PL202759B1 - Dual component antiplaque and tooth whitening composition - Google Patents

Abstract

A dual component tooth whitening composition is disclosed, which composition contains a peroxide whitening and a second ingredient incompatible with the peroxide compound such as a nonionic antibacterial agent, the second ingredient and the peroxide compound each being incorporated in separate dentrifice components which are physically separated until dispensed for use, the components retaining their original physical state when in contact, the first component being a composition containing a peroxide whitening compound in a vehicle thickened with a combination of a particulated water insoluble inorganic compound such as for example a inorganic compound such as fumed silica or Laponite and an organic thickener other than an alkylene oxide polymer such as for example a carboxyl vinyl polymer, and the second component containing the ingredient incompatible with the peroxide.

Description

Description of the invention

Background of the invention

1. Field of the Invention

The present invention relates to a two-component oral care composition that is effective in whitening teeth.

2. Prior art

Bacterial plaque is a soft deposit that forms on the teeth and consists of accumulated bacteria and their products. Plaque adheres permanently to irregularities or discontinuities, e.g., rough stone surfaces, gumline, and the like. In addition to looking ugly, plaque has been linked to gingivitis and other forms of periodontitis.

Many nonionic antibacterial agents have been proposed in the art to delay plaque formation and oral infections and dental diseases associated with plaque formation. For example, halogenated hydroxydiphenyl ethers such as Triclosan are well known in the art for their antimicrobial activity and have been used in oral compositions to prevent plaque formation by bacterial accumulation in the oral cavity.

Many substances, such as tea and coffee, that people come into contact with or come into contact with on a daily basis can "stain" or reduce the "whiteness" of a person's teeth. Consumers find clean, white teeth aesthetically desirable. Dull, stained teeth are undesirable to most people for their cosmetic appearance and also socially as an indicator of inadequate oral hygiene. Dental gels containing active oxygen releasing components such as hydrogen peroxide, urea peroxide, alkali metal and alkaline earth metal percarbonates and perborates have been disclosed in the prior art tooth whitening. For example, U.S. Patent No. 5,766,574 discloses a two-component dental whitening composition that includes a first gel component containing a peroxide compound and a second paste component containing an abrasive, such as silica, which is incompatible with peroxide, the first and second dentifrice components holding the teeth together. up to the point of application and connection for use on teeth requiring whitening.

While the composition disclosed in U.S. Patent No. 5,766,574 is effective for whitening purposes when containing a non-cationic antiplaque such as Triclosan for an abrasive dentifrice component, it was found that when gel and paste components were combined for application to teeth, bioavailability Triclosan was inhibited to a level where little antiplatelet effect was achieved. Investigation of this problem led to the discovery that poly (ethylene oxide) / poly (propylene oxide) block copolymers conventionally used as thickeners for making peroxide gels were the factor responsible for reducing the antiplatelet efficacy of Triclosan.

Thus, there is a clear need in the art to formulate a dental product capable of delivering both an antiplaque agent such as Triclosan and a peroxide whitening agent during tooth brushing, while the ingredients used in making the dentifrice composition do not inhibit the bioavailability of the antiplaque agent such that the bioavailability of the antiplatelet agent is achieved. optimal anti-plaque benefits and beneficial whitening effect.

Summary of the invention

The present invention relates to a two component tooth whitening composition in which when the components are mixed together comprises a peroxide compound and a second component incompatible with the peroxide compound, the second component and the peroxide compound each are included in separate dentifrice components that are physically separated until dispensing. when in use, the components retain their original semi-solid physical state when in contact, the first component is an abrasive-free semi-solid gel, a composition containing a peroxide compound on a support thickened with a combination of a fine water-insoluble inorganic compound as an inorganic thickener, and the peroxide compound is selected from the group consisting of hydrogen peroxide, urea peroxide, glycerin peroxide, benzoyl peroxide, calcium peroxide, and sodium percarbonate, a comminuted water-insoluble inorganic compound containing molecules of an inorganic compound selected from the group include smoked silica, amorphous silica, clay, alumina, and hydrated magnesium aluminum silicate applied to the titanium dioxide, and the inorganic compound particles are present in the first component in an amount of 0.05% to 6% by weight with respect to the first component and the organic thickener other than the polymer oxide

Of alkylene, the organic thickener is selected from natural and synthetic resins and polymers, the organic thickener is present in the first component in an amount of 0.1% to 10% by weight of the first component, and the second component is a semi-solid paste containing a peroxide compound activator that includes a component incompatible with the peroxide compound, the activator comprises manganese gluconate, and the incompatible component further comprises a nonionic antimicrobial agent.

Preferably, in the composition of the invention, the nonionic antibacterial agent is a halogenated diphenyl ether.

Preferably, the incompatible component further comprises sodium tripolyphosphate in the composition of the invention.

In the composition according to the invention, the organic thickener is xanthan or a carboxyvinyl polymer.

