Methods for reducing, alleviating, or treating gum disease

Abstract

Methods for reducing, alleviating, and / or treating gum diseases as well as oral care compositions for use therewith are disclosed herein. In accordance with one aspect, provided is a method for reducing and / or inhibiting gingipains by identifying an individual as having an undesirable amount of proteolytic activity of arginine gingipain and / or an undesirable amount of proteolytic activity and / or rate of lysine gingipain; and applying an oral care composition to an oral cavity, the oral care composition comprising a stannous source, a nitrate ion source, and a pyrophosphate.

Description

METHODS FOR REDUCING, ALLEVIATING, OR TREATING GUM DISEASECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority from U.S. Patent Application No. 63 / 586,525, filed September 29, 2023, titled Methods for Reducing, Alleviating, or Treating Gum Disease, and from U.S. Patent Application No. 63 / 586,554, filed September 29, 2023, titled Methods for Reducing, Alleviating, or Treating Gum Disease, the contents from both of which are hereby incorporated herein in their entireties for all purposes.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 and salivary as well as food by-products, starch, proteins and proteinacious material. Thus, inhibiting the growth of bio-film not only involves dispersing the accumulation of existing proteinacious materials, but also requires prohibiting and minimizing their reattachment to the tooth surface. 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). Besides being unsightly, plaque is implicated in the occurrence of gingivitis and other forms of periodontal disease.

[0003] Gingivitis is the earliest stage of gum disease, an inflammation of the gums caused by plaque buildup at the gumline. If daily brushing and flossing do not remove the plaque, it produces toxins (poisons) that can irritate the gum tissue, causing gingivitis. Symptoms include bleeding during brushing and flossing. At this early stage in gum disease, damage can be reversed, since the bone and connective tissue that hold the teeth in place are not yet affected.

[0004] Periodontitis is more advanced gum disease. At this stage, the supporting bone and fibers that hold teeth in place are irreversibly damaged. Gums may begin to form a pocket below the gumline, which traps food and plaque. Proper dental treatment and improved home care can usually help prevent further damage.

[0005] In advanced Periodontitis, the fibers and bone supporting your teeth are destroyed, which can cause teeth to shift or loosen. This can affect bite and, if aggressive treatment cannot save them, teeth may need to be removed.BRIEF SUMMARY

[0006] 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.

[0007] Aspects the invention are directed to methods for reducing, alleviating, and / or treating gum diseases, such as gingivitis and periodontitis, as well as oral care compositions for use therewith. In accordance with one aspect, provided is a method for reducing and / or inhibiting gingipain by applying an oral care composition to an oral cavity, the oral care composition comprising a stannous source, a nitrate ion source, and a pyrophosphate.

[0008] In accordance with another aspect, provided is a method for reducing, inhibiting, and / or alleviating periodontal disease by applying an oral care composition to an oral cavity, the oral care composition comprising a stannous source, a nitrate ion source, and a pyrophosphate.

[0009] In accordance with a further aspect, provided is a method for shifting biofilm composition in an individual's oral cavity to reduce pathogenic bacterial compared to healthy bacteria, the method comprising applying an oral care composition to an oral cavity, the oral care composition comprising a stannous source, a nitrate ion source, and a pyrophosphate.

[0010] In accordance with yet another aspect, provided is a method for reducing and / or inhibiting gingipain(s) comprising: identifying an individual as having an undesirable amount of proteolytic activity of arginine gingipain and / or an undesirable amount of proteolytic activity and / or rate of lysine gingipain; applying an oral care composition to an oral cavity, the oral care composition comprising a stannous source, a nitrate source, and a phosphate source.BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Implementation of the present technology will now be described, by way of example only, with reference to the attached figures, wherein:

[0012] FIGS. 1A and IB are graphs of the growth results of P. gingivalis after application with a first or a second non-limiting, example composition in accordance with aspects of the invention;

[0013] FIGS. 2A and 2B are graphs of certain protease activities measured immediately after two minutes of treatment with the first or the second example composition in accordance with aspects of the invention;

[0014] FIGS. 3A and 3B are graphs of certain protease activities measured twelve hours after treatment with the first or the second example composition in accordance with aspects of the invention;

[0015] FIG. 4B is a graph of the NF-KB nuclear translocation in cultured oral keratinocytes with and without application of a non-limiting example oral care composition;

[0016] FIG. 4B is a graph illustrating the quantification of the NF-kB translocation of FIG. 4A;

[0017] FIG. 5A provides images of tight junctions in cultured oral keratinocytes with and without application of a non-limiting example oral care composition at different P.g. MOI; and

[0018] FIG. 5B is a graph of the percentage of tight junction fluorescence between samples with or without the application of the non-limiting example oral care composition from FIG. 5A.

[0019] It should be understood that the various aspects are not limited to the arrangements and instrumentality shown in the drawings.DETAILED DESCRIPTION

[0020] 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.

[0021] As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context dictates otherwise. The singular’ form of any class of the ingredients refers not only to one chemical species within that class, but also to a mixture of those chemical species. The terms “a” (or “an”), “one or more” and “at least one” may be used interchangeably herein. The terms “comprising”, “including”, and “having” may be usedinterchangeably. The term “include” should be interpreted as “include, but are not limited to”. The term “including” should be interpreted as “including, but arc not limited to”.

[0022] 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.

[0023] 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.%.

[0024] 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.

[0025] 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.

[0026] 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.

[0027] “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.

[0028] Any member in a list of species that are used to exemplify or define a genus, may be mutually different from, or overlapping with, or a subset of, or equivalent to, or nearly the same as, or identical to, any other member of the list of species. Further, unless explicitly stated, such as when reciting a Markush group, the list of species that define or exemplify the genus is open, and it is given that other species may exist that define or exemplify the genus just as well as, or better than, any other species listed.

[0029] 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.

[0030] 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.

[0031] 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.

[0032] 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.”

