WO1997015277A1

WO1997015277A1 - Enhanced stannous oral composition

Info

Publication number: WO1997015277A1
Application number: PCT/US1996/016691
Authority: WO
Inventors: David Scott Harper; David L. Carlson; Rita Parikh; Anil Kumar Talwar
Original assignee: Warner-Lambert Company
Priority date: 1995-10-23
Filing date: 1996-10-22
Publication date: 1997-05-01
Also published as: AU7453496A

Abstract

An antiplaque oral composition, such as a toothpaste, gel dentifrice, tooth-powder, mouthrinse or mounthwash, tooth hardener, gum or lozenge, comprising stabilized stannous ion source as an antiplaque and antigingivitis component, the antiplaque and antigingivitis action of which is unexpectedly and beneficially increased by the presence in the oral composition of an essential oil, such as eucalyptol, thymol, methyl salicylate, menthol, phenol, halogenated derivatives thereof, and mixtures thereof. Preferred compositions are toothpastes, gel dentifrices and mounthrinses or mounthwashes.

Description

TITLE

ENHANCED STANNOUS ORAL COMPOSITION

BACKGROUND OF THE INVENTION

Field of the Invention

This invention relates to antiplaque and antigingivitis oral compositions. More particularly, it relates to such compositions which contain stabilized stannous ions, as an antiplaque and antigingivitis component, with essential oil compounds, such as phenolic compounds, which unexpectedly increase and enhance the antiplaque and antigingivitis activity of the stabilized stannous ions and also act as a flavoring agent for the composition. Anti-plaque and antigingivitis effects is defined as the ability to inhibit the growth of dental plaque or reduce the occurrence of gingivitis.

Related Background Art

Various prior art oral compositions, such as toothpastes and mouthwashes, which have been manufactured and sold, have included in their formulas various components intended to promote dental health, in addition to components intended primarily to clean teeth and sweeten breath. For example, stannous fluoride has been included in both toothpaste and mouthrinse formulations for its antiplaque and antigingivitis action, as well as for its anticaries action. Flavoring and antibacterial agents present in toothpastes and mouthrinses have also included essential oils, such as phenolic compounds. Additionally, various other known materials have routinely been included in such oral composition formulations for their desired properties, among which are polishing agents, thickening agents, surfactants, humectants, solvents, sweeteners, anticalculus agents and antibacterial agents.

The antiplaque and antigingivitis activity of stannous fluoride and other stannous salts which serve as a source of stannous ions is known. It has been shown that when stannous fluoride is applied as a mouthrinse or in toothpaste, that stannous fluoride is effective in preventing plaque formation and in improving gingival condition. Svatun, B. (1978) Acta. Odontol. Scand. 36 205-210.

There have been many proposals in the prior art which incorporate stannous compounds into oral health care products for the purpose of achieving particular clinical benefits such as caries prevention, plaque control, or the reduction of gingivitis. These stannous compounds are compounds which, upon association with water, are capable of yielding stannous ions. The stannous ion is believed to be the part of the molecule which is active against oral bacteria.

However, the incorporation of stannous compounds and stannous ions into dentifrice compositions presents problems in that the stannous ions tend to react with other components of the dentifrice composition to form insoluble stannous compounds, which reduces the effective amount of stannous ions available in the composition and thus renders the stannous compound less efficacious. In addition, the active stannous ion is particularly prone to oxidation, e.g. by air or an oxidizing agent.

A variety of different methods have been proposed to stabilize stannous containing dentifrice compositions.

Inger Bay and Gunnar Rolla, Scan. J. Dent. Res., 1980, V88 p. 313-15 have shown that the plaque-inhibiting effect of stannous fluoride was maintained in a toothpaste containing 0.4% stannous fluoride and 1% stannous pyrophosphate whereas one containing the same amount of stannous fluoride but without stannous pyrophosphate exhibited no plaque-inhibiting property. A study to investigate the role of stannous pyrophosphate in toothpastes containing various relative amounts of stannous fluoride and stannous pyrophosphate has been reported by Svatun and Rolla, "The role of stannous pyrophosphate in the plaque-inhibiting effect of dentifrices containing stannous fluoride", Tooth Surface Interactions and

Preventive Dentistry. IRL Press Ltd (London) , pp 33 to 37, 1981. This study showed that there was a clear correlation between the content of stannous pyrophosphate and the plaque inhibiting activity. The authors concluded that the role of stannous pyrophosphate in the plaque-inhibiting effect of dentifrices containing stannous fluoride conceivably is to be a reservoir of stannous ions.

