EA042995B1 - ORAL CARE COMPOSITION - Google Patents

Description

The field of technology to which the invention belongs

The present invention relates to oral care compositions such as toothpastes, powders, chewing gums, mouthwashes, and the like. In particular, the present invention relates to an oral composition containing a composite material that results in tooth desensitization and/or tooth remineralization. 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 temporary pain sensation that affects up to 20% of the adult population. Hypersensitive teeth may be sensitive to temperature, pressure, or chemicals.

The dentin of a tooth 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 root surfaces of teeth as a result of periodontal disease, toothbrush abrasion, or fatigue from cyclic loading of thin enamel near the dentin-to-enamel junction. When the root surfaces are exposed, the dentinal tubules are also exposed.

The currently accepted theory of tooth hypersensitivity is the hydrodynamic theory, based on the belief that open, exposed dentinal tubules allow fluid to flow through the tubules. This flow excites the nerve endings in the dental pulp. Clinical replica of sensitive teeth seen in SEM (scanning electron microscopy) reveals varying numbers of open or partially occluded dentinal tubules.

There are different 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 function by interfering with the transduction of a noxious stimulus in the nervous system, making the nerve less sensitive.

Another approach is to use tubular blocking agents that completely or partially plug the tubules, such as polystyrene beads, apatite, polyacrylic acid, mineral hectorite clay, and the like. These tubular blocking agents function by physically blocking 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.

The present inventors have surprisingly found that an oral composition containing a composite material is more effective in treating tooth hypersensitivity. The composite material contains a first component material containing a biomineralizing agent and a second component material capable of interacting with phosphate ions to form an in situ reaction product of calcium and phosphate that adheres to tooth enamel, dentin, or both, and is a reagent for the formation of hydroxyapatite. Such a composite material has been found to effectively adhere to tooth surfaces even during routine oral hygiene procedures such as brushing the teeth. The oral care composition provides excellent tubular occlusion efficacy 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 benefit the 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 a calcium phosphate salt, a second independent composition containing a source of phosphate ions, and means for delivering each of the compositions. to the surface of the teeth. The preferred insoluble calcium salt is calcium silicate.

WO 2014/056713 (Unilever) discloses oral care compositions comprising hydrous calcium silicate containing 20 to 70% SiO ₂ by weight of hydrous calcium silicate and a physiologically acceptable carrier containing humectants, a surfactant, a thickener, or a mixture thereof .

None of the sources of additional information cited above describe an oral care composition containing a composite material, wherein the composite material comprises a first component material containing a biomineralizing agent and a second component material capable of interacting with phosphate ions to form a reaction product in situ calcium and phosphate, which adheres to tooth enamel, dentin, or both, and is a reagent for the formation of hydroxyapatite. And, in particular, such an oral care composition has excellent tubular occlusion efficacy and is more effective for treating tooth hypersensitivity.

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Research and definitions

Means for cleaning teeth.

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.

Toothpaste.

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

Particle size.

The particle size for the purposes of the present invention refers to 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. Particle size can be measured, for example, by dynamic light scattering (DLS).

pH.

The pH is adjusted at atmospheric pressure and a temperature of 25°C. With regard to the pH of an oral care composition, this means the pH measured when 5 parts by weight of the composition are uniformly dispersed and/or dissolved in 20 parts by weight of pure water at 25°C. In particular, pH can be measured manually by mixing 5 g of the oral composition with 20 ml of water for 30 seconds, followed by immediate testing of the pH with an 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. Slightly soluble, therefore, means a source that dissolves in water to produce a solution with a concentration of more than 0.001 mol per liter and less than 0.1 mol per liter.

Essentially does not contain.

Substantially free for the purposes of the present invention means less than 1.5%, and preferably less than 1.0%, and 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 sub-ranges within these limits.

Two-phase.

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

Anhydrous composition.

Anhydrous composition for the purposes of the present invention means that the water content of the composition is less than 1.5%, preferably 0.0 to 0.75% of the total weight of the oral composition.

Viscosity.

The viscosity of the toothpaste is a value measured at room temperature (25°C) using a Brookfield viscometer, No. 4 spindle and at 5 rpm. Results are expressed in centipoise (cP = mPa-s) unless otherwise indicated.

Remineralization.

Remineralization for the purposes of the present invention means in situ (i.e. in the mouth) formation of calcium phosphate on teeth (including layers on teeth with a thickness of 10 nm to 20 µm, and preferably 75 nm to 10 µm and most preferably 150 nm to 5 µm , including all ranges within the indicated intervals) to reduce the likelihood of tooth sensitivity, tooth decay, regenerate enamel and/or improve the appearance of teeth by whitening through the formation of such new calcium phosphate.