[0033] 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 suchas 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.

[0034] 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.

[0035] 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.

[0036] 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.

[0037] 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.

[0038] 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.

[0039] 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.

[0040] 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 “Gram-positive” refer to staining patterns with the Gram-staining process, which is well known in the art. (See e.g., Fincgold 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.

[0041] 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.

[0042] 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.

[0043] Aspects the invention are directed to methods for reducing, alleviating, and / or treating gum diseases, such as gingivitis and periodontitis, as well as oral care compositions for use therewith. The inventors discovered that certain methods and compositions disclosed herein can provide significant reduction, inhibition, and / or alleviation of gingivitis, and particularly periodontitis. The significant reduction, inhibition, and / or alleviation of periodontitis was unexpected. For instance, certain embodiments reduce the growth rate and / or inhibit the growth of Porphyromonas gingivalis in the oral cavity, such as in a periodontal tissue, and / or in the periodontal pocket.

[0044] Preferably, the methods disclosed herein reduce and / or inhibit the growth of Porphyromonas gingivalis in the oral cavity, such as in a periodontal tissue, and / or in the periodontal pocket. In some embodiments, the methods disclosed herein reduce the growth rate of Porphyromonas gingivalis and / or vesicles of Porphyromonas gingivalis by 5% or more, e.g., as compared to the growth rate of Porphyromonas gingivalis under similar conditions without the inventive method. In certain embodiments, the methods disclosed herein reduce the growth rate of Porphyromonas gingivalis and / or vesicles of Porphyromonas gingivalis by about 10% or more,about 15% or more, about 20% or more, about 22% or more, about 24% or more, about 25% or more, about 26% or more, about 28% or more, or about 30% or more, c.g., as compared to the growth rate of Porphyromonas gingivalis under similar conditions without the inventive method. For example, when the method includes applying an oral care composition in the form of a dentifrice by brushing, the method disclosed herein may reduce the growth rate of Porphyromonas gingivalis by one of the foregoing amounts as compared to the growth rate of Porphyromonas gingivalis under similar conditions, such as brushing without the inventive dentifrice disclosed herein. By way of another example, when the method includes applying an oral care composition in the form of a mouthwash by swishing, gargling, and / or rinsing, the method disclosed herein may reduce the growth rate of Porphyromonas gingivalis by one of the foregoing amounts as compared to the growth rate of Porphyromonas gingivalis under similar conditions without the application of the inventive mouthwash disclosed herein.

[0045] The methods disclosed herein may include identifying an individual and / or a subpopulation as having an undesirable amount (e.g., a predetermined threshold) and / or growth rate of Porphyromonas gingivalis in the oral cavity, such as in a periodontal tissue, and / or in the periodontal pocket. An undesirable amount and / or growth rate of Porphyromonas gingivalis may be based on a predetermined threshold. The predetermined threshold may be determined by a doctor, dentist, and / or medical professional, which would readily have knowledge of the undesirable amounts of Porphyromonas gingivalis for the individual. The methods for reducing and / or inhibiting the growth of Porphyromonas gingivalis may include administering the oral care composition in certain amounts and / or for amounts of time described below.

[0046] Additionally or alternatively, the methods disclosed herein may reduce and / or inhibit the proteolytic activity and / or rate of gingipains (e.g., lysine gingipain and arginine gingipain) in the oral cavity, such as in a periodontal tissue, and / or in the periodontal pocket. In some embodiments, the methods disclosed herein reduces the proteolytic activity and / or rate of lysine gingipain by 5% or more after about 2 minutes from application of the oral care composition, e.g., as compared to the proteolytic activity and / or rate of lysine gingipain under similar conditions without the inventive method. For instance, the methods disclosed herein may reduce the proteolytic activity and / or rate of lysine gingipain by about 15% or more, about 20% or more, about 25% or more, about 30% or more, about 35% or more, about 38% or more, about 41% or more, about 44% or more, about 47% or more, about 50% or more, about 53% or more, about 56% or more, or about59% or more, after about 2 minutes from application of the oral care composition, e.g., using whole cell cultures and / or whole wash cell cultures as compared to the proteolytic activity and / or rate of lysine gingipain under similar conditions without the inventive method.

[0047] In some embodiments, the methods disclosed herein reduce the proteolytic activity and / or rate of lysine gingipain by 10% or more after about 12 hours from application of the oral care composition, e.g., as compared to the proteolytic activity and / or rate of lysine gingipain under similar conditions without the inventive method. In some instances, the method may reduce the proteolytic activity and / or rate of the lysine gingipain in the periodontal pocket. For instance, the methods disclosed herein may reduce the proteolytic activity and / or rate of lysine gingipain by about 15% or more, about 20% or more, about 25% or more, about 30% or more, about 35% or more, about 38% or more, about 41% or more, about 44% or more, about 47% or more, about 50% or more, about 53% or more, about 56% or more, or about 59% or more, after about 12 hours from application of the oral care composition, e.g., using whole cell cultures and / or whole wash cell cultures as compared to the proteolytic activity and / or rate of lysine gingipain under similar conditions without the inventive method.

[0048] The method may achieve any of the foregoing reductions in the proteolytic function of the lysine gingipain, after 2 minutes or about 12 hours, as measured in the periodontal pocket. In some embodiments, the method achieves any of the foregoing reductions in the proteolytic activity and / or rate of the lysine gingipain, after 2 minutes or about 12 hours, as measured in the periodontal tissue.