Preferably, the inorganic thickener is Laponite or fumed silica in the composition of the invention and the inorganic thickener is present in the peroxide component in an amount of from 0.05% to 2% by weight.

Description of the preferred varieties

Compounds that are incompatible with peroxide compounds include nonionic antibacterials, anti-limescale agents such as sodium tripolyphosphate, and peroxide activators such as manganese gluconate.

The nonionic antimicrobial agent used in the preparation of the second component of the dental composition in accordance with the practice of the present invention is preferably halogenated diphenyl ether. Halogenated diphenylether antibacterial compounds desirable in view of antiplatelet efficacy and safety include 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Triclosan) and 2,2'-dihydroxy-5,5'-dibromodiphenyl ether. Other useful nonionic antibacterial agents include phenolic compounds, including phenol and its homologs, mono and polyalkyl and aromatic halophenols, resorcinol and its derivatives, and bisphenolic compounds such as phenolic compounds, more fully described in U.S. Patent No. 5,368,844. An antimicrobial agent is included. in the second component of the composition of the present invention at a concentration of about 0.05 to about 3.0% by weight, and preferably about 0.1 to about 1% by weight.

In the practice of the present invention, the peroxide-containing whitening component is formulated as a gel using a peroxide whitening compound carrier in a water / humectant carrier containing a combination of an inorganic thickening agent and an organic thickening compound other than an alkylene oxide polymer.

Examples of suitable peroxide compounds used to prepare the whitening component of the present invention include metal ion-free peroxide components such as hydrogen peroxide and organic peroxides such as urea peroxide, glycerin peroxide and benzoyl peroxide, as well as metal ion-containing peroxides such as calcium peroxide. and sodium percarbonate. A preferred peroxide compound is hydrogen peroxide.

Typically the peroxide compound is used in the compositions of the present invention in amounts such that at least about 0.1% by weight of the whitening component comprises peroxide. Preferably, the peroxide compound comprises from about 1 to about 3% by weight of the whitening component.

Glycerin and polyethylene glycol in combination with water are useful in formulating the carrier for the gel peroxide whitening component of the present invention. Glycerin and polyethylene glycol are present in the gel peroxide component of the present invention in an amount of about 2 to about 80% by weight and preferably about 10 to about 50% by weight. Water is included in the gel component of the present invention at a concentration of about 5 to about 90% by weight of the composition, and preferably about 15 to about 50% by weight.

The thickening agent used to formulate the gel peroxide whitening component that is compatible with the nonionic antibacterials is a combination of an inorganic thickener and an organic thickener other than the alkylene oxide polymer. The combination of thickening agent is present in the gel peroxide component in an amount ranging from about 1 to about 20% by weight and preferably about 3 to 10% by weight.

Examples of inorganic thickeners include fumed silicas such as those available from Cabot & Degussa Corporation under the trademarks Cab-o-Sil and Aerosil, clays such as Laponite and amorphous silicas available from Huber Company under the trade mark Zeodent 115. The inorganic thickener can be incorporated into a gelatinous gel. peroxide at a concentration of 0.05% to 6% by weight.

PL 202 759 B1

Examples of organic thickeners that can be used in the preparation of gel peroxide in combination with an inorganic thickener include natural and synthetic gums such as carrageenan (Icelandic moss), sodium xanthan and carboxymethylcellulose, starch, polyvinylpyrrolidone, hydroxyethylpropyl cellulose, hydroxybutylmethylcellulose, and hydroxybutylmethylcellulose, and hydroxybutylmethylcellulose , commercially available under the trademarks "Carbopol 934, 940, 974 P" from BF Goodrich, these polymers are composed of colloidal water-soluble poly (acrylic acid) polymers cross-linked with from about 0.75% to about 2% polyallyl sucrose or polyallylpentaerythritol as the crosslinking agent, often with molecular weights of 4 to 5 million or more. The organic thickener may be incorporated into the antiplaque peroxide gel component of the present invention at a concentration of about 0.1 to about 5% by weight, and preferably about 0.5 to about 2.0% by weight.

The gel peroxide component can be prepared by suspending the peroxide in a carrier thickened with a combination of inorganic and organic thickeners by mixing in any suitable mixer.

It is very important in the practice of the present invention that a combination of a particulate water-insoluble inorganic compound such as an inorganic thickener and an organic thickener is used to prepare the peroxide gel component. When organic thickeners are used alone in peroxide gel formulations, the rheology of the gel is unlike that of dentifrice and lacks the thickening properties normally associated with dentifrices. If inorganic thickeners alone, such as fumed silica, are used, the gel can become markedly stiff on aging, resulting in a gel peroxide component that will have fluid state rheology and will not extrude from the dual chamber package in proportions to the paste product. If clay alone, such as Laponite, is used, the product will not be stable to the peroxide components.

The second component, which includes the peroxide-incompatible component, is generally prepared as a paste using a carrier that includes water, a humectant, an abrasive, a surfactant, and a thickener.

