Oral care compositions containing oleanolic acid

Abstract

Oral care compositions and, preferably, oral care compositions providing a reduction in gum bleeding as well as methods for producing such oral care compositions are disclosed herein. In accordance with some aspects, provided is an oral care composition having a stannous source; a nitrate source; a phosphate source; a surfactant system comprising a sulfate based anionic surfactant; oleanolic acid; and eugenol.

Description

ORAL CARE COMPOSITIONS CONTAINING OLEANOLIC ACIDCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority from Chinese Patent Application No.202411242336.9, filed September 5, 2024, the contents of which are hereby incorporated herein by reference in their entirety.BACKGROUND

[0002] Gum bleeding is associated with many common oral conditions, such as gingivitis. Gum bleeding may be caused by a buildup of plaque, a soft, sticky, colorless film of bacteria that forms on the teeth and gums, and produces toxins that may inflame or infect the gum tissue to cause gingivitis. Gingivitis is the initial stage of gum disease and, if left untreated, may cause periodontitis.

[0003] Antibacterial agents have been used in oral care products to reduce plaque and gingivitis, and hence reduce gum bleeding. Similarly, hemostatic agents have also been used in oral care products to reduce gum bleeding. Oleanolic acid is believed to have both antibacterial and hemostatic properties, and there is a desire to create oral care compositions incorporating oleanolic acid. However, due to its hydrophobic properties, oleanolic acid is often dissolved in solvents, such as ethanol or dimethyl sulfoxide (DMSO), to facilitate its use. The use of such solvents limits the incorporation of oleanolic acid in oral care compositions which wish to avoid or limit the use of those ingredients.

[0004] Accordingly, it would be useful to develop new methods to incorporate oleanolic acid into oral care compositions, such as toothpastes and mouthwashes, and in particular, aqueous oleanolic acid solutions that can be used to prepare oral care compositions.BRIEF SUMMARY

[0005] This summary is intended merely to introduce a simplified summary of some aspects of one or more implementations of the present disclosure. Further areas of applicability of the present disclosure will become apparent from the detailed description provided hereinafter. This summary is not an extensive overview, nor is it intended to identify key or critical elements of the present1Docket No. 14565-OO-WO-Ol-OC teachings, nor to delineate the scope of the disclosure. Rather, its purpose is merely to present one or more concepts in simplified form as a prelude to the detailed description below.

[0006] Aspects of the invention are directed to oral care compositions and, preferably, oral care compositions providing a reduction in gum bleeding, as well as methods for producing such oral care compositions. In accordance with some aspects, provided is an oral care composition having a stannous source; a nitrate source; a phosphate source; a surfactant system comprising a sulfate based anionic surfactant, wherein the total amount of sulfate based anionic surfactant is about 1.7 wt.% or less; oleanolic acid; eugenol; and sodium hydroxide in an amount from 0.05 to about 0.8 wt.%, wherein all weight percentages are based on the total weight of the oral care composition.

[0007] In accordance with another aspect, provided is an oral care composition having a stannous source; a nitrate source; a phosphate source; a surfactant system comprising a sulfate based anionic surfactant, wherein the total amount of sulfate based anionic surfactant is 2.2 to about 7 wt.%; oleanolic acid; and eugenol, wherein all weight percentages are based on the total weight of the oral care composition. Preferably, in some embodiments, the oral care composition has a pH of from about 6 to about 7.8 or about 6.4 to about 7.4.

[0008] In accordance with yet a further aspect, a method is provided for producing an oral care composition, the method comprising: mixing oleanolic acid and a polyol to obtain an oleanolic acid mixture; and preparing an oral care composition by combining the oleanolic mixture with a stannous source, a nitrate source, a phosphate source, a surfactant system, and eugenol, the oral care composition comprising: a stannous source; a nitrate source; a phosphate source; a surfactant system comprising sodium lauryl sulfate, sodium lauryl ether sulfate, or a combination thereof; oleanolic acid; and eugenol. Preferably, the oral care compositions are free of clumps or fisheyes, such as those formed from oleanolic acid.

[0009] A list of non-limiting, example embodiments according to aspects of the invention is provided below:

[0010] In accordance with an embodiment 1, provided is an oral care composition comprising: a stannous source; a nitrate source; a phosphate source; a surfactant system comprising a sulfate based anionic surfactant, wherein the total amount of sulfate based anionic surfactant is about 1.7 wt.% or less; oleanolic acid; eugenol; and sodium hydroxide in an amount from 0.05 to about 0.8 wt.%, wherein all weight percentages are based on the total weight of the oral care composition.

[0011] In accordance with an embodiment 2, provided is an oral care composition comprising: aDocket No. 14565-OO-WO-Ol-OC stannous source; a nitrate source; a phosphate source; a surfactant system comprising a sulfate based anionic surfactant, wherein the total amount of sulfate based anionic surfactant is 2.2 to about 7 wt.%; oleanolic acid; and eugenol, wherein all weight percentages are based on the total weight of the oral care composition.

[0012] In accordance with an embodiment 3, provided is an oral care composition according to any foregoing embodiment, wherein the stannous source is selected from stannous fluoride, stannous chloride, stannous pyrophosphate, stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate, stannous citrate, stannous ethylene glyoxide, and combinations of two or more thereof.

[0013] In accordance with an embodiment 4, provided is an oral care composition according to any foregoing embodiment, wherein the nitrate source is selected from lithium nitrate, sodium nitrate, potassium nitrate, magnesium nitrate, calcium nitrate, zinc nitrate, silver nitrate, ammonium nitrate, and a combination two or more thereof.

[0014] In accordance with an embodiment 5, provided is an oral care composition according to any foregoing embodiment, wherein the oral care compositions have a molar ratio of nitrate ions to stannous ions, both measured as free ions, of about 0.5:1 to about 2:1.

[0015] In accordance with an embodiment 6, provided is an oral care composition according to any foregoing embodiment, wherein phosphate source is selected from tetrasodium pyrophosphate, dicalcium orthophosphate dihydrate, dicalcium phosphate dihydrate, calcium hydrogen phosphate, calcium pyrophosphate, p-calcium pyrophosphate, tricalcium phosphate, calcium metaphosphate, potassium metaphosphate, sodium metaphosphate, sodium triphosphate, and a combination of two or more thereof.

[0016] In accordance with an embodiment 7, provided is an oral care composition according to embodiment 6, wherein the phosphate source comprises tetrasodium pyrophosphate, sodium triphosphate, or a combination thereof.

[0017] In accordance with an embodiment 8, provided is an oral care composition according to any foregoing embodiment, wherein the surfactant system further comprises an amphoteric surfactant.

[0018] In accordance with an embodiment 9, provided is an oral care composition according to embodiment 8, wherein the amphoteric surfactant comprises a betaine surfactant selected from coca betaine, cocamidopropyl betaine, coco dimethyl carboxymethyl betaine, lauryl dimethylDocket No. 14565-OO-WO-Ol-OC carboxy-methyl betaine, lauryl dimethyl alpha-carboxyethyl betaine, cetyl dimethyl carboxymethyl betaine, lauryl bis-(2-hydroxycthyl)carboxy methyl betaine, stcaryl bis-(2- hydroxypropyl)carboxymethyl betaine, oleyl dimethyl gamma-carboxypropyl betaine, lauryl bis- (2-hydroxypropyl)alpha-carboxyethyl betaine, or a combination thereof.

[0019] In accordance with an embodiment 10, provided is an oral care composition according to any foregoing embodiment further comprising: a polyol, optionally, in an amount 20 to about 60 wt.%.

[0020] In accordance with an embodiment 11, provided is an oral care composition according to embodiment 10, wherein the polyol is selected from sorbitol, xylitol, mannitol, glycerin, ethylene glycol, propylene glycol, butylene glycol, hexylene glycol, polyethylene glycol, a polypropylene glycol, a block polymer of polyethylene glycol and polypropylene glycol, and a combination of two or more thereof.

[0021] In accordance with an embodiment 12, provided is an oral care composition according to any foregoing embodiment further comprising: a thickening agent, optionally, in an amount from about 0.5 to about 20 wt.%.

[0022] In accordance with an embodiment 13, provided is an oral care composition according to embodiment 12, wherein the thickening agent is selected from polysaccharide, a natural gum, a silica thickener, an acrylate, a polymer, and a combination of two or more thereof.

[0023] In accordance with an embodiment 14, provided is an oral care composition according to embodiments 12 or 13, wherein the thickening agent comprises a silica thickener.

[0024] In accordance with an embodiment 15, provided is an oral care composition according to any foregoing embodiment, wherein the thickening agent comprises a natural gum selected from xanthan gum, karaya gum, gum arabic, gum tragacanth, and a combination of two or more thereof.

[0025] In accordance with an embodiment 16, provided is an oral care composition according to any one of embodiments 2 to 15, wherein the oral care composition is free of alkali metal hydroxides.

[0026] In accordance with an embodiment 17, provided is an oral care composition according to any foregoing embodiment, wherein the sulfate based anionic surfactant comprises sodium lauryl sulfate, sodium lauryl ether sulfate, or a combination thereof.

[0027] In accordance with an embodiment 18, provided is an oral care composition according to any foregoing embodiment, wherein the oral care composition has a pH of about 6.4 to 7.4.Docket No. 14565-OO-WO-Ol-OC

[0028] In accordance with an embodiment 19, a method is provided for producing an oral care composition, the method comprising: mixing olcanolic acid and a polyol to obtain an olcanolic acid mixture; and preparing an oral care composition by combining the olcanolic mixture with a stannous source, a nitrate source, a phosphate source, a surfactant system, and eugenol, the oral care composition comprising: a stannous source; a nitrate source; a phosphate source; a surfactant system comprising one or more sulfate based anionic surfactant; oleanolic acid; and eugenol.

[0029] In accordance with an embodiment 20, provided is the method according to embodiment19, wherein the oleanolic acid mixture has a weight ratio of the oleanolic acid to the polyol of about 1:7 to about 1:50.

[0030] In accordance with an embodiment 21, provided is the method according to embodiment20, wherein the weight ratio of the oleanolic acid to the polyol is about 1:10 to about 1:50.

[0031] In accordance with an embodiment 22, provided is the method according to any one of embodiments 19 to 21 further comprising: preparing an oleanolic acid composition by combining the oleanolic acid mixture is combined with the surfactant system, the phosphate source, and optionally eugenol.