Other.

Except in the examples, or when expressly stated otherwise, all numbers in this specification expressing amounts of material or reaction conditions, physical properties of materials, and/or applications are not necessarily to be understood as being preceded by the word about.

All amounts are by weight of the final oral care composition unless otherwise indicated. It should be noted that when specifying any ranges of values, any specified upper value can be associated with any specified lower value.

For the avoidance of doubt, the word containing is intended to mean including, but does not necessarily mean consisting of or composed of. In other words, the steps or options listed are not necessarily exhaustive.

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The description of the invention provided herein is intended to cover all embodiments presented in the claims as being multiple dependent on each other, regardless of the fact that the claims may not be multiple dependent or redundant.

When any feature is disclosed in relation to 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) composite material;

b) a physiologically acceptable carrier; where the composite material contains:

(i) a first component material containing a biomineralizing agent; and (ii) a second component material capable of reacting with phosphate ions to form an in situ reaction product of calcium and phosphate that adheres to tooth enamel, dentin, or both and is a reactant to form hydroxyapatite; and where the biomineralization agent contains amorphous calcium phosphate, α-tricalcium phosphate, βtricalcium phosphate, calcium deficient hydroxyapatite (Ca ₉ (HPO ₄ )(PO ₄ ) ₅ OH), dicalcium phosphate (CaHPO ₄ ) dicalcium phosphate dihydrate (CaHPO ₄ -2H ₂ O), hydroxyapatite (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ), octacalcium phosphate (Ca ₈ H ₂ (PO ₄ ) ₆ -5H ₂ O), tetracalcium phosphate (Ca ₄ (PO ₄ ) ₂ O), or a mixture 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 desensitizing 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.

In a fourth aspect, the present invention relates to a method for making an oral care composition comprising the following steps:

i) mixing the material of the first component with the solvent to obtain a suspension;

ii) heating the suspension to a temperature of 25 to 95° C. for 0.5 to 3 hours;

iii) adding to the suspension a reagent suitable for in situ formation of the second component material to form a reaction mixture;

iv) removing the composite material from the reaction mixture; And

v) combining the composite material with a physiologically acceptable carrier.

The method according to the fourth aspect is particularly suitable for making the composition according to the first aspect. Thus, the present invention also provides an oral care composition according to the first aspect, which is obtained and/or can be obtained using the method according to the fourth aspect of the invention.

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

Detailed description of the invention

It has now been found that an oral composition containing a composite material is more effective in treating tooth hypersensitivity. The only limitation on the composite material that can be used in the present invention is that it is suitable for use in the oral cavity. In addition, such a composition may also increase the effectiveness of tooth remineralization and/or deposition of beneficial agents on tooth surfaces to further benefit the individual's teeth.

A composite material is a compound containing a first component material and a second component material that are microscopically heterogeneous but macroscopically homogeneous. The material of the first component is different from the material of the second component. Typically, the material of the first component of the composite material contains a biomineralizing agent that is suitable for improving tooth remineralization. A particularly suitable biomineralizing agent is amorphous calcium phosphate, α-tricalcium phosphate, β-tricalcium phosphate, calcium deficient hydroxyapatite (Ca ₉ (HPO ₄ )(PO ₄ ) ₅ OH), dicalcium phosphate (CaHPO ₄ ) dicalcium phosphate dihydrate (CaHPO ₄ -2H ₂ O), hydroxyapatite (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ), octacalcium phosphate (Ca ₈ H ₂ (PO ₄ ) ₆ -5H ₂ O), tetracalcium phosphate (Ca ₄ (PO ₄ ) ₂ O) or their mixture.

Preferably the material of the first component contains hydroxyapatite. In a particularly preferred embodiment, the first component material contains at least 50% by weight of hydroxyapatite, and most preferably from 60 to 100% by weight of hydroxyapatite, based on the total weight of the first component material. In another particularly preferred embodiment, the material of the first component is hydroxyapatite.

As a rule, the composite material contains the material of the first component in an amount of from 3 to

98%, more preferably 20 to 90%, and most preferably 50 to 80% by weight of the composite material, based on the total weight of the composite material, and including all ranges within the indicated ranges.

The material of the second component contains a material suitable for adhesion to tooth enamel, dentin, or both. In a preferred embodiment, the second component material reacts with phosphate ions to form an in situ reaction product of calcium and phosphate that adheres to tooth enamel, dentin, or both, and is a reactant to form hydroxyapatite. Adhesive, as used herein, includes attachment and/or effective adhesion to tooth surfaces as a result of interaction between elements in the second component material and elements in the teeth.

