Methods and treatments to improve oral care health

Abstract

Methods for reducing, alleviating, and / or treating an inflammatory condition in a population at risk for an overactive and / or dysregulated inflammatory response as well as methods for reducing, alleviating, and / or treating gum diseases, such as periodontitis and peri-implantitis, are disclosed herein. In accordance with an aspect, provided is a method for reducing, alleviating, and / or treating an inflammatory condition in a population at risk for an overactive and / or dysregulated inflammatory response, the method comprising: determining a subject to be at risk for an overactive and / or dysregulated inflammatory response; an reducing CD40 expression and MMP-13 by applying a composition to the oral cavity, the composition comprising: a stannous source; a nitrate source; and a polyphosphate.

Description

Docket No. 1123319-00-WO-01-OCMETHODS AND TREATMENTS TO IMPROVE ORAL CARE HEALTHCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority from U. S. Patent Application No.63 / 748,611, titled Methods and Treatments to Improve Oral Care Health, which was filed on January 23, 2025, the content of which is hereby incorporated herein by reference in its entirety.BACKGROUND

[0002] Dental plaque or plaque bio-film is a soft deposit that forms on surfaces of the oral cavity, such as tissue and teeth, and comprises a complex mixture of an accumulation of bacteria, food by-products, starch, proteins and proteinaceous material. Thus, inhibiting the growth of bio-film not only involves dispersing the accumulation of existing proteinaceous materials, but also requires prohibiting and minimizing their reattachment to the tooth surface by attacking bacteria.

[0003] Dental plaque adheres tenaciously at the points of irregularity or discontinuity (e.g., on rough calculus surfaces, at the gum line, on tongue surface and within crevices, and the like). Dental plaque is a precursor of calculus. Dental calculus, or tartar, refers to a build-up of hardened (mineralized) plaque on the teeth, formed by the presence of saliva, debris, and minerals. Mature calculus consists of an inorganic portion which is largely calcium phosphate arranged in a hydroxyapatite crystal lattice structure similar to bone, enamel, and dentin. An organic portion is also present and consists of desquamated epithelial cells, leukocytes, salivary sediment, food debris, and various types of microorganisms. Its rough surface provides an ideal medium for bacterial growth, threatening the health of the gums and absorbing unaesthetic stains due to its porous nature far more easily than natural teeth.

[0004] Dental plaque can occur above (supragingival) and below (subgingival) the gumline. Supragingival dental plaque forms on teeth within hours after they are cleaned. In the presence of a diet rich in carbohydrates, shifts occur in the supragingival plaque to more of an acidogenic plaque, with dental caries as an outcome. Plaques that form on subgingival tooth surfaces and coat the epithelium lining of the gingival crevice lead to the development of gingival and periodontal infections (i.e., gingivitis and periodontitis, respectively).

[0005] In gingivitis, the gums become red, swollen and can bleed easily during tooth brushing. Often times, gingivitis is reversible with dental cleanings and proper oral hygiene. It is a surface condition and can be treated by surface instruments such as toothbrushes and floss. Further, theDocket No. 1123319-00-WO-01-OCteeth are typically still firmly planted in their sockets even when suffering from gingivitis. When left untreated, gingivitis will progress to periodontal disease (e.g., periodontitis), which will result in the breakdown of periodontal ligament that attaches the gums to the teeth, thus creating the periodontal pocket.

[0006] In periodontitis, the inner layer of the gums pulls away from the teeth and forms pockets, which are spaces that become inflamed and infected. Bacterial toxins produced by the bacteria in plaque together with the body's natural responses to infections start to break down the bone and the connective tissue that hold the teeth in place. As the disease progresses, the bones and gums are destroyed and the teeth are no longer anchored in place. The teeth become loose and tooth loss may ultimately occur.

[0007] Periodontal disease is a chronic inflammatory condition of the gingiva (gums), the teeth and the attachment apparatus which connects the teeth to the gums and the bone. As pathogenic bacteria grows in the periodontal pocket, the host’s response to the pathogenic bacteria breaks down the soft and hard (bone) tissues through the release of antibodies, polymorphonuclear cells (PMNs), cytokines and other inflammatory factors which end up feeding the invading bacteria. The bacteria, in response to the deepening periodontal pocket, also alter their microbiome population from an initial one of primarily aerobes at the surface to mixture of aerobes and anaerobes. The anaerobes begin to dominate the deeper the pocket gets away from the surface oxygen. The dysbiosis, characterized by a shift in microflora, perpetuates in a positive feedback loop.

[0008] Treatment of periodontal disease falls into two broad categories: surgical (to restore supportive tissues) and non-surgical (to control bacterial growth). Traditionally, there have been two categories of non-surgical treatment for periodontal disease: personal home care and invasive services provided by dental professionals. Dental professionals often will do a cleaning to remove plaque and tartar from above and below the gumline, and a more deep-cleaning scaling.

[0009] A list of non-limiting embodiments in accordance with aspects of the invention is provided below:

[0010] In accordance with an embodiment 1, provided is a method for prophylactically treating an inflammatory condition in a population at risk for an overactive and / or dysregulated inflammatory response, the method comprising: determining a subject to be at risk for an overactive and / or dysregulated inflammatory response; and reducing CD40 expression and MMP-13 by applying anDocket No. 1123319-00-WO-01-OCoral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate.

[0011] In accordance with an embodiment 2, provided is the method according to embodiment 1, wherein the population at risk for an overactive and / or dysregulated inflammatory response is suffering from an autoimmune disease, diabetes respiratory tract infection, cardio-vascular disease, inflammatory bowel disease, lupus, or a combination thereof.

[0012] In accordance with an embodiment 3, provided is the method according to embodiment 1 or embodiment 2, wherein the inflammatory condition is associated with an overexpression of CD40.

[0013] In accordance with an embodiment 4, provided is a method for controlling an overexpression of CD40 in an oral cavity of a subject in need thereof, the method comprising: ascertaining an overexpression of CD40 in the oral cavity; and reducing CD40 expression in the oral cavity by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate.

[0014] In accordance with an embodiment 5, provided is the method according to embodiment 4, wherein the CD40 expression is reduced by about 10% or more, as measured about 24 hours after application of the oral care composition.

[0015] In accordance with an embodiment 6, provided is the method according to embodiment 4 or embodiment 5, comprising reducing the CD40 expressing macrophages, as measured about 24 hours after application of the oral care composition.

[0016] In accordance with an embodiment 7, provided is the method according to any one of embodiment 4 to embodiment 6, comprising increasing the CD80 expressing macrophages, as measured about 18 hours after application of the oral care composition.

[0017] In accordance with an embodiment 8, provided is the method according to embodiment 7, wherein the expression of CD80 is increased by about 10% or more in the presence of bacterial lipopolysaccharide relative to the expression of CD80 without the presence of bacterial lipopolysaccharide, as measured about 18 hours after application of the oral care composition.

[0018] In accordance with an embodiment 9, provided is the method according to any one of embodiment 4 to embodiment 8, wherein the overexpression of CD40 is determined based on a threshold value.Docket No. 1123319-00-WO-01-OC

[0019] In accordance with an embodiment 10, provided is the method according to any one of embodiment 4 to embodiment 9 further comprising: reducing the MMP-13 in the oral care cavity.

[0020] In accordance with an embodiment 11, provided is the method according to embodiment 10, wherein the amount of MMP-13 is reduced by about 10% or more, as measured about 24 hours after application of the oral care composition.

[0021] In accordance with an embodiment 12, provided is a method for promoting a reduction of bacterial lipopolysaccharide, the method comprising: ascertaining the presence of bacterial lipopolysaccharide in an oral cavity; increasing the expression of CD80 and reducing the expression of CD40 and / or MMP-13 by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate.

[0022] In accordance with an embodiment 13, provided is the method according to embodiment 12, wherein the presence of pathogenic bacterial lipopolysaccharide is associated with Porphvromonas gingivalis, Treponema denticola, Prevotella nigrescens,and / or Peptostreptucoccus micro.

[0023] In accordance with an embodiment 14, provided is the method according to embodiment 12 or embodiment 13, wherein the expression of CD80 is increased by about 10% or more, as measured about 18 hours after application of the oral care composition.

[0024] In accordance with an embodiment 15, provided is the method according to any one of embodiment 12 to embodiment 14, comprising increasing the CD80 expressing macrophages, as measured about 18 hours after application of the oral care composition.

[0025] In accordance with an embodiment 16, provided is the method according to any one of embodiment 12 to embodiment 15, wherein the expression of CD40 expression is reduced by about 10% or more, as measured about 24 hours after application of the oral care composition.

[0026] In accordance with an embodiment 17, provided is the method according to any one of embodiment 12 to embodiment 16, comprising reducing the CD40 expressing macrophages, as measured about 24 hours after application of the oral care composition.

[0027] In accordance with an embodiment 18, provided is the method according to any one of embodiment 12 to embodiment 17, comprising reducing the MMP-13 by 10% or more, as measured about 24 hours after application of the oral care composition.

[0028] In accordance with an embodiment 19, provided is a method for prophylactically treating, reducing, or alleviating periodontitis and / or peri-implantitis in a subject suffering therefrom, theDocket No. 1123319-00-WO-01-OCmethod comprising: determining a subject as having periodontitis and / or peri-implantitis; and reducing MMP-13 by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate.

[0029] In accordance with an embodiment 20, provided is the method according to embodiment 19, wherein the MMP-13 is reduced by 10% or more, as measured about 24 hours after application of the oral care composition.

[0030] In accordance with an embodiment 21, provided is the method according to any one foregoing embodiment further comprising: comprising reducing collagenase activity by about 4% or more, as measured about 24 hours after application of the oral care composition.

[0031] In accordance with an embodiment 22, provided is a method for reducing collagenase activity in an oral cavity of a subject, the method comprising: ascertaining the presence of collagenase activity in an oral cavity; and reducing collagenase activity in the oral cavity by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate.

