EA039652B1 - Oral care composition - Google Patents

Abstract

A dual-phase oral care composition is disclosed comprising a first phase comprising a water insoluble and/or slightly soluble calcium source in an amount of from 20 to 75 wt.% of the first phase of the composition, a second phase comprising a potassium phosphate salt in an amount of from 30 to 75 wt.% of the second phase of the composition, wherein the first phase further comprises a tubule blockage enhancer selected from calcium dihydrogen phosphate, calcium sulfate hemihydrate or mixtures thereof.

Description

The present invention relates to oral care compositions such as toothpastes, chewing gums, and the like. In particular, the present invention relates to a biphasic oral composition containing high levels of an insoluble and/or slightly water soluble source of calcium, potassium phosphates, and a tubular occlusion enhancer that desensitizes teeth. The invention also relates to the use of such compositions for the treatment of hypersensitivity and/or remineralization and/or whitening of an individual's teeth.

Prerequisites for the creation of the invention

Dental hypersensitivity is a temporarily induced sensation of pain affecting up to 20% of the adult population. Hypersensitive teeth may be sensitive to temperature, pressure, or chemicals.

The dentin of teeth usually contains channels called tubules that provide osmotic flow between the inner pulp area of the tooth and the outer surfaces of the root. Tooth hypersensitivity may be associated with a general increase in exposed tooth root surfaces as a result of periodontal disease, toothbrush abrasion, or fatigue due to cyclic loading of thin enamel near the enamel-dentin junction. If the root surfaces are exposed, then the dentinal tubules are also exposed.

The currently accepted theory of tooth hypersensitivity is a hydrodynamic theory based on the assumption that open, exposed dentinal tubules allow fluid flow to flow through the tubules. This flow excites the nerve endings in the pulp of the tooth. Clinical casts of sensitive teeth, when viewed with a scanning electron microscope (SEM), show varying numbers of open or partially occluded dentinal tubules.

There are various approaches to the treatment of dental hypersensitivity. One approach is to reduce nerve excitability in a sensitive tooth with nerve depolarizing agents containing strontium ions, potassium salts such as potassium nitrate, potassium bicarbonate, potassium chloride, and the like. These nerve depolarizing agents work by blocking the transmission of pain signals by the nerves, making the nerve less sensitive.

Another approach is to use tubular occluding agents that completely or partially plug the tubules, such as polystyrene beads, apatite, polyacrylic acid, mineral hectorite clay, and the like. These tubular plugging agents function by physically plugging the exposed ends of the dentinal tubules, thereby reducing the movement of dentinal fluid and reducing irritation associated with shear stress as described by hydrodynamic theory.

There remains a need to treat tooth hypersensitivity with a more effective approach. The present inventors have surprisingly found that a biphasic oral composition containing high levels of an insoluble and/or slightly water soluble source of calcium and potassium phosphate in combination with a tubular occlusion enhancer can be effective in instantly occluding dentinal tubules to reduce tooth sensitivity. In addition, such a composition may also increase the effectiveness of tooth remineralization and/or deposition of beneficial agents on tooth surfaces to further improve an individual's teeth.

Additional Information

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

The above publication does not describe a two-phase oral care composition containing a first phase containing an insoluble and/or water-soluble source of calcium in an amount of 20 to 75% based on the weight of the first phase of the composition, a second phase containing potassium phosphate in an amount of 30 to 75% based on the weight of the second phase of the composition; and wherein the first phase further comprises a tubular occlusion enhancer selected from calcium dihydrogen phosphate, calcium sulfate hemihydrates, or mixtures thereof, and in particular, such an oral composition can treat tooth hypersensitivity and/or increase the effectiveness of tooth remineralization.

Research and definitions

two-phase

Biphasic for the purposes of the present invention means a composition having two independent phases that are physically separated.

dentifrice

A dentifrice for the purposes of the present invention means a paste, powder, liquid, chewing gum or other preparation for cleaning teeth or other surfaces in the oral cavity.

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Toothpaste

Toothpaste for the purposes of the present invention means a paste or gel for cleaning teeth with a toothbrush. Particularly preferred are toothpastes suitable for brushing the teeth for about 2 minutes.

Particle size

The particle size for the purposes of the present invention means the particle size D50. The particle size D50 of a particulate material is the particle diameter at which 50% by weight of the particles have a larger diameter and 50% by weight have a smaller diameter. For the purposes of the present invention, particle sizes and distributions are measured using the Malvern Mastersizer 2000 and Malvern ZetaSizer Nano series.

Composite particle

Composite particle for the purposes of the present invention means a particle containing a core as a first component and a coating as a second component, while the core and coating are composed of different materials.

Refractive index

The refractive index is set at a temperature of 25°C and a wavelength of 589 nm.

Tubular occlusion enhancer

A tubular occlusion enhancer for the purposes of the present invention means a material that promotes the precipitation of active substances, such as an insoluble and/or slightly water soluble source of calcium, from the continuous phase of the composition onto the dentin and/or into the dentinal tubules, to induce in situ formation of calcium phosphate, which clogs the dentinal tubules and/or their exposed open ends during application of the composition. When beneficial agents are present in an oral composition, remineralization of the calcium source around the beneficial agents further helps to retain those beneficial agents on tooth surfaces, increasing their shear resistance. Beneficial agents as used herein means active substances typically delivered to human teeth and/or the oral cavity, including gums, to enhance or improve the performance of these dental tissues.

pH

The pH value is set at atmospheric pressure and a temperature of 25°C. With regard to the pH value of the composition for caring for the oral cavity, it means the pH measured when 5 wt.h. compositions uniformly dispersed and/or dissolved in 20 wt.h. pure water at 25°C. In particular, the pH value can be measured manually by mixing 5 g of the oral composition with 20 ml of water for 30 seconds, followed by immediate testing with a pH indicator or pH meter.