Typically, the second component material contains the element calcium and optionally other metals such as potassium, sodium, aluminum, magnesium, and mixtures thereof, thereby providing optional metals such as, for example, sulfates, lactates, oxides, carbonates or silicates. Optionally, the material of the second component may be aluminum oxide or silicon dioxide. In a preferred embodiment, the material of the second component is suitable for providing biological or chemical dental enhancement that is durable (eg, produces hydroxyapatite). Preferably, the second component material 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 metal in the second component material. In a particularly preferred embodiment, the metal in the second component material is from 80% to 100% by weight of elemental calcium, based on the total weight of the metal in the second component material, and including all ranges within the indicated ranges. In another particularly preferred embodiment, the first component material and the second component material are slightly water soluble or insoluble, but most preferably water insoluble.

In a particularly desirable embodiment, the second component material may comprise, for example, calcium oxide, calcium carbonate, calcium hydroxide, calcium sulfate, calcium carboxymethylcellulose, calcium alginate, calcium salts of citric acid, calcium silicate, a mixture thereof, or the like. In another desirable embodiment, the source of calcium in the material of the second component will contain calcium silicate. These compounds are also suitable for inclusion as reagents for calcium sources in the manufacture of a composite material according to this invention. Similar salts with sodium, magnesium, strontium, aluminum and potassium instead of calcium can, for example, be used as reagents to provide the anionic portion of the second component material during the manufacture of the composite material.

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

When calcium silicate is used as the material of the second component, the ratio of calcium to silicon (Ca:Si) may be from 1:10 to 3:1. The Ca:Si ratio is preferably 1:5 to 3:1, and more preferably 1:3 to 3:1, and most preferably about 1:2 to 3:1. The calcium silicate may contain monocalcium silicate, bicalcium silicate or tricalcium silicate, the ratios of calcium to silicon (Ca:Si) being to be understood as atomic ratios.

The preferred material used in this invention for delivering calcium and forming the material of the second component of the composite material may be in a crystalline or amorphous state. In an often preferred embodiment, the calcium delivery material for the second component is in a mesoporous state, ie the source is a material having pores with pore diameters between 1 nm and 1 µm. Mesoporous calcium silicate (MCS) is often preferred.

The MCS that can be used in the material of the second component in the present invention can be obtained by combining a calcium salt (for example, calcium chloride, calcium carbonate, calcium hydroxide), a silicate-like reagent (for example, sodium silicate, potassium silicate, tetraethylorthosilicate or tetraethyl silicate) and a structurant to give a solid suitable for calcination. A more detailed description of the method that can be carried out for the manufacture of MCS suitable for use in this invention is presented in the above-mentioned international patent application published as WO 2008/015117.

In an often desired embodiment, the material of the second component may be formed from CaO-SiO2.

The composite material is preferably particulate, as this provides the maximum surface area for contact with dental tissue. Typically a composite

- 4 042995 has a size of 10 nm to less than 50 μm, and more preferably from 50 nm to 10 μm, and most preferably from 100 nm to 5 μm, including all ranges in the indicated intervals.

Typically, the composite material contains a first component material and a second component material in a weight ratio of 1:10 to 10:1, more preferably 1:3 to 5:1, and most preferably 1:1 to 3:1.

Generally, an oral composition of the present invention contains 0.25% to 60%, and more preferably 0.5% to 40%, and most preferably 1 to 30%, by weight of the composite material, based on the total weight of the oral composition. oral care and including all ranges within the specified intervals.

In another particularly preferred embodiment, the composite material may be supplemented with an additional metal source, such as a calcium source. Such additional metal source may be identical to the source used as the material of the second component of the composite material, such as calcium silicate, calcium oxide, or a mixture thereof. When added, the content of the additional metal source is typically 0.1 to 50%, more preferably 0.2 to 30%, most preferably 1 to 20%, based on the total weight of the oral composition and including all ranges in the specified intervals.

In one embodiment, the oral composition may be substantially free of a phosphate source. This is especially preferred when the composition is a single phase aqueous composition (i.e. contains more than 1.5% water, preferably more than 5% water, more preferably more than 10% water and most preferably 20 to 90% water by the mass of the composition). The presence of composite material and phosphate sources in a single phase aqueous composition can cause the composite material and phosphate to react prematurely and cause product instability.

