; (e) 2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3',6'-bis(phenylamino)spiro[isoindolin-1,9'-xanthene]-3-one; (f) 2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3',6'-bis(pyrrolidin-1-yl)spiro[isoindolin-1,9'-xanthene]-3-one; (g) 2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3',6'-diamino-2',7'-diethylspiro[isoindolin-1,9'-xanthene]-3-one; (h) 2-(2 -(((1H-pyrrol-2-yl)methyl)amino)ethyl)-2',7'-dibutyl-3',6'-bis(diethylamino)spiro[isoindolin-1,9'-xanthene]-3-one)-3-one; (i) 2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3',6'-dimorpholinylspiro[isoindolin-1,9'-xanthene]-3-one; (j) 2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3',6'-di(piperidin-1-yl)spiro[isoindolin-1,9'-xanthene]-3-one; (k) 2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-1', 2',3',4',8',9',10',11'-octahydrospiro[isoindoline-1,6'-pyrano[3,2-g:6,6-g']biquinolin]-3-one; (l) 2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-1',2',3',4',10',11',12',13'-octahydrospiro[isoindoline-1,7'-pyrano[2,3-f:6,5-f']biquinolin]-3-one; (m) 2-(2(((1H-pyrrol-2-yl)methyl)amino)ethyl)-2',7'-dimethyl-3',6'-di(piperidin-1-yl)spiro[isoindoline-1,9'-xanthene]-3-one;and (n) 2-(2(bis((1H-pyrrol-2-yl)methyl)amino)ethyl)-3',6'-bis(diethylamino)spiro[isoindoline-1,9'-xanthen]-3-one. ;

[0114] Typically, these zinc fluorescent probes contain a rhodamine B derivative moiety as the fluorophore, linked to 2-methyl 1H-pyrrole via an amide moiety. Further details are described in WO 2016 / 041138 A1.

[0115] "Microbial fluorescent probe" refers to a fluorescent probe that binds to biofilm microorganisms and fluoresces at a specific wavelength. One class of such probes includes fluorescently labeled oligonucleotides, preferably rRNA-directed oligonucleotides. Non-limiting examples include SYTO TM Brand dyes. A specific example is 9 Green fluorescent nucleic acid stain with excitation at 485 (DNA) and 486 (RNA) and light emission detected at 498 (DNA) and 501 (RNA).

[0116] After treatment and immersion, each half disk was stained with Zn probe and Syto-9 probe (containing 5 μM Syto-9 and 5 μM Zn probe) in the dark for 30 minutes. For samples stained with SYTO-9 / Zn dye, the following parameters were used: λex=488nm / 560nm, λem=500 / 580nm, 20X objective, and 60 μm scan from the bottom of the surface bacteria, where step size=3 μm.

[0117] Fluorescently labeled calcium probes are 2+ Molecules that show an increase in fluorescence when . Biofilms are labeled with calcium fluorescent probes. Examples of calcium fluorescent probes suitable for labeling biofilms may be any one or more of the following compounds:

[0118] (a) Fluo-3 TM , A.M. TM , cell-permeable fluorescent stain;

[0119] (b) Fluo-3 TM , potassium pentaphosphate, a cell-impermeant fluorescent stain;

[0120] (c) Fluo-4 TM , A.M. TM , cell-permeable fluorescent stain;

[0121] (d) Fluo-4 TM , potassium pentaphosphate, a cell-impermeant fluorescent stain;

[0122] (e)Fluo-4 Direct TM Calcium assay kit;

[0123] (f) Mag-Fluo-4 TM , tetrapotassium salt, a cell-impermeant fluorescent stain; and

[0124] (g)Fluo-5F TM , A.M. TM , cell-permeable fluorescent stain.

[0125] One or more of these probes are available from ThermoFisher Scientific Company, Waltham, MA.

[0126] Fluo-3 TM Used to image the spatial dynamics of Ca2+ signaling. Solubilized probes can be added directly to biofilms and then probed with AM TM Ester form of calcium probe for biofilm treatment. Fluo-3 TM 、AM TM , a cell-permeable fluorescent probe for intracellular and extracellular calcium staining using confocal microscopy, flow cytometry, and microplate screening applications (absorption / emission maxima ~506 / 526 nm). Concanavalin A is reported to TM (Con A), Alexa 594 conjugate is a reliable alternative to EPS for staining biofilms. Alexa Fluor 594 conjugates showed Alexa Bright red fluorescence of 594 dye (absorption / emission maxima ~590 / 617 nm). Concanavalin A TM Alexa The 594 conjugate selectively binds to α-mannopyranosyl and α-glucopyranosyl residues enriched in the EPS fraction of biofilms.