Solubility

Soluble and insoluble for the purposes of the present invention means the solubility of the source (eg calcium salts) in water at 25°C and atmospheric pressure. Soluble means a source that dissolves in water to produce a solution with a concentration of at least 0.1 mol per liter. Insoluble means a source that dissolves in water to give a solution with a concentration of less than 0.001 moles per liter. Sparingly soluble is thus defined as a source that dissolves in water to produce a solution with a concentration greater than 0.001 mol/l and less than 0.1 mol/l.

Water hydration

Water of hydration for the purposes of the present invention means water chemically combined with a substance in such a way that it can be removed by heating without substantially changing the chemical composition of the substance, in particular water which can only be removed by heating above 200°C. Water loss is measured by thermogravimetric analysis (TGA) using a Netzsch TG instrument. TGA is carried out in an atmosphere of N ₂ with a heating rate of 10°/min in the range from 30 to 900°C.

Essentially does not contain

Substantially free for the purposes of the present invention means less than 1.5%, preferably less than 1.0%, more preferably less than 0.75%, and even more preferably less than 0.5%, and even more preferably less than 0.1%, and most preferably from 0.0 to 0.01% by weight, based on the total weight of the oral composition, including all ranges within the specified limits.

Viscosity

The viscosity of a toothpaste or gel is a value measured at room temperature (25° C.) with a Brookfield viscometer, No. 4 spindle, and at 5 rpm. Values are in centipoise (cP=mPa-s) unless otherwise noted.

Remineralization

Remineralization for the purposes of the present invention means in situ (i.e., in the oral cavity) formation of calcium phosphate on teeth (including layers on teeth with a thickness of 10 nm to 20 microns, preferably 75 nm to 10 microns, and most preferably 150 nm to 5 microns, including all ranges within the specified limits) to reduce the likelihood of tooth sensitivity, dental

- 2 039652 caries, to regenerate enamel and/or improve the appearance of teeth by whitening through the formation of such new calcium phosphate.

Rest

Except in the examples, or where expressly stated otherwise, all numbers in this specification indicating amounts of material or reaction conditions, physical properties of the materials, and/or application may not necessarily be construed as modified by the word about. All amounts are based on the weight of the final composition for caring for the oral cavity, unless otherwise indicated.

It should be noted that when specifying any ranges of values, any particular upper value can be associated with any specific lower value.

For the avoidance of doubt, the word containing means including, but not necessarily consisting of or consisting of. In other words, the steps or options listed are not meant to be exhaustive.

It is intended that the disclosure of the invention described herein cover all embodiments contained in the claims as multiple dependent claims, regardless of whether the claims can be found without multiple dependency or redundancy.

If a feature is disclosed in part of a particular aspect of the invention (eg, a composition of the invention), such disclosure should also be considered applicable to any other aspect of the invention (eg, a method of the invention), mutatis mutandis.

Brief description of the invention

In a first aspect, the present invention relates to an oral care composition comprising:

a) a first phase containing an insoluble and/or slightly water-soluble source of calcium in an amount of 20 to 75% based on the weight of the first phase of the composition;

b) a second phase containing a potassium phosphate salt in an amount of 30 to 75% based on the weight of the second phase of the composition; and wherein the first phase further comprises a tubular occlusion enhancer selected from calcium dihydrogen phosphate, calcium sulfate hemihydrates, or mixtures thereof.

In a second aspect, the present invention relates to a packaged oral care product containing an oral care composition according to the first aspect of the present invention.

In a third aspect, the present invention relates to a method for desensitising and/or remineralizing and/or whitening an individual's teeth, comprising the step of applying an oral composition according to any embodiment of the first aspect to at least one surface of the individual's teeth.

All other aspects of the present invention will become more apparent after considering the detailed description and examples that follow.

Detailed description of the invention

It has now been found that a biphasic oral composition containing high levels of an insoluble and/or slightly water soluble source of calcium and potassium phosphate in combination with a tubular occlusion enhancer can be effective in instantly occluding dentinal tubules to reduce tooth sensitivity. In addition, such a composition may also increase the effectiveness of tooth remineralization and/or deposition of beneficial agents on tooth surfaces to further improve an individual's teeth.

The water-insoluble and sparingly soluble source of calcium useful in the present invention is limited only to the extent that it can be used in the oral cavity. Illustrative, but non-limiting examples of the types of calcium source that can be used in the invention include, for example, calcium silicate, calcium carbonate, calcium aluminate, calcium oxalate, calcium aluminum silicate, calcium hydroxide, calcium glycerophosphate, calcium oxide, calcium sulfate, calcium carboxymethylcellulose, calcium alginate, calcium salts of citric acid, or mixtures thereof. Preferably, the source of calcium is calcium silicate.