[0032] In accordance with an embodiment 23, provided is the method according to embodiment 22, wherein the collagenase activity is reduced by about 4% or more, as measured about 24 hours after application of the oral care composition.

[0033] In accordance with an embodiment 24, provided is the method according to any foregoing embodiment, wherein the amount of the oral care oral care composition applied to the oral cavity is about 0.1 to about 3 grams.

[0034] In accordance with an embodiment 25, provided is the method according to any foregoing embodiment, wherein 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.

[0035] In accordance with an embodiment 26, provided is the method according to embodiment 25, wherein the stannous source comprises stannous fluoride.

[0036] In accordance with an embodiment 27, provided is the method 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.Docket No. 1123319-00-WO-01-OC

[0037] In accordance with an embodiment 28, provided is the method according to embodiment 27, wherein the nitrate source comprises potassium nitrate.

[0038] In accordance with an embodiment 29, provided is the method 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.

[0039] In accordance with an embodiment 30, provided is the method 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, and a combination of two or more thereof.BRIEF SUMMARY

[0040] 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 present 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.

[0041] Aspects the invention are directed to methods for reducing, alleviating, and / or treating an inflammatory condition in a population at risk for an overactive and / or dysregulated inflammatory response. Additional aspects of the invention are directed to methods for reducing, alleviating, and / or treating gum diseases, such as periodontitis and peri-implantitis.

[0042] In accordance with an aspect, provided is a method for reducing, alleviating, and / or treating an inflammatory condition in a population at risk for an overactive and / or dysregulated inflammatory response, the method comprising: determining a subject to be at risk for an overactive and / or dysregulated inflammatory response; reducing CD40 expression and MMP-13 by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate.

[0043] According to another aspect, provided is a method for controlling an overexpression of CD40 in an oral cavity of a subject in need thereof, the method comprising: ascertaining an overexpression of CD40 in the oral cavity; and reducing CD40 expression in the oral cavity byDocket No. 1123319-00-WO-01-OCapplying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate.

[0044] In accordance with a further aspect, provided is a method for promoting a noninflammatory reduction of bacterial lipopolysaccharide, the method comprising: ascertaining the presence of bacterial lipopolysaccharide in an oral cavity; increasing the expression of CD80 and reducing the expression of CD40 and / or MMP-13 by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate.

[0045] According to yet another aspect, provided is a method prophylactically treating, reducing, or alleviating periodontitis and / or peri-implantitis in a subject suffering therefrom, the method comprising: determining a subject as having periodontitis and / or peri-implantitis; and reducing MMP-13 by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate.

[0046] In accordance with yet a further aspect, provided is a method for reducing collagenase activity in an oral cavity of a subject, the method comprising: ascertaining the presence of collagenase activity in an oral cavity; and reducing collagenase activity in the oral cavity by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate.BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Implementation of the present technology will now be described, by way of example only, with reference to the attached figures, wherein:

[0048] FIGS. 1A-1C are graphs of the evaluation of the markers on the naive macrophage-like cells (“M0 macrophage-like cells”) using a non-limiting, example composition in accordance with aspects of the invention;

[0049] FIGS. 2A-2C are graphs of the evaluation of the markers on the pre-inflamed pro-inflammatory macrophage-like cells (“Ml macrophage- like cells”) using a non-limiting, example composition in accordance with aspects of the invention;

[0050] FIGS. 3A and 3B are graphs of the TNFa secretion for the M0 macrophage-like cells and Ml macrophage-like cells using a non-limiting, example composition in accordance with aspects of the invention;Docket No. 1123319-00-WO-01-OC

[0051] FIGS.4A-4C are graphs of the evaluation of the markers on the MO macrophage-like cells using a non-limiting, example composition in accordance with aspects of the invention;

[0052] FIGS. 5A-5C are graphs of the evaluation of the markers on the pre-inflamed Ml macrophage-like cells using a non-limiting, example composition in accordance with aspects of the invention;

[0053] FIG. 6A is a graph of the TNFa secretion on the MO macrophage-like cells using a nonlimiting, example composition in accordance with aspects of the invention;

[0054] FIG. 6B is a graph of the TNFa secretion on the Ml macrophage-like cells using a nonlimiting, example composition in accordance with aspects of the invention;

[0055] FIG. 6C is a graph of the IL-1B secretion on the Ml macrophage-like cells using a nonlimiting, example composition in accordance with aspects of the invention;

[0056] FIG. 7A is a graph of the MMP-13 secretion on the M0 macrophage-like cells using a nonlimiting, example composition in accordance with aspects of the invention;

[0057] FIG. 7B is a graph of the CCL2 secretion on the M0 macrophage-like cells using a nonlimiting, example composition in accordance with aspects of the invention; and

[0058] FIG. 8 is a graph of the collagenase activity using a non-limiting, example composition in accordance with aspects of the invention.

[0059] It should be understood that the various aspects are not limited to the arrangements and instrumentality shown in the drawingsDETAILED DESCRIPTION

[0060] 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 and 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.

[0061] 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 theDocket No. 1123319-00-WO-01-OCingredients 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”.

[0062] 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.

[0063] 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.%.

[0064] 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.

[0065] 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 “pm” refer to hour, minute, milliliter, nanometer, and micrometer, respectively. The abbreviation “UV-VIS” referring to a spectrometer or spectroscopy, means Ultraviolet- Visible. The abbreviation “rpm” means revolutions per minute.

[0066] 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.

[0067] “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.

[0068] 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, andDocket No. 1123319-00-WO-01-OCit is given that other species may exist that define or exemplify the genus just as well as, or better than, any other species listed.

[0069] 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.

[0070] 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.

[0071] 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 composition 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 sweetener. If a particular oral care composition includes both a polyol and a sweetener, xylitol will serve only as either a polyol or a sweetener—not both.Docket No. 1123319-00-WO-01-OC

[0072] 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.”

[0073] As used herein, the term “oral fluid” refers to any fluid that originated in the oral cavity. Examples include, but are not limited to, saliva and gingival crevicular fluid (GCF). As used herein, the term “host cell” refers to any eukaryotic or prokaryotic cell (e.g., bacterial cells such as E. coli, yeast cells, mammalian cells, avian cells, amphibian cells, plant cells, fish cells, and insect cells), whether located in vitro or in vivo. For example, host cells may be located in a transgenic animal.

[0074] As used herein, the term “prokaryotes” refers to a group of organisms that usually lack a cell nucleus or any other membrane-bound organelles. In some embodiments, prokaryotes are bacteria. The term “prokaryote” includes both archaea and eubacteria.

[0075] As used herein, the term “subject” refers to individuals (e.g., human) to be treated by the methods or compositions of the present invention. Subjects include, but are not limited to, mammals (e.g., murines, simians, equines, bovines, porcines, canines, felines, and the like), and most preferably includes humans. In the context of the invention, the term “subject” generally refers to an individual who will receive or who has received treatment for a condition characterized by the presence of biofilm-forming bacteria, or in anticipation of possible exposure to biofilmforming bacteria.

[0076] As used herein the term, “in vitro” refers to an artificial environment and to processes or reactions that occur within an artificial environment. In vitro environments include, but are not limited to, test tubes and cell cultures. The term “in vivo” refers to the natural environment (e.g., an animal or a cell) and to processes or reaction that occur within a natural environment.

[0077] As used herein, the term “pathogen” refers to a biological agent that causes a disease state (e.g., infection, cancer, etc.) in a host. “Pathogens” include, but are not limited to. viruses, bacteria, archaea, fungi, protozoans, mycoplasma, prions, and parasitic organisms.

[0078] As used herein, the term “microbe” refers to a microorganism and is intended to encompass both an individual organism, or a preparation comprising any number of the organisms.

[0079] As used herein, the term “microorganism” refers to any species or type of microorganism, including but not limited to, bacteria, archaea, fungi, protozoans, mycoplasma, and parasitic organisms.Docket No. 1123319-00-WO-01-OC

[0080] The terms “bacteria” and “bacterium” refer to all prokaryotic organisms, including those within all of the phyla in the Kingdom Procaryotae. It is intended that the term encompass all microorganisms considered to be bacteria including Mycoplasma, Chlamydia, Actinomyces, Streptomyces, and Rickettsia. All forms of bacteria are included within this definition including cocci, bacilli, spirochetes, spheroplasts, protoplasts, etc. Also included within this term are prokaryotic organisms that are Gram-negative or Gram-positive. “Gram-negative” and “Grampositive” refer to staining patterns with the Gram-staining process, which is well known in the art. (See e.g., Finegold and Martin, Diagnostic Microbiology, 6th Ed., CV Mosby St. Louis, pp. 13-15 (1982)). “Gram-positive bacteria” are bacteria that retain the primary dye used in the Gram-stain, causing the stained cells to generally appear dark blue to purple under the microscope. “Gramnegative bacteria” do not retain the primary dye used in the Gram-stain, but are stained by the counterstain. Thus, Gram-negative bacteria generally appear red.

[0081] The term “non-pathogenic bacteria” or “non-pathogenic bacterium” includes all known and unknown non-pathogenic bacterium (Gram-positive or Gram-negative) and any pathogenic bacterium that has been mutated or converted to a non-pathogenic bacterium. Furthermore, a skilled artisan recognizes that some bacteria may be pathogenic to specific species and non-pathogenic to other species; thus, these bacteria can be utilized in the species in which it is non-pathogenic or mutated so that it is non-pathogenic.

[0082] As used herein, the term “cell culture” refers to any in vitro culture of cells, including, e.g., prokaryotic cells and eukaryotic cells. Included within this term are continuous cell lines (e.g., with an immortal phenotype), primary cell cultures, transformed cell lines, finite cell lines (e.g., non-transformed cells), bacterial cultures in or on solid or liquid media, and any other cell population maintained in vitro.

