Oral care GELS with fluoride source and polymer blend

Abstract

Described herein are an oral care compositions comprising a fluoride source, a polymer blend comprising a first polymer that is heat-sensitive and comprises a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer, a second polymer comprising a copolymer of methyl vinyl ether and maleic anhydride, a third polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG).

Description

Docket No. 941166-00- WO-Ol-OCORAL CARE GELSCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority from U.S. Patent Application No. 63 / 704,219, filed October 7, 2024, the content of which is hereby incorporated herein by reference in their entirety.BACKGROUND

[0002] The oral cavity is subject to numerous conditions, including dental erosion. Dental erosion involves demineralization and damage to the tooth structure due to acid attack from nonbacterial sources. Erosion is found initially in the enamel and, if unchecked, may proceed to the underlying dentin. Thus, the need exists for an improved oral care composition that may help prevent dental erosion.BRIEF SUMMARY

[0003] In some embodiments, the present invention is directed to an oral gel composition comprising: a fluoride source; a polymer blend comprising: a first polymer that is heat- sensitive and comprises a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a second polymer comprising a copolymer of methyl vinyl ether and maleic anhydride; a third polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the polymer blend is free of alkali metal hyaluronate.

[0004] In some embodiments, the present invention is directed to an oral gel composition comprising: a fluoride source; a polymer blend comprising: a first polymer that is heat- sensitive and comprising a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a polyacid comprising a copolymer of methyl vinyl ether and maleic anhydride; a second polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the polyacid is substantially free of polyacrylic acid.

[0005] In some embodiments, the present invention is directed to an oral gel composition comprising: a fluoride source; a polymer blend comprising: a first polymer that is heat- sensitiveDocket No. 941166-00- WO-Ol-OC and comprises a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a second polymer comprising polyacrylic acid; a third polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the polymer blend is free of alkali metal hyaluronate.

[0006] In some embodiments, the present invention is directed to an oral gel composition comprising: a fluoride source; a polymer blend comprising: a first polymer that is heat- sensitive and having a lower critical solubility temperature and comprising a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a second polymer comprising polyacrylic acid; a third polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the lower critical solubility temperature ranges from about 19.5 °C to about 35.5 °C; and wherein the oral gel composition exhibits a first viscosity ranging from about 1,000 mPa-s to about 100,000 mPa-s at temperature below the lower critical solubility temperature and a second viscosity ranging from about 100,000 mPa-s to about 5,000,000 mPa-s at a temperature above the lower critical solubility temperature, the first and second viscosity not being equal.

[0007] A list of non-limiting embodiments in accordance with aspects of the invention is provided below:

[0008] In accordance with an embodiment 1, provided is an oral care composition comprising: a fluoride source; a polymer blend comprising: a first polymer that is heat-sensitive and comprises a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a second polymer comprising a copolymer of methyl vinyl ether and maleic anhydride; a third polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the oral care composition is free of hyaluronic acid and / or a salt thereof and free of carbomers.

[0009] In accordance with an embodiment 2, provided is an oral care composition according to embodiment 1, wherein the fluoride source comprises sodium fluoride.

[0010] In accordance with an embodiment 3, provided is an oral care composition according to any one of embodiments 1 or 2, wherein the fluoride source is present in an amount ranging from about 0.1 wt. % to about 1.0 wt. % based on the total weight of the oral care gel.Docket No. 941166-00- WO-Ol-OC

[0011] In accordance with an embodiment 4, provided is an oral care composition according to any forgoing embodiment, wherein the first polymer is present in an amount ranging from about 1.0 wt. % to about 20.0 wt. % based on the total weight of the oral care gel.

[0012] In accordance with an embodiment 5, provided is an oral care composition according to any foregoing embodiment, wherein the second polymer is present in an amount ranging from about 0.1 wt. % to about 6.0 wt. % based on the total weight of the oral care gel.

[0013] In accordance with an embodiment 6, provided is an oral care composition according to any foregoing embodiment, wherein the third polymer is present in an amount ranging from about 3.0 wt. % to about 7.0 wt. % based on the total weight of the oral care gel.

