EA039452B1 - Oral care composition - Google Patents

Abstract

An oral care composition is disclosed comprising from 3 to 80 wt.% of calcium silicate, a soluble calcium source, a phosphate source, a benefit agent and a physiologically acceptable carrier, wherein the calcium silicate and the soluble calcium source is present in a weight ratio from 1:3 to 20:1.

Description

This invention relates to oral care compositions such as toothpastes, powders, chewing gum, rinses, and the like. In particular, this invention relates to an oral composition containing calcium silicate, a soluble source of calcium, and beneficial agents. This invention also relates to the use of such compositions to improve the teeth of an individual.

State of the art

Many foods consumed by people negatively affect the condition of the teeth and oral cavity in general. For example, sweets and acidic drinks and sweets can lead to tooth decay by causing erosion of the tooth enamel, which is the outer covering that protects the teeth. Also, tobacco products, as well as drinks such as tea and coffee, can stain the surface of the teeth or impair their whiteness. These coloring and bleaching agents are often able to penetrate the tooth enamel layer. The results of this exposure accumulate over the years, as a result, the discoloration of the tooth enamel becomes noticeable.

The consumer strives to have healthy white teeth. Oral care compositions often include tooth-beneficial ingredients such as colorants, biomineralizing agents, antibacterial agents that promote whitening and remineralization of teeth and improve overall oral hygiene. Therefore, in order to increase the effectiveness of these beneficial agents, it is always desirable to improve their access to the tissues of the tooth.

However, it is generally difficult to achieve good availability of beneficial agents contained in oral compositions. Such agents generally do not adhere well to the surface of teeth and are therefore easily washed off during daily oral hygiene routines such as brushing teeth.

Thus, there is an ongoing need to improve the efficiency of the availability of beneficial agents to dental tissues. The present inventors have found that deposition of beneficial agents on tooth surfaces can be enhanced by using calcium silicate in combination with soluble calcium sources and a phosphate source. In addition, it has been found that such compositions can also enhance the ability of these beneficial agents to bind to tooth surfaces.

additional information

WO 2008/068149 A (Unilever) describes an oral care product comprising a first composition comprising an insoluble non-calcium phosphate calcium salt, a second independent composition comprising a phosphate ion source, and a means of delivering each of these compositions to tooth surfaces. Preferably the insoluble calcium salt is calcium silicate.

The above additional source of information does not describe an oral composition containing from 3 to 80% (w/w) of calcium silicate, a soluble calcium source, beneficial agents and a phosphate source, in which the calcium silicate and the soluble calcium source are present in a relative amount of from 1:3 to 20:1, and such an oral composition is capable of enhancing the deposition of beneficial agents on tooth surfaces.

Tests and definitions

Means for cleaning teeth.

In the context of this invention, the term dentifrice means a toothpaste, powder, liquid, chewing gum or other preparation for cleaning teeth or other surfaces in the oral cavity.

Toothpaste.

In the context of this invention, the term toothpaste means a paste or gel-like agent applied with a toothbrush. Particularly preferred according to the invention are toothpastes suitable for brushing teeth for about two minutes.

Rinse for the mouth.

In the context of this invention, the term rinse for the oral cavity means a liquid means for caring for the oral cavity, applied by rinsing the mouth. Particularly preferred according to the present invention are mouth rinses suitable for rinsing the mouth by agitating and displacing an ingested amount of liquid in the mouth for about 30 seconds followed by spitting.

Particle size.

In the context of this invention, the term particle size means particle size D50. The particle size D50 of the particulate material is the particle diameter with the size at which 50% by weight of the particles have a larger diameter and 50% by weight have a smaller diameter. For the purposes of this invention, particle size and size distribution were determined using Mastersizer 2000 and ZetaSizer Nano series particle size analyzers (manufactured by Malvern Instruments).

composite particle.

In the context of this invention, the term composite particle means a particle containing

- 1 039452 the first component constituting its core, and the second component covering this core, and the core and the coating consist of different materials.

refractive index.

The refractive index was taken at a temperature of 25°C and a wavelength of 589 nm.

pH.

pH was taken at atmospheric pressure and a temperature of 25°C. When referring to the pH of an oral care composition, this refers to the pH measured when 5 wt.h. the compositions are uniformly dispersed and/or dissolved in 20 wt.h. pure water at a temperature of 25°C. In particular, it is possible to measure the pH as follows: mix manually for 30 s 5 g of the oral composition with 20 ml of water and immediately measure the pH with an indicator or a pH meter.

Solubility.

As used herein, the terms soluble and insoluble refer to the solubility of the source (eg, calcium salts) in water at 25° C. and atmospheric pressure. Soluble means that the source dissolves in water to form a solution with a concentration of at least 0.1 mol/l. Insoluble means that the source dissolves in water to form a solution with a concentration of less than 0.001 mol/l. Moderately/partially soluble means that the source dissolves in water to form a solution with a concentration greater than 0.001 mol/l and less than 0.1 mol/l.

Hydrate water.

In the context of this invention, the term water of hydration means water molecules chemically combined with a given substance in such a way that they can be removed by heating, without substantially changing the chemical composition of this substance. In particular, it is water, which can only be removed by heating above 200°C. Water loss is measured by thermogravimetric analysis (TGA) using a Netzsch instrument. Thermogravimetric analysis was carried out in a nitrogen atmosphere at a heating rate of 10°/min in the temperature range of 30–900°C.

Practically does not contain.

In the context of this invention, the wording practically does not mean that the oral composition contains less than 1.5%, preferably less than 1.0%, more preferably less than 0.75%, even more preferably less than 0.5% and still more preferably less than 0.1%, most preferably 0.0 to 0.01% by weight, based on the total weight of the composition, including all ranges in between.