[0083] Aspects of the invention are directed to methods for reducing, alleviating, and / or treating an inflammatory condition in a population at risk for an overactive and / or dysregulated inflammatory response. Without being limited to any particular theory, it is believed that certain methods disclosed herein may provide significant reduction of, alleviation of, and / or treat an inflammatory condition in a population at risk for an overactive and / or dysregulated inflammatory response. For example, sub-populations suffering from an autoimmune disease, diabetes respiratory tract infection, cardio-vascular disease, inflammatory bowel disease, lupus, or a combination thereof may be particularly benefited by certain methods disclosed herein. AdditionalDocket No. 1123319-00-WO-01-OCaspects of the invention are directed to methods for reducing, alleviating, and / or treating gum diseases, such as periodontitis and peri-implantitis. The inventors discovered that certain methods and compositions disclosed herein can provide significant reduction, inhibition, and / or alleviation of gingivitis, and particularly periodontitis and peri-implantitis.

[0084] In accordance with an aspect of the invention, provided is a method for reducing, alleviating, and / or treating an inflammatory condition in a population or a subpopulation at risk for an overactive and / or dysregulated inflammatory response, the method comprising: determining a subject to be at risk for an overactive and / or dysregulated inflammatory response; and reducing CD40 expression and MMP-13 by applying a composition to the oral cavity, the composition comprising: a stannous source; a nitrate source; and a polyphosphate. The population or subpopulation at risk for an overactive and / or dysregulated inflammatory response may be those suffering from autoimmune disease, diabetes respiratory tract infection, cardio-vascular disease, inflammatory bowel disease, and / or lupus. For example, the method may include determining that the subject is a member of population or subpopulation suffering from an autoimmune disease, diabetes respiratory tract infection, cardio-vascular disease, inflammatory bowel disease, lupus, or a combination thereof. In at least one preferred embodiment, the subject is a member of the population at risk for an overactive and / or dysregulated inflammatory response and is determined and / or identified as suffering from an autoimmune disease. The subject may self-identify as suffering from autoimmune disease, e.g., based on prior consultations with medical professionals. In some embodiments, the inflammatory condition may be associated with an overexpression of CD40. The overexpression of CD40 in an oral care cavity may be determined by comparing the amount of CD40 expression in an oral cavity to a threshold value. The threshold value may be a predetermined value. For instance, the threshold value may be a predetermined value of one standard deviation above, two standard deviations above, or three standard deviations above the average expression level of CD40 for subjects of the same age and gender. The overexpression of CD40 may, additionally or alternatively, be determined and / or ascertained by a medical professional, scientist, and / or lab technician.

[0085] According to another aspect, provided is a method for controlling an overexpression of CD40 in an oral cavity of a subject in need thereof, the method comprising: ascertaining an overexpression of CD40 in the oral cavity; and reducing CD40 expression in the oral cavity by applying an oral care composition to the oral cavity, the oral care composition comprising: aDocket No. 1123319-00-WO-01-OCstannous source; a nitrate source; and a polyphosphate. The method may include controlling the overexpression of CD40 in an oral cavity of a subject in need thereof to within three standard deviations, within two standard deviations, or within one standard deviation of the average expression level of CD40, e.g., based on subjects of the same age and gender.

[0086] As noted above, the overexpression of CD40 in an oral care cavity may be determined and / or ascertained by comparing the amount of CD40 expression in an oral cavity to a threshold value, which may be a predetermined value. Additionally or alternatively, the overexpression of CD40 may be determined by a medical professional, scientist, and / or lab technician.

[0087] In accordance with a further aspect, provided is a method for promoting a reduction of bacterial lipopolysaccharide, the method comprising: ascertaining the presence of bacterial lipopolysaccharide in an oral cavity; increasing the expression of CD80 and reducing the expression of CD40 and / or MMP-13 by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate. The method may comprise ascertaining the presence of bacterial lipopolysaccharide in an oral cavity using an endotoxin activity assay (e.g., a limulus amebocyte lysate assay and / or a recombinant Factor C assay) and / or immunoassays for lipopolysaccharides.

[0088] According to yet another aspect, provided is a method for prophylactically treating, reducing, or alleviating periodontitis and / or peri-implantitis in a subject suffering therefrom, the method comprising: determining a subject as having periodontitis and / or peri-implantitis; and reducing MMP-13 by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate. The subject may be determined as having periodontitis and / or peri-implantitis by a medical professional, scientist, and / or lab technician. In some embodiments, the subject may self-identify as suffering from periodontitis and / or peri-implantitis, e.g., based on prior consultations with medical professionals.

[0089] In accordance with yet a further aspect, provided is a method for reducing collagenase activity in an oral cavity of a subject, the method comprising: ascertaining the presence of collagenase activity in an oral cavity; and reducing collagenase activity in the oral cavity by applying an oral care composition to the oral cavity, the oral care composition comprising: a stannous source; a nitrate source; and a polyphosphate. The method may ascertain the presence of collagenase activity by way of conducting fluorogenic substrate assays.Docket No. 1123319-00-WO-01-OC

[0090] The methods disclosed herein may advantageously reduce CD40 expression, such as CD40 expressing macrophages, in the oral cavity of a subject. Preferably, the method reduces CD40 expression by about 10% or more, as measured about 24 hours after application of the oral care composition to the oral cavity of a subject. For example, CD40 expression may be reduced by preferably about 26% or more, about 37% or more, about 48% or more, about 54% or more or about 60% or more, as measured about 24 hours after application of the oral care composition. In at least one embodiment, the reduction of CD40 expression, such as one of the amounts disclosed herein, is due to a reduction in CD40 expressing macrophages. Preferably, the method reduces CD40 expression by 10% or more for at least 7 hours, preferably at least 12 hours, preferably at least 24 hours, or preferably up to 36 hours after application of the oral care composition. The method may reduce CD40 expression as discussed above when the oral care composition is applied in an amount disclosed herein (e.g., in an amount from about 0.1 to about 3 grams) and / or for a duration of time discussed below (e.g., from about 10 seconds to about 30 minutes).

[0091] In certain embodiments, the methods unexpectedly increased the amount of CD80 expression in the presence of bacterial lipopolysaccharide (hereinafter “bacterial LPS”). Further, it was advantageously discovered that certain embodiments increase the amount of CD80 expression only when in the presence of bacterial LPS. The bacterial LPS may comprise those corresponding to Porphvromonas gingivalis, Treponema denticola, Prevotella nigrescens, and / or Peptostreptucoccus micro. Preferably, the methods disclosed herein increase the expression of CD80 by about 10% or more in the presence of bacterial LPS relative to the expression of CD80 without the presence of bacterial LPS, as measured about 18 hours after application of the oral care composition. In certain preferred embodiments, CD80 expression increases by about 23% or more, about 35% or more, about 47% or more, about 67% or more, about 87% or more, about 97% or more, or about 125% or more, as measured about 18 hours after application of the oral care composition. In at least one embodiment, the increase of CD80 expression, such as one of the amounts disclosed above, is due to an increase in CD80 expressing macrophages. Preferably, the method increases the CD80 expression by 10% or more for at least 7 hours, preferably at least 12 hours, preferably at least 24 hours, or preferably up to 36 hours after application of the oral care composition. The method may increase CD80 expression as discussed above when the oral care composition is applied in an amount disclosed herein (e.g., in an amount from about 0.1 to aboutDocket No. 1123319-00-WO-01-OC3 grams) and / or for a duration of time discussed below (e.g., from about 10 seconds to about 30 minutes).

[0092] The methods may advantageously reduce CD40 expression while simultaneously increasing CD80 only in the presence of bacterial LPS. The method’s simultaneous reduction of CD40 expression may be regardless of the presence of bacterial LPS.

[0093] Additionally or alternatively, the methods disclosed herein may advantageously reduce the amount of MMP-13 in an oral care cavity. The amount of MMP-13 may be reduced by about 10% or more, as measured about 24 hours after application of the oral care composition to an oral cavity. For example, certain embodiments of methods disclosed herein may reduce the amount of MMP-13 by about 35% or more, about 45% or more, about 55% or more, about 65% or more, or about 70% or more, as measured about 24 hours after application of the oral care composition to an oral cavity. Preferably, the method reduces MMP-13 by 10% or more for at least 7 hours, preferably at least 12 hours, preferably at least 24 hours, or preferably up to 36 hours after application of the oral care composition. The method may reduce the amount of MMP-13 as discussed above when the oral care composition is applied in an amount disclosed herein (e.g., in an amount from about 0.1 to about 3 grams) and / or for a duration of time discussed below (e.g., from about 10 seconds to about 30 minutes).

[0094] The methods disclosed herein may reduce the TNFa expression in an oral care cavity. The amount of TNFa expression may be reduced by about 10% or more, as measured about 24 hours after application of the oral care composition to an oral cavity. For example, certain embodiments of methods disclosed herein may reduce the amount of TNFa expression by about 15% or more, about 20% or more, about 30% or more, about 40% or more, or about 50% or more, as measured about 24 hours after application of the oral care composition to an oral cavity. Preferably, the method reduces TNFa expression by 10% or more for at least 7 hours, preferably at least 12 hours, preferably at least 24 hours, or preferably up to 36 hours after application of the oral care composition. The method may reduce TNFa expression as discussed above when the oral care composition is applied in an amount disclosed herein (e.g., in an amount from about 0.1 to about 3 grams) and / or for a duration of time discussed below (e.g., from about 10 seconds to about 30 minutes).