For certain compositions, especially anhydrous compositions (ie, compositions substantially free of water) or two-phase aqueous compositions, it is preferable to add a phosphate source to the oral composition to promote in situ formation of calcium phosphate.

The source of phosphate that can be used in this invention is only limited to the extent that it can be used in a composition suitable for use in the oral cavity. Illustrative examples of types of phosphate source suitable for use in the present invention include trisodium phosphate, monosodium dihydrogen phosphate, disodium hydrogen phosphate, trisodium phosphate, monopotassium dihydrogen phosphate, dipotassium hydrogen phosphate, ammonium phosphate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, mixtures thereof, or the like. The phosphate source is preferably water soluble.

When used, the content of the phosphate source is typically 0.5 to 40% and more preferably 1 to 30% and most preferably 2 to 20% by weight of the oral care composition based on the total weight of the oral care composition. oral cavity, and including all ranges in the indicated intervals. In a preferred embodiment, the phosphate source used is trisodium phosphate and monosodium dihydrogen phosphate in a weight ratio between trisodium phosphate and monosodium dihydrogen phosphate in the range of 1:4 to 4:1, preferably 1:3 to 3:1, and most preferably 1:2 to 2: 1, including all ratios within the specified limits. In another preferred embodiment, the phosphate source used is or at least contains sodium dihydrogen phosphate.

The oral care composition preferably has a pH value greater than 5.0. If the pH of the composition is too low, this can reduce the pH in the oral cavity such that in situ formation of calcium phosphate is delayed. Therefore, it is preferred that the pH of the oral composition be in the range of 5.5 to 11.0, more preferably 6.0 to 10.5 and most preferably 6.5 to 9.0.

The composition of the present invention is an oral care composition and usually contains a physiologically acceptable carrier. The carrier preferably contains at least a surfactant, a thickener, a wetting agent, 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 C ₈ -C ₁₈ alkyl sulfates (eg sodium lauryl sulfate), C ₈ -C ₁₈ alkyl sulfosuccinates (eg sodium dioctyl sulfosuccinate), C ₈ -C ₁₈ alkyl sulfoacetates (such as sodium lauryl sulfoacetate), C ₈ -C ₁₈ alkyl sarcosinates (such as 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

- 5 042995 as optionally polyethoxylated sorbitan fatty acid esters, ethoxylated fatty acids, polyethylene glycol esters, monoglyceride and diglyceride ethoxylates of fatty acids, and ethylene oxide/propylene oxide block polymers. Other suitable surfactants include amphoteric surfactants such as betaines or sulfobetaines. Mixtures of any of the materials 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 thickening agent can also be used in the present invention, which is limited only to the extent that it can be added to a composition suitable for oral use. Illustrative examples of the types of thickeners that can be used in this invention include sodium carboxymethylcellulose (SCMC), hydroxyethylcellulose, methylcellulose, ethylcellulose, gum tragacanth, gum arabic, gum karaya, sodium alginate, carrageenan, guar gum, xanthan gum, Irish moss, starch, modified starch, silica thickeners including silica aerogels, magnesium aluminum silicate (eg Veegum), carbomers (crosslinked acrylates) and mixtures thereof.

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

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

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

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

The thickener is typically 0.01% to about 10%, more preferably 0.1% to 9%, and most preferably 0.1% to 5%, by weight of the oral composition, based on the total weight of the composition and including all ranges in the specified intervals.

When the oral composition of the present invention is in the form of 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 care composition of the present invention and include, for example, glycerin, sorbitol, propylene glycol, dipropylene glycol, diglycerin, triacetin, mineral oil, polyethylene glycol (preferably PEG-400), alkanediols such as 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 in the range of 10 to 90% by weight of the oral composition. More preferably, the content of the wetting agent of the 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 in the indicated intervals.

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 enhance 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. Beneficial agents are present in the oral composition in addition to the composite material that is included in the composition.

Generally, the benefit agent is selected from optic agents, biomineralizing agents, antibacterial agents, gum health agents, desensitizing agents, antistone agents, refreshing agents, or mixtures thereof. Preferably, the benefit agent is selected from optical agents, antibacterial agents, gum health agents, refreshing agents, or mixtures thereof.

