Oral care compositions comprising tin ions

Abstract

The present invention discloses an oral care composition, which comprises tin, a polyol having five or six carbon atoms, a polyol having seven or more hydroxyl functional groups, and a pH greater than 7. The present invention also discloses an oral care composition, which comprises a tin ion source, a fluoride ion source, a polyol having five or six carbon atoms, a non-reducing sugar or sugar alcohol having seven or more hydroxyl functional groups, and a pH greater than 7. These oral care compositions have high tin ion availability.

Description

Technical Field

[0001] The present invention relates to compositions comprising tin, a polyol having five or six carbon atoms, and a polyol having seven or more hydroxyl functional groups at a pH greater than 7. The present invention also relates to oral care compositions comprising stannous fluoride, a stabilizing polyol, and a gum strengthening polyol at a pH greater than 7. Background Art

[0002] Tin ion sources, such as stannous fluoride, are added to dentifrice compositions to deliver antimicrobial and antiallergic benefits. However, due to (i) the reactivity of tin ions with other dentifrice components, such as silica, and (ii) the formation of insoluble tin compounds at specific pHs, tin ion sources can be difficult to incorporate into dentifrice compositions. Therefore, incorporation of tin ions into dentifrice compositions is only possible by minimizing the interactions between tin ions and key dentifrice components during storage to maximize the availability of tin ions for reactivity with oral surfaces, such as enamel, dentin, gums, plaque, and bacteria.

[0003] The chemical instability of tin ion solution can be by reducing the pH value of solution, anion chelating agent such as organic acid anion is provided, or polymer chelating agent such as polyphosphate or polycarboxylate is provided to alleviate.Some of these chelating agents can also prevent the interaction of tin ion and silicon dioxide molecular surface by directly combining with tin ion.However, if chelating agent-tin ion interaction is stronger than the binding affinity between tin ion and the inner surface of oral cavity, then strong chelating agent-tin ion interaction also may be unfavorable for tin ion availability, and this tin ion delivery is the prerequisite for the performances such as antagonism oral diseases such as dental plaque, gingivitis, malodor, caries, sensitivity and tooth erosion.Therefore, even the selection of chelating agent must be balanced with whole dentifrice preparation, so that tin ion availability is maximized.

[0004] Due to the chemical instability of tin ions in water-based dentifrice compositions, stannous fluoride is not usually used in aqueous compositions without the use of chelating agents such as gluconates or citrates. In addition, due to the possibility of forming Sn(OH) 2, which can be precipitated from the dentifrice composition when the pH is greater than 7, high pH aqueous dentifrice compositions are even less preferred. Anhydrous conditions can be used to prepare stable compositions with stannous fluoride. Polyols such as glycerol, sorbitol and xylitol can be added to the anhydrous dentifrice composition to replace water as an alternative carrier material. However, polyols may be expensive relative to other carrier materials in the water-based dentifrice composition. Therefore, a stable water-based dentifrice composition is needed that does not require a chelating agent, which may be detrimental to the availability of tin ions in the dentifrice composition. Summary of the Invention

[0005] This summary is provided to introduce some concepts in a simplified form, which will be further described in the detailed description below. This summary is not intended to identify required or essential features of the claimed subject matter. This summary is also not intended to limit the scope of the claimed subject matter.

[0006] Disclosed herein is an oral care composition comprising (a) from about 0.0025% to about 5%, by weight of the oral care composition, of a tin ion source; (b) from about 5% to about 50%, by weight of the oral care composition, of a stable polyol having five or six carbon atoms; (c) from about 0.0025% to about 20%, by weight of the oral care composition, of a gum strengthening polyol having seven or more hydroxyl functional groups, and (d) up to about 45%, by weight of the oral care composition, of water, wherein the oral care composition has a pH greater than 7.

[0007] Disclosed herein is an oral care composition comprising (a) from about 0.0025% to about 5%, by weight of the oral care composition, of a tin ion source; (b) from about 5% to about 50%, by weight of the oral care composition, of a stable polyol having five or six carbon atoms; (c) from about 0.0025% to about 20%, by weight of the oral care composition, of a gingival polyol having seven or more hydroxyl functional groups, and (d) from about 45% to about 75%, by weight of the oral care composition, of water, wherein the oral care composition has a pH greater than 7.

[0008] Disclosed herein is an oral care composition comprising (a) from about 0.0025% to about 5%, by weight of the oral care composition, of a tin ion source, (b) from about 0.0025% to about 5%, by weight of the oral care composition, of a fluoride ion source comprising sodium fluoride, sodium monofluorophosphate, an amine fluoride, or a combination thereof, (c) from about 5% to about 50%, by weight of the oral care composition, of a stable polyol having five or six carbon atoms; (d) from about 0.0025% to about 20%, by weight of the oral care composition, of a gum-strengthening polyol having seven or more hydroxyl functional groups, and (e) from about 10% to about 45%, by weight of the oral care composition, of water, wherein the oral care composition has a pH greater than 7.

[0009] Disclosed herein is an oral care composition comprising (a) from about 0.0025% to about 5%, by weight of the oral care composition, of a tin ion source, (b) from about 5% to about 50%, by weight of the oral care composition, of a stable polyol having five or six carbon atoms; (c) from about 0.0025% to about 20%, by weight of the oral care composition, of a gum-strengthening polyol having seven or more hydroxyl functional groups, and (d) from about 75% to about 99%, by weight of the composition, of water, wherein the oral composition has a pH greater than 7. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 Graph showing the solubility of tin ions and sorbitol under various pH conditions.

[0011] Figure 2 Graph showing the dissolution of tin ions and trehalose under various pH conditions.

[0012] Figure 3 Graph showing the dissolution of tin ions and isomalt under various pH conditions.

[0013] Figure 4 Graph showing the solubility of tin ions with a 1:1 ratio of trehalose and sorbitol under various pH conditions.

[0014] Figure 5 Graph showing the solubility of tin ions with a 3:1 ratio of trehalose and sorbitol under various pH conditions.