[0095] The methods disclosed herein may reduce the collagenase activity in an oral care cavity. The amount of collagenase activity may be reduced by about 4% or more, as measured about 24Docket No. 1123319-00-WO-01-OChours after application of the oral care composition to an oral cavity. For example, certain embodiments of methods disclosed herein may reduce the amount of collagenase activity by about 6% or more, about 8% or more, about 10% or more, or about 12% or more, as measured about 24 hours after application of the oral care composition to an oral cavity. Preferably, the method reduces collagenase activity by about 4% or more for at least 7 hours, preferably at least 12 hours, preferably at least 24 hours, or preferably up to 36 hours after application of the oral care composition. The method may reduce collagenase activity as discussed above when the oral care composition is applied in an amount disclosed herein (e.g., in an amount from about 0.1 to about 3 grams) and / or for a duration of time discussed below (e.g., from about 10 seconds to about 30 minutes).

[0096] The methods disclosed herein may include administering the oral care composition to an oral cavity for about 10 seconds to about 30 minutes, e.g., about 15 seconds to about 25 minutes, about 20 seconds to about 15 minutes, about 25 seconds to about 5 minutes, or about 30 seconds to about 2 minutes. In some embodiments, the oral care compositions may be administered in a form that is maintained in the oral cavity overnight.

[0097] The method may include administering about 0.1 gram to about 3 grams of oral care composition, e.g., in the form of a dentifrice, to the oral cavity. For example, the oral care composition may applied, e.g., in the form of a dentifrice, to the oral cavity in an amount of about 0.1 to about 3 grams, about 0.3 to about 3 grams, about 0.5 to about 3 grams, about 1 to about 3 grams, about 1.5 to about 3 grams, about 2 to about 3 grams, about 2.5 to about 3 grams; from about 0.1 to about 2.5 grams, about 0.3 to about 2.5 grams, about 0.5 to about 2.5 grams, about 1 to about 2.5 grams, about 1.5 to about 2.5 grams, about 2 to about 2.5 grams; from about 0.1 to about 2 grams, about 0.3 to about 2 grams, about 0.5 to about 2 grams, about 1 to about 2 grams, about 1.5 to about 2 grams; from about 0.1 to about 1.5 grams, about 0.3 to about 1.5 grams, about 0.5 to about 1.5 grams, about 1 to about 1.5 grams; from about 0.1 to about 1 gram, about 0.3 to about 1 gram, about 0.5 to about 1 gram; from about 0.1 to about 0.7 gram, about 0.3 to about 0.7 gram, about 0.5 to about 0.7 gram; from about 0.1 to about 0.4 gram, about 0.3 to about 0.4 gram, or any range or subrange thereof, based on the total weight of the oral care composition. In some embodiments, the oral care composition is in a form selected from a toothpaste; a gel; a mouthwash; a prophy; a spray; a lozenge; a tablet, a capsule; a strip; a patch; and a dissolvable film.Docket No. 1123319-00-WO-01-OC

[0098] The methods disclosed herein, in certain preferred embodiments, employ an oral care composition disclosed herein and further described below. 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.

[0099] The oral care compositions typically comprise a stannous source, preferably in an effective amount. The stannous source may comprise or consist of one or more stannous ion source. The stannous source (e.g., stannous ion 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 (e.g.. stannous ion 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, 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.

[0100] 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 source may comprise stannous fluoride, stannous chloride, stannous acetate, and a combinationDocket No. 1123319-00-WO-01-OCof two or more thereof. In at least one embodiment, the stannous ion source comprises stannous fluoride.

[0101] 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 and / or stannous ion 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 ion 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.

[0102] The oral care compositions typically comprise one or more nitrate source, preferably present in an effective amount. The nitrate source may comprise or consist of nitrate ion source(s). The nitrate source(s) (e.g., nitrate ion source(s)) 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. In some instances, the amount of nitrate source (e.g., nitrate ion 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.

[0103] The one or more nitrate source may be in the form of a salt or an ion derived therefrom, including, e.g., nitrate salt is selected from an alkali or alkaline earth metal nitrate. Examples of nitrate ion sources include lithium nitrate, sodium nitrate, potassium nitrate, magnesium nitrate, calcium nitrate, zinc nitrate, silver nitrate, ammonium nitrate, or a combination two or more thereof. The nitrate source may comprise nitric acid. In at least one embodiment, the nitrate source comprises potassium nitrate.

[0104] 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,Docket No. 1123319-00-WO-01-OCof 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.

[0105] The oral care compositions typically comprise one or more phosphate source(s). The phosphate ion source(s) is preferably present in an effective amount. The one or more phosphate source(s) may comprise or consist of phosphate ion source(s). In some instances, the oral care composition may include one or more phosphate source(s) (e.g., phosphate ion 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 one or more phosphate source(s) (e.g., phosphate ion 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.

[0106] 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 phosphate ion sources include tetrasodium pyrophosphate, dicalcium orthophosphate dihydrate, dicalcium phosphate dihydrate, calcium hydrogen phosphate, calcium pyrophosphate, p-calcium pyrophosphate, tricalcium phosphate, calcium metaphosphate, potassium metaphosphate, sodiumDocket No. 1123319-00-WO-01-OCmetaphosphate, 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.

[0107] Additionally or alternatively, the oral care composition may include one or more anticalculus agent. Examples of anti-calculus agents include, but are 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.

[0108] 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 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 5Docket No. 1123319-00-WO-01-OCwt.%, 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.

[0109] The oral care composition may include a zinc source. When present, the zinc source is preferably in an effective amount. The zinc source may be, comprise, or consist of a zinc ion source. The zinc source (e.g., zinc ion source) may be present in the oral care composition in an amount from about 0.1 to about 8 wt.%, based on the total weight of the oral care composition. For example, the amount of zinc source (e.g., zinc ion source) present 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 0.3 to about 8 wt.%, about 0.3 to about 6 wt.%, 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 8 wt.%, about 0.6 to about 6 wt.%, 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 8 wt.%, about 0.9 to about 6 wt.%, 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 8 wt.%, about 1.2 to about 6 wt.%, 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 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 8 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 8 wt.%, about 3 to about 6 wt.%, about 3 to about 5 wt.%; from about 4 to about 8 wt.%, about 4 to about 6 wt.%, about 4 to about 5 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0110] The zinc source may be in the form of a salt. For example, the zinc source may comprise one or more zinc salt(s) chosen from zinc sulfate, zinc chloride, zinc acetate, zinc phenol sulfonate, zinc borate, zinc bromide, zinc nitrate, zinc glycerophosphate, zinc benzoate, zinc carbonate, zinc camosine, zinc citrate, zinc hexafluorosilicate, zinc diacetate trihydrate, zinc oxide, zinc peroxide, zinc salicylate, zinc silicate, zinc stannate, zinc tannate, zinc titanate, zinc tetrafluoroborate, zinc gluconate, zinc lactate, zinc glycinate, zinc phosphate, and a combinationDocket No. 1123319-00-WO-01-OCof two or more thereof. In some embodiments, the zinc source is selected from zinc citrate, zinc oxide, zinc phosphate, zinc lactate, zinc sulfate, zinc silicate, zinc gluconate, and a combination of two or more thereof.

[0111] The oral care composition may include two or more, three or more, four or more, five or more, or six or more zinc 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 zinc sources. In some embodiments, the oral care composition comprises zinc oxide, zinc citrate, zinc phosphate, or a combination of two or more thereof. In at least one preferred embodiment, the oral care composition comprises zinc phosphate.

[0112] The oral care compositions may be formulated to have a weight ratio of the amount of zinc oxide to zinc citrate of from about 1.5: 1 to about 4.5:1. For instance, the weight ratio of the amount of zinc oxide to zinc citrate may be from about 1.5:1 to about 4.5:1, about 1.5:1 to about 4:1, about 1.5:1 to about 3.5:1, about 1.5:1 to about 3:1, about 1.5:1 to about 2.5:1; from about 2:1 to about 4.5:1, about 2:1 to about 4:1, about 2:1 to about 3.5:1, about 2:1 to about 3:1; from about 2.5:1 to about 4.5:1, about 2.5:1 to about 4:1, about 2.5:1 to about 3.5:1; from about 3:1 to about 4.5:1, about 3:1 to about 4:1, or any range or subrange formed thereof. In some embodiments, the weight ratio of the amount of zinc oxide to zinc citrate is about 2:1, about 2.5:1, about 3:1, about 3.5:1, about 4: 1, or a range formed thereof.

[0113] The oral care composition may include one or more surfactants, e.g., in an amount ranging from about 0.5 to about 8 wt.%, based on the total weight of the oral care composition. For example, the oral care composition may include one or more surfactant in an amount from about 0.5 to about 7 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 to about 9 wt.%, about 1 to about 8 wt.%, about 1 to about 7 wt.%, about 1 to about 6 wt.%, 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 2 to about 9 wt.%, about 2 to about 8 wt.%, 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 2.5 to about 9 wt.%, about 2.5 to about 8 wt.%, about 2.5 to about 7 wt.%, about 2.5 to about 6 wt.%, about 2.5 to about 5 wt.%, about 2.5 to about 4 wt.%, about 2.5 to about 3.5 wt.%; from about 3 to about 9 wt.%, about 3 to about 8 wt.%, about 3 to about 7 wt.%. about 3 to about 6 wt.%, about 3 to about 5 wt.%, about 3 to about 4 wt.%, about 3 to about 3.5 wt.%; from about 4 to about 9 wt.%, about 4Docket No. 1123319-00-WO-01-OCto about 8 wt.%, about 4 to about 7 wt.%, about 4 to about 6 wt.%, about 4 to about 5 wt.%; from about 5 to about 9 wt.%, about 5 to about 8 wt.%, about 5 to about 7 wt.%, about 5 to about 6 wt.%; from about 7 to about 9 wt.%, about 7 to about 8 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0114] The oral care composition may comprise a surfactant system comprising a plurality of surfactants. The surfactant system may comprise a plurality of 2 or more surfactants, e.g., 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, or 9 or more surfactants. In some instances, the oral care composition includes 2, 34, 5, 6, 7, 8, 9, 10 surfactants, or a range formed therefrom. For example, the oral care composition may comprise 2 to 4, 2 or 3, 3 or 4, 4 to 9, 4 to 8, 4 to 7, 4 to 6, 4 or 5; 5 to 9, 5 to 8, 5 to 7, 5 or 6; 6 to 9, 6 to 8, 6 or 7 surfactants.