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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 degrees. These pigments may be selected from one or more of the pigments listed in the Color Index International reference database, which are listed as 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 of mica, interference mica, boron nitride, polymethyl methacrylate flake, composite microspheres, titanium dioxide coated glass flake, inverse opal, cholesteric liquid crystal, photonic sphere, hollow sphere, and zinc oxide. The antibacterial agents may be selected from one or more metal salts, the metal being selected from zinc, copper, silver, or mixtures thereof, triclosan, triclosan monophosphate, triclocarban, curcumin, quaternary ammonium compounds, bisbiguanides, and long chain tertiary amines, preferably zinc salts, including oxide zinc, 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, formate zinc, 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, anti-plaque buffers, biomolecules, protein materials, vitamins, plant extracts, and curcumin. Freshening 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 particulate 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, it is preferable that the material has 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 contains) 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 a combination thereof in an amount of at least 50% by weight of the bleaching agent, and more preferably at least 70%, even more preferably 80 to 100%, and most preferably from 85 to 95%. In a particularly preferred embodiment, the content of the particulate bleaching agent is 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 in the specified ranges. In another particularly preferred embodiment, the particulate bleaching agents are slightly water soluble or insoluble, but most preferably water insoluble.

In a preferred embodiment, the particulate whitening agents are composite particles. Composite particles as used herein means a particle containing a core as a first component and a coating as a second component, wherein the core and coating are composed of different materials. The refractive index of a composite particle containing more than one material can be calculated based on the refractive indices and volume fractions of the components using effective medium theory, as described, for example, in WO 2009/023353.

The composite particle contains a core as the first component and a 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 specifically 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 contains) 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-metal oxides such as strontium titanate and zinc sulfide. In a particularly preferred embodiment, the core 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 core as the first component.

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 provided, for example, as sulfates, lactates, oxides, carbonates or silicates. In a particularly desirable embodiment, the coating as a second component may contain, for example, calcium phosphate, calcium oxide, calcium carbonate, calcium hydroxide, calcium sulfate, calcium carboxymethylcellulose, calcium alginate, calcium salts of citric acid, calcium silicate, a mixture thereof, or the like. . In another desirable embodiment, the source of calcium in the coating is calcium silicate.

Generally, at least 30% of the outer surface area of the core as the first component is coated as 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 as the first component is coated. as 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 various sizes and shapes. The particles may be spherical, lamellar or irregular in shape. The particle diameter of the bleaching agent is often from 10 nm to less than 50 microns, and preferably from 75 nm to less than 10 microns. In a particularly preferred embodiment, the particle diameter is from 100 nm to 5 µm, including all ranges within the specified intervals. Particle size can be measured, for example, using 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 within these ranges.

The oral care composition of the present invention may contain a single beneficial agent or a mixture of two or more beneficial agents. Generally, the beneficial agent is present in an amount of 0.25% to 60%, and 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 the indicated ranges. .

The oral care composition of the present invention may contain a variety of other ingredients that are conventional in the art for improving physical properties and performance. These ingredients include preservatives, pH adjusters, sweeteners, particulate abrasives, polymeric compounds, buffers and salts to maintain the pH and ionic strength of the compositions, and mixtures thereof. Such ingredients generally and together comprise 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 within the ranges indicated.

The oral care composition of this invention can be used in a method of improving the condition of an individual's teeth, comprising applying the composition to at least one surface of the individual's teeth, said benefit 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 used in the manufacture of a medicament to provide an oral care benefit as described herein, for example, to reduce the sensitivity of an individual's teeth. Alternatively, and preferably, the use is non-therapeutic.

In the event that an oral care product containing a phosphate source is desired, in one preferred embodiment the oral composition is a single phase anhydrous composition that is substantially free of water to prevent premature reaction between the composite material and the phosphate source.

In another preferred embodiment, the oral care composition is a two-phase composition comprising a first phase and a second phase, wherein the composite material is present in the first phase and the phosphate source is present in the second phase. 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. When a Biphasic Composition Is Desirable

- 8 042995 for oral care, water can act as a carrier (along with the thickeners and/or additional carriers described herein) and balance each phase in a two-phase composition.

When a two-phase composition is used, the first phase and the second phase should not come into contact with each other until they are dispensed for use. In use, it is preferable to combine the two phases to form a mixture before they are applied 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.

Typically, the delivery of a biphasic composition is by means of 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 extruded 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 inside one tube. In such embodiments, the two phases are extruded from the tube as one, such extrusion being referred to as contact extrusion. The pump nozzle can be used in such a double tube to extrude two phases from the tube as one.