[0015] Figure 6 Graph showing the solubility of tin ions with a 1:1 ratio of isomalt and sorbitol under various pH conditions. DETAILED DESCRIPTION

[0016] The present invention relates to oral care compositions comprising a tin ion source, a polyol having five or six carbon atoms, and a polyol having seven or more carbon atoms at a pH greater than 7 or from about 7.5 to about 10.

[0017] Tin ion sources are generally not used in aqueous dentifrice compositions having a pH greater than 7 because of the formation of Sn(OH)2 which can precipitate from the dentifrice composition either immediately after mixing or when the dentifrice composition is stored prior to consumer use, thereby eliminating any benefit derived from the free tin ions.

[0018] Thus, aqueous dentifrice compositions comprising a tin ion source at a pH greater than 7 are generally expected to be incompatible. Unexpectedly, and as described herein, it has been discovered that stable dentifrice compositions comprising a tin ion source and a polyol having five or more carbon atoms are shelf-stable at a pH greater than 7, with minimal or no formation of Sn(OH)2. Without wishing to be bound by theory, it is believed that when a dentifrice composition comprising a tin ion source and a polyol having five or more carbon atoms is properly formulated, the polyol having five or more carbon atoms can weakly interact with the free tin ions to prevent the formation of insoluble Sn(OH)2 under high pH conditions.

[0019] With regard to highly specified cell-to-cell association and a high turnover capacity, the gingival epithelium is considered a strong but passive barrier and is constantly exposed to environmental stimuli through (i) a rich and diverse tooth-adherent microbiome and bacterial attack and (ii) continuous barrier damage caused by chewing and hygiene regimens.

[0020] Gingival epithelial cells are one of the first host cell types to come into continuous contact with bacterial products. Loss of epithelial integrity, barrier, and disruption are associated with bacterial invasion of the underlying connective tissue, potentially increasing the inflammatory response and subsequent tissue damage, hallmarks of gingivitis and periodontal disease.

[0021] Surprisingly, and as described herein, polyols having seven or more hydroxyl functional groups can additionally result in an improvement in the barrier function of epithelial surfaces present in the oral cavity. Although polyols having seven or more hydroxyl functional groups can (i) stabilize tin ions and / or (ii) improve the barrier function of epithelial surfaces present in the oral cavity, polyols having seven or more hydroxyl functional groups can be cost-prohibitive when added to oral care compositions in the desired amounts. Therefore, the present invention also relates to oral care compositions having a tin ion source, a stabilizing polyol having five or six carbon atoms, and a gingival polyol having seven or more hydroxyl functional groups.

[0022] While the specification concludes with claims which particularly point out and distinctly claim the invention, it is believed the present invention will be better understood from the following description.

[0023] definition

[0024] In order to more clearly define the terms used herein, the following definitions are provided. Unless otherwise indicated, the following definitions all apply to the present disclosure. If a term is used in the present disclosure but is not specifically defined in this article, the definition from the IUPAC Compendium of Chemical Terminology 2nd edition (1997) may be applied, as long as the definition does not conflict with any other disclosure or definition used herein, or does not make any claim to which the definition is applied uncertain or impossible to realize.

[0025] As used herein, the term "oral care composition" includes products that are not intended to be swallowed for the purpose of systemic administration of a particular therapeutic agent during ordinary use, but rather are retained in the oral cavity for a sufficient period of time to contact tooth surfaces or oral tissues. Examples of oral care compositions include dentifrices, tooth gels, subgingival gels, mouthwashes, mousses, foams, mouth sprays, lozenges, chewable tablets, chewing gums, tooth whitening strips, dental floss and dental floss coatings, breath freshening dissolvable strips, or denture care or adhesive products. Oral care compositions can also be incorporated into strips or films for direct application or attachment to oral surfaces.

[0026] Unless otherwise indicated, otherwise as used herein, term " dentifrice composition " comprises tooth or subgingival paste, gel or liquid preparation.Dentifrices composition can be single-phase composition, or can be the combination of two or more independent dentifrice compositions.Dentifrices composition can be in any desired form, as dark stripes, shallow stripes, multilayer, paste has gel or their arbitrary combination around.In the dentifrice that comprises two or more independent dentifrice compositions, every kind of dentifrice composition all can be contained in physically independent dispenser compartment, and distribute side by side.

[0027] Active ingredients and other ingredients useful herein may be categorized or described herein based on their cosmetic and / or therapeutic benefits or their postulated modes of action or operation. However, it should be understood that in some cases, active substances and other ingredients useful herein may provide more than one cosmetic and / or therapeutic benefit, or function or operate via more than one mode of action. Therefore, the categorization herein is for convenience only and is not intended to limit the ingredients to the specifically designated functions or activities listed.

[0028] The term "orally acceptable carrier" includes one or more compatible solid or liquid excipients or diluents suitable for topical oral administration. As used herein, "compatible" means that the components of the composition are able to mix but do not interact with each other, such interaction significantly reducing the stability and / or efficacy of the composition. The carriers or excipients of the present invention may include common and conventional components of mouthwashes or rinses, as described more fully below: Mouthwash or rinse carrier materials generally include, but are not limited to, one or more of water, alcohol, humectants, surfactants, and acceptance-enhancing agents (such as flavorings, sweeteners, colorants, and / or cooling agents).

[0029] As used herein, the term "substantially free" means that no more than 0.05%, preferably no more than 0.01%, and more preferably no more than 0.001% of the specified material is present in the composition, based on the total weight of such composition.

[0030] 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 includes compositions in which the indicated material is present only as an impurity in one of the other intentionally added materials.

[0031] Although compositions and methods are described herein as "comprising" various components or steps, unless otherwise indicated, the compositions and methods can also "consist essentially of" or "consist of" the various components or steps.

[0032] As used herein, the word "or" when used as a conjunction of two or more elements is meant to include the elements individually or in combination; for example, X or Y refers to X or Y or both.