[0032] In accordance with an embodiment 22, provided is the method according to embodiment22, wherein the oleanolic acid composition prepared prior to the addition of the stannous source or nitrate source.

[0033] In accordance with an embodiment 24, provided is the method according to embodiment23, wherein the oleanolic acid composition is mixed to until homogenous.

[0034] In accordance with an embodiment 25, provided is the method according to any one of embodiments 19 to 24, wherein the stannous source is selected from stannous fluoride, stannous chloride, stannous pyrophosphate, stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate, stannous citrate, and combinations of two or more thereof.

[0035] In accordance with an embodiment 26, provided is the method according to any one of embodiments 19 to 25, wherein the nitrate source is selected from lithium nitrate, sodium nitrate, potassium nitrate, magnesium nitrate, calcium nitrate, zinc nitrate, silver nitrate, ammonium nitrate, and a combination two or more thereof.

[0036] In accordance with an embodiment 27, provided is the method according to any one of embodiments 19 to 26, wherein the oral care composition has a molar ratio of nitrate ions toDocket No. 14565-OO-WO-Ol-OC stannous ions, both measured as free ions, of about 0.5:1 to about 2:1 .

[0037] In accordance with an embodiment 28, provided is the method according to any one of embodiments 19 to 27, wherein phosphate source is selected from tetrasodium pyrophosphate, dicalcium orthophosphate dihydrate, dicalcium phosphate dihydrate, calcium hydrogen phosphate, calcium pyrophosphate, p-calcium pyrophosphate, tricalcium phosphate, calcium metaphosphate, potassium metaphosphate, sodium metaphosphate, sodium triphosphate, and a combination of two or more thereof.

[0038] In accordance with an embodiment 29, provided is the method according to embodiment 28, wherein the phosphate source comprises tetrasodium pyrophosphate, sodium triphosphate, or a combination thereof.

[0039] In accordance with an embodiment 30, provided is the method according to any one of embodiments 19 to 29, wherein the surfactant system further comprises an amphoteric surfactant.

[0040] In accordance with an embodiment 31 , provided is the method according to embodiment 30, wherein the amphoteric surfactant comprises a betaine surfactant selected from coca betaine, cocamidopropyl betaine, coco dimethyl carboxymethyl betaine, lauryl dimethyl carboxy-methyl betaine, lauryl dimethyl alpha-carboxyethyl betaine, cetyl dimethyl carboxymethyl betaine, lauryl bis-(2-hydroxyethyl)carboxy methyl betaine, stearyl bis-(2-hydroxypropyl)carboxymethyl betaine, oleyl dimethyl gamma-carboxypropyl betaine, lauryl bis-(2-hydroxypropyl)alpha- carboxyethyl betaine, or a combination thereof.

[0041] In accordance with an embodiment 32, provided is the method according to any one of embodiments 19 to 31 further comprising: a polyol, optionally, in an amount 20 to about 60 wt.%, based on the total weight of the oral care composition.

[0042] In accordance with an embodiment 33, provided is the method according to embodiment 32, wherein the polyol is selected from sorbitol, xylitol, mannitol, glycerin, ethylene glycol, propylene glycol, butylene glycol, hexylene glycol, polyethylene glycol, a polypropylene glycol, a block polymer of polyethylene glycol and polypropylene glycol, and a combination of two or more thereof.

[0043] In accordance with an embodiment 34, provided is the method according to any one of embodiments 19 to 33 further comprising: a thickening agent, optionally, in an amount from about 0.5 to about 20 wt.%, based on the total weight of the oral care composition.

[0044] In accordance with an embodiment 35, provided is the method according to embodimentDocket No. 14565-OO-WO-Ol-OC34, wherein the thickening agent is selected from polysaccharide, a natural gum, a silica thickener, an acrylate, a polymer, and a combination of two or more thereof.

[0045] In accordance with an embodiment 36, provided is the method according to embodiment 34 or embodiment 35, wherein the thickening agent comprises a silica thickener.

[0046] In accordance with an embodiment 37, provided is the method according to any one of embodiments 19 to 36, wherein the thickening agent comprises a natural gum selected from xanthan gum, karaya gum, gum arabic, gum tragacanth, and a combination of two or more thereof.

[0047] In accordance with an embodiment 38, provided is the method according to any one of embodiments 19 to 37, wherein the sulfate based anionic surfactant comprises sodium lauryl sulfate, sodium lauryl ether sulfate, or a combination thereof.

[0048] In accordance with an embodiment 39, provided is the method according to any one of embodiments 19 to 37, wherein the oral care composition is in accordance with one of embodiments 1 to 18.BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The present invention may become more fully understood from the detailed description and the accompanying drawings, wherein like elements are labeled similarly and in which:

[0050] FIG. 1 is a bar graph of the average platelet area increasing ratio of a non-limiting, example composition as compared to a comparative composition according to aspects of the invention;

[0051] FIG. 2 is a bar graph of the velocity decrease of the non-limiting, example composition as compared to a comparative composition according to aspects of the invention; and

[0052] FIG. 3 is a bar graph of the antibacterial effect of a non-limiting, example composition as compared to a comparative composition on an anaerobic biofilm according to aspects of the invention.

[0053] It should be understood that the various aspects are not limited to the arrangements and instrumentality shown in the drawings.DETAILED DESCRIPTION

[0054] For illustrative purposes, the principles of the present invention are described by referencing various exemplary embodiments thereof. Although certain embodiments of the invention are specifically described herein, one of ordinary skill in the art will readily recognize that the same principles are equally applicable to, and can be employed in other compositions andDocket No. 14565-OO-WO-Ol-OC methods. Before explaining the disclosed embodiments of the present invention in detail, it is to be understood that the invention is not limited in its application to the details of any particular embodiment disclosed herein. The terminology used herein is for the purpose of description and not of limitation.

[0055] As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context dictates otherwise. The singular form of any class of the ingredients refers not only to one chemical species within that class, but also to a mixture of those chemical species. The terms “a” (or “an”), “one or more” and “at least one” may be used interchangeably herein. The terms “comprising”, “including”, and “having” may be used interchangeably. The term “include” should be interpreted as “include, but are not limited to”. The term “including” should be interpreted as “including, but are not limited to”.

[0056] 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. Thus, a range from 1-5, includes specifically 1, 2, 3, 4 and 5, as well as subranges such as 2-5, 3-5, 2-3, 2-4, 1-4, etc.

[0057] The term “about” when referring to a number means any number within a range of 10% of the number. For example, the phrase “about 2 wt.%” refers to a number between and including 1.8 wt.% and 2.2 wt.%.

[0058] All references cited herein are hereby incorporated by reference 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.

[0059] The abbreviations and symbols as used herein, unless indicated otherwise, take their ordinary meaning. The abbreviation “wt.%” means percent by weight with respect to the oral care composition. The symbol “°” refers to a degree, such as a temperature degree or a degree of an angle. The symbols “h”, “min”, “mL”, “nm”, and “ m” refer to hour, minute, milliliter, nanometer, and micrometer, respectively. The abbreviation “UV-VIS” as referring to a spectrometer or spectroscopy, means Ultraviolet- Visible. The abbreviation “rpm” means revolutions per minute.

[0060] When referring to chemical structures, and names, the symbols “C”, “H”, and “O” mean carbon, hydrogen, and oxygen, respectively. The symbols“=” and “= ’ mean single bond, double bond, and triple bond, respectively.Docket No. 14565-OO-WO-Ol-OC

[0061] “Volatile”, as used herein, means having a flash point of less than about 100° C. “Nonvolatile”, as used herein, means having a flash point of greater than about 100° C.

[0062] Any member in a list of species that are used to exemplify or define a genus, may be mutually different from, or overlapping with, or a subset of, or equivalent to, or nearly the same as, or identical to, any other member of the list of species. Further, unless explicitly stated, such as when reciting a Markush group, the list of species that define or exemplify the genus is open, and it is given that other species may exist that define or exemplify the genus just as well as, or better than, any other species listed.

[0063] The phrases, “a mixture thereof,” “a combination thereof,” or a combination of two or more thereof’ do not require that the mixture include all of A, B, C, D, E, and F (although all of A, B,C, D, E, and F may be included). Rather, it indicates that a mixture of any two or more of A, B, C,D, E, and F can be included. In other words, it is equivalent to the phrase “one or more elements selected from the group consisting of A, B, C, D, E, F, and a mixture of any two or more of A, B, C, D, E, and F.” Likewise, the term “a salt thereof” also relates to “salts thereof.” Thus, where the disclosure refers to “an element selected from the group consisting of A, B, C, D, E, F, a salt thereof, and a mixture thereof,” it indicates that that one or more of A, B, C, D, and F may be included, one or more of a salt of A, a salt of B, a salt of C, a salt of D, a salt of E, and a salt of F may be included, or a mixture of any two of A, B, C, D, E, F, a salt of A, a salt of B, a salt of C, a salt of D, a salt of E, and a salt of F may be included.

[0064] All components and elements positively set forth in this disclosure can be negatively excluded from the claims. In other words, the oral care compositions of the instant disclosure can be free or essentially free of all components and elements positively recited throughout the instant disclosure. In some instances, the oral care compositions of the present disclosure may be substantially free of non-incidental amounts of the ingredient(s) or compound(s) described herein. A non-incidental amount of an ingredient or compound is the amount of that ingredient or compound that is added into the oral care composition by itself. For example, an oral care composition may be substantially free of a non-incidental amount of an ingredient or compound, although such ingredient(s) or compound(s) may be present as part of a raw material that is included as a blend of two or more compounds.

[0065] Some of the various categories of components identified may overlap. In such cases where overlap may exist and the oral care composition includes both components (or the compositionDocket No. 14565-OO-WO-Ol-OC includes more than two components that overlap), an overlapping compound does not represent more than one component. For example, certain compounds may be characterized as both a polyol and a humectant. If a particular oral care composition recites both a polyol and a humectant, glycerin will serve only as either a polyol or a humectant — not both.

[0066] For readability purposes, the chemical functional groups are in their adjective form; for each of the adjectives, the word “group” is assumed. For example, the adjective “alkyl” without a noun thereafter, should be read as “an alkyl group.”