[0127] A specific example is Concanavalin A TM , Fluorescein Conjugate TM , where excitation is at 494 nm and maximum light emission is detected at 518 nm. Details of these EPS fluorescent probes and procedures for how to use them to quantitatively determine the location and / or amount of EPS are widely available.

[0128] Examples of EPS fluorescent probes suitable for labeling biofilms can be any of the following compounds:

[0129] (a) Molecular Probes TM Concanavalin ATM Alexa 350Conjugate TM ;

[0130] (b)Molecular Probes TM Concanavalin A TM Alexa 488Conjugate TM ;

[0131] (c)Molecular Probes TM Concanavalin A TM Alexa 594Conjugate TM ;

[0132] (d)Molecular Probes TM Concanavalin A TM Alexa 633Conjugate TM ;

[0133] (e)Molecular Probes TM Concanavalin A TM Alexa 647Conjugate TM ;

[0134] (f)Molecular Probes TM Concanavalin A TM Fluorescein Conjugate TM ;

[0135] (g)Molecular Probes TM Concanavalin A TM Oregon 488Conjugate TM ;

[0136] (h)Molecular Probes TM Concanavalin A TM tetramethylrhodamine Conjugate TM ;

[0137] (i)Molecular ProbesTM Concanavalin A TM Texas Conjugate TM .

[0138] One or more of these probes are available from ThermoFisher Scientific Company, Waltham, MA.

[0139] After treatment and immersion, each half-disk sample was stained with Fluo-3 TM 、AM TM , cell-permeable fluorescent probes together with Concanavalin A TM Alexa 594 conjugate probe (containing 5uM Fluo-3 TM +5uM Con-A TM ) was stained in the dark for 30 minutes. After staining, each sample was statically immersed in 500ul to 1000ul PBS solution for 2 minutes.

[0140] (h) Confocal laser scanning microscopy

[0141] Using Leica TM TCS SP8 AOBS spectral confocal microscope. Confocal system by Leica TM DM6000B upright microscope and Leica TM The DMIRE2 consists of an inverted microscope. The upright stand is used for applications involving slide-mounted samples; while the vertical stand with a 37°C incubation chamber and CO2 enrichment accessories provides live cell applications. The microscopes share a replaceable laser scanning head and, in addition to their own motor-driven stage, have a galvanometer-driven high-precision Z stage, which facilitates rapid imaging in the focal plane (Z). In addition to radiofluorescence, the microscope supports a variety of transmitted light contrast methods, including brightfield, polarized light, and differential interference contrast, and is equipped with 5x, 20x, 40x, 63x (oil and dry), and 100x (oil) Leica TM Objective lens.

[0142] Laser scanning and detection systems are described. The TCS SP8 AOBS confocal system is supplied with four lasers (one diode, one argon and two helium-neon lasers), thus allowing the excitation of a wide range of fluorescent dyes in the UV, visible and far infrared ranges of the electromagnetic spectrum. The design of the laser scanning head (including an acousto-optic tunable filter ("AOTF"), an acousto-optic beam splitter ("AOBS") and a four-prism spectrophotometer detector) allows the simultaneous excitation and detection of three fluorescent dyes. The upright microscope also has a transmitted light detector, making it possible to overlay the transmitted light image on the fluorescence recording.

[0143] Using Leica TM The confocal software LAS AF3.3.0 was used with a dual monitor and Leica TM The confocal software was controlled by a standard Pentium PC. The Leica confocal software LAS AF 3.3.0 (purchased from Leica Lasertechnik GmbH (Heidelberg, Germany)) provides an interface for multidimensional image series acquisition, processing and analysis, including 3D reconstruction and measurement, physiological recording and analysis, time-lapse, fluorescent dye colocalization, photobleaching techniques such as FRAP and FRET, spectral mixing and multicolor repair.

[0144] (i) Image analysis

[0145] Zn analysis; Select the SYTO-9 / Zn dye stained sample to quantify the overlap efficiency of red pixels and green pixels. Using the software, the pixel overlap of the "green" bacteria probe and the pixel overlap of the "red" zinc probe are identified, and then this value is divided by all non-black pixels (including non-overlapping stannous probes) to provide the co-localization percentage of zinc in bacteria. Generally, the higher the co-localization percentage, the more effective the oral care product is in delivering zinc to bacteria.

[0146] Ca:EPS; for Fluo-3 TM / Con-A TM For stained samples, two fluorescence channels were selected to quantify the fluorescence intensity ratio of green pixels (calcium) to red pixels (EPS), and Con-A TM Fluorescence channel was used to measure biofilm thickness. Thus, Con-A TM Six selected fields of the fluorescence channel. These fields were considered representative of the entire sample after general inspection by the observer. The distance was measured from the surface of the biofilm to its bottom, the thickness of the field was measured, and the average thickness of the biofilm of the corresponding sample was subsequently calculated.