In a preferred embodiment, the calcium silicate used, which has low water solubility, is commercially available under the name Sorbosil CA40 from PQ Corporation. In another preferred embodiment, the calcium silicate is insoluble, present as a calcium oxide-silica (CaO-SiO ₂ ) composite material, which is described, for example, in the international patent application published as WO 2008/01517 (Unilever), the full content which is incorporated herein by reference. For a calcium silicate composite material, the atomic ratio of calcium to silicon (Ca:Si) can range from 1:30 to 5:1. The Ca:Si ratio is preferably 1:20 to 3:1, more preferably 1:10 to 3:1, and most preferably about 1:7 to 3:1. The calcium silicate may contain monocalcium silicate, bicalcium silicate or tricalcium silicate. The calcium silicate may be in a crystalline or amorphous state, or even in a mesoporous state.

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In addition to calcium oxide, silica, particles containing calcium silicate that is not hydrated may contain other components such as metal cations, anions (such as phosphate), and the like. However, it is preferred that the particles contain calcium oxide, silica in an amount of at least 70% by weight of the particles, more preferably at least 80%, even more preferably at least 90%, and even more preferably at least 95%. Most preferably, the particles consist of (or at least essentially consist of) calcium oxide, silicon dioxide.

In another preferred embodiment, the calcium silicate is calcium silicate hydrate. The calcium silicate hydrate for use in the present invention contains at least calcium oxide (CaO), silicon dioxide (SiO ₂ ) and water. Compared to conventional calcium silicate which is not hydrated, calcium silicate hydrate contains water of hydration in an amount of at least 5% by weight of 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 usually not more than 50% by weight of the calcium silicate hydrate, more preferably not more than 40%, even more preferably not more than 35%, and most preferably not more than 30%.

The calcium silicate hydrate preferably contains at least 20% silica based on the weight of calcium silicate hydrate, more preferably at least 30%, even more preferably at least 40% and most preferably at least 55%. The silica content is preferably not more than 70% by weight of calcium silicate hydrate, more preferably not more than 65% and most preferably not more than 60%.

To provide the calcium needed for remineralization, the calcium silicate hydrate preferably contains calcium oxide in an amount of at least 5% by weight of the calcium silicate hydrate, more preferably at least 7%, even more preferably at least 10%, even more preferably at least 12% and most preferably at least 15%. The content of calcium oxide is generally not more than 50% by weight of calcium silicate hydrate, more preferably not more than 40%, even more preferably not more than 30%, and most preferably not more than 25%.

The calcium silicate hydrate preferably contains Ca and Si in an atomic ratio (Ca:Si) of less than 3:1, more preferably less than 1:1, even more preferably from 1:1.5 to 1:4, and most preferably from 1:1 .7 to 1:3.

The calcium silicate may be amorphous or at least partially crystalline or mesoporous. The calcium silicate is preferably in particulate form, as this provides the maximum surface area for contact with dental tissue. Thus, preferably the composition contains particles containing calcium silicate. Preferably 10 to 100% and especially 25 to 100% and most preferably 70 to 100% by weight of the calcium silicate containing particles used in this invention have a particle size of 100 nm to less than 50 microns, preferably 500 nm up to 30 microns, more preferably 1 to 20 microns, most preferably 1 to 10 microns.

In addition to calcium oxide, silica, and water, the particles that contain calcium silicate hydrate may contain other components such as metal cations, anions (such as phosphate), and the like. However, it is preferred that the particles contain CaO, SiO ₂ and water in an amount of at least 70% by weight of the particles, more preferably at least 80%, even more preferably at least 90% and even more preferably at least 95%. Most preferably, the particles consist of (or at least essentially consist of) CaO, SiO2 and water.

Typically, the water-insoluble and/or sparingly soluble calcium source is present in an amount of 20% to 75%, more preferably 25% to 60%, most preferably 28% to 50%, based on the total weight of the first phase of the oral composition. and including all ranges within the specified limits.

Preferably, the first phase of the oral composition is substantially free of phosphate sources.

Potassium phosphate suitable for use in the present invention is capable of reacting with the calcium source used to form hydroxyapatite in situ.

The potassium phosphate salt that can be used in the present invention includes potassium dihydrogen phosphate, dipotassium hydrogen phosphate, tripotassium phosphate, or mixtures thereof. Preferably, the potassium phosphate salt is potassium dihydrogen phosphate, dipotassium hydrogen phosphate, or mixtures thereof. In a particularly preferred embodiment, the potassium phosphate salt contains or is a mixture of dipotassium hydrogen phosphate and potassium dihydrogen phosphate.

Typically, the potassium phosphate salt is present in an amount of 20% to 75%, more preferably 30% to 70%, most preferably 35% to 60%, based on the total weight of the second phase of the oral composition and including all ranges therein.

Preferably, the second phase of the composition is substantially free of calcium sources.

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Preferably the second phase of the composition is an aqueous composition. The water content of the second phase of the composition is greater than 1.5%, preferably greater than 5%, more preferably 20 to 90% and most preferably 40 to 60% of the total weight of the second phase of the composition.

Preferably the second phase of the composition has a pH of less than 11.0, more preferably 3.0 to 10.0 and most preferably 5 to 8.0.

Other sources of phosphate may also be used in the second phase of the oral composition in addition to the potassium phosphate salt included in the composition. Such a phosphate source includes, for example, trisodium phosphate, monosodium dihydrogen phosphate, disodium hydrogen phosphate, sodium pyrophosphate, tetrasodium pyrophosphate, sodium hexametaphosphate, mixtures thereof, or the like.