The humectant is usually a mixture of humectants such as glycerin, sorbitol, and polyethylene glycol with a molecular weight in the range 200-1000, but other blends of humectants may also be used and a single humectant may also be used. The humectant content is in the range of about 10% to about 80% by weight, and preferably about 40 to about 50% by weight. The water content ranges from about 10 to about 80% by weight, and preferably from 20% to 50%.

Thickeners that can be used in preparing the antimicrobial paste component include thickening silicas such as the amorphous silica available from J.M. Huber Company under the trade name Zeodent 115, natural and synthetic gums such as carrageenan (Icelandic moss), xanthan and sodium carboxymethylcellulose, starch, polyvinylpyrrolidone, hydroxyethylpropyl cellulose, hydroxybutylmethylcellulose, hydroxypropylmethylcellulose, and hydroxypropylmethylcellulose. The thickener may be included in the antimicrobial paste component of the present invention at a concentration of about 0.1 to about 3% by weight, and preferably about 0.5 to about 1% by weight.

Surfactants are included in the second component of the paste to achieve a foaming property. The surfactant is preferably anionic. Suitable examples of anionic surfactants include higher alkyl sulfates such as potassium or sodium lauryl sulfate which is preferred, monoglyceride monoglyceride of a higher fatty acid such as monoglyceride monosulfate salt or hydrogenated coconut oil fatty acids, alkylarylsulfonates such as sodium dodecyl benzene sulfonates, higher fatty sulfonates 1,2-dihydroxypropanesulfonate fatty acid, and substantially saturated higher aliphatic acylamides of lower aliphatic amino carboxylic acids, such as those having 12 to 16 carbon atoms in the fatty acid, alkyl or acyl radicals, and the like. Examples of said amides are N-lauroyl sarcosine, and the salts of N-lauroyl, N-myristoyl, or N-palmitoyl sarcosine. The surfactant is generally present in the antiplaque paste component at a concentration of from about 0.5 to about 5.0% by weight of the component.

Abrasives that can be included in the second component of the paste include siliceous materials such as silica and alumina. A preferred silica is a precipitated amorphous hydrated silica such as Sorbosil AC-35, sold by Crossfield Chemicals, or Zeodent 165 from Huber Company. Abrasive alumina include aluminum trihydroxide, aluminum silicate, calcined alumina, and bentonite. Concentration of the abrasive in the antiplaque paste component according to

The composition of the present invention will typically be in the range of 15 to about 50% by weight and preferably 20 to 40% by weight.

Fluoride ion-providing salts exhibiting anti-caries efficacy may also be included in the second component of the paste of the present invention. They are characterized by the ability to release fluoride ions in water and include sodium fluoride, potassium fluoride, tin fluoride such as stannous fluoride, sodium fluorosilicate, ammonium fluorosilicate, and sodium monofluorophosphate. It is preferred to use a fluoride salt that releases about 10-1500 ppm of fluoride ion.

Synthetic anionic polycarboxylates can optionally be incorporated into the antiplaque paste component. Anionic polycarboxylates are well known and are often used in the form of their free acids or preferably partially or more preferably fully neutralized water-soluble alkali metal (e.g. potassium and preferably sodium) or ammonium salts. Preferred are 1: 4 to 4: 1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether (maleic anhydride) having a molecular weight (MW) of about 30,000 to 1,000,000. These copolymers are available e.g. as Gantrez AN 139 (MW 500,000), AN 119 (MW 250,000) and preferably S-97 Pharmaceutical Grade from GAF Corporation. Other useful polymeric polycarboxylates include those disclosed in U.S. Patent 3,956,480, such as 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or ethylene, the latter available e.g. as Monsanto EMA No. 1103 MW 10000 and EMA Grade 61, and 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

Additional suitable polymeric polycarboxylates include those disclosed in U.S. Patent No. 4,138,477 and U.S. Patent No. 4,183,914, such as copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic, itaconic and maleic acids, and sulfoacrylic oligomers. molecular weight as low as 1000, available as Uniroyal ND-2.

Anti-calculus agents effective against tartar can be used in the preparation of the second dentifrice component and include pyrophosphate salts such as mono-, di-, tri- and tetra-alkali metal and ammonium pyrophosphate and tripolyphosphate salts. Such agents are used in amounts sufficient to reduce the amount of calculus, and preferably in amounts that will release at least about 1.0% by weight of the P2O7 ion, and include salts such as sodium tripolyphosphate and tetrasodium tetrapotassium pyrophosphate present in the second dentifrice components. in an amount of from about 2% to 10% by weight and preferably about 2 to about 7% by weight.

Platelet buffers such as calcium lactate, calcium glycerophosphate, and strontium polyacrylates can also be included in the abrasive component. Other optional ingredients include vitamins such as vitamin A, C, E, B6, B12, K, plant extracts, as well as potassium salts useful in the treatment of dentine hypersensitivity such as potassium citrate, potassium chloride, potassium sulfate, potassium tartrate, and potassium nitrate .