[0014] In accordance with an embodiment 7, provided is an oral care composition according to any foregoing embodiment, further comprising a liquid carrier present in an amount ranging from about 72 wt. % to about 88 wt. % - based on the total weight of the gel composition.

[0015] In accordance with an embodiment 8, provided is an oral care composition according to any foregoing embodiment, further comprising a surfactant present in an amount ranging from about 0.1 wt. % to about 5.0 wt. %, based on the total weight of the oral gel composition.

[0016] In accordance with an embodiment 9, provided is an oral care composition according to embodiment 8, wherein the surfactant is selected from: cocamidopropyl betaine, sodium lauryl sulfate, sodium lauryl ether sulfate, ammonium lauryl sulfate, cocomonoethanolamide, cocodiethanolamide, laurylamidopropyl dimethylamine oxide, myristylamidopropyl dimethylamine oxide, decyl glucoside, sodium N-cocoyl-N-methyl taurate, sodium cocoyl isoethioniate, sodium dioctyl sulfosuccinate and a combination of two or more thereof.

[0017] In accordance with an embodiment 10, provided is an oral care composition according to any foregoing embodiment, further comprising a humectant in an amount ranging from about 0.1 wt. % to 10.0 wt. % - based on the total weight of the oral gel composition.

[0018] In accordance with an embodiment 11, provided is an oral care composition according to any foregoing embodiment, wherein the oral care composition is in the form of a gel (e.g., a leave- on gel) or a paste.

[0019] In accordance with an embodiment 12, provided is an oral care composition comprising: a fluoride source; a polymer blend comprising: a first polymer that is heat- sensitive and comprising a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a polyacid comprising a copolymer of methyl vinyl ether and maleic anhydride; a second polymerDocket No. 941166-00- WO-Ol-OC comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the poly acid is substantially free of polyacrylic acid.

[0020] In accordance with an embodiment 13, provided is an oral care composition according to embodiment 12, wherein the fluoride source comprises sodium fluoride.

[0021] In accordance with an embodiment 14, provided is an oral care composition according to embodiment 12 or embodiment 13, wherein the fluoride source is present in an amount ranging from about 0.1 wt. % to about 1.0 wt. % based on the total weight of the oral care gel.

[0022] In accordance with an embodiment 15, provided is an oral care composition according to any one of embodiments 12 to 14, wherein the first polymer is present in an amount ranging from about 1.0 wt. % to about 20.0 wt. % based on the total weight of the oral care gel.

[0023] In accordance with an embodiment 16, provided is an oral care composition according to any one of embodiments 12 to 15, wherein the second polymer is present in an amount ranging from about 3.0 wt. % to about 7.0 wt. % based on the total weight of the oral care gel.

[0024] In accordance with an embodiment 17, provided is an oral care composition according to any one of embodiments 12 to 16, wherein the polyacid is present in an amount ranging from about 0.1 wt. % to about 6.0 wt. % based on the total weight of the oral care gel.

[0025] In accordance with an embodiment 18, provided is an oral care composition according to any one of embodiments 12 to 17, further comprising a liquid carrier present in an amount ranging from about 72 wt. % to about 88 wt. %, based on the total weight of the gel composition.

[0026] In accordance with an embodiment 19, provided is an oral care composition according to any one of embodiments 12 to 18, further comprising a surfactant present in an amount ranging from about 0.1 wt. % to about 5.0 wt. %, based on the total weight of the oral gel composition.

[0027] In accordance with an embodiment 20, provided is an oral care composition according to embodiment 19, wherein the surfactant is selected from cocamidopropyl betaine, sodium lauryl sulfate, sodium lauryl ether sulfate, ammonium lauryl sulfate, cocomonoethanolamide, cocodiethanolamide, laurylamidopropyl dimethylamine oxide, myristylamidopropyl dimethylamine oxide, decyl glucoside, sodium N-cocoyl-N-methyl taurate, sodium cocoyl isoethioniate, sodium dioctyl sulfosuccinate, and a combination of two or more thereof.Docket No. 941166-00- WO-Ol-OC

[0028] In accordance with an embodiment 21 , provided is an oral care composition according to any one of embodiments 12 to 20, further comprising a humectant in an amount ranging from about 1.0 wt. % to 4.5 wt. %, based on the total weight of the oral gel composition.