The oral care composition preferably contains an insoluble and/or slightly water soluble source of calcium and a potassium phosphate salt in a weight ratio of 10:1 to 1:10, more preferably 5:1 to 1:5, most preferably 4:1 up to 1:4.

The tubular occlusion enhancer suitable for use in the present invention is limited only to the extent that it can be taken orally. In a preferred embodiment, the tubular occlusion enhancer provides a high amount of calcium ions in the mouth and is inexpensive and readily available. In a particularly preferred embodiment, the tubular occlusion enhancer is calcium salts in addition to the insoluble and/or sparingly water soluble source of calcium that is included in the composition.

The materials used as a tubular occlusion enhancer in the present invention have been found to be biocompatible and undergo rapid reaction in water and complete resorption on dentin and/or tooth enamel, so they can be used to promote the deposition of oral care actives, such as an insoluble and/or slightly water soluble source of calcium, on the dentin and/or in the dentinal tubules, to induce in situ formation of calcium phosphate which plugs the dentinal tubules and/or their exposed open ends.

Illustrative, but non-limiting examples of the types of tubular occlusion enhancers that can be used in the present invention include, for example, calcium sulfate hemihydrates, calcium dihydrogen phosphate, calcium monohydrogen phosphate, mixtures thereof, or the like. In a preferred embodiment, the tubular occlusion enhancer is calcium sulfate hemihydrate, calcium dihydrogen phosphate, or mixtures thereof. Most preferably, the tubular occlusion enhancer is calcium dihydrogen phosphate.

Typically, the tubular occlusion enhancer is present in an amount of 0.1 to 40%, more preferably 0.5 to 30%, even more preferably 1 to 20%, most preferably 2 to 10%, based on the total weight of the first phase of the composition for caring for the oral cavity and including all ranges within the specified limits.

The oral care composition preferably contains an insoluble and/or slightly water soluble source of calcium and a tubular occlusion enhancer in a weight ratio of 30:1 to 1:5, more preferably 15:1 to 1:3, most preferably 10:1 up to 1:1.

The oral care composition may further comprise beneficial agents that are typically delivered to a person's teeth and/or oral cavity, including gums, to enhance or improve the characteristics of those dental tissues. The only limitation on beneficial agents that can be used in this invention is that they are suitable for use in the mouth.

Typically, the beneficial agent is selected from optic agents, biomineralizing agents, antibacterial agents, gum treatment agents, desensitizing agents, anti-stone agents, refreshing agents, or mixtures thereof. Preferably, the benefit agent is selected from optical agents, biomineralizing agents, antibacterial agents, gum health agents, refreshing agents, or mixtures thereof.

For example, optical agents such as coloring agents like whitening agents and pigments. Preferably the pigment, if used, is violet or blue having a hue angle, h, in the CIELAB system of 220° to 320°. These pigments may be selected from one or more of the pigments listed in Color Index International, listed from Pigment Blue 1 to Pigment Blue 83 and Pigment Violet 1 to Pigment Violet 56. In another preferred embodiment, the optical agents may be selected from one or more mica, interference mica, boron nitride, polymethylmethacrylate flakes, composite microspheres, titanium dioxide coated glass flakes, reverse opal, cholesteric liquid crystal, photonic sphere, hollow sphere and zinc oxide. Biomineralizing agents for remineralizing tooth enamel can be selected from one or more of fluoride sources, biomolecules, proteinaceous materials, amorphous calcium phosphate, α-tricalcium phosphate, β-tricalcium phosphate, calcium deficient hydroxyapatite Ca ₁₀ .X(HPO4) _X (PO4) ₆ - _X (OH) ₂ -X, 0<x<1), dicalcium phosphate (CaHPO ₄ ), dicalcium phosphate dihydrate (CaHPO4-2H2O), hydroxyapatite

- 5 039652 (Ca ₁₀ (PO ₄ ) b (OH) 2), monocalcium phosphate monohydrate (Ca (H ₂ PO ₄ ) ₂ -H ₂ O), octacalcium phosphate (Ca ₈ H ₂ (PO ₄ ) 6-5H ₂ O) and tetracalcium phosphate (Ca ₄ (PO ₄ ) ₂ O). The antibacterial agents may be selected from one or more of the metal salts, the metal being selected from zinc, copper, silver, or mixtures thereof, triclosan, triclosan monophosphate, triclocarban, curcumin, quaternary ammonium compounds, bisguanidines, and long chain tertiary amines, preferably zinc salts, including zinc oxide, zinc chloride, zinc acetate, zinc ascorbate, zinc sulfate, zinc nitrate, zinc citrate, zinc lactate, zinc peroxide, zinc fluoride, zinc ammonium sulfate, zinc bromide, zinc iodide, zinc gluconate, zinc tartrate, zinc succinate , zinc formate, zinc phenolsulfonate, zinc salicylate, zinc glycerophosphate, or a mixture thereof. The gum health agents may be selected from one or more of anti-inflammatory agents, plaque buffers, biomolecules, protein materials, vitamins, plant extracts, and curcumin. Refreshing agents may be flavors selected from one or more of peppermint, spearmint, menthol, vegetable oil, clove oil, and citrus oil.

