Novel aqueous dentifrice compositions

Abstract

An improved aqueous dentifrice composition comprising stabilised stannous fluoride.

Description

[0001] Novel Aqueous Dentifrice Compositions

[0002] Field of invention

[0003] The invention relates to an aqueous dentifrice composition comprising a stabilised stannous fluoride.

[0004] Background to the invention

[0005] Stannous Fluoride is a well-known ingredient in oral care products. It has been used commercially for over 70 years. Fluoride helps to convert the calcium mineral apatite in teeth into fluorapatite, which makes tooth enamel more resistant to bacteria-generated acid attacks. The calcium present in plaque and saliva reacts with fluoride to form calcium fluoride on the tooth surface and over time, this calcium fluoride dissolves to allow calcium and fluoride ions to interact with the tooth and form fluoride- containing apatite within the tooth structure.

[0006] This chemical reaction inhibits demineralisation of the tooth structure and can promote remineralisation of tooth decay. The resulting fluoride-containing apatite is more insoluble, and more resistant to acid and tooth decay.

[0007] There are several sources of fluoride that are used in oral care compositions to give this benefit, including sodium fluoride (NaF) and sodium mono fluorophosphate.

[0008] Stannous fluoride is beneficial compared with alternative sources of fluoride as it has additional properties including antimicrobial activity that can help combat gingivitis, and anti-sensitivity properties.

[0009] One of the difficulties of using stannous fluoride in oral care products is its stability. SnF2is readily soluble in water and in aqueous solutions it is easily oxidised to form insoluble precipitates of Sn(IV), which are ineffective as a dental prophylactic. While SnF2is reasonably stable in an acidic solution, it rapidly reacts at neutral to basic pH to form Sn(IV) species. This is problematic as low pH conditions can cause damage to tooth structure and are to be avoided for oral care compositions.

[0010] To avoid the decomposition of the SnF2before reaching the oral cavity, a number of stabilising strategies have been employed. These include physically separating the SnF2from moisture (using non aqueous formulations) and using chemical stabilizers.

[0011] All of the current methods have their drawbacks. From cost implications to hindering the effectiveness of the SnF2in the oral cavity in use. It would be desired to have a simple solution to this stability problem that would allow the use of high levels of water in oral compositions.

[0012] Summary of the invention

[0013] In its broadest aspect the invention relates to a dentifrice composition comprising;

[0014] 0.1% - 50 % by weight water; 0.1% - 2 % by weight stannous fluoride; 0.1% - 10 % by weight of STP, 0.1 -10 % of at least one further Chelant, wherein the at least one further Chelant is selected from Pullulan or chitosan or mixtures thereof; and wherein the pH of the composition is 6.0 or greater. In a further embodiment the at least one further chelating agent consists of pullulan.

[0015] In a further embodiment the pullulan comprises between 0.1 and 1% by weight.

[0016] In a further embodiment the at least one further chelating agent consists of chitosan.

[0017] In a further embodiment the chitosan comprises between 0.1 and 1% by weight.

[0018] In a further embodiment the pH of the composition is 6.5 or greater.

[0019] In a further embodiment wherein the pH of the composition is 7.0 or greater.

[0020] In a further embodiment wherein water comprises between 20 and 40 % by weight of the composition.

[0021] In a further embodiment the composition further comprises at least one solvent between 20 and 55 % by weight.

[0022] In a further embodiment the solvent comprises glycerol.

[0023] In a further embodiment the solvent comprises polyethylene glycol.

[0024] In a further embodiment the composition comprises at least one abrasive.

[0025] In a further embodiment the composition comprises at least one surfactant.

[0026] In a further embodiment the composition comprises an additional source of fluoride.

[0027] In a further embodiment the composition further comprises: In a further embodiment the composition comprises pullulan at between 0.2 and 0.5 % by weight.

[0028] In a further embodiment the composition comprises chitosan at between 0.2 and 0.5% by weight.

[0029] Detailed description of the invention

[0030] The applicants have surprisingly found that stannous fluoride may be stabilised in an aqueous dentifrice composition at pH levels of 6 or higher utilising STP and at least one additional chelating agent selected from the group of pullulan and chitosan.

[0031] The applicants screened many different possible chelating agents and found several that had a positive effect on stannous ion stability in near neutral pH levels.

