WO2019029917A1

WO2019029917A1 - Oral care composition

Info

Publication number: WO2019029917A1
Application number: PCT/EP2018/068177
Authority: WO
Inventors: Jiang Chang; Xiaoke Li; Weining LIU; Jinfang Wang; Yanling Zhou
Original assignee: Unilever N.V.; Unilever Plc; Conopco, Inc., D/B/A Unilever
Priority date: 2017-08-10
Filing date: 2018-07-05
Publication date: 2019-02-14

Abstract

An oral care composition is disclosed comprising from 1 to 80% by weight of calcium silicate, a phosphate source, from 0.01 to 20% by weight of a water soluble metal compound, and a physiologically acceptable carrier, wherein the metal comprises magnesium, strontium or a mixture thereof, wherein the water soluble metal compound comprises magnesium acetate, magnesium chloride, magnesium bromide, magnesium citrate, magnesium gluconate, magnesium iodide, magnesium sulfate, magnesium nitrate, strontium acetate, strontium chloride, strontium bromide, strontium carbonate, strontium citrate, strontium gluconate, strontium sulfate, strontium nitrate or mixtures thereof, and wherein the calcium silicate and the metal compound are present in a weight ratio of from 10 1:5 to 30:1.

Description

Oral Care Composition

Technical Field of the Invention

The present invention relates to oral care compositions such as tooth pastes, powders, gums, mouthwashes and the like. In particular the present invention relates to an oral care composition comprising calcium silicate and a water soluble metal compound that results in remineralizing and/or whitening of and/or imparting acid resistance to teeth of an individual. The invention also relates to a method for remineralizing and/or whitening of and/or imparting acid resistance to teeth of an individual.

Background of the Invention

The primary component of the enamel and dentin in teeth is calcium phosphate in the form of hydroxyapatite (HAP). Owning to the tightly packed hierarchical microstructure of HAP nanocrystals, nature enamel has extremely high hardness and unique mechanical properties. However, many products we consume have a negative impact on our teeth. Acidic drinks and sweets, for example, can result in tooth erosion by attacking enamel which is the outer coating that protects the teeth.

In the mouth, there is a natural equilibrium between HAP being dissolved from the enamel of teeth which is referred to as demineralization, and hydroxyapatite being formed on or in the teeth from substances occurring naturally in the saliva which is referred to as remineralization. This equilibrium is shifting continuously. As long as the rate of demineralization and the rate of remineralization remain in balance, teeth remain strong and healthy. Caio(P0₄)6(OH)2(soifci) + 8H⁺ _(aq) <→ 10Ca²⁺ _(aq) + 6HP0₄ ²-_(aq) + 2H₂0

Exposure of the dental hard tissues to acid causes demineralization, resulting in surface softening and a decrease in mineral density. Imbalance in this process results in the formation of dental caries which occurs when more minerals are lost from teeth than can be replaced.

Efforts have been made over the years to address the problem of dissolution or demineralization of tooth enamel and the resultant formation of dental caries. Products comprising calcium silicate based biomaterials have been developed due to their favourable bioactivity and teeth remineralization ability. Such products may generate a new remineralization layer that binds to tooth surfaces to counteract enamel demineralization caused by acid erosion.

Hierarchical structure of enamel is another important factor to resist acid dissolution. It is found that HAP (001 ) facets can be more resistant against dissolution than (100) facets under acidic conditions, and so enamel hardness is associated with the size of apatite crystals along the c-axis. It is reported that metal ions may change enamel crystallographic structure through a process of dissolution and re-precipitation to make the teeth harder so that the metal ions may have the potential to help resist acid erosion and inhibit enamel demineralization.

There is continuing need for building stronger and healthier teeth. The present inventors have now found unexpectedly that the tooth remineralization efficacy can be enhanced by using calcium silicate in combination with a water soluble metal compound. It has been further found that such an oral care composition is effective in protecting tooth enamel from acid erosion through inhibiting demineralization and promoting remineralization, which results in enhanced tooth enamel protection efficacy against acid challenges. In addition, such composition can also enhance the tooth remineralization efficacy and/or the deposition of benefit agents on tooth surfaces to further benefit teeth of an individual.

Additional Information

WO 2008/068149 A (Unilever) discloses an oral care product comprising a first composition comprising an insoluble calcium salt that is not a calcium phosphate salt, a second independent composition comprising a source of phosphate ions, and a means for delivering each of the compositions to the surface of the teeth. The preferred insoluble calcium salt is calcium silicate.

WO 2015/036277 (Unilever) discloses an oral care composition comprising calcium silicate and high refractive index composite particles wherein the refractive index of the composite particle is in the range from 1 .9 to 4.0, and wherein the calcium silicate and high refractive index composite particles are present at a calcium silicate to composite particles weight ratio of 1 :10 to 2:1 .

The additional information above does not describe an oral care composition comprising calcium silicate, a water soluble metal compound, a phosphate source and a physiologically acceptable carrier, wherein the metal comprises magnesium, strontium or a mixture thereof, and especially such an oral care composition provides enhanced tooth enamel protection efficacy against acid challenges. Tests and Definitions

Dentifrice

"Dentifrice" for the purposes of the present invention means a paste, powder, liquid, gum or other preparation for cleaning the teeth or other surfaces in the oral cavity. Tooth Paste

"Tooth paste" for the purpose of the present invention means a paste or gel dentifrice for use with a toothbrush. Especially preferred are tooth pastes suitable for cleaning teeth by brushing for about two minutes. Particle Size

"Particle size" for the purpose of the present invention means D50 particle size. The D50 particle size of a particulate material is the particle size diameter at which 50 wt% of the particles are larger in diameter and 50 wt% are smaller in diameter. The D50 particle size of a particulate material is the particle size diameter at which 50 wt% of the particles are larger in diameter and 50 wt% are smaller in diameter. For the purpose of the present invention, particle sizes and distribution are measured using Malvern Mastersizer 2000 and Malvern ZetaSizer Nano series.