[0115] The surfactant system may comprise one or more anionic surfactant, one or more cationic surfactant, one or more nonionic surfactants, one or more amphoteric surfactants, one or more zwitterionic surfactants, one or more bacterial surfactant, or combinations of two or more thereof. For example, the surfactant system comprises one or more non-sulfate based anionic surfactant, one or more amphoteric surfactant, one or more nonionic surfactant, and one or more amino acid surfactant. In some embodiments, the surfactant system comprises a single non-sulfate based anionic surfactant, a single amphoteric surfactant, a single nonionic surfactant, and a single amino acid surfactant. In at least one embodiment, the surfactant system comprises a single non-sulfate based anionic surfactant, a single amphoteric surfactant, a single nonionic surfactant, and a single amino acid surfactant. In further embodiments, the surfactant system consists of one or more anionic surfactant, one or more amphoteric surfactant, one or more nonionic surfactant, and one or more amino acid surfactant.

[0116] The oral care compositions typically comprise one or more anionic surfactant(s). The one or more anionic surfactant(s) may be in an amount that ranges 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 anionic 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 5 wt.%, about 0.8 to about 4 wt.%, about 0.8 to about 3 wt.%, about 0.8 to about 2Docket No. 1123319-00-WO-01-OCwt.%; 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.

[0117] The one or more anionic surfactant(s) may be selected from sulfate based anionic surfactants and / or from non- sulfate based anionic surfactants, such as sulfonated monoglycerides of fatty acids, isethionates, sarcosinates, taurate, and a combination of two or more thereof. Examples of sulfate based anionic surfactants include ammonium lauryl sulfate, ammonium lauryl ether sulfate, sodium dodecyl sulfate, sodium coco-sulfate, ammonium coco-sulfate, and a combination of two or more thereof. In at least one embodiment, the oral care composition includes a sulfate based anionic surfactant, wherein the oral care composition is substantially free of or free of sodium lauryl sulfate and / or sodium lauryl ether sulfate.

[0118] The anionic surfactant(s) may have at least one acyl group, preferably, comprising a carbon chain of 8 to 21 carbons. In some instance, the alkyl group(s) of the anionic surfactant(s) comprise a carbon chain of 8 to 19 carbons, 8 to 17 carbons, 8 to 15 carbons, 8 to 13 carbons, 8 to 11 carbons; 9 to 21 carbons, 9 to 19 carbons, 9 to 17 carbons, 9 to 15 carbons, 9 to 13 carbons, 9 to 11 carbons; 11 to 21 carbons, 11 to 19 carbons, 11 to 17 carbons, 11 to 15 carbons, 11 to 13 carbons; 13 to 21 carbons, 13 to 19 carbons, 13 to 17 carbons, or any range or subrange thereof. The anionic surfactants disclosed herein may be incorporated in a salt form. The salt form of the anionic surfactants may have an alkali metal (e.g., sodium or potassium) and / or ammonium group.

[0119] Non-limiting examples of isethionates include sodium isethionate, sodium cocoyl isethionate, sodium lauroyl methyl isethionate, and sodium cocoyl methyl isethionate. Sulfonated monoglycerides of fatty acids include sodium coconut monoglyceride sulfonates and the like. Examples of acyl sarcosinates include potassium lauroyl sarcosinate, potassium cocoyl sarcosinate, sodium cocoyl sarcosinate, sodium lauroyl sarcosinate, sodium myristoyl sarcosinate, sodium oleoyl sarcosinate, sodium palmitoyl sarcosinate, ammonium lauroyl sarcosinate, and combinations of two or more thereof.

[0120] The anionic surfactant may be selected from taurates having a structure according to the following formula:Docket No. 1123319-00-WO-01-OCo R2II IR1—C—N—CH2—CH2—SO3-M+wherein Ri is a saturated or unsaturated, straight or branched alkyl chain with 6 to 18 carbon atoms, R2 is H or methyl, and M+is H, sodium, or potassium (e.g., sodium methyl cocoyl taurate).

[0121] Additional examples of taurate surfactants include sodium cocoyl taurate. potassium cocoyl taurate, potassium methyl cocoyl taurate, sodium caproyl methyl taurate, sodium cocoyl taurate, sodium lauroyl taurate, sodium methyl cocoyl taurate (SMCT), sodium methyl lauroyl taurate, sodium methyl myristoyl taurate, sodium methyl oleoyl taurate, sodium methyl palmitoyl taurate, sodium methyl stearoyl taurate, and combinations of two or more thereof. In some embodiments, the oral care composition comprises sodium lauroyl methyl taurate (or sodium methyl lauroyl taurate), sodium methyl cocoyl taurate (SMCT), or a combination thereof. In at least one preferred embodiment, the surfactant system comprises sodium methyl cocoyl taurate.

[0122] 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.

[0123] 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 orDocket No. 1123319-00-WO-01-OCbranched. 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 water 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.

[0124] 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, 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.

[0125] 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 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.%,Docket No. 1123319-00-WO-01-OCabout 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.

[0126] 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. 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. In some embodiments, the surfactant system includes one or more nonionic surfactant(s) chosen from lauryl glucoside, lauroyl ethyl glucoside, myristoyl ethyl glucoside, oleoyl ethyl glucoside, and a combination of two or more thereof. Additionally or alternatively, the glucoside surfactant may be chosen from polyglucosides, such as alkylpolyglucosides.

[0127] Further examples of nonionic surfactants include poloxamers, 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, acids, and esters, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides and mixtures of such materials. Additional examples of nonionic surfactants include polyoxyethylene, polyoxyethylene sorbitan esters, polyoxyl 40 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, block copolymers of polyethylene glycol and polypropylene glycol, glycerol alkyl esters, polyoxyethytene glycol octylphenol ethers, sorbitan alkyl esters, polyoxyethylene glycol sorbitan alkyl esters, or a combination of two or more thereof.

[0128] The surfactant system may comprise one or more the amino acid derived surfactant(s) in an amount that may vary, but may be present 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 amino acid derived surfactant(s) is present in the surfactant system in an amount from about 0.1 to about 6 wt.%, aboutDocket No. 1123319-00-WO-01-OC0.1 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.

[0129] The amino acid derived surfactant may be anionic, non-ionic, amphoteric, or cationic. In some embodiments, the amino acid derived surfactant is an anionic surfactant. The amino acid derived surfactant may be based on alanine, arginine, aspartic acid, glutamic acid, glycine, isoleucine, leucine, lysine, phenylalanine, serine, tyrosine, valine, sarcosine, threonine, and taurine. The amino acid derived surfactants disclosed herein may be present in the oral care composition in a salt form. The most common cation associated with the acyl amino acid can be sodium or potassium. Alternatively, the cation can be an organic salt such as triethanolamine (TEA) or a metal salt.

[0130] The amino acid derived surfactant may be an acyl amino acid derived surfactant having an aliphatic carbon chain of 3 to 21 carbons. For instance, the amino acid derived surfactant may include an alkyl group comprised of a carbon chain of 3 to 21 carbons, 3 to 19 carbons, 3 to 17 carbons, 3 to 15 carbons, 3 to 13 carbons, 3 to 11 carbons, 3 to 9 carbons, 3 to 7 carbons; 4 to 21 carbons, 4 to 19 carbons, 4 to 17 carbons, 4 to 15 carbons, 4 to 13 carbons, 4 to 11 carbons, 4 to 9 carbons, 4 to 7 carbons; 6 to 21 carbons. 6 to 19 carbons. 6 to 17 carbons. 6 to 15 carbons. 6 to 13 carbons, 6 to 11 carbons, 6 to 9 carbons; 9 to 21 carbons, 9 to 19 carbons, 9 to 17 carbons, 9 to 15 carbons, 9 to 13 carbons, 9 to 11 carbons; 11 to 21 carbons, 11 to 19 carbons, 11 to 17 carbons, 11 to 15 carbons, 11 to 13 carbons; 13 to 21 carbons, 13 to 19 carbons, 13 to 17 carbons, or any range or subrange thereof.

[0131] The amino acid derived surfactant may be selected from a glutamic acid derived surfactant. The glutamic acid derived surfactant may be selected from an acyl glutamic acid derivedDocket No. 1123319-00-WO-01-OCsurfactants having an alkyl group comprised of a carbon chain having 3 to 21 carbons or any of the ranges for the carbon chain described above with respect to the amino acid derived surfactant. For instance, the carbon chain of the acyl glutamic acid derived surfactant may be 4 to 19 carbons, optionally 6 to 17 carbons, or optionally 9 to 13 carbons. In some preferred embodiments, the amino acid derived surfactant comprises sodium cocoyl glutamate.

[0132] Additionally or alternatively, the oral care compositions may be formulated to have certain weight ratios of the amount of amino acid based surfactant(s) to the amount of nonionic surfactant(s). For example, the oral care composition may have a weight ratio of the total amount of amino acid based surfactant(s) to the total amount of nonionic surfactant(s) of from about 1:5 to about 5:1, about 1:4 to about 5:1, about 1:3 to about 5:1, about 1:2 to about 5:1, about 1:1 to about 5:1; from about 1:5 to about 4:1, about 1:4 to about 4:1, about 1:3 to about 4:1, about 1:2 to about 4:1, about 1:1 to about 4:1; from about 1:5 to about 3:1, about 1:4 to about 3:1, about 1:3 to about 3:1, about 1:2 to about 3:1, about 1:1 to about 3:1; from about 1:5 to about 2:1, about 1:4 to about 2:1, about 1:3 to about 2:1, about 1:2 to about 2:1, about 1: 1 to about 2:1; from about 1:5 to about 1:1, about 1:4 to about 1:1, about 1:3 to about 1:1, about 1:2 to about 1:1, or about 1:1, including ranges or subranges formed thereof.