Two-phase.

In the context of this invention, the term biphasic refers to a composition in which there are two independent, physically separate phases.

Viscosity.

The viscosity of toothpaste refers to the value obtained from the readings of the Brookfield viscometer (spindle No. 4) at room temperature (25°C) and a rotation speed of 5 rpm. Viscosities are expressed in centipoise (mPa-s, international - mPa.s; cP=mPa.s), unless otherwise specified.

Remineralization.

In the context of this invention, the term remineralization means the formation in situ (i.e. in the oral cavity) of calcium phosphate on the teeth (including layers on the surface of the teeth with a thickness of from 10 nm to 20 μm, preferably from 75 nm to 10 μm, most preferably from 150 nm to 5 µm, preferably including all intermediate ranges within the specified limits), which serves to reduce the likelihood of tooth sensitivity and decay, to restore tooth enamel and / or improve the appearance of teeth by whitening them due to the formation of new calcium phosphate.

Miscellaneous.

In the present description, except as given in the examples or where otherwise indicated, all numerical values relating to the amount of material or reaction conditions, the physical properties of the materials and/or application, if necessary, can be understood as accompanied by the word about.

In this document, unless otherwise specifically noted, all amounts are by weight relative to the weight of the final composition for caring for the oral cavity.

It should be noted that where any ranges of values are given, any particular upper value may be associated with any particular lower value.

For the avoidance of ambiguity, the expression containing implies the meaning of including, but not necessarily consisting of or formed from. In other words, this list of steps or options is not exhaustive.

The description of the present invention provided herein is to be considered as covering all embodiments of the present invention set forth in the claims, without multiple dependence or redundancy.

- 2 039452

Where a particular feature is described in the context of a particular aspect of the invention (eg, the composition of this invention), such description should also be considered applicable to any other aspects of the invention (eg, the method of this invention), mutatis mutandis.

Disclosure of invention

In its first aspect, this invention relates to an oral care composition containing

a) from 3 to 80% by weight of calcium silicate,

b) a soluble source of calcium,

c) source of phosphate,

d) beneficial agent,

e) a physiologically acceptable carrier, wherein the calcium silicate and the soluble calcium source are present in a weight ratio of 1:3 to 20:1.

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

In a third aspect, this invention relates to a method for improving the teeth of an individual, comprising the step of applying an oral composition according to any of the embodiments of the first aspect of this invention to at least one tooth surface of the individual. In particular, this invention relates to a method for remineralizing and/or whitening teeth in an individual.

All other aspects of the present invention will become clear by considering the implementation of the invention and the following examples.

Implementation of the invention

It has been found that an oral care composition containing calcium silicate, a soluble source of calcium and a source of phosphate can increase the effectiveness of beneficial agents applied to dental surfaces, providing enhanced utility of those agents. It has also been found that such compositions can enhance the binding affinity of beneficial agents to dental surfaces. The expression delivery efficiency as used herein means the ability to deliver a beneficial agent to and deposit on an individual's tooth surface.

calcium silicate

In one preferred embodiment of the present invention, calcium silicate is used, which has low water solubility and is commercially available under the name Sorbosil CA40 (manufactured by PQ Corporation). In another preferred embodiment of the present invention, the calcium silicate is insoluble when represented by the calcium oxide-silica (CaOSiO ₂ ) composite material described, for example, in International Patent Application Publication WO 2008/01517 (Unilever), which is incorporated herein by reference in its entirety. . When the calcium silicate is a composite material, the ratio of calcium and silicon atoms (Ca:Si) can be from 1:30 to 3:1. The Ca:Si ratio is preferably 1:20 to 3:1, more preferably 1:10 to 3:1, most preferably 1:7 to 3:1. The calcium silicate may comprise a single calcium silicate, a dicalcium silicate or a tricalcium silicate. The calcium silicate may be in a crystalline or amorphous state, or even in a mesoporous state.

In addition to calcium oxide and silica, particles containing non-hydrated calcium silicate may include other components, such as metal cations, anions (eg, phosphate), and so on. However, it is preferred that the particles contain calcium oxide and silica in an amount of at least 70% by weight based on the total weight of the particles, more preferably at least 80%, even more preferably at least 90%, and even more preferably at least 95% . The most preferred particles consist of (or at least essentially consist of) calcium oxide and silicon dioxide.

In another preferred embodiment of the invention, the calcium silicate is calcium silicate hydrate. The calcium silicate hydrate for use in this invention contains at least calcium oxide (CaO), silicon dioxide (SiO ₂ ) and water. Compared to the commonly used calcium silicate, which is not hydrated, the calcium silicate hydrate contains water of hydration in an amount of at least 5 wt.% relative to the total mass of calcium silicate hydrate, preferably at least 10%, more preferably at least 15%, still more preferably at least 20%, most preferably at least 25%. The water content generally does not exceed 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% by weight.

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

To provide the amount of calcium required for remineralization, the calcium silicate hydrate preferably contains calcium oxide in an amount of at least 5 wt.% of the total mass of 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% by weight.

In the calcium silicate hydrate, calcium and silicon atoms are preferably present in a (Ca:Si) ratio of less than 1:1, more preferably less than 1:1.2, even more preferably 1:1.5 to 1:4, and most preferably 1:1.7 to 1: 3.