PH

pH is quoted at atmospheric pressure and a temperature of 25°C. When referring to the pH of an oral care composition, this means the pH measured when 5 parts by weight of the composition is uniformly dispersed and/or dissolved in 20 parts by weight pure water at 25°C. In particular the pH may be measured by manually mixing 5 g oral care composition with 20 mL water for 30 s, then immediately testing the pH with indicator or a pH meter.

Solubility

"Soluble" and "insoluble" for the purpose of the present invention means the solubility of a source (e.g., like calcium salts) in water at 25°C and atmospheric pressure. "Soluble" means a source that dissolves in water to give a solution with a concentration of at least 0.1 moles per litre. "Insoluble" means a source that dissolves in water to give a solution with a concentration of less than 0.001 moles per litre. "Slightly soluble", therefore, is defined to mean a source that dissolves in water to give a solution with a concentration of greater than 0.001 moles per litre and less than 0.1 moles per litre. Substantially Free

"Substantially free of for the purpose of the present invention means less than 3.0%, and preferably less than 2.0%, and more preferably less than 1 .0% and most preferably less than 0.5% by weight, based on total weight of the oral care composition, including all ranges subsumed therein.

Dual-Phase

"Dual-Phase" for the purpose of the present invention means a composition having two independent phases which are physically separate. Anhydrous Composition

"Anhydrous composition" for the purpose of the present invention means the water content of the composition is less than 3.0%, and preferably less than 2.0%, and more preferably less than 1 .0% and most preferably less than 0.5% by total weight of the oral care composition.

Viscosity

Viscosity of a tooth paste is the value taken at room temperature (25 °C) with a Brookfield Viscometer, Spindle No.4 and at a speed of 5 rpm. Values are quoted in centipoises (cP=mPa.s) unless otherwise specified.

Remineralization

"Remineralization" for the purpose of the present invention means in situ (i.e. in the oral cavity) generation of calcium phosphate on teeth (including layers on teeth from 10 nm to 20 microns, and preferably from 75 nm to 10 microns, and most preferably, from 150 nm to 5 microns thick including all ranges subsumed therein) to reduce the likelihood of tooth sensitivity, tooth decay, regenerate enamel and/or improve the appearance of teeth by whitening through the generation of such new calcium phosphate. Miscellaneous

Except in the examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or conditions of reaction, physical properties of materials and/or use may optionally be understood as modified by the word "about".

All amounts are by weight of the final oral care composition, unless otherwise specified. It should be noted that in specifying any ranges of values, any particular upper value can be associated with any particular lower value. For the avoidance of doubt, the word "comprising" is intended to mean "including" but not necessarily "consisting of" or "composed of". In other words, the listed steps or options need not be exhaustive.

The disclosure of the invention as found herein is to be considered to cover all embodiments as found in the claims as being multiply dependent upon each other irrespective of the fact that claims may be found without multiple dependency or redundancy.

Where a feature is disclosed with respect to a particular aspect of the invention (for example a composition of the invention), such disclosure is also to be considered to apply to any other aspect of the invention (for example a method of the invention) mutatis mutandis.

Summary of the Invention

In a first aspect, the present invention is directed to an oral care composition comprising: a) from 1 to 80% by weight of calcium silicate;

b) a phosphate source;

c) from 0.01 to 20% by weight of a water soluble metal compound; and

d) a physiologically acceptable carrier;

wherein the metal comprises magnesium, strontium or a mixture thereof;

wherein the water soluble metal compound comprises magnesium acetate, magnesium chloride, magnesium bromide, magnesium citrate, magnesium gluconate, magnesium iodide, magnesium sulfate, magnesium nitrate, strontium acetate, strontium chloride, strontium bromide, strontium carbonate, strontium citrate, strontium gluconate, strontium sulfate, strontium nitrate or mixtures thereof; and

wherein the calcium silicate and the metal compound are present in a weight ratio of from 1 :5 to 30:1 .

In a second aspect, the present invention is directed to a packaged oral care product comprising the oral care composition of the first aspect of this invention.

In a third aspect, the present invention is directed to a method for remineralizing and/or whitening of and/or imparting acid resistance to teeth of an individual comprising the step of applying the oral care composition of any embodiment of the first aspect to at least one surface of the teeth of the individual.

All other aspects of the present invention will more readily become apparent upon considering the detailed description and examples which follow.

Detailed Description

It has now been found that an oral care composition comprising calcium silicate, a water soluble metal compound and a phosphate source can protect tooth enamel from acid erosion through inhibiting demineralization and promoting remineralization, which results in enhanced tooth enamel protection efficacy against acid challenges. In addition, such composition can also enhance the tooth remineralization efficacy and/or the deposition of benefit agents on tooth surfaces to further benefit teeth of an individual.

The calcium silicate suitable for use in this invention may comprise mono-calcium silicate, bi-calcium silicate, or tri-calcium silicate. In one preferred embodiment, the calcium silicate used is one which has low water solubility and is made commercially available under the name Sorbosil CA40 by PQ Corporation. In another preferred embodiment, the calcium silicate is insoluble, present as the composite material calcium oxide-silica (CaO-SiC>2), which is described, for example, in international patent application published as WO 2008/01517(Unilever) which is hereby incorporated by reference in its entirety. For a calcium silicate composite material, the atom ratio of calcium to silicon (Ca:Si) may be from 1 :30 to 3:1 . The Ca:Si ratio is preferably 1 :20 to 3:1 , and more preferably, from 1 :10 to 3:1 , and most preferably, from about 1 :7 to 3:1. The calcium silicate may be in a crystalline or amorphous state or even in a mesoporous state.

In addition to calcium oxide, silica, the particles comprising the calcium silicate may comprise other components, such as metal cations, anions (such as phosphate) and the like. However, it is preferred that the particles comprise calcium oxide, silica in an amount of at least 70% by weight of the particles, more preferably at least 80%, more preferably still at least 90% and even more preferably at least 95%. Most preferably the particles consist of (or at least consist essentially of) calcium oxide, silica.