[0049] The reduced proteolytic activity and / or rate of lysine gingipain can be determined by measuring Kgp activity. For example, when the method includes applying an oral care composition in the form of a dentifrice by brushing, the method disclosed herein may reduce the proteolytic activity and / or rate of lysine gingipain (e.g., as measured by Kgp activity) by one of the foregoing amounts as compared to the proteolytic activity and / or rate of lysine gingipain (e.g., as measured by Kgp activity) under similar conditions, such as brushing without the inventive dentifrices disclosed herein. By way of another example, when the method includes applying an oral care composition in the form of a mouthwash by swishing, gargling, and / or rinsing, the method disclosed herein may reduce the proteolytic activity and / or rate of lysine gingipain (e.g., as measured by Kgp activity) by one of the foregoing amounts as compared to the proteolytic activityand / or rate of lysine gingipain (e.g., as measured by Kgp activity) under similar conditions without the application of the inventive mouthwashes disclosed herein.

[0050] The methods disclosed herein may, additionally or alternatively, reduce the proteolytic activity and / or rate of arginine gingipain by 5% or more after about 2 minutes from application of the oral care composition, e.g., as compared to the proteolytic activity and / or rate of arginine gingipain under similar conditions without the inventive method. In some embodiments, the method reduces the proteolytic activity and / or rate of arginine gingipain by about 15% or more, about 30% or more, about 45% or more, about 60% or more, about 70% or more, about 75% or more, about 80% or more, about 83% or more, about 86% or more, about 89% or more, about 91% or more, about 93% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more, after about 2 minutes from application of the oral care composition, e.g., using whole cell cultures and / or whole wash cell cultures as compared to the proteolytic activity and / or rate of arginine gingipain under similar conditions without the inventive method.

[0051] In some embodiments, the methods disclosed herein reduce the proteolytic activity and / or rate of arginine gingipain by 25% or more after about 12 hours from application of the oral care composition, e.g., as compared to the proteolytic activity and / or rate of arginine gingipain under similar conditions without the inventive method. In some instances, the method may reduce the proteolytic activity and / or rate of the arginine gingipain in the periodontal pocket. For example, the methods disclosed herein may reduce the proteolytic activity and / or rate of arginine gingipain by about 15% or more, about 20% or more, about 25% or more, about 30% or more, about 35% or more, about 38% or more, about 41% or more, about 44% or more, about 47% or more, about 50% or more, about 53% or more, about 56% or more, or about 59% or more, after about 12 hours from application of the oral care composition, e.g., using whole cell cultures and / or whole wash cell cultures as compared to the proteolytic activity and / or rate of arginine gingipain under similar conditions without the inventive method.

[0052] The method may achieve any of the foregoing reductions in the proteolytic activity and / or rate of the arginine gingipain, after 2 minutes or about 12 hours, as measured in the periodontal pocket. In some embodiments, the method achieves any of the foregoing reductions in the proteolytic activity and / or rate of the arginine gingipain, after 2 minutes or about 12 hours, as measured in the periodontal tissue.

[0053] The reduced proteolytic activity and / or rate of arginine gingipain can be determined by measuring Rgp activity. For example, when the method includes applying an oral care composition in the form of a dentifrice by brushing, the method disclosed herein may reduce the proteolytic activity and / or rate of arginine gingipain (e.g., as measured by Rgp activity) by one of the foregoing amounts as compared to the proteolytic activity and / or rate of arginine gingipain (e.g., as measured by Rgp activity) under similar conditions, such as brushing but without the inventive dentifrices disclosed herein. By way of another example, when the method includes applying an oral care composition in the form of a mouthwash by swishing, gargling, and / or rinsing, the method disclosed herein may reduce the proteolytic activity and / or rate of arginine gingipain (e.g., as measured by Rgp activity) by one of the foregoing amounts as compared to the proteolytic activity and / or rate of arginine gingipain (e.g., as measured by Rgp activity) under similar conditions without the application of the inventive mouthwashes disclosed herein.

[0054] The methods disclosed herein preferably comprise identifying an individual and / or a subpopulation as having an undesirable amount (e.g., a predetermined threshold) of proteolytic activity and / or rate of gingipains (e.g., lysine gingipain and arginine gingipain) in the oral cavity, such as in a periodontal tissue, and / or in the periodontal pocket. For example, the method may comprise identifying an individual as having an undesirable amount (e.g., a predetermined threshold) of proteolytic activity and / or rate of arginine gingipain by measuring Rgp activity. By way of another example, the method may comprise identifying an individual as having an undesirable amount (e.g., a predetermined threshold) of proteolytic activity and / or rate of lysine gingipain by measuring Kgp activity.

[0055] An undesirable amount of proteolytic activity and / or rate of gingipains (e.g., lysine gingipain and arginine gingipain) may be based on a predetermined threshold. The predetermined threshold may be determined by a doctor, dentist, and / or medical professional that would readily have knowledge of the undesirable amounts of proteolytic activity and / or rate of lysine gingipain and / or arginine gingipain for said individual. The methods for reducing proteolytic activity and / or rate of gingipains (e.g., lysine gingipain and arginine gingipain) may include administering the oral care composition in certain amounts and / or for amounts of time described below.

[0056] In accordance with another aspect, provided is a method for reducing inflammation, e.g., in oral cavity cells, preferably oral keratinocytes. The methods disclosed herein may reduce NF- kB translocation in oral keratinocytes and reduce inflammation mediated by Porphyromonasgingivalis (P.g.) in certain preferred embodiments. For example, the method may reduce NF-kB nuclear translocation in oral kcratinocytcs by at least 56%, preferably about 68% or more, preferably about 73% or more, preferably about 86% or more, preferably about 91% or more, as measured by the NF-kB nuclear translocation in oral keratinocytes in the presence of P.g. across multiplicities of infection (MOI) (e.g., P.g. MOI 50, P.g. MOI 100, and / or P.g. MOI 200). The methods may, additionally or alternatively, mitigate and / or reduce the loss of tight junctions in cultured oral keratinocytes in the presence of P.g. across varying multiplicities of infection (MOI) (e.g., P.g. MOI 50, P.g. MOI 100, and / or P.g. MOI 200, by at least 4%, preferably about 10% or more, preferably about 18% or more, preferably about 28% or more, preferably 38% or more, preferably 48% or more, or preferably 60% or more, relative to the same cultured oral keratinocytes in the presence of the same P.g. and MOI but without the application of an oral care composition disclosed herein.

