RU2816006C2 - Dentifrice composition containing carboxylic acid or its alkali metal salt and source of free fluoride ions - Google Patents

Abstract

FIELD: hygiene; pharmaceutics.

SUBSTANCE: group of inventions relates to the field of teeth cleaning agents and their use. Proposed toothpaste composition contains a carboxylic acid or an alkali metal salt thereof in amount of 1.5% to 3.0% of the weight of said composition, where said acid is selected from a list consisting of malonic acid, glutaric acid, tartaric acid, lactic acid and mixtures thereof; copolymer of methyl vinyl ether (MVE) with maleic anhydride or acid, wherein said copolymer is present in amount of 0.2% to 0.3% of the weight of said composition; and a source of free fluoride ions, and wherein the pH of the suspension prepared from said toothpaste composition and distilled water in a weight ratio of the composition to water of 1:3 is in range of 5.0 to 6.5. Also disclosed is the use of said toothpaste composition for protecting teeth from dental erosion for protecting teeth from caries.

EFFECT: composition of the composition provides a significant increase in the fluoride absorption by the teeth due to the use of the specific carboxylic acid(s) from the above list; wherein the inclusion of a copolymer of methyl vinyl ether with maleic anhydride or acid provides a significant increase in the reduction of enamel solubility without adversely affecting fluoride absorption.

14 cl, 11 tbl, 10 ex, 13 dwg

Description

Field of the present invention

The present invention relates to a dentifrice composition for strengthening and protecting the enamel of natural teeth, thereby providing them with protection from acid attacks. The composition of the present invention contains a particular carboxylic acid or an alkali metal salt thereof, a source of free fluoride ions, and optionally a copolymer of methyl vinyl ether (MVE) with maleic anhydride or acid. It is important that said dentifrice composition is moderately acidic, with a pH of the suspension ranging from 5.0 to 6.5.

BACKGROUND OF THE INVENTION

The tooth mineral consists primarily of calcium hydroxyapatite, Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ , which may be partially replaced by anions such as carbonate or fluoride and cations such as zinc or magnesium. The tooth mineral may also contain non-apatite mineral phases such as octacalcium phosphate and calcium carbonate.

Tooth decay can result from dental caries, which is a multifactorial disease in which bacterial acids such as lactic acid produced from the metabolism of dietary sugars lead to subsurface demineralization that is not fully remineralized between periods of sugar exposure, resulting in progressive loss tissues and, over time, cavity formation. The presence of plaque biofilm is a prerequisite for dental caries, and acidogenic bacteria such as Streptococcus mutatis can become pathogenic when levels of Sugars (i.e., easily fermentable carbohydrates such as sucrose) increase over long periods of time.

Even in the absence of plaque biofilm, loss of dental hard tissue can occur as a result of acid erosion and/or physical wear of the teeth, and these processes are thought to act synergistically. The effect of acid on the hard tissues of the tooth can cause demineralization, which leads to a softening of the surface and a decrease in mineral density. This softened mineral is susceptible to wear by physical contact. Under normal physiological conditions, partially demineralized tissues repair themselves due to the remineralizing effect of saliva. Saliva is oversaturated with calcium and phosphate, and in healthy individuals, salivary secretion serves to flush out the acid load and to raise the pH to tip the balance in favor of mineral deposition.

Tooth erosion (i.e. acid erosion or acid wear) is a surface phenomenon that involves demineralization and eventual complete dissolution of the tooth surface by acids of non-bacterial origin. These are most often food-grade acids such as citric acid from fruits or sodas, phosphoric acid from cola drinks, and acetic acid such as from vinaigrettes. Tooth erosion can also be caused by repeated exposure to hydrochloric acid (HCl) produced by the stomach, which can enter the mouth as an involuntary reaction such as gastroesophageal reflux, or as an induced reaction, which can occur in bulimics.

Tooth wear (i.e. physical wear and tear of teeth) is caused by wear and/or abrasion. Abrasion occurs when the surfaces of teeth rub against each other, a form of wear caused by the interaction of two bodies. An often prominent example is the phenomenon observed in patients with bruxism, that is, the habit of grinding teeth during sleep when the applied forces are high, and this example is characterized by accelerated wear, especially on the occlusal surfaces. Abrasion usually occurs as a result of wear and tear from the interaction of three bodies, and the most common example is brushing your teeth with toothpaste. In the case of fully mineralized enamel, the amount of wear caused by commercially available toothpastes is minimal and has virtually no clinical consequences. However, if the enamel has been demineralized and softened by erosive action, the enamel becomes more susceptible to wear. Enamel is thinnest at the junction with dentin, which is normally located just below the gum edge. However, gum recession (especially associated with aging) can expose the enamel-dentin junction, and wear of the enamel in this area can expose the dentin, leading to hypersensitivity, as described below.

Dentin is a vital tissue that in vivo is usually covered by enamel or cementum depending on the location, i.e. crown or root, respectively. Dentin has a much higher organic content than enamel, and its structure is characterized by the presence of fluid-filled tubules that extend from the dentin-enamel or dentin-cementum interface to the pulp interface. Dentin is much softer than enamel and therefore more susceptible to wear. Patients with exposed dentin should avoid using highly abrasive toothpastes. Again, softening of dentin through erosive action increases the tissue's susceptibility to wear. It is widely accepted that the causes of dentin hypersensitivity are related to changes in fluid flow in open tubules (hydrodynamic theory), which lead to stimulation of mechanoreceptors believed to be located close to the pulp interface. Not all exposed dentin is sensitive, as it is usually covered by a smear layer, an occlusal mixture consisting primarily of minerals and proteins derived from the dentin itself, but also containing organic components from saliva. Over time, the lumen of the tubule may become completely clogged with mineralized tissue. The formation of reparative dentin in response to trauma or chemical irritation of the pulp is also well documented. However, erosive action can remove the smear layer and tubule plugs, releasing a flow of dentinal fluid that makes the dentin much more susceptible to external stimuli such as heat, cold, and pressure. As stated earlier, erosive stress can also make the dentin surface more susceptible to wear. In addition, dentin hypersensitivity worsens as the diameter of the exposed tubules increases, and since the diameter of the tubules increases toward the pulpal margin, progressive wear of dentin can lead to increased hypersensitivity, especially in cases where rapid dentin wear occurs.

Thus, erosion and/or wear of teeth caused by acid exposure are the main etiological factors in the development of dentin hypersensitivity.

It has been argued that increased consumption of dietary acids and a shift away from formalized meal times are accompanied by an increase in the incidence of dental erosion and tooth wear among the population of developed countries. Therefore, oral care compositions are preferred which can help prevent tooth erosion and tooth wear and which provide protection against dental caries.

Oral care compositions often contain a source of fluoride ions to stimulate remineralization of teeth and to increase the acid resistance of dental hard tissues. To be effective, fluoride ions must be available for absorption by the hard tissues of the teeth being treated.

It has been observed that demineralized enamel will absorb more fluoride from an acidic solution than from a neutral one (e.g., Friberger, The effect of pH upon fluoride uptake in intact enamel. Scand. J. Dent. Res. (1975) 83:339-344) . Friberger's study examined in vitro fluoride uptake from a dental slurry composition and from sodium fluoride solutions of varying pH ranging from 7.1 to 4.5. The pH value was adjusted using a few drops of 0.1 M HCl acid or NaOH. The study showed that there was no significant difference when using different agents (namely, a sodium fluoride dentifrice composition, a potassium fluoride and manganese chloride dentifrice composition, and a sodium fluoride solution of the same fluoride concentration), but the effect of pH was significant. Fluoride uptake in the form of fluorapatite was more than five times greater at lower pH levels.