[0033] As used herein, the articles "a" and "an" are understood to refer to one or more materials being claimed or described, for example, an "oral care composition" or a "bleaching agent."

[0034] Unless otherwise indicated, all measurements mentioned herein were made at about 23°C (ie, room temperature).

[0035] Generally, element groups are indicated using the numbering scheme shown in the version of the periodic table published in Chemical and Engineering News, 63(5), 27, 1985. In some cases, an element group may be indicated using the common name assigned to the group; for example, alkali metal elements for Group 1, alkaline earth metal elements for Group 2, and so on.

[0036] Several types of ranges are disclosed herein. When any type of range is disclosed or claimed, it is intended to disclose or claim individually every possible value that such range can reasonably encompass, including the endpoints of the range and any subranges and combinations of subranges encompassed therein.

[0037] The term "about" means that quantities, sizes, formulas, parameters and other quantities and characteristics are not and do not have to be exact, but may be approximate and / or larger or smaller as needed to reflect tolerances, conversion factors, rounding, measurement errors, etc., as well as other factors known to those skilled in the art. Generally speaking, whether or not such explicit representation is made, quantities, sizes, formulas, parameters or other quantities or characteristics are "about" or "approximately". The term "about" also encompasses quantities that differ due to different equilibrium conditions for the composition resulting from a particular initial mixture. Whether or not modified by the term "about", the claims include equivalents of the quantities. The term "about" may mean a value within 10% of the reported value, preferably a value within 5% of the reported value.

[0038] Dentifrice composition can be any suitable form, such as solid, liquid, powder, paste or their combination.Oral care composition can be dentifrice, tooth gel, subgingival gel, mouthwash, mousse, foam, mouth spray, lozenge, chewable tablet, chewing gum, teeth whitening strip, dental floss and dental floss coating, breath freshening soluble strip or denture care or adhesive product.The component of dentifrice composition can be incorporated in film, strip, foam or fiber-based dentifrice composition.Dentifrice composition can comprise multiple active and inactive ingredients, such as but not limited to tin ion source, stable polyol, gum strengthening polyol, abrasive, water, fluoride ion source, zinc ion source, one or more polyphosphates, additional wetting agent, surfactant, other compositions etc. and their any combination, as described below.

[0039] tin

[0040] The oral care composition of the present invention comprises tin. Tin can be provided by a tin ion source. The tin ion source can be any suitable compound that provides tin ions in the oral care composition and / or delivers tin ions to the oral cavity when the dentifrice composition is applied to the oral cavity. The tin ion source can comprise one or more tin-containing compounds, such as stannous fluoride, stannous chloride, stannous bromide, stannous iodide, stannous oxide, stannous sulfate, stannous sulfide, stannous fluoride, stannous chloride, stannous bromide, stannous iodide, stannous sulfide and / or a mixture thereof. Preferably, the tin ion source can comprise stannous fluoride, stannous chloride and / or a mixture thereof.

[0041] The oral care composition may comprise from about 0.0025% to about 5%, from about 0.2% to about 1%, from about 0.5% to about 1.5%, or from about 0.3% to about 0.6%, by weight of the oral care composition, of a tin ion source.

[0042] Stable polyols

[0043] The oral care composition of the present invention comprises one or more stable polyols. A polyol is an organic compound having more than one hydroxyl functional group. The stable polyol can be any suitable polyol that can weakly associate, interact, or bond with the tin ions when the oral care composition is stored prior to use. The stable polyol can be a sugar alcohol, a monosaccharide, a disaccharide, a polysaccharide, or a non-reducing sugar. Sugar alcohols are a class of polyols that can be characterized by having a formula (CHOH) n H2 (wherein n = 4-6) is obtained by hydrogenation of a sugar compound. Preferably, n is 5 and / or 6, as these compounds have been shown to unexpectedly interact with a source of tin ions at reasonable formulation costs to form soluble complexes as described herein. Non-reducing sugars are a class of sugars that do not generate any compounds containing an aldehyde functional group. Non-reducing sugars are stable in water and do not react with weak oxidants to produce sugar alcohols. Examples of suitable non-reducing sugars include, but are not limited to, sucrose, trehalose, raffinose, stachyose, verbascose, or combinations thereof. Preferably, the stable polyol is a sugar alcohol.

[0044] The stabilizing polyol may be xylitol, sorbitol, mannitol, lactitol, galactitol, isomalt and / or a combination thereof. Preferably, the stabilizing polyol may be a polyol having the formula (CHOH) n H2 (wherein n=5 and / or 6) is a sugar alcohol. More preferably, the stabilizing polyol may be xylitol, sorbitol, galactitol and / or a mixture thereof.

[0045] The oral care composition may comprise from 0.01% to about 70%, from about 5% to about 70%, from about 5% to about 50%, from about 10% to about 60%, or from about 20% to about 80%, by weight of the oral care composition, of a stabilizing polyol.

[0046] Oral care compositions may also contain additional humectants, have low levels of additional humectants, or contain no additional humectants. Generally, humectants are used to increase the consistency or "mouth feel" of an oral care composition or dentifrice and to prevent the oral care composition from drying out. Suitable humectants include polyethylene glycols (having a variety of different molecular weights), propylene glycol, glycerin, erythritol, xylitol, sorbitol, mannitol, butylene glycol, lactitol, hydrogenated starch hydrolysates, and / or mixtures thereof.

[0047] The oral care composition can comprise a polyol and an additional humectant, such as xylitol, which interacts with the tin ion source, and glycerin, which prevents the oral care composition from drying out during storage or adds bulk to the oral care composition. The oral care composition can also be free of an additional humectant, as the polyol can serve as both the polyol and the additional humectant, such as when the polyol is xylitol, sorbitol, or a combination thereof.

[0048] The oral care composition may comprise one or more humectants, each present at a level of from about 0.01% to about 70%, from about 5% to about 50%, from about 10% to about 60%, or from about 20% to about 80%, by weight of the oral care composition.

