RU2469700C2 - Oral care compositions containing tin (ii) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: compositions contain a) a tin (II) ion source, b) a source of polyvalent cations specified in zinc (Zn⁺²), copper (Cu⁺²), aluminium (Al⁺³), iron (Fe⁺², Fe⁺³), strontium (Sr⁺²), calcium (Ca⁺²), barium (Ba⁺²), magnesium (Mg⁺²), manganese (Mn⁺²) or their mixture in the amount sufficient to provide a molar ratio of polyvalent cations to tin (II) within the range of 1.5:1-3:1, c) an agent active with respect to mineral surfaces, showing substantivity with respect to teeth and chelating activity with respect to tin (II) and said polyvalent cations and specified in polycarboxylates or carboxy-substituted polymers or their mixture; and d) abrasive polish containing silicone dioxide. What is also presented is an oral care procedure for reduction of plaque and gingivitis with the use of said compositions. The compositions may be prepared in the form of one-phase or two-phase compositions.

EFFECT: formulation of the compositions provides higher stability, bioavailability and effectiveness of tin and optimal antimicrobial activity of the compositions with a low level of teeth staining, as well as low bonding properties that leads to improved aesthetic characteristics of the composition.

9 cl, 2 ex

Description

Technical field

The present invention relates to improved oral care compositions containing tin (II) salts, such as tin (II) fluoride. These advanced formulations provide a range of oral benefits from tin (II) fluoride and / or other tin (II) salts, including antimicrobial effects, anti-bad breath, anti-plaque growth and metabolism, weakened gingivitis, and slow disease progression periodontal disease, a decrease in dentinal hypersensitivity and a decrease in caries and erosion of crowns and tooth roots. The above beneficial effects are provided along with significant improvements over conventional tin (II) compositions, including: 1) reduced levels of staining on the teeth; 2) reduced astringency, which improves the aesthetic characteristics of the compositions; 3) a decrease in the formation of tartar and 4) increased stability, bioavailability and, thus, the effectiveness of tin (II) as an antimicrobial agent, an agent against plaque and gingivitis. Improved compositions containing tin (II) provide these beneficial effects by combining the effects of tin (II), a second polyvalent cation and mineral surfaces and chelating agents, preferably polymeric, and in particular including anionic polymers, such as condensed polyphosphate, polyphosphonate or polycarboxylate. The invention also relates to methods for enhancing therapeutic efficacy while reducing staining and improving the aesthetic preference for oral care compositions containing tin (II) salts, such as tin (II) fluoride.

Prior art

It is well known that tin (II) fluoride is effective when incorporated into oral care products. Tin (II) fluoride was the first fluoride source included in toothpastes due to its therapeutic efficacy in combating tooth decay. Since then, gels, rinses and dentifrice with tin (II) fluoride have been shown to provide clinical efficacy in reducing tooth decay, dentinal hypersensitivity, plaque and gingivitis. In addition to these clinical effects, tin (II) fluoride compositions may also contribute to the improved beneficial effects of breath freshening due to chemical and antibacterial effects. Tin (II) fluoride compositions typically include stabilizing systems designed to maintain bioavailable (i.e., soluble and reactive) tin (II) levels over their shelf life, taking into account loss of tin (II) loss due to oxidation or formation draft. As a result, tin (II) fluoride compositions were formulated with additional tin (II) containing ingredients that provide a high concentration of tin (II) as a tin (II) reservoir to maintain clinical efficacy. Unfortunately, although it is known that tin (II) fluoride compositions are highly effective, successful commercial use is complicated by the difficulty of developing compositions providing sufficient tin (II) fluoride stability and side effects of tin (II). Compositions that provide enhanced or improved efficacy typically cause enhanced side effects. This limits clinical and commercial use.

One of the most noticeable side effects of regular use of tin (II) fluoride is the formation of yellow-brown spots on the teeth. These spots are formed as a result of the reactions of the pellicle, plaque and food components with available tin (2), deposited on the surfaces of the teeth when treated with effective tin (II) fluoride compositions.

The second side effect commonly observed when using effective tin (II) fluoride compositions is the unacceptable astringent properties of the composition. Astringents are localized protein precipitants, whose low cellular permeability limits their action to cell surfaces and interstitial spaces. Strong astringents can cause tissue compression and wrinkling, and mucous secretion can stop or decrease. In the composition of oral care products, this chemical effect causes an unpleasant “drying” sensation in the oral cavity, for example, on the tongue, in the gingival tissues or buccal epithelium. Compositions with tin (2) containing a sufficient amount of tin (II) to ensure bioavailability are usually described by patients and consumers as binders, and this property is undesirable. Astringent properties are most noticeable after using the product.

A third side effect of the regular use of the tin (II) fluoride dentifrice composition is the reduced effectiveness of reducing tartar formation by these compositions. It has been found that tin (II) fluoride dentifrices with proven antimicrobial, anti-gingivitis, and other expected beneficial effects do not always produce reproducible clinical results in preventing the accumulation of unwanted supragingival calculus. The fight against supragingival tartar formation along with other clinical beneficial effects is desirable for professionals, patients and consumers. The multifunctional activity of oral care compositions can simplify hygiene and provide a holistic approach to maintaining a therapeutically healthy oral health.

Previous attempts to develop effective and consumer-friendly tin (II) fluoride compositions for oral care were aimed at eliminating these cumulative harmful effects, but none of them were completely successful. US patent 5004597, issued in the name of Majeti et al., Discloses compositions for caring for the oral cavity containing fluoride and gluconate salts of tin (II). The inclusion of tin (II) gluconate leads to an increase in the effectiveness of the composition and stability. Being effective, this composition creates undesirable levels of staining on the teeth. In addition, the composition has unacceptable aesthetic characteristics caused mainly by the astringent properties of tin (II). Similarly, US Pat. No. 5,578,293, issued to Prencipe et al., Discloses the use of an organic acid compound to stabilize tin (II) ion concentration. Along with tin (II) fluoride and citrate, soluble pyrophosphate salts are also included in the composition as an organic acid. US patent 4323551, in the name of Parran et al., Discloses the use of pyrophosphate salts to provide anticalculus beneficial effects. Clinical studies have established the potential of anionic inhibitors active on mineral surfaces, such as pyrophosphates, to prevent natural and antimicrobial-induced staining of teeth (Grossman, Bollmer, Sturzenberger and Vick; Journal of Clinical Dentistry 6 (4): 185-187 , 1995). In Prencipe et al., All examples include a sufficient amount of citric acid and / or sodium citrate dihydrate to stabilize tin (II) ions and to prevent precipitation. These levels also directly inhibit the binding of tin (II) to pyrophosphate salts. Studies confirm that the binding of tin (II) to pyrophosphate salts reduces the antimicrobial activity of tin (II) fluoride. The level of citrate required to effectively stabilize the tin (II) ion from the precipitation and binding of pyrophosphate also significantly impairs the aesthetic characteristics of the tin (II) composition. The composition acquires a salty, sourish taste and tin (II) associated with citrate retains an astringent effect, which reduces the overall acceptability of taste characteristics. U.S. Patent 5,213,790, issued to Lukacovic et al., Also discloses the use of a citrate ion source in a tin (II) composition. US patent 5780015, issued in the name of Fisher et al., Discloses the use of a two-phase dentifrice containing potassium salt and tin (II) salt, in which hydrogenated castor oil is used to reduce astringent properties. The tin (II) salt is stabilized by using an organic acid compound as described by Prencipe et al. Another attempt to obtain an effective tin (II) composition is described in US Pat. No. 5,716,600 to Zahradnik et al. This patent discloses compositions with a low water content, which helps prevent the destruction of tin (II) fluoride over time. Attempts to reduce the formation of stains from the composition were not undertaken.

US Pat. No. 5,017,363, issued to Suhonen, discloses a tin (II) ion chelating copolymer of alkyl vinyl ether and maleic anhydride or acid in an amount that can effectively stabilize tin (II) ions. Suhonen also discloses that the compositions are substantially free of silicon dioxide, soluble phosphates such as soluble pyrophosphates (e.g. tetrasodium pyrophosphate and tetracal pyrophosphate), and compounds containing an aldehyde group, since the stabilizing function of the tin (II) ion-chelating polymer is ineffective the presence of these ingredients.

U.S. Patent 5,338,537 to White, Jr. et al. discloses the use of low molecular weight diphosphonic acid, which is used as a tin (II) binding agent to reduce the tendency to stain the composition. Despite the potential effectiveness to reduce staining, laboratory studies have shown that the antibacterial activity of compositions containing tin (II) in the form of complexes with low molecular weight diphosphonic acid is very low. Similar results were obtained for compositions with soluble pyrophosphate salts, in the absence of strong complexation with citrate, as described above.

Based on the foregoing, it seems likely that the same chemical and biochemical binding sites can be involved both in the manifestation of antibacterial / anti-plaque activity and in the ability to stabilize tin (II) fluoride and to reduce the formation of stains on teeth. Thus, in order to achieve stabilization and / or reduction of staining on the teeth, a decrease in antibacterial / plaque activity may be required. This complicates the development of optimal tin (II) fluoride compositions for oral care and explains the limited availability of tin (II) fluoride compositions on the market today. To improve consumer acceptance and readiness to use tin (II) oral care compositions, a tin (II) composition is required that is highly effective but has low staining and other negative aesthetic characteristics such as astringency . In addition, it is desirable that these compositions simultaneously provide efficacy in reducing tartar formation and controlling it.

SUMMARY OF THE INVENTION

The present invention relates to an oral composition containing a tin (II) ion source, a polyvalent cation source and a tin (II) binding agent active on the mineral surface, these compositions providing improved therapeutic efficacy with minimal side effects of formation stains on teeth and astringent properties. Compositions at the same time provide a decrease in education and the fight against supragingival calculus. Agents that are active on a mineral surface are agents that have substantiality on mineral surfaces, such as teeth, and additionally have chelating activity on polyvalent cations, such as tin (Sn ^{+ 2} ), zinc (Zn ^{+ 2} ), copper (Cu ⁺² ), aluminum (Al ⁺³ ), iron (Fe ⁺² , Fe ⁺³ ), strontium (Sr ⁺² ), calcium (Ca ⁺² ), barium (Ba ⁺² ), magnesium (Mg ^{+ 2} ) and manganese (Mn ⁺² ). The composition may also include a source of fluoride ion. The oral care compositions of the present invention can be formulated as single-phase or biphasic compositions. The present invention also provides a method for the effective delivery of tin (II) compositions, having minimal side effects of staining the teeth or astringent properties and providing effective control of tartar by administering to the subject a stable dentifrice composition containing a clinically effective amount of tin fluoride (II) and / or other salts of tin (II) in combination with an agent active on a mineral surface, preferably phosphate, phosphonate or carboxy won a polymer, and a source of multivalent cation.