GB 1018665 (Unilever Ltd) describes a fluoride dentifrice composition comprising a water-soluble buffer system which includes a weak organic acid and an alkali metal salt, for example acetic acid/sodium acetate and malic acid/sodium malate, and wherein the pH of the suspension of said dentifrice is teeth in simulated saliva is from 5 to 6. It is described that the specified composition for cleaning teeth is capable of reducing the solubility of enamel compared to solutions at neutral pH.

US 2009/0087391 A1 (Joziak) describes a foaming fluoride dental composition containing a surfactant selected from the group consisting of nonionic, zwitterionic or betaine surfactants or mixtures thereof, and an acidifying agent in an amount sufficient to bring pH to range from 3 to 5. Suitable acidifying agents are organic acids such as malic acid, succinic acid, citric acid and tartaric acid or mixtures thereof.

WO 01/66074 (Colgate) describes a two-component dentifrice composition in which one phase is alkaline and contains fluoride ions and the other phase is acidic and contains phosphate ions, which when mixed before use gives an acidic phosphate fluoride composition (pH from 4 to 6). It is believed that using the composition for brushing teeth at an acidic pH may enhance the uptake of fluoride ions by tooth enamel.

US Pat. No. 4,363,794 (Lion Corporation) discloses an oral care composition that contains a stannous salt such as stannous fluoride, a water-soluble fluoride salt such as sodium fluoride, and an orally acceptable acid such as L-ascorbic acid, lactic acid , malonic acid, tartaric acid, citric acid, hydrochloric acid and pyrophosphoric acid, wherein the molar ratio of fluoride ion to stannous ion is in the range of 3.2 to 7:1, preferably 3.5 to 6:1, in aqueous state, and the pH of the composition is in the range of 2 to 4. It is disclosed that the composition exhibits excellent effects in inhibiting dental caries. According to US Pat. No. 4,363,794, the use of a specified pH range results in increased efficiency in increasing the acid resistance of the treated enamel and the stability of the stannous ion. Low pH (below 2) tends to interfere with oral administration of the composition, while pH above 4 often causes a decrease in the availability and stability of the stannous ion.

The use of fluoride-containing dentifrice compositions having a substantially neutral pH has also been described in the art for remineralizing and strengthening teeth. WO 2006/1000071 (Glaxo Group Ltd) discloses dentifrice compositions which contain, among other ingredients, a source of fluoride ions and have a pH in the range of 6.5 to 7.5. Such compositions have been commercialized as SENSODYNE Pronamel toothpaste for use in protecting teeth from food acids.

In one aspect, the present invention is based on the discovery that the inclusion of specific carboxylic acid(s) as described herein in a weakly acidic dentifrice composition containing a source of fluoride ions significantly increases the uptake of fluoride ions into tooth enamel over with the same composition at neutral pH or compared with the same weakly acidic composition but containing another carboxylic acid (such as malic acid) or inorganic acid (such as phosphoric acid).

In a further aspect, the present invention is based on the discovery that the inclusion of a copolymer of methyl vinyl ether with maleic anhydride or acid provides the additional benefit of significantly increasing the reduction in enamel solubility without negatively affecting fluoride absorption.

The use of methyl vinyl ether-maleic acid copolymers in oral care compositions is known in the art. For example, US Pat. No. 4,485,090 discloses a dentifrice composition containing a polymeric anionic membrane-forming material such as Gantrez AN. According to US Pat. No. 4,485,090, the material adheres to the surface of teeth and forms a substantially continuous barrier thereon, complexing with calcium present in the teeth. The barrier formed is described as significantly reducing the leaching of a previously applied therapeutic agent (eg, dental fluoride treatment), thereby prolonging the effectiveness of such agent. According to US Pat. No. 4,485,090, the compositions of this invention need to be applied only intermittently (eg, once daily) to achieve the desired reduction in elution and consequent control of caries and plaque.

More recently filed US patent application US 2004/0146466 (Baig et al.) discloses that specific polymeric mineral surfactants such as synthetic anionic polymers such as polyacrylates and maleic anhydride or acid-methyl vinyl ether copolymers (eg Gantrez) have strong affinity for the surface of tooth enamel, and such polymers form a layer or coating on the surface of the enamel. Effective amounts of polymeric mineral surfactant are described in the range of from about 1% to about 35%, preferably from about 2 to about 30%, more preferably from about 5% to about 25%, and most preferably from about 6% to about 20% from the weight of the entire oral care composition.

WO 2007/069429 (Lion Corporation) describes toothpaste compositions containing (A) from 0.3 to 1.2% by weight of at least one linear and water-soluble polyphosphate represented by the general formula M _n+2 P _n O _{3n +1} (where M is Na or K; and n is an integer 2 or 3), (B) 0.1% to 2.0% by weight methyl vinyl ether/maleic anhydride copolymer, 2.0% aqueous solution which has a viscosity of 5 to 1000 mPa⋅s at 25°C and pH 7.0, (C) from 0.6 to 2.0% by weight of lauryl sulfate, and (D) from 0.2 to 1.0% by weight weight of an amphoteric surfactant of the betaine type, and the composition ratio by weight of components (C)/(D) is in the range from 1 to 4. Such compositions are described as causing mild irritation of the oral mucosa and providing favorable foaming during use, and also having an excellent effect in preventing the adhesion of coloring substances to the surfaces of teeth.

WO 2011/094499 (Colgate-Palmolive Company) discloses anti-erosion oral care compositions containing a methyl vinyl ether-maleic anhydride copolymer, such as Gantrez, and a metal compound or salt that becomes more soluble at acidic pH. According to WO 2011/094499, a mucoadhesive polymer such as Gantrez may be included in an orally acceptable carrier in an amount of from 0.01 to 20% by weight, preferably from 0.1 to 10% by weight and most preferably from 0.5 up to 7% by weight of the component. The “Low Polymer Formulation” and the “High Polymer Content Formulation” exemplified in WO 2011/094499 contain 0.5% and 2.0% by weight of Gantrez, respectively.

Technical Information Bulletin VC-862A, published by Ashland Specialty Chemicals (Rev. 02-2015), reports that superior enamel resistance to acid erosion was observed in an in vitro study after pretreating enamel with toothpaste containing 2% Gantrez S-97 polymer. , and that the presence of Gantrez is believed to be the main reason for the improvement observed in the reduction of acid erosion.

WO 2015/171836 (Procter & Gamble) describes oral care compositions containing 5% metal ions, at least 0.001% tin ions, and optionally from about 0.001% to about 4% zinc ions; at least about 100 ppm by weight of fluoride ions and at least about 0.03% by weight of a mineral surfactant selected from, among others, copolymers of maleic anhydride or acid with methyl vinyl ether; at least 5% water; less than 10% by weight of fused silica, calcium-based abrasive and mixtures thereof, less than 5% polyphosphates having n+3 or higher, wherein the mass ratio of total metal ion (tin and optionally zinc) is equal to or less than 0.5 . WO 2015/171836 discloses, by appropriately balancing the ratio of total metal ions to a selected group of mineral surfactants, that fluoride uptake can be improved and certain benefits (antibacterial effectiveness, fluoride uptake, demineralization and stain reduction) required to reach " "golden mean" in relation to oral care can be achieved in one composition. According to WO 2015/171836, the compositions described therein provide enhancement of remineralization and inhibition of demineralization by controlling the deposition of surface protecting agents which, when applied in excess, negatively affect fluoride uptake and remineralization of subsurface dental lesions. The inclusion of a buffering agent is optional, and oral care compositions will typically have a pH of from about 4 to about 7, preferably from about 4.5 to about 6.5, and more preferably from about 5 to about 6. In WO 2015/171836 disclosed that the inclusion of Gantrez does not affect fluoride uptake from a NaF-containing formulation.