The benefit agent is preferably in particulate form as this provides the maximum surface area for contact with the dental tissue.

In a preferred embodiment, the benefit agent is a particulate whitening agent for whitening teeth.

Generally, the particulate whitening agent contains a material suitable for physical and immediate improvement of the characteristics of the teeth and especially the whitening of the teeth. In order to provide an excellent whitening effect, the material should preferably 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 at least 2.4 and most preferably at least 2.5. The maximum refractive index of the material is not particularly limited, but is preferably up to 4.0. Preferably the material has a refractive index in the range of 1.9 to 4.0.

Particularly suitable materials are metal compounds, and compounds in which the metal is selected from zinc (Zn), titanium (Ti), zirconium (Zr) or combinations thereof are preferred. Preferably, the metal compound is (or at least includes) a metal oxide such as titanium dioxide (TiO ₂ ), zinc oxide (ZnO), zirconia (ZrO ₂ ), or a combination thereof. In addition, the particulate whitening agent may also contain non-metal oxides such as strontium titanate and zinc sulfide.

In a preferred embodiment, the particulate bleaching agent comprises metal oxides, non-metal oxides, or combinations thereof, in an amount of at least 50% by weight of the bleaching agent, more preferably at least 70%, even more preferably 80 to 100%, and most preferably from 85 to 95%. In a particularly preferred embodiment, the particulate bleaching agent contains at least 50% by weight of titanium dioxide and most preferably from 60 to 100% by weight of titanium dioxide, based on the total weight of the bleaching agent and including all ranges within the specified ranges. In another particularly preferred embodiment, the particulate bleaching agents are sparingly or water insoluble, but most preferably water insoluble.

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

The composite particle contains the core as the first component and the coating as the second component. Generally, the core of the composite particle contains a material suitable for physical and immediate improvement of the characteristics of the teeth and especially the whitening of the teeth. In order to provide an excellent whitening effect, the material should preferably 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 at least 2.4 and most preferably at least 2.5. The maximum refractive index of the material is not particularly limited, but is preferably up to 4.0. Preferably the material has a refractive index in the range of 1.9 to 4.0.

Particularly suitable materials are metal compounds, and compounds in which the metal is selected from zinc (Zn), titanium (Ti), zirconium (Zr) or combinations thereof are preferred. Preferably, the metal compound is (or at least includes) a metal oxide such as titanium dioxide (TiO ₂ ), zinc oxide (ZnO), zirconia (ZrO ₂ ), or a combination thereof. In addition, the core of the composite particle may also contain non-metallic oxides such as strontium titanate and zinc sulfide.

The core of the composite particle typically comprises 3 to 98%, preferably 6 to 65% and most preferably 10 to 55% by weight of the composite particle, based on the total weight of the lump.

- 6 039652 positive particles and including all ranges within the specified limits. In a preferred embodiment, the core contains metal oxides, non-metal oxides, or combinations thereof, in an amount of at least 50% by weight of the core, more preferably at least 70%, even more preferably 80 to 100%, and most preferably 85 to 95%. In a particularly preferred embodiment, the core comprises at least 50% by weight of titanium dioxide, and most preferably from 60 to 100% by weight of titanium dioxide, based on the total weight of the core of the first component.

The second component as a coating contains a material suitable for adhesion to tooth enamel, dentin, or both. Typically, the coating material contains the element calcium and optionally other metals such as potassium, sodium, aluminum, magnesium, as well as mixtures thereof, such optional metals being present, for example, as sulfates, lactates, oxides, carbonates or silicates. Optionally, the coating material may be alumina or silicon dioxide. In a preferred embodiment, the coating material is suitable for providing biological or chemical dental enhancement that is long term (eg, produces hydroxyapatite). Preferably the coating used contains at least 50% by weight of elemental calcium and most preferably at least 65% by weight of elemental calcium, based on the total weight of the metal in the coating. In a particularly preferred embodiment, the metal in the coating is between 80% and 100% by weight of elemental calcium, based on the total weight of the metal in the second component of the coating, and including all ranges therein. In another particularly preferred embodiment, the core and coating are sparingly or water insoluble, but most preferably water insoluble.

In a particularly preferred embodiment, the second coating component may comprise, for example, calcium phosphate, calcium oxide, calcium carbonate, calcium hydroxide, calcium sulfate, carboxymethyl cellulose, calcium alginate, calcium salts of citric acid, calcium silicate, a mixture thereof, or the like. In another desirable embodiment, the calcium source in the coating comprises calcium silicate.

In yet another preferred embodiment, the coating may contain a calcium element which is derived from insoluble calcium silicate present as a calcium oxide-silica (CaO-SiO ₂ ) composite material as described in international patent applications published as WO 2008/015117 and WO 2008/068248.

When a calcium silicate composite is used as the coating, the ratio of calcium to silicon (Ca:Si) can be from 1:10 to 3:1. The Ca:Si ratio is preferably 1:5 to 3:1, more preferably 1:3 to 3:1, and most preferably about 1:2 to 3:1. The calcium silicate may be a monocalcium silicate, a bicalcium silicate or a tricalcium silicate, wherein the ratios of calcium to silicon (Ca:Si) are to be understood as atomic ratios.

As a rule, at least 30% of the outer surface area of the core containing the first component is coated containing the second component, preferably at least 50% of the core is coated, most preferably from 70 to 100% of the outer surface area of the core containing the first component, has a coating containing the second component.