These and other features, aspects, and advantages of the present invention will be apparent to those skilled in the art from the detailed description below.

DETAILED DESCRIPTION OF THE INVENTION

Although at the end of the description is a claim that specifically indicates and clearly states the invention, it is believed that the present invention can be better understood from the description below.

All percentages used herein are by weight of the dentifrice composition unless otherwise indicated. The ratios used here are molar ratios from the composition as a whole, unless otherwise indicated. All measurements were performed at 25 ° C, unless otherwise indicated.

As used herein, “comprising” means that other steps and other ingredients that do not affect the end result can be added. This term covers the terms "consisting of" and "essentially consisting of."

As used here, the word “include” and its variants should be considered as non-limiting, so the listing of the list items does not exclude other similar terms that can also be used in the materials, compositions, devices and methods of the present invention.

As used herein, the words “preferred,” “preferred,” and variations refer to embodiments of the invention that achieve certain beneficial effects in certain circumstances. However, other embodiments may also be preferred in the same or other circumstances. In addition, listing one or more preferred embodiments does not imply that other embodiments are not suitable and does not exclude other embodiments from the scope of the invention.

The oral composition of the present invention may be in the form of a toothpaste, dentifrice, tooth powder, topical gel for oral administration, a dental elixir, a denture care product, an oral aerosol care product, lozenges, tablets for oral cavity or chewing gum.

The term “dentifrice”, as used herein, means paste, gel or liquid formulations, unless otherwise indicated. The dentifrice composition may be of any desired shape, such as with inner strips, with superficial strips, multilayer, with the gel surrounding the paste, or any combination thereof.

The oral composition may be a single phase oral composition or may be a combination of two or more oral compositions, each in a separate phase. "One or a separate phase" means here that all the components of each composition are mixed together into one mixture, which may contain liquid, solid and gaseous components. Thus, each phase can be homogeneous or non-homogeneous. An oral care composition is a product that, in the normal course of administration, is not swallowed specifically for the systemic administration of specific therapeutic agents, but is retained in the oral cavity for a time sufficient to contact substantially all surfaces of the teeth and / or tissues of the oral cavity in order to exhibit activity in the oral cavity. The term "composition as a whole" as used here means the entire composition delivered to the oral cavity, regardless of whether it contains one phase or multiple phases.

If a two-phase oral composition is desired, each oral composition will be placed in a physically separate section of the metering device and dispensed in parallel. The term "dispensing device", as used here, means any pump, tube or container suitable for dispensing toothpaste.

The term “orally acceptable carrier,” as used herein, includes safe and effective materials for use in the compositions of the present invention. Such materials are conventional additives for oral care compositions, including, without limitation, fluoride ion sources, anticalculus or anti-tartar agents, buffers, abrasives such as silica, bleaching agents such as peroxide sources, bicarbonate alkali metal salts, thickeners, moisturizers, water, surfactants, titanium dioxide, flavoring system, sweeteners, xylitol, coloring agents and mixtures thereof.

In this description, the terms "hard deposits" and "tartar" are used interchangeably and refer to mineralized plaque biofilms.

The term “tin (II)” as used herein is used to mean tin (II) present in a dentifrice or other oral care product and coming from a source such as tin (II) salts, including tin fluoride (Ii) It may relate to tin (II) ions, the source of which is a tin (II) salt, other than tin (II) fluoride, added to stabilize.

Active and other ingredients suitable for use in this invention can be classified or described here by their cosmetic and / or therapeutic effect or by their intended mechanism of action or function. However, it should be understood that active and other ingredients suitable for use in the present invention can, in some cases, provide more than one cosmetic and / or therapeutic effect or function, or act on more than one mechanism. Thus, the classification is carried out here for convenience and should not limit the ingredient to the specifically indicated use or the listed uses.

The present invention relates to an oral composition containing a source of tin (II) ion, a source of polyvalent cations other than tin (II), and an agent active on a mineral surface, having a chelating activity on tin (II) and polyvalent cations, said compositions providing improved therapeutic efficacy of tin (II) with minimal side effects of staining on teeth and astringent properties. The “therapeutic efficacy of tin (II)” as used herein includes antimicrobial effects, controlling bad breath, controlling the growth and metabolism of plaque, reducing gingivitis, slowing down the development of periodontal disease, and decreasing dentinal hypersensitivity. The compositions preferably include a fluoride source, which may be tin (II) fluoride, other fluoride salts, or combinations thereof. Compositions simultaneously provide a decrease in education and the fight against supragingival calculus. Reducing stains on teeth and astringent properties can also be enhanced by the corresponding concomitant components of the composition, including the use of suitable poloxamer ingredients.

The mineral surface active agent (MSA) is preferably polymeric, in particular anionic polymers, such as polyphosphate with an average chain length of about 4 or more, polyphosphonate or other phosphate or phosphonate or carboxy-containing polymers. An ordinary person skilled in the art is able to suggest that a polymeric binding agent, such as polyphosphate with an average chain length of about 4 or more, will behave similarly to pyrophosphate or tripolyphosphate in tin (II) dentifrice systems. It was found that chemical bonding or chelation of tin (II) using pyrophosphate, diphosphonate or tripolyphosphate to prevent staining, also leads to an unacceptable loss of therapeutic potential. However, an unexpected result is observed for longer chain polyphosphates and other phosphate or phosphonate-containing polymers, since they can reduce the side effects of staining on the teeth and the astringent properties of the composition without significantly reducing the effectiveness of tin (II). Indeed, it has been found that the inclusion of these polymeric MSA in tin (II) salt-containing oral care compositions, such as tin (II) fluoride, provides significant therapeutic efficacy with reduced stain levels and astringent properties, while providing a reduction supragingival tartar compared with prior art compositions containing tin (II) fluoride or tin (II) fluoride with stabilizing agents such as citrate.

The oral care compositions of the present invention can be formulated as single-phase or two-phase compositions. One embodiment of the present invention provides a two-phase oral care composition comprising a first composition comprising a source of tin (II) ion and a source of polyvalent metal ions other than tin (II), preferably zinc, and a second composition containing MSA. The MSA in this embodiment may be a linear polyphosphate with an average chain length of about 4 or more. A polyphosphate-containing composition will preferably have a limited water content of up to about 20% to minimize hydrolysis of the polyphosphate.

Another embodiment of the present invention relates to a single phase oral care composition comprising a source of tin (II) ion, a source of polyvalent metal ions other than tin (II) and MSA, such as linear polyphosphate with an average chain length of about 4 or more. The single-phase composition is formulated so that the linear polyphosphate is stabilized against hydrolytic decomposition.

The present invention also relates to single-phase or biphasic compositions comprising a source of tin (II) ion, a source of polyvalent metal ions other than tin (II), and an anionic polymer with a molecular weight (MW) of 500 or more, containing one or a combination of phosphonate, diphosphonate and carboxy functionalities.

The invention also provides a method for the effective delivery of tin (II) containing compositions with minimal side effects of staining on the teeth or astringent properties and effective control of tartar by administering to the subject a stable dentifrice composition containing a clinically effective amount of tin fluoride ( II) and / or other salts of tin (II) in combination with a source of polyvalent metal ions other than tin (II) and active in relation to mineral surfaces and chelating agent Ohm, such as a phosphate or phosphonate-containing polymer. One way of delivering such an improved tin (II) oral composition is to use a dentifrice comprising two dentifrice compositions that are housed in physically separated sections. Another method involves administering to the subject a stable single-phase dentifrice composition. One embodiment of a stable single-phase composition includes polyphosphate or another phosphate or phosphonate-containing anionic polymer, tin (II) fluoride as a source of tin (II) ion, a zinc ion source, where the composition may have a low total water content, depending on stability requirements.

A preferred method for delivering the improved tin (II) containing compositions of the present invention involves the use of a dentifrice comprising two dentifrice compositions that are housed in physically separated sections. Physical separation provides sufficient stabilization of each phase of the dentifrice and its ingredients. After combining in use, the chemical interactions of tin (II) (from tin (II) fluoride and / or another tin (II) salt) from one phase of a dentifrice with MSA from a separate phase of a dentifrice ensure proper delivery of both ingredients, thereby creating a complete therapeutic activity while ensuring significant effectiveness in reducing the formation of tartar and with a significant reduction in undesirable side effects of staining on the teeth and astringent properties. The first dentifrice composition will include a tin (II) ion source, while the second dentifrice composition preferably contains polyphosphate or another anionic polymer or copolymer containing phosphate, phosphonate, carboxyl groups or mixtures thereof. A source of polyvalent cations other than tin (II) can be included in either of the first and second compositions, or both, depending on the interaction with other components.

The essential and optional components of the compositions of the present invention are described in the following paragraphs.

Sources of tin (II) ion

The present invention includes a source of tin (II) ion as one of the essential components. Tin (II) ions are formed from tin (II) fluoride and / or another tin (II) salt added to the oral composition. Tin (II) fluoride has been found to help reduce tooth decay, gingivitis, plaque and sensitivity and improves breathing. Tin (II) present in an oral composition will provide efficacy to a subject using the composition. Other salts of tin (II) include tin (II) chloride dihydrate, tin (II) acetate, tin (II) gluconate, tin (II) oxalate, tin (II) sulfate, tin (II) lactate and tin (II) tartrate. Preferred sources of tin (II) ion are tin (II) fluoride and tin (II) chloride dihydrate. The combined salts of tin (II) will be present in an amount of from about 0.05% to about 11%, by weight of the composition as a whole. Preferably, tin (II) salts are present in an amount of from about 0.1 to about 7%, more preferably from about 0.4% to about 3%. The compositions typically include levels of tin (II), tin fluoride generated (II) salts and other tin (II), ranging from about 3000 ppm (mn ^-1) to about 15,000 ppm stannous ion (II) in the whole composition.

Dental care products containing tin (II) salts, especially tin (II) fluoride and tin (II) chloride, are described in US Pat. No. 5,005,597 to Majeti et al. Other descriptions of tin (II) salts are given in US Pat. No. 5,578,293 issued to Prencipe et al. And US Pat. No. 5,282,410 to Lukacovic et al. In addition to the source of tin (II) ion, other ingredients necessary for stabilizing tin (II) may be included, such as those described in Majeti et al. and Prencipe et al.