[0049] Gum Strengthening Polyols

[0050] The oral care composition of the present invention comprises one or more gum strengthening polyols. Although polyols with five or more carbon atoms have been shown to stabilize tin ions, polyols with seven or more hydroxyl functional groups have been shown to additionally enhance the barrier function of epithelial cells in the oral cavity. Although, as described herein, polyols with seven or more hydroxyl functional groups may be too costly, the combination of polyols with five or six carbon atoms ("stabilizing polyols") and polyols with seven or more hydroxyl functional groups ("gum strengthening polyols") can provide similar benefits at a reasonable cost.

[0051] The gum strengthening polyols can be sugar alcohols, monosaccharides, disaccharides, polysaccharides or non-reducing sugars. Sugar alcohols are a class of polyols that can be identified by their formula (CHOH) n The gum strengthening polyol is obtained by hydrogenation of a sugar compound H2 (wherein n is seven or greater), such as isomalt, maltitol, lactitol, maltotriitol, maltotetraitol, polyglucitol, or a combination thereof. Preferably, n is from about 7 to about 12. Even more preferably, the gum strengthening polyol is isomalt, maltitol, lactitol, or a combination thereof.

[0052] Non-reducing sugars are a class of sugars that do not form any compounds containing aldehyde functional groups. Non-reducing sugars are stable in water and do not react with weak oxidants to produce sugar alcohols. Non-reducing sugars cannot donate electrons to other molecules and are typically disaccharides, trisaccharides, tetrasaccharides, pentasaccharides, such as sucrose, trehalose, raffinose, stachyose, verbascose, or combinations thereof. Preferably, the gum-strengthening polyol is trehalose. Gum barrier properties can be obtained from a combination of polyols, all of which have seven or more hydroxyl functional groups.

[0053] The oral care composition may comprise from 0.025% to about 20%, from about 0.01% to about 15%, from about 1% to about 10%, from about 0.01% to about 15%, or from about 0.0025% to about 10%, by weight of the oral care composition, of a gum strengthening polyol.

[0054] abrasive

[0055] The oral care composition of the present invention may comprise an abrasive. An abrasive may be added to an oral care formulation to assist in removing surface stains on teeth. Preferably, the abrasive is a calcium abrasive or a silica abrasive.

[0056] The calcium abrasive can be any suitable abrasive compound that can provide calcium ions in the oral care composition and / or deliver calcium ions to the oral cavity when the oral care composition is applied to the oral cavity. The oral care composition can comprise from about 5% to about 70%, from about 10% to about 60%, from about 20% to about 50%, from about 25% to about 40%, or from about 1% to about 50% of a calcium abrasive. The calcium abrasive can comprise one or more calcium abrasive compounds such as calcium carbonate, precipitated calcium carbonate (PCC), ground calcium carbonate (GCC), chalk, dicalcium phosphate, calcium pyrophosphate, and / or mixtures thereof.

[0057] The oral care composition may also include a silica abrasive, such as silica gel (alone or in any structure), precipitated silica, amorphous precipitated silica (alone or in any structure), silica hydrate, and / or combinations thereof. The oral care composition may include from about 5% to about 70%, from about 10% to about 60%, from about 10% to about 50%, from about 20% to about 50%, from about 25% to about 40%, or from about 1% to about 50% of a silica abrasive.

[0058] The oral care composition may also include another abrasive, such as bentonite, perlite, titanium dioxide, aluminum oxide, hydrated aluminum oxide, calcined aluminum oxide, aluminum silicate, insoluble sodium metaphosphate, insoluble potassium metaphosphate, insoluble magnesium carbonate, zirconium silicate, particulate thermosetting resin, and other suitable abrasive materials. The oral care composition may include from about 5% to about 70%, from about 10% to about 60%, from about 10% to about 50%, from about 20% to about 50%, from about 25% to about 40%, or from about 1% to about 50% of another abrasive.

[0059] Alternatively, the oral care composition may be substantially free, essentially free, or free of silica, alumina, or any other non-calcium abrasive. The oral care composition may comprise less than about 5%, less than about 1%, less than about 0.5%, less than about 0.1%, or 0% of non-calcium abrasives, such as silica and / or alumina.

[0060] water

[0061] The oral care compositions of the present invention can be anhydrous dentifrice compositions, low-water formulations, or high-water formulations. Generally speaking, the oral care compositions can comprise from 0% to about 99%, about 20% or more, about 30% or more, about 50% or more, up to about 45%, or up to about 75% water by weight of the composition. Preferably, the water is USP water.

[0062] In high water dentifrice formulations, the dentifrice composition comprises from about 45% to about 75% water, by weight of the composition. High water dentifrice compositions may comprise from about 45% to about 65%, from about 45% to about 55%, or from about 46% to about 54%, by weight of the composition, of water. Water may be added to high water dentifrice formulations and / or may enter the composition due to the inclusion of other ingredients.

[0063] In low-water dentifrice formulations, the dentifrice composition comprises from about 10% to about 45% water, by weight of the composition. The low-water dentifrice composition may comprise from about 10% to about 35%, from about 15% to about 25%, or from about 20% to about 25%, by weight of the composition, of water. Water may be added to the low-water dentifrice formulation and / or may enter the composition as a result of the inclusion of other ingredients.

[0064] In an anhydrous dentifrice formulation, the dentifrice composition comprises less than about 10% water by weight of the composition. Anhydrous dentifrice compositions comprise less than about 5%, less than about 1%, or 0% water by weight of the composition. Water may be added to an anhydrous formulation and / or may enter the dentifrice composition due to the inclusion of other ingredients.

[0065] Dentifrice compositions may also contain other orally acceptable carrier materials such as alcohols, humectants, polymers, surfactants, and acceptance-enhancing agents (such as flavorings, sweeteners, colorings, and / or cooling agents).

[0066] The oral care composition may also be a mouthwash formulation.The mouthwash formulation may comprise from about 75% to about 99%, from about 75% to about 95%, or from about 80% to about 95% water.