Peroxide activators such as manganese coordination complexes such as manganese gluconate may also be included in the second component of the present invention. The activating compound, upon contact with the peroxide component of the peroxide gel, activates the peroxide compound and accelerates the release of active oxygen to achieve a rapid whitening effect. Other examples of manganese coordination complexes useful for inclusion in an abrasive dentifrice component as peroxide activators are described in U.S. Patent No. 5,648,064, hereinafter incorporated as manganese coordination complexes, are included in the antiplaque paste component at a concentration of about 0.005% to about 3% by weight. and preferably about 0.05 to about 1.75% by weight.

Synthetic anionic polycarboxylates can optionally be included in the second paste component. Anionic polycarboxylates are well known, often used in the form of free acids or preferably partially or more preferably fully neutralized water-soluble alkali metal (e.g. potassium and preferably sodium) or ammonium salts. Preferred are 1: 4 to 4: 1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether (maleic anhydride) having a molecular weight (MW) of about 30,000 to 1,000,000. These copolymers are available e.g. as Gantrez AN 139 (MW 500,000), AN 119 (MW 250,000) and preferably S-97 Pharmaceutical Grade from GAF Corporation. Other useful polymeric polycarboxylates include those disclosed in U.S. Patent 3,956,480, such as 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or ethylene, the latter available e.g. as Monsanto EMA No. 1103,

PL 202 759 B1

M.W. 10000 and EMA Grade 61, and 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

Additional suitable polymeric polycarboxylates include those disclosed in U.S. Patent No. 4,138,477 and U.S. Patent No. 4,183,914, such as copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic, itaconic and maleic acids, and sulfoacrylic oligomers. molecular weight as low as 1000, available as Uniroyal ND-2.

Platelet buffers such as calcium lactate, calcium glycerophosphate, and strontium polyacrylates can also be included in the abrasive component. Other optional ingredients include vitamins such as vitamin A, C, E, B6, B12, K, plant extracts, as well as potassium salts useful in the treatment of dentine hypersensitivity such as potassium citrate, potassium chloride, potassium sulfate, potassium tartrate, and potassium nitrate .

Other ingredients that may be included in the components of the present invention include pigments, dyes, flavors, and sweeteners. A striped dental product will be prepared in accordance with the practice of the present invention when the contrasting color dyes are included in each of the components used in the practice of the present invention, the dyes being pharmacologically and physiologically non-toxic when used in the proposed amounts. Colorants used in the practice of the present invention include pigments and dyes.

The pigments used in the practice of the present invention include non-toxic, water-insoluble inorganic pigments such as titanium dioxide and chromium oxide green, ultramarine blues and roses, and iron oxides, as well as water-insoluble wax dyes made by dispersing calcium or aluminum salts of the FD&C dyes on the oxide aluminum lakes such as FD&C Green # 1, FD&C Blue # 2, FD&C R&D # 30 and FD&C # Yellow 15 lakes. The pigments have particle sizes in the range 5-1000 µm, preferably 250-500 µm, and are present at a concentration of 0.5 up to 3% by weight.

The dyes used in the practice of the present invention are distributed homogeneously throughout the dentifrice ingredient and are typically food dyes certified under the Food Drug & Cosmetic Act for use in food and ingested medications, including dyes such as FD&C Red # 3 (sodium tetraiodofluorescein) , FD&C Yellow # 5 (4-p-sulfophenyloxo-B-naphthol-6-monosulfonate sodium), FD&C Green # 3 (4 - {[4- (N-ethyl-p-sulfobenzylamino) -phenyl] -4 disodium salt) -hydroxy-2-sulfonio-phenyl) -methylene} - [1- (N-ethyl-Np-sulfobenzyl) -3,5-cyclohexadienimine], FD&C Blue # 1 (disodium anhydride of dibenzyldiethyl diaminotriphenylcarbinolotrisulfonic acid), FD&C Blue # 2 Indigo disulfonic acid sodium salt) and mixtures thereof in various proportions. The dye concentration for the best result in the present invention is from about 0.0005% to about 2% by weight.

Preferably the colorant contained in one of the components is a pigment such as TiO2 and the colorant dispersed throughout the second component is a dye, and the colorant is a different color than the colorant incorporated in the first dentifrice component.

Any suitable flavoring or sweetening agent may also be included in the components of the present invention. Examples of suitable perfume ingredients are perfume oils, e.g., essential oils of spearmint, peppermint, arugula, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon and orange, and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, sorbitol, xylitol, sodium cyclamate, perylartin and sodium saccharin. Suitably flavorings and sweeteners may together constitute from 0.01% to 5% by weight or more of the preparations.