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

The composite material of the present invention can be obtained by mixing the material of the first component with a solvent to form a slurry. A suitable solvent comprises water, low molecular weight alcohols such as C _2-6 alkanols, low molecular weight ketones such as acetone, or mixtures thereof. Preferably the solvent is water. The suspension is heated to a temperature of from 25 to 95°C and preferably from 40 to 90°C and most preferably from 50 to 80°C, including all ranges in the indicated intervals. During heating, a reagent for the anionic portion of the second component material is added to the heated slurry. After addition of the anionic moiety reagent, the suspension is incubated for 0.5 to 3 hours and preferably 1 to 2.5 hours at an alkaline pH (preferably pH 7 to 11 and most preferably 8 to 10). A suitable reagent for the anionic portion of the second component material comprises sodium silicate, potassium silicate, sodium alginate, sodium sulfate, tetraethylorthosilicate, or mixtures thereof. Then, a reagent for the cationic portion of the second component material, such as calcium ions, is added to the slurry. A suitable reagent for the cationic portion of the second component material is calcium gluconate, calcium oxide, calcium lactate, calcium acetate, calcium hydroxide, calcium sulfate, calcium carboxymethylcellulose, calcium chloride, potassium chloride, magnesium chloride, strontium chloride, aluminum chloride, or mixtures thereof. The resulting mixture is incubated for 0.5 to 3 hours, preferably 1 to 2.5 hours, and kept overnight. The resulting composite material can be recovered by conventional methods including filtration and/or centrifugation and then dried.

The oral care compositions of the present invention are prepared by conventional methods of making oral care compositions which involve mixing the ingredients under moderate shear and atmospheric pressure.

Typically, the composition may be packaged. As a toothpaste or gel form, the composition may be packaged in a conventional laminated plastic, metal tube or single compartment dispenser. Such a composition can be applied to tooth surfaces by any physical means such as a toothbrush, fingertip or applicator directly to the sensitive area.

The composition can be effective even when used in everyday life for oral hygiene. For example, the composition may be brushed onto the teeth. The composition may, for example, be in contact with the teeth for a period of time from one second to 20 hours. More preferably 1 second to 10 hours, even more preferably 10 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. When the oral care composition is a two-phase composition, the two phases of the composition are mixed upon application. The mixed phases are usually left on the teeth for a period of 3 minutes to 10 hours, more preferably 3 minutes to 8 hours. Application can be carried out daily.

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

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Examples

Example 1

This example demonstrates improved occlusion of dentinal tubules by using a composite material. All amounts of ingredients are expressed as weight percent of the total weight of the composition and as the level of active ingredient.

Table 1

Ingredient Samples 1 2 3 4 NAR 5.0 — 3.6 — calcium silicate — — 1.4 5.0 Composite material HAR/calcium silicate — 5.0 — — Glycerol 95.0 95.0 95.0 95.0

Ways.

Composite material manufacturing.

g of hydroxyapatite powder was added to 100 ml of distilled water to form a suspension. After homogenization at 5000 rpm for 10 min, the suspension was continuously stirred while maintaining the temperature at 70° C. with an IKA stirrer. After 0.5 hours, 16.7 ml of 1 M sodium silicate was added dropwise to the suspension, and the pH of the suspension was maintained in the range of 8.5-9.5 using 1 M hydrochloric acid. After adding sodium silicate, the suspension was incubated for 2 hours. Then the heating was turned off and the suspension continued to stir. 1.24 g of calcium hydroxide powder was added to the suspension, then the resulting mixture was stirred for 2 hours and kept overnight. The composite material was washed and collected by centrifugation.

Sample making.

To evaluate the effectiveness of occlusion of the dentinal tubules, the test sample was mixed with water in a ratio of 4 g per 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. Eight human dentin discs were divided into four groups (n=2). Dentin discs were cleaned with the slurry using a dentifrice equipped with toothbrushes. The brushing load was 170 g ± 5 g, and the automatic brushing occurred at 150 rpm. After brushing for 1 min, the dentin discs were soaked in the toothpaste slurry for 1 min. The dentin discs were then rinsed with deionized water. The dentin discs were then rinsed with distilled water and placed in simulated oral fluid (SOF) under shaking conditions in a water bath at 37°C and 60.0 rpm for at least 3 hours. Cleaning was repeated three times in one day, the dentin discs were then incubated in SOF overnight (> 12 h) in a shaking water bath at 37° C. to mimic the oral environment. Dentin samples were cleaned 3 and 7 times.

Simulated oral fluid was made by combining the ingredients shown in table. 2:

table 2

Ingredient Qty/g NaCl 16.07 _NaHCO3 0.7 KS1 0.448 K ₂ NRO ₄ * ZN ₂ O 3.27 MgCl ₂ *6H ₂ O 0.0622 IM HCl 40 ml _CaCl2 0.1998 _{Na2SO4 _} 0.1434 Buffer Adjusting the pH to 7.0 Water Balance up to 2 l

Standard for assessing tubular occlusion.