Brief Description of the Present Invention

In one aspect, the present invention provides a dentifrice composition containing a carboxylic acid or an alkali metal salt thereof, wherein said acid is selected from the group consisting of malonic acid, glutaric acid, tartaric acid, lactic acid and mixtures thereof; and a source of free fluoride ions; and wherein said composition has a pH of the suspension in the range of 5.0 to 6.5.

In a further aspect, the present invention provides a dentifrice composition containing a carboxylic acid or an alkali metal salt thereof, wherein the acid is selected from the group consisting of malonic acid, glutaric acid, tartaric acid, lactic acid and mixtures thereof; source of free fluoride ions; and a copolymer of methyl vinyl ether with maleic anhydride or acid; and wherein said composition has a pH of the suspension in the range of 5.0 to 6.5.

Such compositions are used to protect teeth from dental erosion. Such compositions are also used to protect teeth from caries.

Brief description of drawings

Fig. 1: Effect of malonic acid and pH on PFE

Fig. 2: Effect of malonic acid and citric acid (at pH 5.50) on PFE

Fig. 3: Effect of malonic acid and pH on PFE

Fig. 4: Effect of specific carboxylic acids and phosphoric acid on PFE

Fig. 5: Effect of lactic acid and pH on PFE

Fig. 6: Effect of PVME/MA (pH 6.2) on PFE

Fig. 7: Effect of PVME/MA (pH 6.2) on SRE

Fig. 8: Brief description of VMTP after 4 hours of remineralization

Fig. 9: Summary of average % TER after 4 hours of remineralization

Fig. 10: Brief description of PFE after 4 hours of remineralization

Fig. 11: Data on tissue loss after treatment of human enamel with a composition for cleaning teeth followed by erosive testing

Fig. 12: Change in average fluoride absorption at 50 µm depth

Fig. 13: Average relative absorption of 44Ca at a depth of 20 µm

Detailed Description of the Present Invention

The composition according to the present invention includes a carboxylic acid or an alkali metal salt thereof, wherein said acid is selected from the group consisting of malonic acid, glutaric acid, tartaric acid, lactic acid and mixtures thereof. In one embodiment, the carboxylic acid is lactic acid or an alkali metal salt thereof. Typical examples of suitable alkali metal salts include the sodium and potassium salts of the above carboxylic acids. In one embodiment, said alkali metal salt is potassium salt(s) of malonic, glutaric, tartaric, lactic acids and mixtures thereof. In one embodiment, said alkali metal salt is selected from sodium salt(s) of malonic, glutaric, tartaric, lactic acids and mixtures thereof. In one embodiment, said carboxylic acid salt is potassium lactate. In one embodiment, said carboxylic acid salt is sodium lactate.

Said carboxylic acid or a salt thereof may be present in the form of a solid or an aqueous solution, for example, sodium lactate solution (60% by weight).

Accordingly, said carboxylic acid or an alkali metal salt thereof is present in an amount of from 0.5% to 5.0% by weight of the entire composition, for example from 1.0% to 4.5% or from 1.5% to 3.0 % by weight of the entire composition. The preferred amount is 2.0% acid or 2.5% salt, based on the weight of the total composition.

The composition according to the present invention contains a source of free fluoride ions. Suitable examples of the source of free fluoride ions include alkali metal fluoride such as sodium or potassium fluoride, polyvalent metal ion fluoride salts such as stannous fluoride, or fluoride salts with cationic organic ions such as ammonium fluoride or bis(hydroxyethyl)aminopropyl-ion. N-hydroxyethyloctadecylamine dihydrofluoride (amine fluoride) or a mixture thereof in an amount providing from 25 to 5000 ppm. fluoride ions, preferably from 100 to 1500 ppm. In one embodiment, the source of free fluoride ions is stannous fluoride. In one embodiment, the source of free fluoride ions is not stannous fluoride. In one embodiment, the source of free fluoride ions is an alkali metal fluoride, such as sodium fluoride. A suitable composition contains from 0.05% to 0.5% by weight sodium fluoride, for example 0.1% by weight (corresponding to 450 ppm fluoride ions), 0.205% by weight (corresponding to 927 ppm fluoride -ions), 0.2542% by weight (corresponding to 1150 ppm fluoride ions) or 0.3152% by weight (corresponding to 1426 ppm fluoride ions).

The composition according to the present invention is slightly acidic, i.e. has a pH of the suspension in the range of greater than 5.0 to less than 6.5, for example pH 5.1 to 6.4, 5.4 to 6.3, or 5.5 to 6.2. In one embodiment, the pH is about 6.2. This is the pH measured when the dentifrice composition is suspended with water at a weight ratio of the composition to water of 1:3. Said suspension is suitably prepared by mixing the dentifrice composition with water in a mass ratio of one part dentifrice composition and three parts distilled water. The pH value is determined using a standard pH meter.

A suitable dentifrice composition according to the present invention includes a pH modifying agent to adjust the pH of the composition to the desired pH. Suitable pH modifying agents include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, or inorganic acids such as hydrochloric acid or sulfuric acid. In one embodiment, said pH modifying agent is sodium hydroxide. The pH modifying agent may be used in an amount of 0.005% to 5% by weight of the composition, for example 0.01% to 2% or 0.02% to 1% by weight of the composition.

In one aspect, the composition of the present invention contains a surface protecting agent that is a copolymer of methyl vinyl ether (MVE) with maleic anhydride or acid. In one embodiment, the surface protectant is MVE with maleic acid. Typically, said copolymer is a linear copolymer containing alternating units of MVE and maleic anhydride or acid. In one embodiment, said copolymer comprises a 1:4 to 4:1 MBE:maleic anhydride or acid ratio, such as a 1:1 MBE:maleic anhydride or acid ratio, i.e. the MVE content is about 50 mol% and the maleic anhydride or acid content is about 50 mol%. In one embodiment, said copolymer is the acid form of a copolymer of MVE with maleic anhydride, where the anhydride is fully or partially hydrolyzed, for example, after copolymerization to produce the corresponding acid. In one embodiment, the copolymer has a molecular weight in the range of 100,000 to 2,000,000, such as 500,000 to 1,900,000 or 1,000,000 to 1,800,000. A suitable copolymer for use in the present invention is commercially available under the trade name GANTREZ®, such as a solution of GANTREZ® S-97 HSU (Mw 1,500,000), GANTREZ® S-97 BF (Mw 1,200,000), GANTREZ® S-96 (Mw 700,000) and GANTREZ® S-95 (Mw 150,000), all of which are copolymers of MVE with maleic acid. In one embodiment, the copolymer is GANTREZ® S-97, which is a copolymer of MBE with maleic acid having an approximate molecular weight of 1,200,000 or 1,500,000.

GANTREZ® S-97 can be provided in the form of a solid (powder) or in the form of a liquid such as an aqueous solution, for example, GANTREZ® S-97 HSU solution. In one embodiment, said copolymer comprises a GANTREZ® polymer with the following structure and properties as follows:

Dibasic acid with pKa ₁ =3.5, pKa ₂ =6.5

Accordingly, the rheological properties of the copolymer can be modified by the addition of salts and bases. GANTREZ® copolymers are commercially available from a variety of sources, including Ashland Specialty Chemicals, Bound Brook, N.J. 08805, USA, and International Specialty Products, Wayne, NJ, USA.

