Novel aqueous dentifrice composition

Abstract

The present invention relates to an improved aqueous dentifrice composition comprising a stabilized stannous fluoride.

Description

Technical Field

[0001] This invention relates to aqueous dental cleaning compositions comprising stabilized stannous fluoride. Background Technology

[0002] Stannous fluoride is a well-known ingredient in oral care products. It has been commercially used for over 70 years. Fluoride helps convert the calcium mineral apatite in teeth into fluorapatite, making tooth enamel more resistant to acid erosion produced by bacteria. 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 teeth and form fluorapatite within the tooth structure.

[0003] This chemical reaction inhibits demineralization of tooth structure and promotes remineralization of cavities. The resulting fluorapatite is less soluble and more resistant to acid and cavities.

[0004] Several sources of fluoride are used in oral care compositions to produce this benefit, including sodium fluoride (NaF) and sodium monofluorophosphate.

[0005] Stannous fluoride is beneficial compared to alternative sources of fluoride because it has additional properties, including antimicrobial activity and desensitizing properties that can help combat gingivitis.

[0006] One of the challenges of using stannous fluoride in oral care products is its stability. SnF2 is readily soluble in water, and in aqueous solutions it is easily oxidized to form an insoluble Sn(IV) precipitate, rendering Sn(IV) ineffective as a dental preventative agent. While SnF2 is relatively stable in acidic solutions, it reacts rapidly at neutral to alkaline pH levels to form Sn(IV) substances. This is problematic because low pH conditions can damage tooth structure and are something to be avoided in oral care compositions.

[0007] To prevent SnF2 from decomposing before reaching the oral cavity, numerous stabilization strategies have been employed. These strategies include physically isolating SnF2 from moisture (using non-aqueous formulations) and using chemical stabilizers.

[0008] All current methods have their drawbacks, ranging from cost to hindering the effectiveness of SnF2 in oral use.

[0009] It is hoped that there is a simple solution to this stability problem that would allow the use of high water content in oral compositions. Summary of the Invention

[0010] In its broadest aspect, the present invention relates to a dental cleaning composition comprising:

[0011] 0.1 wt%-50 wt% water; 0.1 wt%-2 wt% stannous fluoride; 0.1 wt%-10 wt% STP; 0.1 wt%-10% of at least one other chelating agent, wherein the at least one other chelating agent is selected from pullulan or chitosan or mixtures thereof; and wherein the pH of the composition is 6.0 or higher.

[0012] In a further embodiment, the at least one other chelating agent is composed of pullulan.

[0013] In a further embodiment, the pullulan contains 0.1 to 1% by weight.

[0014] In a further embodiment, the at least one other chelating agent is composed of chitosan.

[0015] In a further embodiment, the chitosan comprises 0.1 to 1% by weight.

[0016] In a further embodiment, the pH of the composition is 6.5 or higher.

[0017] In a further embodiment, the pH of the composition is 7.0 or higher.

[0018] In a further embodiment, water comprises 20% to 40% by weight of the composition.

[0019] In a further embodiment, the composition further comprises 20% to 55% by weight of at least one solvent.

[0020] In a further embodiment, the solvent comprises glycerol.

[0021] In a further embodiment, the solvent comprises polyethylene glycol.

[0022] In a further embodiment, the composition comprises at least one abrasive.

[0023] In a further embodiment, the composition comprises at least one surfactant.

[0024] In a further embodiment, the composition contains an additional source of fluoride.

[0025] In a further embodiment, the composition further comprises:

[0026] purified water 25-35 % At least one solvent 40-55 % At least one thickener 5-10 % At least one abrasive 0.1-10 % STP 0.1 – 10% pullulan or chitosan or a mixture thereof 0.1-8 % Tin fluoride 0.1% to 2% At least one surfactant 0.1% to 10% Secondary components 0.01 to 5%

[0027] In a further embodiment, the composition comprises 0.2 to 0.5% by weight pullulan.

[0028] In a further embodiment, the composition comprises 0.2 to 0.5% by weight of chitosan. Detailed Implementation

[0029] The applicant unexpectedly discovered that, using STP and at least one additional chelating agent selected from pullulan and chitosan, stannous fluoride can be stabilized in aqueous dental cleaning compositions at pH levels of 6 or higher.

[0030] The applicant screened many different possible chelating agents and found several that had a positive effect on the stability of stannous ions at near-neutral pH levels.