[0029] In accordance with an embodiment 22, provided is an oral care composition according to any one of embodiments 12 to 21, wherein the oral care composition exhibits a first viscosity ranging from about 1,000 mPa-s to about 100,000 mPa-s at temperature below 19 °C and a second viscosity ranging from about 100,000 mPa-s to about 5,000,000 mPa-s at a temperature above 35 °C, the second viscosity being greater than the first viscosity.

[0030] In accordance with an embodiment 23, provided is an oral care composition according to any one of embodiments 12 to 22, wherein the oral care composition is in the form of a gel (e.g., a leave-on gel) or a paste.

[0031] In accordance with an embodiment 24, provided is an oral gel comprising: a fluoride source; a polymer blend comprising: a first polymer that is heat-sensitive and comprises a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a second polymer comprising polyacrylic acid; a third polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the polymer blend is free of alkali metal hyaluronate.

[0032] In accordance with an embodiment 25, provided is an oral gel according to embodiment 24, wherein the fluoride source comprises sodium fluoride.

[0033] In accordance with an embodiment 26, provided is an oral gel according to any one of embodiment 24 or embodiment 25, wherein the fluoride source is present in an amount ranging from about 0.1 wt. % to about 1.0 wt. %, based on the total weight of the oral gel.

[0034] In accordance with an embodiment 27, provided is an oral gel according to any one of embodiments 24 to 26, wherein the first polymer is present in an amount ranging from about 0.1 wt. % to about 20.0 wt. %, based on the total weight of the oral gel.

[0035] In accordance with an embodiment 28, provided is an oral gel according to any one of embodiments 24 to 27, wherein the second polymer is present in an amount ranging from about 0.1 wt. % to about 1.0 wt. %, based on the total weight of the oral gel.

[0036] In accordance with an embodiment 29, provided is an oral gel according to any one of embodiments 24 to 28, wherein the third polymer is present in an amount ranging from about 1.0 wt. % to about 20.0 wt. %, based on the total weight of the oral gel.Docket No. 941166-00- WO-Ol-OC

[0037] In accordance with an embodiment 30, provided is an oral gel according to any one of embodiments 24 to 29, further comprising a liquid carrier present in an amount ranging from about 72 wt. % to about 88 wt. %, based on the total weight of the oral gel.

[0038] In accordance with an embodiment 31, provided is an oral gel according to any one of embodiments 24 to 30, further comprising a surfactant present in an amount ranging from about 0.1 wt.% to about 5.0 wt.%, based on the total weight of the oral gel.

[0039] In accordance with an embodiment 32, provided is an oral gel according to embodiment 31, wherein the surfactant is selected from cocamidopropyl betaine, sodium lauryl sulfate, sodium lauryl ether sulfate, ammonium lauryl sulfate, cocomonoethanolamide, cocodiethanolamide, laurylamidopropyl dimethylamine oxide, myristylamidopropyl dimethylamine oxide, decyl glucoside, sodium N-cocoyl-N-methyl taurate, sodium cocoyl isoethioniate, sodium dioctyl sulfosuccinate, and a combination of two or more thereof.

[0040] In accordance with an embodiment 33, provided is an oral gel according to any one of embodiments 24 to 32, further comprising a humectant in an amount ranging from about 0.1 wt.% to 10.0 wt.%, based on the total weight of the oral gel.

[0041] In accordance with an embodiment 34, provided is an oral gel according to any one of embodiments 24 to 33, wherein the oral gel exhibits a first viscosity ranging from about 1,000 mPa-s to about 100,000 mPa-s at temperature below 19 °C and a second viscosity ranging from about 100,000 mPa-s to about 5,000,000 mPa-s at a temperature above 35 °C, the second viscosity greater than the first viscosity.