Mineral Surface Active Agent (MSA)

The present invention includes a mineral surface active agent (MSA) that has tooth substantivity and also has chelating or binding activity to tin (II) and other polyvalent cations. The abbreviation "MSA" as used herein refers to such agents. The “mineral” descriptor indicates that the surface activity or substance of the surface-active agent is manifested in relation to mineral surfaces, such as calcium phosphate minerals or teeth. Preferred MSA are polymeric, in particular polymers containing anionic groups selected from phosphate, phosphonate, carboxyl and mixtures thereof. Such anionic functionalities provide the ability of these agents to interact with cationic or positively charged moieties.

These agents have the ability to bind tin (II), in particular by chelating a tin (II) ion, as evidenced by the release of ionic fluoride from tin (II) fluoride (SnF ₂ ) and the release of an increased amount of the ionic form of fluoride upon binding of tin (II) ) Effective agents also exhibit reactivity to the surfaces of minerals based on calcium phosphate, and therefore it is assumed that they will slow down the formation of tartar or solid deposits. Agents can also provide stain control, surface conditioning and erosion control effects. Ideally, these agents will bind tin (II), but still allow the combined mixture to provide the desired effects of combating tartar, staining and conditioning the surface, without adversely affecting the effectiveness of tin (II) fluoride in combating tooth decay, unpleasant odor from mouth and periodontal diseases, including gingivitis.

The binding or chelation of tin (II) MSA provides a means of stabilizing tin (II), especially in an aqueous environment where tin (II) can form tin (IV) compounds or can precipitate from solution, thereby reducing the amount of tin (II) ions available ) and, therefore, the effectiveness of the composition. For example, in US Pat. No. 5,017,363 to Suhonen, it is reported that tin (II) fluoride compositions are stabilized by a copolymer of alkyl vinyl ether and maleic anhydride or acid. It is reported that the copolymers are capable of forming chelates with a tin (II) ion, which are strong enough to prevent the oxidation of tin (II) or precipitation from solution.

In addition to binding or chelating tin (II), preferred polymeric MSAs will have a strong affinity for enamel surfaces and will deposit as a polymer layer or coating on the enamel surface and provide the desired surface protection and conditioning effects. Suitable examples of such polymers are polyelectrolytes, such as condensed phosphorylated polymers; polyphosphonates; copolymers of phosphate or phosphonate-containing monomers or polymers with other monomers, such as ethylenically unsaturated monomers and amino acids, or with other polymers, such as proteins, polypeptides, polysaccharides, poly (acrylate), poly (acrylamide), poly (methacrylate), poly (ethacrylate ), poly (hydroxyalkyl methacrylate), poly (vinyl alcohol), poly (maleic anhydride), poly (maleate) poly (amide), poly (ethyleneamine), poly (ethylene glycol), poly (propylene glycol), poly (vinyl acetate) and poly ( vinylbenzyl chloride); polycarboxylates and carboxy-substituted polymers; and mixtures thereof. Suitable polymeric agents active on the mineral surface include carboxy-substituted alcohol polymers described in US Pat. Nos. 5,292,501; 5213789, 5093170; 5,009,882; and 4939284; all in the name of Degenhardt et al .; diphosphonate-derivatized polymers in US Pat. No. 5,011,913 to Benedict et al .; and synthetic anionic polymers, including polyacrylates and copolymers of maleic anhydride or acid and methyl vinyl ether (e.g., Gantrez), as described, for example, in US Pat. No. 4,627,977 to Gaffar et al. A preferred polymer is diphosphonate-modified polyacrylic acid. Polymers with activity have sufficient ability to bind to the surface for desorption of pellicle proteins and fixation on enamel surfaces. For tooth surfaces, polymers with phosphate or phosphonate functions at the ends or in the side chains may all be preferred, although other polymers capable of binding to minerals may be effective depending on adsorption affinity.

Additional examples of suitable phosphonates containing polymeric MSA include geminal diphosphonate polymers disclosed as anticalculus agents in US Pat. No. 4,877,603 to Degenhardt et al .; phosphonate group copolymers disclosed in US 4,749,758 to Dursch et al. and GB 1290724 (both referred to by Hoechst) as being suitable for use in detergent and cleaning agent compositions; and copolymers and stelomeres disclosed as being suitable for use, including scale and corrosion inhibition, coatings, adhesives and ion exchange resins, in US 5,980,776, to Zakikhani et al., and to US 6071434, to Davis et al. Preferred polymers include water-soluble copolymers of vinylphosphonic acid and acrylic acid and its salts, disclosed in GB 1290724, where the copolymers contain from about 10% to about 90% wt. vinylphosphonic acid and from about 90% to about 10% wt. acrylic acid, more specifically, where the copolymers have a weight ratio of vinylphosphonic acid to acrylic acid of 70% vinylphosphonic acid to 30% acrylic acid; 50% vinylphosphonic acid to 50% acrylic acid; or 30% vinylphosphonic acid to 70% acrylic acid. Other preferred polymers include the water-soluble polymers disclosed by Zakikhani and Davis, obtained by copolymerization of diphosphonate or polyphosphonate monomers having one or more unsaturated C = C bonds (e.g. vinylidene-1,1-diphosphonic acid and 2- (hydroxyphosphinyl) ethylidene-1, 1-diphosphonic acid), with at least one additional compound having unsaturated C = C bonds (for example, acrylate and methacrylate monomers), such as having the following structure:

1. A copolymer of acrylic acid and 2- (hydroxyphosphinyl) ethylidene-1,1-diphosphonic acid, having the structure:

2. A copolymer of acrylic acid and vinyl diphosphonic acid having the structure:

Suitable polymers include diphosphonate / acrylate polymers sold by Rhodia under the brand name ITC 1087 (average molecular weight 3000-60000) and Polymer 1154 (average molecular weight 6000-55000).

Preferred MSAs will be stable with other components of the composition, such as ionic fluoride, and will not hydrolyze in high water compositions, thereby allowing the preparation of simple single-phase dentifrice or dental elixir compositions. If the MSAs do not have these stability properties, one option is to prepare a two-phase composition with MSAs that are physically separated from the incompatible component (s).

A preferred polymeric MSA is polyphosphate. It is generally understood that polyphosphate consists of two or more phosphate molecules located predominantly with a linear configuration, although some cyclic derivatives may be present. Polyphosphates with an average chain length of about four or more phosphate groups are particularly effective, so that surface adsorption at effective concentrations provides a sufficient number of unbound phosphate functions that increase the anionic surface charge and also enhance the hydrophilic nature of the surface. Pyrophosphates and tripolyphosphates are discussed separately in the section on additional anticalculus agents. Longer chain polyphosphate salts include, but are not limited to, tetrapolyphosphate and hexametaphosphate. Polyphosphates larger than tetrapolyphosphate usually have the form of amorphous glassy materials. Examples of suitable polyphosphates are linear "glassy" polyphosphates having the formula:

where X is sodium, potassium or ammonium and n is on average from about 6 to about 125. Polyphosphates manufactured by FMC Corporation, commercially known as Sodaphos (n = 6), Hexaphos (n = 13) and Glass H (n = 21). The most preferred polyphosphate is Glass H. These polyphosphates can be used alone or in combination.

Polyphosphates with an average chain length of greater than about 4 are known to react with ionic fluoride in oral care compositions at ambient temperature to form monofluorophosphate ions, in addition to changing the pH of the compositions. This reaction impairs the effectiveness of the oral composition and its ability to provide stable ionic fluoride and polyphosphate to the surfaces of the oral cavity. Polyphosphates are also known to undergo hydrolysis. Thus, the preparation of compositions with such polyphosphates is faced with certain problems. One way to stabilize polyphosphate against hydrolysis and / or interaction with incompatible ingredients is to reduce the total water content of dentifrice compositions. US patent 5939052, issued in the name of White, Jr. et al., further describes polyphosphates. Phosphate sources are also described in more detail in Kirk-Othmer Encyclopedia of Chemical Technology, Fourth Edition, Volume 18, Wiley-Interscience Publishers (1996).

For compositions containing a condensed polyphosphate having an average of 21 phosphate repeating units, it was found that the ideal ratio of the total number of moles of the phosphate anion to the total number of moles of the tin (II) ion corresponds to a molar ratio of phosphate anion to tin (II) of about 0, 2: 1 to about 5: 1, preferably from about 0.5: 1 to about 3: 1, more preferably from about 0.6: 1 to about 2: 1, and most preferably from about 0.7: 1 to about 1: 1.

Other polyphosphorylated compounds can be used as an MSA / chelating agent in addition to or instead of polyphosphate, in particular polyphosphorylated inositol compounds such as phytic acid, myoinositol pentakis (dihydrogen phosphate); myoinositide tetrakis (dihydrogen phosphate), myoinositrite (dihydrogen phosphate) and their salts of alkali metals, alkaline earth metals or ammonium. Preferred in the present invention are phytic acid, also known as myoinositol-1,2,3,4,5,6-hexakis (dihydrogen phosphate) or inositol hexaphosphoric acid and its salts of alkali metals, alkaline earth metals or ammonium. As used herein, the term “phytate” includes phytic acid and its salts, as well as other polyphosphorylated inositol compounds.

Other non-polymer MSAs that can be used are chelating materials proposed in the literature to slow the formation of tartar and remove tartar after its formation. The chemical approach to tartar inhibition generally involves chelation of calcium ion and / or inhibition of crystal growth, which prevents the formation of tartar and / or destroys the formed tartar by removing calcium. These chemical chelating agents are described in more detail below in the section Anticalculus agents.

The required amount of MSA is an amount that effectively binds tin (II), provides sufficient antimicrobial activity, reduces stain on the teeth and the astringency of the composition, and can reduce the formation of tartar. An effective amount of MSA will typically be from about 0.05% to about 35%, preferably from about 1% to about 30%, more preferably from about 5% to about 25%, and most preferably from about 6% to about 20% of the total weight of the oral composition.

In addition to the effective binding of tin (II) ions, some MSA / chelating agents have been found to be suitable as solubilizing agents for the insoluble components of the composition. For example, it was found that Glass H polyphosphate solubilizes insoluble tin (II) salts, as well as tin (II) oxides and hydroxides.