[0031] NMR screening was used to detect Sn in solution. 2+ Compounds with high chelation potential. 119 Sn NMR studies have shown that certain chelating compounds have the potential to alter the tin nucleus environment in aqueous solutions. Further screening of those identified will be conducted to determine their suitability for use in dental cleaning compositions.

[0032] The chelating agents suitable for aqueous stannous fluoride dental cleaning compositions are detailed below.

[0033] Pentasodium tripolyphosphate (STP) – also known as sodium triphosphate (STP), or sodium tripolyphosphate (STPP) or tripolyphosphate (TPP)[1], is an inorganic compound with the chemical formula Na5P3O 10 It is the sodium salt of the pentaphosphate anion and is the conjugate base of triphosphate.

[0034]

[0035] Figure 1

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

[0037]

[0038] Figure 2

[0039] Chitosan (Figure 3) (CAS 9012-76-4) is a linear polysaccharide composed of randomly distributed β-(1→4)-linked D-glucosamine (deacetylation units) and N-acetyl-D-glucosamine (acetylation units). It is produced by treating the chitinous shells of shrimp and other crustaceans with an alkaline substance such as sodium hydroxide.

[0040]

[0041] Figure 3

[0042] The applicant discovered that by using 0.1 to 10% by weight of these chelating agents (STP in combination with chitosan or pullulan or a mixture thereof) in typical dental cleaning compositions containing water and SnF2, stannous compounds can be prevented from decomposing at pH levels above 6.0.

[0043] Not wanting to be bound by theory, it is believed that chelating agents prevent the usual decomposition pathway of SnF2 degradation in neutral-alkaline aqueous conditions.

[0044] The precise amount of chelating agent required depends on the amount of SnF2 used in the dental cleaning formulation. However, at typical tin loading levels (approximately 1100-1350 ppm), 0.1% to 10% by weight of chelating agent can be added to provide the required stability.

[0045] Chitosan and pullulan can preferably be used in the compositions of the present invention at a typical SnF2 loading of about 0.5 wt%, preferably from 0.1 wt% to 1 wt%, more preferably from 0.1 wt% to 0.6 wt%, and more preferably from 0.2 wt% to 0.5 wt%.

[0046] STP can be used at 0.1% to 8% by weight, preferably 4% to 6% by weight.

[0047] Each of the three chelating agents has its own effect on stabilizing Sn in aqueous dental cleaning compositions. 2+ Ions are effective. However, they can also stabilize fluoride levels only when used in specific combinations. Combining STP with pullulan or chitosan provides an environment that stabilizes stannous and fluoride ion levels in aqueous dental cleaning compositions.

[0048] In particularly preferred combinations, the dental cleaning composition comprises 4-6% by weight of STP, 0.1-0.6% by weight of pullulan, and 0.454% by weight of SNF. 2。 More preferably, pullulan can be used at 0.2 to 0.5% by weight.

[0049] A particularly preferred combination comprises 4-6% by weight of STP, 0.1-0.6% by weight of chitosan, and 0.454% by weight of SNF2. More preferably, chitosan may be used at 0.2 to 0.5% by weight.

[0050] The chelating agent for comparison is sodium gluconate.

[0051]

[0052] Sodium gluconate has the chemical formula NaC6H. 11O7 is a compound. It is the sodium salt of gluconate, with the E designation E576. Sodium gluconate is widely used in textile dyeing, printing, and water treatment of metal surfaces. It is also used as a chelating agent, a steel surface cleaner, a glass bottle cleaner, and as a chelating agent in the cement, electroplating, and alumina dyeing industries. It is a white powder that is highly soluble in water.

[0053] pass 119 Sn NMR analysis showed that sodium gluconate had some positive effects, but was ineffective in dental cleaning compositions. In dental cleaning agents containing sodium gluconate at pH levels above 6.0, stannous ion levels decreased rapidly.

[0054] As used herein, the term "dental cleaning agent" includes any semi-solid preparation in the form of a paste, cream, or gel intended for cleaning all or part of an individual's oral cavity.

[0055] As used herein, the term “oral cavity” refers to an individual’s teeth and gums, including all periodontal regions, including teeth extending down to the gingival margin and / or periodontal pockets.

[0056] The dental cleaning composition of the present invention is an aqueous composition. The composition may contain 0.1% to 50% by weight of water.

[0057] Preferably, the composition contains 10% to 40% by weight of water, more preferably 25% to 35% by weight of water.

[0058] The pH of the dental cleaning composition is greater than 6.0. Preferably greater than 6.5, and more preferably greater than pH 7.0.

[0059] In an aqueous environment, SnF2 becomes increasingly unstable as the pH changes from acidic to neutral.