In another preferred embodiment, the calcium silicate is calcium silicate hydrate. The calcium silicate hydrate for use in the present invention comprises at least calcium oxide (CaO), silica (S1O2) and water. Compared with conventional calcium silicate which are not hydrated, the calcium silicate hydrate comprises the water of hydration in an amount of at least 5% by weight of the calcium silicate hydrate, preferably at least 10%, more preferably at least 15%, even more preferably at least 20% and most preferably at least 25%. The water content is typically no greater than 50% by weight of the calcium silicate hydrate, more preferably no greater than 40%, even more preferably no greater than 35% and most preferably no greater than 30%.

The calcium silicate hydrate preferably comprises at least 20% silica by weight of the calcium silicate hydrate, more preferably at least 30%, more preferably still at least 40% and most preferably at least 55%. The silica content is preferably no greater than 70% by weight of the calcium silicate hydrate, more preferably no greater than 65% and most preferably no greater than 60%.

To provide calcium necessary for remineralization, the calcium silicate hydrate preferably comprises calcium oxide in an amount of at least 5% by weight of the calcium silicate hydrate, more preferably at least 7%, more preferably still at least 10%, even more preferably at least 12% and most preferably at least 15%. The calcium oxide content is typically no greater than 50% by weight of the calcium silicate hydrate, more preferably no greater than 40%, even more preferably no greater than 30% and most preferably no greater than 25%. The calcium silicate hydrate preferably comprises Ca and Si in an atom ratio (Ca:Si) less than 1 :1 , more preferably less than 1 :1 .2, more preferably still from 1 :1.5 to 1 :4 and most preferably from 1 :1 .7 to 1 :3.

In addition to calcium oxide, silica and water, the particles which comprise the calcium silicate hydrate may comprise other components, such as metal cations, anions (such as phosphate) and the like. However, it is preferred that the particles comprise CaO, S1O2 and water in an amount of at least 70% by weight of the particles, more preferably at least 80%, more preferably still at least 90% and even more preferably at least 95%. Most preferably the particles consist of (or at least consist essentially of) CaO, S1O2 and water.

The calcium silicate may be amorphous or at least partly crystalline or mesoporous. The calcium silicate is preferably particulate as this allows for maximum surface area for contact with dental tissue. Thus preferably the composition comprises particles comprising the calcium silicate. Preferably from 10 to 100%, and especially, from 25 to 100%, and most especially, from 70% to 100% by weight of the particles comprising calcium silicate used in this invention have a particle size from 100 nm to less than 50 microns, preferably from 500 nm to 30 microns, more preferably from 1 micron to 20 microns, most preferably from 3 micron to 15 microns. The oral care composition of the present invention comprises from 1 to 80% by weight of the calcium silicate, preferably from 3 to 50%, more preferably from 5 to 30%, based on the total weight of the oral care composition and including all ranges subsumed therein.

The only limitation with respect to the water soluble metal compound for use in the present invention is that the same is suitable for oral use. The metal comprises magnesium, strontium or a mixture thereof. As to the compounds of any of these metals include, for example, chlorides, bromides, iodides, carbonates, sulfates, nitrates, acetates, lactates, citrates, gluconates or mixtures thereof. The metal compound may be used either singly or in the form of a mixture.

Illustrative yet non-limiting examples of the types of metal compound that may be used in the invention include, for example, magnesium acetate, magnesium chloride, magnesium bromide, magnesium citrate, magnesium gluconate, magnesium iodide, magnesium sulfate, magnesium nitrate, strontium acetate, strontium chloride, strontium bromide, strontium carbonate, strontium citrate, strontium gluconate, strontium sulfate, strontium nitrate or mixtures thereof. In a preferred embodiment, the metal compound comprises or is magnesium chloride, strontium chloride or a mixture thereof.

The oral care composition of the present invention comprises from 0.01 to 20% by weight of the water soluble metal compound, preferably from 0.05 to 15%, more preferably from 0.1 to 10%, based on the total weight of the oral care composition and including all ranges subsumed therein.

The oral care composition comprises the calcium silicate and the metal compound in a weight ratio from 1 :5 to 30:1 , preferably from 1 :3 to 25:1 , more preferably from 1 :1.5 to 20:1 , and most preferably from 1 :1 to 15:1.

The phosphate source that may be used in this invention is limited only to the extent that the same may be used in a composition suitable for use in the mouth. The phosphate source is able to provide phosphate ions to react with the calcium silicate to produce a calcium phosphate in situ reaction product that is a precursor for hydroxyapatite formation.

Illustrative examples of the types of phosphate source suitable for use in this invention include trisodium phosphate, monosodium dihydrogen phosphate, disodium hydrogen phosphate, ammonium phosphate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, tripotassium phosphate, monopotassium dihydrogen phosphate, dipotassium hydrogen phosphate, mixtures thereof or the like. The phosphate source is preferably one which is water soluble. When used, the phosphate source typically makes up from 0.1 to 40%, and more preferably, from 0.5 to 30%, and most preferably, from 1 to 20% by weight of the oral care composition, based on total weight of the oral care composition and including all ranges subsumed therein. In a preferred embodiment, the phosphate source used is trisodium phosphate and monosodium dihydrogen phosphate at a trisodium phosphate to monosodium dihydrogen phosphate weight ratio of 1 :4 to 4:1 , preferably 1 :3 to 3:1 , and most preferably, from 1 :2 to 2:1 , including all ratios subsumed therein. In another preferred embodiment, the phosphate source is monopotassium dihydrogen phosphate, dipotassium hydrogen phosphate or a mixture thereof, preferably monopotassium dihydrogen phosphate.

Preferably, the phosphate source results in an oral are composition having a pH from 4.0 to 10.0, more preferably from 5.0 to 8.0, and most preferably from 5.5 to 7.5. The oral care composition preferably comprises the calcium silicate and the phosphate source in a weight ratio from 1 :10 to 30:1 , more preferably from 1 :5 to 20:1 , most preferably from 1 :3 to 15:1 .