In US Patent No. 5,258,173 it was found that the inclusion of slightly soluble stannous compounds, e.g. stannous pyrophosphate, still gives rise to the formation of inactive stannic compounds. According to that patent the conversion of stannous ions in a dentifrice composition into inactive stannic ions can be significantly reduced or prevented by the inclusion in the dentifrice composition of an antioxidant which is a radical inhibitor. Since dentifrice compositions do not normally contain an oxidizing agent and are usually packed in a closed container, it was found that the use of an antioxidant of the radical inhibitor type reduced and prevented the conversion of stannous ions into stannic ions in such a dentifrice composition.

US Patent No. 5,258,173 describes a method of inhibiting conversion of stannous ions into inactive stannic ions within a toothpaste composition comprising stabilizing said stannous ions with an antioxidant which is a radical inhibitor, said toothpaste composition consisting essentially of:

(a) from 10 to 99% by weight of a liquid phase formed of a material selected from the group consisting of water, humectants and combinations thereof;

(b) from 0 to 75% by weight of an abrasive cleaning agent;

(c) from 0.01 to 10% by weight of a stannous compound capable of yielding said stannous ions upon association with water, said stannous compounds being selected from the group consisting of stannous chloride, stannous acetate, stannous hexa-fluorozironate, stannous sulphate, stannous tartrate, stannous gluconate, stannous pyrophosphate, stannous fluoride, stannous metaphosphate, stannous oxalate, stannous phosphate and combinations thereof; and (d) from 0.001 to 2% by weight of an antioxidant selected from the group consisting of propyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, ethyl vanillin, rosemary oil, lecithin, vitamin E, rutin, morin fisetin and mixtures thereof.

US Patent No. 5,096,702 is a dentifrice composition having an improved antiplaque effect consisting essentially of from 10 to 90% by weight of a liquid vehicle which comprises water and a humectant, from 10 to 75% by weight of an abrasive cleaning agent, from 0.1 to 5% by weight of stannous pyrophosphate and from 0.1 to 5% by weight of a fluorocompound, the dentifrice composition being essentially free from a phytate salt, and wherein the fluorocompound is a water-soluble monofluorophosphate salt.

US Patents Nos. 5,057,308; 5,057,309 and 5,057,310 describe an oral hygiene preparation, comprising a nonionic surfactant, a coating substance insoluble in said surfactant and SnF₂;

wherein said preparation: (a) is non-aqueous, abrasive free, and free from substances that interfere with the microbial activity of SnF_2>

(b) is characterized as ingestible, non-foaming, and substantive to hard and soft tissue in the oral cavity,

(c) has a pH from between about 3.4 and about 6.5,

(d) is antimicrobially active towards S. mutans, and (e) is in a delivery form selected from the group consisting of liquids and solids.

US Patents Nos. 4,418,057 and 4,533,544 describe methods for producing stable stannous fluoride dental gels comprising:

A method for producing a commercial-scale size batch of a stable gel consisting essentially of from about 96% to about 98% of anhydrous glycerin, from about 1.8% to about 2.2% of hydroxyethyl cellulose and from about 0.38% to about 0.43% of stannous fluoride wherein the concentration of stannous fluoride in said gel is stable during storage against deterioration to levels below that enabling the use of said gel as a topical treating agent for the prevention of dental caries.

The first stage of said method comprising the sequential steps:

(a) dissolving 50% of the stannous fluoride present in said gel from about 15% to about 18% of the anhydrous glycerin present in said gel at a temperature in the range of from about 150 'C to about 180 °C;

(b) adding a sufficient quantity of anhydrous glycerin to said mixture to reduce the temperature thereof of from about 130^ to about 150°C;

(c) dissolving in said mixture 50% of the hydroxyethyl cellulose present in said gel; and

(d) adding to said mixture sufficient anhydrous glycerin to bring the volume thereof up to about 50% of the volume of said gel; and the second stage of said method comprising repeating the said sequential steps of said first stage and combining the product of said second stage with the product of said first stage; and

a method of producing a commercial-scale size batch of a stable gel consisting essentially of from about 0.38% to about 0.42% of stannous fluoride, from about 0.25% to about 0.45% hydroxyethyleelluose and the remainder anhydrous glycerin, wherein the concentration of stannous fluoride in said gel is stable during storage against deterioration to levels below that enabling the use of said gel as a topical treating agent for the prevention of dental caries, comprising the steps:

(a) dissolving the stannous fluoride present in said gel from about 7.1% to about 7.2% of the anhydrous glycerin present in said gel at a temperature in the range of from about 150 ^°C to about 180 ^°C to form a first stannous fluoride;

(b) admixing said first stannous fluoride solution with from about 23% to about 28% of the anhydrous glycerin present in said gel at ambient temperature to form a second stannous fluoride solution;

(c) dissolving the hydroxyethylcellulose present in said gel in from about 33% to about 38% of the anhydrous glycerin present in said gel at a temperature in the range of from about 130 'C to about 180°C;

(d) intimately admixing said hydroxyethylcelluose solution with said second stannous fluoride solution; and (e) intimately admixing said solution with the remainder of the anhydrous glycerin present in said gel.