[0057] The methods disclosed herein may include identifying an individual and / or a subpopulation as having an inflammation of the gums, periodontal tissue, and / or oral keratinocytes. Identification of the inflammation may be conducted by a doctor, dentist, and / or medical professional, which would readily have knowledge and / or be able to identify inflammation of the gums, periodontal tissue, and / or oral keratinocytes. The method for reducing inflammation, e.g., in oral cavity cells, may include administering the oral care composition in certain amounts and / or for amounts of time described below.

[0058] In accordance with another aspect, provided is a method for shifting biofilm composition in an individual's oral cavity to reduce pathogenic bacterial compared to healthy bacteria, the method comprising applying an oral care composition to an oral cavity, the oral care composition comprising a stannous source, a nitrate ion source, and a pyrophosphate. For instance, aspects of the disclosure, provide methods that reduce the amount of pathogenic bacteria, e.g., as compared to the growth rate of such pathogenic bacteria under similar conditions without the application of the inventive methods disclosed herein. Periodontal pathogens participate in inflammation and disease progression and reducing them is important for maintaining health. Oral commensal bacteria actively participate with gingival tissue to maintain healthy neutrophil surveillance and normal tissue and bone turnover processes. Without being limited to any particular theory, it is believed that the methods disclosed herein may increase the amount of commensal bacteria, relative to the total amount of commensal bacteria and pathogenic bacteria.

[0059] The methods disclosed herein may include administering the oral care composition to an oral cavity for about 10 seconds to about 30 minutes, c.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.

[0060] 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.

[0061] Additionally or alternatively, the method may comprise reducing the biovolume of pathogenic bacteria, e.g., in an oral biofilm, by about 5%. In some embodiments, the biovolume of the pathogenic bacteria is decreased by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95%.

[0062] 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 formof 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.

[0063] 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.

[0064] 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 combination of two or more thereof. In at least one embodiment, the stannous ion source comprises stannous fluoride.

[0065] 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 5stannous 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.

[0066] 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.

[0067] 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. In at least one embodiment, the nitrate source comprises potassium nitrate.

[0068] The oral care compositions may be formulated to have a molar ratio of nitrate ions to stannous ions, both measured as free ions, that is about 2:1 or less. For example, the oral care composition may have a molar ratio of nitrate ions to stannous ions, both measured as free ions, of from about 0.5:1 to about 2:1, about 0.5:1 to about 1.8:1, about 0.5:1 to about 1.6:1, about 0.5:1 to about 1.4:1, about 0.5:1 to about 1.2:1, about 0.5:1 to about 1:1; from about 0.7:1 to about 2:1, about 0.7:1 to about 1.8:1, about 0.7:1 to about 1.6:1, about 0.7:1 to about 1.4:1, about 0.7:1 to about 1.2:1, about 0.7:1 to about 1:1; from about 0.9:1 to about 2:1, about 0.9:1 to about 1.8:1, about 0.9:1 to about 1.6:1, about 0.9:1 to about 1.4:1, about 0.9:1 to about 1.2:1, about 0.9:1 to about 1:1, or any range or subrange thereof. In some embodiments, the oral care composition isformulated to have a molar ratio of nitrate ions to stannous ions, both measured as free ions, of about 1:1.

[0069] 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.

[0070] 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, sodium metaphosphate, or a combination thereof. The phosphate source may be a pyrophosphate salt, such as an alkali metal pyrophosphate salt. In certain embodiments, the alkali metal pyrophosphate is selected from a tetra alkali metal pyrophosphate, dialkali metal diacid pyrophosphate, trialkali metal monoacid pyrophosphate and mixtures thereof, wherein the alkali metals are sodium or potassium. For instance, the phosphate source may include tetrasodium pyrophosphate (TSPP), tetrapotassium pyrophosphate, sodium tripolyphosphate, tetrapolyphosphate, sodiumtrimetaphosphate, sodium hexametaphosphate or a comhination 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.

[0071] 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.

[0072] The oral care composition may include the anti-calculus agents in an amount from about 0.1 to about 7 wt.%, based on the total weight of the oral care composition. For example, the anticalculus agent(s) may be present in the oral care composition in an amount from about 0.1 to about6 wt.%, about 0.1 to about 5 wt.%, about 0.1 to about 4 wt.%, about 0.1 to about 3 wt.%, about 0.1 to about 2 wt.%, about 0.1 to about 1 wt.%; from about 0.4 to about 7 wt.%, about 0.4 to about 6 wt.%, about 0.4 to about 5 wt.%, about 0.4 to about 4 wt.%, about 0.4 to about 3 wt.%, about 0.4 to about 2 wt.%, about 0.4 to about 1 wt.%; from about 0.8 to about 7 wt.%, about 0.8 to about 6 wt.%, about 0.8 to about 5 wt.%, about 0.8 to about 4 wt.%, about 0.8 to about 3 wt.%, about 0.8 to about 2 wt.%; from about 1.4 to about 7 wt.%, about 1.4 to about 6 wt.%, about 1.4 to about 5 wt.%, about 1.4 to about 4 wt.%, about 1.4 to about 3 wt.%; from about 2 to about 7 wt.%, about 2 to about 6 wt.%, about 2 to about 5 wt.%, about 2 to about 4 wt.%, about 2 to about 3 wt.%; from about 3 to about 7 wt.%, about 3 to about 6 wt.%, about 3 to about 5 wt.%; from about 4 to about7 wt.%, about 4 to about 6 wt.%, about 5 to about 7 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0073] 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 ionsource. 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.

[0074] 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 combination of 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.

[0075] 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 twoor more thereof. In at least one preferred embodiment, the oral care composition comprises zinc phosphate.

[0076] 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.

[0077] 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 4 to 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.