Regardless of the original shape of the dentin discs, a square (4x4 mm) is selected and one image is obtained at 50x magnification. Five spots (each 150x150 µm, one in the middle and one in each corner) are selected within this square and observed at 1000x magnification. Tubular obstruction is evaluated according to the standards described in Table 1. 3. The measurement is carried out for two dentinal discs of each test group.

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Results.

SEM (scanning electron microscopy) images of dentin discs were obtained after brushing 3 and 7 times. The images were analyzed and evaluated. The results are summarized in table. 4 (error represents the standard deviation for repeated measurements).

Table 3

score Blockage of tubules 0 All dentinal tubules are open 1 <20% of dentinal tubules are completely occluded 2 20-50% of dentinal tubules are completely occluded 3 50-80% of dentinal tubules are completely occluded 4 80-100% of dentinal tubules are completely occluded 5 All dentinal tubules are completely occluded

Table 4

Tubular evaluation blockages Samples 1 2 3 4 3 purges 2.0±0.82 4.7 ± 0.48 2.4±0.52 1.1±0.32 7 purges 3.9±0.74 4.8 ± 0.42 3.6±0.52 2.0±0.67

The results showed that sample 2 containing the composite material had a significantly better (p<0.01) tubular occlusion efficiency compared to the other samples after 3 or 7 purges. The SEM images clearly showed that almost all dentinal tubules were significantly occluded after treatment with Sample 2.

Example 2

This example demonstrates improved occlusion of dentinal tubules when used in composite material compositions. All amounts of ingredients are expressed as weight percent of the total weight of the composition and as the level of active ingredient.

Table 5

Ingredients Samples 5 6 Glycerol 66.84 66.84 Sodium monofluorophosphate 1,I 1,I Saccharin sodium 0.25 0.25 calcium silicate ³ 15.00 — Composite material NAR / force ikatkaltion — 15.00 Monosodium dihydrogen phosphate 3.20 3.20 Trisodium phosphate 3.80 3.80 Sodium lauryl sulfate 2.00 2.00 Silicon dioxide abrasive ^b 6.00 6.00 Silica-based abrasive ^with 0.50 0.50 xanthan gum 0.10 0.10 flavoring 1.20 1.20

^a Commercially available calcium silicate (CaSiO ₃ ) under the tradename Sorbosil CA40 from PQ Corporation.

^b Commercially available silicon dioxide under the trade name Sorbosil AC77 from PQ Corporation.

^c Commercially available silicon dioxide under the tradename Sorbosil AC43 from PQ Corporation.

Comparative A is a commercial anti-sensitivity toothpaste claimed to have satisfactory restorative properties, which contains glycerin, PEG-400, silicon dioxide, sodium calcium phosphosilicate, sodium lauryl sulfate, sodium monofluorophosphate, fragrance, titanium dioxide, carbomer , acesulfame potassium.

Ways.

The same protocol was used to evaluate the effectiveness of occlusion of the dentinal tubules as described in Example 1. The dentin discs were cleaned 3 and 7 times.

Results.

SEM (scanning electron microscopy) images of dentin discs were obtained after brushing 3 and 7 times. The images were analyzed and evaluated. The results are summarized in table. 6 (error represents the standard deviation for repeated measurements).

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Table 6

Tubular assessment blockages Samples A 5 6 3 purges 1.5±0.71 1.3±0.48 2.3±0.95 7 purges 2.2 ± 1.23 2.2 ± 0.79 3.9±0.57

After 7 brushings, SEM images of the dentin discs were obtained. Sample 6 containing the composite had a significantly better (p<0.01) tubular occlusion efficiency than the other samples. In the top views of the SEM images, it can be seen that sample 6 showed good deposition on dentin surfaces and the dentinal tubules were significantly occluded.

Example 3

This example demonstrates improved deposition on tooth surfaces when using a composite material in compositions. The samples used in this example were samples A, 5 and 6 as described in example 2.

Ways.

The same protocol was used to evaluate the effectiveness of dentinal tubular occlusion as described in Example 1, except that bovine enamel blocks were used instead of dentin discs. The enamel blocks were cleaned 28 times.

Results.

SEM images of enamel block surfaces were obtained after 28 cleanings. In the top view of the SEM images, it can be seen that sample 6 containing composite showed better deposition on enamel surfaces than the other samples. In addition, the corresponding cross-sectional SEM images showed that a much thicker new layer formed on the enamel surfaces after treatment with Sample 6 compared to the enamel surfaces treated with Sample 5, while the enamel blocks treated with Sample A had no layer, formed on their surfaces. Analysis using EDX identified elements Si, Ca and P in the new layer, indicating that the composite material caused good remineralization of the teeth.