The composition of the present invention is an oral care composition and typically comprises a physiologically acceptable carrier. The carrier preferably comprises at least surfactant, thickener, humectant or a combination thereof.

Preferably the oral care composition comprises a surfactant. Preferably the composition comprises at least 0.01 % surfactant by weight of the composition, more preferably at least 0.1 % and most preferably from 0.5 to 7%. Suitable surfactants include anionic surfactants, such as the sodium, magnesium, ammonium or ethanolamine salts of Cs to Cie alkyl sulphates (for example sodium lauryl sulphate), Cs to Cis alkyl sulphosuccinates (for example dioctyl sodium sulphosuccinate), Cs to Cis alkyl sulphoacetates (such as sodium lauryl sulphoacetate), Cs to Cis alkyl sarcosinates (such as sodium lauryl sarcosinate), Cs to Cie alkyl phosphates (which can optionally comprise up to 10 ethylene oxide and/or propylene oxide units) and sulphated monoglycerides. Other suitable surfactants include nonionic surfactants, such as optionally polyethoxylated fatty acid sorbitan esters, ethoxylated fatty acids, esters of polyethylene glycol, ethoxylates of fatty acid monoglycerides and diglycerides, and ethylene oxide/propylene oxide block polymers. Other suitable surfactants include amphoteric surfactants, such as betaines or sulphobetaines. Mixtures of any of the above described materials may also be used. More preferably the surfactant comprises or is anionic surfactant. The preferred anionic surfactants are sodium lauryl sulphate and/or sodium dodecylbenzene sulfonate. Most preferably the surfactant is sodium lauryl sulphate, sodium coco sulfate, cocamidopropyl betaine, sodium methyl cocoyl taurate or mixtures thereof.

Thickener may also be used in this invention and is limited only to the extent that the same may be added to a composition suitable for use in the mouth. Illustrative examples of the types of thickeners that may be used in this invention include, sodium carboxymethyl cellulose (SCMC), hydroxyl ethyl cellulose, methyl cellulose, ethyl cellulose, gum tragacanth, gum arabic, gum karaya, sodium alginate, carrageenan, guar, xanthan gum, Irish moss, starch, modified starch, silica based thickeners including silica aerogels, magnesium aluminum silicate (e.g., Veegum), Carbomers (cross-linked acrylates) and mixtures thereof. Typically, xanthan gum and/or sodium carboxymethyl cellulose and/or a Carbomer is/are preferred. When a Carbomer is employed, those having a weight-average molecular weight of at least 700,000 are desired, and preferably, those having a molecular weight of at least 1 ,200,000, and most preferably, those having a molecular weight of at least about 2,500,000 are desired. Mixtures of Carbomers may also be used herein.

In an especially preferred embodiment, the Carbomer is Synthalen PNC, Synthalen KP or a mixture thereof. It has been described as a high molecular weight and cross-linked polyacrylic acid and identified via CAS number 9063-87-0. These types of materials are available commercially from suppliers like Sigma.

In another especially preferred embodiment, the sodium carboxymethyl cellulose (SCMC) used is SCMC 9H. It has been described as a sodium salt of a cellulose derivative with carboxymethyl groups bound to hydroxy groups of glucopyranose backbone monomers and identified via CAS number 9004-32-4. The same is available from suppliers like Alfa Chem.

In another especially preferred embodiment, the thickener is xanthan gum. Thickener typically makes up from 0.01 to about 10%, more preferably from 0.1 to 9%, and most preferably, from 0.1 to 5% by weight of the oral care composition, based on total weight of the composition and including all ranges subsumed therein.

When the oral care composition of this invention is a toothpaste or gel, the same typically has a viscosity from about 30,000 to 180,000 centipoise, and preferably, from 60,000 to

170,000 centipoise, and most preferably, from 65,000 to 165,000 centipoise.

Suitable humectants are preferably used in the oral care composition of the present invention and they include, for example, glycerin, sorbitol, propylene glycol, dipropylene glycol, diglycerol, triacetin, mineral oil, polyethylene glycol (preferably, PEG-400), alkane diols like butane diol and hexanediol, ethanol, pentylene glycol, or a mixture thereof. Glycerin, polyethylene glycol, sorbitol or mixtures thereof are the preferred humectants.

The humectant may be present in the range of from 10 to 90% by weight of the oral care composition. More preferably, the carrier humectant makes up from 25 to 80%, and most preferably, from 30 to 60% by weight of the composition, based on total weight of the composition and including all ranges subsumed therein.

The oral care composition may further comprise benefit agents that are typically delivered to human teeth and/or the oral cavity including the gums to enhance or improve a characteristic of those dental tissues. The only limitation with respect to the benefit agents that may be used in this invention is that the same is suitable for use in the mouth. The benefit agents are present in the oral care composition in addition to the calcium silicate and the water soluble metal compound that are included in the composition.

Typically the benefit agent is selected from optical agents, biomineralization agents, antibacterial agents, gum health agents, desensitizing agents, anti-calculus agents, freshness agents or mixtures thereof. Preferably, the benefit agent is selected from optical agents, biomineralization agents, antibacterial agents, gum health agents, freshness agents or mixtures thereof.