[0078] The oral care composition may comprise a surfactant system comprising of 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 someinstances, the oral care composition includes 2, 3 4, 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.

[0079] 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.

[0080] 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 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.

[0081] The one or more anionic surfactant(s) may be selected be selected from sulfate basedanionic surfactants and / or from non-sulfate based anionic surfactants, such as sulfonated monoglyccridcs of fatty acids, isethionates, sarcosinatcs, tauratc, 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.

[0082] 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.

[0083] 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.

[0084] The anionic surfactant may be selected from taurates having a structure according to the following formula: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).

[0085] 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 lauroyltaurate, sodium methyl myristoyl taurate, sodium methyl oleoyl taurate, sodium methyl palmitoyl tauratc, 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.

[0086] 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.

[0087] Amphoteric surfactants are typically characterized by a combination of high surfactant activity, lather forming and mildness. The amphoteric surfactant may comprise a substituent containing 8 to 18 carbon atoms and a substituent containing one or more carboxylate, sulfonate, sulfate, phosphate, or phosphonate. For instance, the amphoteric surfactant may have an alkyl group comprising from 8 to 20 carbon atoms, 8 to 16 carbon atoms, 10 to 16 carbon atoms, or 10 to 13 carbon atoms. The amphoteric surfactant(s) may include, but are not limited to, derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight chain or branched. In some cases, one of the aliphatic substituents of the amphoteric surfactant contains about 8 to about 18 carbon atoms and one of the aliphatic substituents contains an anionic 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.

[0088] 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 toherein 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.

[0089] 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 about5 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 about6 wt.%, about 5 to about 7 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0090] 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.

[0091] 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, polyoxyethylene glycol octylphenol ethers, sorbitan alkyl esters, polyoxyethylene glycol sorbitan alkyl esters, or a combination of two or more thereof.

[0092] 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.%, 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 6wt.%, about 2 to about 5 wt.%, about 2 to about 4 wt.%, about 2 to about 3 wt.%; from about 3 to about 7 wt.%, about 3 to about 6 wt.%, about 3 to about 5 wt.%; from about 4 to about 7 wt.%, about 4 to about 6 wt.%, about 5 to about 7 wt.%, or any range or subrange thereof, based on the total weight of the oral care composition.

[0093] The 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.

[0094] 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.

[0095] 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 derived surfactants 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.

[0096] 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 nonionicsurfactant(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.

[0097] 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.%, 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.

[0098] 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. Additional examples of fluoride ion source are disclosed in U.S. Patent No. 3,535,421, U.S. Patent No.4,885,155, and U.S. Patent No. 3,678,154, the disclosure of each of which is hereby incorporated by reference in their entirety.

[0099] 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.

[0100] 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.

[0101] 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, composite resins, 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.

[0102] 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.

[0103] The oral care compositions may include an abrasive system comprising two or more abrasives. For example, an abrasive system 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 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 hairiness 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.

[0104] 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 about3 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.

[0105] 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.

[0106] 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 are typically physically and functionally distinct from the particulate silica abrasives as the silica thickeners are very finely divided and provide little or no abrasive action.

[0107] 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. Polyvinyl pyrrolidones that have average molecular weights of 10,000, 30,000 and 40,000 may be commercially available from Sigma Chemjeal Co., GAF Corporation and Sigma Chemical Co. The polyvinyl pyrrolidone may form a hydrogen peroxide -polyvinyl pyrrolidone polymer complexes. Examples of polyvinyl pyrrolidone complexes include those disclosed in U.S. Pat. No. 5,122,370, the contents of which are incorporated herein by reference. In some embodiments, the polymer comprises crosslinked polyvinyl pyrrolidone (crosslinked PVP). In at least one embodiment, the polymer consists of polyvinyl pyrrolidone.

[0108] 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.

[0109] 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.

[0110] 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, isobornyl methacrylate, 2-hydroxyethyl methacrylate, 2- hydroxypropyl methacrylate, dimethylaminoethyl methacrylate, diethylaminoethyl methacrylate, glycidyl 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.

[0111] Examples of acrylamides include, but are not limited to, acrylamide, methacrylamide and di(Ci-C3o) alkyl-acrylamidcs 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-hydroxy methyl acrylamide, N-isopropylacrylamide, N-methylacrylamide, N,N'-methylenebisacrylamide, N-isobutoxymethylacrylamide, N,N- dimethylacrylamide, and 2-acrylamido-2-methylpropanesulfonic acid.

[0112] 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.

[0113] 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 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.%, 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 4wt.%, 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.

[0114] 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.

[0115] In some cases, the oral care composition includes one or more polyol selected from the group consisting of C2-C32 polyols. The one or more polyols may have from 2 to 32 carbon atoms, from 3 to 16 carbon atoms, or from 3 to 12 carbon atoms. For example, the oral care composition may comprise ethylene glycol, propylene glycol, butylene glycol, hexylene glycol, glycerin, diglycerin, diethylene glycol, and dipropylene glycol, or a combination of two or more thereof. Additional, non-limiting examples of polyols that may, optionally, be included in the oral care include and / or may be chosen from alkanediols such as glycerin, 1,2,6-hexanetriol, trimethylolpropane, ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, dipropylene glycol, 2-butene-l,4-diol, 2-ethyl-l,3-hexanediol, 2-methyl-2,4-pentanediol, caprylyl glycol, 1 ,2-hexanediol, 1 ,2-pentanediol, and 4-methyl-l,2-pentanediol; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monomethyl ether acetate, diethylene glycol monomethyl ether, diethyleneglycol monoethyl ether, diethylene glycol mono-n-propyl ether, ethylene glycol mono-iso-propyl ether, dicthylcnc 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.

[0116] 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 (CAS-25322-68-3). 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.

[0117] 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 about 1 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 4to 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.

[0118] 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.

[0119] 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.

