Oral Care Compositions and Methods of Use

Abstract

This invention relates to oral care compositions comprising a first source of stannous, a second source of stannous, wherein the second source of stannous contains stannous pyrophosphate, and a zinc source selected from the group consisting of: zinc oxide, zinc citrate, zinc lactate, and combinations thereof, as well as to methods of using and of making these compositions.

Claims

1. An oral care composition comprising: a zinc source selected from the group consisting of: zinc oxide, zinc citrate, zinc lactate, and combinations thereof; a first source of stannous; and a second source of stannous, wherein the second source of stannous comprises stannous pyrophosphate.

2. The oral care composition of claim 1, wherein the zinc source comprises zinc oxide.

3. The oral care composition of claim 1, wherein the zinc source comprises zinc oxide and zinc citrate.

4. The oral care composition of claim 3, wherein the ratio of the amount of zinc oxide to zinc citrate is from 1.5:1 to 4.5:1.

5. The oral care composition of claim 3, comprising zinc citrate and zinc oxide, wherein the zinc citrate is present in an amount of from 0.25 to 1.0 wt %, and the zinc oxide may be present in an amount of from 0.75 to 1.25 wt %, based on the total weight of the composition.

6. The oral care composition of claim 1, wherein the zinc source comprises zinc oxide and zinc lactate.

7. The oral care composition of claim 6, wherein the ratio of the amount of zinc oxide to zinc lactate is from 1.2:1 to 4.5:1.

8. The oral care composition of claim 6, wherein the zinc lactate is in an amount of from 0.5 to 0.9 wt %, and zinc oxide may be present in an amount of from 0.75 to 1.25 wt %, based on the total weight of the composition.

9. The oral care composition of claim 1, wherein the first stannous ion source is stannous fluoride, other stannous halides such as stannous chloride dihydrate, stannous pyrophosphate, organic stannous carboxylate salts such as stannous formate, acetate, gluconate, lactate, tartrate, oxalate, malonate and citrate, stannous ethylene glyoxide, or a mixture thereof

10. The oral care composition of claim 1, wherein the first stannous ion source is stannous fluoride.

11. The oral care composition of claim 1, wherein the composition comprises one or more alkali phosphate salts selected from sodium phosphate dibasic, potassium phosphate dibasic, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, disodium hydrogen orthophosphate, monosodium phosphate, pentapotassium triphosphate and mixtures thereof.

12. The oral care composition of claim 11, wherein the composition comprises an alkali phosphate salt in an amount of from 1-20% by weight, based on the total weight of the composition.

13. The oral care composition of claim 11, wherein the alkali phosphate salt is tetrapotassium pyrophosphate.

14. The oral care composition of claim 11, wherein the alkali phosphate salt is sodium tripolyphosphate.

15. The composition of claim 1, wherein the composition comprises: a. Zinc Oxide at about 1.0 wt. %; b. Zinc Citrate at about 0.5 wt %; c. Stannous pyrophosphate at about 1.0 wt %; d. Tetrasodium pyrophosphate at about 2.0 wt %.

16. A The composition of claim 1, wherein the composition comprises: a. Zinc Oxide at about 1.0 wt. %; b. Zinc lactate at about 0.5 wt %; c. Stannous pyrophosphate at about 1.0 wt %; d. Sodium tripolyphosphate at about 2.0 wt %.

17. The composition of claim 15, further comprising a citrate buffer system, wherein the buffer system comprises tri-sodium citrate and citric acid.

18. The composition of claim 1, wherein the composition may be any of the following selected from: a toothpaste, transparent paste, gel, mouth rinse, spray and chewing gum.

19. A method to improve oral health comprising applying an effective amount of the oral composition of claim 1, wherein the oral care composition is applied to the oral cavity of a subject in need thereof.