[0067] Aspects of the invention are directed to oral care compositions and, preferably, oral care compositions providing a reduction in gum bleeding, as well as methods for producing such oral care compositions. It has been discovered that oleanolic acid readily clumps and / or forms fisheyes in certain aqueous oral care compositions. The inventors discovered that certain combinations of components in particular amounts and ratios thereof can produce oral care compositions that are free of clumps or fisheyes, such as those formed from oleanolic acid. Additionally, the inventors discovered that certain methods for producing the oral care compositions disclosed herein can yield oral care compositions that are free of clumps or fisheyes, such as those formed from oleanolic acid.

[0068] In accordance with some aspects, provided is an oral care composition having a stannous source; a nitrate source; a phosphate source; a surfactant system comprising a sulfate based anionic surfactant, wherein the total amount of sulfate based anionic surfactant is about 1.7 wt.% or less; oleanolic acid; eugenol; and sodium hydroxide in an amount from 0.05 to about 0.8 wt.%, wherein all weight percentages are based on the total weight of the oral care composition.

[0069] In accordance with another aspect, provided is an oral care composition having a stannous source; a nitrate source; a phosphate source; a surfactant system comprising a sulfate based anionic surfactant, wherein the total amount of sulfate based anionic surfactant is 2.2 to about 7 wt.%; oleanolic acid; and eugenol, wherein all weight percentages are based on the total weight of the oral care composition. The oral care compositions disclosed herein are preferably free of clumps or fisheyes formed from oleanolic acid.

[0070] In accordance with yet a further aspect, a method is provided for producing an oral care composition, the method comprising: mixing oleanolic acid and a polyol to obtain an oleanolic acid mixture; and preparing an oral care composition by combining the oleanolic mixture with a stannous source, a nitrate source, a phosphate source, a surfactant system, and eugenol, the oralDocket No. 14565-OO-WO-Ol-OC care composition comprising: a stannous source; a nitrate source; a phosphate source; a surfactant system comprising sodium lauryl sulfate, sodium lauryl ether sulfate, or a combination thereof; oleanolic acid; and eugenol. Preferably, the methods disclosed herein produce oral care compositions that are free of clumps or fisheyes formed from oleanolic acid.

[0071] The oral care compositions may be in the form of dentifrice, toothpaste, mouthwash, gels, varnishes, leave-on products (e.g., in the form of a gel, varnish, etc.), and / or the like. Suitable components, such as those listed below, may be included or excluded from the formulations for the oral care compositions depending on the specific combination of other ingredients and the form of the oral care compositions. Additionally or alternatively, the oral care compositions may in some embodiments have a single phase, which contains that components and / or ingredients of the oral care composition. In other embodiments, the oral care composition may include two or more phases, such as two, three, four, or five phases.

[0072] The oral care compositions typically have a stannous source, which may be a stannous ion source. The stannous source may, in some embodiments, consist of stannous ion source(s). The stannous source may be present in the oral care composition in an amount from about 0.1 to about 5 wt.%, based on the total weight of the oral care composition. For example, the amount of stannous source present in the oral care composition may be from about 0.1 to about 4 wt.%, about 0.1 to about 3 wt.%, about 0.1 to about 2 wt.%; from about 0.3 to about 5 wt.%, about 0.3 to about 4 wt.%, about 0.3 to about 3 wt.%, about 0.3 to about 2 wt.%; from about 0.6 to about 5 wt.%, about 0.6 to about 4 wt.%, about 0.6 to about 3 wt.%, about 0.6 to about 2 wt.%; from about 0.9 to about 5 wt.%, about 0.9 to about 4 wt.%, about 0.9 to about 3 wt.%, about 0.9 to about 2 wt.%; from about 1.2 to about 5 wt.%, about 1.2 to about 4 wt.%, about 1.2 to about 3 wt.%, about 1.2 to about 2 wt.%; from about 1.5 to about 5 wt.%, about 1.5 to about 4 wt.%, about 1.5 to about 3 wt.%; from about 2 to about 5 wt.%, about 2 to about 4 wt.%, about 2 to about 3 wt.%; from about 3 to about 5 wt.%, about 4 to about 5 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition. In at least one embodiment, the oral care composition includes about 0.4 to about 0.5 wt.% of stannous ion source, such as about 0.45 wt.% of stannous ion source.

[0073] The stannous source may be selected from the group consisting of stannous fluoride, stannous chloride, stannous pyrophosphate, stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate, stannous citrate, stannous ethylene glyoxide, and combinations of two or more thereof. The stannous sourceDocket No. 14565-OO-WO-Ol-OC may comprise or consists of stannous fluoride, stannous chloride, stannous pyrophosphate, and a combination of two or more thereof. In some embodiments, the stannous ion source comprises stannous fluoride. In further embodiments, the stannous ion source comprises stannous pyrophosphate.

[0074] The oral care composition may include two or more, three or more, four or more, five or more, or six or more of stannous sources. For instance, oral care composition may comprise 2 to 7, 2 to 6, 2 to 5, 2 to 5, or 2 to 4; 3 to 7, 3 to 6, 2 to 5, or 3 to 5 stannous sources. In some embodiments, the oral care composition comprises stannous fluoride and stannous pyrophosphate. Additionally or alternatively, the oral care composition may comprise stannous fluoride and stannous chloride.

[0075] The oral care compositions typically comprise one or more nitrate source, which may comprise or consist of nitrate ion source(s). The nitrate source(s) may be present in the oral care composition in an amount from about 0.1 to about 7 wt.%, based on the total weight of the oral care composition. For example, the one or more nitrate source(s) may be present in the oral care composition in an amount from about 0.1 to about 6 wt.%, about 0.1 to about 5 wt.%, about 0.1 to about 4 wt.%, about 0.1 to about 3 wt.%, about 0.1 to about 2 wt.%, about 0.1 to about 1 wt.%; from about 0.4 to about 7 wt.%, about 0.4 to about 6 wt.%, about 0.4 to about 5 wt.%, about 0.4 to about 4 wt.%, about 0.4 to about 3 wt.%, about 0.4 to about 2 wt.%, about 0.4 to about 1 wt.%; from about 0.8 to about 7 wt.%, about 0.8 to about 6 wt.%, about 0.8 to about 5 wt.%, about 0.8 to about 4 wt.%, about 0.8 to about 3 wt.%, about 0.8 to about 2 wt.%; from about 1.4 to about 7 wt.%, about 1.4 to about 6 wt.%, about 1.4 to about 5 wt.%, about 1.4 to about 4 wt.%, about 1.4 to about 3 wt.%; from about 2 to about 7 wt.%, about 2 to about 6 wt.%, about 2 to about 5 wt.%, about 2 to about 4 wt.%, about 2 to about 3 wt.%; from about 3 to about 7 wt.%, about 3 to about 6 wt.%, about 3 to about 5 wt.%; from about 4 to about 7 wt.%, about 4 to about 6 wt.%, about 5 to about 7 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0076] The one or more nitrate source may be in the form of a salt or an ion derived therefrom, including, e.g., a nitrate salt selected from an alkali or alkaline earth metal nitrate. Examples of nitrate sources include lithium nitrate, sodium nitrate, potassium nitrate, magnesium nitrate, calcium nitrate, zinc nitrate, silver nitrate, ammonium nitrate, or a combination two or moreDocket No. 14565-OO-WO-Ol-OC thereof. In at least one embodiment, the nitrate ion source comprises or consists of potassium nitrate, sodium nitrate, or a combination thereof.

[0077] The oral care compositions may be formulated to have a molar ratio of nitrate ions to stannous ions, both measured as free ions, that is about 2:1 or less. For example, the oral care composition may have a molar ratio of nitrate ions to stannous ions, both measured as free ions, of from about 0.5:1 to about 2:1, about 0.5:1 to about 1.8:1, about 0.5:1 to about 1.6:1, about 0.5:1 to about 1.4: 1, about 0.5: 1 to about 1.2: 1, about 0.5: 1 to about 1 : 1; from about 0.7: 1 to about 2: 1, about 0.7:1 to about 1.8:1, about 0.7:1 to about 1.6:1, about 0.7:1 to about 1.4:1, about 0.7:1 to about 1.2: 1, about 0.7: 1 to about 1 : 1; from about 0.9: 1 to about 2: 1, about 0.9: 1 to about 1.8: 1, about 0.9:1 to about 1.6:1, about 0.9:1 to about 1.4:1, about 0.9:1 to about 1.2:1, about 0.9:1 to about 1:1, or any range or subrange thereof. In some embodiments, the oral care composition is formulated to have a molar ratio of nitrate ions to stannous ions, both measured as free ions, of about 1:1.

[0078] The oral care compositions typically comprise one or more phosphate source(s). The phosphate source may in some preferred embodiments be a phosphate ion source(s). In some instances, the oral care composition may include one or more phosphate source(s) in an amount from about 0.1 to about 7 wt.%, based on the total weight of the oral care composition. For example, the total amount of phosphate source(s) in the oral care composition may be from about 0.1 to about 6 wt.%, about 0.1 to about 5 wt.%, about 0.1 to about 4 wt.%, about 0.1 to about 3 wt.%, about 0.1 to about 2 wt.%, about 0.1 to about 1 wt.%; from about 0.4 to about 7 wt.%, about 0.4 to about 6 wt.%, about 0.4 to about 5 wt.%, about 0.4 to about 4 wt.%, about 0.4 to about 3 wt.%, about 0.4 to about 2 wt.%, about 0.4 to about 1 wt.%; from about 0.8 to about 7 wt.%, about 0.8 to about 6 wt.%, about 0.8 to about 5 wt.%, about 0.8 to about 4 wt.%, about 0.8 to about 3 wt.%, about 0.8 to about 2 wt.%; from about 1.4 to about 7 wt.%, about 1.4 to about 6 wt.%, about 1.4 to about 5 wt.%, about 1.4 to about 4 wt.%, about 1.4 to about 3 wt.%; from about 2 to about 7 wt.%, about 2 to about 6 wt.%, about 2 to about 5 wt.%, about 2 to about 4 wt.%, about 2 to about 3 wt.%; from about 3 to about 7 wt.%, about 3 to about 6 wt.%, about 3 to about 5 wt.%; from about 4 to about 7 wt.%, about 4 to about 6 wt.%, about 5 to about 7 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0079] The phosphate source may preferably comprise a soluble phosphate compound, such as a phosphate salt. The phosphate source may be a phosphate ion source. Examples of phosphateDocket No. 14565-OO-WO-Ol-OC sources include tetrasodium pyrophosphate, dicalcium orthophosphate dihydrate, dicalcium phosphate dihydratc, calcium hydrogen phosphate, calcium pyrophosphate, p-calcium pyrophosphate, tricalcium phosphate, calcium metaphosphate, potassium metaphosphate, sodium metaphosphate, or a combination thereof. The phosphate source may be a pyrophosphate salt, such as an alkali metal pyrophosphate salt. In certain embodiments, the alkali metal pyrophosphate is selected from a tetra alkali metal pyrophosphate, dialkali metal diacid pyrophosphate, trialkali metal monoacid pyrophosphate and mixtures thereof, wherein the alkali metals are sodium or potassium. For instance, the phosphate source may include tetrasodium pyrophosphate (TSPP), tetrapotassium pyrophosphate, sodium tripolyphosphate, tetrapolyphosphate, sodium trimetaphosphate, sodium hexametaphosphate, or a combination of two or more thereof. The phosphate source may be chosen from orthophosphates, polymetaphosphates, pyrophosphates, and a combination of two or more thereof. In some instances, the phosphate source includes tetrasodium pyrophosphate (TSPP), sodium tripolyphosphate (STPP), or a combination thereof. In at least one embodiment, the phosphate source comprises tetrasodium pyrophosphate. The phosphate source, when in the form of a salt, maybe in their hydrated and / or unhydrated forms.