[0032] NMR screening was used to detect compounds that had a high possibility of chelating with Sn2+in solution.119Sn NMR studies showed certain chelating compounds had the potential to modify the environment of the tin nucleus in aqueous solution. Of those identified, further screening was carried out to determine their suitability for use in dentifrice compositions.

[0033] The chelating agents suitable for the aqueous stannous fluoride dentifrice compositions are detailed below.

[0034] Pentasodium triphosphate (STP) - also known as, Sodium triphosphate (STP), also known as sodium tripolyphosphate (STPP), or tripolyphosphate (TPP),[1]) is an inorganic compound with formula NasPsOio. It is the sodium salt of the polyphosphate penta-anion, which is the conjugate base of triphosphoric acid.

[0035] Figure 1

[0036] Pullulan (Figure 2) (CAS 9057-02-7) is a biopolymer produced by strains of the polymorphic fungus Aureobasidium pulluians as an extracellular, water-soluble polysaccharide.

[0037] Figure 2

[0038] Chitosan (Figure 3) (CAS 9012-76-4) is a linear polysaccharide composed of randomly distributed p-(l ^4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit). It is made by treating the chitin shells of shrimp and other crustaceans with an alkaline substance, such as sodium hydroxide.

[0039] Figure 3

[0040] The applicants have found that by using these chelating agents (STP in combination with either chitosan or pullulan or mixtures thereof) at between 0.1 and 10% by weight in typical dentifrice compositions comprising water and SnFz, it is possible to prevent the decomposition of the stannous at pH levels higher than 6.0.

[0041] Without wishing to be bound by theory it is believed that the chelating agents prevent the usual breakdown pathways that degrade SnFz in neutral-basic aqueous conditions.

[0042] The precise amounts of the chelating agents required depends on the amount of SnFz used in the dentifrice formulations. But at typical levels of stannous loading (around 1100 -1350 ppm) the chelants can be added between 0.1 % and 10 % by weight and provide the required stability. Chitosan and Pullulan may preferably be used in compositions of the present invention between 0.1 % and 1 % by weight, preferably between 0.1 and 0.6 % and more preferably between 0.2 and 0.5 % at typical SnF2loadings of around 0.5 % by weight.

[0043] STP may be used between 0.1 % and 8 % by weight, preferably between 4 % and 6 % by weight.

[0044] Each of the three chelants is effective on their own at stabilizing Sn2+ions in aqueous dentifrice compositions. However only when used in particular combination they can also stabilize fluoride levels STP in combination with either Pullulan or Chitosan provided an environment for SnF2in aqueous dentifrice compositions that stabilised both stannous ion and fluoride ion levels.

[0045] In particularly preferred combination, the dentifrice composition comprises STP 4-6 % by weight, pullulan 0.1-0.6 % by weight and SNF2at 0.454 % by weight. More preferably the pullulan may be used between 0.2 and 0.5 % by weight.

[0046] In particularly preferred combination comprises STP 4-6 % by weight, chitosan 0.1-0.6 % by weight and SNF2at 0.454 % by weight. More preferably the chitosan may be used between 0.2 and 0.5 % by weight.

[0047] A comparator chelant is Sodium Gluconate

[0048] Sodium gluconate is a compound with formula NaCsHnO?. It is the sodium salt of gluconic acid. Its E number is E576. Sodium gluconate is widely used in textile dyeing, printing and metal surface water treatment. It is also used as a chelating agent, a steel surface cleaning agent, a cleaning agent for glass bottles, and as a chelating agent for cement, plating and alumina dyeing industries. It is a white powder that is very soluble in water.

[0049] Gluconate showed some positive effect by119Sn NMR but was not effective in dentifrice compositions.

[0050] Stannous ion levels dropped rapidly in dentifrices with sodium gluconate at pH levels above 6.0. As used herein the term "dentifrice" includes any semi-solid preparation in the form of a paste, cream or gel for use in cleaning all or a portion of the oral cavity of an individual.

[0051] As used herein the term "oral cavity" means an individual's teeth and gums including all periodontal regions including teeth down to the gingival margins and / or the periodontal pockets.

[0052] The dentifrice compositions of the present invention are aqueous compositions. The compositions may comprise between 0.1 % and 50 % by weight water.

[0053] Preferably the compositions comprise between 10 % and 40 % by weight water, more preferably between 25 % and 35 % by weight water.