Providing a dentifrice composition that provides improved fluoridation when the composition contains a surface protecting agent (ie, a copolymer used in the present invention as defined above) is difficult. This is because the agent coats the areas on the tooth surface where fluoridation typically occurs. Advantageously, in the present invention, said copolymer can be combined with a source of fluoride ions without adversely affecting the delivery of fluoride to tooth enamel. The present inventors have surprisingly found that a small amount of copolymer provides an improvement in reducing enamel solubility without significantly adversely affecting fluoride absorption. Accordingly, when said copolymer is present, it is used in an amount of from 0.05% to 2% by weight of the composition, for example from 0.1% to 1%, or from 0.15% to 0.5%, or from 0. 2% to 0.4% by weight of the composition. In one embodiment, said copolymer is used in an amount of about 0.25% by weight of the composition. In the in vitro tests described herein, it was surprisingly discovered that when using a small amount (0.2% to 0.3% by weight of the composition, as an example here about 0.25% by weight of the composition) of the copolymer can There was a significant improvement in inhibition of demineralization without a negative effect on fluoride absorption. These results were further confirmed by the results of an in situ erosion study, also described herein, where it was shown that the composition according to the present invention containing about 0.25 wt. % methyl vinyl ester copolymer of maleic acid, superior to all other tested dentifrice compositions in terms of fluoride uptake, enhancement of remineralization and inhibition of demineralization. In one embodiment, said copolymer is used in an amount of about 0.25% by weight of the composition, and said composition has a slurry pH of about 6.2.

In one embodiment, the composition of the present invention does not contain stannous ions and/or zinc ions. For example, in one embodiment, the composition of the present invention does not contain from about 0.001% to about 5% metal ions, where the metal ions include at least 0.001% stannous ions and optionally from about 0.001% to about 4% zinc ions. In one embodiment, the composition does not contain a metal compound or salt that becomes more soluble at an acidic pH. In one embodiment, said composition does not contain a calcium or zinc compound or salt.

The compositions of the present invention may contain suitable formulation agents selected from those typically used in oral care compositions for such purposes, such as dental abrasives, surfactants, thickeners, humectants, flavorings, sweetening agents, opacifiers or coloring agents. agents, preservatives and water.

Examples of suitable dental abrasives include silica-based abrasives, such as those sold under the trade names Zeodent, Sident, Sorbosil or Tixosil from Huber, Degussa, Ineos and Rhodia, respectively. The silica abrasive must be present in an amount sufficient to provide adequate cleaning of the teeth by the dentifrice composition without causing abrasion of the teeth.

The silica abrasive is typically present in an amount of up to 15% of the total weight of the composition, for example 2% to 10%, and preferably at least 5%, for example 5% to 7%, especially 6% of the total weight of the composition. Reducing the level of silica abrasive has the advantage of not only reducing the abrasiveness of the dentifrice composition, but also minimizing any interaction of the abrasive with fluoride ions, thereby increasing the availability of free fluoride ions.

Suitable surfactants for use in the present invention include amphoteric surfactants, for example, long chain alkyl betaines, such as the product sold under the trade name "Empigen BB" by Albright & Wilson, and preferably long chain alkyl amidoalkyl betaines, such as cocamidopropyl betaine or low ionic surface active agents. - active substances such as sodium methyl cocoyl taurate, which is sold under the trade name Adinol CT by Croda, or mixtures thereof. The amphoteric surfactant can be used alone as the sole surfactant or can be combined with a low ionic surfactant. In one embodiment, the surfactant is not a C _10-18 alkyl sulfate surfactant, such as sodium lauryl sulfate, commonly used in oral care compositions.

Accordingly, the surfactant is present in the range of 0.1% to 10%, preferably 0.1% to 5%, and more preferably 0.5 to 1.5% of the total weight of the composition.

Suitable thickeners include, for example, nonionic thickeners such as, for example, (C _1-6 )alkylcellulose ethers, for example methylcellulose; hydroxy-(C _1-6 )-alkylcellulose ethers, for example hydroxyethylcellulose and hydroxypropylcellulose; (C _2-6 ) alkylene oxide modified (C _1-6 ) alkyl cellulose ethers, for example, hydroxypropyl methylcellulose, and mixtures thereof. Other thickeners may also be used, such as natural and synthetic gums or gums such as Irish moss, xanthan gum, tragacanth gum, sodium carboxymethylcellulose, polyvinylpyrrolidone, starch and thickening silicas. Preferably, said thickener is a mixture of silica thickener and xanthan gum.

Advantageously, the thickener is present in the range of 0.1% to 30%, preferably 1% to 20%, more preferably 5% to 15% of the total weight of the composition.

Suitable humectants for use in the compositions of the present invention include, for example, glycerin, xylitol, sorbitol, propylene glycol or polyethylene glycol or mixtures thereof; the humectant may be present in the range of 10% to 80%), preferably 20% to 60%, more preferably 25% to 50% of the total weight of the composition.

The preferred opaque agent is titanium dioxide, which may be present in the range of 0.05% to 2%, preferably 0.075% to 0.2%, for example 0.1% of the total weight of the composition. This amount improves the appearance of the composition.

Flavoring agents that can be used in the composition of the present invention include various flavoring aldehydes, esters, alcohols and the like, as well as menthol, carvone and ethyl, and mixtures thereof. Examples of essential oils include mint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Accordingly, the flavoring agent can be used in an amount of from 0.01% to 4%, for example from 0.1% to 3% or from 0.5% to 2% by weight of the said composition.

Sweeteners that can be used in the composition of the present invention include, for example, sucrose, glucose, saccharin, sucralose, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol, saccharin salts (for example, sodium saccharin), acesulfame and mixtures of them. In one embodiment, sodium saccharin is used as the sweetening agent. Accordingly, the sweetening agent can be used in an amount of from 0.005% to 10%, for example from 0.01% to 3% or from 0.1% to 1% by weight of the said composition.

A suitable dentifrice composition according to the present invention is an aqueous dentifrice composition. Water may form the balance of the dentifrice composition. In one embodiment, said composition contains from 5% to 80%, for example from 10% to 60%, from 15% to 40% or from 20% to 30% water. This amount of water includes added free water plus that amount that is administered with other components of the dentifrice composition, such as sorbitol.

The dentifrice composition of the present invention is typically formulated as toothpastes or gels.

Additional oral care actives may be included in the compositions of the present invention.

The compositions of the present invention may further contain an anti-irritant agent to combat dentin hypersensitivity. Examples of the anti-irritant agent include a tubule blocking agent or a nerve anti-irritant agent and mixtures thereof, for example as described in WO 02/15809.

Suitable tubule blocking agents include strontium salts such as strontium chloride, strontium acetate or strontium nitrate. Suitably, the strontium salt is typically used in an amount of 5 to 15% by weight of the composition.

In one embodiment, the tubule blocking agent is a calcium carbonate salt of arginine. Accordingly, the arginine salt is present in an amount of from 0.5% to 30% by weight of said composition, for example, from 1% to 10% by weight of said composition, or from 1% to 10% by weight of said composition, for example, from 2% to 8% by weight of said composition.

In one embodiment, the tubule blocking agent is a bioactive glass. Suitably, the bioactive glass consists of 45 wt. % silicon dioxide, 24.5 wt. % sodium oxide, 6 wt. % phosphorus oxide and 24.5 wt. % calcium oxide. One such bioactive glass is commercially available under the trade name NOVAMIN, also known as 45S5 BIOGLASS. Suitably, the bioactive glass is typically used in an amount of from 1% to 10% by weight of the composition.