Claims (15)

1. An oral care composition comprising: a) composite material; b) a physiologically acceptable carrier; where the composite material contains: (i) a first component material containing a biomineralizing agent; and (ii) a second component material capable of reacting with phosphate ions to form an in situ reaction product of calcium and phosphate that adheres to tooth enamel, dentin, or both, and which is a reagent for the formation of hydroxyapatite; where the biomineralization agent contains amorphous calcium phosphate, α-tricalcium phosphate, βtricalcium phosphate, calcium deficient hydroxyapatite (Ca ₉ (HPO ₄ )(PO ₄ ) ₅ OH), dicalcium phosphate (CaHPO ₄ ) dicalcium phosphate dihydrate (CaHPO ₄ -2H2O), hydroxyapatite (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ), octacalcium phosphate (Ca ₈ H ₂ (PO ₄ ) ₆ -5H ₂ O), tetracalcium phosphate (Ca ₄ (PO ₄ ) ₂ O), or a mixture thereof; and where the material of the second component contains calcium oxide, calcium carbonate, calcium hydroxide, calcium sulfate, calcium carboxymethylcellulose, calcium alginate, calcium salts of citric acid, calcium silicate, or a mixture thereof; where the composite material is a compound containing the material of the first component and the material of the second component, which are microscopically heterogeneous, but macroscopically homogeneous. 2. An oral care composition according to claim 1, characterized in that the biomineralizing agent is hydroxyapatite. 3. The oral care composition according to claim 1 or 2, characterized in that the composite material contains the material of the first component in an amount of from 3 to 98%, preferably from 20 to 90% by weight of the composite material. 4. An oral care composition according to any one of the preceding claims, characterized in that the material of the second component contains calcium silicate. 5. An oral care composition according to any one of the preceding claims, characterized in that the composite material has a particle size in the range of 50 nm to 10 µm, preferably 100 nm to 5 µm. 6. The oral care composition according to any one of the preceding claims, characterized in that the composite material contains the material of the first component and the material of the second component in a weight ratio of from 1:10 to 10:1, preferably from 1:3 to 5:1. 7. The oral care composition according to any one of the preceding claims, characterized in that the composite material is present in an amount of from 0.25 to 60% by weight of the composition, pre- - 12 042995 respectfully from 0.5 to 40% by weight of the composition. 8. An oral care composition according to any of the preceding claims, characterized in that the composition further comprises a phosphate source selected from 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 mixtures thereof, preferably trisodium phosphate, monosodium dihydrogen phosphate or mixtures thereof. 9. An oral care composition according to any one of the preceding claims, characterized in that the composition further comprises a metal source, preferably calcium silicate, calcium oxide, or a mixture thereof. 10. An oral care composition according to any one of the preceding claims, characterized in that the composition further comprises a beneficial agent, preferably titanium dioxide coated with calcium silicate. 11. An oral care composition according to any one of the preceding claims, characterized in that the composition is a single-phase anhydrous composition. 12. An oral care composition according to any one of claims 8 to 10, characterized in that the oral care composition is a two-phase composition containing a first phase and a second phase, wherein a composite material is present in the first phase and a phosphate source is present. in the second phase. 13. A process for making an oral care composition according to any one of the preceding claims, comprising the steps of: i) mixing the material of the first component with the solvent to obtain a suspension; ii) heating the suspension to a temperature of 25 to 95° C. for 0.5 to 3 hours; iii) adding a reagent suitable for in situ formation of the second component material to the slurry to form a reaction mixture; iv) removing the composite material from the reaction mixture; And v) combining the composite material with a physiologically acceptable carrier. 14. The method according to claim 13, characterized in that the reagent suitable for the anionic part of the material of the second component contains sodium silicate, potassium silicate, sodium alginate, sodium sulfate, tetraethylorthosilicate or mixtures thereof, and the reagent suitable for the cationic part of the material the second component contains calcium gluconate, calcium oxide, calcium lactate, calcium acetate, calcium hydroxide, calcium sulfate, calcium carboxymethylcellulose, calcium chloride, potassium chloride, magnesium chloride, strontium chloride, aluminum chloride or mixtures thereof. 15. A method of desensitizing and/or remineralizing and/or whitening an individual's teeth, comprising applying a composition according to any one of claims 1 to 12 to at least one surface of the individual's teeth.