[0042] In accordance with an embodiment 35, provided is an oral gel comprising: a fluoride source; a polymer blend comprising: a first polymer that is heat-sensitive and having a lower critical solubility temperature and comprising a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a second polymer comprising polyacrylic acid; a third polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the lower critical solubility temperature ranges from about 19.5 °C to about 35.5 °C; and wherein the oral gel composition exhibits a first viscosity ranging from about 1,000 mPa-s to about 100,000 mPa-s at temperature below the lower critical solubility temperature and a second viscosity ranging from about 100,000 mPa-s to about 5,000,000 mPa-s at a temperature above the lower critical solubility temperature, the first and second viscosity not being equal.Docket No. 941166-00- WO-Ol-OC

[0043] In accordance with an embodiment 36, provided is an oral gel according to embodiment 35, wherein the fluoride source comprises sodium fluoride.

[0044] In accordance with an embodiment 37, provided is an oral gel according to any one of embodiment 35 or embodiment 36, wherein the fluoride source is present in an amount ranging from about 0.1 wt.% to about 1.0 wt.%, based on the total weight of the oral gel.

[0045] In accordance with an embodiment 38, provided is an oral gel according to any one of embodiments 35 to 37, wherein the first polymer is present in an amount ranging from about 1.0 wt.% to about 20.0 wt.%, based on the total weight of the oral gel.

[0046] In accordance with an embodiment 39, provided is an oral gel according to any one of embodiments 35 to 38, wherein the second polymer is present in an amount ranging from about 0.1 wt.% to about 6.0 wt.%, based on the total weight of the oral gel.

[0047] In accordance with an embodiment 40, provided is an oral gel according to any one of embodiments 35 to 39, wherein the third polymer is present in an amount ranging from about 3.0 wt.% to about 7.0 wt.%, based on the total weight of the oral gel.

[0048] In accordance with an embodiment 41, provided is an oral gel according to any one of embodiments 35 to 40, further comprising a liquid carrier present in an amount ranging from about 72 wt.% to about 88 wt.%, based on the total weight of the oral gel.

[0049] In accordance with an embodiment 42, provided is an oral gel according to any one of embodiments 35 to 41, further comprising a surfactant present in an amount ranging from about 0.1 wt.% to about 5.0 wt.%, based on the total weight of the oral gel.

[0050] In accordance with an embodiment 43, provided is an oral gel according to embodiment 42, wherein the surfactant is selected from cocamidopropyl betaine, sodium lauryl sulfate, sodium lauryl ether sulfate, ammonium lauryl sulfate, cocomonoethanolamide, cocodiethanolamide, laurylamidopropyl dimethylamine oxide, myristylamidopropyl dimethylamine oxide, decyl glucoside, sodium N-cocoyl-N-methyl taurate, sodium cocoyl isoethioniate, sodium dioctyl sulfosuccinate, and a combination of two or more thereof.

[0051] In accordance with an embodiment 44, provided is an oral gel according to any one of embodiments 35 to 43, further comprising a humectant in an amount ranging from about 0.1 wt.% to 10.0 wt.%, based on the total weight of the oral gel.

[0052] In accordance with an embodiment 45, provided is an oral gel according to any one of embodiments 35 to 44, wherein a ratio of the second viscosity to the first viscosity is at least 3:1.Docket No. 941166-00- WO-Ol-OC

[0053] In accordance with an embodiment 46, provided is an oral gel according to embodiment 45, wherein the ratio of the second viscosity to the first viscosity is at least 10:1.

[0054] In accordance with an embodiment 47, provided is a method of treating, preventing, inhibiting or ameliorating a symptom associated with, a disease, disorder or condition of the oral cavity comprising administering an oral care composition according to any one of embodiments 1 to 23, or an oral gel according to any one of embodiments 24 to 46, to an oral cavity surface of a subject in need thereof.

[0055] In accordance with an embodiment 48, provided is the method according to embodiment 47, wherein the disease, disorder or condition of the oral cavity is selected from: gingivitis; caries; periodontitis; hypersensitivity; and dental erosion.