[0054] The pH of the dentifrice compositions are greater than 6.0. Preferably greater than 6.5 and more preferably greater than pH 7.0.

[0055] In an aqueous environment SnF2is increasingly unstable as the pH moves from acidic to neutral.

[0056] Preferably the compositions of the present invention additionally comprise solvent.

[0057] Suitable solvents for use in the present invention include glycerin, sorbitol, propylene glycol, polyethylene glycol or mixtures thereof. In one embodiment the solvent comprises glycerin.

[0058] In one embodiment the solvent comprises polyethylene glycol. Suitably, the polyethylene glycol will be selected from PEG 300, PEG 400 and mixtures thereof. In one embodiment the polyethylene glycol comprises PEG 400.

[0059] In one embodiment the solvent comprises a mixture of glycerin and polyethylene glycol.

[0060] In another embodiment the solvent comprises polyethylene glycol only.

[0061] Preferably the total amount of solvent will be between 20 % and 55 % by weight of the composition. In one embodiment the solvent comprises a mixture of glycerin and polyethylene glycol in a weight ratio of from 3:2 to 2:3. In a particularly preferred embodiment, the composition comprises between 25 % and 30 % by weight of glycerol and between 15 % and 25 % of polyethylene glycol.

[0062] The dentifrice compositions according to the invention may comprise at least one surfactant. In certain embodiments the surfactant system consists of a first surfactant and at least one second surfactant.

[0063] The invention is not limited to particular surfactants or surfactant combinations.

[0064] A suitable surfactant composition according to the invention belongs to the class of compounds known as betaines. Structurally, betaine compounds contain an anionic functional group such as a carboxylate functional group and a cationic functional group such as quaternary nitrogen functional group separated by a methylene moiety. They include n-alkyl betaines such as cetyl betaine and behenyl betaine, and n-alkylamido betaines such as cocoamidopropyl betaine.

[0065] In one embodiment the betaine is cocoamidopropyl betaine, commercially available under the trade name Tego Betain. Suitably the betaine is present in an amount ranging from about 0.05 % to about 4 % by weight of the non-aqueous composition, for example from about 0.2 % to about 2.0 % by weight of the non-aqueous composition.

[0066] A second suitable class of surfactants are the taurates. Taurate surfactants useful in the present invention are salts of fatty acid amides of N-methyl taurine. They conform generally to the structural formula:

[0067] RC(O)N(CH3)CH2CH2SO3l\ / l

[0068] Where RC(O)- represents a fatty acid radical and M represents sodium, potassium, ammonium or triethanolamine. Fatty acids having carbon chain lengths of from 10 to 20, including those derived from coconut, palm and tall oil are used. In one embodiment the fatty acid is derived from coconut.

[0069] In one embodiment, sodium salts are used.

[0070] In one embodiment the taurate is sodium methyl cocyl taurate. This taurate surfactant is sold under the trademark by Adinol® CT by Croda. The taurate surfactant may be present in an amount from about 0.1 to about 10% of the composition. In one embodiment the taurate surfactant is present in an amount from about 0.1 to about 5% by weight of the composition. In one embodiment the taurate surfactant is present in an amount from about 0.5 % to about 2.0 % by weight of the composition.

[0071] Alkyl sulphate surfactants use in the invention have the following structural formula:

[0072] ( OSChM

[0073] R1represents a fatty alcohol moiety and M represents sodium, potassium, ammonium or triethanolamine. Fatty alcohols having carbon chain lengths of from about 10 to about 20, including those derived from coconut, palm oil and tall oil. In one embodiment, the fatty alcohol is lauryl alcohol. In one embodiment, a sodium salt is used. In one embodiment the alkyl sulphate is sodium lauryl sulphate.

[0074] The alkyl sulphate surfactant may be present in an amount from about 0.1 % to about 10 % of the composition. In one embodiment the alkyl sulphate surfactant may be present in an amount from about 0.1 % to about 5 % by weight of the composition. In one embodiment the alkyl sulphate surfactant is present in an amount from about 0.5 % to about 2.0 % by weight of the composition.

[0075] In one embodiment the surfactant system consists of a first surfactant which is sodium lauryl sulphate and a second surfactant which consists of sodium methyl cocyl taurate.

[0076] Advantageously, a thickening agent may be present in the formulation to give the product a rheology required of a conventional dentifrice.