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

The particulate whitening agent according to the present invention may have different sizes and shapes. The particles may be spherical, lamellar or irregular in shape. The diameter of the particulate whitening agent is often 10 nm to less than 50 μm, and preferably 75 nm to less than 10 μm. In a particularly preferred embodiment, the particle diameter is from 100 nm to 5 μm, including all ranges within the indicated ranges. For composite particles, in a preferred embodiment, at least 40%, preferably at least 60%, and most preferably from 75 to 99.5% of the composite particle diameter is the core, including all ranges within the specified ranges.

The oral care composition of the present invention may contain a single beneficial agent or a mixture of two or more beneficial agents. Beneficial agents may be present in either of the two phases of the oral composition. Generally, the beneficial agent is present in an amount of 0.25% to 60%, more preferably 0.5% to 40%, and most preferably 1 to 30% of the total weight of the oral composition, and includes all ranges within these limits.

When beneficial agents are included in an oral composition, the relative weight ratio of insoluble and/or slightly water-soluble calcium source to beneficial agent may vary from 1:10 to 30:1, preferably from 1:5 to 10:1, most preferably from 1:3 to 5:1.

The oral composition of the present invention has been found to be effective in instantly plugging dentinal tubules to reduce sensitivity

- 7 039652 teeth. Without wishing to be limited by theory, the present inventors believe that this may be due to the fact that the insoluble and/or slightly water soluble source of calcium in the oral composition of the present invention reacts with potassium phosphate to form calcium phosphate, which may have affinity for dentin and/or tooth enamel. The tubular occlusion enhancer of the present invention may further assist in depositing the calcium source on the dentin and/or in the dentinal tubules to induce in situ formation of calcium phosphate, which occludes the dentinal tubules and/or their exposed open ends, thereby increasing the effectiveness of the occlusion of the tubules. When beneficial agents are present in an oral composition, remineralization of the calcium source around the beneficial agents further helps to retain those beneficial agents on tooth surfaces by increasing their shear resistance.

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

Preferably, the oral composition contains a surfactant. Preferably the composition contains at least 0.01% surfactant by weight of the composition, more preferably at least 0.1% and most preferably 0.5 to 7%. Suitable surfactants include anionic surfactants such as sodium, magnesium, ammonium or ethanolamine salts of C ₈ -C ₁₈ alkyl sulfates (eg sodium lauryl sulfate), C ₈ -C ₁₈ alkyl sulfosuccinates (eg dioctyl sodium sulfosuccinate) , C ₈ -C ₁₈ -alkylsulfoacetates (for example, sodium lauryl sulfoacetate), C ₈ -C ₁₈ alkyl sarcosinates (for example, sodium lauryl sarcosinate), C ₈ -C ₁₈ -alkyl phosphates (which may optionally contain up to 10 units of ethylene oxide and/or propylene oxide) and sulfated monoglycerides. Other suitable surfactants include nonionic surfactants such as optionally polyethoxylated sorbitan fatty acid esters, ethoxylated fatty acids, polyethylene glycol esters, fatty acid monoglyceride and diglyceride ethoxylates, and ethylene oxide/propylene oxide block polymers. Other suitable surfactants include amphoteric surfactants such as betaines or sulfobetaines. Mixtures of any of the compounds described above may also be used. More preferably, the surfactant contains or is an anionic surfactant. Preferred anionic surfactants are sodium lauryl sulfate and/or sodium dodecylbenzenesulfonate. Most preferably, the surfactant is sodium lauryl sulfate, sodium coco sulfate, cocamidopropyl betaine, sodium methyl cocoyl taurate, or mixtures thereof.

A thickener can also be used in this invention and is limited only to the extent that it can be added to a composition suitable for oral administration. Illustrative examples of the types of thickeners that can be used in this invention include sodium carboxymethyl cellulose (SCMC), hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, gum tragacanth, gum arabic, karaya gum, sodium alginate, carrageenan, guar, xanthan gum, Irish moss, modified starch starch, silica thickeners including aerogels, magnesium aluminum silicate (eg Veegum), carbomers (crosslinked acrylates) and mixtures thereof.

Usually xanthan gum and/or sodium carboxymethyl cellulose and/or carbomer is/are preferred. When a carbomer is used, those carbomers are desirable that have a weight average molecular weight of at least 700,000 and preferably those that have a molecular weight of at least 1,200,000, and most preferably those that have a molecular weight of at least about 2,500,000. mixtures of carbomers can be used.

In a particularly preferred embodiment, the carbomer is Synthalen PNC, Synthalen KP, or a mixture thereof. It has been described as a high molecular weight and crosslinked polyacrylic acid and identified under CAS number 9063-87-0. These types of materials are available from suppliers such as Sigma.

In another particularly preferred embodiment, the sodium carboxymethyl cellulose (SCMC) used is SCMC 9H. It is described as the sodium salt of a cellulose derivative with carboxymethyl groups linked to the hydroxy groups of the glucopyranose backbone monomers and identified under CAS number 9004-32-4. It is also available from suppliers such as Alfa Chem.

In another particularly preferred embodiment, the thickener is xanthan gum.