In one embodiment, the tubule blocking agent is stannous fluoride. Stannous fluoride, as a result of hydrolysis and oxidation reactions, forms insoluble metal salts, which are deposited in the dentinal tubules and on the surface of the dentin, affecting dentin hypersensitivity.

Stannous fluoride can also be used as a source of fluoride to provide protection against dental caries and plaque/gingivitis.

Suitable nerve desensitizers include potassium salts such as potassium citrate, potassium chloride, potassium bicarbonate, potassium gluconate and especially potassium nitrate. The desensitizing amount of potassium salt is usually from 2 to 8% by weight of the total composition, for example, 5% by weight of potassium nitrate can be used.

The compositions of the present invention may contain a bleaching agent, for example selected from a polyphosphate, for example sodium tripolyphosphate (STP) and/or any additional silica abrasive may have high cleaning properties. STP may be present in an amount of 2% to 15%, for example 5% to 10%, of the total weight of the composition.

The compositions of the present invention may contain an anti-bad breath agent, for example, a zinc salt such as zinc oxide or chloride.

The composition of the present invention is suitable for dispensing and dispensing from an aluminum-plastic laminate tube or a plastic pump commonly used in the art.

The compositions of the present invention can be prepared by mixing the ingredients in appropriate relative amounts in any convenient order and adjusting the pH to obtain the desired value.

An exemplary dentifrice composition according to the present invention contains:

an alkali metal salt of lactic acid such as sodium lactate in an amount of 0.5% to 5.0%; a source of free fluoride ions such as sodium fluoride in an amount of 0.05% to 0.5%; a copolymer of MVE with maleic anhydride or acid, such as GANTREZ® S-97 in an amount of 0.05% to 2%; wherein said composition has a pH of the suspension in the range from more than 5.0 to less than 6.5.

The present invention provides the composition described above for use in protecting teeth from dental erosion. The present invention further provides the composition described above for use in protecting teeth from caries.

The present invention provides the composition described above for use in treating and/or inhibiting dental erosion on a tooth surface.

The present invention provides the composition described above for use in the treatment and/or suppression of caries on the surface of teeth.

The present invention also provides a method of protecting teeth from dental erosion, which includes applying an effective amount of the composition described above to an individual in need thereof. The present invention also provides a method of protecting teeth from caries, which includes applying an effective amount of the composition described above to an individual in need thereof.

The present invention provides a method of treating and/or inhibiting dental erosion on the surface of teeth, comprising contacting the surface of the teeth with the composition described above.

The present invention provides a method of treating and/or suppressing dental caries on the surface of teeth, comprising contacting the surface of the teeth with the composition described above. The present invention is further illustrated by the following examples.

Example 1

The dentifrice composition (Formulation 1) described in Table 1 was prepared as follows. Purified water, sorbitol and glycerin were added to a suitable vessel. Sodium hydroxide, sodium lactate solution, sodium saccharin, sodium fluoride, potassium nitrate, gantrez, titanium dioxide and 20% flavor were then added and mixed under high shear until the solids dissolved. While stirring under vacuum, dental silica was added, then stirred until wet. The cocamidopropyl betaine solution and the remaining 80% flavor were added and mixed. Separately, in a premix vessel, the xanthan gum was mixed with approximately 95% polyethylene glycol to form a slurry. Under vacuum, this suspension was added to the main vessel with high shear mixing. The remainder of the polyethylene glycol was added to the premix container and the resulting mixture was poured into the main container. The resulting paste was mixed in a vacuum until homogeneous, then transferred to suitable test tubes.

pH of Composition 1 (suspension in water in a ratio of 1:3) = 6.2

Example 2

Fluoride absorption by enamel (FFE)

The present example describes a study of fluoride uptake into enamel that occurs when using a dentifrice composition according to the present invention.

Preparation of a composition for cleaning teeth

Formulations 2-4 were prepared with the composition compositions indicated in Table 2:

Composition 2 was the control composition.

*Compositions 3 and 4 were the original compositions for cleaning teeth, which were used in the subsequent preparation of suspensions. Formulations 3 and 4 were slightly different from Formulation 2 to allow acid to be added later and adjust the pH of the suspension. Formulations 3 and 4 (see Table 2 above) indicate the percentage of each ingredient present in the “final” dentifrice composition after subsequent addition to the original dentifrice composition of the carboxylic acid and any pH modifying agent necessary to achieve the desired pH .

Preparation of suspensions of compositions for cleaning teeth

Suspensions of compositions for cleaning teeth were prepared using Formulations 2-4. Suspensions were prepared consisting of 1 part paste (Composition 2, 3 or 4) mixed with 3 parts diluent. The thinner consisted of 2 parts acid solution and 1 part water. For “control,” the acid solution was replaced with water. The total amount of suspension was 36 g in all cases, therefore, the total composition of the suspension consisted of 9 g paste, 18 g acid solution, 9 g water. This approach was used to create suspensions from a common base that would have the correct composition as if the paste contained all the ingredients. For example, if Formulation 3 contained 2% malonic acid and was mixed with water only, the concentration in the final suspension would be 0.5% (9 g paste + 27 g water, diluted fourfold). Adding 18 g of a 1% malonic acid solution to 9 g of a malonic acid-free base paste plus 9 g of water also gives a final suspension concentration of 0.5% (18 g of malonic acid plus a total of 18 g of paste and water, diluting the malonic acid solution twice acid). Then the resulting suspensions were centrifuged at 10,000 rpm (~ 16,000 g) for 10 minutes. Details of the composition of the suspensions and their corresponding pH values are given below in Table 3.

Method

The PFE testing procedure was based on Procedure 40 described in the US Food and Drug Administration (FDA) testing procedures. In this case, the incipient lesion was formed using 0.1 M lactic acid pH 5.0 containing 0.2 wt. % / about. polyacrylic acid (Carbopol 907), which was 50% saturated with hydroxyapatite.

Healthy bovine upper central incisors were cleared of all adhering soft tissue. An enamel core with a diameter of 3 mm was prepared from each tooth using a hollow diamond drill under running water. The samples were placed on the end of a Plexiglas rod using methyl methacrylate and polished with 600 grit wet/dry paper followed by microfine gamma alumina. Twelve samples in each group were used in the study.

Each enamel sample was etched by immersion in 0.5 ml of 1 M perchloric acid (HClO ₄ ) solution for 15 seconds with continuous stirring.

The fluoride content of this solution was determined using a fluoride electrode to determine the background fluoride content in enamel samples.

The samples were again ground and polished as described above. An incipient lesion was formed in each enamel sample by immersion in a solution of 0.1 M lactic acid/0.2% Carbopol 907 for 24 hours at 37°C. These samples were washed with water and stored in a humid environment until use.

The indicated pH of some suspensions was adjusted by dropwise addition of 1 M hydrochloric acid or 1 M sodium hydroxide to achieve the desired pH value shown in Table 3. The samples were immersed in 25 ml of the supernatant of the suspension with constant stirring (350 rpm) for 30 minutes. After treatment, the samples were washed with water. One layer of enamel was removed from each sample by etching as described above. The etching solution was analyzed for fluoride (ion-specific electrode) and calcium content. The pre-treatment (natural) fluoride level in each sample was then subtracted from the post-treatment value to determine the change in enamel fluoride content as a result of the treatment under study.

Statistical analyzes

Statistical analyzes of individual means were performed using a one-way ANOVA model. The significance of differences was analyzed using the Newman-Keuls Student test.

results

The results of the study are presented in Table 4 (average PFE ± standard error of the mean) and Fig. 1-3 below.