Source of Polyvalent Cation

The compositions of the present invention preferably include a source of polyvalent cations other than tin (II), including inorganic ions such as zinc (Zn ⁺² ), copper (Cu ⁺² ), aluminum (Al ⁺³ ), iron (Fe ⁺² , Fe ⁺³ ), strontium (Sr ⁺² ), calcium (Ca ⁺² ), barium (Ba ⁺² ), magnesium (Mg ⁺² ) and manganese (Mn ⁺² ). Such polyvalent cations compete with tin (II) for the MSA / chelating agent included in the compositions for stabilizing tin (II) by binding or chelation. It has been found that although chelation is effective for stabilizing tin (II), such chemically stabilized tin (II) ions can have very limited bioavailability and thus reduced therapeutic efficacy. Due to the presence of competing cations in the same system with tin (II), it is possible to avoid excessive stabilization of tin (II) with a chelating agent, which leads to the availability of tin (II) when exchanged with competing cation (s). The inclusion of the second polyvalent cation, thus, allows the use of chelating agents, such as low molecular weight diphosphonates, pyrophosphates and tripolyphosphates, capable of chelating tin (II), but tending to reduce the therapeutic efficacy of tin (II).

The source of the polyvalent cation is typically present in an amount sufficient to create a molar ratio of the polyvalent cation to tin (II) equal to preferably 1: 1 or more. This provides a sufficient concentration of another polyvalent cation competing with tin (II) for MSA. The level of other polyvalent cations, of course, also depends on secondary considerations, such as aesthetic characteristics and stability of the compositions, and may be lower than the preferred ratio of 1: 1. Preferred polyvalent cations are inorganic cations formed from salts such as nitrate, chloride, fluoride, phosphate, pyrophosphate, polyphosphate, sulfate, carbonate, citrate, lactate and oxalate, or from oxides or hydroxides. The source of the polyvalent cation may be water soluble, sparingly soluble or insoluble.

In a preferred embodiment, the composition comprises tin (II) fluoride as a source of tin (II), a zinc salt as a source of zinc ions, and polyphosphate as an MSA / chelating agent. The composition may be formulated as a single phase product or a two phase product with tin (II) fluoride and a zinc salt in the first composition and polyphosphate MSA in the second composition. In another embodiment of the biphasic composition, the second composition comprises a copolymer of maleic anhydride or acid and methyl vinyl ether (Gantrez) as MSA. In these embodiments, the preferred molar ratio of zinc ions to tin (II) ions varies from about 0.5: 1 to about 5: 1.

In another embodiment, the composition, which may be single-phase or biphasic, contains a calcium salt as a source of calcium ions, tin (II) fluoride as a source of tin (II) and fluoride and, as MSA, a polyphosphate, a copolymer of maleic anhydride or acid and methyl vinyl ether or mixtures thereof. The biphasic composition contains tin (II) fluoride in the first composition and calcium chloride and MSA in the second composition.

Orally acceptable carrier materials

In preparing the compositions of the present invention, it is desirable to add one or more carrier materials or excipients to the compositions. Such materials are well known to those skilled in the art and can be easily selected by one of ordinary skill in the art based on the physical, aesthetic and functional properties desired for the compositions to be prepared. These carriers may be included in amounts of typically from about 50% to about 99%, preferably from about 70% to about 98%, and more preferably from about 90% to about 95%, by weight of the oral composition. Examples of such optional media are described in the following paragraphs.

Total water content

The water used to make commercially available oral care compositions should preferably have a low ion content and no organic impurities. In an oral composition, water may comprise from 0% to about 95%, preferably from about 5% to about 50%, by weight of the composition of the present invention. This water content may be present in the single-phase oral composition or may be the total total water content of the two-phase oral composition. If the oral composition contains a polyphosphate with an average chain length of about 4 or more, the composition or phase containing the polyphosphate will have a lower water content, typically up to about 20% of the total water. Preferably, the total water content is from about 2% to about 20%, more preferably from about 4% to about 15%, and most preferably from about 5% to about 12% by weight of the oral composition. The amount of water includes free water, which is added to the composition, plus water, which is added with other materials, such as sorbitol, silicon dioxide, surfactant solutions, and / or dye solutions.

Buffer agent

The compositions of the present invention may contain a buffering agent. Buffer agents, as used herein, refer to agents that can be used to adjust the pH of the compositions in the range of from about pH 3.0 to about pH 10. The phase of the oral composition containing tin (II) will typically be have a suspension pH of from about 3.0 to about 7.0, preferably from about 3.25 to about 6.0, more preferably from about 3.5 to about 5.5. The phase containing the MSA / chelating agent will typically have a suspension pH of from about 4.0 to about 10, preferably from about 4.5 to about 8, and more preferably from about 5.0 to about 7.0. An oral composition containing both tin (II) and an MSA / chelating agent in one phase 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.

Suitable buffering agents include alkali metal hydroxides, carbonates, sesquicarbonates, borates, silicates, phosphates, imidazole, and mixtures thereof. Specific buffering agents include monosodium phosphate, trisodium phosphate, sodium benzoate, benzoic acid, sodium hydroxide, potassium hydroxide, carbonate salts of alkali metals, sodium carbonate, imidazole, pyrophosphate salts, citric acid and sodium citrate.

Preferred buffers are those that allow you to control the pH in the desired range without complexing with tin (II) ions. Preferred buffering agents include acetic acid, sodium acetate, citric acid, sodium citrate, benzoic acid and sodium benzoate. Buffer agents are used in amounts of from about 0.1% to about 30%, preferably from about 1% to about 10%, and more preferably from about 1.5% to about 3% by weight of the composition of the present invention.

Sources of fluoride ion

The oral compositions of the present invention will optionally include a soluble fluoride source capable of releasing bioavailable and effective fluoride ions. Soluble sources of fluoride ion include sodium fluoride, tin (II) fluoride, indium fluoride, amine fluoride and sodium monofluorophosphate. Tin (II) fluoride is the preferred soluble fluoride source. This ingredient can serve as a source of tin (II), as well as a source of fluoride. Norris et al., US Pat. No. 2,946,725, issued July 26, 1960, and Widder et al., US Pat. No. 3,678,154, issued July 18, 1972, disclose such sources of fluoride, as well as others.

The present compositions may contain a soluble fluoride ion source capable of providing from about 50 ppm (mn ^-1) to about 3500 ppm, and preferably from about 500 ppm to about 3000 ppm of free fluoride ions. To deliver the desired amount of fluoride ions, fluoride ion sources may be present in the oral composition in an amount of from about 0.1% to about 5%, preferably from about 0.2% to about 1%, and more preferably from about 0.3% to about 0.6%, of the total weight of the composition delivered to the oral cavity.

Anticalculus agent

Materials known as effectively reducing the deposition of minerals associated with the formation of tartar can also be used here as an MSA / chelating agent or stabilizer for tin (II). Chelating agents are capable of complexing with calcium present in bacterial cell membranes and can also destroy plaque by removing calcium from calcium bridges to help keep this biomass intact. However, it is undesirable to use a chelating agent that has too high an affinity for calcium, as this can lead to demineralization of the teeth, which is contrary to the objectives and idea of the present invention. Suitable chelating agents will typically have a calcium binding constant of about 10 to 10 to provide improved cleaning with reduced plaque and tartar formation. Chelating agents also have the ability to form complexes with metal ions and, thus, can be used to stabilize tin (II).

Such chelating agents useful due to their anticalculus activity include pyrophosphates, tripolyphosphates and diphosphonates such as EHDP and AHP. Pyrophosphate salts suitable for use as a source of pyrophosphate ion in the compositions of the present invention include disubstituted alkali metal pyrophosphate salts, tetrasubstituted alkali metal pyrophosphate salts and mixtures thereof. Disodium dihydropyrophosphate (Na ₂ H ₂ P ₂ O ₇ ), tetrasodium pyrophosphate (Na ₄ P ₂ O ₇ ) and tetracal pyrophosphate (K ₄ P ₂ O ₇ ) in their unhydrated as well as hydrated forms are preferred materials. In the compositions of the present invention, the pyrophosphate salt can be present in one of three ways: predominantly dissolved, predominantly insoluble, or a mixture of dissolved and insoluble pyrophosphate.

Compositions containing predominantly dissolved pyrophosphate relate to compositions in which at least one source of pyrophosphate ion is present in an amount sufficient to provide at least about 1.0% free pyrophosphate ions. The amount of free pyrophosphate ions can be from about 1% to about 15%, from about 1.5% to about 10%, in one embodiment, and from about 2% to about 6% in another embodiment. Free pyrophosphate ions may be present in various protonated states, depending on the pH of the compositions.

Compositions containing predominantly undissolved pyrophosphate relate to compositions containing not more than about 20% of the total amount of pyrophosphate salt dissolved in the composition, preferably less than about 10% of the total amount of pyrophosphate dissolved in the composition. The tetrasodium pyrophosphate salt is the preferred pyrophosphate salt in these compositions. Tetrasodium pyrophosphate may be an anhydrous salt form or a decahydrate form or any other materials stable in solid form in dentifrice compositions. The salt is in the form of solid particles, which may be in a crystalline and / or amorphous state, the particle size of the salt being preferably small enough to provide aesthetic acceptability and good solubility in use. The amount of pyrophosphate salt suitable in the manufacture of these compositions is any amount effective for controlling tartar, typically from about 1.5% to about 15%, preferably from about 2% to about 10%, and most preferably from about 3% to about 8%, by weight of the composition of the dentifrice.

The composition may also include a mixture of dissolved and undissolved pyrophosphate salts. Any of the above pyrophosphate salts may be used.

Pyrophosphate salts are described in more detail in Kirk-Othmer Encyclopedia of Chemical Technology, Third Edition, Volume 17, Wiley-Interscience Publishers (1982).