US Patent No. 4,647,451 describes an anhydrous dentifrice comprising at least about 50% by weight of glycerin humectant, at least 0.1% by weight of deacetylated heteropolysaccharide S-60 to provide a rigid gel consistency to said dentifrice, about 5 to 50% by weight of dentally acceptable polishing agent selected from the group consisting of anhydrous zeolite, sodium bicarbonate, alpha-alumina hydrate, calcium sulfate, aluminum silicate, dicalcium phosphate, tricalcium phosphate, insoluble sodium metaphosphate, silica aerogel, sodium aluminasilicate, magnesium carbonate, calcium carbonate, calcium pyrophosphate and bentonite and said anhydrous dentifrice further contains a fluoride-providing compound in an amount which provides about 0.01 to 1% by weight of water-soluble fluoride content to said anhydrous dentifrice upon contact with water or saliva, said fluoride-providing compound being selected from the group consisting of sodium fluoride, stannous fluoride, manganese fluoride, potassium fluoride, potassium stannous fluoride, sodium hexafluorostannate, stannous chlorofluoride, sodium fluorozirconate, potassium fluorozirconates and sodium monofluorophosphate.

US Patent No. 5,004,597 describes an oral composition effective in treating plaque/gingivitis comprising:

(a) a safe and effective amount of stannous fluoride;

(b) a safe and effective amount of stannous gluconate; and (c) a pharmaceutically acceptable carrier wherein the pH of said composition is from about 3.0 to about 4.79 and said composition is substantially free of a calcium ion source (s) .

US Patent 5,145,666 describes an oral composition effective in treating plaque/gingivitis with reduced staining having a first composition comprising:

(a) a safe and effective amount of stannous fluoride;

(b) a safe and effective amount of stannous gluconate; and

(c) a pharmaceutically acceptable carrier wherein the pH of said composition is from about 3.0 to about 5.0 and said composition is substantially free of a calcium ion source (s) ; and a second composition comprising:

(i) a safe and effective amount of a pyrophosphate ion source; (ii) a pharmaceutically acceptable carrier wherein said compositions are packaged as a kit of separate containers.

US Patent 5,213,790 describes an oral, bi-phasic, dual-formulation dentifrice or toothpaste composition effective in treating plaque/gingivitis with reduced staining having a first dentifrice or toothpaste composition comprising:

(a) a safe and effective amount of stannous fluoride;

(b) a safe and effective amount of stannous gluconate; and (c) a pharmaceutically acceptable dentifrice or toothpaste carrier wherein the pH of said composition is from about 3.0 to about 5.0 and said composition is substantially free of both a citric ion source as well as a calcium ion source;

and a second dentifrice or toothpaste composition comprising:

(a) a safe and effective amount of a citrate ion source; and

(b) a pharmaceutically acceptable dentifrice or toothpaste carrier which is substantially free of stannous fluoride and stannous gluconate.

US Patent 5,281,410 describes an oral composition effective in treating plaque/gingivitis with reduced staining having a first composition comprising:

(a) a safe and effective amount of stannous fluoride;

(b) a safe and effective amount of stannous salt of a alpha hydroxy acid, phytic acid, ethylenediamine tetra acetic acid, or glycine; and

(c) a pharmaceutically acceptable carrier wherein said composition is substantially free of a calcium ion source (s) ;

and a composition comprising:

(a) a safe and effective amount of a pyrophosphate ion source;

(b) a pharmaceutically acceptable carrier. US Patent 5,281,411 describes an oral composition effective in treating plaque/gingivitis consisting essentially of:

(a) a safe and effective amount of stannous gluconate; and

(b) a pharmaceutically acceptable fluoride toothpaste carrier wherein the pH of said composition is from about 3.0 to about 5.0 and said composition contains less than about 2.0% of a calcium ion source (s) and less than about 0.05% stannous fluoride.

US Patent 5,338,537 describes an oral anticalculus antiplaque/gingivitis composition with reduced tendency to stain consisting essentially of:

(a) a safe and effective amount of stannous fluoride;

(b) a safe and effective amount of stannous gluconate;

(c) a safe and effective amount of polyphosp onate anion source having the following structure:

wherein R can be hydrogen or lower alkyl and n is an integer from 3 to 5; and

(d) an acceptable oral dentifrice carrier. US Patent No. 4,363,794 describes an oral composition for caries prophylaxis comprising a stannous salt, a water-soluble fluoride salt selected from the group consisting of sodium fluoride, potassium fluoride and mixtures thereof, and an orally acceptable acid selected from the group consisting of a monocarboxylic acid, a dicarboxylic acid, a tricarboxylic acid, a mineral acid and mixtures thereof, said stannous salt being present in the range of from 0.07% by weight of the total amount of the composition as stannous ion to the saturated state in water, the molar ratio of fluoride ion to stannous ion being in the range of from 3.5:1 to 5.7:1 in the aqueous condition, the molar ratio of said monocarboxylic acid to stannous ion being in the range of from 0.8 x 0.5nil, the exponent "n" being the weight percent content of the stannous ion in the composition, and said orally acceptable acid being present in the composition in such an amount that the pH of the composition is in the range of from 2 to 4.