The thickener content is typically 0.01 to 10%, more preferably 0.1 to 9% and most preferably 0.1 to 5% by weight of the oral composition, based on

- 8 039652 the total weight of the composition and including all ranges within the specified limits.

When the oral care composition of the present invention is a toothpaste or gel, it typically has a viscosity of about 30,000 to 180,000 centipoise and preferably 60,000 to 170,000 centipoise, and most preferably 65,000 to 165,000 centipoise.

Suitable humectants are preferably used in the oral composition of the present invention and include, for example, glycerin, sorbitol, propylene glycol, dipropylene glycol, diglycerin, triacetin, mineral oil, polyethylene glycol (preferably PEG400), alkanediols like butanediol and hexanediol, ethanol, pentylene glycol or a mixture thereof. Glycerin, polyethylene glycol, sorbitol, or mixtures thereof are preferred humectants. The humectant may be present in an amount of 10 to 90% by weight of the oral composition. More preferably, the content of the humectant-carrier is from 25 to 80%, and most preferably from 30 to 60% by weight of the composition, based on the total weight of the composition and including all ranges within the specified limits.

The oral care composition of the present invention may contain a variety of other ingredients that are common in the art to improve physical properties and performance. These ingredients include preservatives, pH adjusting agents, sweeteners, particulate abrasives, polymeric compounds, buffers, and salts for adjusting the pH and ionic strength of the compositions and mixtures thereof. Such ingredients typically and collectively comprise less than 20% by weight of the composition, preferably 0.0 to 15% by weight, and most preferably 0.01 to 12% by weight of the composition, including all ranges within the indicated ranges.

The oral care composition of the present invention may be used in a method for improving the condition of an individual's teeth, comprising applying the composition to at least one surface of the individual's teeth, said effects including desensitization, remineralization, whitening, and combinations thereof. The oral care composition of the present invention may additionally or alternatively be used as a medicament and/or in the manufacture of a medicament to provide oral care effects as described herein, such as reducing tooth sensitivity in an individual. Alternatively, and preferably, the use is non-therapeutic.

The oral care composition is a two-phase composition containing a first phase (calcium phase) and a second phase (phosphate phase), wherein an insoluble and/or slightly water-soluble source of calcium and a tubular blockage enhancer are present in the first phase and potassium phosphate is present in second phase. The two phases are physically separated from each other, being in independent phases. In the case of a two-phase composition, the first phase and the second phase should not come into contact with each other until they are distributed for use.

Delivery of two independent phases to the teeth can be simultaneous or sequential. In a preferred embodiment, the phases are delivered at the same time. In another preferred embodiment, the two phases are combined to form a mixture prior to their application to the teeth. Typically, the weight ratio of the first phase to the second phase in this mixture is from 1:3 to 10:1, more preferably from 1:2 to 7:1, most preferably from 1:1.5 to 5:1.

Preferably the insoluble and/or slightly water soluble source of calcium is present in an amount of more than 10%, more preferably more than 15% of the total weight of the mixture.

Preferably the potassium phosphate salt is present in an amount of more than 5%, more preferably more than 8% of the total weight of the mixture.

Typically, a biphasic composition is delivered using a double tube having a first compartment for the first phase and a second compartment for the second phase, which allows the two phases to be squeezed together.

In a preferred embodiment, such a double tube has one of the compartments surrounding the other. In such embodiments, one phase is present as a shell, surrounding the other phase in the core. In a particularly preferred embodiment, the core is the first phase and the sheath is the second phase.

In another preferred embodiment, such a double tube has two compartments located next to each other within one tube. In such embodiments, the two phases are extruded from the tube as one, which extrusion is referred to as contact extrusion. The pump head can be used in such a double tube to extrude two phases from the tube as one.

The biphasic oral composition may be a gel composition that contains two independent gel phases. The delivery means may include a cotton swab or spoon onto which the first phase and second phase are applied prior to bringing the spoon into contact with the teeth.

Usually the composition will be packaged. In the form of a toothpaste or gel, the composition can be packaged in a conventional plastic laminate, metal tube or single compartment dispenser. It can be applied to dental surfaces by any physical means such as a toothbrush,

- 9 039652 fingertip or applicator, directly on the sensitive area.

The biphasic oral care composition can be effective even when used in daily human oral hygiene. For example, the composition may be brushed onto the teeth. The composition may, for example, contact the teeth for a period of 1 second to 20 hours. More preferably 10 seconds to 10 hours, even more preferably 30 seconds to 1 hour, and most preferably 30 seconds to 5 minutes. The composition can be applied daily, for example, for use by an individual once, twice or three times a day. During application, the two phases of the composition are mixed before they are applied to the teeth. The mixed phases are usually left on the teeth for 3 minutes to 10 hours, more preferably 3 minutes to 8 hours. Application can be carried out one to five times a month.

The following examples are provided to facilitate understanding of the present invention. The examples are presented not to limit the scope of the claims.

Examples

Example 1

This example demonstrates improved occlusion of dentinal tubules by using high levels of an insoluble and/or slightly water soluble source of calcium and potassium phosphate in combination with a tubular occlusion enhancer. All ingredients are expressed as weight percent of the total composition and as active ingredient level.