In FIG. 1, at a significance level of 5%, all treatment methods were statistically significantly different from each other. A small improvement was observed when malonic acid was included at neutral pH, and a slightly greater benefit was observed when the pH was lowered to pH 5.5 without adding carboxylic acid by adding dropwise 1 M HCl. By combining the two factors - pH 5.5 and a carboxylic acid - a significantly greater effect was observed than either effect alone, demonstrating the unexpected synergistic effect of lowering the pH and adding a specific carboxylic acid.

In FIG. Figure 2 shows that the effect of malonic acid at 2% at pH 5.5 was much greater than the effect of citric acid at 2% at pH 5.5, demonstrating an unexpected dependence on the nature of the acid used.

In FIG. 3, as pH decreased, PFE increased until pH 5.5 was reached. No further increase in PFE due to a decrease in pH 5.5 to pH 5.25 was observed.

Conclusion

A synergistic effect on PFE was observed by lowering the pH to pH 5.5 and adding the indicated carboxylic acid, malonic acid, to a content of 2%. The maximum benefit for PPE in 2% carboxylic acid was observed at pH 5.5 for malonic acid: below this value PPE did not increase. The increase in PFE from the inclusion of malonic acid under these conditions was much greater than the increase from the inclusion of citric acid.

Example 3

Fluoride absorption by enamel (FFE)

This example describes an enamel fluoride uptake study conducted on dentifrice compositions of the present invention.

Toothbrushing compositions (Formulations 5-11) were prepared (see Table 5 below) and PFE was determined as described in Example 2 above. The results are presented in Table 6 and FIG. 4.

results

At the 5% significance level, all acid-added treatments at pH 5.5 had PFE values that were statistically significantly higher than those of the acid-free toothpaste at pH 7.2. The 2% lactic acid product was superior to all other treatments, followed by the 2% tartaric acid product.

The PFE values for the Phosphoric Acid Examples and the Malic Acid Examples were significantly lower than those observed for the carboxylic acids used in the present invention.

Conclusion

When added to toothpaste 2 wt. % at pH 5.5, different acids had significantly different effects on PFE. Lactic acid was the most effective in these tests. The results of this study demonstrate that a significant effect on fluoride absorption is not achieved either by formulating the dentifrice at an acidic pH (5.5) or simply by using any carboxylic acid. The results observed for phosphoric acid and malic acid were significantly less impressive compared to the results observed for the carboxylic acids used in the present invention.

Example 4

Fluoride absorption by enamel (FFE)

Formulations 12 - 14 of the dentifrice compositions described below were prepared (see Table 7) and the PFE was determined as described in Example 2 above. The results obtained are shown in Table 8 and FIG. 5.

results

Conclusion

Formulation 14 was superior to the control Formulation 13 with fluoride. Both formulations containing fluoride were superior to the control formulation without fluoride.

Example 5 - PFE Study

Formulations 15-21 of the dentifrice compositions described below were prepared (see Table 9) and the PFE was determined as described in Example 2 above. The results obtained are shown in Table 10 and Fig. 6.

results

At the 5% significance level, the performance of all fluoride-containing formulations was statistically significantly higher than placebo without fluoride. A formulation containing 0.25% PVME/MA copolymer (Formulation 19) was statistically significantly superior to all other formulations tested. There were no significant differences between the other Compositions.

Conclusion

All fluoride-containing formulations were superior to placebo without fluoride.

However, there was evidence that using 0.25% polymer was unexpectedly beneficial for PFE.

Example 6 - Study on reducing enamel solubility

The dentifrice compositions 15-21 described above in Table 10 were prepared and the ESR was determined as described below. The results obtained are shown in Table 11 and Fig. 7.

Preparing your teeth

Three healthy human molars were placed in wax so that only the enamel surfaces were exposed, then they were cleaned and polished. Twelve sets of three teeth each were prepared for the study.

Preparation of lactate buffer

A 0.1 M lactic acid solution was prepared, buffered to pH 4.5. Removing protection

The tooth surfaces were etched in a 0.1 M solution of lactate buffer for two hours at room temperature, then thoroughly washed with water.

Etching pre-treatment

The test was performed using pre-warmed (37°C) sets of teeth and lactate buffer in an incubator. Sets of teeth, pre-treated with acid, were mounted on the ends of acrylic rods using molten wax. A small hole was drilled in the lid of each container for a plastic rod on which sets of teeth were installed. Each container was filled with 40 ml of 0.1 M lactic acid buffer. The rod of the first dentition was pushed through the hole in the lid, placed in the first container and adjusted so that the entire surface of the enamel was immersed in the lactic acid solution. After 15 minutes in the buffered lactate solution with stirring, the tooth sets were removed from the container and rinsed with water. Lactate buffer solutions were stored and analyzed for phosphorus content. The tooth sets were then placed back into the 37°C water bath to prepare for the processing step.

Treatment

All sets of teeth were processed simultaneously (one for each product). The treatment procedure was similar to the etching procedure except that a suspension of the dentifrice composition was used instead of an acid. 30 ml of pre-warmed dentifrice composition was added to each container, then the teeth were immersed in the dentifrice composition and mixed for 5 minutes. The remaining sets of teeth were treated in a similar manner with a different dentifrice composition. At the end of the treatment, the dentition was removed and washed well with water.

Post-processing

The second lactic acid exposure was carried out in the same manner as the pre-etch of samples treated with dentifrice compositions, and the treatment solutions were analyzed for phosphorus content. Pre- and post-treatment solutions were analyzed for phosphorus content using a Klett-Summerson photoelectric colorimeter.

The sets of teeth were etched again and the procedure was repeated once more so that each set of teeth was treated with each dentifrice composition. Treatments were distributed in a Latin square to provide variety in the treatment sequence.

Calculation of EPS

The percent reduction in enamel solubility (PRES) was calculated as the difference between the amount of phosphorus in the pre- and post-acid solutions divided by the amount of phosphorus in the pre-acid solution multiplied by 100.

results

results

All fluoride-containing dentifrice compositions showed ESR values that were statistically superior to the fluoride-free placebo. A clear dose-response relationship for PVME/LA copolymer content was observed between 0% and 0.25%. An increase in SRE of approximately 15% was observed due to the presence of 0.25% PVME/MA copolymer. Above 0.25%, no further increase in SRE was observed until at least 1% PVME/MA copolymer.

Conclusion

The addition of PVME/MA copolymer to 0.25% caused a significant increase in the decrease in enamel solubility. No further increase was observed with the addition of higher levels of copolymer.

Example 7

Introduction

To evaluate the effectiveness of the study formulations, an in situ clinical study was conducted to compare the effectiveness of the study formulations with a fluoride-free placebo control and a comparison toothpaste also recommended for the prevention of enamel erosion. The study design used in this paper has previously been widely used to study the effectiveness of formulations in the remineralization of acid-softened enamel [Creeth, 2018; Zero, 2006; Barlow, 2009; Creeth, 2015].

The study protocol was published on ClinicalTrials.gov on September 28, 2017 (Clinicaltrials.gov (Identifier: NCT03296072)).

Compositions

The study formulation, Formulation 1, is described in Example 1. The fluoride-free placebo formulation was identical to the study formulation, but with water replacing the fluoride, and the comparison toothpastes were Crest ProHealth Sensitivity and Enamel Shield.

Study details

This study was a single-center, controlled, single-blind (dentist and sample analyst), randomized, triplicate, triplicate, in situ crossover design to test the remineralizing ability of a dentifrice composition. The treatment was carried out once and the results were assessed 2 and 4 hours after application. A 2-day washout phase (using a fluoride-free dentifrice composition) was performed before each treatment visit.