[0080] In addition to the stannous source, nitrate source, and phosphate source, the oral care compositions typically include eugenol and oleanolic acid. The oral care compositions typically comprise oleanolic acid, eugenol, and one or more zinc source in certain amounts and ratios thereof. The oleanolic acid may be incorporated into the oral care composition in the form of a salt. The amount of oleanolic acid and / or a salt thereof in the oral care composition may be from about 0.01 to about 3 wt.%, based on the total weight of the oral care composition. For instance, the oral care composition may include oleanolic acid and / or a salt thereof in an amount from about 0.01 to about 3 wt.%, about 0.01 to about 2 wt.%, about 0.01 to about 1 wt.%, about 0.01 to about 0.5 wt.%, about 0.01 to about 0.3 wt.%, about 0.01 to about 0.2 wt.%, about 0.01 to about 0.1 wt.%; from about 0.05 to about 3 wt.%, about 0.05 to about 2 wt.%, about 0.05 to about 1 wt.%, about 0.05 to about 0.5 wt.%, about 0.05 to about 0.3 wt.%, about 0.05 to about 0.2 wt.%, about 0.05 to about 0.1 wt.%; from about 0.1 to about 3 wt.%, about 0.1 to about 2 wt.%, about 0.1 to about 1 wt.%, about 0.1 to about 0.5 wt.%, about 0.1 to about 0.3 wt.%, about 0.1 to about 0.2 wt.%; from about 0.2 to about 3 wt.%, about 0.2 to about 2 wt.%, about 0.2 to about 1 wt.%, about 0.2 to about 0.5 wt.%, about 0.2 to about 0.3 wt.%; from about 0.5 to about 3 wt.%, about 0.5 toDocket No. 14565-OO-WO-Ol-OC about 2 wt.%, about 0.5 to about 1 wt.%; from about 1 to about 3 wt.%, about 1 to about 2 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0081] The oleanolic acid may be obtained from certain medicinal plants, such as Calendula officinalis L. (marigold), Ligustrum lucidum Ait (oleaceae), and Hemsleya Chinensis Cogn. The following is the chemical structure of oleanic acid:

[0082] Eugenol is typically present in the oral care composition. The amount of eugenol may be present in an amount from about 0.01 to about 1.5 wt.%, based on the total weight of the oral care composition. For instance, the oral care composition may include from about 0.01 to about 1.5 wt.%, about 0.01 to about 1 wt.%, about 0.01 to about 0.8 wt.%, about 0.01 to about 0.6 wt.%, about 0.01 to about 0.4 wt.%, about 0.01 to about 0.2 wt.%, about 0.01 to about 0.1 wt.%; from about 0.05 to about 1.5 wt.%, about 0.05 to about 1 wt.%, about 0.05 to about 0.8 wt.%, about 0.05 to about 0.6 wt.%, about 0.05 to about 0.4 wt.%, about 0.05 to about 0.2 wt.%, about 0.05 to about 0.1 wt.%; from about 0.1 to about 1.5 wt.%, about 0.1 to about 1 wt.%, about 0.1 to about 0.8 wt.%, about 0.1 to about 0.6 wt.%, about 0.1 to about 0.4 wt.%, about 0.1 to about 0.2 wt.%; from about 0.2 to about 1.5 wt.%, about 0.2 to about 1 wt.%, about 0.2 to about 0.8 wt.%, about 0.2 to about 0.6 wt.%, about 0.2 to about 0.4 wt.%; from about 0.5 to about 1.5 wt.%, about 0.5 to about 1 wt.%, about 0.5 to about 0.8 wt.%, about 1 to about 1.5 wt.%, or any range or subrange formed therefrom, based on the total weight of the oral care composition.

[0083] Eugenol (4-allyl-2-methoxyphenol), is a naturally occurring phenol essential oil extracted from, e.g., cloves, nutmeg, cinnamon, basil, and bay leaf. Eugenol may also be provided as methyl eugenol or iso-eugenol. For instance, the oral care composition may comprise methyl eugenol, isoeugenol, or a combination thereof.Docket No. 14565-OO-WO-Ol-OC

[0084] The oral care composition may, in some embodiments, be specifically formulated to have certain weight ratios of the olcanolic acid to the eugenol. For instance, the oral care composition may have a weight ratio of the oleanolic acid to the eugenol of about 1:1 to about 3:1. In some embodiments, the oral care composition has a weight ratio of the oleanolic acid to the eugenol of about 1.5:1 to about 3:1, about 2:1 to about 3:1, about 2.5:1 to about 3:1, about 1:1 to about 2.5:1, about 1.5:1 to about 2.5:1, about 2:1 to about 2.5: 1, about 1:1 to about 2:1, about 1.5:1 to about 2: 1, or any range or subrange thereof.

[0085] The oral care composition typically comprises a surfactant system, which may be present in an amount from about 0.5 to about 10 wt.%, based on the total weight of the oral care composition. The surfactant system may be present in a total amount from about 0.5 to about 8 wt.%, about 0.5 to about 6 wt.%, about 0.5 to about 5 wt.%, about 0.5 to about 4 wt.%, about 0.5 to about 3 wt.%, about 0.5 to about 2 wt.%; from about 1.5 to about 10 wt.%, about 1.5 to about 8 wt.%, about 1.5 to about 6 wt.%, about 1.5 to about 5 wt.%, about 1.5 to about 4 wt.%, about 1.5 to about 3 wt.%; from about 2 to about 10 wt.%, about 2 to about 8 wt.%, about 2 to about 6 wt.%, about 2 to about 5 wt.%; from about 3 to about 10 wt.%, about 3 to about 8 wt.%, about 3 to about 6 wt.%, about 3 to about 5 wt.%; or any range or subrange thereof, based on the total weight of the oral care composition.

[0086] The surfactant system may be specifically formulated, e.g., depending on the other components in the oral care composition. For example, the surfactant system may comprise a total amount of sulfate based anionic surfactant of about 1.7 wt.% or less, e.g., when the oral care composition comprises sodium hydroxide in an amount from 0.05 to about 0.8 wt.%, wherein all weight percentages are based on the total weight of the oral care composition. In some embodiments, the surfactant system comprises a total amount of sulfate based anionic surfactant of about 0.5 to about 1.7 wt.%, about 0.5 to about 1.5 wt.%, about 0.5 to about 1.2 wt.%, about 0.5 to about 1 wt.%; from about 1 to about 1.7 wt.%, about 1 to about 1.5 wt.%, about 1 to about 1.2 wt.%, or any range or subrange therebetween, based on the total weight of the oral care composition.

[0087] In other embodiments, however, the surfactant system may comprise 2.2 to about 7 wt.% of a sulfate based anionic surfactant, based on the total weight of the oral care composition, e.g., when the oral care composition does not have sodium hydroxide. For example, in some embodiments, the oral care composition has from 2.2 to about 7 wt.%, 2.2 to about 5 wt.%, 2.2 toDocket No. 14565-OO-WO-Ol-OC about 4 wt.%, 2.2 to about 3 wt.%; from about 2.5 to about 7 wt.%, about 2.5 to about 5 wt.%, about 2.5 to about 4 wt.%, about 2.5 to about 3 wt.%; from about 3 to about 7 wt.%, about 3 to about 5 wt.%, about 3 to about 4 wt.%, from about 4 to about 7 wt.%, about 4 to about 6 wt.%, or any range or subrange therebetween, based on the total weight of the oral care composition.

[0088] The sulfate based anionic surfactants may comprise or consist of sodium lauryl sulfate, sodium lauryl ether sulfate, ammonium lauryl sulfate, ammonium lauryl ether sulfate, sodium dodecyl sulfate, sodium coco-sulfate, ammonium coco-sulfate, or a combination of two or more thereof. In some cases, the sulfate based anionic surfactants comprise or consist of sulfate based anionic surfactants selected from sodium lauryl sulfate, sodium lauryl ether sulfate, or a combination thereof.

[0089] The surfactant system may comprise one or more amphoteric surfactant(s), e.g., in an amount from about 0.1 to about 5 wt.%, based on the total weight of the oral care composition. For example, the one or more amphoteric surfactant(s) may be present in the surfactant system in an amount from about 0.1 to about 4 wt.%, about 0.1 to about 3 wt.%, about 0.1 to about 2 wt.%, about 0.1 to about 1 wt.%; from about 0.3 to about 5 wt.%, about 0.3 to about 4 wt.%, about 0.3 to about 3 wt.%, about 0.3 to about 2 wt.%, about 0.3 to about 1 wt.%; from about 0.6 to about 5 wt.%, about 0.6 to about 4 wt.%, about 0.6 to about 3 wt.%, about 0.6 to about 2 wt.%, about 0.6 to about 1 wt.%; from about 1 to about 5 wt.%, about 1 to about 4 wt.%, about 1 to about 3 wt.%, about 1 to about 2 wt.%; from about 1.5 to about 5 wt.%, about 1.5 to about 4 wt.%, about 1.5 to about 3 wt.%; from about 2 to about 5 wt.%, about 2 to about 4 wt.%, about 2 to about 3 wt.%; from about 3 to about 5 wt.%, about 3 to about 4 wt.%, about 4 to about 5 wt.%, including any range or subrange thereof, based on the total weight of the oral care composition.