Table 1

Ingredient Sample one 2 First phase Second phase First phase Second phase Glycerol 64.9 — 69.9 — calcium silicate ³ 30.0 — thirty — calcium dihydrogen phosphate 5.0 — — — xanthan gum OD — 0.1 — Dipotassium hydrogen phosphate — 30.14 — 30.14 Potassium dihydrogen phosphate — 11.86 — 11.86 Water — 58.00 — 58.00

a) Commercially available calcium silicate (CaSiO ₃ ) from PQ Corporation (Sorbosil CA40) Methods

For samples 1 and 2, the first phase and the second phase were mixed in a 3:1 weight ratio. To evaluate the effectiveness of occlusion of the dentinal tubules, 4 g of the mixture was mixed with 8 ml of water to prepare a suspension.

Human dentin discs were eroded with 37% phosphoric acid for 1 min, then treated with different suspensions by brushing following the same protocol. The dentin discs were cleaned with the slurry by a dentifrice equipped with toothbrushes. The brushing load was 170±5 g and the automatic brushing was operated at 150 rpm. After brushing for 1 min, the dentin discs were soaked in the suspension for 1 min. The dentin discs were then rinsed with distilled water and placed in simulated oral fluid (SOF) with shaking in a water bath at 37°C and 60.0 rpm. After wetting for about 3-4 hours, the dentin discs were cleaned with a slurry machine using the same procedure as in the first step. Cleaning was repeated three times within one day, then the dentin discs were stored in SOF overnight (>12 h) in a shaking water bath at 37°C to simulate the oral environment. Dentin discs were brushed 1, 4 and 7 times.

The simulated oral fluid was obtained by combining the ingredients presented in table. 2.

table 2

Ingredient Quantity/g NaCl 16.07 _NaHCO3 0.7 KS1 0.448 K2NRO ₄ *ZN ₂ O 3.27 MgCl ₂ *6H ₂ O 0.0622 1MNS1 40 ml CaCl ₂ 0.1998 _Na2SO4 0.1434 Buffer Adjusting the pH to 7.0 Water Balance up to 2 l

results

After one brushing, SEM (scanning electron microscopy) pictures of the dentin discs were taken. The results after one purge were recorded as the effect of instantaneous tubular occlusion in vitro.

For each sample, four spots on the dentin disc were randomly selected and observed.

- 10 039652

In top view of the SEM images, it can be seen that Sample 1 containing calcium silicate and tubular occlusion enhancer showed better tubular occlusion performance than Sample 2 containing commercial calcium silicate alone. The measurement was repeated twice for each sample.

After 4 and 7 brushings, both samples showed good deposition on the dentin surface and the dentinal tubules were widely occluded.

CLAIM

Claims (14)

CLAIM 1. A two-phase composition for oral care, containing: a) the first phase containing an insoluble and/or slightly soluble source of calcium in an amount of 20 to 75% based on the weight of the first phase of the composition, while the calcium source contains calcium silicate, calcium carbonate, calcium aluminate, calcium oxalate, calcium aluminum silicate , calcium hydroxide, calcium glycerophosphate, calcium oxide, calcium sulfate, calcium carboxymethylcellulose, calcium alginate, calcium salts of citric acid or mixtures thereof; b) a second phase containing a potassium phosphate salt in an amount of 30 to 75% by weight of the second phase of the composition; and wherein the first phase further comprises a tubular occlusion enhancer, which is calcium dihydrogen phosphate. 2. The oral care composition of claim 1, wherein the potassium phosphate salt is potassium dihydrogen phosphate, dipotassium hydrogen phosphate, tripotassium phosphate, or mixtures thereof. 3. An oral care composition according to claim 2, wherein the potassium phosphate salt is potassium dihydrogen phosphate, dipotassium hydrogen phosphate or mixtures thereof, preferably a mixture of potassium dihydrogen phosphate and dipotassium hydrogen phosphate. 4. An oral care composition according to any one of the preceding claims, wherein the potassium phosphate salt is present in an amount of 30 to 70%, preferably 35 to 60%, based on the weight of the second phase of the composition. 5. An oral care composition according to any one of the preceding claims, wherein the second phase of the composition has a pH of 3.0 to 10.0. 6. An oral care composition according to any of the preceding claims, wherein the calcium source comprises calcium silicate. 7. The oral care composition of claim 6 wherein the calcium silicate has a Ca:Si ratio of 1:30 to 5:1, preferably 1:20 to 3:1. 8. An oral care composition according to any one of the preceding claims, wherein the calcium source is present in an amount of 25 to 60%, preferably 28 to 50%, based on the weight of the first phase of the composition. 9. An oral care composition according to any one of the preceding claims, wherein the calcium source and tubular occlusion enhancer are present in a weight ratio of 30:1 to 1:5, preferably 15:1 to 1:3. 10. An oral care composition according to any one of the preceding claims, wherein the composition further comprises a benefit agent, preferably a particulate whitening agent. 11. The oral care composition of claim 10, wherein the particulate whitening agent is a composite particulate, preferably titanium dioxide, coated with calcium silicate. 12. An oral care composition according to any one of the preceding claims, wherein the first phase and the second phase are physically separated prior to application of the composition. 13. An oral care composition according to any one of the preceding claims, wherein the first phase and the second phase are combined to form a mixture prior to their application to the teeth, wherein the weight ratio of the first phase to the second phase in the mixture is from 1:3 to 10: 1, preferably from 1:2 to 7:1. 14. An oral composition according to any one of claims 1 to 13 for desensitization and/or remineralization and/or whitening of teeth.