For example, optical agents such as coloring agents like whitening agents and pigments. Preferably, the pigment, when used, is violet or blue having a hue angle, h, in the CI ELAB system of from 220 to 320 degrees. These pigments may be selected from one or more of those listed in the Colour Index International, listed as pigment blue 1 through to pigment blue 83, and pigment violet 1 through to pigment violet 56. In another preferred embodiment, the optical agents may be selected from one or more of mica, interference mica, boron nitride, poly(methyl methacrylate) flake, composite microspheres, titanium dioxide coated glass flake, inverse opal, cholesteric liquid crystal, photonic sphere, hollow sphere and zinc oxide. Biomineralization agents for tooth enamel remineralization may be selected from one or more of fluoride sources, biomolecules, proteinaceous materials, amorphous calcium phosphate, otricalcium phosphate, β-tricalcium phosphate, calcium deficient hydroxyapatite Caio-x(HP04)x(P04)6-x(OH)2-x, 0 < x < 1 ), dicalcium phosphate (CaHPC ), dicalcium phosphate dihydrate (CaHP04-2H20), hydroxyapatite (Caio(P04)6(OH)2), monocalcium phosphate monohydrate (Ca(H2P04)2-H20), octacalcium phosphate (Ca8H2(P04)6-5H20) and tetracalcium phosphate (Ca4(P04)20). Antibacterial agents may be selected from one or more of metal salts where the metal is selected from zinc, copper, silver or a mixture thereof, triclosan, triclosan monophosphate, triclocarban, curcumin, quaternary ammonium compounds, bisbiguanides and long chain tertiary amines, preferably zinc salts including zinc oxide, zinc chloride, zinc acetate, zinc ascorbate, zinc sulphate, zinc nitrate, zinc citrate, zinc lactate, zinc peroxide, zinc fluoride, zinc ammonium sulfate, zinc bromide, zinc iodide, zinc gluconate, zinc tartarate, zinc succinate, zinc formate, zinc phenol sulfonate, zinc salicylate, zinc glycerophosphate or a mixture thereof. Gum health agents may be selected from one or more of anti-inflammatory agents, plaque buffers, biomolecules, proteinaceous materials, vitamin, plant extracts and curcumin. Freshness agents may be flavors selected from one or more of peppermint, spearmint, menthol, flora oil, clove oil and citrus oil.

The benefit agent is preferably particulate as this allows for maximum surface area for contact with dental tissue.

In a preferred embodiment, the benefit agent is a particulate whitening agent for tooth whitening. Typically, the particulate whitening agent comprises a material suitable to physically and immediately improve characteristics of teeth and especially whiten teeth. In order to provide excellent whitening effect, the material is preferred to have a high refractive index of at least 1 .9, more preferably at least 2.0, even more preferably at least 2.2, even more preferably still at least 2.4 and most preferably at least 2.5. The maximum refractive index of the material is not particularly limited but preferably up to 4.0. Preferably, the material has a refractive index ranging from 1.9 to 4.0.

Particularly suitable materials are metal compounds and preferred are compounds where the metal is selected from zinc (Zn), titanium (Ti), zirconium (Zr) or a combination thereof. Preferably, the metal compound is (or at least comprises) a metal oxide such as titanium dioxide (T1O2), zinc oxide (ZnO), zirconium dioxide (ZrC>2) or a combination thereof. In addition, the particulate whitening agent can also comprise non-metal oxides such as strontium titanate and zinc sulfide. In a preferred embodiment, the particulate whitening agent comprises metal oxides, non- metal oxides or a combination thereof in an amount of at least 50% by weight of the whitening agent and more preferably at least 70%, more preferably still from 80 to 100% and most preferably from 85 to 95%. In an especially preferred embodiment, the particulate whitening agent is at least 50% by weight titanium dioxide, and most preferably, from 60 to 100% by weight titanium dioxide, based on total weight of the whitening agent and including all ranges subsumed therein. In another especially preferred embodiment, the particulate whitening agents are slightly soluble or insoluble in water, but most preferably, insoluble in water.

In a preferred embodiment, the particulate whitening agents are composite particles. The refractive index of a composite particle comprising more than one material can be calculated based on the refractive indices and volume fractions of the constituents using effective medium theory, as is described for example in WO 2009/023353.

The composite particle comprises a first component core and a second component coating. Typically, the core of the composite particle comprises a material suitable to physically and immediately improve characteristics of teeth and especially whiten teeth. In order to provide excellent whitening effect, the material is preferred to have a high refractive index of at least 1 .9, more preferably at least 2.0, even more preferably at least 2.2, even more preferably still at least 2.4 and most preferably at least 2.5. The maximum refractive index of the material is not particularly limited but preferably up to 4.0. Preferably, the material has a refractive index ranging from 1.9 to 4.0.

Particular suitable materials are metal compounds and preferred are compounds where the metal is selected from zinc (Zn), titanium (Ti), zirconium (Zr) or a combination thereof. Preferably, the metal compound is (or at least comprises) a metal oxide such as titanium dioxide (T1O2), zinc oxide (ZnO), zirconium dioxide (ZrC>2) or a combination thereof. In addition, the core of the composite particle can also comprise non-metal oxides such as strontium titanate and zinc sulfide. The core of the composite particle typically makes up from 3 to 98%, and preferably from

6 to 65%, and most preferably from 10 to 55% by weight of the composite particle, based on total weight of the composite particle and including all ranges subsumed therein. In a preferred embodiment, the core comprises metal oxides, non-metal oxides or a combination thereof in an amount of at least 50% by weight of the core and more preferably at least 70%, more preferably still from 80 to 100% and most preferably from 85 to 95%. In an especially preferred embodiment, the core is at least 50% by weight titanium dioxide, and most preferably, from 60 to 100% by weight titanium dioxide, based on total weight of the first component core. The second component coating comprises material suitable to adhere to tooth enamel, dentin or both. In a preferred embodiment, the second component coating is suitable to interact with phosphate ions to produce calcium and phosphate in situ reaction products that adhere well to tooth enamel, dentin or both.

Typically the coating material comprises the element calcium, and optionally, other metals like potassium, sodium, aluminium, magnesium as well as mixtures thereof whereby such optional metals are provided as, for example, sulphates, lactates, oxides, carbonates or silicates. Optionally, the coating material may be aluminium oxide or silica. In a preferred embodiment, the coating material is suitable to provide a biological or chemical improvement to teeth which is long term (e.g., results in hydroxyapatite formation). Preferably, the coating employed comprises at least 50% by weight elemental calcium, and most preferably, at least 65% by weight elemental calcium based on total weight of metal in the coating. In an especially preferred embodiment, the metal in the coating is from 80 to 100% by weight of elemental calcium, based on total weight of metal in the second component coating and including all ranges subsumed therein. In another especially preferred embodiment, the core and the coating are slightly soluble or insoluble in water, but most preferably, insoluble in water.