The calcium silicate may be in an amorphous state, or at least partially crystalline or mesoporous. The calcium silicate is preferably particulate as this provides the maximum surface for contact with the dental tissues. Thus, the composition according to the invention preferably contains particles containing calcium silicate. In this case, preferably from 10 to 100%, in particular from 25 to 100%, most preferably in particular from 70 to 100%, relative to the total mass of particles used according to the invention, containing calcium silicate, characterized by sizes from 100 nm to less than 50 μm, preferably 500 nm to 30 µm, more preferably 1 to 20 µm, most preferably 1 to 10 µm.

In addition to calcium oxide, silica and water, particles containing calcium silicate hydrate may include other components, such as metal cations, anions (eg, phosphate), and so on. However, it is preferred that the particles contain calcium oxide, silica and water in an amount of at least 70% (w/w) of the total weight of the particles, more preferably at least 80%, even more preferably at least 90% and still more preferably at least 95%. The most preferred particles consist of (or at least mainly consist of) calcium oxide, silicon dioxide and water.

The oral care composition of this invention typically contains 3 to 80% by weight of calcium silicate, more preferably 3 to 50%, most preferably 5 to 30%, based on the total weight of the oral composition by weight. of this invention, including all intermediate ranges.

Soluble source of calcium

The soluble source of calcium suitable for use in the present invention is only limited insofar as it can be used in the oral cavity.

Illustrative (non-limiting) examples of calcium sources suitable for use in this invention include, for example, calcium chloride, calcium nitrate, calcium acetate, calcium lactate, calcium gluconate, calcium formate, calcium malate, calcium propionate, calcium butyrate, bicarbonate calcium, mixtures thereof or the like. In one of the preferred embodiments of this invention, the calcium source is calcium chloride, calcium nitrate, or a mixture thereof.

The oral care composition of this invention typically contains 0.1 to 20% by weight of a soluble source of calcium, more preferably 1 to 15%, most preferably 2 to 10%, based on the total weight of the oral care composition. mouth according to this invention, including all intermediate ranges.

The oral care composition of this invention preferably contains calcium silicate and a soluble source of calcium in a weight ratio of 1:3 to 20:1, more preferably 1:3 to 10:1, most preferably 1:3 to 7: one.

Phosphate source

The source of phosphate useful in this invention is only limited insofar as it can be used in an oral composition. Illustrative examples of phosphate sources suitable for use in this invention include trisodium phosphate (trisodium phosphate), monosodium phosphate (monosodium dihydrogen phosphate), disodium phosphate (disodium hydrogen phosphate), ammonium phosphate, diammonium phosphate (diammonium hydrogen phosphate), dibasic phosphate ammonium (monoammonium dihydrogen phosphate), tripotassium phosphate (tricalium phosphate), dipotassium phosphate (monopotassium hydrogenphosphate), dipotassium phosphate (dicalium hydrogenphosphate), mixtures thereof, or the like. According to this invention, water-soluble sources of phosphate are preferred.

When used in this invention, the source of phosphate is typically 0.5 to 40%, more preferably 1 to 30%, most preferably 2 to 20% of the total weight of the oral composition, including all ranges in between. In one of the preferred embodiments of this invention, the phosphate source is trisodium phosphate and monosodium phosphate, taken in a weight ratio (Na ₃ PO ₄ :NaH ₂ PO ₄ ) from 1:4 to 4:1, preferably from 1:3 to 3: 1, most preferably from 1:2 to 2:1, including all ranges in between. In another preferred embodiment of the present invention, the phosphate source used is monosodium phosphate or at least contains monosodium phosphate.

The oral care composition of this invention preferably contains calcium silicate and a phosphate source in a weight ratio of 10:1 to 1:5, more preferably 5:1 to 1:3, most preferably 3:1 to 1:1.

Beneficial Agents

The term "beneficial agent" as used herein means an active substance, typically applied to the teeth and/or other structures of the human oral cavity, including gums, to enhance or improve the properties of these tissues. Beneficial agents useful in this invention are limited only by how suitable they are for the oral cavity. Generally, the benefit agent of this invention is selected from materials having an optical effect; agents that promote biomineralization; antibacterial agents; gum health agents; desensitizers; agents that counteract the formation of tartar; refreshing agents or mixtures thereof. Preferably, the benefit agent of this invention is selected from agents having an optical effect; agents that promote biomineralization; antibacterial agents; gum health agents; refreshing agents or mixtures thereof.

Examples of agents having an optical effect are coloring agents, bleaching agents and pigments. Of the pigments according to the invention, violet or blue pigments are preferably used with a hue angle (h) in the CIELAB coordinate system from 220° to 320°. The pigments of this invention may be selected from those listed in the International Dyestary Guide, blue #1 to #83 and violet #1 to #56. In another preferred embodiment of the present invention, the optical effect agents are selected from mica, pearl mica, boron nitrogen, poly(methyl methacrylate) flake pigment, composite microspheres, titanium dioxide coated glass flakes, inverted opal, cholesteric liquid crystals, magnetochromatic (photonic ) microspheres, hollow microspheres and zinc oxide. Biomineralizing agents for tooth enamel are selected from fluorine sources, biological molecules, proteinaceous materials, amorphous calcium phosphate, a-Ca ₃ PO ₄ , β-Ca ₃ PO ₄ calcium carbonate, calcium hydroxyapatite Ca ₁₀ . _x (HPO ₄ )x (RO ₄ ) ₆ . _x (OH) ₂ . _x , 0<x<1), dicalcium phosphate (CaHPO ₄ ), dicalcium phosphate dihydrate (CaHRO ₄ -2H ₂ O), hydroxyapatite (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ), monocalcium phosphate monohydrate (Ca (H ₂ PO ₄ ) ₂ -H ₂ O), octahalcium phosphate (Ca ₈ H ₂ (PO ₄ ) ₆ -5H ₂ O) and tetracalcium phosphate (Ca ₄ (PO ₄ ) ₂ O). The antibacterial agents of this invention are selected from metal salts selected from zinc, copper, silver or mixtures thereof; triclosan; triclosan monophosphate; triclocarban; curcumin; quaternary ammonium compounds; long chain bisbiguanides and tertiary amines, with zinc oxide and peroxide and zinc salts being preferred, including chloride, acetate, ascorbate, sulfate, nitrate, citrate, lactate, fluoride, bromide, iodide, gluconate, tartrate, succinate, formate, phenolsulfonate, salicylate, glycerophosphate, zinc ammonium sulfate or mixtures thereof. The gum health agents are selected from anti-inflammatory agents, plaque inhibitors, biological molecules, proteinaceous materials, vitamins, plant extracts, and curcumin. Flavors selected from peppermint, spearmint, menthol, vegetable oils including clover oil and citrus oils can serve as refreshing agents of this invention.