[0147] result: The subjects were treated with the following substances: Example 3 of the present invention (i.e., zinc citrate + 2% glycine), Example 5 (i.e., zinc lactate + 2% glycine), Comparative Composition Example 2 (i.e., only zinc citrate), Comparative Composition Example 4 (i.e., only zinc lactate), Commercial Product Composition Example 6 (i.e., Colgate Total TM Whole Mouth Health, Daily Repair, which contains zinc citrate / zinc oxide + arginine), and a control (PBS) as a negative control. The results are provided in Table 2.

[0148] Table 2: Permeability of active substances in biofilm

[0149]

[0150] * Example 6 is a commercial product composition (Colgate Total TM Whole Mouth Health,DailyRepair)

[0151] The data is discussed. Referring to Table 2, the fluorescence intensity of zinc in the in situ dental plaque biofilm and the average biofilm thickness measured for various embodiments (2 to 5) and toothpaste formulations (commercial embodiments) are provided. The first column of Table 2 identifies the product with the key active substance. Then, each product includes the embodiments described in Table 1 above (i.e., embodiments 2-5) and a commercial product embodiment 6. It is worth noting that embodiment 6 contains zinc citrate and zinc oxide as zinc ion sources, and 1.5% arginine (basic amino acid). The second column of Table 2 indicates the dental biofilm thickness. The smaller the biofilm thickness, the more effective the composition. The third column indicates zinc penetration (%). The higher the percentage, the more effective the zinc penetration into the biofilm. The fourth column and the fifth column indicate the total zinc amount (ppm) and the soluble zinc amount (ppm) present in the embodiment, respectively. When the embodiment is diluted to 3 times water, the soluble zinc amount is measured.

[0152] Still referring to Table 2, Example 1 ("Ex 1") phosphate buffered saline solution ("PBS") was used as a negative control. Therefore, Example 1 had the least effect (compared to the other compositions) in both the fluorescence ratio of calcium ("Ca") / EPS and the effect on dental biofilm thickness. Compared to Comparative Example 2, Example 3 of the present invention showed a significantly reduced biofilm thickness and a significantly increased zinc permeability. Similarly, Example 5 of the present invention showed a significantly reduced biofilm thickness and a significantly increased zinc permeability compared to Comparative Example 4. It is noteworthy that Example 3 and Example 5 of the present invention (containing only 2% glycine) even showed a significantly reduced biofilm thickness compared to the commercial product Example 6 (which contains a higher amount of zinc ions, and a higher amount of the amino acid arginine (1.5%)).

[0153] Example C: Consumer sensory testing

[0154] Consumer sensory testing was conducted to measure consumer preference for Inventive Examples 3 and 5 relative to Comparative Examples 2 and 4.

[0155] 18 trained sensory panelists were instructed to use the series of test products, unaware of the product identity, i.e., brand, ingredients, etc. They were asked to brush their teeth with the paired comparison products (2 vs. 3, 4 vs. 5) in a random brushing order. Each assigned toothpaste was dispensed on an Oral B Navigator brush and brushed for a controlled 2 minutes, with each panelist recording the sensory attributes (i.e., regarding astringency) on a standard questionnaire on a 1 to 5 scale. Table 3 shows the average ranking of Examples 2 to 5. It can be clearly shown that the addition of glycine to zinc citrate / lactate significantly reduced the apparent astringency of the dentifrice, with a 90% confidence level.

[0156] Table 3: Sensory results

[0157]

[0158] *Highly astringent 5; Mildly astringent 3; No astringency 0

[0159] The dimensions and values ​​disclosed herein are not to be understood as being strictly limited to the exact numerical values ​​cited. Instead, unless otherwise indicated, each such dimension is intended to represent the stated value and a functionally equivalent range around that value. For example, a dimension disclosed as "40 mm" is intended to mean "about 40 mm".

[0160] Unless expressly excluded or otherwise limited, each document cited herein, including any cross-referenced or related patent or patent application and any patent application or patent to which this application claims priority or the benefit of, is hereby incorporated by reference in its entirety. The citation of any document is not an admission that it is prior art to any of the present invention disclosed or claimed herein, or an admission that it, by itself or in combination with any one or more of the references, proposes, suggests, or discloses any such invention. In addition, to the extent that any meaning or definition of a term in this invention conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this invention shall govern.

[0161] Although specific embodiments of the present invention have been illustrated and described, it will be apparent to those skilled in the art that various other changes and modifications may be made without departing from the spirit and scope of the present invention. Therefore, it is intended that all such changes and modifications within the scope of the present invention be covered in the appended claims.