To prepare the second paste component of the present invention, water, a humectant, e.g., sorbitol, a thickener and a sweetener are dispersed in a conventional mixer until the mixture becomes a homogeneous gel phase. A pigment such as TiO2 and a fluoride anti-caries agent such as sodium fluoride are added to the gel phase. These ingredients are mixed until a homogeneous phase is obtained. The smoothing agent, polycarboxylate compound, antimicrobial agent, perfume and surfactant ingredients are then added and the ingredients mixed at high speed under reduced pressure of about 20-100 mmHg. The resulting product is a homogeneous, semi-solid, extrudable paste-like product.

The two-component oral composition of the present invention is packaged in a suitable container where the ingredients remain physically separate and from which the separated components can be withdrawn simultaneously. Such containers are known in the art. An example of such a container is the collapsible two-compartment dispensing container disclosed in U.S. Patent Nos. 4,487,757 and 4,687,663, wherein the container is formed from

Is compressible plastic and has an interior partition defining a separate compartment in which to store the physically separated components and from which to extrude them through a suitable dosing outlet.

The following examples illustrate the present invention. The individual components described below were prepared using the procedures described above. The amounts of the various ingredients are by weight unless otherwise stated. The resulting ingredients were deaerated, packaged in tubes or other containers provided with a device for physically separating the individual dentifrice components.

The following examples further illustrate but do not limit this invention.

P r z k ł a d I

The combined two-component composition of the present invention is designated "Composition X", consisting of a 1: 1 (by volume) mixture of paste component A and Gel component B of the present invention, where Gel component B was thickened with a combination of fumed silica and xanthan gum prepared using the ingredients and amounts shown in Table I. For comparison purposes, the comparative two-component composition is designated composition Y, composed of 1: 1 (by volume) paste component A and gel component C thickened with Pluronic F-127 (poly (ethylene oxide) / poly (propylene oxide) block copolymer )) was prepared using ingredients also listed in Table I.

T a b e l a I

Ingredients Dentifrice components A (Triclosan) B (Peroxide) C. Glycerine 20.0 52.0 30.0 Carboxymethylcellulose 0.8 - - Carrageenan 0.3 - - Xanthan - 1.50 - Pluronic F-127 - - 21.0 Hydrogen peroxide (35% solution) - 5.71 5.71 Water 12.510 31.84 30.43 NaF 0.486 - - Gluconate Mn 0.5 - - Saccharin 0.3 - - Sorbitol 9.00 - - Poly (ethylene glycol) 600 - 1.50 10.00 Gantrez Liquid (S-97) 30.00 - - NaOH (50%) 2.40 - - Abrasive Silica * ¹ 20.00 - - Silica thickener * ² 1.00 - - Fumed silica - 5.75 - Fragrance 1.00 - - Triclosan 0.600 - - Sodium Lauryl Sulfate 1,500 - - Phosphoric acid - 0.50 1.00 Tetrasodium pyrophosphate - 0.50 - FD&C Blue # 1 (1% solution) - 0.70 -

* ¹ Zeodent 165 * ² Zeodent 115

PL 202 759 B1

The antiplatelet activity of Composition X and Comparative Composition Y was assessed using a model saliva flow cell of the type disclosed in American Journal of Dentistry, Vol. 3, pp. S9-S10 (1990).

In the flow cell system, single-pass germanium trapezoidal prisms, 50 x 20 x 1 mm (Harrick Scientific Corporation, Ossining, NY) were used as substrate for platelet growth and for infrared analysis of internal reflection in the resulting plaques. The plates were cleaned by wiping with an alcohol-saturated KOH, followed by washing with 5% sodium Sparkleen ^® (Fisher Scientific Company, Pittsburgh, PA) to prepare a plate surface having a surface energy characteristics similar to that of human tooth enamel. This method was effective in removing all organic matter from the plates as assessed by internal reflection infrared spectroscopy. In all cases, the attenuated total reflectance (ATR) was recorded on a Perkin-Elmer 1725X Fourier transform infrared spectrophotometer (Perkin-Elmer, Norwalk, CT) incorporating an instrument specific multiple internal reflectance measuring device.

The flow system was placed in an incubator at 37 ° C with the flow cells in an upright position to minimize air entrapment. The peristaltic pump provided a constant flow rate.

For each experiment, Paraphilm-stimulated saliva was collected on ice from one of 3 healthy men who had not performed oral care on the day of collection. To reduce the amount of food remaining, saliva was collected at least 2 hours after the meal. Immediately after collection, the saliva was diluted twice with an artificial salivary buffer, pH 7.4, containing ammonium chloride, calcium chloride, manganese chloride, potassium chloride, potassium dihydrogen phosphate, potassium thiocyanate, sodium citrate, sodium bicarbonate, di-sodium hydrogenorthophosphate and urea (Shellis 1978). Dilutions were made to reduce the viscosity and increase the volume of saliva.

Whole saliva was circulated through the flow system at a rate of 1 ml ^/ min - then replaced with supplemented saliva which consisted of 35 parts whole saliva, 35 parts saliva buffer, 10 parts 2X modified Eagle's medium (Life Technologies, Inc.), 10 parts porcine 25 mg ^ ml ^-1 gastric mucin (Sigma Chemical Company, St. Louis, MO) and 10 parts trypsinized soybean medium. Circulation continued for 96 hours with saliva replaced every 24 hours.