Beneficial agents of this invention are preferably particulate material (particles), as such materials provide the maximum surface area for contact with dental tissues.

In one of the preferred embodiments of the present invention, the benefit agent is a particulate whitening agent for whitening teeth.

Generally, the particulate whitening agent of this invention contains a material that is physiologically suitable and immediately improves certain properties of the teeth, namely whitening them. In order to provide a good whitening effect, this material preferably has a high refractive index, namely at least 1.9, more preferably at least 2.0, even more preferably at least 2, even more preferably at least 2.4 and most preferably at least 2.5. The upper limit of the values of the refractive index of the specified material is not particularly limited, but preferably does not exceed 4.0. Preferably, the refractive index of said material is between 1.9 and 4.0.

Particularly suitable tooth whitening materials of this invention are metal compounds, preferably zinc (Zn), titanium (Ti), zirconium (Zr), or combinations thereof. Preferred metal compounds in this case are (or at least contain) oxides, such as titanium dioxide (TiO ₂ ), zinc oxide (ZnO), zirconia (ZrO ₂ ) or combinations thereof. The bleaching agent may also contain non-metal oxides such as silicon oxide (SiO).

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In one of the preferred embodiments of this invention, the particulate bleaching agent contains metal oxides, non-metal oxides, or a combination thereof in a relative amount of at least 50 wt.%, more preferably at least 70%, even more preferably at least 80 to 100 % and most preferably from 85 to 95%. In one particularly preferred embodiment of the present invention, the particulate bleaching agent is at least 50 wt. % titanium dioxide, most preferably 60 to 100 wt. % titanium dioxide, based on the total weight of the bleaching agent, including all ranges in between. In another particularly preferred embodiment of the present invention, the particulate bleaching agents are slightly water soluble or water insoluble, most preferably water insoluble.

In one of the preferred embodiments of the present invention, 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 volumes of its constituent components using effective medium theory as described, for example, in WO 2009/023353.

The first component of the composite particle is its core, the second component is the shell (coating). As a rule, the core of the composite particle according to the present invention contains a physiologically acceptable material and immediately improves the properties of the teeth, in particular whitens them. To ensure a good whitening effect, this material should preferably have a 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; most preferably at least 2.5. The maximum value of the refractive index of said material is not particularly limited, but preferably does not exceed 4.0. The core material of the composite particle has a refractive index of preferably 1.9 to 4.0.

As material for the core of the composite particle of this invention, metal compounds are particularly suitable, preferably those in which the metal is selected from zinc (Zn), titanium (Ti), zirconium (Zr), or combinations thereof. Preferably, said metal compound is (or at least contains) a metal oxide, such as titanium dioxide (TiO ₂ ), zinc oxide (ZnO), zirconia (ZrO ₂ ), or combinations thereof. Also, the core of the composite particle may contain non-metal oxides, such as silicon monoxide (SiO).

Typically, the core of the composite particle is from 3% to 98%, preferably from 6% to 65%, most preferably from 10% to 55% by weight of the total weight of the composite particle, including all ranges in between. In one of the preferred embodiments of this invention, the composite particle core contains metal oxides, non-metal oxides, or combinations thereof in a weight relative amount of at least 50% of the total weight of the composite particle core, more preferably at least 70%, even more preferably at least 80 to 100%, most preferably 85 to 95%. In one of the particularly preferred embodiments of the present invention, the first component (core) of the composite particle consists of titanium dioxide at least 50 wt.%, most preferably 60-100 wt.%.

The second component (shell) of the composite particle contains a material suitable for adhesion to tooth enamel, dentin, or both. As a rule, the shell material of the composite particle according to this invention contains elemental calcium and, if necessary, other metals, such as potassium, sodium, aluminum, magnesium, as well as mixtures thereof, and these metals, added if necessary, can be represented by, for example, sulfates, lactates , oxides, carbonates or silicates. Optionally, the sheath material is alumina or silicon dioxide. In one of the preferred embodiments of the present invention, the shell material of the composite particle is suitable to provide long-term improvement in the biological or chemical properties of the teeth (eg, lead to the formation of hydroxyapatite). The composite particle shell materials used in this invention contain at least 50% by weight, based on the total weight of the metals in the shell, of elemental calcium, most preferably at least 65%. In one of the particularly preferred embodiments of the present invention, the sheath metals are 80-100% by weight, based on the total weight of the sheath metals, of elemental calcium. In another particularly preferred embodiment of the present invention, the core and shell of the composite particle are slightly water soluble or water insoluble, most preferably water insoluble.