[0067] pH

[0068] Oral care compositions may include one or more buffers. As used herein, a buffer refers to an agent that can be used to adjust the slurry pH of an oral care composition to a range of greater than 7, greater than 7 to about 14, about 7.5 or greater, about 8 or greater, about 7.5 to about 10, greater than 7 to about 10, about 8 to about 10, about 8 to about 9.5, or about 8.5 to about 9. The pH of a mouthwash solution can be determined as the pH of a pure solution. The pH of a dentifrice composition can be determined as a slurry pH, which is the pH of a mixture of a dentifrice composition and water (such as a 1:4, 1:3, or 1:2 mixture of a dentifrice composition and water). These buffers include alkali metal hydroxides, carbonates, sesquicarbonates, borates, silicates, phosphates, imidazoles, and mixtures thereof. Specific buffers include monosodium phosphate, trisodium phosphate, sodium hydroxide, potassium hydroxide, alkali metal carbonates, sodium carbonate, imidazoles, pyrophosphates, citric acid, and sodium citrate. The oral care compositions may comprise one or more buffering agents, each buffering agent present at a level of from about 0.1% to about 30%, from about 1% to about 10%, or from about 1.5% to about 3%, by weight of the composition.

[0069] zinc

[0070] The oral care composition may include zinc. The zinc may be provided by a zinc ion source. The zinc ion source may include one or more zinc-containing compounds such as zinc fluoride, zinc lactate, zinc oxide, zinc phosphate, zinc chloride, zinc acetate, zinc hexafluorozirconate, zinc sulfate, zinc tartrate, zinc gluconate, zinc citrate, zinc malate, zinc glycinate, zinc pyrophosphate, zinc metaphosphate, zinc oxalate, and / or zinc carbonate.

[0071] The zinc ion source may be present in the total oral care composition in an amount from about 0.01% to about 5%, from about 0.2% to about 1%, from about 0.5% to about 1.5%, or from about 0.3% to about 0.6% by weight of the oral care composition.

[0072] Fluoride

[0073] The oral care composition may contain fluoride. Fluoride may be provided by a fluoride ion source. The fluoride ion source may include one or more fluoride-containing compounds such as stannous fluoride, sodium fluoride, potassium fluoride, amine fluoride, sodium monofluorophosphate, zinc fluoride, and / or mixtures thereof.

[0074] The fluoride ion source and the tin ion source can be the same compound, for example, stannous fluoride, which can generate tin ions and fluoride ions. Alternatively, the fluoride ion source and the tin ion source can be separate compounds, such as when the tin ion source is stannous chloride and the fluoride ion source is sodium monofluorophosphate or sodium fluoride.

[0075] The fluoride ion source and the zinc ion source can be the same compound, for example, zinc fluoride, which can generate zinc ions and fluoride ions. Alternatively, the fluoride ion source and the zinc ion source can be separate compounds, such as when the zinc ion source is zinc phosphate and the fluoride ion source is stannous fluoride.

[0076] The oral care composition may include a fluoride ion source capable of providing from about 50 ppm to about 3500 ppm, and preferably from about 500 ppm to about 3000 ppm, of free fluoride ions. To deliver the desired amount of fluoride ions, the fluoride ion source may be present in the total oral care composition in an amount from about 0.0025% to about 5%, from about 0.2% to about 1%, from about 0.5% to about 1.5%, or from about 0.3% to about 0.6%, by weight of the oral care composition.

[0077] polyphosphates

[0078] Oral care compositions may include polyphosphates. The polyphosphates may be provided by a polyphosphate source. The polyphosphate source may comprise one or more polyphosphate molecules. Polyphosphates are a class of substances obtained by dehydrating and condensing orthophosphates to form linear and cyclic polyphosphates of varying chain lengths. Therefore, polyphosphate molecules are typically identified by the average number (n) of polyphosphate molecules, as described below. Although some cyclic derivatives may exist, polyphosphates are generally considered to consist of two or more phosphate molecules arranged primarily in a linear configuration.

[0079] Preferred polyphosphates are those having an average of two or more phosphate groups so that surface adsorption at an effective concentration produces sufficient unbound phosphate functional groups, which enhances the anionic surface charge and the hydrophilic nature of the surface. Preferred in the present invention are linear polyphosphates having the formula: XO(XPO3) n X, wherein X is sodium, potassium, ammonium or any other alkali metal cation, and n is, on average, from about 2 to about 21. Alkaline earth metal cations, such as calcium, are not preferred because they tend to form insoluble fluoride salts from aqueous solutions containing fluoride ions and alkaline earth metal cations. Thus, the oral care compositions disclosed herein can be free of or substantially free of calcium pyrophosphate.

[0080] Some examples of suitable polyphosphate molecules include, for example, pyrophosphate (n=2), tripolyphosphate (n=3), tetrapolyphosphate (n=4), sodium polyphosphate (n=6), hexapolyphosphate (n=13), benzene polyphosphate (n=14), hexametaphosphate (n=21), which is also known as Glass H. Polyphosphates may include those polyphosphate compounds produced by FMC Corporation, ICL Performance Products, and / or Astaris.

[0081] The oral care composition may comprise from about 0.01% to about 15%, from about 0.1% to about 10%, from about 0.5% to about 5%, from about 1% to about 20%, or about 10% or less, by weight of the oral care composition, of a polyphosphate source.

[0082] surfactants

[0083] The oral care composition may comprise one or more surfactants. Surfactants may be used to make the composition more cosmetically acceptable. The surfactant is preferably a detersive material that imparts detersive and foaming properties to the composition. Suitable surfactants are safe and effective amounts of anionic, cationic, nonionic, zwitterionic, and amphoteric betaine surfactants, such as sodium lauryl sulfate, sodium lauryl isethionate, sodium lauroyl methyl isethionate, sodium cocoyl glutamate, sodium dodecylbenzenesulfonate, alkali metal or ammonium salts of lauroyl sarcosine, myristoyl sarcosine, palmitoyl sarcosine, stearoyl sarcosine, and oleoyl sarcosine, polyoxyethylene sorbitan monostearate, isostearate, and laurate, sodium lauryl sulfoacetate, N-lauroyl sarcosine, sodium, potassium, and ethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoyl sarcosine, polyethylene oxide condensates of alkylphenols, cocoamidopropyl betaine, lauroylamidopropyl betaine, palmityl betaine, sodium cocoyl glutamate, etc. Sodium lauryl sulfate is a preferred surfactant. The oral care composition may comprise one or more surfactants, each present at a level of from about 0.01% to about 15%, from about 0.3% to about 10%, or from about 0.3% to about 2.5%, by weight of the oral care composition.