[0133] The oral care compositions may include a fluoride ion source. The fluoride ion source may be present in an effective amount. In some cases, the fluoride ion source is present in the oral care composition in an amount of about 0.01 to about 5 wt.%, based on the total weight of the oral care composition. For example, the fluoride ion source is present in an amount of about 0.01 to about 5 wt.%, about 0.01 to about 4 wt.%, about 0.01 to about 3 wt.%, about 0.01 to about 2 wt.%, about 0.01 to about 1 wt.%; from about 0.05 to about 5 wt.%, about 0.05 to about 4 wt.%, about 0.05 to about 3 wt.%, about 0.05 to about 2 wt.%, about 0.05 to about 1 wt.%; from 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.%; 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.%,Docket No. 1123319-00-WO-01-OCabout 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.

[0134] The fluoride ion source may be selected from soluble fluoride ion salts. For example, the fluoride ion source may comprise sodium fluoride, potassium fluoride, calcium fluoride, zinc fluoride, zinc ammonium fluoride, lithium fluoride, ammonium fluoride, stannous fluoride, stannous fluorozirconate, sodium monofluorophosphate, potassium monofluorophosphate, laurylamine hydrofluoride, diethylaminoethyloctoylamide hydrofluoride, didecyldimethylammonium fluoride, cetylpyridinium fluoride, dilaurylmorpholinium fluoride, sarcosine stannous fluoride, glycine potassium fluoride, glycine hydrofluoride, amine fluorides or a combination of two or more thereof. In some embodiments, the fluoride ion source comprises sodium fluoride, sodium monofluorophosphate, or a combination thereof.

[0135] In certain embodiments, the oral care composition of the disclosure may contain stannous fluoride and a source of fluoride ions or fluorine-providing agents in amounts sufficient to deliver, in total, from 25 ppm to 25,000 ppm (mass fraction) of fluoride ions, generally at least 500 ppm, e.g., from about 500 to about 2000 ppm, from about 800 to about 1800 ppm, from about 1000 to about 1600 ppm, from about 1200 to about 1550 ppm, or about 1450 ppm.

[0136] The oral care compositions may include one or more abrasive(s), e.g., in an amount from about 5 to about 35 wt.%, based on the total weight of the oral care composition. In some embodiments, the one or more abrasive(s) is present in an amount from about 5 to about 30 wt.%, about 5 to about 25 wt.%, about 5 to about 21 wt.%, about 5 to about 17 wt.%, about 5 to about 14 wt.%, about 5 to about 11 wt.%; from about 10 to about 35 wt.%, about 10 to about 30 wt.%, about 10 to about 25 wt.%, about 10 to about 21 wt.%, about 10 to about 17 wt.%, about 10 to about 14 wt.%; from about 15 to about 35 wt.%, about 15 to about 30 wt.%, about 15 to about 25 wt.%, about 15 to about 21 wt.%, about 15 to about 19 wt.%; from about 18 to about 35 wt.%. about 18 to about 30 wt.%, about 18 to about 25 wt.%. about 18 to about 21 wt.%; from about 21 to about 35 wt.%, about 21 to about 30 wt.%, about 21 to about 25 wt.%; from about 24 to about 35 wt.%, about 24 to about 30 wt.%; from about 27 to about 35 wt.%, about 27 to about 30 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0137] The one or more abrasive(s) may include: silica, silicate, silicon, alumina (including calcined aluminum oxide), aluminosilicates, such as bentonite, zeolite, kaolin, and mica, siliceous or diatomaceous earth, pumice, calcium carbonate, cuttlebone, insoluble phosphates, compositeDocket No. 1123319-00-WO-01-OCresins, such as melamine resin, phenolic resin, and urea-formaldehyde resin, polycarbonate, silicon carbide, boron carbide, microcrystalline wax, microcrystalline cellulose, including combinations of colloidal microcrystalline cellulose and carboxymethylcellulose, and combinations and derivatives thereof.

[0138] As used herein, “mica” refers to any of a group of hydrous aluminum silicate minerals with plate morphology and / or perfect basal (micaceous) cleavage. Mica can be, for example, sheet mica, scrap mica or flake mica, as exemplified by muscovite, biotite or phlogopite type micas. The abrasive may be selected from insoluble phosphates, such as orthophosphates, polymetaphosphates, pyrophosphates, and a combination thereof. Synthetic silicas include both silica gels and precipitated silicas that are prepared by the neutralization of aqueous silicate solutions with a strong mineral acid. Abrasives comprising silica may be useful in certain embodiments of the oral care composition. In certain embodiments, the oral compositions may comprise a particularly efficacious combination of silica abrasive particle species. For example, the abrasive(s) be selected from high cleaning silica, tetrasodium pyrophosphate (TSPP), sodium tripolyphosphate (STPP), and a combination of two or more thereof.

[0139] The oral care compositions may include an abrasive system comprising two or more abrasives. For example, an abrasive system comprises 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 abrasives. The abrasives may comprise one or more cleaning abrasive and / or one or more polishing abrasives. As appreciated by one of skill in the art, a single abrasive species typically performs at least some cleaning and polishing simultaneously. However, particles are generally categorized in the art by the predominant effect they have on a target oral surface. Typically, “polishing abrasives” are considered to be relatively small particles having high hardness, where abrasives with relatively large particle sizes and low hardness are considered to be “cleaning abrasives.” In certain embodiments, the oral care composition comprises two or more abrasives comprising silica. In some embodiments, the first abrasive is selected to be a harder and smaller abrasive, e.g., a higher cleaning and / or polishing abrasive, and the second abrasive is a typical cleaning abrasive. In some embodiments, the oral care composition includes at least one polishing abrasive and / or at least one cleaning abrasive. Further examples of abrasives are disclosed in U. S. Patent Publication No. 2007 / 140986, which is incorporated herein in its entirety by reference for all purposes.Docket No. 1123319-00-WO-01-OC

[0140] 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.

[0141] 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.

[0142] 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 arabic, and gum tragacanth can also be incorporated. Colloidal magnesium aluminum silicate can also be used as a component of 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 areDocket No. 1123319-00-WO-01-OCtypically physically and functionally distinct from the particulate silica abrasives as the silica thickeners are very finely divided and provide little or no abrasive action.

[0143] 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. The monomeric unit may include a polar imide group, four non-polar methylene groups, and a non-polar methane group. The polyvinyl pyrrolidone may have an average molecular weight in the range 5,000 to 100,000, preferably in the range 5,000 to 50,000. The polyvinyl pyrrolidones may be selected from those having an average molecular weight of 10,000, 30,000, 40,000, and / or a range formed therefrom. The polyvinyl pyrrolidone may form a hydrogen peroxide-polyvinyl pyrrolidone polymer complexes. In some embodiments, the polymer comprises crosslinked polyvinyl pyrrolidone (crosslinked PVP). In at least one embodiment, the polymer consists of polyvinyl pyrrolidone.

[0144] 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.

[0145] The acrylate may be chosen from diacrylates. 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.

[0146] Acrylates further include methacrylates, such as methyl methacrylate, ethyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, tert-butyl methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate, alkyl methacrylate, tridecyl methacrylate, stearyl methacrylate, cyclohexyl methacrylate, benzyl methacrylate, isobomyl methacrylate, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, dimethylaminoethyl methacrylate, diethylaminoethyl methacrylate,Docket No. 1123319-00-WO-01-OCglycidyl methacrylate, tetrahydrofurfuryl methacrylate, allyl methacrylate, ethylene glycol methacrylate, triethylene glycol methacrylate, tetraethylene glycol methacrylate, 1,3-butyleneglycol methacrylate, 1.6-hexanediol methacrylate, trimethylopropane methacrylate, ethoxyethyl methacrylate, trifluoroethyl methacrylate, or a combination of two or more thereof.

[0147] Examples of acrylamides include, but are not limited to, acrylamide, methacrylamide and di(C1-C30) alkyl-acrylamides and -methacrylamides such as those of methyl, ethyl, propyl, butyl, pentyl, hexyl and the like. N-substituted acrylamides that may be suitable include N-ethylacrylamide, N-tert-butylacrylamide, N-tert-octylacrylamide, N-octylacrylamide, N-decylacrylamide, N-dodecylacrylamide and the corresponding N-substituted methacrylamides. Other N-substituted acrylamides include N-hydroxymethyl acrylamide, N-isopropylacrylamide, N-methylacrylamide, N. N'-methylenebisacrylamide, N-isobutoxymethylacrylamide. N, N-dimethylacrylamide, and 2-acrylamido-2-methylpropanesulfonic acid.

[0148] 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 1 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.

[0149] In other embodiments, the oral care composition may include polyol(s) in an amount 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 toDocket No. 1123319-00-WO-01-OCabout 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.%, about 0.5 to about 2 wt.%, about 0.5 to about 1 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.%, about 1 to about 2 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.

[0150] 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.

[0151] 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,Docket No. 1123319-00-WO-01-OCdipropylene 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.

[0152] 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 oral care compositions of the disclosure comprise one or more polyethylene glycols, for example, polyethylene glycols in a molecular weight range from 200 to 800. 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.