[0077] The thickening agent may comprise a carboxyvinyl polymer such as a carbomer. A carbomer comprises synthetic high molecular-weight cross-linked polymers of acrylic acid. The polymer chains formed of repeating units of acrylic acid may be cross-linked with, for example: allyl sucrose to provide a carbomer available commercially in one form as Carbopol™ 934; ethers of pentaerythritol to provide a carbomer available commercially in one form as Carbopol™ 974; or with divinyl glycol, available commercially in one form as Noveon™ AA-1. Carbopol polymers are manufactured by B.F. Goodrich Company. In one embodiment the carboxyvinyl polymer comprises Carbopol 974. The carboxyvinyl polymer may be present in the range of from about 0.1 to about 7.5% by weight of the non-aqueous composition. In one embodiment the carboxyvinyl polymer is present in an amount from about 0.3 to about 1.0% by weight of the composition.

[0078] Suitably a composition according to the invention may further comprise an inorganic thickening agent such as a thickening silica. Suitably, the thickening agent is a thickening silica, for example, a colloidal hydrated silica, available commercially for example as Sident 22S or Syloid 244FP.

[0079] In one embodiment the thickening silica is present in the range of from about 0 % to about 15 %, suitably from about 5.0 % to about 15.0 % by weight of the composition.

[0080] A dentally acceptable abrasive may optionally be added to the composition.

[0081] Suitable abrasives for use in the non-aqueous composition include, for example, amorphous, gelled, precipitated or fumed silica, zinc orthophosphate, sodium bicarbonate (baking soda), plastic particles, alumina, hydrated alumina, calcium carbonate, calcium pyrophosphate, insoluble metaphosphates or mixtures thereof.

[0082] The silica abrasive may be a natural amorphous silica, for instance diatomaceous earth; or a synthetic amorphous silica such as a precipitated silica. By way of example, silica abrasives include those marketed under the following trade names Zeodent, Sident, Sorbosil or Tixosil by Huber, Degussa, Ineos and Rhodia respectively.

[0083] Suitably a silica abrasive may be present in an amount up to 25 % by weight of the total composition, for example from 2 % to 20 % by weight for example from 5 % to 15 % by weight of the total composition.

[0084] Generally, an amount of abrasive suitable for use in the composition of the present invention will be empirically determined to provide an acceptable level of cleaning and polishing, in accordance with the techniques well known in the art. Suitably, the abrasive is present in an amount from about 0 % to about 30 %, typically from about 5 % to about 25 %, by weight of the composition.

[0085] The compositions of the invention may additionally optionally contain one or more oral care active agents conventionally used in dentifrice formulations. Such agents may include, by way of example, an additional fluoride source, a desensitizing agent, an anti-calculus agent, an anti-erosion agent, an antimicrobial agent, an anti-plaque agent, a whitening agent, an oral malodour agent or a mixture of at least two thereof.

[0086] Suitable additional sources of fluoride ions for use in the compositions of the present invention include an alkali metal fluoride such as sodium fluoride, an alkali metal monofluorophosphate such a sodium monofluorophosphate, or an amine fluoride in an amount to provide from 25 to 3500 ppm of fluoride ions, preferably from 100 to 1500 ppm.

[0087] Stannnous fluoride has desensitizing properties. However a further desensitizing agent, including a tubule blocking agent or a nerve desensitizing agent and mixtures thereof, for example as described in WO 02 / 15809 (Block) may be included in a composition according to the invention. Such further optional desensitizing agent(s) include a strontium salt such as strontium chloride, strontium acetate or strontium nitrate or a potassium salt such as potassium citrate, potassium chloride, potassium bicarbonate, potassium gluconate and especially potassium nitrate.

[0088] Polyphosphates are known to help retard calculus formation and are examples of anti-calculus agents suitable for use in the invention. A polyphosphate is generally understood to consist of two or more phosphate groups arranged primarily in a linear configuration, although some cyclic derivatives may be present. Polyphosphates of use in the invention include pyrophosphates, polyphosphates having three or more polyphosphate groups and polyphosphates having four or more polyphosphate groups such as tetrapolyphosphate and hexametaphosphate among others.

[0089] Compositions of the invention may further comprise an anti-erosion agent, for example a polymeric mineral surface active agent as described in WO 04 / 054529 (Procter & Gamble).