Other examples of chelating agents used as an anticalculus agent include ethylenediaminetetraacetic acid, nitrilotriacetic acid, and related compounds disclosed in British Patent 490384, February 15, 1937; polyphosphonates in US Pat. No. 3,368,154, July 18, 1972, to Widder et al., US Patent No. 5,338,537, issued August 16, 1994, to White, Jr., and US Patent No. 5,451,401, issued September 19, 1995. , in the name of Zerby et al .; carbonyl diphosphonates in US patent No. 3737533, June 5, 1973, in the name of Francis; a zinc-polymer combination obtained by reacting or reacting a zinc compound with an anionic polymer containing carboxylic, sulfonic and / or phosphonic acid radicals in US Pat. No. 4,138,477 issued February 6, 1979 to Gaffar; tartaric acid in US patent No. 5849271 issued December 15, 1998, and 5622689, issued April 22, 1997, both in the name of Lukacovic; the acid or salt form of monosuccinate tartrate, disuccinate tartrate, and mixtures thereof in US Pat. No. 5,015,467, issued May 14, 1991, to Smitherman; a polymer or copolymer of acrylic acid in US patent No. 4847070, July 11, 1989, in the name of Pyrz et al., and in US patent No. 46661341, April 28, 1987, in the name of Benedict et al .; sodium alginate in US patent No. 4775525, issued October 4, 1988, in the name of Pera; polyvinylpyrrolidone in GB 741315, published November 30, 1955, WO 99/12517, published March 18, 1999, and US patent No. 5538714, issued July 23, 1996, addressed to Pink et al .; and vinylpyrrolidone-carboxylate copolymers in US Patent No. 5670138, issued September 23, 1997, to Venema et al., and in JP Publication No. 2000-0633250, to Lion Corporation, published February 29, 2000. Other chelating agents which can be used as anticalculus agents, include gluconic acid, tartaric acid, citric acid and their pharmaceutically acceptable salts. Examples include gluconate and sodium or potassium citrate; a combination of citric acid / alkali metal citrate; zinc citrate trihydrate; disodium tartrate; dipotassium tartrate; sodium potassium tartrate; acidic sodium tartrate; potassium tartrate. The amount of such chelating agents suitable for use in the present invention is from about 0.1% to about 2.5%, preferably from about 0.5% to about 2.5%, and more preferably from about 1.0 % to about 2.5%.

Other anticalculus agents suitable for use in the present invention are the polymeric polycarboxylates disclosed in US Pat. No. 4,138,477, February 6, 1979, and US Pat. No. 4,183,914, January 15, 1980, to Gaffar et al., And include maleic copolymers anhydride or acid with another polymerizable ethylenically unsaturated monomer such as methyl vinyl ether (methoxyethylene), styrene, isobutylene or ethyl vinyl ether. Such materials are well known to those skilled in the art and are used in the form of free acids or partially or preferably completely neutralized, water-soluble salts of alkali metals (e.g., potassium and, preferably, sodium) or ammonium. Examples are copolymers of maleic anhydride with methyl vinyl ether in a ratio of from 1: 4 to 4: 1, having a molecular weight (MW) of from about 30,000 to about 1,000,000. These copolymers are available, for example, under the name Gantrez AN 139 (MW 500000), AN 119 (MW 250,000) and S-97 Pharmaceutical Grade (MW 70,000), from GAF Chemicals Corporation.

Other suitable polymeric polycarboxylates include 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or ethylene, the latter of which is available, for example, under the names Monsanto EMA No. 1103, 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.

Abrasive polishing materials

Abrasive polishing materials may also be included in oral compositions. Abrasive polishing material suitable for use in the compositions of the present invention may be any material that does not cause excessive dentin abrasion. Additionally, the abrasive polishing material must be incorporated into the oral composition so that it does not impair the stability of tin (II) or fluoride. For example, in a two-phase oral composition, the abrasive polishing material is preferably in a separate phase from the source of the fluoride ion and the source of the tin (II) ion.

Typical abrasive polishing materials include silicon dioxide, including gels and precipitates; aluminum oxides; phosphates, including orthophosphates, polymetaphosphates and pyrophosphates; and mixtures thereof. Specific examples include dicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate, insoluble sodium polymetaphosphate, hydrated alumina, calcium beta-pyrophosphate, calcium carbonate and resinous abrasives such as dispersed urea condensates and other formaldehyde, et al. US Pat. No. 3,070,510, issued December 25, 1962. Abrasive mixtures may also be used. If the oral composition or the specific phase comprises a polyphosphate with an average chain length of about 4 or more, calcium abrasives and alumina are not preferred abrasives. The most preferred abrasive is silica.

Various types of silica-based tooth abrasives are preferred due to their unique effects of exceptionally good toothbrushing and polishing properties without excessive abrasion of tooth enamel or dentin. The silica abrasive polishing materials of the present invention, as well as other abrasives, typically have an average particle size in the range of from about 0.1 to about 30 microns, and preferably from about 5 to about 15 microns. The abrasive may be precipitated silica or silica gels, such as silica xerogels described by Pader et al., US Pat. No. 3,538,230, issued March 2, 1970, and DiGiulio, US Pat. No. 3,862,307, issued January 21, 1975. Xerogels are preferred. silica marketed under the brand name "Syloid" by WR Grace & Company, Davison Chemical Division, also preferred precipitated silica-based materials, such as those marketed by J.M. Huber Corporation under the trademark "Zeodent", especially silica under the name "Zeodent 119". The types of silica-based dental abrasives suitable for use in the toothpastes of the present invention are described in more detail. Wason, US Pat. No. 4,340,583, issued July 29, 1982. Other suitable silica-based abrasives are described by Rice, US Pat. 5,604,920; 5,651,958; 5,658,553; 5716601, and White, Jr., et al., US Pat. No. 6,740,311. The abrasive in the oral composition described herein is typically present in amounts of about 6% to about 70% by weight of the composition. Preferably, the oral composition contains from about 10% to about 50% abrasive, based on the weight of the oral composition.

Peroxide source

The compositions of the present invention may include a source of peroxide. The peroxide source is selected from the group consisting of hydrogen peroxide, calcium peroxide, urea peroxide and mixtures thereof. A preferred source of peroxide is calcium peroxide. Preferably, to increase stability, the source of peroxide is in different phases with the source of tin (II) ions. The following amounts represent the amount of peroxide raw material, although the peroxide source may contain ingredients other than the peroxide raw material. The composition of the present invention may contain from about 0.01% to about 10%, preferably from about 0.1% to about 5%, more preferably from about 0.2% to about 3%, and most preferably from about 0.3% to about 0.8% of the peroxide source, based on the weight of the oral composition.

Alkali metal bicarbonate salt

The present invention may also include an alkali metal bicarbonate salt. Bicarbonate salts of alkali metals are soluble in water and, not being stabilized, tend to release carbon dioxide in the aqueous system. Sodium bicarbonate, also known as baking soda, is the preferred alkali metal bicarbonate salt. The alkali metal bicarbonate salt also serves as a buffering agent. Due to the pH at which bicarbonate salts of alkali metals exhibit buffering properties, the bicarbonate salt is preferably in a phase separate from the source of tin (II) ion. The composition of the present invention may contain from about 0.5% to about 50%, preferably from about 0.5% to about 30%, more preferably from about 2% to about 20%, and most preferably from about 5% up to about 18% alkali metal bicarbonate salt, based on the weight of the oral composition.

Additional media

The compositions of the present invention are in the form of toothpastes, dentifrices, topical gels, oral elixirs, denture care products, oral care aerosols, lozenges, oral tablets or chewing gums and typically contain a certain amount of thickener or binders to provide the desired consistency. The amount and type of thickener will depend on the shape of the product. Preferred thickeners are carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose and water soluble salts of cellulose ethers such as carboxymethyl cellulose sodium and hydroxyethyl cellulose sodium. Natural resins such as karaya gum, xanthan gum, gum arabic and tragacanth gum can also be used. Colloidal magnesium aluminum silicate or finely divided silica can be used as a thickener component to further improve texture. Thickeners can be used in an amount of from about 0.1% to about 15%, by weight of the oral composition.

Another optional component of the compositions desirable for the present invention is a humectant. A humectant is used to prevent the curing of oral care compositions in contact with air, and some humectants may also impart a desirable sweet taste to toothpaste compositions. Suitable humectants for use in the invention include glycerin, sorbitol, polyethylene glycol, propylene glycol, xylitol and other edible polyhydric alcohols.

A humectant typically comprises from about 0% to 70%, preferably from about 15% to 55%, by weight of the oral composition.

The compositions of the present invention may also include surfactants, also commonly referred to as blowing agents. Suitable surfactants are those that are sufficiently stable and foam over a wide range of pH values. The surfactant may be anionic, nonionic, amphoteric, zwitterionic, cationic, or mixtures thereof. Anionic surfactants suitable for use in the present invention include water-soluble salts of alkyl sulfates containing from 8 to 20 carbon atoms in an alkyl radical (e.g. sodium alkyl sulfate) and water-soluble salts of sulfonated fatty acid monoglycerides containing from 8 to 20 carbon atoms. Sodium lauryl sulfate and the sodium salts of coconut oil fatty acid monoglyceride sulfonates are examples of this type of anionic surfactants. Other suitable anionic surfactants are sarcosinates, such as sodium lauroyl sarcosinate, taurates, sodium lauryl sulfoacetate, sodium lauroyl isethionate, sodium laureth carboxylate and sodium dodecylbenzenesulfonate. Mixtures of anionic surfactants may also be used. Many suitable anionic surfactants are disclosed by Agricola et al., US Pat. No. 3,959,458, issued May 25, 1976. Nonionic surfactants that can be used in the compositions of the present invention can be generally defined as compounds obtained by condensation of alkylene oxide groups (hydrophilic in nature) with organic hydrophobic compounds, which may be aliphatic or alkyl aromatic in nature. Examples of suitable non-ionic surfactants include poloxamers (sold under the Pluronic trademark), polyoxyethylene, polyoxyethylene sorbitan esters (sold under the Tweens trademark), Polyoxyl 40 hydrogenated castor oil, fatty alcohol ethoxylates, condensates of polyethylene oxide with alkyl phenols, resulting products condensation of ethylene oxide with the reaction product of propylene oxide and ethylene diamine, condensates of ethylene oxide with aliphatic alcohols, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides and mixtures of such materials. The non-ionic surfactant poloxamer 407 is one of the most preferred surfactants since it has been found that poloxamer helps reduce the astringent properties of tin (II). Amphoteric surfactants suitable for use in the present invention can be generally described as derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be linear or branched and where one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic water solubilizing group, for example, a carboxylate, sulfonate, sulfate, phosphate or phosphonate. Other suitable amphoteric surfactants are betaines, in particular cocamidopropyl betaine. Mixtures of amphoteric surfactants may also be used. Many suitable non-ionic and amphoteric surfactants are disclosed by Gieske et al., US Pat. No. 4,051,234, issued September 27, 1977. The composition of the present invention typically contains one or more surfactants, each in an amount of from about 0.25% to about 12%, preferably from about 0.5% to about 8%, and most preferably, from about 1% to about 6%, by weight of the composition.

Titanium dioxide may also be added to the composition of the present invention. Titanium dioxide is a white powder that gives the compositions opacity. Titanium dioxide typically ranges from about 0.25% to about 5%, by weight of the composition.

Coloring agents can also be added to the composition of the present invention. The coloring agent may be in the form of an aqueous solution, preferably 1% coloring agent in the form of a solution in water. Dye solutions typically comprise from about 0.01% to about 5%, by weight of the composition.