In this study, subjects were equipped with an intraoral device capable of holding 8 samples of enamel in the palate area of the mouth. Enamel samples were cut from permanent cattle incisors and serially polished to a mirror finish. Samples were demineralized in vitro by contact with grapefruit juice for 25 minutes. The samples were then placed in intraoral devices and worn by subjects throughout the testing period. Treatment with toothpaste was carried out by applying it with a brush to the buccal surfaces of the teeth for 25 seconds, then the resulting suspension was rinsed in the mouth for 95 seconds, spat out and washed off with water. Four enamel samples were removed from the device 2 hours after treatment, and the remaining 4 samples were removed 4 hours after treatment. The enamel was then immersed again in grapefruit juice in vitro.

The degree of remineralization was determined by measuring the microhardness of the enamel surface using a Knoop microindenter. Indentations were made into healthy enamel before contact with grapefruit juice, before oral administration, after a 2- or 4-hour remineralization period, and after a second treatment with grapefruit juice. Based on the length of the dents, the percentage of restoration of surface microhardness (% VMTP) and the percentage of relative resistance to erosion (% RUE) were calculated:

% VMTP=[(E1-R) / (E1-B)] * 100 [from Gelhard, 1979]

% TUE = [(E1-E2) / (E1-B)] * 100 [from Corpron, 1986], where B = indentation length (µm) in healthy enamel at baseline; E1 = indentation length (µm) after first treatment with grapefruit juice; R = indentation length (µm) after in situ remineralization and E2 = indentation length (µm) after the second grapefruit juice treatment.

The amount of fluoride incorporated into the remineralized lesion (enamel fluoride uptake (EFA)) was also determined chemically (using Sakkab's method [Sakkab, 1984]) after the enamel samples were removed from the mouth, but before the second grapefruit juice treatment.

results

The results obtained are shown in Fig. 8-10. The study toothpaste demonstrated statistically significantly greater remineralization (as demonstrated by % BMTP) than the placebo control or comparison toothpaste. The tested toothpaste was also statistically more effective at preventing demineralization (as measured by % TER) than the placebo or comparison toothpaste. In addition, enamel treated with the study toothpaste included in the remineralizing injury (REI) was statistically superior to enamel treated with either a fluoride-free placebo or a comparison toothpaste.

Conclusion

These results indicate that the test toothpaste was more effective in remineralizing acid-softened enamel and preventing further demineralization than a fluoride-free control toothpaste or a comparator product indicated for use in erosion.

Links

Barlow AR, Sufi F, Mason SC. Evaluation of different fluoridated dentifrice formulations using an in-situ erosion remineralization model. The Journal of Clinical Dentistry. 2009;20(6): 192-8.

Corpron RE, Clark JW, Tsai A, More FG, Merrill DF, Kowalski CJ, Tice TR, Rowe CE. Intraoral effects of a fluoride-releasing device on acid-softened enamel. The Journal of the American Dental Association. 1986 Sep l;113(3):383-8.

Creeth JE, Kelly SA, Martinez-Mier EA, Hara AT, Bosma ML, Butler A, Lynch RJ, Zero DT. Dose-response effect of fluoride dentifrice on remineralization and further demineralization of erosive lesions: A randomized in situ clinical study. Journal of Dentistry. 2015 Jul 1;43(7):823-31.

Creeth JE, Parkinson CR, Burnett GR, Sanyal S, Lippert F, Zero DT, Hara AT. Effects of a sodium fluoride-and phytate-containing dentifrice on remineralization of enamel erosive lesions-an in situ randomized clinical study. Clinical oral investigations. 2018 Feb 8:1-0. Gelhard TV, Ten Cate JM, Arends J. Rehardening of artificial enamel lesions in vivo. Caries Research. 1979;13(2):80-3.

Sakkab NY, Cilley WA, Haberman JP. Fluoride in deciduous teeth from an anti-caries clinical study. Journal of Dental Research. 1984 Oct;63(10):1201-5.

Zero DT, Hara AT, Kelly SA, Gonzalez-Cabezas C, Eckert GJ, Barlow AP, Mason SC. Evaluation of a desensitizing test dentifrice using an in-situ erosion remineralization model. The Journal of Clinical Dentistry. 2006; 17(4): 112-6.

Example 8 - Interferometric analysis of white color (enamel protection)

Introduction

The purpose of this study was to monitor and quantify the effect of in vitro treatment of human enamel with dentifrice compositions on subsequent erosion by dietary acid.

White light interferometry techniques can provide rapid visualization of surface topography. Determination of roughness parameters can be carried out in a non-contact mode, and height resolution on the nanometer scale is achieved.

C1 - Crest Prohealth Smooth Formula Toothpaste (Ingredients: stannous fluoride 0.454% (0.14% fluoride ion), water, sorbitol, hydrated silica, sodium lauryl sulfate, carrageenan, sodium gluconate, flavor, xanthan gum, zinc citrate, chloride Tin, Sodium Hydroxide, Sodium Saccharin, Sucralose, Titanium Oxide, Blue 1).

C2 - Colgate Enamel Health Toothpaste (Ingredients: Potassium Nitrate 5%, Sodium Fluoride 0.24%) (0.15% Fluoride Ion), Water, Sorbitol, Hydrated Silicon Dioxide, Glycerin, PEG-12, Tetrasodium Pyrophosphate, Lauryl Sulfate sodium, flavor, microcrystalline cellulose, zinc phosphate, cellulose gum, cocamidopropyl betaine, gasoline alcohol, sodium saccharin, xanthan gum, mica, titanium dioxide, FD&C Blue No. 1).

Methodology

Twenty samples of human enamel were polished to a flat surface and a portion of this surface was sealed with acid-resistant tape. The samples were then divided into four treatment groups (n = 5 for each group) and immersed in one of the dentifrice suspensions (1:3 wt.% in deionized water) with manual brushing for 2 minutes. The samples were then washed for 1 minute with deionized water. After treatment with the dentifrice composition, the samples were suspended in 1% citric acid, pH 3.8, for 5 minutes without stirring. Samples were washed with deionized water and air dried, then analyzed using white light interferometry.

The surface topography of the samples was studied using a white ADE PhaseShift MicroXAM interferometer. Data were obtained from multiple regions (687 μm × 511 μm and 215 μm × 160 μm) for each sample. After removal of the mask tape, additional measurements were taken to assess tissue mass loss. Statistical analysis was performed using a two-tailed Student's t test with unequal variance to a confidence level of >95%.

results

The results obtained are shown in Fig. eleven.

Weight loss in treatment groups followed the following trend:

[The largest difference in height] C3>C2>C1>T1 [The smallest difference in height]. The difference in step height between all treatment groups is statistically significant at the 95% confidence level.

Surface roughness for treatment groups followed the following trend:

[Highest surface roughness] C3>C2>C1>T1 [Lowest surface roughness].

The difference in surface roughness between all treatment groups is statistically significant at the 95% confidence level, except for cases C2 and C1.

Conclusion

The data above shows that pretreatment T1 provides the greatest protection against erosion, followed by pretreatment C1 and then pretreatment C2, with the lowest protection provided by pretreatment C3.

Example 9 - Dynamic secondary ion mass spectrometry (fluoride absorption)

Introduction

Dynamic secondary ion mass spectrometry (DSIMS) can be used to semi-quantitatively determine elemental depth profiles of materials with nanometer-scale resolution. This method was used to determine the extent of fluoride and calcium absorption by human enamel surfaces following treatment of erosive lesions with a dentifrice and mouth rinse composition. The purpose of this study was to determine the extent of fluoride uptake by human artificial enamel erosions following treatment with four dentifrice compositions tested in the white light interferometry test detailed above.