[0056] In accordance with an embodiment 49, provided is a method of manufacturing an oral care composition according to any one of embodiments 1 to 23, or an oral gel according to any one of embodiments 24 to 46, comprising: admixing the first polymer, the second polymer, and the third polymer with a solvent under conditions effective to solubilize the first, second and third polymers in the solvent.

[0057] The following description of the embodiment(s) is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses.DETAILED DESCRIPTION

[0058] As used throughout, ranges are used as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range. In addition, all references cited herein are hereby incorporated by reference in their entireties. In the event of a conflict in a definition in the present disclosure and that of a cited reference, the present disclosure controls.

[0059] Unless otherwise specified, all percentages and amounts expressed herein and elsewhere in the specification should be understood to refer to percentages by weight. The amounts given are based on the active weight of the material.

[0060] The terms “comprising,” “having,” and “including” are used in their open, non-limiting sense.

[0061] The compositions and methods of the present disclosure can comprise, consist of, or consist essentially of the essential elements and limitations of the disclosure described herein, as well asDocket No. 941166-00- WO-Ol-OC any additional or optional ingredients, components, or limitations described herein or otherwise useful.

[0062] The description of illustrative embodiments according to principles of the present invention is intended to be read in connection with the accompanying drawings, which are to be considered part of the entire written description. In the description of embodiments of the invention disclosed herein, any reference to direction or orientation is merely intended for convenience of description and is not intended in any way to limit the scope of the present invention.

[0063] Unless otherwise specified, all percentages and amounts expressed herein and elsewhere in the specification should be understood to refer to percentages by weight. The amounts given are based on the active weight of the material.

[0064] Additionally, all numerical values are “about” or “approximately” the indicated value, and take into account experimental error and variations that would be expected by a person having ordinary skill in the art. It should be appreciated that all numerical values and ranges disclosed herein are approximate values and ranges, whether “about” is used in conjunction therewith. It should also be appreciated that the term “about,” as used herein, in conjunction with a numeral refers to a value that may be ±0.01% (inclusive), ±0.1% (inclusive), ±0.5% (inclusive), ±1% (inclusive) of that numeral, ±2% (inclusive) of that numeral, ±3% (inclusive) of that numeral, ±5% (inclusive) of that numeral, ±10% (inclusive) of that numeral, or ±15% (inclusive) of that numeral. It should further be appreciated that when a numerical range is disclosed herein, any numerical value falling within the range is also specifically disclosed.

[0065] According to the present application, the term “substantially free” is less than about 0.1 wt. % based on the total of the referenced value. According to the present application, the term “free” is 0.0 wt. % based on the total of the referenced value.

[0066] All ranges and values disclosed herein are inclusive and combinable. For example, any value or point described herein that falls within a range described herein can serve as a minimum or maximum value to derive a sub-range, etc. Furthermore, all ranges provided are meant to include every specific range within, and combination of sub ranges between, the given ranges. Thus, a range from 1-5, includes specifically 1, 2, 3, 4 and 5, as well as sub ranges such as 2-5, 3-5, 2-3, 2-4, 1-4, etc.

[0067] As used herein, the use of a compound comprising several isomers or stereoisomers includes all the isomeric forms of that compound. When referring to chemical structures, andDocket No. 941166-00- WO-OLOC 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. 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.”

[0068] As used herein, the expression “at least one” is interchangeable with the expression “one or more” and thus includes individual components as well as mixtures / combinations.

[0069] The term “treat” (and its grammatical variations) as used herein refers to the application of compositions of the present disclosure onto the surface of an oral cavity.

[0070] The term “active material” as used herein with respect to the percent amount of an ingredient or raw material, refers to 100% activity of the ingredient or raw material.

[0071] The term, “a mixture thereof” or “a blend thereof” does 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.”

[0072] 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, E, 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 ofE, and a salt of F may be included.

[0073] The salts referred to throughout the disclosure may include salts having a counter-ion such as an alkali metal, alkaline earth metal, or ammonium counter-ion. This list of counter-ions, however, is non-limiting.