To evaluate the effect of various test samples on plaque formation, flow cells were pulsed twice daily with test samples at a flow rate of 10 mlmin ^-1 for a specified time. To determine the amount of dentifrice in the flow system, suspensions were prepared by dissolving the dentifrice in water (2: 1 w / w dentifrice / water) followed by centrifugation for 10 minutes at 10,000 rpm and 25 ° C. . The resulting supernatants were used in the process. Residual test solutions were removed by rinsing the flow cell for 30 minutes. At the end of the experiment period, flow cells were rinsed with deionized distilled water for 20 minutes to remove loosely bound substances. The flow system was then disassembled and the test plates were air dried in a vertical position prior to analysis.

Between experiments the flow cell components, connectors and silicone tubes were washed with a 5% solution of Sparkleen ^®, rinsed with deionized distilled water and then autoclaved for 30 minutes at 121 ° C.

After drying overnight, the plates were analyzed by infrared spectroscopy which allows a semi-quantitative evaluation of the chemical composition of the resulting plates. Scanning was performed at an intensity of 0.2 cmrs ^-1 and a resolution of 4 cm ^-1 . Data processing software from Perkin-Elmer was used to manipulate the spectra.

Tile index

Platelet scores were calculated using the intensities of the FITR absorption bands at 3300, 1650, 1545 and 1080 cm- ¹ from the infrared spectrum as follows:

Plate rating = abs3300 + abs1650 + abs1545 + abs1080 where abs is the maximum absorbance at the different wavenumbers. The selected wave numbers represent infrared adsorption by saliva components and bacteria on Ge prisms. The extent of surface coverage is measured because a layer thickness greater than 1 µm is not sufficient for ATR analysis by infrared spectroscopy. Test agents were assessed for cumulative inhibition of platelets versus controls that were simultaneously run through the system. The results are recorded in Table II below. The control sample was a commercial antiplaque toothpaste containing 0.3 wt% Triclosan, labeled "Composition T.

PL 202 759 B1

T a b e l a II

Composition Tile evaluation X 0.72 Y 3.07 T. 1.06

The results recorded in Table II show that compared to commercial toothpaste T, the antiplatelet activity of Composition X was not impaired, while the antiplatelet activity of comparative Composition Y was significantly inhibited.

P r z x l a d II

The procedure of Example 1 was repeated except that xanthan and fumed silica combination peroxide formulations (Component D) were prepared, as well as comparative dentifrice formulations containing only smoked silica (Component E) and xanthan alone (Component F). The ingredients of the peroxide Components D, E and F are listed in Table III below.

T a b e l a III

Ingredients A component of the dentifrice D E. F. Glycerine 52.0 52.0 52.0 Xanthan 1.00 - 1.00 H2O2 (35% solution) 5.71 5.71 5.71 PEG 600 1.5 1.5 1.50 Fumed silica 5.75 5.75 - Phosphoric acid 0.50 0.50 0.50 Tetrasodium pyrophosphate 0.50 0.50 0.50 FD&G Blue # (1% solution) 0.70 0.70 0.70 Water - qs to 100%

The viscosity stability of the peroxide component was measured for 4 weeks at room temperature (22 ° C) stored in sealed plastic tubes using a Brookfield Viscometer Model RUTD2 viscometer. Measurements were made at 5 rpm with an E spindle at room temperature. The results are set out in Table IV below.

T a b e l a IV

Brookfield viscosity (x 100,000 cps) 1 Day 1 week 4 weeks D 25 - 33 E. - 60 100

The results in Table IV show that when silica alone is used to make the peroxide gel (Component E), the gel progressively thickens over time to an unacceptable level (i.e. Brookfield viscosity to 1,000,000 cps after 4 weeks at room temperature), whereas very little progressive thickening for xanthan / fumed silica thickened peroxide gel (Component D). The peroxide gel, Component F, thickened with xanthan gum alone does not exhibit the stiffness required for a semi-solid dentifrice formulation.

P r z x l a d III

Tea and coffee stained beef teeth were soaked overnight in Composition X. The beef teeth were measured for their L * values before and after treatment using a Minolta Chromometer. The L * value is

Tooth whiteness is a measure of whiteness: the higher the L * value, the whiter the teeth. The L * values for the teeth before and after treatment with Composition X are set out in Table V below.

T a b e l a V

Tooth # L * value before soaking L * value after soaking 1 27 53 2 29 49 3 36 58 4 34 51

The L * values noted in Table V show the significant increase in whiteness after soaking the bovine teeth in Composition X, and this increase was also readily visible to the naked eye.

P r x l a d IV

Dentifrice Component A, when tested for aging stability by filling tubes or pumps with Component B, sealing the tubes and exposing the tubes to 120 ° F, showed no gassing or peroxide when tested after 6 weeks of exposure.