US Patent No. 4,335,102 describes an oral composition for caries prophylaxis comprising: a highly soluble stannous compound selected from the group consisting of stannous fluoride, stannous chloride, stannous chloride fluoride, sodium stannous fluoride, potassium stannous fluoride, stannous acetate, stannous hexafluorozirconate, stannous sulfate, stannous tartrate, stannous gluconate and mixtures thereof, said highly soluble stannous compound being present in the range of 0.03% to 5% by weight of the composition as stannous tin; a difficulty soluble stannous compound selected from the group consisting of stannous pyrophosphate, stannous metaphosphate, stannous oxide, stannous oxalate, stannous phosphate and mixtures thereof, said difficulty soluble stannous compound being present in the range of 0.05% to 10% by weight of the composition a stannous tin; and 0.1% to 20% by weight of the composition of a phytic acid compound selected from the group consisting of phytic acid, sodium phytate, potassium phytate, lithium phytate, ammonium phytate, magnesium phytate, zinc phytate, calcium phytate, aluminum phytate, phytin, double salts thereof and mixtures thereof, said composition being acidic.

US Patent 4,259,316 describes an oral composition for caries prophylaxis comprising stannous fluoride and a phytic acid compound, the content of stannous fluoride being 0.1 to 4% by weight of the total amount of the composition, the content of the phytic acid compound being 0.5 to 10% by weight of the total amount of the composition, the molar ratio of the phytic acid compound to stannous fluoride being in the range of from 0.025:1 to 2.5:1, and the composition being acidic.

As noted previously, essential oils, e.g. phenolic compounds, have been employed alone and in combination to flavor oral compositions. In addition, some of them have been included in compositions such as mouthwash and toothpaste for their antibacterial properties.

U.S. Patent 5,094,843 discloses the use of essential oils, such as phenolic compounds, in fluoride toothpastes, and pending Application No. 08/280,098 filed July 25, 1994, assigned to Warner-Lambert Company, describes toothpaste with antimicrobial properties in which essential oils are present. However, it was not known that the presence of the essential oils in combination with stabilized stannous ions and, in particular, as stabilized stannous fluoride compositions, would give a surprising and unexpected increase in the effectiveness of the oral composition against plaque and gingivitis. It now appears to be possible to use one or more of the aforementioned stabilizing technologies in combination with certain known essential oils to provide a stable stannous oral composition, such as a toothpaste, which has enhanced efficacy against plaque and gingivitis.

Although the toothpaste art discloses the use of stabilized stannous fluoride as an antiplaque agent as well as antigingivitis agent and the use of essential oils as flavoring and antibacterial agents in oral compositions, there is no disclosure or suggestion in the prior art of the use of both stabilized stannous ions and antimicrobial effective amounts of essential oils in the same oral composition. Moreover, there is no disclosure or suggestion that the antiplaque and antigingivitis activity of an oral composition containing stabilized stannous ions would be greatly improved and enhanced by the presence of antimicrobially effective amounts of essential oils.

SUMMARY OF THE INVENTION

This invention relates to an antiplaque and antigingivitis oral composition comprising: (a) an antimicrobial effective amount of at least one essential oil; (b) a source of stabilized stannous ions in an amount effective to provide at least about 300 ppm of soluble stannous ions in the composition; and (c) an orally acceptable vehicle.

The oral composition may be in the form of a dentrifice, e.g., a toothpaste, gel or tooth powder, a mouthwash, a lozenge, candy, chewing gum or the like. Preferably, the oral composition takes the form of a toothpaste or gel. DETAILED DESCRIPTION OF THE INVENTION

According to the present invention, it has now been found that the antigingivitis and antiplaque activity of a stabilized stannous oral compositions, preferably a stabilized stannous dentifrice and more preferably a stabilized stannous fluoride dentifrice can be enhanced by the addition of an effective amount of antiplaque or antigingivitis essential oils, such as the essential oils found in commercial antiseptic mouthrinses such as LISTERINE^®, i.e. , menthol, thymol, eucalyptol and methyl salicylate.