In one particularly desirable embodiment of the present invention, the second component of the composite particle (shell) may comprise, for example, calcium phosphate, calcium gluconate, calcium oxide, calcium lactate, calcium carbonate, calcium hydroxide, calcium sulfate, calcium carboxymethylcellulose, calcium alginate, calcium salts and citric acid, calcium silicate, mixtures thereof and the like. In another desirable embodiment of the present invention, the coated calcium source comprises calcium silicate.

In another preferred embodiment of this invention, the shell contains elemental

- 6 039452 calcium derived from insoluble calcium silicate, represented by a composite material calcium oxide - silicon dioxide (CaO-SiO ₂ ), as described in international patent applications published as WO 2008/015117 and WO 2008/068248.

When a calcium silicate composite material is used as the shell of the composite particle, the ratio of calcium to silicon (Ca:Si) is from 1:10 to 3:1. The Ca:Si ratio is preferably 1:5 to 3:1, more preferably 1:3 to 3:1, most preferably about 1:2 to 3:1. Said calcium silicate may comprise a monocalcium silicate, a dicalcium silicate or a tricalcium silicate, with the calcium to silicon ratio (Ca:Si) being understood as an atomic ratio.

Typically, in a composite particle, at least 30% of the outer surface of the first component (core) is covered by the second component (shell), preferably at least 50% of the core of the composite particle is coated, most preferably from 70 to 100% of the outer surface of the first component (core). ) of the composite particle are covered with the second component (shell).

In one particularly preferred embodiment of the present invention, the particulate bleaching agent is titanium dioxide coated with calcium silicate.

The particles in the particulate whitening agent of this invention may be of various sizes and shapes. These particles may be spherical, lamellar, or irregular in shape. Their diameter is often from 10 nm to less than 50 μm, preferably from 75 nm to less than 10 μm. In one of the particularly preferred embodiments of this invention, the particle diameter is from 100 nm to 5 microns, including all ranges in between. In the case of composite particles in a preferred embodiment of the present invention, at least 40%, preferably at least 60%, most preferably 75 to 99.5% of the particle diameter is in the core, including all ranges in between.

The oral care composition of this invention may contain a single beneficial agent or a mixture of two or more beneficial agents. Typically, the beneficial agent is present in such a composition in an amount of 0.25% to 60%, more preferably 0.5% to 40%, most preferably 1 to 30% of the total weight of the oral composition, including all ranges in between. .

The ratio (wt./wt.) calcium silicate:beneficial agent varies from 1:10 to 20:1, preferably from 1:5 to 10:1, most preferably from 1:3 to 5:1.

Carrier

The composition of this invention is an oral care composition and generally contains a physiologically acceptable carrier. This carrier preferably contains at least a surfactant, a thickener, a humectant, or a combination thereof.

The oral care composition of this invention preferably contains a surfactant. This composition preferably contains at least 0.01 wt.% surfactant relative to the total weight of said composition, more preferably at least 0.1%, most preferably from 0.5 to 7%. Suitable surfactants according to the invention include anionic surfactants, for example sodium, magnesium, ammonium or ethanolamine (C ₈ -C ₁₈ )alkyl sulfates (for example, sodium lauryl sulfate), (C ₈ -C ₁₈ ) alkyl sulfosuccinates (for example, dioctyl sulfosuccinate sodium), (C ₈ C ₁₈ )alkyl sulfoacetates (for example, sodium lauryl sulfoacetate,), (C ₈ -C ₁₈ ) alkyl sarcosinates (for example, sodium lauryl sarcosinate), (C ₈ -C ₁₈ ) alkyl phosphates (which optionally contain up to 10 ethylene oxide and /or propylene oxide monomers) and sulfated monoglycerides. Other surfactants useful in this invention include non-ionic surfactants, for example, optionally polyethoxylated sorbitan fatty acid esters, ethoxylated fatty acids, polyethylene glycol ethers, fatty acid monoglyceride and diglyceride ethoxylates, ethylene oxide/propylene oxide block polymers. Other suitable surfactants according to the invention include amphoteric surfactants such as betaines or sulfobetaines. Mixtures of any of the materials listed above may also be used. According to this invention, it is more preferred if the surfactant is anionic or contains such a surfactant. Preferred anionic surfactants are sodium lauryl sulfate and/or sodium dodecylbenzenesulfonate. More preferably, the surfactant is sodium lauryl sulfate, sodium coco sulfate, cocamidopropyl betaine, sodium methyl cocoyl taurate, or a mixture thereof.

Thickening agents may also be used in accordance with the present invention, which are limited only by how suitable they are for the oral cavity. Illustrative examples of thickeners used in this invention include sodium carboxymethylcellulose (SCMC), hydroxyethylcellulose, methylcellulose, ethylcellulose, gum tragacanth, gum arabic, gum karai, sodium alginate, carrageenan, guar gum, xanthan gum, Chondrus crispus (Irish

- 7 039452 moss), starch, modified starch, silica thickeners (including aerogels), magnesium aluminum silicate (eg Veegum), carbomers (cross-linked acrylates) and mixtures thereof.

Generally, xanthan gum and/or sodium carboxymethyl cellulose and/or carbomers are preferred in this invention. When a carbomer is used, it is desirable to use a carbomer with an average molecular weight of at least 700,000, preferably at least 1,200,000, most preferably at least about 2,500,000. Mixtures of carbomers may also be used.

In one particularly preferred embodiment of the present invention, the carbomer Synthalen PNC, Synthalen KP or a mixture thereof is used. This carbomer has a high molecular weight; it is a cross-linked polyacrylic acid (Chemical Abstracts Service (CAS) accession number 9063-87-0). These types of materials are commercially available, for example, from Sigma.