[0060] Preferably, the compositions of the present invention further comprise a solvent.

[0061] Suitable solvents for use in this invention include glycerol, sorbitol, propylene glycol, polyethylene glycol, or mixtures thereof. In one embodiment, the solvent comprises glycerol.

[0062] 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.

[0063] In one embodiment, the solvent comprises a mixture of glycerol and polyethylene glycol.

[0064] In another embodiment, the solvent contains only polyethylene glycol.

[0065] Preferably, the total amount of solvent is 20% to 55% by weight of the composition.

[0066] In one embodiment, the solvent comprises a mixture of glycerol and polyethylene glycol in a weight ratio of 3:2 to 2:3.

[0067] In a particularly preferred embodiment, the composition comprises 25% to 30% by weight of glycerol and 15% to 25% by weight of polyethylene glycol.

[0068] The dental cleaning composition according to the present invention may contain at least one surfactant. In some embodiments, the surfactant system consists of a first surfactant and at least one second surfactant.

[0069] This invention is not limited to a specific surfactant or combination of surfactants.

[0070] Suitable surfactant compositions according to the invention belong to the class of compounds called betaines. Structurally, betaine compounds contain anionic functional groups, such as carboxylic acid functional groups, and cationic functional groups, such as quaternary nitrogen functional groups, separated by methylene moieties. They include n-alkyl betaines (e.g., cetyl betaine and behenyl betaine) and n-alkyl amide betaines (e.g., cocamidopropyl betaine).

[0071] In one embodiment, the betaine is cocamidopropyl betaine, commercially available under the trade name Tego Betain. Suitably, the betaine is present in an amount of about 0.05% by weight to about 4% by weight of the non-aqueous composition, for example, about 0.2% by weight to about 2.0% by weight of the non-aqueous composition.

[0072] The second type of suitable surfactant is taurates. Taurate surfactants that can be used in this invention are salts of fatty acid amides of N-methyltauric acid. They generally conform to the following structural formula:

[0073] RC(O)N(CH3)CH2CH2SO3M

[0074] Wherein RC(O)- represents a fatty acid group, and M represents sodium, potassium, ammonium, or triethanolamine. Fatty acids with a carbon chain length of 10-20 are used, including those derived from coconut oil, palm oil, and tall oil. In one embodiment, the fatty acid is derived from coconut oil.

[0075] In one implementation, a sodium salt is used.

[0076] In one embodiment, the taurine is sodium methylcocoyl taurate. This taurine surfactant is marketed by Croda under the trademark Adinol® CT.

[0077] The taurine surfactant may be present in an amount of about 0.1% to about 10% of the composition. In one embodiment, the taurine surfactant is present in an amount of about 0.1% to about 5% by weight of the composition. In another embodiment, the taurine surfactant is present in an amount of about 0.5% by weight to about 2.0% by weight of the composition.

[0078] The alkyl sulfate surfactant used in this invention has the following structural formula:

[0079] R 1 OSO3M

[0080] R 1 The symbol represents the fatty alcohol moiety, and M represents sodium, potassium, ammonium, or triethanolamine. The fatty alcohol has a carbon chain length of about 10 to about 20, including those derived from coconut oil, 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 sulfate is sodium dodecyl sulfate.

[0081] The alkyl sulfate surfactant may be present in an amount of about 0.1% to about 10% of the composition. In one embodiment, the alkyl sulfate surfactant may be present in an amount of about 0.1% by weight to about 5% by weight of the composition. In another embodiment, the alkyl sulfate surfactant may be present in an amount of about 0.5% by weight to about 2.0% by weight of the composition.

[0082] In one embodiment, the surfactant system comprises a first surfactant (which is sodium dodecyl sulfate) and a second surfactant (which is composed of sodium methyl cocoyl taurate).

[0083] Advantageously, thickeners can be present in the formulation to impart the rheological properties required for conventional dental cleaning agents.

[0084] The thickener may comprise a carboxyvinyl polymer, such as carbomer. Carbomer comprises a synthetic high molecular weight crosslinked polymer of acrylic acid. The polymer chain formed from repeating units of acrylic acid may be crosslinked with, for example, allyl sucrose to provide a carbomer commercially available in the form of Carbopol™ 934; a pentaerythritol ether to provide a carbomer commercially available in the form of Carbopol™ 974; or crosslinked with divinyl glycol, commercially available in the form of Noveon™ AA-1. The carbomer polymer is manufactured by BF Goodrich. In one embodiment, the carboxyvinyl polymer comprises Carbopol 974. The carboxyvinyl polymer may be present in the range of about 0.1 to about 7.5% by weight of the non-aqueous composition.