While stabilized stannous ions alone in oral compositions can decrease plaque formation when such compositions are applied to the teeth, and while essential oils, in addition to flavoring such compositions, can also act to decrease plaque formation on the teeth, it is believed that the reduction in plaque formation when both are employed in the same oral composition is surprisingly better than would have been expected from the additive activities of the stabilized stannous ion and the essential oils. Because plaque formation is often associated with gingivitis, the novel oral compositions of this invention are also useful for preventing the development of such a condition.

Essential oils are known to provide good bactericidial activity. On the other hand, stannous ions are believed to inhibit antimicrobial growth through substantive bacteristatic mechanisms. Without being bound to theory, it is believed that the combinations of these two antimicrobial mechanisms of actions will result in an unexpectedly advantageous antiplaque and antigingivitis efficacy for the inventive composition. In accordance with the present invention, an antiplaque and antigingivitis oral composition comprises an orally acceptable vehicle or base for such composition, an effective antiplaque and antigingivitis amount of stabilized stannous ion, and an essential oil in an amount which significantly increases the antiplaque and antigingivitis action of the stannous ion on the teeth of a user of the oral composition.

The oral compositions of this invention contains at least one source of stabilized stannous ions. By stabilized, it is meant that the composition delivers an efficacious and concomitantly bioavailable quantity of Sn²⁺ ion. Generally, known methods may be used to stabilize the stannous ion by, for example, (i) the use of anhydrous compositions, (ii) the introduction of stannous chelating agents in the compositions, (iii) the provision of a reservoir of stannous ions in the composition, and/or (iv) the inclusion of antioxidants in the composition. These exemplary means of stabilization are not limiting, since this invention encompasses any stannous ion source that provides at least 300 ppm of bioavailable stannous ions in the composition.

Known stabilized stannous ion compositions and stannous salts, particularly stannous fluoride salts, are useful in this invention. Stannous fluoride and stannous chloride are preferred, with stannous fluoride being most preferred. Examples from several U.S. patents are included herein to illustrate useful stannous fluoride formulations, and the disclosure of those U.S. patents are incorporated by reference in this disclosure. In order to be effective against plague and gingivitis the level of soluble stannous ions in the oral composition should be in the range of about 300 ppm to about 13,000 ppm, preferably about 800 ppm to about 10,000 ppm and most preferably about 3000 ppm to about 7500 ppm.

Essential oils include, for example, phenolic compounds having phenolic groups, or derivatives thereof, which are orally acceptable and which have an acceptable flavor. Such essential oils may be selected from the group consisting of eucalyptol, thymol, methyl salicylate, menthol, chlorothymol and phenol, and halogenated and other derivatives thereof, with the first six being more preferred, and the first four being even more preferred as the essential oils used for many years in LISTERINE^® brand antiseptic mouthwash. Although any of such essential oils may be employed alone it may normally be preferred to utilize mixtures of two or more thereof and preferably all four (of the first four listed) will be in the oral composition. In such a composition, it is desirable that there be a total amount of at least about 0.1-5 %w/w of the combined four essential oils, preferably at least about 0.05-5 %w/w of at least one essential oil, and more preferably at least about 0.1-5 %w/w of each wherein the total amount of the combined essential oils is about 0.1-10 %w/w.

The oral compositions of this invention are preferably dentifrices, such as toothpastes and gels, but various other compositions such as mouthwashes or mouthrinses may also be given the described improved antiplaque properties by including in them stabilized stannous ions and an antimicrobial effective amount of at least one essential oil. Such compositions include tooth powders, tooth hardeners (usually of the professionally applied type), anticalculus compositions, gums, tablets and lozenges. The dentifrice composition of the invention may contain the following essential oils in percentages by weight:

(a) thymol from about 0.01% w/w to about 1.5%w/w; (b) menthol from about 0.01% w/w to about 3.0% w/w; (c) eucalyptol from about 0.01% w/w to about 2.5% w/w; and

(d) methyl salicylate from about 0.01% w/w to about 3.0% w/w.

In the preferred embodiment of the dentifrice composition of the present invention, the dentifrice composition may contain the following essential oils in percentages by weight: (a) thymol from about 0.025% w/w to about 1.0% w/w; (b) menthol from about 0.05% w/w to about 2.5% w/w; (c) eucalyptol from about 0.025% w/w to about 2.0% w/w; and (d) methyl salicylate from about 0.05% w/w to about 2.5% w/w.

In the most preferred embodiment of the dentifrice composition of the present invention, the dentifrice composition may contain the following essential oils in percentages by weight: (a) thymol from about 0.05% w/w to about 0.8% w/w; (b) menthol from about 0.1% w/w to about 2.0% w/w; (c) eucalyptol from about 0.05% w/w to about 1.5% w/w; and (d) methyl salicylate from about 0.1% to about 2.0% w/w.

The pH of the dentrifice composition according to the present invention is from about 3 to about 8, more preferably from about 3 to about 6.