Description

EXAMPLE 1

Dentifrice Formulation A

[0130]

TABLE-US-00001 Ingredient Weight DEMINERALIZED WATER Q. S. CITRIC ACID—ANHYDROUS 0.60 USP, EP TIUSODIUM CITRATE 1.5 DIHYDRATE—USP STANNOUS FLUORIDE, USP 0.454 ZINC OXIDE 1.0 ZINC L-LACTATE 0.85 DIHYDRATE 99,0%-101.0% GLYCERIN—USP, 42.3 EP VEG POLYETHYLENE GLYCOL 600 3.0 PROPYLENE GLYCOL USP, EP 4.0 THICKENERS 6.4 POLYVINYL PYRROLIDONE 1.25 STANNOUS 1.0 PYROPHOSPHATE ABRASIVES 19.0 TETRASODIUM 2.0 PYROPHOSPHATE—FINE FCC ANIONIC SURFACTANT 1.75 ZWITTERIONIC SURFACTANT 1.0 FLAVORS, COLORS AND 2.15 SWEETENERS PVM/MA COPOLYMER 0.606 SODIUM 1.0 PHOSPHATE, TRIBASIC, 12-HYDRATE PHOSPHORIC ACID 85% 0.50 REAGENT GRADE TOTAL COMPONENTS 100.0

EXAMPLE 2

Dentifrice Formulation B

[0131]

TABLE-US-00002 Ingredient Weight DEMINERALIZED WATER Q. S. CITRIC ACID—ANHYDROUS 0.6 USP, EP TRISODIUM CITRATE 1.5 DIHYDRATE—USP STANNOUS FLUORIDE, USP 0.454 ZINC OXIDE 1.0 ZINC CITRATE TRIHYDRATE 0.5 99.0%-101.0% GLYCERIN—USP, 42.84 EP VEG POLYETHYLENE GLYCOL 600 1.0 PROPYLENE GLYCOL USP, EP 4.0 THICKENERS 6.5 POLYVINYL PYRROLIDONE 1.25 STANNOUS PYROPHOSPHATE 1.0 ABRASIVES 19.0 TETRASODIUM 2.0 PYROPHOSPHATE—FINE FCC ANIONIC SURFACTANT 1.75 ZWITTERIONIC 1.0 SURFACTANT FLAVORS, COLORS AND 2.15 SWEETENERS GANTREZ S-97 (B.F.)—HIGH 0.606 SOLIDS SOLN SODIUM 1.0 PHOSPHATE, TRIBASIC, 12-HYDRATE PHOSPHORIC ACID 85% 0.25 REAGENT GRADE TOTAL COMPONENTS 100.0

EXAMPLE 3

[0132] In Vitro Assay for Monitoring Metal Ion Deposition

[0133] Test Formulations with [0134] a. Dentifrice Formulation A: 0.454% SnF.sub.2, 1.0% Zn) and 0.5% Zn lactate, and 2% Tetrasodium Pyrophosphate (TSPP), 2.1% Citrate Buffer (comprising 1.5% sodium citrate and 0.6% citric acid) and 1% Stannous Pyrophosphate (Listed in Example 1) [0135] b. Dentifrice Formulation C: 0.454% SnF.sub.2, 1.0% ZnO and 0.5% Zn Citrate, and 2% Sodium Tripolyphosphate (STPD), 2.1% Citrate Buffer (comprising 1.5% sodium citrate and 0.6% citric acid) and 1% Stannous Pyrophosphate;
demonstrate improved metal deposition, in in vitro bovine uptake assays when compared to control formulations which contain 0.454% SnF.sub.2 and 2.5% zinc lactate, but which do not contain stannous pyrophosphate:

TABLE-US-00003 TABLE 1 Total Stannous Metal Total Zinc Metal Deposition (ppm) Deposition (ppm) Control Formulation (0.454 0.74 1.69 wt % SnF.sub.2, and 2.5 wt. % zinc lactate) Dentifrice Formulation A 1.30 4.72 Dentifrice Formulation C 0.80 6.17
Dentifrice Formulation C is also compared to formulations with the following backbone: 0.454% SnF.sub.2, 1.0% ZnO and 0.5% Zn Citrate, 3% STPP, and 3.6% Citrate Buffer (3.0% trisodium citrate dihydrate, 0.6% citric acid). There is roughly a 32% increase in the amount of soluble zinc in the Formulation C samples, with comparable tin levels in both samples.