[0090] Amphoteric surfactants are typically characterized by a combination of high surfactant activity, lather forming and mildness. The amphoteric surfactant may comprise a substituent containing 8 to 18 carbon atoms and a substituent containing one or more carboxylate, sulfonate, sulfate, phosphate, or phosphonate. For instance, the amphoteric surfactant may have an alkyl group comprising from 8 to 20 carbon atoms, 8 to 16 carbon atoms, 10 to 16 carbon atoms, or 10 to 13 carbon atoms. The amphoteric surfactant(s) may include, but are not limited to, derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight chain or branched. In some cases, one of the aliphatic substituents of the amphoteric surfactant contains about 8 to about 18 carbon atoms and one of the aliphatic substituents contains an anionic waterDocket No. 14565-OO-WO-Ol-OC solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate. The amphoteric surfactants disclosed herein may be present in the oral care composition in a salt form.

[0091] The amphoteric surfactants may include alkyl amphopropionates, betaines, alkyl sultaines, alkyl amphoacetates, or a combination of two or more thereof. Preferably, the oral care composition includes an amphoteric surfactant selected from betaine surfactants (also referred to herein as betaines). Examples of betaine surfactants include, e.g., alkyl betaines, such as coco dimethyl carboxymethyl betaine, lauryl dimethyl carboxy-methyl betaine, lauryl dimethyl alphacarboxyethyl betaine, cetyl dimethyl carboxymethyl betaine, lauryl bis-(2-hydroxyethyl)carboxy methyl betaine, stearyl bis-(2-hydroxypropyl)carboxymethyl betaine, oleyl dimethyl gammacarboxypropyl betaine, lauryl bis-(2-hydroxypropyl)alpha-carboxyethyl betaine. In some instances, the betaine surfactant is selected from coca betaine, cocamidopropyl betaine, lauryl betaine, laurylhydroxy sulfobetaine, lauryldimethyl betaine, behenyl betaine, capryl / capramidopropyl betaine, lauryl hydroxysultaine, stearyl betaine, and a combination of two or more thereof. For instance, the betaine surfactant may be coco betaine, cocamidopropyl betaine, behenyl betaine, capryl / capramidopropyl betaine, and lauryl betaine, or a combination of two or more thereof. In at least one embodiment, the oral care composition comprises coco betaine, cocamidopropyl betaine, or a combination thereof. In at least one embodiment, the amphoteric surfactant comprises or consists of a betaine surfactant selected from coca betaine, cocamidopropyl betaine, coco dimethyl carboxymethyl betaine, lauryl dimethyl carboxy-methyl betaine, lauryl dimethyl alpha-carboxyethyl betaine, cetyl dimethyl carboxymethyl betaine, lauryl bis-(2-hydroxyethyl)carboxy methyl betaine, stearyl bis-(2-hydroxypropyl)carboxymethyl betaine, oleyl dimethyl gamma-carboxypropyl betaine, lauryl bis-(2-hydroxypropyl)alpha- carboxyethyl betaine, or a combination thereof.

[0092] The surfactant system may comprise one or more nonionic surfactant(s). The one or more nonionic surfactant(s) may be present in an amount from about 0.1 to about 7 wt.%, based on the total weight of the oral care composition. In some instances, the one or more nonionic surfactant(s) is present in the surfactant system in an amount from about 0.1 to about 6 wt.%, about 0.1 to about 5 wt.%, about 0.1 to about 4 wt.%, about 0.1 to about 3 wt.%, about 0.1 to about 2 wt.%, about 0.1 to about 1 wt.%; from about 0.4 to about 7 wt.%, about 0.4 to about 6 wt.%, about 0.4 to about 5 wt.%, about 0.4 to about 4 wt.%, about 0.4 to about 3 wt.%, about 0.4 to about 2 wt.%, about 0.4 to about 1 wt.%; from about 0.8 to about 7 wt.%, about 0.8 to about 6 wt.%, about 0.8 to about 5Docket No. 14565-OO-WO-Ol-OC wt.%, about 0.8 to about 4 wt.%, about 0.8 to about 3 wt.%, about 0.8 to about 2 wt.%; from about 1.4 to about 7 wt.%, about 1.4 to about 6 wt.%, about 1.4 to about 5 wt.%, about 1.4 to about 4 wt.%, about 1.4 to about 3 wt.%; from about 2 to about 7 wt.%, about 2 to about 6 wt.%, about 2 to about 5 wt.%, about 2 to about 4 wt.%, about 2 to about 3 wt.%; from about 3 to about 7 wt.%, about 3 to about 6 wt.%, about 3 to about 5 wt.%; from about 4 to about 7 wt.%, about 4 to about 6 wt.%, about 5 to about 7 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0093] The one or more nonionic surfactant(s) may be selected from glucosides, compounds produced by the condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound, which may be aliphatic or alkylaromatic in nature, poloxamers, and combinations of two or more thereof. Examples of glucoside surfactants include decyl glucoside, stearyl glucoside, lauryl glucoside, coco-glucoside, cetearyl glucoside, decyl lauryl glucoside, lauroyl ethyl glucoside, myristoyl ethyl glucoside, oleoyl ethyl glucoside, or a combination of two or more thereof. Additionally or alternatively, the glucoside surfactant may be chosen from polyglucosides, such as alkylpolyglucosides. Additional examples of nonionic surfactants include polyoxyethylene, polyoxyethylene sorbitan esters, hydrogenated castor oil, fatty alcohol ethoxylates, polyethylene oxide condensates of alkyl phenols, products derived from the condensation of ethylene oxide with the reaction product of propylene oxide and ethylene diamine, ethylene oxide condensates of aliphatic alcohols, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides, or a combination of two or more thereof. In some instances, the nonionic surfactant comprises amine oxides, fatty acid amides, ethoxylated fatty alcohols, or a combination of two or more thereof. In some embodiments, the oral care composition may be substantially free of or free of one or more of the above anionic, amphoteric, or nonionic surfactants.

[0094] The oral care compositions may comprise sodium hydroxide in an amount from 0.05 to about 0.8 wt.%, based on the total weight of the oral care composition. For example, the amount of sodium hydroxide in the oral care composition may be from 0.05 to about 0.8 wt.%, 0.05 to about 0.6 wt.%, 0.05 to about 0.4 wt.%, 0.05 to about 0.2 wt.%, 0.05 to about 0.1 wt.%; from about 0.1 to about 0.8 wt.%, about 0.1 to about 0.6 wt.%, about 0.1 to about 0.4 wt.%, about 0.1 to about 0.2 wt.%; from about 0.15 to about 0.8 wt.%, about 0.15 to about 0.6 wt.%, about 0.15 to about 0.4 wt.%, about 0.15 to about 0.2 wt.%; from about 0.25 to about 0.8 wt.%, about 0.25 to aboutDocket No. 14565-OO-WO-Ol-OC0.6 wt.%, about 0.25 to about 0.4 wt.%; from about 0.35 to about 0.8 wt.%, about 0.35 to about 0.6 wt.%, about 0.35 to about 0.5 wt.%, about 0.1 to about 0.2 wt.%; from about 0.5 to about 0.8 wt.%, about 0.5 to about 0.7 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition. In some embodiments, however, the oral care composition may be substantially free or free of sodium hydroxide.

[0095] The oral care compositions may include one or more polyol(s). The one or more polyol(s) may be present in the oral care composition in an amount from about 20 to about 60 wt.%, based on the total weight of the oral care composition. For example, the oral care composition may include polyol(s) in an amount from about 20 to about 55 wt.%, about 20 to about 50 wt.%, about 20 to about 45 wt.%, about 20 to about 40 wt.%, about 20 to about 37 wt.%, about 20 to about 34 wt.%, about 20 to about 31 wt.%, about 20 to about 28 wt.%; from about 25 to about 60 wt.%, about 25 to about 55 wt.%, about 25 to about 50 wt.%, about 25 to about 45 wt.%, about 25 to about 40 wt.%, about 25 to about 37 wt.%, about 25 to about 34 wt.%, about 25 to about 31 wt.%; from about 28 to about 60 wt.%, about 28 to about 55 wt.%, about 28 to about 50 wt.%, about 28 to about 45 wt.%, about 28 to about 40 wt.%, about 28 to about 37 wt.%, about 28 to about 34 wt.%, about 28 to about 31 wt.%; from about 31 to about 60 wt.%, about 31 to about 55 wt.%, about 31 to about 50 wt.%, about 31 to about 45 wt.%, about 31 to about 40 wt.%, about 31 to about 37 wt.%; from about 34 to about 50 wt.%, about 34 to about 45 wt.%, about 34 to about 40 wt.%; from about 37 to about 60 wt.%, about 37 to about 55 wt.%, about 37 to about 50 wt.%, about 37 to about 45 wt.%; from about 40 to about 60 wt.%, about 40 to about 55 wt.%, about 40 to about 50 wt.%, about 40 to about 45 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0096] The polyol(s) may be chosen from glycols or compounds with numerous hydroxyl groups. The one or more polyols may be liquid at ambient temperature (25 °C). The polyol may be a humectant. In some preferred embodiments, the polyol(s) comprises glycerin, glycol, inositol, maltitol, mannitol, sorbitol, xylitol, propylene glycol, polypropylene glycol (PPG), polyethylene glycol (PEG), a block copolymer of PPG and PEG, a saccharide (e.g., fructose, glucose, sucrose and mixtures of saccharides, such as honey), or a combination of two or more thereof. For instance, the oral care composition comprises maltitol, mannitol, sorbitol, xylitol, a polypropylene glycol (PPG), a polyethylene glycol (PEG), a block copolymer of PPG and PEG, or a combination or two or more thereof.Docket No. 14565-OO-WO-Ol-OC

[0097] In some cases, the oral care composition includes one or more polyol selected from the group consisting of C2-C32 polyols. The one or more polyols may have from 2 to 32 carbon atoms, from 3 to 16 carbon atoms, or from 3 to 12 carbon atoms. For example, the oral care composition may comprise ethylene glycol, propylene glycol, butylene glycol, hexylene glycol, glycerin, diglycerin, diethylene glycol, and dipropylene glycol, or a combination of two or more thereof. Additional, non-limiting examples of polyols that may, optionally, be included in the oral care include and / or may be chosen from alkanediols such as glycerin, 1,2,6-hexanetriol, trimethylolpropane, ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, dipropylene glycol, 2-butene-l,4-diol, 2-ethyl-l,3-hexanediol, 2-methyl-2,4-pentanediol, caprylyl glycol, 1,2-hexanediol, 1,2-pentanediol, and 4-methyl-l,2-pentanediol; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monomethyl ether acetate, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol mono-n-propyl ether, ethylene glycol mono-iso-propyl ether, diethylene glycol mono-iso-propyl ether, ethylene glycol mono-n-butyl ether, ethylene glycol mono-t-butyl ether, diethylene glycol mono-t-butyl ether, 1 -methyl- 1-methoxybutanol, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol mono-t- butyl ether, propylene glycol mono-n-propyl ether, propylene glycol mono-iso-propyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol mono-n-propyl ether, dipropylene glycol mono-iso-propyl ether, sorbitol, sorbitan, triacetin, and a mixture thereof.