Twenty human enamel samples were polished and suspended in 1% citric acid, pH 3.8, for 5 minutes without stirring to create artificial erosive lesions. After rinsing with deionized water, samples were divided into 4 treatment groups (n=5) and immersed in dentifrice suspensions (1:3 wt%) for 2 minutes before rinsing for 1 minute with deionized water. After treatment, these samples were air dried and analyzed using fluoride DSIMS.

DSIMS image analysis was performed on a Cameca ims 6f instrument using a 15 keV (~50 pA ⁾ O ₂₊ primary ion beam and an electron gun for charge compensation. Images were acquired from 100 μm × 100 μm areas. Negative secondary ion detection was used with a nominal extraction field of −5.0 keV. Integrated fluoride/oxygen values were determined for the 50 µm depth range, that is, a measure of the relative absorption of fluoride by the upper surfaces of tooth enamel at a depth of 50 µm. A graphical comparison of the fluoride uptake results of the four treatment groups is shown in FIG. 3.

Methodology

Twenty human enamel samples were polished and suspended in 1% citric acid, pH 3.8, for 5 minutes without stirring to create artificial erosive lesions. After rinsing with deionized water, samples were divided into 4 treatment groups (n=5) and immersed in dentifrice suspensions (1:3 wt%) for 2 minutes before rinsing for 1 minute with deionized water. After treatment, these samples were air dried and analyzed using fluoride DSIMS.

DSIMS image analysis was performed on a Cameca ims 6f instrument using a 15 keV (~50 pA ⁾ O ₂₊ primary ion beam and an electron gun for charge compensation. Images were acquired from 100 μm × 100 μm areas. Negative secondary ion detection was used with a nominal extraction field of −5.0 keV. Integrated fluoride/oxygen values were determined for the 50 µm depth range, that is, a measure of the relative absorption of fluoride by the upper surfaces of tooth enamel at a depth of 50 µm. A graphical comparison of the fluoride uptake results of the four treatment groups is shown in FIG. 12.

results

The results of DSIMS fluoride analysis and retrospective line scan showed that fluoride uptake is greatest for samples treated with dentifrice composition T1, followed by composition C2, followed by dentifrice composition C1. Treatment with the C3 dentifrice composition results in very low fluoride uptake. To evaluate any statistically significant differences in fluoride uptake between treatment groups, a Student's t test was performed. All differences between treatment groups were statistically significant.

Example 10 - Dynamic secondary ion mass spectrometry (calcium absorption)

Introduction

The purpose of this study was to determine the extent of calcium absorption by human artificial enamel erosions following treatment with three dentifrice compositions.

Methodology

Twenty human enamel samples were polished and suspended in 1% citric acid, pH 3.8, for 5 minutes without stirring. After rinsing with deionized water, samples were divided into 4 treatment groups (n=5) and immersed in dentifrice suspensions (1:3 wt%) for 2 minutes before rinsing for 1 minute with deionized water. Enamel samples from two of the four treatment groups were incubated in a suspension prepared from the T1 dentifrice composition. Then the specified enamel was placed in a solution of artificial saliva for 24 hours. This solution contained calcium significantly enriched with calcium-44 (as calcium chloride) for three treatments. For enamel in the second dentifrice composition C3 (placebo for T1), a standard artificial saliva solution (identical to the artificial saliva used for the other treatments, but containing calcium-40 as calcium chloride) was used as a control. The samples were then rinsed for 1 minute with deionized water, air dried, and analyzed using DSIMS for Kalysh-44.

DSIMS image analysis was performed on a Cameca ims 4F instrument using ^a 15 keV (~100 pA) O ₂₊ primary ion beam. Images for samples ⁴⁰ Ca, ⁴² Ca, ⁴⁴ Ca and ⁴⁰ Ca ¹⁹ F were obtained from at least two areas per sample, typically measuring an area of 100 µm x 100 µm. Positive secondary ion detection was used with a sample surface output field of +4.5 keV and a normal incidence electron gun for charge compensation. Line scan data were subsequently acquired for each image using Cameca ims 4f data processing software. A graphical representation of the results obtained is shown in Fig. 13.

results

DSIMS imaging of enamel and retrospective scan line analysis showed that calcium uptake was negligible in samples treated with C3 but subsequently incubated in an artificial saliva solution consisting of normal isotopic calcium. For samples incubated in calcium-44-enriched artificial saliva, the degree of calcium-44 incorporation was greatest for samples pretreated with dentifrice composition T1, followed by samples treated with dentifrice composition C2, followed by dentifrice composition C1. (Fig. 13). Although calcium-44 uptake occurs at depths greater than 20 μm for the first three treatments, the largest between-group differences in mean calcium uptake occur in the upper ~10 μm of the enamel surface. In this region, T1 treatment results in approximately three and a half times greater calcium-44 uptake than C2 treatment and approximately five times greater than C1 treatment. Treatment C2 results in ~1.5 times greater calcium-44 uptake than treatment C1. To evaluate any statistically significant differences in calcium absorption between treatment groups, a Student's t test was performed. All differences in calcium absorption were observed to be statistically significant.

Conclusion

The higher calcium absorption value observed for the test dentifrice composition (T1) compared to the comparison compositions (C1 and C2) indicates increased remineralization of the tooth enamel surface for the tested dentifrice composition.

Claims (14)

1. A toothpaste composition containing a carboxylic acid or an alkali metal salt thereof in an amount of from 1.5% to 3.0% by weight of the said composition, where said acid is selected from the list consisting of malonic acid, glutaric acid, tartaric acid, lactic acid acids and their mixtures; a copolymer of methyl vinyl ether (MVE) with maleic anhydride or acid, wherein said copolymer is present in an amount of from 0.2% to 0.3% by weight of said composition; and a source of free fluoride ions, and the pH of the suspension prepared from the specified composition of toothpaste and distilled water at a weight ratio of the composition to water of 1:3 is in the range from 5.0 to 6.5. 2. The toothpaste composition according to claim 1, characterized in that said alkali metal salt is a sodium salt of said carboxylic acid. 3. The toothpaste composition according to claim 2, characterized in that said alkali metal salt is sodium lactate. 4. The toothpaste composition according to any one of paragraphs. 1-3, characterized in that the specified source of free fluoride ions is an alkali metal fluoride. 5. The toothpaste composition according to claim 4, characterized in that said alkali metal fluoride is sodium fluoride present in an amount of from 0.05% to 0.5% of the total weight of said composition. 6. The toothpaste composition according to any one of paragraphs. 1-5, characterized in that said composition has a pH of the suspension in the range from 5.4 to 6.3. 7. The toothpaste composition according to any one of paragraphs. 1-6, characterized in that said composition contains a pH-modifying agent. 8. The toothpaste composition according to claim 7, characterized in that said pH-modifying agent is sodium hydroxide. 9. The toothpaste composition according to any of the preceding claims, characterized in that said copolymer is a copolymer of MBE with maleic acid. 10. The toothpaste composition according to claim 9, characterized in that the specified copolymer is a copolymer of MVE with maleic acid in a 1:1 ratio. 11. The toothpaste composition according to any of the preceding claims, characterized in that said copolymer has a molecular weight in the range of 100,000 to 2,000,000. 12. The toothpaste composition according to any of the preceding claims, further containing a desensitizing agent. 13. Use of the toothpaste composition according to any one of paragraphs. 1-12 to protect teeth from dental erosion. 14. Use of the toothpaste composition according to any one of paragraphs. 1-12 to protect teeth from caries.