In another particularly preferred embodiment of the present invention, sodium carboxymethyl cellulose is used, namely SCMC 9H. This substance is the sodium salt of a cellulose derivative in which the carboxymethyl groups are linked to the hydroxyl groups of the glucopyranose monomers (Chemical Abstracts Service (CAS) accession number 9004-32-4); it is commercially available, for example, from Alfa Chem.

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

In the oral composition of this invention, the thickener is typically 0.01 to about 10%, more preferably 0.1 to 9%, most preferably 0.1 to 5% by weight, based on total the weight of the composition, including all intermediate ranges.

When the oral composition of this invention is a toothpaste or gel, it typically has a viscosity of from about 30,000 to 180,000 centipoise, preferably from 600,000 to 170,000 centipoise, most preferably from 65,000 to 165,000 centipoise.

Suitable humectants are preferably used in the oral care compositions of this invention, which include, for example, glycerol, sorbitol, propylene glycol, dipropylene glycol, diglycerin, triacetin, mineral oil, polyethylene glycol (preferably PEG-400), alkanediols (for example , butanediol and hexanediol), ethyl alcohol, pentylene glycol or mixtures thereof. As water-retaining agents according to this invention, polyethylene glycol, sorbitol or mixtures thereof are preferred.

The humectant is present in the oral composition of this invention in an amount of 10 to 90% by weight relative to the total weight of the composition. More preferably, the moisture-retaining carrier is from 25% to 80%, most preferably from 30% to 60% by weight, based on the total weight of the composition, including all ranges in between.

Optional Components

The oral composition of the present invention has been found to be effective in enhancing the availability and contact of beneficial agents with the tooth surface. Without wishing to be bound by theory, it is believed by the present inventors that the presence of a soluble calcium source increases the concentration of calcium ions in the composition, which promotes interaction between the calcium salts and the phosphate source to form calcium phosphate in the oral cavity. The precipitation of calcium phosphate promotes the deposition of calcium silicate and/or beneficial agents on the surface of the teeth. The remineralization of calcium silicate around the beneficial agents also helps to retain these beneficial agents on the surface of the teeth, increasing their resistance to shear forces.

The oral care composition of this invention may also contain a deposition agent. Deposition agents suitable for use in the present invention are only limited insofar as they are suitable for use in the oral cavity. In one of the preferred embodiments of this invention, the precipitation agent provides a significant amount of calcium ions in the oral cavity, and it is inexpensive and readily available. In one particularly preferred embodiment of the present invention, the precipitating agent is a calcium salt in addition to the soluble calcium source included in the oral composition.

Illustrative (non-limiting) precipitants suitable for use in the present invention include, for example, calcium sulfate hemihydrate, calcium dihydrogen phosphate, calcium aluminate, calcium monohydrogen phosphate, or mixtures thereof, or the like. In one of the preferred embodiments of the present invention, the precipitation agent is calcium dihydrogen phosphate, calcium sulfate hemihydrate, or mixtures thereof.

The materials used as deposition agents of the present invention have been found to be biocompatible, react rapidly with water, and are completely sorbed onto tooth surfaces, so that they can be used to promote the deposition of active agents, e.g., calcium silicate and/or other beneficial agents on the surface of the teeth.

Typically, the oral care composition of this invention contains from 0.1 to 20% by weight based on the total weight of the deposition agent composition, more preferably

- 8 039452 from 0.2 to 15%, even more preferably from 0.5 to 10%, most preferably from 1 to 5%, including all ranges in between.

The oral care composition of the present invention contains calcium silicate and a depositing agent in a weight ratio preferably from 20:1 to 1:5, more preferably from

15:1 to 1:3, most preferably 10:1 to 1:1.

The oral care composition of this invention may contain a variety of other ingredients commonly used in the art to improve physical properties and performance. Such ingredients include preservatives, pH adjusting agents, sweeteners, particulate abrasives, polymeric compounds, buffers and salts to achieve the desired pH and ionic strength of the composition and mixtures thereof. Such ingredients generally collectively comprise less than 20% by weight of the composition, preferably from 0.01% to 15% by weight, most preferably from 0.01% to 12%, based on the total weight of the composition, including all ranges in between.

The oral care composition of this invention may be used in a method for improving the teeth of an individual, comprising applying said composition to at least one tooth surface in the individual's oral cavity. The oral care composition of this invention can be used as an adjunct or alternative as a medicament and/or in the manufacture of an oral health medicament as described herein, for example, to remineralize and/or whiten an individual's teeth. Preferably, or alternatively, said use is non-therapeutic.

The oral care composition of the present invention is preferably substantially free of water, which prevents the calcium salts from reacting prematurely with the phosphate source.

In one of the preferred embodiments of this invention, the proposed composition for caring for the oral cavity is single-phase and anhydrous.

In another preferred embodiment of the present invention, the oral composition according to the invention is a two-phase composition comprising a calcium phase and a phosphate phase, wherein calcium silicate and a soluble calcium source are present in the calcium phase and the phosphate source is present in the phosphate phase. The beneficial agent may be in either of these two phases. These two phases are physically separated, being in independent phases. The contact of these two independent phases with the teeth may be simultaneous or sequential. In one of the preferred embodiments of the present invention, these two phases are in contact with the teeth at the same time.

As a rule, the two-phase composition is fed into the oral cavity from a container in which there are two compartments: one for the calcium phase and the other for the phosphate phase, which allows their simultaneous release into the oral cavity.