[0084] thickener

[0085] Oral care compositions may include one or more thickeners. Thickeners can be used in oral care compositions to provide a gel-like structure to stabilize toothpaste and prevent phase separation. Suitable thickeners include polysaccharides, polymers, and / or silica thickeners. Some non-limiting examples of polysaccharides include starch; starch glycerol; gums such as karaya gum (gum karaya), tragacanth gum, gum arabic, gum ghatti, gum arabic, xanthan gum, guar gum, and cellulose gum; magnesium aluminum silicate (colloidal magnesium aluminum silicate); carrageenan; sodium alginate; agar; pectin; gelatin; cellulose compounds such as cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxymethyl carboxypropyl cellulose, methyl cellulose, ethyl cellulose, and sulfated cellulose; natural and synthetic clays such as hectorite clay; and mixtures thereof.

[0086] Thickening agents may include polysaccharides. Suitable polysaccharides for use herein include carrageenan, gellan gum, locust bean gum, xanthan gum, carbomer, poloxamer, modified cellulose, and mixtures thereof. Carrageenan is a polysaccharide derived from seaweed. There are several types of carrageenans, which can be distinguished by their seaweed source and / or by their degree of sulfation and location. Thickening agents may include kappa-carrageenan, modified kappa-carrageenan, iota-carrageenan, modified iota-carrageenan, lambda-carrageenan, and mixtures thereof. Suitable carrageenans for use herein include those commercially available from FMC Company under the serial name "Viscarin," including but not limited to Viscarin TP 329, Viscarin TP388, and Viscarin TP 389.

[0087] The thickening agent may comprise one or more polymers. The polymer may be polyethylene glycol (PEG), polyvinyl pyrrolidone (PVP), polyacrylic acid polymers, polymers derived from at least one acrylic acid monomer, copolymers of maleic anhydride and methyl vinyl ether, cross-linked polyacrylic acid polymers, having various weight percentages of the oral care composition and various ranges of average molecular weight ranges.

[0088] Thickeners may include inorganic thickeners. Some non-limiting examples of suitable inorganic thickeners include colloidal magnesium aluminum silicate, silica thickeners. Non-limiting examples of useful silica thickeners include, for example, amorphous precipitated silica, such as 165 Silica. Other non-limiting silica thickeners include 153, 163 and 167 and 177 and 265 silica products (both available from Evonik Corporation), and Fumed silica.

[0089] Preferably, the thickener may include at least one of a linear sulfated polysaccharide, a natural gum, a cellulose derivative, a polyacrylic acid polymer, or a combination thereof.

[0090] The oral care composition can comprise from 0.01% to about 15%, from 0.1% to about 10%, from about 0.2% to about 5%, or from about 0.5% to about 2% of one or more thickening agents.

[0091] chelating agents

[0092] The oral care composition may comprise one or more chelating agents having a molecular weight (MW) of less than 1000. As used herein, the term "chelating agent" refers to a bidentate or multidentate ligand having at least two groups capable of binding divalent metal ions. Those chelating agents used herein can also typically form water-soluble complexes with stannous ions. Oral care compositions comprising silica abrasives typically comprise one or more chelating agents to reversibly bind tin ions, thereby preventing the tin ions from irreversibly binding to the surface of the silica particles. Suitable chelating agents herein include C2-C6 dicarboxylic acids and tricarboxylic acids, such as succinic acid, malic acid, tartaric acid, and citric acid; C3-C6 monocarboxylic acids substituted with hydroxy groups, such as gluconic acid; picolinic acid; amino acids, such as glycine; phytic acid, their salts, and mixtures thereof. Preferably, the chelating agent is sodium gluconate or citrate.

[0093] The oral care composition may include one or more chelating agents, each present in an amount of from about 0.01% to about 5%, from about 0.2% to about 2%, from about 0.5% to about 1.5%, or from about 1% to about 3%, by weight of the oral care composition. Alternatively, the oral care composition may be substantially free, essentially free, or free of chelating agents, as the oral care compositions of the present invention include a calcium abrasive rather than a silica abrasive. Alternatively, the oral care composition may include one or more chelating agents, each present in an amount of less than about 1%, less than about 0.5%, less than about 0.1%, or less than about 0.01%, by weight of the oral care composition.

[0094] Other ingredients

[0095] The oral care composition may contain various other ingredients, such as flavoring agents, sweeteners, coloring agents, preservatives, buffering agents, or other ingredients suitable for use in oral care compositions, as described below.

[0096] Flavoring agents can also be added to the oral care composition. Suitable flavoring agents include wintergreen oil, peppermint oil, spearmint oil, clove bud oil, menthol, p-propenylanisole, methyl salicylate, eucalyptol, cinnamon, 1-menthyl acetate, sage, eugenol, parsley oil, hydroxyphenyl butanone, α-ionone, oregano, lemon, orange, propenyl ethyl guaiacol, cassia bark, vanillin, ethyl vanillin, heliotropein, 4-cis-heptenal, diacetyl, methyl p-tert-butylphenyl acetate, and mixtures thereof. Cooling agents can also be part of the flavoring system. Preferred cooling agents in the compositions of the present invention are p-menthanecarbamoyl agents, such as N-ethyl-p-menthane-3-carboxamide (commercially known as "WS-3") or N-(ethoxycarbonylmethyl)-3-p-menthanecarboxamide (commercially known as "WS-5"), and mixtures thereof. The flavor system is typically used in the composition at a level of from about 0.001% to about 5% by weight of the oral care composition. These flavoring agents typically comprise mixtures of aldehydes, ketones, esters, phenols, acids, and aliphatic, aromatic, and other alcohols.