P r z k ł a d V

Toothpaste components labeled Paste A-1 and A-2 were prepared containing ingredients (abrasive silica, tetrasodium pyrophosphate, sodium tripolyphosphate, and triclosan) that were incompatible with peroxide compounds, and the composition of the pastes, in% by weight, is reported in Table VI below. A series of gels according to the present invention were also prepared containing organic and inorganic thickeners labeled Gel B, D, E, as well as a comparative gel, labeled Gel C, which did not contain a particulate water-insoluble inorganic compound. The compositions of these gels in wt.% Are also listed in Table VI below.

T a b e l a VI

Ingredients Dentifrice component (wt%) A-1 paste Paste A-2 Gel B Gel C Gel D Gel E 1 2 3 4 5 6 7 Glycerine 12.00 20.00 40.00 30.00 38.00 29.75 Carboxymethylcellulose 0.55 0.8 - - - - Carbopol 974P - - 2.0 - 1.75 2.0 Carrageenan 0.24 0.3 - - - - Xanthan - - 0.40 - 0.5 0.4 Pluronic F-127 - - - 21.0 - - Hydrogen peroxide (35% solution) - - 5.71 5.71 5.71 5.71 NaF 0.243 0.243 0.243 0.243 0.243 0.243 Gluconate Mn 0.05 0.50 - - - - Saccharin 0.45 0.30 0.25 0.1 0.1 0.25 Sorbitol 22.6 9.00 - - - - Poly (ethylene glycol) - - 10.0 10.0 10.0 10.0 Gantrez Liquid 7.69 30.00 - - - - NaOH (50%) 2.00 2.40 - - - - Abrasive silica 31.00 20.0 - - - 0.2 Silica thickener - 1.0 - - - - Fumed silica - - - - 0.1 -

PL 202 759 B1 cont. table VI

1 2 3 4 5 6 7 Laponite - - 0.10 - - - Flavoring agent 1.9 1.90 0.3 0.3 0.3 0.3 Triclosan - 0.60 - - - - SLS 2.0 2.50 - - - - Tetrasodium pyrophosphate 1.00 - 0.10 - - - Sodium tripolyphosphate 7.00 - - - - - FD&C Blue # 1 (1% solution) - - 1.05 0.70 1.05 1.05 Phosphoric acid - - - 1.0 - - TiO2 1.00 0.50 - - - - Water qs 100% qs qs qs qs qs

A two-compartment tube was filled with Paste A-1 in one compartment and Gel B in the other. Prior to filling, needle holes were formed in the partition wall which divided the tubes into compartments. For comparison purposes, the tube filling procedure was repeated except that Gel C was used in place of Gel B. After storage at 120 ° F for 3 weeks, Gel C liquefied while Gel B was still in its original semi-squeezable state.

P r x l a d VI

A series of Carbopol thickened peroxide gels were prepared and the viscosity of the gels was measured using a Caramed Rheometer and is reported in Table VII.

T a b e l a VII

Ingredients Gel component (% by weight) F. G. H. Glycerine 40.0 38.0 40.0 Xanthan 0.4 0.4 0.4 Carbopol 974 2.0 1.75 2.0 H2O2 5.71 5.71 5.71 PEG 600 10.0 10.0 10.0 Fumed silica - 0.10 - Laponite 0.1 - - FD&C Blue # 1 (1% solution) 0.7 0.70 0.70 Water qs to 100 qs to 100 qs to 100 Ph 4.7 4.6 4.7 Viscosity Pa-s * 96 101 16

* Viscosity measured at 5s ^-1 at 25 ° C using a Carrimed Rheometer equipped with 4 cm parallel plates.

Table VII indicates that Gel H made with the organic thickeners, Carbopol and xanthan, and without the inorganic thickener, had a very low structure as indicated by the low viscosity measured at 5s- ¹ . However, when small amounts of inorganic thickeners such as 0.1% by weight Laponite (Dentifrice Component F) or 0.1% fumed silica (Dentifrice Component G) were incorporated into the composition, the viscosity improved greatly. Gels F and G showed acceptable stiffness and reduced flossing.

P r o x l a d VII

Tea and coffee stained beef teeth were soaked in the 1: 1 Paste A-1 and Gel B composition of Table VI, the combined ingredients are designated Composition X.

The% of impurity removed as a function of time is recorded in Table VII below. For comparison purposes, the procedure of Example 5 was repeated except that a commercial abrasive dentifrice containing 24 wt.% Silica was used as the control and the amount of soil removed during the soaking was also recorded in Table VIII below.

T a b e l a VIII

Product Soak time (hours) % of impurity removed Commercial cleaning composition 6 6.5 teeth with abrasive silica 24 6.3 Composition X 6 24 95.3 100.0

The results in Table VIII indicate that after 6 hours, 95% of the soil was removed from the teeth by soaking in Composition X, indicating that Gel B did not affect the whitening performance of H2O2. By comparison, the commercial dentifrice did not remove any significant amount of contamination even after 24 hours of soaking.