In an especially desired embodiment, the second component coating can comprise, for example, calcium phosphate, calcium oxide, calcium carbonate, calcium hydroxide, calcium sulphate, calcium carboxymethyl cellulose, calcium alginate, calcium salts of citric acid, calcium silicate, mixture thereof or the like. In another desired embodiment, the calcium source in the coating comprises calcium silicate. In yet another preferred embodiment, the coating can comprise the element calcium which originates from insoluble calcium silicate, present as the composite material calcium oxide- silica (CaO-SiC>2) as described in international patent applications published as WO 2008/0151 17 and WO 2008/068248. When a calcium silicate composite material is employed as coating, the ratio of calcium to silicon (Ca:Si) may be from 1 :10 to 3:1 . The Ca:Si ratio is preferably from 1 :5 to 3:1 , and more preferably, from 1 :3 to 3:1 , and most preferably, from about 1 :2 to 3:1. The calcium silicate may comprise mono-calcium silicate, bi-calcium silicate, or tri-calcium silicate whereby ratios of calcium to silicon (Ca:Si) should be understood to be atom ratios. Usually, at least 30% of the outer surface area of the first component core is coated with the second component coating, preferably at least 50% of the core is coated with the coating, most preferably, from 70 to 100% of the outer surface area of the first component core is coated with the second component coating.

In an especially preferred embodiment, the particulate whitening agent is titanium dioxide coated with calcium silicate.

The particulate whitening agent according to the present invention can be of different sizes and shapes. The particles may be of spherical, platelet or irregular shape form. The diameter of the particulate whitening agent is often from 10 nm to less than 50 microns, and preferably, from 75 nm to less than 10 microns. In an especially preferred embodiment, the diameter of particles is from 100 nm to 5 microns, including all ranges subsumed therein. Particle size can be measured, for example, by dynamic light scattering (DLS). For composite particles, in a preferred embodiment, at least 40%, and preferably, at least 60%, and most preferably, from 75 to 99.5% of the diameter of the composite particle is the core, including all ranges subsumed therein.

The oral care composition of the present invention may comprise a single benefit agent or a mixture of two or more benefit agents. Typically, the benefit agent is present in an amount from 0.25 to 60%, and more preferably, from 0.5 to 40%, and most preferably, from 1 to 30% by total weight of the oral care composition and including all ranges subsumed therein.

When the benefit agent is incorporated into the oral care composition, the relative weight ratio of the calcium silicate to the benefit agent typically ranges from 1 :10 to 30:1 , more preferably from 1 :5 to 10:1 , most preferably from 1 :3 to 5:1.

The oral care composition of the present invention is found to be effective in inhibiting tooth demineralization and promoting remineralization thus protects tooth enamel from acid erosion. Without wishing to be bound by theory the present inventors believe that this may be because calcium silicate reacts with the phosphate source to form a new layer of hydroxyapatite that adheres to tooth enamel, dentin or both, which serves as a sacrificing layer or shield to prevent acid erosion. The presence of metal ions may be able to inhibit tooth teeth demineralization through ion exchange and interactions with enamel surfaces that induces the re-precipitation of smaller apatite crystallites along the c-axis to enhance the surface hardness of enamel. The present inventors have also found unexpectedly that the metal ions can even enhance the reaction between the calcium silicate and the phosphate source in the mouth to promote tooth remineralization efficacy that further helps resist acid erosion. When benefit agents are included in the oral care composition, the remineralization of the calcium silicate around the benefit agents helps the retention of those benefit agents on tooth surfaces by enhancing their resistance to shear force.

The oral care composition may further comprise a fluoride source to enhance enamel protection efficacy. Suitable fluoride sources include sodium fluoride, stannous fluoride sodium monofluorophosphate, zinc ammonium fluoride, tin ammonium fluoride, calcium fluoride, cobalt ammonium fluoride or mixtures thereof. The composition preferably comprises the fluoride source in an amount of at least 0.001 %, and more preferably from 0.01 to 12%, and most preferably from 0.1 to 5% by weight of the oral care composition, based on total weight of the oral care composition and including all ranges subsumed therein.

The oral care composition of the present invention may contain a variety of other ingredients which are common in the art to enhance physical properties and performance. These ingredients include preservatives, pH-adjusting agents, sweetening agents, particulate abrasive materials, polymeric compounds, buffers and salts to buffer the pH and ionic strength of the compositions, and mixtures thereof. Such ingredients typically and collectively make up less than 20% by weight of the composition, and preferably, from 0.0 to 15% by weight, and most preferably, from 0.01 to 12% by weight of the composition, including all ranges subsumed therein. The oral care composition of this invention can be used in a method for benefiting teeth of an individual comprising applying in the composition to at least one surface of the teeth of an individual, said benefits includes imparting acid resistance, remineralization, whitening and combinations thereof. The oral care composition of this invention may additionally or alternatively be for use as a medicament and/or used in the manufacture of a medicament for providing an oral care benefit as described herein, such as for imparting acid resistance to the teeth of an individual. Alternatively and preferably, the use is non-therapeutic.

In a preferred embodiment, the oral care composition is a monophase anhydrous composition. The composition is substantially free of water to prevent the premature reaction between the calcium silicate and the phosphate source. ln another preferred embodiment, the oral care composition is a dual-phase composition comprising a calcium phase and a phosphate phase, wherein the calcium silicate and the water soluble metal compound are present in the calcium phase and the phosphate source is present in the phosphate phase. The two phases are physically separate from one another by being in independent phases. The delivery of the two independent phases to the teeth may be simultaneous or sequential. In a preferred embodiment, the phases are delivered simultaneously. When a dual-phase oral care composition is desired, the calcium phase is preferred to be substantially free of water. Water may act as a carrier (along with thickeners and/or additional carriers herein described) and make up the balance of the phosphate phase in the dual-phase composition.