[0098] Additionally or alternatively, the oral care composition may include polyol(s) having a molecular weight of from about 100 to 5000 g / mol. For instance, the polyol may comprise a polyethylene glycol, a polypropylene glycol, a block polymer of polyethylene glycol and polypropylene glycol, or a combination of two or more thereof. In some embodiments, the polyol comprises a polypropylene glycol, a polypropylene glycol, and / or a block polymer of polyethylene glycol and polypropylene glycol having a molecular weight of about 100 to about 900, about 200 to about 800, about 400, about 1500 to about 2500, about 2000 to about 4500 or any range or subrange thereof. In some embodiments, the polyol is a polyethylene glycol, such as polyethylene glycol 600. In some embodiments, the compositions of the disclosure comprise one or more polyethylene glycols, for example, polyethylene glycols in a molecular weight range from 200 toDocket No. 14565-OO-WO-Ol-OC800. For example, the compositions may comprise one or more of polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol, 600 or polyethylene glycol 800.

[0099] The oral care composition may include one or more thickening agent(s), e.g., in an amount from about 0.5 to about 20 wt.%, based on the total weight of the oral care composition. For example, the amount of thickening agent(s) in the oral care composition may be from about 0.5 to about 17 wt.%, about 0.5 to about 14 wt.%, about 0.5 to about 11 wt.%, about 0.5 to about 9 wt.%, about 0.5 to about 7 wt.%, about 0.5 to about 5 wt.%, about 0.5 to about 4 wt.%, about 0.5 to about 3 wt.%; from about 1 to about 20 wt.%, about 1 to about 17 wt.%, about 1 to about 14 wt.%, about 1 to about 11 wt.%, about 1 to about 9 wt.%, about 1 to about 7 wt.%, about 1 to about 5 wt.%, about 1 to about 4 wt.%, about 1 to about 3 wt.%; from about 2 to about 20 wt.%, about 2 to about 17 wt.%, about 2 to about 14 wt.%, about 2 to about 11 wt.%, about 2 to about 9 wt.%, about 2 to about 7 wt.%, about 2 to about 5 wt.%, about 2 to about 4 wt.%, about 2 to about 3 wt.%; from about 4 to about 20 wt.%, about 4 to about 17 wt.%, about 4 to about 14 wt.%, about 4 to about 11 wt.%, about 4 to about 9 wt.%, about 4 to about 7 wt.%; from about 7 to about 20 wt.%, about 7 to about 17 wt.%, about 7 to about 14 wt.%, about 7 to about 11 wt.%; from about 10 to about 20 wt.%, about 10 to about 17 wt.%, about 10 to about 14 wt.%; from about 14 to about 20 wt.%, about 14 to about 17 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0100] Thickening agents may be referred to as “thickeners” or “viscosity modifying agents.” Thickening agents are typically included to increase the viscosity of the oral care compositions. Nonetheless, in some instances, certain thickening agents provide additional, surprising benefits to the oral care compositions.

[0101] The one or more thickening agent(s) may be selected from a polysaccharide, a silica thickener, an acrylate, a polymer, and a combination of two or more thereof. Examples of polysaccharides include cellulose, carboxymethyl hydroxyethylcellulose, cellulose acetate propionate carboxylate, hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, methyl hydroxyethylcellulose, microcrystalline cellulose, sodium cellulose sulfate, carrageenan, or a combination of two more thereof. Natural gums such as xanthan gum, karaya gum, gum arabic, and gum tragacanth can also be incorporated. Colloidal magnesium aluminum silicate can also be used as a component ofDocket No. 14565-OO-WO-Ol-OC the thickening composition to further improve the composition's texture. Silica thickeners, which form polymeric structures or gels in aqueous media, may be present. Silica thickeners arc typically physically and functionally distinct from the particulate silica abrasives as the silica thickeners are very finely divided and provide little or no abrasive action. Fumed silica is an example of a silica thickener that may be suitable in some embodiments of the oral care composition.

[0102] In certain preferred embodiments, the thickening agents comprise or consist of a silica thickening agent and a natural gum, such as xanthan gum, karaya gum, gum arabic, and gum tragacanth. In at least one embodiment, the thickening agents consist of a silica thickening agent and xanthan gum.

[0103] In some embodiments, the one or more thickening agent(s) comprises a polymer selected from polysaccharides, acrylates, polyvinyl pyrrolidone, polyitaconates, an acrylamides, and combinations thereof. Polyvinyl pyrrolidone generally refers to a polymer containing vinylpyrrolidone (e.g., N-vinylpyrrolidone, N-vinyl-2-pyrrolidione, and N-vinyl-2-pyrrolidinone) as a monomeric unit.

[0104] Examples of acrylates that may be included in the oral care composition include, e.g., isobutyl acrylate, tert-butyl acrylate, 2-ethylhexyl acrylate, lauryl acrylate, lauryl / tridecyl acrylate, cetyl acrylate, stearyl acrylate, cyclohexyl acrylate, benzyl acrylate, isobornyl acrylate, 2- methoxyethyl acrylate, 2-ethoxyethyl acrylate, 2-ethoxyethoxyethyl acrylate, 2-phenoxyethyl acrylate, tetrahydrofurfuryl acrylate, 2-hydroxyethyl acrylate, 2-hydroxypropyl acrylate, 4- hydroxybutyl acrylate, dimethylaminoethyl acrylate, 1 ,4-butanediol acrylate, or a combination of two or more thereof.

[0105] The acrylate may be chosen from diacrylates, methacrylates, and a combination of two or more thereof. In some embodiments, the oral care composition includes a diacrylate chosen from 1,4-butanediol, 1,6-hexanediol, tetraethylene glycol, tripropylene glycol, ethoxylated bisphenol- A, and a combination of two or more thereof. Triacrylate monomers include trimethylol propane, ethoxylated, glyceryl propoxy, and pentaerythritol. Examples of methacrylates include such as methyl methacrylate, ethyl methacrylate, n-butyl methacrylate, and / or the like. Examples of acrylamides include, but are not limited to, acrylamide, methacrylamide and di(Ci-C3o) alkylacrylamides and -methacrylamides such as those of methyl, ethyl, propyl, butyl, pentyl, hexyl and the like.Docket No. 14565-OO-WO-Ol-OC

[0106] Additionally or alternatively, the oral care composition may include one or more anticalculus agent. Examples of anti-calculus agents include, but arc not limited to: phosphates and polyphosphates, polyaminopropane sulfonic acid (AM PS), polyolefin sulfonates, polyolefin phosphates, diphosphonates such as azacycloalkane-2, 2-diphosphonates (e.g., azacycloheptane- 2,2-diphosphonic acid), N-methyl azacyclopentane-2,3-diphosphonic acid, ethane- 1 -hydroxy- 1,1- diphosphonic acid (EHDP) and ethane- 1 -amino- 1,1 -diphosphonate, phosphonoalkane carboxylic acids and. Useful inorganic phosphate and polyphosphate salts include monobasic, dibasic and tribasic sodium phosphates. Soluble pyrophosphates, such as those disclosed herein may be useful anticalculus agents. The pyrophosphate salts can be any of the alkali metal pyrophosphate salts.

[0107] The oral care composition may include the anti-calculus agents in an amount from about 0.1 to about 7 wt.%, based on the total weight of the oral care composition. For example, the anticalculus agent(s) may be present in the oral care composition in an amount from about 0.1 to about6 wt.%, about 0.1 to about 5 wt.%, about 0.1 to about 4 wt.%, about 0.1 to about 3 wt.%, about 0.1 to about 2 wt.%, about 0.1 to about 1 wt.%; from about 0.4 to about 7 wt.%, about 0.4 to about 6 wt.%, about 0.4 to about 5 wt.%, about 0.4 to about 4 wt.%, about 0.4 to about 3 wt.%, about 0.4 to about 2 wt.%, about 0.4 to about 1 wt.%; from about 0.8 to about 7 wt.%, about 0.8 to about 6 wt.%, about 0.8 to about 5 wt.%, about 0.8 to about 4 wt.%, about 0.8 to about 3 wt.%, about 0.8 to about 2 wt.%; from about 1.4 to about 7 wt.%, about 1.4 to about 6 wt.%, about 1.4 to about 5 wt.%, about 1.4 to about 4 wt.%, about 1.4 to about 3 wt.%; from about 2 to about 7 wt.%, about 2 to about 6 wt.%, about 2 to about 5 wt.%, about 2 to about 4 wt.%, about 2 to about 3 wt.%; from about 3 to about 7 wt.%, about 3 to about 6 wt.%, about 3 to about 5 wt.%; from about 4 to about7 wt.%, about 4 to about 6 wt.%, about 5 to about 7 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0108] The oral care compositions may include water in some embodiments. The water may be present in the oral care composition in an amount from about 5 to about 37 wt.%, based on the total weight of the oral care composition. For example, the oral care composition may include water in an amount from about 5 to about 34 wt.%, about 5 to about 31 wt.%, about 5 to about 28 wt.%, about 5 to about 25 wt.%, about 5 to about 20 wt.%; from about 10 to about 37 wt.%, about 10 to about 34 wt.%, about 10 to about 31 wt.%, about 10 to about 28 wt.%, about 10 to about 25 wt.%; from about 15 to about 37 wt.%, about 15 to about 34 wt.%, about 15 to about 31 wt.%, about 15 to about 28 wt.%, about 15 to about 25 wt.%; from about 20 to about 37 wt.%, about 20Docket No. 14565-OO-WO-Ol-OC to about 34 wt.%, about 20 to about 31 wt.%, about 20 to about 28 wt.%; from about 25 to about 37 wt.%, about 25 to about 34 wt.%, about 25 to about 31 wt.%; from about 28 to about 37 wt.%, about 28 to about 34 wt.%, about 28 to about 31 wt.%; or any range or subrange thereof, based on the total weight of the oral care composition.