A flavoring system may also be added to the composition. Suitable flavoring components include wintergreen oil, peppermint oil, spearmint oil, clove flower bud oil, menthol, anethole, methyl salicylate, eucalyptol, cassia, 1-methyl acetate, sage, eugenol, parsley oil, oxanone, alpha irisone, lemon, orange, propenyl guaethol, cinnamon, vanillin, ethyl vanillin, heliotropin, 4-cis-heptenal, diacetyl, methyl para-tert-butyl phenyl acetate and mixtures thereof. Substances that create a feeling of cold can also be part of the flavor system. Preferred cold-sensing substances in the compositions of the present invention are paramentanocarboxyamide agents, such as N-ethyl-p-menthane-3-carboxamide (commercially known as "WS-3") and mixtures thereof. The flavoring system is typically used in compositions in amounts of from about 0.001% to about 5%, by weight of the composition.

Sweeteners may be added to the composition. These include saccharin, dextrose, sucrose, lactose, xylitol, maltose, levulose, aspartame, sodium cyclamate, D-tryptophan, dihydrochalcones, acesulfame and mixtures thereof. Various coloring agents may also be included in the present invention. Sweeteners and coloring agents are typically used in toothpastes in amounts of from about 0.005% to about 5%, by weight of the composition.

The present invention may also include other agents in addition to tin (II) to provide an antimicrobial effect. These agents may be included in amounts that do not interfere with the interaction between tin (II) and MSA. Such antimicrobial agents include water-insoluble non-cationic antimicrobial agents, such as halogenated diphenyl ethers, phenolic compounds, including phenol and its homologues, mono- and polyalkyl and aromatic halogen phenols, resorcinol and its derivatives, bisphenol compounds and halogenated salicylanilides, benzenes and benzoides . Water-soluble antimicrobial agents include, but are not limited to, quaternary ammonium salts and bis-biguanide salts. Triclosan monophosphate is an additional water-soluble antimicrobial agent. Quaternary ammonium nitric agents include compounds in which one or two of the substituents on the quaternary nitrogen atom has a carbon chain (typically alkyl group) length of from about 8 to about 20, typically from about 10 to about 18 carbon atoms, while the rest substituents (typically an alkyl or benzyl group) contain fewer carbon atoms, such as from about 1 to about 7 carbon atoms, typically a methyl or ethyl group. Dodecyltrimethylammonium bromide, tetradecylpyridinium chloride, domiphene bromide, N-tetradecyl-4-ethylpyridinium chloride, dodecyldimethyl- (2-phenoxyethyl) ammonium bromide, benzyl dimethylstearylammonium chloride, cetylpyridinium-2-chloride-2-chloridin-2-chloridin-2-benzylinidinium 5-methylhexahydropyrimidine, benzalkonium chloride, benzetonium chloride and methylbenzetonium chloride are examples of typical quaternary ammonium antibacterial agents. Other compounds are bis [4- (R-amino) -1-pyridinium] alkanes disclosed in US Pat. No. 4,206,215, issued June 3, 1980, to Bailey. Other antimicrobial agents may also be included, such as copper bisglycinate, copper glycinate, zinc citrate and zinc lactate. Also suitable are enzymes, including endoglycosidase, papain, dextranase, mutanase, and mixtures thereof. Such agents are disclosed in US Pat. No. 2,946,725, July 26, 1960, in the name of Norris et al., And in US Pat. No. 4,051,234, in the name of Gieske et al. Specific antimicrobial agents include chlorhexidine, triclosan, triclosan monophosphate, and extraction essential oils such as thymol. Triclosan and other agents of this type are disclosed in US Pat. No. 5,015,466 to Parran, Jr. et al. and US Pat. No. 4,894,220 to Nabi et al. If there are two phases, then water-insoluble antimicrobial agents, water-soluble agents and enzymes may be present in any of the first or second oral compositions. These agents may be present in amounts of from about 0.01% to about 1.5%, by weight of the oral composition.

The dentifrice composition may be a paste, gel, or any configuration or combination thereof. If a biphasic dentifrice is desired, then the first and second dentifrice compositions will be physically separated in the metering device of the dentifrice. It is usually preferred that the first dentifrice composition be a paste and the second dentifrice a gel composition. The dispensing device may be a tube, pump or any other container suitable for dispensing toothpaste. Two-section packages suitable for this purpose are described in US Pat. No. 4,528,180; U.S. Patent 4,687,663; and 4849213, all in the name of Shaeffer. The dispenser will dispense approximately equal portions of each dentifrice composition through the opening. The compositions may be mixed with each other after dosing. Alternatively, the oral care composition may be delivered from a kit containing two separate dispensing devices that are used to deliver two dental care compositions that are used simultaneously.

Performance measurement

The overall effectiveness of the compositions of the present invention can be determined using the ratio of the indicator of effectiveness / rate of staining, where the effectiveness is measured using the in vitro model of glycolysis and re-growth of plaque (i-PGRM) and staining is measured using the in vitro model of staining from Pellicle tea (i-PTSM). The compositions of the present invention provide a ratio of efficacy to stain of at least 1, 2, which represents a practical improvement in maintaining sufficient therapeutic efficacy while achieving reduced staining. An improvement in the astringent properties of a composition is defined as an increase of more than 50% in the organoleptic parameters of the composition, such as dry mouth and mouth feel, as determined by random consumer testing. The effectiveness of the fight against supragingival calculus is determined by the activity of preventing calcification of plaque using a modified analysis of the growth and mineralization of plaque.

Antimicrobial activity

The concentration and bioavailability of tin (II) ions, necessary to provide a therapeutic effect, may vary for different types of clinical action, for example, to combat caries or gingivitis. However, it is critical to establish a minimum level of antimicrobial activity, since the therapeutic activity of tin (II) may drop below this level. It is especially important to maintain efficacy in compositions in which tin (II) binding occurs, since tin (II) binding can easily lead to a loss of antimicrobial activity. In this description, the minimum efficiency created by the source of tin (II) ion is determined by the effect of creating a metabolic inhibition of bacterial plaque biofilms responsible for numerous undesirable oral conditions. Efficiency is thus determined by the marked and significant decrease in in situ plaque metabolism measured using the in vitro glycolysis and plaque re-growth model (i-PGRM) developed in our laboratories. It has been demonstrated that i-PGRM provides an excellent correlation with the bioavailability of tin (II) fluoride, necessary to create clinical antimicrobial activity and anti-gingivitis and plaque activity of tin (II) fluoride oral compositions. The efficacy of tin (II) containing compositions against gingivitis can be directly compared with a tin (II) containing dentifrice composition, such as described in US 5004597, to Majeti et al., Or a commercially available care product for teeth Crest Gum Care containing tin (II) fluoride.

i-PGRM is a technique in which plaque is grown from human saliva and treated with agents that create different levels of antimicrobial activity. The aim of this technique is to provide a simple and quick way to determine whether compounds have a direct effect on the metabolic pathways used by microorganisms to produce toxins that adversely affect gum health. In particular, the model focuses on the production of organic acids, including lactic, acetic, propionic and butyric. This method uses plaque grown on polished glass rods, which are dipped in saliva during the night, soy broth and sucrose for 6 hours, and again in saliva during the night. A plaque mass grown on glass rods is then treated for 1 minute with a suspension containing water and a dentifrice in a ratio of 3: 1. The mass is then placed in soy broth / sucrose solution for 6 hours and the pH of the incubation solution is measured after 6 hours. Thus, measured pH values are obtained before incubation and pH after incubation for the test compositions and controls. This test is typically performed with a series of parallel experiments to minimize experimental discrepancies and the average pH is calculated from parallel measurements. Due to their strong reactivity with saccharolytic organisms, compositions containing high levels of bioavailable tin (II) create significant inhibition of plaque acid formation in the i-PGRM assay. This makes it relatively easy to compare the variations of the compositions in terms of stability and bioavailability of tin (II).

Tin (II) fluoride and / or other tin (II) salts are present in the oral compositions described herein in an effective amount to provide the desired i-PGRM. The desired i-PGRM is measured in comparison with tin (II) free formulations (negative control) and tin (II) free formulations (positive control), such as those described in US 5004597, to Majeti et al. The most preferred i-PGRM scores differ significantly from the placebo controls and are ideally similar to those created with conventional tin (II) fluoride compositions that have proven plaque and gingivitis reduction effectiveness. Studies have shown that anti-gingivitis effectiveness can be expected for compositions providing at least about 60%, preferably at least about 70%, and more preferably at least about 80% of an effective tin (II) -containing care product teeth, such as in Example II, Comparative example below.

The i-PGRM is calculated by the formula:

Average pH values refer to the pH of the incubation medium obtained after treatment and control of sucrose. Tin plaque control samples without tin (II) produce large amounts of acid, and therefore their pH is lower than plaque samples treated with a positive control (stabilized dentifrice with tin (II) fluoride, as described in Example II, Comparative example). The effectiveness of a composition prepared from a combination of a tin (II) ion source and MSA will ideally be comparable to a tin (II) containing control, and therefore the ideal i-PGRM should be close to 100%.

Stain reduction

Staining of teeth is a common undesirable side effect of the use of tin (II) fluoride compositions. The improved tin (II) fluoride dentifrice agents described herein provide reduced stain formation due to more efficient delivery of tin (II) from tin (II) associated with MSA. Stain formation on the surface of teeth, typically caused by tin (II), is measured in a clinical setting using a stain index such as the Lobene or Meckel indices described in the literature. An in vitro stain model has also been developed that provides a quantitative assessment of the stain potential of a tin (II) fluoride composition, which correlates well with clinical observations. Thus, the compositions can be tested before conducting clinical trials using these methods.

The in vitro Pellicule Tea Stain Model (i-PTSM) is a technique in which the in vitro plaque biomass is grown on glass rods from pooled human saliva for three days. Plaque biomass is treated with supernatants of a 3: 1 mixture of water and dentifrices from which the abrasive and insoluble solids were removed by centrifugation to determine potential levels of staining on the teeth for various agents. The purpose of this technique is to provide a simple and quick way to determine whether compounds have a direct effect on the number of stains on the teeth. This method uses plaque grown on polished glass rods from a pool of human saliva, with a duration of each treatment of 5 minutes, followed by 10-minute treatment with tea. The treatment procedure is repeated at least three times, after which the mass of plaque is hydrolyzed to remove from the rods, filtered and absorbance measured at 380 nm. This test is usually carried out with a series of parallel experiments to minimize experimental discrepancies and the average absorption value is calculated from the results of parallel experiments.