When a dual-phase composition is used, the calcium phase and the phosphate phase should not come into contact with each other until dispensed for use. In use, it is preferably to combine the two phases to form a mix prior to their application to the teeth. Typically, the weight ratio of the calcium phase and the phosphate phase in this mix is from 1 :3 to 10:1 , more preferably from 1 :2 to 7:1 , most preferably from 1 :1 .5 to 5:1 .

Typically, the dual-phase composition is delivered by a dual-tube having a first compartment for calcium phase and a second compartment for phosphate phase, which allows for co-extrusion of the two phases.

In a preferred embodiment, such a dual-tube has one of the compartments surrounding the other. In such embodiments, one phase is present as a sheath, surrounding the other phase in the core. In an especially preferred embodiment, the core is the calcium phase and the sheath is the phosphate phase.

In another preferred embodiment, such a dual-tube has the two compartments side by side within the same tube. In such embodiments, the two phases are extruded from the tube as one, such extrusion being termed "contact extrusion". A pump head may be used in such a dual-tube for squeezing the two phases from the tube as one.

The dual-phase oral care composition may be a gel composition that comprises two independent gel phases, the first is the calcium phase and the second is the phosphate phase. The means of delivery may involve a cotton rod, or a tray, onto which the calcium phase and the phosphate phase are applied, prior to the tray being placed in contact with the teeth.

The oral care composition of the present invention is prepared by conventional methods of making oral care compositions. Such methods include mixing the ingredients under moderate shear and atmospheric pressure.

Typically the composition will be packaged. In tooth paste or gel form, the composition may be packaged in a conventional plastic laminate, metal tube or a single compartment dispenser. The same may be applied to dental surfaces by any physical means, such as a toothbrush, fingertip or by an applicator directly to the sensitive area. In liquid mouthwash form the composition may be packaged in a bottle, sachet or other convenient container.

The composition can be effective even when used in an individual's daily oral hygiene routine. For example, the composition may be brushed onto the teeth. The composition may, for example, be contacted with the teeth for a time period of one second to 20 hours. More preferably from 1 s to 10 hours, more preferably still from 10 s to 1 hour and most preferably from 30 s to 5 minutes. The composition may be used daily, for example for use by an individual once, twice or three times per day. When the oral care composition is a dual-phase composition, the two phases of the composition are mixed during application. The mixed phases are typically left on the teeth for from 3 minutes to 10 hours, more preferably from 3 minutes to 8 hours. The application may be carried out one to five times monthly. The following examples are provided to facilitate an understanding of the present invention.

The examples are not provided to limit the scope of the claims.

Examples

Example 1

This example demonstrates the microhardness change of tooth enamel.

Materials

Tri-calcium silicate (CasSiOs) powder were prepared by the sol-gel method as described in Zhao et al {Biomaterials, 2005, 26, 61 13-6121 ) and sieved to 300 meshes for use. Potassium dihydrogen phosphate (KH2PO4) was purchased from Sinopharm Chemical Reagent Co. Ltd, China and used as received. Magnesium chloride (MgC ), calcium chloride (CaC ), strontium chloride (SrC ) and zinc chloride (ZnC ) were purchased from Sinpharm Chemical Reagent Co., Ltd, China.

TABLE 1

Methods

Samples Preparation

MgC , CaC , SrC and ZnC were made into 0.1 mol/L water solution and used. The weight ratio of CasSiOs powder to KH2PO4 powder was kept at 15:7, and the liquid/powder ratio was kept at 20 mL/2.2g for all test samples. As Mg²⁺ and Sr²⁺ ions slightly hydrolyze in water, the pH of 0.1 mol/L MgC and SrCb were around 5.6. In order to keep the same pH of liquid phase, the pH of 0.1 mol/L CaC and ZnCb was adjusted to 5.6 with HCI solution. pH of Sample 3 was 6.8, but pH of Sample 4 was adjusted to 5.6 with HCI solution. For each test sample, the powders and solution were mixed and agitated on a mini-shaker for 20 seconds and the resulted slurry was used immediately.

Intact bovine enamel teeth were cut into blocks of approximately 4mm x 4mm by diamond- coated band saw (SYJ-150; Kejing, Shenyang, China). The enamel surface were polished through different roughness (180, 800, 1200, 1500 and 2000 grit, 3 μηι and final 0.25 m) under water irrigation and then cleaned ultrasonically in distilled water. To evaluate the microhardness of tooth enamel, the bovine enamel blocks were divided into seven treatment groups (n=9 per group) with similar baseline values of surface microhardness. The bovine enamel blocks were soaked in 20 mL freshly prepared slurry for 3 mins and then placed in 40 mL water and agitated on a flatbed shaker at 150 rpm for 1 min. After that, the enamel blocks were placed in simulated oral fluid (SOF) under the condition of a shaking water bath at 37°C and 60.0 rpm. After soaking for about 3 hours, the enamel blocks were subjected to acid erosion (1 % citric acid, pH 3.6) for 2 mins at room temperature and then rinsed with water immediately. The enamel blocks were soaked in SOF and eroded by acid again using the same procedure for one more time before soaked in SOF for another 3 hours. Then the enamel blocks were soaked in freshly prepared slurry for 3 mins and rinsed with water. The enamel blocks were then kept in in SOF overnight (>12 hours) in a shaking water bath at 37°C to mimic oral environment. The whole treatment within one day was called one pH-cycling treatment.

Simulated oral fluid was made by combining the ingredients in Table 2:

TABLE 2

Microhardness Test

The enamel surface microhardness was measured with a microhardness tester (Struers Durascan) using a Knoop indenter at 50g load for 10s. Five indentations were made per test point for each specimen in different regions to avoid residual stress.