EXAMPLE 4

[0136] In Vitro ATP Assay

[0137] In order to screen for preliminary efficacy, the dual stannous dentifrice is subjected to an ATP- bacteria viability test. This method determines the number of viable bacterial cells in culture based on the quantification of ATP present. ATP is an indicator of metabolically active cells. This method uses a luciferase reporter to measure the amount of cellular ATP present, hence the more effective the dentifrice is, the less ATP found.

[0138] In the ATP assay, Dentifrice Formulation A (detailed in Example 1) shows, roughly, greater than 80% reduction in bacterial cell viability when compared to control formulations which contain 0.454% SnF.sub.2 and 2.5% zinc lactate, but which do not contain stannous pyrophosphate.

EXAMPLE 5

[0139] ESCA Uptake Assay

[0140] The purpose of the Uptake assay is to determine the percentage of metal ion uptake on the surface of bovine enamel after pellicle growth, 1% citric acid challenge, and treatment of a test dentifrice (Dentifrice Z) as detailed in the below Table 2.

TABLE-US-00004 TABLE 2 Sn Ratio of Sn Zn Ratio of Zn (Atomic on Enamel (Atomic on Enamel %) Surface %) Surface Positive 0.12% 1 1.4% 1 Control Formulation (0.454% SnF, 1% ZnO, 0.5% Zn citrate and no Stannous Pyrophoshpate) Dentifrice 0.3     1.61 2.5% 1.15 Formulation Z (0.454% SnF, 1% ZnO, 0.5% Zn citrate, and 1% Stannous Pyrophosphate (Values are normalized to “1”)

[0141] Bovine enamel is treated with saliva for 2 hrs, subject to an acid etch, and treated with dentifrice slurry. Specifically, saliva is removed and the bovine enamel is subject to 1% citric acid treatment and subsequently rinsed with deionized water. One group is treated with deionized water in order to establish a baseline. The subsequent test groups are treated with a 1:2 ratio of dentrifrice and deionized water slurry then rinsed with deionized water. Bovine enamel are then subject to ESCA analysis.

EXAMPLE 6

[0142] Representative Formula 1

TABLE-US-00005 Weight Ingredient % DEMINERAISZED WATER Q.S. CITRIC ACID—ANHYDROUS 0.6 USP, EP TIUSODIUM CITRATE 1.5 DIHYDRATE—USP STANNOUS FLUORIDE, USP 0.454 ZINC OXIDE 1 ZINC CITRATE TRIEYDRATE 0.5 99.5% VEG REFINED GLYCERIN 42.74 POLYETHYLENE GLYCOL 600 3 PROPYLENE GLYCOL USP, EP 4 Microcrystalline cellulose/Sodium 1 CMC Polyvinyl pyrrolidone 1.25 STANNOUS PYROPHOSPHATE 1 Abrasives 19 TETRASODIUM 2 PYROPHOSPHATE—FINE FCC Anionic Surfactant 1.75 Zwitterionic Surfactant 1 Flavors, Colors and Sweeteners 3.2 GANTREZ 5-97 (B.F.)—HIGH 0.606 SOLIDS SOLN Sodium Phosphate,Tribasic, 1 12-Hydrate Phosphoric acid 85% Reagent 0.25 Grade SYNTHETIC AMORPHOUS 5 SILICA Total Components 100

[0143] As used throughout, ranges are used as shorthand for describing each and every value that is within the range, Any value within the range can be selected as the terminus of the range. In addition, all references cited herein are hereby incorporated by referenced in their entireties. In the event of a conflict in a definition in the present disclosure and that of a cited reference, the present disclosure controls.

[0144] Unless otherwise specified, all percentages and amounts expressed herein and elsewhere in the specification should be understood to refer to percentages by weight. The amounts given are based on the active weight of the material.

[0145] While the present invention has been described with reference to embodiments, it will be understood by those skilled in the art that various modifications and variations may be made therein without departing from the scope of the present invention as defined by the appended claims.