It has been found that stain formation, typically caused by effective agents with tin (II) fluoride, is reduced by combining tin (II) fluoride with one or a mixture of MSA described above. The beneficial effect of reducing staining caused by tin (II) is achieved by the compositions of the present invention without significantly compromising the effectiveness of tin (II), fluoride and MSA. The amount of stains formed by the oral care compositions of the present invention is significantly less than the number of stains formed by using typical tin (II) dentifrice products. The term "reduced", as used here, means a statistically significant decrease. Thus, a decrease in the formation of tin (II) stains means that the number of spots is statistically significantly reduced compared to the positive control containing tin (II). The absence of a decrease in the effectiveness of tin (II) means that the effectiveness of tin (II) does not statistically significantly decrease in comparison with the positive control containing tin (II). Alternatively, stain formation can be measured compared to typical oral care compositions not containing tin (II) fluoride or other antimicrobial agent that are known to cause staining. Thus, measurements for the compositions can be carried out in comparison with a very slight staining or lack thereof.

The i-PTSM can be calculated from the results of this stain analysis using the formula:

The average values of optical absorption refer to colorimetric indicators for hydrolyzed plaque obtained after treatment with a dentifrice and a control sample of tea. The tin (II) control used is typically a tin (II) fluoride composition with a high tendency to stain, such as described in Example II, Comparative Example below. Control samples with tin (II) have large values of absorption of tea and, as a result, increased values of colorimetric absorption. Thus, the i-PTSM is a measure of the relative level of staining. The lower the value of the indicator, the lower the level of staining. The combination of a tin (II) ion source and MSA provides stain reduction and will ideally have an i-PTSM of less than about 75%, preferably less than 60%, more preferably less than 50%, most preferably less than 25%.

The ratio of i-PGRM and i-PTSM

A key identifier of the improvement for the tin (II) compositions claimed herein is the ratio of the tin (II) effectiveness compared to the staining potential, since these characteristics are most important to the consumer. The effectiveness of the oral composition of the present invention is measured using a ratio of i-PGRM and i-PTSM.

The ratio of i-PGRM and i-PTSM is calculated by the formula:

Ratio = i-PGRM / i-PTSM

In accordance with the present invention, the ratio obtained using these methods should be at least about 1.2 to significantly improve the effectiveness of the tin (II) composition compared to the side effects of staining on the teeth. The ratio is preferably above about 1.3, more preferably above about 1.5, and most preferably above about 2.0. If staining is negligible or absent, the ratio tends to infinity, which is preferred.

Binding of Tin (II)

As described above, effective stabilization of tin (II) (effectiveness with reduced side effects) can be achieved by in situ binding or complexation of the tin (II) ion with an agent active on the mineral surface (MSA). In mixed compositions containing tin (II) fluoride, evidence of binding of tin (II) is readily determined by potentiometric determination of available ionic fluoride. For example, the binding of tin (II) to a polyphosphate MSA ligand results in the exchange of fluoride from tin (II) fluoride and release in the form of ionic fluoride into solution. Corresponding tin (II) binding indices can be estimated using this technique, since fluoride is the strongest ligand in the system after the MSA binding agent. Thus, the release of fluoride indicates the binding of tin (II) to MSA under these conditions.

This approach was used to determine the complexation of tin (II) and zinc ions with polyphosphate MSA. Fluoride release analysis using an ion-selective fluoride electrode was used to control the release and complexation of fluoride with a tin (II) ion in the form of a complex with a polyphosphate anion. In a tin (II) fluoride solution, the addition of Glass H polyphosphate leads to the formation of a free fluoride ion due to the formation of a tin (II) polyphosphate complex and the subsequent release of fluoride ion from tin (II) fluoride complexes. Since the zinc ion can have a higher affinity for the polyphosphate anion than the tin (II) ion, the addition of the zinc salt to the mixture of tin (II) fluoride and polyphosphate will contribute to the formation of the zinc-polyphosphate complex and the release of tin (II) ions, which then form a complex with free fluoride. Thus, the level of free fluoride ions will decrease with the addition of zinc ion.

Solutions containing only tin (II) fluoride and tin (II) fluoride plus zinc salt were prepared. A Glass H polyphosphate solution was added in portions to these solutions and the fluoride ion was monitored using an electrode selective for fluoride ion. The following two solutions were prepared.

Solution 1: SnF ₂ 0.454%

Solution 2: SnF ₂ 0.454% + ZnCl ₂ 1.25% (6000 ppm zinc ion)

Each of these solutions was titrated with 0.1 M Glass H polyphosphate (22% w / v) and fluoride ion was measured. For the obtained data, a graph of the concentration of free fluoride on the amount of titrant added was plotted. The results of this in vitro study of metal-ligand complexation are presented in the table below. The theoretical release of fluoride from 0.454% of tin (II) fluoride will be 1100 ppm of free fluoride. Since most of the fluoride in the solution containing tin (II) fluoride forms complexes with the tin (II) ion, the amount of free fluoride will be very small. With the addition of polyphosphate, the amount of free fluoride ion increases significantly and approaches a theoretical value of 1100 ppm. This is due to the complexation of tin (II) fluoride with a polyphosphate anion with the formation of a tin (II) -polyphosphate complex with the simultaneous release of fluoride ion from tin (II) fluoride complexes. The addition of zinc ion to a tin (II) fluoride solution reduces the level of free fluoride ion with an increase in the level of polyphosphate. This indicates that zinc ion helps release tin (II) ion from the tin (II) -polyphosphate complex through competitive binding to the polyphosphate anion.

Solution composition Free ion fluoride (ppm) SnF ₂ (0.454%) 29th SnF ₂ (0.454%) mixed with polyphosphate (6.2%) 669 SnF ₂ (0.454%) + ZnCl ₂ (1.2%) + polyphosphate (6.2%) 355

Decreasing astringency

Astringent properties are an additional side effect of many tin (II) containing compositions, which is greatly improved in the compositions of the present invention containing MSA in combination with tin (II) and a second polyvalent cation. The astringent properties of the compositions can be measured using panels to study the sensation in the mouth, the subjects of which evaluate the state of the mouth before and after brushing the teeth with the tested compositions. In these studies, the time-dependent effects of dentifrices on the subjective perception of consumers can be studied. According to one protocol, panelists begin the conditioning sequence by brushing their teeth with vigorous, self-cleaning oral hygiene, including brushing their teeth for two to three minutes, flossing the interdental spaces and revealing plaque to ensure complete plaque removal. Subjects are then given a test product and are instructed to brush their teeth twice a day, as usual. When conducting these tests, subjects come to the clinic in the morning before performing any oral hygiene procedures or eating or drinking. Panel members are then asked to fill out a questionnaire for a subjective organoleptic assessment, including questions about the feeling of clean teeth, the feeling of smoothness of the surface of the teeth and the feeling of cleanliness in the mouth, as well as an assessment of moisture in the mouth. Panel members then brush their teeth for one minute with the prescribed oral product. At this time, before lunch and before lunch (afternoon), subjects again fill out a questionnaire of subjective organoleptic sensations. The results of these tests showed that the compositions of the present invention containing tin (II) salts in combination with MSA, such as Glass H polyphosphate, provide a marked improvement in the astringency of the composition after brushing. Astringent properties are reduced compared to conventional tin (II) compositions without MSA. According to the degree of acceptability, the compositions of the present invention are comparable to conventional dentifrices with sodium fluoride (NaF) and anti-calculus, respectively.

Reducing education and combating tartar

Providing an anticalculus effect is another desirable aspect of the tin (II) fluoride compositions of the present invention. Anticalculus activity can be predicted by measuring activity against mineral surfaces and by performing plaque growth and mineralization analyzes. The compositions of the present invention include MSA, such as polyphosphates, which bind tin (II) ions. Preferred compositions contain phosphate polymer MSA with significant affinity for tooth surfaces consisting of calcium hydroxyapatites. Preferred MSAs will include phosphate polymers that provide a significant reduction in calcium phosphate mineralization, as established in controlled mineralization assays. It has been found that polyphosphates (in particular linear polyphosphates with an average chain length of more than about 4) provide better activity and substance to the surfaces of the oral cavity compared to pyrophosphate and some other commonly used toothbrushing ingredients. Increased activity and substantiality lead to a significant improvement in the prevention of staining of teeth and supragingival tartar and non-abrasive stain removal. Without wishing to be limited by theory, we indicate that polyphosphates are believed to prevent the formation of supragingival tartar essentially by disrupting the mineralization process, which is the formation of solid deposits of calcium phosphate minerals on tooth enamel. Due to binding to the surfaces of the teeth, polyphosphates disrupt the accumulation of minerals, since their structures do not fit properly into the growing crystal lattice of the mineral, which becomes tartar.

Method of treatment

The present invention also relates to a method for treating gingivitis and controlling plaque with reduced staining by using the compositions of the present invention containing a source of tin (II) ion, a source of polyvalent metal ions other than tin (II), and active against mineral surfaces / chelating agents such as linear polyphosphate with an average chain length of about 4 or more. The source of fluoride ions is preferably included in the compositions, especially if the source of tin (II) ion does not contain tin (II) fluoride or tin (II) fluorophosphate. Additionally provided are methods for providing oral care compositions having beneficial effects in relation to caries, gingivitis, plaque, tartar, stains on teeth, sensitivity, aesthetic characteristics, breathing, mouthfeel and cleaning. The beneficial effects of these compositions may increase over time with repeated use of the composition. More specifically, the treatment method will include the reduction of gingivitis and plaque as measured by the i-PGRM method, while the reduction in staining caused by the tin (II) oral composition is measured by the i-PTSM method. The ratio of i-PGRM to the i-PTSM stain pattern is above about 1.2.

The present invention also relates to methods for reducing the frequency of formation of tartar on tooth enamel and to methods for providing desired aesthetic beneficial effects in the oral cavity, including reduced astringency and conditioning effects of the surface of the oral cavity. The beneficial effects of these compositions may increase over time with repeated use of the composition.

Methods of treatment include preparing an oral composition containing a source of tin (II) ion, a source of a polyvalent cation other than tin (II), and an agent active against a mineral surface (MSA), and administering the composition to a subject. Administration to a subject can be defined as bringing the oral composition into contact with the surfaces of the subject’s teeth by brushing them with a dentifrice or rinsing with a suspension of dentifrice. The introduction can also be carried out by contacting the surfaces of the teeth with a gel for topical application in the oral cavity, a dental elixir, a product for the care of dentures, an aerosol oral care product, an oral tablet, lozenges or chewing gum. The subject may be any special or animal in need of treatment or prevention of oral conditions, including plaque, gingivitis, tartar, stains on the teeth and sensitivity. It is implied that the "animal" includes, in particular, pets or other domesticated animals or animals held in captivity.