[0120] The one or more sweetener(s) may be present in the oral care composition in an amount from about 0.1 to about 50 wt.%, based on the total weight of the oral care composition. For example, the oral care composition may have a total amount of sweetener(s) from about 0.1 to about 40 wt.%, about 0.1 to about 30 wt.%, about 0.1 to about 20 wt.%, about 0.1 to about 10 wt.%, about 0.1 to about 5 wt.%, about 0.1 to about 3 wt.%; from about 1 to about 50 wt.%, about 1 to about 40 wt.%, about 1 to about 30 wt.%, about 1 to about 20 wt.%, about 1 to about 10 wt.%, about 1 to about 5 wt.%, about 1 to about 3 wt.%; from about 5 to about 50 wt.%, about 5 to about40 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.

[0121] 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.

[0122] The oral care compositions of the present disclosure may include a flavoring agent. The flavoring agent is typically incorporated in the oral care composition at a concentration of about 0.01 to about 3 wt.% by weight of the oral care composition. For example, the amount of flavoring agent(s) present in the oral care composition may be from about 0.01 to about 2 wt.%, about 0.01 to about 1 wt.%, about 0.01 to about 0.5 wt.%, about 0.01 to about 0.1 wt.%; from about 0.1 to about 3 wt.%, about 0.1 to about 2 wt.%, about 0.1 to about 1 wt.%, about 0.1 to about 0.5 wt.%; from about 0.5 to about 3 wt.%, about 0.5 to about 2 wt.%, about 0.5 to about 1 wt.%; from about 1 to about 3 wt.%, about 1 to about 2 wt.%; from about 2 to about 3 wt.%, including any range or subrange thereof, based on the total weight of the oral care composition.

[0123] 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.

[0124] 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.

[0125] 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.

[0126] The amount of the pH adjuster in the oral care composition may be based on the desired pH of the final oral care composition and / or product. For example, the total amount of the pH adjuster may range from about 0.05 to about 20 wt.%, based on the total weight of the oral care composition. In some instances, the total amount of pH adjuster is from about 0.05 to about 15 wt.%, about 0.1 to about 10 wt.%, or about 0.12 to about 5 wt.%, including ranges and sub-ranges therebetween, based on the total weight of the oral care composition.

[0127] 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.

[0128] 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

[0129] Two non-limiting example compositions (Example Composition A and B) were prepared in accordance with aspects of the invention. Example Composition A contained 0.908 wt.% of stannous fluoride (SnFo), 1.172 wt.% of potassium nitrate (KNO3), and 3.082 wt.% of tetrasodium pyrophosphate (TSPP), with the remainder being water. Example Composition B contained 0.454 wt.% of stannous fluoride, 0.586 wt.% of potassium nitrate, 1.541 wt.% of tetrasodium pyrophosphate, with the remainder being water. The pH of Example Compositions A and B were about 7.Example 2

[0130] Example Compositions A and B were evaluated to assess their effect on P. gingivalis. The specific P. gingivalis employed were BAA-308 (W83 wild type) and ATCC33277, which were obtained from American Type Culture Collection (ATCC). P. gingivalis W83 and ATCC 33277were grown in an anaerobic chamber containing 80 vol.% of N2, 10 vol.% of CO2, 10 vol.% of Hi for 24 hours at a temperature of 37 °C in enriched Tryptic Soy Broth (Tryptic Soy Broth; Sigma- Aldrich and Bacto™ Yeast extract; gibco) supplemented with 0.1% (w / v) of Hemin, 0.05% (w / v) of Menadione, and 5% (w / v) of L- Cysteine.

[0131] Samples containing the P. gingivalis were subsequently treated with either Example Composition A or Example Composition B for 2 minutes in a water bath at a temperature of 37 °C. To produce a control, a sample containing P. gingivalis was not treated with Example Composition A or Example Composition B but the same procedures were followed to produce such control. After 2 minutes, the tubes were centrifuged for 5 minutes to obtain pellets. The obtained pellets were resuspended in lOmL of 0.9 wt.% of NaCl, vortexed and centrifuged for 5 minutes. The pellets were then resuspended in lOmL eTSB media. Thereafter, ImL of resuspended pellets were transferred into glass tubes containing 6 mL eTSB media. The first reading was taken at Time 0 and the glass tubes were incubated in a water bath at a temperature of 37 °C. Readings were then taken every 1 to 2 hours for a period of 12 hours. Sample size was four for each group.

[0132] A gingipain enzymatic activity assay was conducted to assess the effect of Example Compositions A and B. Specifically, to determine the effects of Example Compositions A and B on the enzymatic activity of P. gingivalis, a 12-hour whole culture was adjusted to an optical density (“OD”) of 1.0. To assess the gingipain activity of P. gingivalis strains, 20 pL bacterial sample was mixed with 80 pL activity assay buffer — having the following parameters: 200 mM Tris, 150 mM NaCl, 5mM CaCh, and 0.02% NaNa; pH 7.6 mixed with IM L- Cysteine — and 100 pL of ImM Ac-Lys-pNA hydrochloride substrate (Ac-Lys-pNA hydrochloride salt; BACHEM) for Kgp activity. Whereas 10 pL bacterial sample was mixed with 90 pL activity assay buffer — having the following parameters: 200 mM Tris, 150 mM NaCl, 5mM CaCh, 0.02% NaNa; pH 7.6 mixed with IM L- Cysteine — and 100 pL of ImM Bz-Arg-pNA. HCL substrate (Bz-Arg-pNA. HCL; BACHEM) for Rgp activity. The Kinetic absorbance (mOD / pL / min) at 405 nm was measured every 30 seconds interval for 10 minutes using SpectraMax M5 spectrophotometer. Assays were performed in a quartet.