The preferred embodiment of the present invention may also contain conventional dentifrice additives including but not limited to humectants, binders, thickeners, surfactants, preservatives, sweeteners, flavors, colors, and a buffer. These additives are present in amounts that do not interfere with the antiplaque and antigingivitis properties of the composition of the present invention.

Surfactants or surface active agents are organic compounds which reduce surface tension between liquids and aid in the dispersion of a composition throughout the oral cavity. The surfactant in the present invention may be anionic, nonionic, or amphoteric. The dentifrice compositions of the present invention may contain surfactants in amounts up to about 5.0% w/w; preferably from about 0.1% w/w to about 3.0% w/w of the dentifrice composition; and most preferably from about 0.2% w/w to about 2.5% w/w of the dentifrice composition.

The most preferred surfactants are anionic. These anionic surfactants include but are not limited to sodium lauryl sulfate, sodium lauroyl sarcosinate, sodium methyl cocyl taurate, and disodium lauryl sulfosuccinate.

In the most preferred embodiment the surfactant is the anionic surfactant sodium lauryl sulfate.

Amphoteric surfactants having the capacity to behave as either an acid or a base and include quaternized imidazole derivatives useful in the present invention. Preferred amphoteric surfactants include long chain (alkyl) amino-alkylene aklyated amine derivatives, also known as MIRANOL^®, manufactured by Rhone-Poulanc, Cranberry, New Jersey.

Sweeteners well known in the art, including natural and artificial sweeteners, may be used. The sweetener may be selected from a wide range of materials including naturally occurring water-soluble sweeteners, artificial water-soluble sweeteners and modified water- soluble sweeteners derived from naturally occurring water-soluble sweeteners. Artificial water-soluble sweeteners include, but are not limited to, soluble saccharin salts, e.g., sodium or calcium saccharin salts, cyclamate salts, the sodium, ammonium or calcium salt of 3,4-dihydro-6-methyl-1,2,3, -oxathiazine-4-one- 2,2-dioxide, the potassium salt of 3,4-dihydro-6- methyl-1,2,3-oxathiazine-4-one-2,2-dioxide (Acesulfame- K) , the free acid form of saccharin, and the like; dipeptide based sweeteners, such as L-aspartic acid derived sweeteners, e.g., L-aspartyl-L-phenylalanine methyl ester (Aspartame) and materials described in U.S. Patent No. 3,492,131, L-alpha-aspartyl-N- (2,2,4,4- tetramethyl-3-thietanyl) -3-alaninamide hydrate (Alitame) , methyl esters of L-aspartyl-L- phenylglycerine, and L-aspartyl-L-2, 5- dihydrophenylglycine, L-aspartyl-2,5-dihydro-L- phenylalanine; L-aspartyl-L- (1-cyclohexene) -alanine, and the like. Naturally occurring water-soluble sweeteners include, but are not limited to, sugar alcohols, including sorbitol as 70% sorbitol solution, mannitol, xylitol, maltitol, hydrogenated starch hydrolysates and mixtures thereof.

Water-soluble sweeteners derived from naturally occurring water-soluble sweeteners include, but are not limited to, chlorinated derivatives of sucrose, known, for example, under the product designation of Sucralose; and protein-based sweeteners such as thaumaoccous danielli (Thaumatin I and II) .

Sorbitol solution supplies sweetness and body to the composition and gives a desirable mouth feel. Sorbitol solution also enhances flavor, prevents harsh taste and provides a fresh and lively sensation in the mouth. It also prevents caking of the dentifrice. In general, an effective amount of sweetener is utilized to provide the level of sweetness desired in any particular embodiment of the dentifrice compositions according to the present invention. This amount will vary with the sweetener selected and the final oral hygiene product. The amount of sweetener normally present is from about 0.0025% w/w to about 60% w/w of the dentifrice composition. The exact range of amounts for each type of sweetener in a dentifrice is well known in the art and is not the subject of the present invention.

The flavors which may be used in the invention include natural and artificial flavors known in the dentifrice art. Suitable flavors include, but are not limited to, mints, such as peppermint, citrus flavors such as orange and lemon, artificial vanilla, cinnamon, various fruit flavors, and the like. Anethole (or anise camphor, p-propenyl anisole) is a flavor constituent of anise and fennel oils which are used widely as flavoring agent and antiseptic, and has been found useful in masking the harsh taste of thymol.

The amount of flavor is normally a matter of preference subject to such factors as the type of final dentifrice composition, the individual flavor employed, and the strength of flavor desired. The flavors are preferably utilized in amounts that may range in total amounts from about 0.01% w/w to about 6% w/w of the dentifrice composition.