Results

Knoop microhardness (Knoop hardness number, KHN) was measured before (baseline surface microhardness) and after 1 , 3, and 5 pH-cycling treatments. The results are summarized in Table 3 (error represents standard deviation for duplicate measurements). The Knoop microhardness reduction percentage from baseline is calculated and summarized in Table 4 (error represents standard deviation for duplicate measurements). Knoop microhardness reduction percentage (%) = (KH Ntreated-KH Nbaseiine) x 100/KH Nbaseiine

TABLE 3

Knoop Samples

Microhardn 1 2 3 4 5 6 7

ess

Baseline 329±31 . 329±26. 329±25. 328±34. 329±29. 330±26. 329±25.

9 8 7 9 0 1 2

One cycle 275±13. 299±24. 303±30. 287±40. 330±30. 307±33. 332±21.

2 5 1 8 0 9 3

Three 227±27. 263±8.4 256±21 . 268±35. 31 1 ±27. 285±29. 284±14. cycles 4 3 8 0 7 5

Five cycles 172±19. 237±15. 246±20. 250±24. 276±33. 268±27. 265±13.

7 0 4 9 2 3 2

TABLE 4

Knoop Samples

Microhardn 1 2 3 4 5 6 7

ess

Reduction/

%

One cycle -16 ± -9 ± 4.3 -8 ± 4.7 -13 ± 0 ± 5.7 -7 ± 7.7 1 ± 4.7

5.1 5.6

Three -31 ± -20 ± -22 ± -18 ± -5 ± 6.6 -14 ± -13 ± cycles 8.4 6.2 3.9 4.1 5.8 5.0

Five cycles -48 ± -28 ± -25 ± -24 ± -16 -19 ± -19 ±

6.6 7.0 4.1 6.5 ±10.5 6.3 4.0 TABLE 5

Sample 1 comprising double distilled water was used as negative control and Sample 2 comprising 1450 ppm sodium fluoride was used as positive control. It showed that all samples had significantly higher surface microhardness values (p<0.05) than Sample 1 after pH-cycling treatments, which demonstrated that all samples had better enamel protection efficacy compared to Sample 1. Sample 3 comprising a combination of tri- calcium silicate and phosphates showed comparable protection efficacy to Sample 2 comprising sodium fluoride.

After 5 pH-cycling treatments, Samples 5 to 7 comprising additional metal ions all showed significantly higher surface microhardness values (p<0.05) and less microhardness reduction (p<0.05) than Sample 3, which demonstrated better resistance to acid challenges and enhanced enamel protection efficacy.

Table 5 further showed that Samples 5 and 7 exhibited significantly less microhardness reduction (p<0.01 ) than Sample 3 after one pH-cycling treatment. But Sample 8 comprising additional zinc ions exhibited comparable microhardness reduction to Sample 3. In addition, the pH of the liquid phase was dropped to about 5.6 by incorporating different metal ions. To evaluate the effect of weakly acidic liquid phase on the changes in microhardness, Sample 3 comprising a combination of tri-calcium silicate and phosphates (pH 6.8) was compared with Sample 4 (pH was adjusted to 5.6 with HCI solution). The results clearly showed that the two samples had comparable surface microhardness values before and after pH-cycling treatments, which indicates the pH drop from 6.8 to 5.6 of liquid phase did not affect the changes in microhardness of enamel surface.

Claims

1. An oral care composition comprising:

a) from 1 to 80% by weight of calcium silicate;

b) a phosphate source;

c) from 0.01 to 20% by weight of a water soluble metal compound; and

d) a physiologically acceptable carrier;

wherein the metal comprises magnesium, strontium or a mixture thereof;

2. The oral care composition according to claim 1 , wherein the calcium silicate comprises Ca and Si in an atom ratio of from 1 :30 to 3:1 , preferably from 1 :20 to 3:1 .

3. The oral care composition according to any of the preceding claims, wherein the calcium silicate is present in an amount of from 3 to 50% by weight of the composition.

4. The oral care composition according to any of the preceding claims, wherein the metal compound comprises magnesium chloride, strontium chloride or a mixture thereof. 5. The oral care composition according any of the preceding claims, wherein the calcium silicate and the metal compound are present in a weight ratio of from 1 :3 to 25:1 , preferably from 1 :1 .

5 to 20:1.

6. The oral care composition according to any of the preceding claims, wherein the phosphate source is trisodium phosphate, monosodium dihydrogen phosphate, disodium hydrogen phosphate, ammonium phosphate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, tripotassium phosphate, monopotassium dihydrogen phosphate, dipotassium hydrogen phosphate or a mixture thereof, preferably trisodium phosphate, monosodium dihydrogen phosphate or a mixture thereof.

7. The oral care composition according to any of the preceding claims, wherein the calcium silicate and the phosphate source are present in a weight ratio of from 1 : 10 to 30: 1 , preferably from 1 :5 to 20:1 .

8. The oral care composition according to any of the preceding claims, wherein the composition has a pH from 4.0 to 10.0, preferably from 5.0 to 8.0.

9. The oral care composition according to any of the preceding claims, wherein the composition further comprises a fluoride source including sodium fluoride, stannous fluoride sodium monofluorophosphate, zinc ammonium fluoride, tin ammonium fluoride, calcium fluoride, cobalt ammonium fluoride or mixtures thereof.

10. The oral care composition according to any of the preceding claims, wherein the composition further comprises a benefit agent, preferably a particulate whitening agent.

1 1 . The oral care composition according to claim 10, wherein the particulate whitening agent is a composite particle, preferably titanium dioxide coated with calcium silicate.

12. The oral care composition according to any of the preceding claims, wherein the oral care composition is a monophase anhydrous composition.

13. The oral care composition according to any one of claims 1 to 1 1 , wherein the composition is a dual-phase composition comprising a calcium phase and a phosphate phase, wherein the calcium silicate and the water soluble metal compound are present in the calcium phase, and the phosphate source is present in the phosphate phase.

14. A method for remineralizing and/or whitening of and/or imparting acid resistance to teeth of an individual comprising the step of applying the composition as claimed in any of the preceding claims to at least one surface of the teeth of the individual.