[0133] To assess activity for Kgp and Rgp, P. gingivalis W83 and ATCC 33277 were plated on blood agar plates. The blood agar plates were incubated (5-7 days) until clear colonies were observed. A colony was picked and inoculated into 5mL eTSB (enriched Tryptic Soy Broth) media and called Pre- seed culture. The pre-seed culture tubes were incubated for 72 hours. After 72hours, ODeoo, gingipain activity were measured for pre-seed culture. ODeoo was adjusted to 1 and 10 mL prc-sccd culture was inoculated into 150 mL cTSB media (1:15 inoculation) to produce a seed-culture. The seed-culture was incubated for 24 hours. On the same day, 1.172 wt.% potassium nitrate and 3.082 wt.% tetrasodium pyrophosphate solution, fresh eTSB media, and sterilized glass tubes were prepared for the experiment. 500 mL eTSB was filtered, 0.9% sodium chloride (NaCl) was prepared and filtered and kept them overnight in an anaerobic chamber.

[0134] Subsequently, four sterile glass tubes were prepared for evaluation with Example Composition A, four sterile glass tubes for evaluation with Example Composition B, and four sterile glass tubes were prepared for a control group. 6 mL of fresh eTSB media was added to each tube and kept them in an anaerobic chamber overnight. On the next day, the experiment was performed by measuring ODeoo of the seed-culture. The activity for Kgp and Rgp of the seedculture was measured by taking 20pL sample for Kgp and lOpL sample for Rgp. The ODeoo of the Seed culture must be 1.

[0135] Additionally, 10 mL of culture with ODeoo 1.0 was transferred to four sterile centrifugation tubes for evaluation with Example Composition A, 10 mL of culture was transferred to four sterile centrifugation tubes for evaluation of Example Composition B, and 10 mL of culture was transferred to four sterile centrifugation tubes for a control group. The tubes containing 10 mL culture (12 tubes) were centrifuged at 4700K RPM for 10 minutes to pellet the bacteria for collection and treatment.

[0136] The bacterial pellet was resuspended in 10 mL respective media containing either 0.908 wt.% of stannous fluoride, 1.172 wt.% of potassium nitrate, 3.082 wt.% of tetrasodium pyrophosphate, and a remainder of water (Example Composition A); 0.454 wt.% of stannous fluoride, 0.586 wt.% of potassium nitrate, 1.541% tetrasodium pyrophosphate, and a remainder of water (Example Composition B); or eTSB media for control. Each tube was vortexed for 7 seconds and incubated in water bath at a temperature of 37 °C for 2 minutes. After 2 minutes, all the tubes were centrifuged at 4700 K RPM for 5 minutes. After 5 minutes, the supernatant was discarded and the pellet was resuspended in 10 mL, 0.9% Sodium Chloride (NaCl). Each tube was vortexed for 7 seconds and centrifuged at 4700 RPM for 5 minutes. This step was to wash away the remaining chemical components. After 5 minutes, the supernatant was discarded, and the pellets were resuspended in 10 mL fresh eTSB media.

[0137] Subsequently, the centrifuged tubes with resuspended pellets were brought inside ananaerobic chamber. ImL of resuspended pellet was transferred into appropriately numbered glass tubes containing 6mL cTSB media prepared and incubated the day before in an anaerobic chamber. The glass tubes were brought under the bio-safety cabinet and a 250 pL sample was pipetted out from each tube for gingipain activity assay for Kgp and Rgp for Time 0. The caps of the glass tubes were tightened and ODeoofor time 0 was measured using spectrophotometer. The tubes were incubated in a water bath at a temperature of 37 °C. ODeoo for each tube was measured at 1-2 hour intervals of time, up to 12 hours.

[0138] For the activity assay for Time 0, 50 pL sample was taken for Kgp (Lysine Gingipain) activities and 50pL sample was taken for Rgp (Arginine gingipain) activities. After 12 hours, samples were taken from each tube for gingipain activity assay in Whole Cell Culture (WCC). The ODeoo for each sample was adjusted to 1.0 and gingipain activity was performed by taking 20pL sample for Kgp and lOpL sample for Rgp activity. Then after, the samples adjusted to OD 1.0 were centrifuged at 4700 RPM for 10 minutes. After 10 minutes, the supernatant was discarded, and the pellets were resuspended in 1 mL DPBS (Dulbecco’s Phosphate Buffered Saline) and vortexed for 7 seconds. The micro-centrifuge tubes were centrifuged at 4700 RPM for 5 minutes. After 5 minutes, the supernatant was discarded, and the pellets were resuspended in ImL DPBS and vortexed, we called it Whole Washed Cells (WWC). The data obtained from experiments were analyzed using Graph Pad Prism.

[0139] A summary of the growth results of the P. gingivalis after application with Example Composition A or Example Composition B is shown in FIGS. 1 A and IB. The results of the lysine gingipain and arginine gingipain (i.e., the protease activity) measured immediately after two minutes of treatment with Example Composition A or Example Composition B is shown in FIGS. 2A and 2B, respectively. A summary of the results of the lysine gingipain and arginine gingipain (i.e., the protease activity) measured 12 hours after the treatment with Example Composition A or Example Composition B is shown in FIGS. 3 A and 3B, respectively.Example 3

[0140] A non-limiting example composition (Example Composition C) was prepared and evaluated to assess its effect on inflammation. Example Composition C was a simple solution containing 4.06 mg / mL of SnF2, 5 mg / mL of KNO3, and 12 mg / mL of TSPP.

[0141] Example Composition C was evaluated by detecting the reduction of inflammation mediated by Porphyromonas gingivalis (P.g.) through the application of Example Composition C,which inhibited NF-kB translocation in cultured oral keratinocytes. The reduction in inflammation markers was significant, as demonstrated by reduced NF-kB translocation and subsequent stabilization of tight junctions in the presence of P.g. across varying multiplicities of infection (MOI).