[0097] Sweeteners can be added to the oral care composition to impart a pleasant taste to the product. Suitable sweeteners include saccharin (e.g., sodium saccharin, potassium saccharin, or calcium saccharin), cyclamate salts (e.g., sodium, potassium, or calcium salts), acesulfame-K, african sweetener, neohesperidin dihydrochalcone, glycyrrhizin, dextrose, levulose, sucrose, mannose, sucralose, stevioside, and glucose.

[0098] Colorants are added to improve the aesthetic appearance of the product. Suitable colorants include, but are not limited to, those approved by appropriate regulatory agencies such as the FDA and those listed in the European Food and Drug Directive, and include pigments such as TiO2, and colors such as FD&C and D&C dyes.

[0099] Preservatives may also be added to the oral care composition to prevent bacterial growth. Suitable preservatives approved for use in oral compositions, such as methylparaben, propylparaben, benzoic acid, and sodium benzoate, may be added in safe and effective amounts.

[0100] Titanium dioxide can also be added to the compositions of the present invention. Titanium dioxide is a white powder that adds opacity to the composition. Titanium dioxide is generally present in an amount of from about 0.25% to about 5% by weight of the oral care composition.

[0101] Other ingredients may be used in the oral care compositions, such as desensitizing agents, healing agents, other anticaries agents, chelating / sequestering agents, vitamins, amino acids, proteins, other antiplaque / anticarctic agents, sunscreens, antibiotics, antienzymes, enzymes, pH control agents, oxidants, antioxidants, and the like.

[0102] Example

[0103] The present invention is further illustrated by the following examples, which should not be construed as limiting the scope of the present invention in any way. After reading the description herein, various other aspects, modifications and equivalents thereof may be proposed to those of ordinary skill in the art without departing from the spirit of the present invention or the scope of the appended claims.

[0104] Experimental methods

[0105] Solubility of tin ions at pH greater than 7

[0106] Prepare 30% (w / w) solution of every kind of polyol, or use the pure polyol of appropriate amount and deionized water to prepare polyol combination.Next, 46g 30% (w / w) polyol solution is placed in 250mL glass beaker, wherein stirring bar is on the top of magnetic stirring apparatus.21g deionized water is added in the glass beaker, and magnetic stirring apparatus begins to stir solution.pH electrode is connected to pH meter (VWR Scientific, model 9100, Radnor, PA), and pH electrode (ThermoFisher Scientific, Orion 8165BNWP, Waltham, MA) is placed in the polyol solution of stirring.

[0107] Add 0.45 grams of a tin ion source such as stannous fluoride to the stirred polyol solution. Once the tin ion source is completely added, record the pH. Raise the pH of the solution by dropwise addition of 33% (w / w) NaOH solution.

[0108] Solubility of tin ions at pH less than 7

[0109] Prepare 30% (w / w) solution of every kind of polyol, or use the pure polyol of appropriate amount and deionized water to prepare polyol combination.Next, 46g 30% (w / w) polyol solution is placed in 250mL glass beaker, wherein stirring bar is on the top of magnetic stirring apparatus.21g deionized water is added in the glass beaker, and magnetic stirring apparatus begins to stir solution.pH electrode is connected to pH meter (VWR Scientific, model 9100, Radnor, PA), and pH electrode (ThermoFisher Scientific, Orion 8165BNWP, Waltham, MA) is placed in the polyol solution of stirring.

[0110] Add 0.45 grams of a tin ion source such as stannous fluoride to the stirred polyol solution. Once the tin ion source is completely added, record the pH. Lower the pH of the solution by dropwise addition of 33% (w / w) HCl solution.

[0111] Table 1: Polyol solutions containing SnF2

[0112]

[0113] Table 1 shows the formation of insoluble tin compounds such as Sn(OH)2 in the presence of various polyols or polyol combinations over different pH ranges. Solutions that appear turbid indicate the formation of insoluble tin complexes. At a pH greater than 7, turbid solutions indicate the formation of Sn(OH)2. Figures 1 to 6 Table 1 is illustrated by showing the appearance of each solution described in Table 1.

[0114] Polyols are screened for their effectiveness in preventing the formation of Sn(OH)2. For example, aqueous solutions of sorbitol and stannous fluoride are clear at a pH between 2 and 4. However, as the pH increases, the solution of sorbitol and stannous fluoride becomes turbid until a pH of 8 to 10, at which point the solution becomes clear.

[0115] Aqueous solutions of trehalose and stannous fluoride were clear at pH values ​​between 2 and 4. However, solutions of trehalose or isomalt with stannous fluoride appeared turbid at every point above pH 4 as the pH increased.

[0116] A 1:1 or 1:3 mixture of sorbitol and trehalose with stannous fluoride was clear at a pH of 2 to 4 and 8 to 10. Additionally, a 1:1 solution of sorbitol and isomalt with stannous fluoride was clear at a pH of 2 to 4 and 8 to 10. Thus, stabilizing polyols can help solubilize stannous fluoride.

[0117] Although aqueous solutions below pH 4 have been observed to be clear, these pH ranges are undesirable because the solubility of inorganic calcium phosphate compounds such as hydroxyapatite increases at lower pH conditions. In other words, although stannous acid is stable at pH 4, tooth enamel will also dissolve under these conditions.

[0118] Importantly, Table 1 surprisingly demonstrates that tin ions can form soluble complexes with polyols, which prevent the formation of insoluble tin compounds, such as Sn(OH)2, at high pH. The formation of insoluble tin compounds can reduce the availability of tin ions, which can reduce the effectiveness of the tin ion source. Without being bound by theory, it is believed that sugar alcohols with five or more carbon atoms, such as xylitol (5 carbon atoms) and / or sorbitol (6 carbon atoms), can form complexes with tin ions, such as stannous, that are soluble in water-based dentifrice compositions at a pH greater than 7.