[0153] The oral care compositions may, in some cases, comprise one or more amino acid(s) in an effective amount. In some embodiments, the one or more amino acid(s) may be present in the oral care composition in an amount from about 0.1 to about 10 wt.%, about 0.1 to about 8 wt.%, about 0.1 to about 6 wt.%, about 0.1 to about 4 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 10 wt.%, about 0.5 to about 8 wt.%, about 0.5 to about 6 wt.%, about 0.5 to about 4 wt.%, about 0.5 to about 2 wt.%, about 0.5 to aboutDocket No. 1123319-00-WO-01-OC1 wt.%; from about 1 to about 10 wt.%, about 1 to about 8 wt.%, about 1 to about 6 wt.%, about 1 to about 4 wt.%, about 1 to about 2 wt.%; from about 2 to about 10 wt.%, about 2 to about 8 wt.%, about 2 to about 6 wt.%, about 2 to about 4 wt.%; from about 3 to about 10 wt.%, about 3 to about 8 wt.%, about 3 to about 6 wt.%, about 3 to about 4 wt.%; from about 4 to about 10 wt.%, about 4 to about 8 wt.%, about 4 to about 6 wt.%; from about 6 to about 10 wt.%, about 6 to about 8 wt.%; from about 8 to about 10 wt.%. including any range or subrange thereof, based on the total weight of the oral care composition.

[0154] The one or more amino acids may be selected from basic amino acids, neutral amino acids, and combinations thereof. The basic amino acids may be selected from naturally occurring basic amino acids, such as arginine, lysine, and histidine, and non-naturally occurring basic amino acids having a carboxyl group and an amino group in the molecule, which are water-soluble and provide an aqueous solution with a pH of 7 or greater. Examples of basic amino acids include arginine, lysine, serine, citrulline, ornithine, creatine, histidine, diaminobutanoic acid, diaminoproprionic acid, salts thereof or combinations thereof. In some embodiments, the basic amino acids are selected from arginine, citrulline, and ornithine. In certain embodiments, the basic amino acid is arginine, e.g., L- arginine, or a salt thereof. Additionally or alternatively, the one or more amino acid can be chosen from neutral amino acids, which can include, but are not limited to, one or more neutral amino acids selected from the group consisting of alanine, aminobutyrate, asparagine, cysteine, cystine, glutamine, glycine, hydroxyproline, isoleucine, leucine, methionine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine, valine, and combinations thereof.

[0155] 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.

[0156] 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 toDocket No. 1123319-00-WO-01-OCabout 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 37 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.

[0157] 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.

[0158] 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.%;Docket No. 1123319-00-WO-01-OCfrom 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.

[0159] 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.

[0160] 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 concentrations 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.

[0161] 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.

[0162] 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 careDocket No. 1123319-00-WO-01-OCcomposition. Tn 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.

[0163] The oral care compositions may have a pH from 4.5 to about 10, 4.5 to about 9, 4.5 to about 8, 4.5 to about 7, 4.5 to about 6; from about 5 to about 10, about 5 to about 9, about 5 to about 8, about 5 to about 7, about 5 to about 6; from about 6 to about 10, about 6 to about 9, about 6 to about 8, or about 6 to about 7; from about 7 to about 10, about 7 to about 9, or about 7 to about 8, including any ranges and subranges therebetween.

[0164] 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 20 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.EXAMPLESExample 1

[0165] THP-1 monocyte-like cells were cultured and then plated at 0.05 × 106cells per well in a 50 nM PM A culture medium over 72 hours until they were differentiated into macrophages. The macrophages were washed two times with PBS and complete culture media was placed into the respective wells. For the Ml macrophage-like cells, 100 ng / mL of bacterial p.g. lipopolysaccharide (“hereafter bacterial LPS”) was also included. The cells were then cultured for 48 hours in this media. A non-limiting example solution (Example Composition A) was prepared in accordance with aspects of the disclosure. Example Composition A included stannous fluoride (SnF), potassium nitrate (KNO3), tetrasodium pyrophosphate (TSPP) and water. A 100 ppm sample ofDocket No. 1123319-00-WO-01-OCExample Composition A included 0.454 ppm of SnF, 0.3-0.8 ppm of KNO3, and 1-1.5 ppm of TSPP. A 500 ppm sample of Example Composition A included 2.27 ppm of SnF, 2.2-2.8 ppm of KNO3, and 5.2-6 ppm of TSPP. A 1000 ppm sample of Example Composition A included 4.54 ppm of SnF, 7-8 ppm of KNO3, and 10.5-13 ppm of TSPP.

[0166] Using the culture media and Example Composition A, the following experimental test samples were prepared for evaluation: samples having naive macrophage-like cells (“M0 macrophage-like cells”) (Samples 1); samples having M0 macrophage-like cells and 500 ppm of Example Composition A (Samples 2); samples having M0 macrophage-like cells and 100 ppm of Example Composition A (Sample 3); samples having M0 macrophage-like cells and bacterial LPS (Samples 4); samples having M0 macrophage-like cells, 500 ppm of Example Composition A, and bacterial LPS (Samples 5); samples having M0 macrophage-like cells, 100 ppm of Example Composition A, and bacterial LPS (Samples 6); samples having Ml macrophage-like cells (Samples 7); samples having Ml macrophage-like cells and bacterial LPS (Samples 8); samples having Ml macrophage-like cells and 500 ppm of Example Composition A (Samples 9); samples having Ml macrophage-like cells and 100 ppm of Example Composition A (Sample 10); samples having Ml macrophage-like cells, 500 ppm of Example Composition A, and bacterial LPS (Samples 11); and samples having Ml macrophage-like cells, 100 ppm of Example Composition A, and bacterial LPS (Samples 12). Wells having the Ml macrophage-like cells were polarized to Ml, but did not receive additional LPS after 48 hours. Instead, they received just complete media. The bacterial LPs was added to the samples using 100 ng / ml of p.g. (Porphyromonas gingivalis) bacteria.

[0167] The samples of culture media were then incubated for 24 hours at a temperature of 37 °C.After the 24 hours of incubation, the culture media was collected and frozen at a temperature of -80 °C. The cells were then washed and treated with Tryple Express dissociation solution for 40 min until cells were scraped to fully detach. The cells were spun down and placed into a 96 well U-bottom plate for staining with Live / Dead and antibody markers. Samples were read on an Attune NxT cytometer. Samples were analyzed and gated in FlowJo (BD Life Sciences) software. The 4th sample of each group was combined to make a control population for unstained, dead and FMO controls for gating purposes.Docket No. 1123319-00-WO-01-OC

[0168] A peprotech IL-1 B ELISA (900-K95) and invitrogen TNFa ELISA (88-7346-88) were used to find protein concentrations. Samples were thawed and diluted according to plate layout. Samples were run according to manufacturers’ instructions.

[0169] A summary of the evaluation is shown in FIGS. 1A-2C. FIGS. 1A-1C are bar graphs of the evaluation of the markers on the MO macrophage-like cells. FIGS. 2A-2C are bar graphs of the evaluation of the markers on the pre-inflamed Ml macrophage-like cells. FIGS. 3 A and 3B are bar graphs of the TNFa secretion from the MO macrophage-like cells and Ml macrophage-like cells.

[0170] As seen in FIGS. 1A-2B, Example Composition A had an effect on CD40 and CD80. Specifically, Example Composition A reduced CD40 while in the presence of LPS, regardless of if the macrophage was initially inactivated or inflamed. Example Composition A also promoted CD80 expression, but only in the presence of LPS. This is an unexpected finding as typical antibacterial effects do not increase CD80 expression and instead act on bacteria independent of the immune system. Without being limited to any particular theory, it is believed that Example Composition A promotes the expression of CD80 in macrophage cells when in the presence of bacterial LPS while reducing the expression of CD40 to prevent an overly inflamed environment.Example 2

[0171] THP-1 macrophage-like cells were evaluated after application of Example Composition A from Example 1 to further evaluate the efficacy for controlling and / or effecting the activation of macrophages as well as effects on activated macrophages. THP-1 monocyte-like cells were cultured in and then plated at 0.25 × 106cells per well in a 50 nM PMA culture medium over 72 hours until they were differentiated into macrophages. The THP-1 cells were prepared and evaluated based on the below experimental design according to procedures substantially similar to those described in Example 1. Example Composition A from Example 1 was utilized in the following experimental tests. Briefly, a 100 ppm sample of Example Composition A included 0.454 ppm of SnF, 0.3-0.8 ppm of KNO3, and 1-1.5 ppm of TSPP. A 500 ppm sample of Example Composition A included 2.27 ppm of SnF, 2.2-2.8 ppm of KNO3, and 5.2-6 ppm of TSPP. A 1000 ppm sample of Example Composition A included 4.54 ppm of SnF, 7-8 ppm of KNO3, and 10.5-13 ppm of TSPP.

[0172] Similar to in Example 1, the following experimental test samples were prepared for evaluation: samples having M0 macrophage-like cells (Samples 1); samples having M0 macrophage-like cells and 500 ppm of Example Composition A (Samples 2); samples having M0Docket No. 1123319-00-WO-01-OCmacrophage-like cells and 100 ppm of Example Composition A (Sample 3); samples having MO macrophage-like cells and bacterial LPS (Samples 4); samples having MO macrophage-like cells, 500 ppm of Example Composition A, and bacterial LPS (Samples 5); samples having MO macrophage-like cells, 100 ppm of Example Composition A, and bacterial LPS (Samples 6); samples having Ml macrophage-like cells (Samples 7); samples having Ml macrophage-like cells and bacterial LPS (Samples 8); samples having Ml macrophage-like cells and 500 ppm of Example Composition A (Samples 9); samples having Ml macrophage-like cells and 100 ppm of Example Composition A (Sample 10); samples having Ml macrophage-like cells. 500 ppm of Example Composition A, and bacterial LPS (Samples 11); and samples having M1 macrophage-like cells, 100 ppm of Example Composition A, and bacterial LPS (Samples 12). Wells having the Ml macrophage-like cells were polarized to Ml, but did not receive additional LPS after 48 hours. Instead, they received just complete media. The bacterial LPs were added to the samples using 100 ng / ml of p.g. (Porphyromonas gingivalis) bacteria.