[0085] In one embodiment, the carboxyvinyl polymer is present in an amount of about 0.3 to about 1.0% by weight of the composition.

[0086] Suitably, the compositions according to the invention may further comprise an inorganic thickener, such as thickening silica. Preferably, the thickener is thickening silica, such as colloidal hydrated silica, which is commercially available, for example, as Sident 22S or Syloid 244FP.

[0087] In one embodiment, the thickened silica is present in the range of about 0% to about 15% by weight of the composition, suitably from about 5.0% to about 15.0% by weight.

[0088] Dental-acceptable abrasives may optionally be added to the composition.

[0089] Suitable abrasives for use in non-aqueous compositions include, for example, amorphous, gelled, precipitated or fumed silica, zinc orthophosphate, sodium bicarbonate (baking soda), plastic granules, alumina, hydrated alumina, calcium carbonate, calcium pyrophosphate, insoluble metaphosphates or mixtures thereof.

[0090] Silica abrasives can be natural amorphous silica, such as diatomaceous earth; or synthetic amorphous silica, such as precipitated silica. For example, silica abrasives include those marketed by Huber, Degussa, Ineos, and Rhodia under the trade names Zeodent, Sident, Sorbosil, or Tixosil.

[0091] Suitable, the silica abrasive may be present in an amount of up to 25% by weight of the total composition, for example, from 2% to 20% by weight of the total composition, for example, from 5% to 15% by weight of the total composition.

[0092] Typically, the amount of abrasive suitable for use in the compositions of the present invention is determined empirically based on techniques well known in the art to provide an acceptable level of cleaning and polishing. Suitably, the abrasive is present in an amount from about 0% to about 30% by weight of the composition, typically from about 5% to about 25% by weight.

[0093] The compositions of the present invention may optionally additionally contain one or more oral care active agents conventionally used in dental floss formulations. Such agents may include, for example, additional sources of fluoride, desensitizing agents, anti-tartar agents, anti-erosion agents, antimicrobial agents, anti-plaque agents, whitening agents, anti-bad breath agents, or mixtures of at least two of these.

[0094] Suitable additional fluoride ion sources for use in the compositions of the present invention include alkali metal fluorides such as sodium fluoride, alkali metal monofluorophosphates such as sodium monofluorophosphate, or fluorinated amines, which can provide 25 to 3500 ppm of fluoride ions, preferably 100 to 1500 ppm of fluoride ions.

[0095] Stannous fluoride possesses desensitizing properties. However, other desensitizing agents may be included in the compositions according to the invention, including tubule blocking agents or neurosensitizers and mixtures thereof, such as those described in WO 02 / 15809 (Block). Other alternative desensitizing agents of this kind include strontium salts such as strontium chloride, strontium acetate, or strontium nitrate, or potassium salts such as potassium citrate, potassium chloride, potassium bicarbonate, potassium gluconate, and especially potassium nitrate.

[0096] Polyphosphates are known to help delay tartar formation and are examples of anti-tartar agents suitable for use in this invention. Polyphosphates are generally understood to consist of two or more phosphate groups arranged primarily in a linear configuration, although some cyclic derivatives may exist. The polyphosphates used in this invention include pyrophosphates, polyphosphates having three or more polyphosphate groups, and polyphosphates having four or more polyphosphate groups, such as tetrapolyphosphates and hexametaphosphates.

[0097] The compositions of the present invention may further comprise an anti-corrosion agent, such as the polymeric mineral surfactant described in WO 04 / 054529 (Procter & Gamble).

[0098] The compositions of the present invention may contain additional minor agents, such as flavoring agents, sweeteners, opacifiers or colorants and preservatives, selected from those conventionally used in the field of oral hygiene compositions for such purposes.

[0099] Typically, optional reagents may be used in minute amounts or proportions of the whole formulation. For example, these components are typically present in the composition at about 0.01 to about 5% by weight.

[0100] Dental cleaning compositions typically have a viscosity suitable for oral application. The viscosity will vary depending on the type of dental cleaning composition prepared and its end use. Based on the teachings provided herein, those skilled in the art can readily prepare compositions with suitable viscosity for oral use.

[0101] The compositions according to the invention can be prepared by mixing the components in appropriate relative amounts in any convenient order.