[0142] Specifically, cultured oral keratinocytes received an application of Example Composition C followed by exposure to P.g. at different MOI. More specifically, cultured oral keratinocytes were either pre-treated with a stannous simple solution for 2 minutes prior to adding P.g. or cotreated with the stannous simple solution and P.g. Cells were then treated or challenged overnight before being fixed and stained for NF-kB or a tight-junction staining marker. The application resulted in a notable decrease in NF-kB translocation, as observed through fluorescence imaging and quantified data. Additionally, the integrity of tight junctions between keratinocytes is preserved, highlighting the protective effect of Example Composition C against P.g. -induced disruptions.

[0143] A summary of the results of the evaluation of Example Composition C is shown in FIGS. 4A-5B. With regard to FIGS. 4A-5B, “UNT” refers to untreated; “2 min SNaP 1:800” refers to a solution of Example Composition C diluted by 800 times to have 5.07 pg / mL of SnF2, 6.25 of pg / mL of KNOa, and 15 of pg / mL of TSPP; and “ON SNaP 1:8000” refers to samples treated over night with a solution of Example Composition C diluted 8000 times to have 0.507 pg / mL of SnFi, 0.625 pg / mL of KNO3, and 1.5 pg / mL of TSPP.

[0144] FIG. 4A depicts images of NF-kB translocation in cultured oral keratinocytes with and without stannous treatment at varying P.g. MOI. This figure illustrates the cellular localization of NF-kB, demonstrating reduced translocation to the nucleus in the presence of stannous sources. FIG. 4B is a graph illustrating the quantification of NF-kB translocation under the conditions shown in FIG. 4A. The graph provides a comparative analysis of NF-kB translocation levels, highlighting the statistically significant reduction achieved by stannous treatment. FIG. 5A shows images of tight junctions in cultured oral keratinocytes with and without stannous treatment at different P.g. MOI. These images illustrate the morphological preservation of tight junctions due to the anti-inflammatory effect of the stannous-containing composition. FIG. 5B presents graphs of the percentage of tight junction fluorescence between treated and untreated samples, as depicted in FIG. 6A. These graphs quantify the integrity of tight junctions and demonstrate the protective effect of stannous treatments against P.g. -induced disruptions.

Claims

CLAIMSWhat Is Claimed Is:

1. A method for reducing and / or inhibiting gingipain by applying an oral care composition to an oral cavity, the oral care composition comprising a stannous source, a nitrate source, and a pyrophosphate.

2. The method according to claim 1, wherein the gingipain is selected from lysine gingipains, arginine gingipains, and a combination thereof.

3. The method according to claim 2, comprising reducing the proteolytic activity of the lysine gingipains by at least 5% after applying the oral care composition for about 2 minutes.

4. The method according to claim 2, comprising reducing the proteolytic activity of the arginine gingipains by at least 5% after applying the oral care composition for about 2 minutes.

5. The method according to any one of claims 2 to 4, comprising reducing the proteolytic activity of the lysine gingipains by at least 25% after applying the oral care composition for about 2 minutes.

6. The method according to any one of claims 2 to 4, comprising reducing proteolytic activity of the arginine gingipains by at least 25% after applying the oral care composition for about 2 minutes.

7. The method according to any foregoing claim further comprising reducing Porphyromonas gingivalis by at least 10%.

8. The method according to claim 7, wherein Porphyromonas gingivalis is reduced by at least9. The method according to any foregoing claim, wherein the amount of oral care composition applied to the oral cavity is about 0.1 to about 3 grams.

10. The method according to any foregoing claim, 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.

11. The method according to claim 10, wherein the stannous source comprises stannous fluoride.

12. The method according to any foregoing claim, 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.

13. The method according to claim 10, wherein the nitrate source comprises potassium nitrate.

14. The method according to any foregoing claim, 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.

15. The method according to any foregoing claim, 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.

16. A method for shifting biofilm composition in an individual's oral cavity to reduce pathogenic bacterial compared to healthy bacteria, the method comprising applying an oral care composition to an oral cavity, the oral care composition comprising a stannous source, a nitrate source, and a pyrophosphate.

17. The method according to claim 16 comprising reducing the proteolytic activity of the lysine gingipains by at least 5% after applying the oral care composition for about 2 minutes.

18. The method according to claim 16 or claim 17, comprising reducing the proteolytic activity of the arginine gingipains by at least 5% after applying the oral care composition for about 2 minutes.

19. The method according to any one of claims 16 to 18, comprising reducing the proteolytic activity of the lysine gingipains by at least 25% after applying the oral care composition for about 2 minutes.

20. The method according to any one of claims 16 to 19, comprising reducing the proteolytic activity of the arginine gingipains by at least 25% after applying the oral care composition for about 2 minutes.

21. The method according to any one of claims 16 to 20, further comprising reducing Porphyromonas gingivalis by at least 10%.

22. The method according to claim 21, wherein Porphyromonas gingivalis is reduced by at least 30%.

23. The method according to any one of claims 16 to 22, wherein the amount of oral care composition applied to the oral cavity is about 0.1 gram to about 3 grams.

24. The method according to any one of claims 16 to 23, 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.

25. The method according to claim 24, wherein the stannous source comprises stannous fluoride.

26. The method according to any one of claims 16 to 25, wherein the nitrate source is selected from lithium nitrate, sodium nitrate, potassium nitrate, magnesium nitrate, calcium nitrate, zinc nitrate, silver nitrate, ammonium nitrate, and a combination two or more thereof.

27. The method according to claim 26, wherein the nitrate source comprises potassium nitrate.

28. The method according to any one of claims 16 to 27, 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.

29. The method according to any one of claims 16 to 28, 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.

30. A method for reducing and / or inhibiting gingipain comprising: identifying an individual as having an undesirable amount of proteolytic activity of arginine gingipain and / or an undesirable amount of proteolytic activity and / or rate of lysine gingipain; and applying an oral care composition to an oral cavity, the oral care composition comprising a stannous source, a nitrate source, and a phosphate source.

31. The method according to claim 30, wherein the undesirable amount is a predetermined threshold.

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