In one of the preferred embodiments of the present invention in such a container with two compartments, one of them surrounds the other. In such embodiments of the present invention, one of the phases is represented by a shell surrounding the other phase located in the middle. In one particularly preferred embodiment of the present invention, said core is a calcium phase and the shell surrounding it is a phosphate phase.

In another preferred embodiment of the present invention, in such a container with two compartments, these compartments are located side by side, forming a double tube. In such embodiments of the present invention, these two phases are separated from this tube together; such separation is called co-extrusion. A pump head can be used to separate two phases together.

The biphasic oral composition of this invention may be a gel containing two independent gel phases, one of which is calcium and the other is phosphate. The means for applying such a composition to the dental surfaces can be a cotton rod or mouth guard, on which the calcium and phosphate phases are applied, after which the mouth guard is put on the teeth.

As a rule, the composition according to this invention is packaged in a certain way. If it is in the form of a paste or gel, then it can be placed in a regular plastic, laminate or metal tube or in a single-chamber dispenser. Also, the composition of this invention in the form of a paste or gel can be applied to dental surfaces by any physical means, such as toothpaste, fingertips or an applicator that is brought into contact with the sensitive area to be treated.

The composition of the present invention is effective even if used as part of a daily oral hygiene routine. For example, you can use it to brush your teeth with a toothbrush. The contact of the composition of this invention with the teeth can last for a period of time ranging from 1 second to 20 hours. from to 5 min. The composition of this invention can be applied daily, for example once, twice or three times a day. When the oral composition of the present invention is biphasic, the two phases constituting it are mixed during application to the teeth. Mixed phases remain on tooth surfaces, as a rule, for 3 minutes to 10 hours, more

- 9 039452 preferably from 3 minutes to 8 hours Apply the composition according to this invention on the teeth can be daily.

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

Examples

Example 1

This example demonstrates improved deposition of particles on dental surfaces when using a soluble calcium source in combination with calcium silicate. The amounts of all ingredients are indicated as a percentage by weight, based on the total weight of the composition, and as the level of the active ingredient.

Table 1

Ingredient Samples one 2 3 4 5 Glycerol 67.34 57.34 54.34 54.34 54.34 Sodium monofluorophosphate 1,I 1.11 1,I 1,I 1,I Sodium saccharin 0.25 0.25 0.25 0.25 0.25 Calcium silicate ³ — 10.00 10.00 7.00 7.00 calcium chloride — — 3.00 3.00 — calcium carbonate — — — — 3.00 Titanium dioxide coated with calcium ^silicate 15.00 15.00 15.00 15.00 15.00 Sodium lauryl sulfate 2.00 2.00 2.00 2.00 2.00 Sodium monobasic phosphate 3.20 3.20 3.20 3.20 3.20 Sodium trisubstituted phosphate 3.80 3.80 3.80 3.80 3.80 Silica abrasive ^with 6.00 6.00 6.00 6.00 6.00 xanthan gum 0.10 0.10 0.10 0.10 0.10 flavoring 1.20 1.20 1.20 1.20 1.20

a. Commercially available calcium silicate (CaSi _O3 ); trade name Sorbosil CA40 (manufactured by PQ Corporation)

b. Commercially available calcium silicate coated titanium dioxide (manufactured by KOBO Products Inc.)

c. Commercially available silicon dioxide; trade name Sorbosil AC77 (manufactured by PQ Corporation)

Methods

To determine the deposition of particles of the composition on the tooth surface, the test samples were mixed with water in a ratio of 4 g/8 ml of deionized (DI) water, so that a thick suspension was obtained. Sample 1, which contained only composite particles, served as a control.

Pieces of bovine tooth enamel were treated with various suspensions using a dentifrice equipped with toothbrushes. The load was 170+/-5 g, the automatic movement of the toothbrush was at 150 rpm. After such cleaning for 1 min, the pieces of enamel were placed in a suspension of toothpaste for 1 min. They were then rinsed with deionized water and kept in simulated oral fluid (SOF) in a shaking (60.0 rpm) water bath at 37°C. After 3-4 hours, the enamel pieces were cleaned with a dentifrice with a brush in the presence of a suspension in the same way as in the first stage of the described treatment. Brushing was repeated three times for 1 day, then the enamel pieces were kept in SOF overnight (>12 h) in a shaking (60.0 rpm) 37° C. water bath to mimic an oral environment. Enamel samples were brushed 14 times.

Simulation of oral fluid was made, as shown in table. 2.

table 2

Ingredient Quantity/g NaCl 16.07 _NaHCO3 0.7 KS1 0.448 K ₂ HPO ₄ *3H ₂ O 3.27 MgCl ₂ *6H ₂ O 0.0622 IM HCl 40 ml _CaCl2 0.1998 _{Na2SO4 _} 0.1434 buffering agent up to pH 7.0 Water up to 2 l

- 10 039452

results

After 14 brushings, the enamel pieces were examined using a scanning electron microscope (SEM). In the obtained images (top view), it was seen that the composite particles were deposited randomly on the surface of the enamel of samples 1, 2 and 5. But in the case of samples 3 and 4 containing a soluble source of calcium, the formation of a new layer on the enamel surface was found and particles or aggregates particles were evenly immersed in the newly formed layer.

SEM images of the respective cross sections showed that a new layer about 3-5 µm thick was formed on the surface of the enamel pieces after treatment with Sample 3, with the particles immersed in the new layer; and no new layer formed on the surface of the enamel pieces treated with Sample 1. SEM images of the cross sections also showed that a new layer about 2 µm thick was formed on the surface of the enamel pieces after treatment with sample 4, with the particles immersed in the new layer.