[0109] In some embodiments, the oral care compositions may include one or more sweeteners. The oral care composition may include caloric sweeteners and / or non-caloric sweeteners. Examples of non-caloric sweeteners include saccharin, for example, sodium saccharin, acesulfame, neotame, cyclamate or sucralose; natural high-intensity sweeteners, such as thaumatin, stevioside or glycyrrhizin; or sugar alcohols, such as sorbitol, xylitol, maltitol and mannitol. Examples of caloric sweeteners include sugars, such as fructose, glucose, sucrose, and high fructose syrups.

[0110] The one or more sweetener(s) may be present in the oral care composition in an amount from about 0.1 to about 50 wt.%, based on the total weight of the oral care composition. For example, the oral care composition may have a total amount of sweetener(s) from about 0.1 to about 40 wt.%, about 0.1 to about 30 wt.%, about 0.1 to about 20 wt.%, about 0.1 to about 10 wt.%, about 0.1 to about 5 wt.%, about 0.1 to about 3 wt.%; from about 1 to about 50 wt.%, about 1 to about 40 wt.%, about 1 to about 30 wt.%, about 1 to about 20 wt.%, about 1 to about 10 wt.%, about 1 to about 5 wt.%, about 1 to about 3 wt.%; from about 5 to about 50 wt.%, about 5 to about 40 wt.%, about 5 to about 30 wt.%, about 5 to about 20 wt.%, about 5 to about 10 wt.%; from about 10 to about 50 wt.%, about 10 to about 45 wt.%, about 10 to about 40 wt.%, about 10 to about 35 wt.%, about 10 to about 30 wt.%, about 10 to about 25 wt.%; from about 15 to about 50 wt.%, about 15 to about 45 wt.%, about 15 to about 40 wt.%, about 15 to about 37 wt.%, about 15 to about 34 wt.%, about 15 to about 31 wt.%, about 15 to about 28 wt.%, about 15 to about 25 wt.%; from about 20 to about 50 wt.%, about 20 to about 45 wt.%, about 20 to about 40 wt.%, about 20 to about 37 wt.%, about 20 to about 34 wt.%, about 20 to about 31 wt.%, about 20 to about 28 wt.%; from about 25 to about 50 wt.%, about 25 to about 45 wt.%, about 25 to about 40 wt.%, about 25 to about 37 wt.%, about 25 to about 34 wt.%, about 25 to about 31 wt.%; from about 28 to about 50 wt.%, about 28 to about 45 wt.%, about 28 to about 40 wt.%, about 28 to about 37 wt.%, about 28 to about 34 wt.%, about 28 to about 31 wt.%; from about 31 to about 50 wt.%, about 31 to about 45 wt.%, about 31 to about 40 wt.%, about 31 to about 37 wt.%; from about 34 to about 50 wt.%, about 34 to about 45 wt.%, about 34 to about 40 wt.%; from about 37Docket No. 14565-OO-WO-Ol-OC to about 50 wt.%, about 37 to about 45 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0111] In some embodiments, the oral care composition preferably is substantially free or free of caloric sweeteners. For example, the oral care compositions may have about 4 wt.% or less, about 3 wt.% or less, about 2 wt.% or less, about 1 wt.% or less, about 0.5 wt.% or less, or about 0.1 wt.% or less, based on the weight of the oral care composition. In at least one embodiment, the oral care composition contains about 0 wt.% or 0 wt.% of caloric sweeteners, based on the weight of the oral care composition.

[0112] The oral care compositions of the present disclosure may include a flavoring agent. The flavoring agent is typically incorporated in the oral care composition at a concentration of about 0.01 to about 3 wt.% by weight of the oral care composition. For example, the amount of flavoring agent(s) present in the oral care composition may be from about 0.01 to about 2 wt.%, about 0.01 to about 1 wt.%, about 0.01 to about 0.5 wt.%, about 0.01 to about 0.1 wt.%; from about 0.1 to about 3 wt.%, about 0.1 to about 2 wt.%, about 0.1 to about 1 wt.%, about 0.1 to about 0.5 wt.%; from about 0.5 to about 3 wt.%, about 0.5 to about 2 wt.%, about 0.5 to about 1 wt.%; from about 1 to about 3 wt.%, about 1 to about 2 wt.%; from about 2 to about 3 wt.%, including any range or subrange thereof, based on the total weight of the oral care composition.

[0113] Suitable flavoring agents include, but are not limited to, essential oils and various flavoring aldehydes, esters, alcohols, and similar materials. Examples of the essential oils include oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Also useful are such chemicals as menthol, carvone, and anethole. Additional flavoring agents may include, but are not limited to menthol, artificial vanilla, cinnamon derivatives, and various fruit flavors, spearmint oil, peppermint oil, cinnamon oil, oil of wintergreen (methylsalicylate), clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, oil of nutmeg, oil of sage, oil of bitter almonds, cassia oil, and a combination of two or more thereof.

[0114] The oral care compositions may include one or more colorants. Exemplary colorants can include natural or uncertified colors from natural sources or certified colors for the effect of color. In some embodiments, the colorant can include dyes, certified aluminum lakes or colors derived from a natural source. The colorant may be water-based, oil-based or dry. The colorants can be primary colors, blends of colors or discrete mixtures of colors, such as confetti. The concentrationsDocket No. 14565-OO-WO-Ol-OC of the colorant in the oral care composition may be from trace amount to about 0.6 wt.%, from about 0.1 to about 0.5 wt.%, about 0.2 to about 0.4 wt.%, or about 0.15 to about 0.35 wt.%, based on the total weight of the oral care composition.

[0115] The oral care composition may include one or more pH adjusters to increase or decrease the overall pH of the oral care composition. For example, one or more acids may be included to decrease the pH of the oral care composition. Examples of suitable acids for decreasing the pH of the oral care composition include, but are not limited to, citric acid, acetic acid, and the like. The oral care composition may include one or more bases, such as sodium hydroxide, potassium hydroxide and the like, to increase the pH of the oral care composition. Additional or alternative acids and bases that are suitable for adjusting the pH of the oral care composition are readily known to one of ordinary skill in the art.

[0116] The amount of the pH adjuster in the oral care composition may be based on the desired pH of the final oral care composition and / or product. For example, the total amount of the pH adjuster may range from about 0.05 to about 20 wt.%, based on the total weight of the oral care composition. In some instances, the total amount of pH adjuster is from about 0.05 to about 15 wt.%, about 0.1 to about 10 wt.%, or about 0.12 to about 5 wt.%, including ranges and sub-ranges therebetween, based on the total weight of the oral care composition.

[0117] The oral care compositions may have a pH from about 6 to about 8. For example, the pH of the oral care composition may be from about 6 to about 8, about 6.4 to about 8, about 6.8 to about 8, about 7.2 to about 8; from about 6 to about 7.7, about 6.4 to about 7.7, about 6.8 to about 7.7; from about 6 to about 7.4, about 6.4 to about 7.4, about 6.8 to about 7.4; from about 6 to about 7, about 6.4 to about 7, or any range or subrange thereof. For example, the oral care composition may have a pH of or within one of the foregoing pH ranges while having sodium hydroxide in an amount from 0.05 to about 0.8 wt.%. In some embodiments, the oral care composition has a pH of or within one of the foregoing pH ranges while having sodium hydroxide in an amount from 0.05 to about 0.8 wt.% as the only pH adjuster in the oral care composition.

[0118] In accordance with yet a further aspect, a method is provided for producing an oral care composition, such as the oral care compositions disclosed herein. The methods of the present disclosure typically employ the components and / or ingredients disclosed herein with regard to the oral care composition. It was unexpectedly discovered that certain methods for producing the oral care composition can produce an oral care composition without the oleanolic acid clumping orDocket No. 14565-OO-WO-Ol-OC forming fisheyes, e.g., even without the addition of certain components / ingredients to dissolve the olcanolic acid. In some instances, the methods can produce oral care compositions that do not have oleanolic acid clumping or fisheyes formed from oleanolic acid and do not contain a strong base, such as a strong alkali metal base (e.g., sodium hydroxide and / or the like) and / or strong Lewis base.

[0119] As a brief overview, the method for producing an oral care composition may include mixing oleanolic acid and a polyol to obtain an oleanolic acid mixture; and preparing an oral care composition by combining the oleanolic mixture with a stannous source, a nitrate source, a phosphate source, a surfactant system, and eugenol, the oral care composition comprising: a stannous source; a nitrate source; a phosphate source; a surfactant system comprising sodium lauryl sulfate, sodium lauryl ether sulfate, or a combination thereof; oleanolic acid; and eugenol.

[0120] The mixing of oleanolic acid and a polyol to obtain an oleanolic acid mixture may, in some instances, be performed by mixing the oleanolic acid with an amount of polyol that is at least 700% greater than the amount of oleanolic acid. Mixing may occur using a stirrer or another device known to one of ordinary skill in the art. In some embodiments, the oleanolic acid and the polyol are mixed together in a weight ratio of the oleanolic acid to the polyol of about 1:7 to about 1:50, e.g., about 1:10 to about 1:50, about 1:15 to about 1:50, about 1:20 to about 1:50, about 1:30 to about 1 :50; from about 1 :7 to about 1:40, about 1 : 10 to about 1:40, about 1 : 15 to about 1 :40, about 1 :20 to about 1 :40, about 1:30 to about 1:40; from about 1 :7 to about 1 :30, about 1 : 10 to about 1 :30, about 1 : 15 to about 1 :30, about 1 :20 to about 1 :30; from about 1:7 to about 1:20, about 1:10 to about 1:20, or any range or subrange thereof.

[0121] The method may in some instances include a step of obtaining an oleanolic acid composition prior to preparing the oral care composition (e.g., final oral care composition product). For instance, the oleanolic acid composition may be prepared prior to the stannous source being added to the oleanolic acid mixture. Additionally or alternatively, the oleanolic acid composition may be prepared prior to the nitrate source being added to the oleanolic acid mixture.