[0090] Compositions of the present invention may contain additional minor agents such as flavouring agents, sweetening agents, opacifying or colouring agents and preservatives, selected from those conventionally used in an oral hygiene composition art for such purposes.

[0091] In general, the optional agents may be used in a minor amount or proportion of the overall formulation. By way of example, such components are usually present in from about 0.01 to about 5% by weight of the composition. The dentifrice composition typically has a viscosity suitable for application to the oral cavity. The viscosity will vary depending on the type of dentifrice composition made and the ultimate use thereof. One of skill in the art can readily prepare compositions with suitable viscosities for use in the oral cavity from the teachings provided herein.

[0092] The compositions according to the present invention may be prepared by admixing the ingredients in the appropriate relative amounts in any order that is convenient.

[0093] A typical general formula of the present invention comprises:

[0094] Table 1

[0095] A more preferred general formula of the present invention comprises:

[0096] Table 2

[0097] Table 3 discloses formulations of the present invention and four control formulations:

[0098] Table 3

[0099] Examples 4 & 5 are formulations according to the present invention.

[0100] Examples 1, 2, 3 & 6 are control formulations. The pH levels of examples 1 -6 were adjusted to >6 with NaOH. The 6 batches were tested using the USP titration method for Sn2+assay. Initially post preparation, and then after accelerated stability testing at 40°C and 75% relative humidity. The results are shown below in table 4.

[0101] Those examples that passed Sn2+ testing were then subjected to free fluoride analysis under the same accelerated stability testing conditions. The results are shown in table 5.

[0102] Table 4

[0103] Fluoride assay (USP method)

[0104] Table s

[0105] • Examples 2 and 3 failed the minimum Sn2+assay (0.279%) by the end of the first month.

[0106] • Examples 1, 4 and 5 passed all Sn2+assay tests. However, Example 1 failed free Fluoride analysis after 1 month of accelerated stability conditions.

[0107] • Examples 4 and 5 also passed all stability testing at pH 6.0. These examples were also tested and passed both assays when adjusted to pH 6.5 and 7.0.

[0108] • Example 6 had no detectable stannous ions in solution on initial testing. (When repeated with pH modified to < 5.5, Example 6 showed good initial Sn2+stability)

[0109] Only dentifrice compositions comprising STP and Chitosan or STP and pullulan were effective in stabilizing SnF2 in aqueous environment at pH 6.0 or higher.

Claims

Claims1. A dentifrice composition comprising;0.1 % - 50 % by weight water;0.1 % - 2 % by weight stannous fluoride;0.1 % - 10 % by weight of sodium tripolyphosphate (STP),0.1 % - 10 % by weight of at least one further chelating agent; wherein the at least one further chelating agent is selected from the group consisting of pullulan and chitosan, and wherein the pH of the composition is 6.0 or greater.

2. The dentifrice composition according to claim 1 wherein the at least one further chelating agent consists of pullulan and wherein the pullulan comprises between 0.1 and 1% by weight.

3. The dentifrice composition according to claims 1 wherein the at least one further chelating agent consists of chitosan and wherein the chitosan comprises between 0.1 and 1% by weight.

4. The dentifrice composition according to any of the preceding claims wherein the pH of the composition is 6.5 or greater.

5. The dentifrice composition according to any of the previous claims wherein water comprises between 20 and 40 % by weight.

6. The dentifrice composition according to any of the previous claims wherein the composition further comprises at least one solvent between 20 and 55 % by weight.

7. The dentifrice according to claim 6 wherein the at least one solvent comprises glycerol.

8. The dentifrice according either claim 6 or 7 wherein the at least one solvent comprises polyethylene glycol.

9. The dentifrice composition according to any of the previous claims wherein the composition comprises at least one abrasive.

10. The dentifrice composition according to any of the previous claims wherein the composition comprises at least one surfactant.

11. The dentifrice composition according to any of the previous claims wherein the composition comprises an additional source of fluoride.

12. The dentifrice composition according to claim 1 wherein the composition further comprises:

13. The composition according to claim 12 wherein the chelant comprises pullulan and wherein the pullulan comprises between 0.2 and 0.5 % by weight.

14. The composition according to claim 12 wherein the chelant is chitosan and wherein the chitosan comprises between 0.2 and 0.5 % by weight.

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