Claims

1. A dentifrice composition comprising: a) from 0.1% to 0.5% by weight of the composition of zinc ions; b) 0.1% to 6.0% by weight of the composition of glycine or a salt thereof, or a combination thereof; c) from 500 ppm to 1500 ppm by weight of the composition of fluoride ions, and wherein the dentifrice composition is free of a stannous ion source, the zinc ions are provided by a zinc ion source, the zinc ion source is zinc lactate, and the dentifrice composition comprises a total water content of 0% to 5% by weight of the composition.

2. The dentifrice composition according to claim 1, further comprising a chelating agent selected from the group consisting of citrate, gluconate, lactate, and combinations thereof.

3. The dentifrice composition according to claim 2, wherein the molar ratio between the zinc ion and the chelating agent is 1.5:1 or less.

4. The dentifrice composition according to claim 2, wherein the molar ratio between the zinc ion and the chelating agent is 1.5:1 to 0.2:

1.

5. The dentifrice composition according to claim 1 or 2, wherein the composition has a pH in the range of: 5.0 to 10.

5.

6. The dentifrice composition according to claim 1 or 2, wherein the composition has a pH in the range of: 5.5 to 8.

0.

7. The dentifrice composition according to claim 1 or 2, wherein the composition has a pH in the range of: 6.0 to 7.

8.

8. The dentifrice composition of claim 1 or 2, wherein the fluoride ions are provided by a fluoride ion source selected from the group consisting of sodium fluoride, indium fluoride, amine fluoride, sodium monofluorophosphate, potassium fluoride, zinc fluoride, and combinations thereof.

9. The dentifrice composition of claim 1 or 2, wherein the fluoride ions are provided by a fluoride ion source selected from the group consisting of sodium fluoride, sodium monofluorophosphate, and combinations thereof.

10. A dentifrice composition according to claim 1 or 2, wherein the glycine is present at a level of 0.2% to 5%.

11. A dentifrice composition according to claim 1 or 2, wherein the glycine is present at a level of 0.5% to 4%.

12. The dentifrice composition of claim 1 or 2, further comprising 0.01% to 5%, by weight of the composition, of a thickening system, wherein the thickening system is selected from a thickening polymer, a thickening silica, or a combination thereof.

13. The dentifrice composition of claim 1 or 2, wherein the zinc ion penetration into the dental biofilm is greater than 50%.

14. The dentifrice composition of claim 1 or 2, wherein the zinc ion penetration into the dental biofilm is greater than 60%.

15. The dentifrice composition of claim 1 or 2, wherein the zinc ion penetration into the dental biofilm is greater than 70%.

16. The dentifrice composition of claim 1 or 2, further comprising 1% to 35% by weight of the composition of an abrasive, wherein the abrasive is selected from a calcium-containing abrasive, a silica abrasive, or a combination thereof.

17. The dentifrice composition of claim 1 or 2, further comprising 5% to 25% by weight of the composition of an abrasive, wherein the abrasive is selected from a calcium-containing abrasive, a silica abrasive, or a combination thereof.

18. The dentifrice composition of claim 1 or 2, further comprising 1% to 35%, by weight of the composition, of an abrasive, wherein the abrasive is a silica abrasive.

19. The dentifrice composition of claim 1 or 2, further comprising from 1% to 60%, by weight of the composition, of a humectant.

20. The dentifrice composition of claim 1 or 2, further comprising 25% to 55%, by weight of the composition, of a humectant.

21. The dentifrice composition of claim 1 or 2, further comprising 1% to 60% by weight of the composition of a humectant, and the humectant is a polyol.

22. The dentifrice composition according to claim 1 or 2, further comprising 1% to 60% by weight of the composition of a humectant, and the humectant is a polyol selected from sorbitol, glycerin, or a combination thereof.

23. Use of a dentifrice composition according to any one of claims 1 to 22 in the preparation of a product for treating dental plaque biofilm in a subject, comprising: A dentifrice composition according to any one of claims 1 to 22 is used to brush the teeth of a subject.

24. Use of a dentifrice composition according to any one of claims 1 to 22 in the preparation of a product for treating dental plaque biofilm in a subject, comprising: Using the dentifrice composition of any one of claims 1 to 22 to brush the teeth of a subject, wherein the brushing occurs at least once a day.

25. Use of a dentifrice composition according to any one of claims 1 to 22 in the preparation of a product for treating dental plaque biofilm in a subject, comprising: Using the dentifrice composition of any one of claims 1 to 22 to brush the teeth of a subject, wherein the brushing occurs at least twice a day.

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