For example, a treatment method may include a person who brushes the dog’s teeth with one of the dentifrice compositions. Another example involves rinsing a cat's mouth with an oral composition for a period of time sufficient to exhibit a beneficial effect. Pet care products, such as chews and toys, can be formulated to contain the oral care compositions of the present invention. A composition comprising tin (II), a second cation and MSA is included in a relatively pliable but strong and durable material such as rawhide, ropes made of natural or synthetic fibers, and polymer products made of nylon, polyester or thermoplastic polyurethane . When an animal chews, licks or gnaws a product, the active elements included in it are released into the animal's oral cavity into the saliva medium, which is comparable to effective brushing or rinsing.

Examples

The following examples and descriptions further clarify embodiments within the scope of the present invention. These examples are for illustrative purposes only and should not be construed as limitations of the present invention, since many variations are possible without departing from its scope and spirit.

Example I

Example I illustrates biphasic dentifrice compositions containing tin (II) fluoride and / or other tin (II) salts in the first dentifrice composition and containing MSA, such as sodium polyphosphate (Glass H, available from FMC Corporation , n = 21, condensed phosphate polymer) or copolymers of maleic anhydride or acid and methyl vinyl ether (Gantrez) in a second dentifrice composition. A second source of polyvalent cation is included in any of the compositions. These compositions may conveniently be prepared by conventional methods selected by the developer.

The first dentifrice compositions

Ingredient 1a 2a 3a 4a 5a Tin (II) Fluoride 1,062 1,062 1,062 1,062 - Tin (II) Chloride 1,500 - - - 1,500 Zinc Lactate - - 5,000 - Zinc carbonate - - 5,000 - - Sodium fluoride - - - - 0.486 Sodium lauryl sulfate, 27.9% solution - - 2,500 2,500 7,500 Sodium Gluconate 3,290 1,300 2,940 1,840 4,135 Sodium hydroxide, 50% solution 0,600 0,600 0,600 0.280 0,900 Saccharin sodium 0.400 0.400 0.400 0,300 0.400 Flavoring 1,500 1,300 1,300 1,200 1,100 Dye FD&C blue # 1, 1% solution 0,300 0,300 0,300 0,100 0,500 Polyethylene glycol - - - - 6,000 Poloxamer 407 15,500 15,500 17,500 16,500 7,000 Sorbitol, 70% solution 23,000 23,000 - - 36,879 Glycerol 31,008 31,008 22,000 22,000 20,000 Xanthan gum - - 0.850 - 1,100 Hydroxyethyl cellulose - - - - 0,500 Polyoxyethylene - - 0,200 - - Water 21,840 25,530 45,348 49,218 12,000

Second dentifrice compositions

Ingredient 1b 2b 3b 4b 5b Polyphosphate Glass H 25,800 20,800 26,000 - 18,000 Gantrez - 5,000 - 5,000 - Zinc Lactate - - - - 5,000 Calcium chloride 1,712 1,712 - - - Carboxymethyl cellulose 0,500 0,500 0,200 0,200 0,300 Water 2,210 2,210 - 32,150 1,400 Flavoring 1,500 1,500 1,100 1,100 1,100 Glycerol 28,178 28,178 45,550 20,550 34,850 Polyethylene glycol 1,500 1,500 - - 6,000 Propylene glycol 8,000 8,000 - - - Polyoxyethylene 0,200 0,200 - - - Sodium lauryl sulfate, 27.9% solution 10,000 10,000 8,000 10,000 6,000 Silica 15,000 15,000 18,150 30,000 26,000 Hydrogenated Castor Oil Polyoxyl 40 2,500 2,500 Benzoic acid 0,600 0,600 - - 0,300 Sodium benzoate 0,600 0,600 - - 0,300 Saccharin sodium 0.400 0.400 0.400 0.400 0.350 Titanium dioxide 1,000 1,000 0,500 0,500 0.400 Xanthan gum 0,300 0,300 0,100 0,100 -

EXAMPLE II

Example II illustrates single-phase dentifrice compositions containing tin (II) salt (s) as a source of tin (II) ion, a polyvalent cation source, and Glass H or Gantrez sodium polyphosphate as MSA. Compositions can be prepared using conventional methods.

Ingredient BUT AT FROM D E F Tin (II) Fluoride 0.454 0.454 0.454 0.454 0.454 - Tin (II) Chloride 1,500 Sodium polyphosphate 13,000 - 13,000 7,000 - - Gantrez - 2,000 - 2,000 2,000 2,000 Zinc Lactate 2,500 1,500 - 2,000 - 2,000 Zinc carbonate - - - - 2,000 - Calcium chloride - - 0.423 - - Sodium fluoride - - - - - 0.243 Silica 20,000 20,000 20,000 20,000 20,000 20,000 Propylene glycol 7,000 7,000 7,000 7,000 - - Polyethylene glycol 7,000 7,000 7,000 7,000 - - Poloxamer 407 - - - - - - Sodium lauryl sulfate, 27.9% solution 3,400 3,400 3,400 3,400 4,300 4,300 Glycerol 42,244 54,244 44,321 46,744 16,894 15,605 Sorbitol, 70% solution - - - - 20,000 20,000 Sodium Phosphate Trisubstituted 1,100 1,100 1,100 1,100 1,100 1,100 Flavoring 1,000 1,000 1,000 1,000 1,300 1,300 Sodium Gluconate 0.652 0.652 0.652 0.652 0.652 0.652 Carrageenan 0,600 0,600 0,600 0,600 - - Saccharin sodium 0,500 0,500 0,500 0,500 0,500 0,500 FD&C blue # 1.1% solution 0,300 0,300 0,300 0,300 0,300 0,300 Xanthan gum 0.250 0.250 0.250 0.250 0.250 0.250 Carboxymethyl cellulose - - - - 0.250 0.250 Water - - - - 30,000 30,000

The dimensions and values disclosed herein should not be construed as strictly limited by the exact numerical values provided. Instead, unless otherwise indicated, each such size shall mean both the indicated value and the functionally equivalent interval surrounding this value. For example, a dimension disclosed as “40 mm” should mean “about 40 mm”.

All documents referred to in the detailed description of the invention, in the relevant part, are incorporated herein by reference; the citation of any document should not be construed as an assumption that it is a prior art in relation to the present invention. To the extent that any meaning or definition of a term in this written document is contrary to any meaning or definition of a term in a document incorporated by reference, the meaning or definition given to a term in this written document is considered to be paramount.

Although specific embodiments of the present invention have been illustrated and described, it will be apparent to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. Therefore, it is intended that the appended claims cover all such changes and modifications that are within the scope of this invention.

Claims (9)

1. An oral composition comprising:
but. source of tin (II) ion,
b. source of polyvalent cations selected from zinc (Zn ⁺² ), copper (Cu ⁺² ), aluminum (Al ⁺³ ), iron (Fe ⁺² , Fe ⁺³ ), strontium (Sr ⁺² ), calcium (Ca ⁺² ), barium (Ba ⁺² ), magnesium (Mg ⁺² ), manganese (Mn ⁺² ) or their mixtures in an amount sufficient to ensure a molar ratio of polyvalent cations to tin (II) in the range of 1.5: 1-3: one,
from. an agent that is active with respect to mineral surfaces, has substance with respect to teeth and chelates with tin (II) and the indicated polyvalent cations and contains one of the polycarboxylates or carboxy-substituted polymers, or mixtures thereof; and
d. silica abrasive polishing material. 2. The oral composition according to claim 1, characterized in that the source of tin (II) ion is selected from tin (II) fluoride, tin (II) chloride dihydrate, tin (II) acetate, tin (II) gluconate, tin (II) oxalate, tin (II) sulfate, tin (II) lactate, tin (II) tartrate and mixtures thereof. 3. The oral composition according to claim 1, characterized in that the agent active with respect to the mineral surface includes a copolymer of maleic anhydride or acid with methyl vinyl ether and is contained in an amount of from about 1% to about 30% by weight of the composition . 4. The oral composition according to claim 1, characterized in that it further comprises materials selected from the group consisting of sources of fluoride ion, antibacterial agents, surfactants, thickeners, humectants, buffers, titanium dioxide, flavoring systems, sweeteners, coloring agents and mixtures thereof. 5. The oral composition according to claim 4, characterized in that the fluoride ion source is selected from the group consisting of sodium fluoride, tin (II) fluoride, indium fluoride, amine fluoride, sodium monofluorophosphate and mixtures thereof. 6. The oral composition according to claim 4, characterized in that the thickener is selected from the group consisting of carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose, sodium salt of carboxymethyl cellulose, sodium salt of hydroxyethyl cellulose, gum karaya, xanthan gum, gum arabic gum, tragacanum magnesium aluminosilicate, silicon dioxide and mixtures thereof. 7. An oral composition comprising:
(a) a first composition comprising a source of tin (II) ion,
(b) a second composition containing an agent active with respect to mineral surfaces, containing one of polycarboxylates or carboxy-substituted polymers, or mixtures thereof, and having a substantiality with respect to mineral surfaces and chelating activity to tin (II) and polyvalent cations, selected from zinc (Zn ⁺² ), copper (Cu ⁺² ), aluminum (Al ⁺³ ), iron (Fe ⁺² , Fe ⁺³ ), strontium (Sr ⁺² ), calcium (Ca ⁺² ), barium ( Ba ⁺² ), magnesium (Mg ⁺² ), manganese (Mn ⁺² ), or mixtures thereof, and
(c) a source of said polyvalent cations other than tin (II), present in any one or both of the first and second compositions in an amount sufficient to provide a molar ratio of polyvalent cations to tin (II) in the range of 1.5: 1-3: 1, and
(d) an abrasive polishing material containing silicon dioxide, present in either one or both of the first and second compositions,
wherein said agent is active with respect to mineral
surfaces, chelates tin (II) ions upon contact in the oral cavity of the first composition with the second composition. 8. The oral composition according to claim 7, characterized in that the source of tin (II) ion contains tin (II) fluoride, the source of the polyvalent cation contains a zinc salt, and the agent active with respect to mineral surfaces contains maleic copolymers anhydride or acid with methyl vinyl ether and is contained in an amount of from about 1% to about 30% by weight of the composition. 9. A method of caring for the oral cavity to reduce the formation of plaque and gingivitis, according to which the composition for caring for the oral cavity according to claim 1 is used.