[0102] A typical formulation of this invention includes:

[0103] Element quantity purified water 15-35 % At least one solvent 20-55 % At least one thickener 5-20 % At least one abrasive 0.1-10 % STP 0.1-10 % Chelating agents (pullulan / chitosan or mixtures thereof) 0.1-8 % Tin fluoride 0.1 - 2 % At least one surfactant 0.1 - 10 % Secondary components 0.01 - 5 %

[0104] Table 1

[0105] A more preferred formulation of the present invention includes:

[0106] Element quantity purified water 25 - 35 % solvent 40 - 55 % Thickener 5 - 10 % abrasive 0.1 - 10 % STP 4 – 6 % Chelating agents (pullulan / chitosan or mixtures thereof) 0.1 – 1 % Tin fluoride 0.1 - 2 % At least one surfactant 0.1 - 10 % Secondary components 0.01 - 5 %

[0107] Table 2

[0108] Table 3 discloses the formulation of the present invention and four comparative formulations:

[0109]

[0110] Table 3

[0111] Examples 4 and 5 are formulations according to the present invention.

[0112] Examples 1, 2, 3, and 6 are control formulations. The pH levels of Examples 1-6 were adjusted to >6 using NaOH.

[0113] Use for Sn 2+ The USP titration method was used to test six batches. Initially, this was done after preparation, followed by accelerated stability testing at 40°C and 75% relative humidity. The results are shown in Table 4 below.

[0114] Then those through Sn 2+ The tested examples underwent free fluoride analysis under the same accelerated stability test conditions. The results are shown in Table 5.

[0115] Example initial 1 month 2 months 3 months Example 1 pass pass pass pass Example 2 pass fail X X Example 3 pass fail X X Example 4 pass pass pass pass Example 5 pass pass pass pass Example 6 fail X X X

[0116] Table 4

[0117] Fluoride Determination (USP Method)

[0118] Example initial 1 month 2 months 3 months Example 1 pass fail X X Example 4 pass pass pass pass Example 5 pass pass pass pass

[0119] Table 5

[0120] • Examples 2 and 3 failed to meet the minimum Sn requirement at the end of the first month. 2+ The result was 0.279%.

[0121] Examples 1, 4, and 5 passed all Sn tests. 2+ The test was performed. However, Example 1 failed the free fluoride analysis after 1 month of accelerated stability conditions.

[0122] Examples 4 and 5 also passed all stability tests at pH 6.0. These examples were also tested when adjusted to pH 6.5 and 7.0, and passed both determinations.

[0123] • Example 6 showed no detectable stannous ions in solution during the initial test. (When repeated with a pH adjusted to <5.5, Example 6 showed good initial Sn...) 2+ stability)

[0124] Only dental cleaning compositions containing STP and chitosan or STP and pullulan are effective in stabilizing SnF2 in an aqueous environment at pH 6.0 or higher.

Claims

1. A dentifrice composition comprising: 0.1 wt% - 50 wt% water; 0.1 wt% - 2 wt% stannous fluoride; 0.1 wt% - 10 wt% sodium tripolyphosphate (STP), 0.1 wt% - 10 wt% of at least one other chelating agent; wherein the at least one other chelating agent is selected from pullulan and chitosan, and wherein the pH of the composition is 6.0 or higher.

2. The dentifrice composition of claim 1, wherein the at least one other chelating agent consists of pullulan, and wherein the pullulan comprises 0.1 wt% to 1 wt%.

3. The dentifrice composition of claim 1, wherein the at least one other chelating agent consists of chitosan, and wherein the chitosan comprises 0.1 wt% to 1 wt%.

4. The dentifrice composition of any one of the preceding claims, wherein the pH of the composition is 6.5 or higher.

5. The dentifrice composition of any one of the preceding claims, wherein water comprises 20 wt% to 40 wt%.

6. The dentifrice composition of any one of the preceding claims, wherein the composition further comprises 20 wt% to 55 wt% of at least one solvent.

7. The dentifrice of claim 6, wherein the at least one solvent comprises glycerin.

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

9. The dentifrice composition of any one of the preceding claims, wherein the composition comprises at least one abrasive.

10. The dentifrice composition of any one of the preceding claims, wherein the composition comprises at least one surfactant.

11. The dentifrice composition of any one of the preceding claims, wherein the composition comprises an additional fluoride source.

12. The dentifrice composition of claim 1, wherein the composition further comprises: 。 13. The composition of claim 12, wherein the chelating agent comprises pullulan, and wherein the pullulan comprises 0.2 wt% to 0.5 wt%.

14. The composition of claim 12, wherein the chelating agent is chitosan, and the chitosan comprises 0.2 wt% to 0.5 wt%.

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