[0119] Cell culture

[0120] Human gingival epithelial (HGE) cells were maintained in an incubator at 37°C with 5% CO2 saturation. Dulbecco's modified Eagle's medium (DMEM, Gibco) containing 10% fetal bovine serum and 1% penicillin-streptomycin was used as a complete culture medium and replaced every 2-3 days.

[0121] Barrier protection assay by real-time cell analyzer (RTCA)

[0122] The barrier protection of polyols was monitored using an impedance-based real-time cell analyzer (RTCA) xCELLigence RTCA DP (ACEABioscience Inc., San Diego, CA) device. 50 μl of complete culture medium was added to the E-plate to obtain a background reading, followed by the addition of 100 μl of cell suspension. The E-plate containing 28,000 cells / well was incubated at 37°C, 5% CO2 for 22h-24h until the cells were fully paved. The culture medium was replaced with DMEM or DMEM containing 1% polyols, non-reducing sugars, or a combination thereof, and incubated at 37°C, 5% CO2 for 2h. A barrier disruptor (in this case, a final concentration of capsaicin of 75 μM) was added to the wells of the E-plate. The impedance reflected by the cell index (CI) was continuously recorded for 16h-24h.

[0123] The CI curves were normalized at the time point just before the addition of the polyol. The normalized CI at 3 h after the addition of the barrier disruptor was compared with the blank control to obtain the percentage of % disruption of barrier function.

[0124] Table 2: Barrier functions

[0125] deal with Barrier function blank 100％ Barrier disruptor capsaicin (75 μM) 28％ sorbitol 46％ glycerin 44％ Trehalose 102％ Isomalt 85％ Trehalose:Sorbitol 1:1 81％ Trehalose:Sorbitol 3:1 89％

[0126] Table 2 shows the gingival barrier protection benefits provided by one or more polyols in response to barrier disruptors. Treatment with a barrier disruptor (75 μM solution of capsaicin) resulted in a barrier function value of 28%. The sugar alcohols sorbitol and glycerol provided a moderate barrier function benefit of 46% and 44%, respectively. Trehalose provided a barrier function benefit of 102%. Isomalt provided a barrier function benefit of 85%. However, neither trehalose nor isomalt stabilized stannous fluoride, as shown in Tables 1 and Figures 1 to 6 shown.

[0127] Importantly, the mixture of trehalose and sorbitol provided improved barrier function (81% at 1:1 or 89% at 3:1). In addition, the mixture of trehalose and sorbitol was able to stabilize stannous fluoride at a pH of 8 to 10. Thus, the mixture of stabilizing polyols and gum strengthening polyols stabilizes tin ions at a pH of 8 to 10 and provides gum barrier protection benefits.

[0128] The dimensions and values ​​disclosed herein are not to be understood as being strictly limited to the exact numerical values ​​recited. Instead, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed as "40 mm" is intended to mean "about 40 mm."

[0129] 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 presently disclosed or claimed inventions, 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. Further, to the extent that any meaning or definition of a term in this document 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 document shall govern.

[0130] 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. It is therefore intended that all such changes and modifications within the scope of the present invention be encompassed in the appended claims.

Claims

1. An oral care composition comprising: (a) 0.0025% to 5% tin, by weight of the oral care composition; (b) 5% to 50%, by weight of the oral care composition, of a stabilizing polyol comprising five or six carbon atoms; (c) 1% to 20%, by weight of the oral care composition, of a gum strengthening polyol, the gum strengthening polyol comprising seven or more hydroxyl functional groups, and (d) up to 45% by weight of the oral care composition of water, wherein the oral care composition has a pH of 8 to 10, and the gum strengthening polyol is trehalose, isomalt or a combination thereof, and the stabilizing polyol is sorbitol, wherein the ratio of the stabilizing polyol to the gum strengthening polyol is 1:1 to 1:

3.

2. The oral care composition of claim 1, wherein the oral care composition comprises 10% to 50% of silica abrasive.

3. An oral care composition according to any one of claims 1 to 2, wherein the oral care composition comprises from 10% to 50% calcium abrasive by weight of the oral care composition.

4. An oral care composition according to claim 3, wherein the calcium abrasive is calcium carbonate.

5. An oral care composition according to any one of claims 1 to 2, wherein the oral care composition comprises from 0.01% to 5% zinc, by weight of the oral care composition.

6. An oral care composition according to any one of claims 1 to 2, wherein the oral care composition comprises from 0.01% to 15%, by weight of the oral care composition, of one or more surfactants.

7. The oral care composition of claim 1, wherein the oral care composition comprises 1% or less of silicon dioxide, by weight of the oral care composition.

8. The oral care composition of any one of claims 1 to 2, wherein the oral care composition comprises a thickener.

9. The oral care composition of claim 8, wherein the thickener comprises a linear sulfated polysaccharide, a natural gum, a cellulose, a polyacrylic acid polymer, or a combination thereof.

10. The oral care composition of claim 8, wherein the thickener comprises carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxymethyl carboxypropyl cellulose, methyl cellulose, ethyl cellulose, sulfated cellulose, or combinations thereof.

11. The oral care composition of any one of claims 1 to 2, wherein the tin comprises stannous fluoride, stannous chloride, or a combination thereof.

12. The oral care composition of any one of claims 1 to 2, wherein the oral care composition comprises from 0.0025% to 5% fluoride by weight of the oral care composition.

13. The oral care composition of claim 12, wherein the fluoride comprises sodium fluoride, stannous fluoride, sodium monofluorophosphate, amine fluoride, zinc fluoride, or a combination thereof.

14. An oral care composition according to any one of claims 1 to 2, wherein the oral care composition comprises from 0.01% to 15%, by weight of the oral care composition, of a polyphosphate.

15. An oral care composition according to any one of claims 1 to 2, wherein the oral care composition comprises from 0.01% to 15%, by weight of the oral care composition, of one or more anticalculus agents.

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