[0122] The oleanolic acid composition may be prepared by combining the oleanolic acid mixture with the surfactant system, the phosphate source, and optionally the eugenol. For example, the oleanolic acid composition may be prepared by mixing the oleanolic acid mixture with the surfactant system, the phosphate source, and optionally the eugenol, e.g., until the oleanolicDocket No. 14565-OO-WO-Ol-OC composition is homogenous. In some embodiments, the method for producing an oral care composition may be for producing one of the oral care compositions disclosed herein.

[0123] In at least one embodiment, the oleanolic acid composition is prepared by homogenizing the oleanolic acid with the surfactant system, the phosphate source, and optionally the eugenol, using a homogenizer until the oleanolic composition is homogenous. In accordance with another aspect, the present disclosure provides a method of treatment or prevention of gingivitis, plaque, dental caries, and / or dental hypersensitivity, the method comprising the application to the oral cavity of a person in need thereof, of an oral care composition according to the invention, e.g., by brushing, for example, one or more times per day. In some embodiments, the oral care compositions for use in the treatment or prevention of gingivitis, plaque, dental caries, and / or dental hypersensitivity. The oral care composition may be one of the oral care compositions disclosed herein.

[0124] The methods may comprise applying any of the compositions as described herein to the teeth, e.g., by brushing, gargling or rinsing, or otherwise administering the oral care composition to the oral cavity of a subject in need thereof. The oral care composition can be administered regularly, such as, for example, one or more times per day (e.g., twice per day). In various embodiments, administering the compositions of the present disclosure to teeth may provide one or more of the following specific benefits: (i) reduce or inhibit formation of dental caries, (ii) reduce, repair or inhibit pre-carious lesions of the enamel, e.g., as detected by quantitative light- induced fluorescence (QLF) or electrical caries measurement (ECM), (iii) reduce or inhibit demineralization and promote remineralization of the teeth, (iv) reduce hypersensitivity of the teeth, (v) reduce or inhibit gingivitis, (vi) promote healing of sores or cuts in the mouth, (vii) reduce levels of acid producing and / or malodor producing bacteria, (viii) treat, relieve or reduce dry mouth, (ix) clean the teeth and oral cavity, (x) whiten the teeth, (xi) reduce tartar build-up, (xii) reduce or prevent oral malodor, and / or (xiii) promote systemic health, including cardiovascular health, e.g., by reducing potential for systemic infection via the oral tissues.

[0125] The oral care compositions disclosed herein may be produced by methods comprising mixing a stannous source; a nitrate source; a phosphate source; a surfactant system comprising a sulfate based anionic surfactant; oleanolic acid; and eugenol. The oral care compositions may also be produced and / or manufactured to be in a container according to known methods disclosed inDocket No. 14565-OO-WO-Ol-OCU.S. Patent No. 4,849,213 and U.S. Patent No. 4,81 ,306, which are incorporated herein in their entirety for all purposes.EXAMPLESExample 1

[0126] A non-limiting, example oral care composition (Example Composition A) was prepared in accordance with aspects of the invention. Example Composition A was prepared in the form of a dentifrice according to the formulation shown in Table 1. A comparative composition (Comparative Composition 1) was prepared in the form of a dentifrice according to the formulation shown in Table 1.Table 1Example 2

[0127] Example Composition A and Comparative Composition 1 were evaluated to assess the antibleeding efficacy of such oral care compositions. Specifically, a platelet aggregation assay was conducted to assess the hemostasis capability of Example Composition A and Comparative Composition 1. The platelet area increasing ratio and platelet velocity decreasing ratio wereDocket No. 14565-OO-WO-Ol-OC evaluated as said ratios are indicative of the hemostasis capability. A greater platelet area increasing ratio and a greater velocity decreasing ratio indicate better bleeding reduction efficacy. The platelet area increasing ratio and platelet velocity decreasing ratio for Example Composition A and Comparative Composition 1 are shown in FIGS. 1 and 2.Example 3

[0128] Example Composition A and Comparative Composition 1 were evaluated using a growth inhibition university of Manchester Model for anaerobic bacterial biofilm to assess the antibacterial properties of such dentifrices. Specifically, saliva collected from four healthy volunteers was pooled together and used as an inoculum. An anaerobically grown biofilm was then produced. Although the specific strains of bacteria were not verified, the anaerobically grown biofilm would likely have contained diverse anaerobic bacteria, including genera like Actinomyces, Bacteroides, Bifidobacterium, Eubacterium, Fusobacterium, Lactobacillus, Leptotrichia, Peptostreptococcus, Propionibacterium, Selenomonas, Treponema, and Veillonella.

[0129] HAP discs were immersed in a mixture of inoculum and artificial saliva in a 1 : 1 proportion. The HAP discs were incubated for twenty-four hours to allow for the biofilm to develop. Dentifrice slurries were produced by mixing samples of Example Composition A or Comparative Composition 1 with water in a weight ratio of the respective dentifrice to water of 1:2. The dentifrice slurries were individually applied to respective HAP discs twice a day for eight days. Each sample of dentifrice was evaluated in triplicate.

[0130] Recovery and quantification of the biofilms on the HAP discs was completed on day 10. ATP measurements (RLU) were taken using a Microbial Cell Viability kit, such as those provided by Promega BactitreGlo, to evaluate the amount of viable bacteria and, ultimately, determine the antibacterial properties of the respective dentifrices. The antibacterial effect of Example Composition A and Comparative Composition 1 on the anerobic biofilm are shown in FIG. 3.

Claims

Docket No. 14565-OO-WO-Ol-OCCLAIMSWhat is Claimed is:

1. An oral care composition comprising; a stannous source; a nitrate source; a phosphate source; a surfactant system comprising a sulfate based anionic surfactant, wherein the total amount of sulfate based anionic surfactant is about 1.7 wt.% or less; oleanolic acid; eugenol; and sodium hydroxide in an amount from 0.05 to about 0.8 wt.%, wherein all weight percentages are based on the total weight of the oral care composition.

2. An oral care composition comprising; a stannous source; a nitrate source; a phosphate source; a surfactant system comprising a sulfate based anionic surfactant, wherein the total amount of sulfate based anionic surfactant is 2.2 to about 7 wt.%; oleanolic acid; and eugenol, wherein all weight percentages are based on the total weight of the oral care composition.

3. The oral care composition according to claim 1 or claim 2, wherein the stannous source is selected from stannous fluoride, stannous chloride, stannous pyrophosphate, stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate, stannous citrate, stannous ethylene glyoxide, and combinations of two or more thereof.

4. The oral care composition according to any one of claims 1 to 3, wherein the nitrate source is selected from lithium nitrate, sodium nitrate, potassium nitrate, magnesium nitrate,Docket No. 14565-OO-WO-Ol-OC calcium nitrate, zinc nitrate, silver nitrate, ammonium nitrate, and a combination two or more thereof.

5. The oral care composition according to any one of claims 1 to 4, wherein the oral care compositions have a molar ratio of nitrate ions to stannous ions, both measured as free ions, of about 0.5:1 to about 2:1.

6. The oral care composition according to any one of claims 1 to 5, wherein the phosphate source comprises tetrasodium pyrophosphate, sodium triphosphate, or a combination thereof.

7. The oral care composition according to any one of claims 1 to 6, wherein the surfactant system further comprises an amphoteric surfactant.8 The oral care composition according to claim 7, wherein the amphoteric surfactant comprises a betaine surfactant selected from coca betaine, cocamidopropyl betaine, coco dimethyl carboxymethyl betaine, lauryl dimethyl carboxy-methyl betaine, lauryl dimethyl alphacarboxyethyl betaine, cetyl dimethyl carboxymethyl betaine, lauryl bis-(2-hydroxyethyl)carboxy methyl betaine, stearyl bis-(2-hydroxypropyl)carboxymethyl betaine, oleyl dimethyl gammacarboxypropyl betaine, lauryl bis-(2-hydroxypropyl)alpha-carboxyethyl betaine, or a combination thereof.

9. The oral care composition according to any one of claims 1 to 8 further comprising: a polyol, optionally, in an amount 20 to about 60 wt.%.

10. The oral care composition according to claim 9, wherein the polyol is selected from sorbitol, xylitol, mannitol, glycerin, ethylene glycol, propylene glycol, butylene glycol, hexylene glycol, polyethylene glycol, a polypropylene glycol, a block polymer of polyethylene glycol and polypropylene glycol, and a combination of two or more thereof.

11. The oral care composition according to any one of claims 1 to 10 further comprising: a thickening agent, optionally, in an amount from about 0.5 to about 20 wt.%.Docket No. 14565-OO-WO-Ol-OC12. The oral care composition according to claim 11, wherein the thickening agent is selected from polysaccharide, a natural gum, a silica thickener, an acrylate, a polymer, and a combination of two or more thereof.

13. The oral care composition according to any one of claims 2 to 12, wherein the oral care composition is free of alkali metal hydroxides.

14. The oral care composition according to any one of claims 1 to 13, wherein the oral care composition has a pH of about 6.4 to 7.4.

15. The oral care composition according to any one of claims 1 to 14, wherein the stannous source comprises stannous pyrophosphate.

16. A method for producing an oral care composition, the method comprising: mixing oleanolic acid and a polyol to obtain an oleanolic acid mixture; and preparing an oral care composition by combining the oleanolic mixture with a stannous source, a nitrate source, a phosphate source, a surfactant system, and eugenol, the oral care composition comprising: a stannous source; a nitrate source; a phosphate source; a surfactant system comprising one or more sulfate based anionic surfactant; oleanolic acid; and eugenol.

17. The method according to claim 16, wherein the oleanolic acid mixture has a weight ratio of the oleanolic acid to the polyol of about 1:7 to about 1:50.

18. The method according to claim 17, wherein the weight ratio of the oleanolic acid to the polyol is about 1:10 to about 1:50.Docket No. 14565-OO-WO-Ol-OC19. The method according to any one of claims 16 to 18 further comprising: preparing an oleanolic acid composition by combining the oleanolic acid mixture is combined with the surfactant system, the phosphate source, and optionally eugenol.

20. The method according to claim 19, wherein the oleanolic acid composition prepared prior to the addition of the stannous source or nitrate source.

21. The method according to claim 20, wherein the oleanolic acid composition is mixed to until homogenous.

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