On the surface of the pieces of enamel treated with samples 2 and 5, no new layer was formed due to the short duration of treatment. By analyzing X-ray energy dispersion spectroscopy (EDX) in the newly formed layer on the surface of the enamel pieces, the following elements were identified: Si, Ca, P and Ti, indicating the deposition of particles on the enamel surface.

Example 2

This example demonstrates the ability of a newly formed layer containing particles immersed in it to adhere to dental surfaces. Sample 3 from Example 1 was used in this experiment.

Methods

To determine the ability of the newly formed layer containing particles embedded in it to adhere to dental surfaces, the test specimens were mixed with deionized water at a ratio of 4 g/8 ml, so that a thick suspension was obtained. Pieces of bovine tooth enamel were treated with the slurry using a dentifrice equipped with toothbrushes in the same manner as described above. The load was 170+/-5 g, the automatic movement of the toothbrush was at 150 rpm. After such cleaning for 1 min, the pieces of enamel were placed in a suspension of toothpaste for 1 min. They were then rinsed with deionized water and kept in simulated oral fluid (SOF) in a shaking (60.0 rpm) water bath at 37°C. After at least 3 hours, the enamel pieces were cleaned with a dentifrice and brush in deionized water. The load was 170+/-5 g, the automatic movement of the toothbrush was at 150 rpm. After this cleaning for 1 min, the enamel pieces were placed in SOF in a shaking (60.0 rpm) water bath at 37°C. After at least 3 hours, the enamel pieces were brushed with a dentifrice and brush in deionized water for 1 minute at a load of 170+/-5 g and a speed of 150 rpm. The pieces of tooth enamel were then brushed with a dentifrice with fresh toothpaste slurry for 1 min (170+/-5 g; 150 rpm) and kept in toothpaste slurry for 1 min. Thereafter, the enamel pieces were washed with deionized water and kept in SOF overnight (>12 h) in a shaking (60.0 rpm) water bath at 37° C. to simulate an oral environment. The enamel pieces were then cleaned using a dentifrice with brushes in deionized water for 1 min (170+/-5 g; 150 rpm). These stages were considered a full processing cycle per day. Pieces of enamel were treated in this way for 14 days.

results

After 14 days of the above treatment of the enamel pieces, SEM images of their surface were obtained. The top view showed that a plurality of particles and particle aggregates were immersed in the newly formed layer on the surface of the enamel pieces.

SEM images of the respective cross sections showed that a new layer was formed on the surface of the enamel pieces after treatment with Sample 3, with the particles immersed in the new layer. The results obtained clearly demonstrate that the newly formed layer was not removed by brushing in water, indicating an increased ability of the newly formed layer to adhere to the enamel surface. By analyzing X-ray energy dispersion spectroscopy (EDX) in the newly formed layer on the surface of the enamel pieces, the following elements were identified: Si, Ca, P and Ti, indicating the deposition of particles on the enamel surface.

CLAIM

Claims (12)

CLAIM 1. An oral care composition comprising: a) from 3 to 80% by weight of calcium silicate, b) a soluble source of calcium, c) source of phosphate, d) beneficial agent, e) a physiologically acceptable carrier, - 11 039452 wherein the calcium silicate and the soluble calcium source are present in a weight ratio of 1:3 to 20:1, in which the soluble calcium source is calcium chloride, calcium nitrate, calcium acetate, calcium lactate, calcium gluconate, calcium formate, calcium malate, calcium propionate, calcium butyrate, calcium bicarbonate or mixtures thereof; wherein the phosphate source is trisodium phosphate, monosodium dihydrogen phosphate, disodium hydrogen phosphate, ammonium phosphate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, tripotassium phosphate, monopotassium dihydrogen phosphate, dipotassium hydrogen phosphate, or mixtures thereof; and in which the beneficial agent is selected from substances having an optical effect; agents that promote biomineralization; antibacterial agents; gum health agents; desensitizers; agents that counteract the formation of tartar; refreshing agents or mixtures thereof. 2. The oral care composition of claim 1, wherein the soluble calcium source is calcium chloride, calcium nitrate, or mixtures thereof. 3. An oral care composition according to claim 1 or 2, wherein the calcium silicate is present in an amount of 3 to 50% by weight, preferably 5 to 30%. 4. An oral care composition according to any one of the preceding claims, wherein the calcium silicate and the soluble calcium source are present in a weight ratio of 1:3 to 10:1, preferably 1:3 to 7:1. 5. An oral care composition according to any one of the preceding claims, wherein the phosphate source is trisodium phosphate, monosodium dihydrogen phosphate, or mixtures thereof. 6. An oral care composition according to any one of the preceding claims, which contains calcium silicate and a source of phosphate in a weight ratio of 10:1 to 1:5, preferably 5:1 to 1:3. 7. An oral care composition according to any one of the preceding claims, wherein the benefit agent is a particulate whitening agent containing a material with a refractive index of 1.9 to 4.0. 8. The oral care composition of claim 7 wherein the particulate whitening agent is composite particles, preferably the composite particles are titanium oxide coated with calcium silicate 9. An oral care composition according to any one of the preceding claims, wherein the weight ratio of calcium silicate to benefit agent is 1:10 to 20:1, preferably 1:5 to 10:1. 10. An oral care composition according to any one of the preceding claims, which is a single phase anhydrous composition. 11. An oral care composition according to any one of claims 1 to 9, which is biphasic, comprising a calcium phase and a phosphate phase, wherein the calcium silicate and the soluble calcium source are in the calcium phase and the phosphate source is in the phosphate phase. 12. A method for improving the condition of an individual's teeth, comprising the step of applying a composition according to any one of paragraphs. 1-11 on at least one tooth surface of a given individual.