P r x l a d VIII

The antiplatelet activity of the combined 1: 1 dentifrice components Paste A-2 and Gel D of Table I designated Composition Y was assessed using a saliva flow cell model of the type disclosed in Journal of Dental Research, Vol. 73 (11), pp. 1748-1755. (1994).

In the flow cell system, after each experiment, approximately 5 hours after the last treatment, the flow cells were rinsed with distilled water for 15 minutes at a flow of 1 ml / min. Bacterial plaques formed on hydroxyapatite (HAP) disks were removed by immersing the disks in 2 ml of 0.1 mol / L NaOH in a shaking water bath at 37 ° C for 45 minutes. After the disks were removed, the sample was sonicated to disperse the plates. The turbidity of the resulting solution was measured at 610 nm in a spectrophotometer.

The mass of the platelets accumulated on HAP disks is directly proportional to the measured optical density: the lower the mass of the platelets, the lower the optical density, and the higher the antiplatelet performance of the composition. A commercial antiplatelet toothpaste containing 0.3 wt% Triclosan, designated Composition Z, was used as a control. The plaque weight measurement results are recorded in Table IX below.

T a b e l a IX

Composition The mass of the plates Y 0.12 WITH 0.26

The results in Table IX show that, compared to commercial Triclosan Z toothpaste, the antiplatelet activity of Composition Y was not impaired.

P r x l a d IX

A series of Carbopol thickened peroxide gels were prepared and the gels aged for 3 weeks at 120 ° F. The ingredients of the gels are listed in Table X below.

T a b e l a X

Ingredients Gel J Gel K Gel L 1 2 3 4 Carbopol 974 2.0 2.0 2.0 Glycerine 27.75 27.75 27.75 Water 50.072 50.072 50.072 Sodium hydroxide (50% solution) 0.2 0.2 0.2 Poly (ethylene glycol) 600 10.0 10.0 10.0 Xanthan 0.4 0.4 0.4

PL 202 759 B1 cont. Table X

Sodium Fluoride 0.243 0.243 0.243 Sodium saccharin 0.25 0.25 0.25 Hydrogen peroxide 5.71 5.71 5.71 Fragrance 0.3 0.3 0.3 Glycerine 2 2 2 Alumina 0 0.2 0 Timeron * 0 0 0.2 Blue Dye # 1 (1% solution) 0.875 0.875 0.875 Brookfield viscosity (3 parts at room temperature) ** 11.00 18.00 18.00

* Hydrated magnesium aluminum silicate deposited on titanium dioxide ** Brookfield Viscosity Spindle No. 95T at 5 rpm for min.

Zele J, K and L were semi-solid compositions exhibiting acceptable stiffness and reduced threading. Gels J, K and L were stable after aging for 3 weeks at 120 ° F.

Claims (8)

A two-component tooth whitening composition wherein the components are mixed together to contain a peroxide compound and a second component incompatible with the peroxide compound, the second component and the peroxide compound each are included in separate dentifrice components that are physically separated up to and including dosed when in use, the components retain their original semi-solid physical state when in contact, the first component is an abrasive-free semi-solid gel, a composition containing a peroxide compound on a medium thickened with a combination of a fine water-insoluble inorganic compound as an inorganic thickener, and the compound the peroxide is selected from the group consisting of hydrogen peroxide, urea peroxide, glycerin peroxide, benzoyl peroxide, calcium peroxide, and sodium percarbonate, a comminuted water-insoluble inorganic compound containing inorganic molecules selected from the group consisting of smoked c zemionka, amorphous silica, clay, alumina and hydrated magnesium aluminum silicate deposited on the titanium dioxide, and the particles of the inorganic compound are present in the first component in an amount of 0.05% to 6% by weight in relation to the first component and the organic thickener other than the alkylene oxide polymer , the organic thickener is selected from natural and synthetic resins and polymers, the organic thickener is present in the first component in an amount of 0.1% to 10% by weight of the first component, and the second component is a semi-solid paste containing a peroxide compound activator which it contains a component incompatible with the peroxide compound, the activator contains manganese gluconate, and the incompatible component further comprises a non-ionic antibacterial agent. 2. A composition according to claim 1 The process of claim 1 wherein the nonionic antibacterial agent is a halogenated diphenyl ether. 3. A composition according to p. The composition of claim 1, wherein the unworthy component further comprises sodium tripolyphosphate. 4. A composition according to p. The process of claim 1, wherein the organic thickener is xanthan. 5. A composition according to p. The process of claim 1, wherein the organic thickener is a carboxyvinyl polymer. 6. A composition according to p. The process of claim 1, wherein the inorganic thickener is Laponite. 7. The composition according to p. The process of claim 1, wherein the inorganic thickener is fumed silica. 8. A composition as claimed in p. The method of claim 1, wherein the inorganic thickener is present in the peroxide component in an amount from 0.05% to 2% by weight.