Coloring agents in this invention are used in amounts effective to produce a dentifrice of the desired color. These coloring agents may be incorporated in amounts up to about 3% by weight of the dentifrice composition of the present invention. The coloring agents may also include natural food colors and dyes suitable for food, drug and cosmetic applications. These coloring agents are known as FD & C dyes and lakes. The materials acceptable for the foregoing uses are preferably water¬ soluble. Illustrative nonlimiting examples include the indigoid dye known as FD & C Blue No. 1, and D & C Yellow No. 10. A full recitation of all FD & C colorants and their corresponding chemical structures may be found in the Kirk-Oth er Encyclopedia of Chemical Technology, 3rd Edition, in volume 5 at pages 857-884. A preferred opacifier, titanium dioxide, may be incorporated in amounts up to about 3.0% w/w, preferably less than about 2.0% w/w of the composition, and most preferably less than about 1.0% w/w

Suitable humectants in this invention include sorbitol, as 70% sorbitol solution, glycerin, propylene glycol, polyethylene glycol, mixtures thereof, and the like. Humectants may be present in amounts from about 1.0% to about 75.0% by weight of the dentifrice composition.

Suitable abrasive substances for use in this invention include hydrated silica, calcium carbonate, calcium pyrophosphate, dicalcium phosphate dihydrate, or alkali metal meta-phosphates. Silica abrasives in the dentifrice composition according to this invention may include among others, ZEODENT^® (113), manufactured by J. M. Huber Corp. and SYLOID^® or SYLODENT^®, manufactured by W.R. Grace Co. These polishing agents may be used in amounts up to about 75.0% w/w of the composition, preferably in amounts from about 5.0% w/w to about 50% w/w of the composition, and most preferably from about 5.0% w/w to about 40.0% w/w of the composition.

In the preferred embodiment of this invention, the dentifrice composition includes an oral vehicle and is in the form of toothpaste or a dental gel. The dentifrice composition of this invention may also include binders or gelling agents to give the products their characteristic consistency. Gelling agents such as hydroxyethyl cellulose, carboxymethyl cellulose, methyl cellulose, xanthan gum, gelling silicas, and the like may be used singly or in combination. The preferred gelling system is a mixture of carboxy methyl cellulose, xanthan gum and gelling silica. Gelling agents may be used in amounts from about 0.1% w/w to about 30% w/w, preferably from about 0.2% w/w to about 15.0% w/w of the dentifrice composition, and most preferably from about 0.4% w/w to about 10% w/w of the composition.

The dentifrice composition of this invention may also contain a desensitizing agent such as strontium chloride, potassium nitrate or sodium citrate-citric acid, which may be used in an amount from about 0.5% w/w to about 10% w/w.

Suitable preservatives in this invention include benzoic acid, butylated hydroxyanisole (BHA) , butylated hydroxytoluene (BHT) , ascorbic acid, methyl paraben, propyl paraben, tocopherols and mixtures thereof. Preservatives when used are generally present in amounts up to about 1.0% w/w, and preferably from about 0.01% w/w to about 0.5% w/w of the dental gel composition.

The dentifrice compositions of this invention may be prepared by mixing the desired ingredients using methods well known to those of ordinary skill in the art. The preparation of a dental gel employing the ingredients of this invention is also readily accomplished by those having ordinary skill in the art. For the paste, gel, solid and particulate solid state compositions of the invention, such as toothpastes, gel dentifrices, toothpowders, chewing gums, tablets and lozenges, the base or the vehicle for the active components will usually be any which is conventionally employed in known oral compositions. However, bases or vehicles which deleteriously affect the stability, and hence the bioavailability, of the stannous ion should be avoided.

Another preferred embodiment of the present invention is a mouthwash composition. Conventional mouthwash composition components include, for example, an aqueous/alcoholic carrier, surfactants, particularly nonionic surfactants or anionic surfactants, flavors, sweeteners and surfactants such as previously described for the dentrifice compositions of this invention. Generally, the mouthwashes of this invention comprise 1 to 65% w/v alcohol, preferably 10 to 30% w/v alcohol and most preferably the alcohol is ethanol. The pH of the mouthwash compositions of this invention typically range between about 3 to about 8, most preferably about 3 to 6. Substantially anhydrous mouthwash formulations are also preferred to assist in stannous stabilization.

Other metallic cations such as zinc and copper may also be useful in this invention. In particular, the compositions of this invention may contain an anticalculus effective amount of zinc, generally between about 0.25 to about 2 % w/w. The Examples which follow are intended as an illustration of certain preferred embodiments of the invention and no limitation of the invention is implied.

Two dentrifice compositions of the present invention were prepared by mixing the igredients described below.