[0173] As seen in FIGS. 4A-5C, Example Composition A had had an effect on CD40 expression and CD80 expression on macrophages. Additionally, the Example Composition A reduced CD40 while in the presence of LPS, regardless of if the macrophage was initially inactivated or inflamed. Example Composition A also promoted CD80 expression, but only in the presence of LPS. As noted about, the results further support that Example Composition A promotes the expression of CD80 in macrophage cells when in the presence of bacterial LPS while reducing the CD40 expression to prevent an overly inflamed environment.

[0174] Additionally, as seen in FIGS. 6A and 6B, TNFa secretion was unaltered by Example Composition A. However, IL-1B secretion was reduced at 500 ppm concentration by the administration of Example Composition A.Example 3

[0175] Macrophage cells were evaluated after application of Example Composition A to assess the effect on MMP13 and CCL2 secretion. THP-1 monocyte-like cells were cultured in and then plated at 0.25 × 106cells per well in a 50 nM PMA culture medium over 72 hours until they were differentiated into macrophages. The macrophage cells were then incubated for 24 hours at a temperature of 37 °C for a rest period. Samples of the macrophage cells were then given media or media having Example Composition A for 24 hours. Then, samples of the macrophage cells were given media, media having Example Composition A, media having pathogenic bacterial LPS, orDocket No. 1123319-00-WO-01-OCmedia having Example Composition A and pathogenic bacterial LPS. Example Composition A was the same as Example Composition A from Examples 1 and 2. Specifically, a 100 ppm sample of Example Composition A included 0.454 ppm of SnF, 0.3-0.8 ppm of KNO3. and 1-1.5 ppm of TSPP. A 500 ppm sample of Example Composition A included 2.27 ppm of SnF, 2.2-2.8 ppm of KNO3, and 5.2-6 ppm of TSPP. A 1000 ppm sample of Example Composition A included 4.54 ppm of SnF, 7-8 ppm of KNO3, and 10.5-13 ppm of TSPP.

[0176] The following experimental test samples were prepared for evaluation: samples having M0 macrophage-like cells (Samples 1); samples having M0 macrophage-like cells and 500 ppm of Example Composition A (Samples 2); samples having M0 macrophage-like cells that were pretreated with 500 ppm of Example Composition A and then treat only with bacterial LPS (Samples 3); samples having M0 macrophage-like cells and bacterial LPS (Samples 4); samples having M0 macrophage-like cells, 500 ppm of Example Composition A, and bacterial LPS (Samples 5); and samples having M0 macrophage-like cells, 1000 ppm of Example Composition A, and bacterial LPS (Samples 6).

[0177] The macrophage cells were incubated for 18 hours before the media and the macrophage cells were collected for analysis. The media was collected into 2 mL tubes and frozen at a temperature of -80 °C. The macrophage cells were then removed from the culture plates via TryplExpress for 8 minutes at a temperature of 37 °C. Cells were removed and placed into tubes.

[0178] A summary of the results of the evaluation for MMP-13 and CCL2 expression is shown in FIGS. 7A and 7B. FIG. 7A provides a bar graph of the MMP-13 secretions from THP-1 macrophage cells. FIG. 7B provides a bar graph of the Secretion levels of CCL2 (MCP-1) from THP-1 macrophage cells. Unexpectedly, MMP-13 expression was significantly reduced by the administration of Example Composition A. CCL2 expression was also reduced when Example Composition A was administered.Example 4

[0179] A non-limiting exemplary composition (Example Composition B) was prepared in accordance with aspects of the disclosure. Example Composition B was evaluated in comparison to a comparative oral care composition (Comparative Composition 1) to assess the effect on collagenase inhibition. The formulations for producing Example Composition B and Comparative Composition 1 are provided in Table 1.Table 1Docket No. 1123319-00-WO-01-OCComp. 1 Ex. BUS INCI Compound Name(wt.%) (wt.%) Sorbitol QS to 100 QS to 100 Water 29.3 24.6 Surfactants (Sodium Lauryl Sulfate and3.5 2.8 Cocamidopropyl Betaine)Thickening Agents (Thickening Silica, Sodium8.5 8.4 CMC, and / or Xanthan Gum)Sodium Fluoride 0.2Stannous Fluoride 0.5 Potassium Nitrate 0.4-0.7 Tetrasodium Pyrophosphate 1-1.5 Silica Abrasive 8 15 Polyethylene Glycol 600 1 2Flavor (Flavoring Agents and Sweeteners) 1.7 2 Colorants, Opacifiers, and / or Other Visual0.2 0.5Aesthetics (e.g., White Film Aesthetics)

[0180] Samples of Example Composition B and Comparative Composition 1 were used to prepare toothpaste slurries. The toothpaste slurries were tested by using EnzChek™ Gelatinase / Collagenase Assay Kit follow the manufacturer’s instruction. Specifically, the following experimental steps were followed to evaluate Example Composition B and Comparative Composition 1. Dilute the slurry of interest (1: 10, 1 part of toothpaste and 10 parts of distilled water) in IX Reaction buffer at final 1: 1000. Make dilutions of 1,10-phenanthroline to 0.5 mM in IX Reaction Buffer. Add 80 µL of the slurry (from step 1) or diluted inhibitor (from step 2 as control) to each assay well. Add 20 pL of DQ gelatin stock solution to each assay well. Add 100 pL of the diluted Clostridium collagenase ( at 0.2U / ml) to the sample wells preloaded with substrate and test slurry / inhibitor. Incubate the samples at room temperature, protected from light, for 2 hours. Measure the fluorescence intensity at Excitation at 495 nm and Emission at 515nm.

[0181] A summary of the evaluation of Example Composition B and Comparative Composition 1 is shown in FIG. 8. Notably, Example Composition B attenuates collagenase activity and, thus, may reduce and / or alleviate soft tissue degradation.

Claims

Docket No. 1123319-00-WO-01-OCCLAIMSWhat is Claimed is:

1. A method for prophylactically treating an inflammatory condition in a population at risk for an overactive and / or dysregulated inflammatory response, the method comprising:determining a subject to be at risk for an overactive and / or dysregulated inflammatory response; andreducing CD40 expression and MMP-13 by applying an oral care composition to the oral cavity, the oral care composition comprising:a stannous source;a nitrate source; anda polyphosphate.

2. The method according to claim 1, wherein the population at risk for an overactive and / or dysregulated inflammatory response is suffering from an autoimmune disease, diabetes respiratory tract infection, cardio-vascular disease, inflammatory bowel disease, lupus, or a combination thereof.

3. The method according to claim 1 or claim 2, wherein the inflammatory condition is associated with an overexpression of CD40.

4. A method for controlling an overexpression of CD40 in an oral cavity of a subject in need thereof, the method comprising:ascertaining an overexpression of CD40 in the oral cavity; andreducing CD40 expression in the oral cavity by applying an oral care composition to the oral cavity, the oral care composition comprising:a stannous source;a nitrate source; anda polyphosphate.

5. The method according to claim 4, wherein the CD40 expression is reduced by about 10% or more, as measured about 24 hours after application of the oral care composition.Docket No. 1123319-00-WO-01-OC6. The method according to claim 4 or claim 5, comprising reducing the CD40 expressing macrophages, as measured about 24 hours after application of the oral care composition.

7. The method according to any one of claim 4 to claim 6, comprising increasing the CD80 expressing macrophages, as measured about 18 hours after application of the oral care composition.

8. The method according to claim 7, wherein the expression of CD80 is increased by about 10% or more in the presence of bacterial lipopolysaccharide relative to the expression of CD80 without the presence of bacterial lipopolysaccharide, as measured about 18 hours after application of the oral care composition.

9. The method according to any one of claim 4 to claim 8, wherein the overexpression of CD40 is determined based on a threshold value.

10. The method according to any one of claim 4 to claim 9 further comprising: reducing the MMP-13 in the oral care cavity.

11. A method for promoting a reduction of bacterial lipopolysaccharide, the method comprising:ascertaining the presence of bacterial lipopolysaccharide in an oral cavity; increasing the expression of CD80 and reducing the expression of CD40 and / or MMP-13 by applying an oral care composition to the oral cavity, the oral care composition comprising:a stannous source;a nitrate source; anda polyphosphate.

12. The method according to claim 11, wherein the presence of pathogenic bacterial lipopolysaccharide is associated with Porphvromonas gingivalis, Treponema denticola, Prevotella nigrescens, and / or Peptostreptucoccus micro.Docket No. 1123319-00-WO-01-OC13. The method according to claim 11 or claim 12, wherein the expression of CD80 is increased by about 10% or more, as measured about 18 hours after application of the oral care composition and / or wherein the expression of CD40 expression is reduced by about 10% or more, as measured about 24 hours after application of the oral care composition.

14. The method according to any one of claim 11 to claim 13, comprising reducing the MMP-13 by 10% or more, as measured about 24 hours after application of the oral care composition.

15. A method for prophylactically treating, reducing, or alleviating periodontitis and / or peri-implantitis in a subject suffering therefrom, the method comprising:determining a subject as having periodontitis and / or peri-implantitis; andreducing MMP-13 by applying an oral care composition to the oral cavity, the oral care composition comprising:a stannous source;a nitrate source; anda polyphosphate.

16. The method according to claim 15, wherein the MMP-13 is reduced by 10% or more, as measured about 24 hours after application of the oral care composition.

17. The method according to any foregoing claim, the method further comprising:comprising reducing collagenase activity by about 4% or more, as measured about 24 hours after application of the oral care composition.

18. A method for reducing collagenase activity in an oral cavity of a subject, the method comprising:ascertaining the presence of collagenase activity in an oral cavity; andreducing collagenase activity in the oral cavity by applying an oral care composition to the oral cavity, the oral care composition comprising:Docket No. 1123319-00-WO-01-OCa stannous source;a nitrate source; anda polyphosphate.

19. The method according to claim 18, wherein the collagenase activity is reduced by about 4% or more, as measured about 24 hours after application of the oral care composition.

20. The method according to any foregoing claim, wherein the amount of the oral care oral care composition applied to the oral cavity is about 0.1 to about 3 grams.

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