INGREDIENT Example 1 Example 2

%(w/w) %(w/w)

Water, Deionized 20.17 20.27

Sorbitol Solution (70%) 40.00 40.00

Glycerin 10.00 10.00

Titanium Dioxide 0.53 0.53 Silica . 20.00 20.00

Na Carboxymethyl Cellulose 1.00 1.00

Na Carrageenan 0.35 0.35

Sodium Lauryl Sulfate 1.25 1.25

Na Gluconate 2.50 2.50 Stannous Fluoride 0.45 0.45

Stannous Chloride 0.00 1.500

Na Saccharin 0.20 0.20

FD&C Blue 1 0.05 0.05

THYMOL 0.60 0.30 Methyl Salicylate 0.60 0.20

Menthol 0.40 0.20

Eucalyptol 0.90 0.20

Flavor 1.00 1.00 Two additional dentrifice compostions were prepared by mixing the following ingredients:

INGREDIENT Example 3 Example 4

% (w/w) % (w/w)

Xanthan gum 0.50

Carboxy methyl cellulose 0.60

Carbopol 0.90

Sorbitol solution (70%) 10.00

Dye 0.0023 0.0023

Butylparaben 0.01

Sodium Saccharin 0.20 0.25

Propylene glycol 3.00

Polyethylene glycol 5.00

Pentasodium phytate 2.50

NaOH 0.14

Silica 25.00 16.00

Ti0₂ 0.35 0.35

Glycerin 10.00 73.40

Stannous Fluoride 0.40 0.45

Thymol 0.40 0.40

Methyl Salicylate 0.60 0.10

Menthol 0.18 0.10

Eucalyptol 0.10 0.10

Flavor 0.82 0.80

Sodium Lauryl Sulfate 2.00 1.00

Water 43.88 1.00

Anticeptic assays were performed to evaluate the potential antiplaque and antiginivitis activity of the stabilized stannous toothpastes of Examples 3 and 4. The anticeptic assays were also performed on commercially available Listerine Cool Mint Tooth Paste^®, Crest Regular^® and Crest Gum Care^®. The results of the anticeptic assays are illustrated below as the percent of surviving salivary organisms relative to Listerine Cool Mint Tooth Paste^®.

Sample Tested Relative Surviving Salivary Organisms

Listerine Cool Mint Tooth 100 Paste^®

Example 3 90.8

Example 4 75

Crest Regular^® 6270

Crest Gum Care^® 4883

Other variations and modifications of this invention will be obvious to those skilled in this art. This invention is not to be limited except to set forth in the following claims.

Claims

What is claimed is:

1. An oral composition comprising:

(a) an antimicrobial effective amount of at least one essential oil;

(b) a source of stabilized stannous ions in an amount effective to provide at least about 300 ppm of soluble stannous ions in the composition; and

(c) an orally acceptable vehicle or base.

2. An oral composition according to claim 1, wherein said at least one essential oil is selected from the group consisting of thymol, eucalyptol, methyl salicylate, menthol and mixtures thereof.

3. An oral composition according to claim 2, wherein said stabilized stannous ions are selected from the group consisting of stannous fluoride, stannous chloride and mixtures thereof.

4. An oral composition according to claim 3, wherein said oral composition is a toothpaste or gel.

5. An oral composition according to claim 4, wherein said stabilized stannous ions are stabilized by at least one of (i) an anhydrous orally acceptable vehicle, (ii) a chelating agent, (iii) a reservoir of stannous ions or (iv) an antioxidant.

6. An oral composition according to claim 5, wherein thymol is present in an amount between about 0.01 to about 1.5 % w/w.

7. An oral composition according to claim 6, wherein said source of stabilized stannous ions provides between about 300 ppm to about 13,000 ppm of soluble stannous ions in the composition.

8. An oral composition according to claim 7, wherein eucalyptol is present in an amount between about 0.01 to about 1.5 % w/w, methyl salicylate is present in an amount between about 0.01 to about 3.0 % w/w, and menthol is present in an amount between about 0.01 to about 3.0 % w/w.

9. A dentrifice composition comprising:

(a) an antimicrobial effective amount of thymol;

(b) a source of stabilized stannous ions selected from stannous salts in an amount effective to provide at least about 300 ppm soluble stannous ions in the composition; and

(c) an orally acceptable vehicle or base.

10. A dentrifice composition according to claim 9, further comprising eucalyptol, methyl salicylate and menthol .

11. A dentrifice composition according to claim 10, wherein said stannous salt is stannous fluoride.

12. A dentrifice composition according to claim 11, wherein said stabilized stannous ions are stabilized by at least one of (i) an anhydrous orally acceptable vehicle, (ii) a chelating agent, (iii) a reservoir of stannous ions or (iv) an antioxidant.

13. A dentrifice composition according to claim 11, wherein said source of stabilized stannous ions provides between about 300 ppm to about 13,000 ppm of soluble stannous ions in the composition.

14. A dentrifice composition according to claim 13, wherein said dentrifice composition is a toothpaste or gel.