[0074] The expression “inclusive” for a range of concentrations means that the limits of the range are included in the defined interval.

[0075] The term “weight ratio” or “mass ratio” as used herein, references the amount of a substance in proportion to a mixture containing said substance, and is calculated by dividing the amount of said substance by weight contained in the mixture by the weight of the mixture containing said substance. As an example, a weight ratio of 0.4 for substance A in a mixture of A,Docket No. 941166-00- WO-Ol-OCB, and C indicates that the weight of substance A divided by the total weight of substances A, B, and C is 0.4.

[0076] Some of the various categories of components identified may overlap. In such cases where overlap may exist and the 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, a fatty acid may be characterized as both a nonionic surfactant and a fatty compound. If a particular composition includes both a nonionic surfactant and a fatty compound, a single fatty acid will serve as only the nonionic surfactant or as only the fatty compound (the single fatty acid does not serve as both the nonionic surfactant and the fatty compound).

[0077] The term “volatile”, as used herein, means having a flash point of less than about 100 °C. The term “non-volatile”, as used herein, means having a flash point of greater than about 100 °C.

[0078] The term “polymers,” as defined herein, include homopolymers and copolymers formed from at least two different types of monomers. The term “polymer” further includes linear and branched polymer structures, and also encompasses crosslinked polymers as well as copolymers (which may or may not be crosslinked), thus including block copolymers, alternating copolymers, random copolymers, and the like. Those compounds referred to herein as “oligomers” are polymers having a molecular weight below about 1000 Da, preferably below about 800 Da.

[0079] All publications and patent applications cited in this specification are herein incorporated by reference, and for any and all purposes, as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. In the event of an inconsistency between the present disclosure and any publications or patent application incorporated herein by reference, the present disclosure controls.

[0080] 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.

[0081] 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 canDocket No. 941166-00- WO-Ol-OC 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.

[0082] 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, caprylyl glycol may be characterized as both a humectant and a preservative. If a particular oral care composition includes both a humectant and a preservative, caprylyl glycol will serve only as either a humectant or a preservative — not both.

[0083] As used herein, the terms “composition” and “formulation” can be used interchangeably within the specification.

[0084] The term “tooth” and “teeth” refers to natural teeth and any other hard surfaces, such as crowns, caps, fillings, bridges, dental implants, and the like, that are permanently fixed within the oral cavity and cleansed in situ within the oral cavity of a subject.

[0085] This invention is not limited to specific hydrogel materials or manufacturing processes, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. It must be noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a hydrophilic polymer” includes not only a single hydrophilic polymer but also a combination or mixture of two or more different hydrophilic polymers, reference to “a plasticizer” includes a combination or mixture of two or more different plasticizers as well as a single plasticizer, and the like.

[0086] The definitions of “hydrophobic” and “hydrophilic” polymers are based on the amount of water vapor absorbed by polymers at 100% relative humidity. According to this classification, hydrophobic polymers absorb only up to 1 wt. % water at 100% relative humidity (“rh”), whileDocket No. 941166-00- WO-Ol-OC moderately hydrophilic polymers absorb 1-10% wt. % water, hydrophilic polymers are capable of absorbing more than 10 wt. % of water, and hygroscopic polymers absorb more than 20 wt. % of water. A “water-swellable” polymer is one that absorbs an amount of water greater than at least 25 wt. % of its own weight, and preferably at least 50 wt. % of its own weight, upon immersion in an aqueous medium.

[0087] The term “crosslinked” herein refers to a composition containing intramolecular and / or intermolecular crosslinks, whether arising through covalent or noncovalent bonding. “Noncovalent” bonding includes both hydrogen bonding and electrostatic (ionic) bonding.

[0088] The term “hydrogel” is used in the conventional sense to refer to water-swellable polymeric matrices that can absorb a substantial amount of water to form elastic gels, wherein “matrices” are three-dimensional networks of macromolecules held together by covalent or noncovalent crosslinks. Upon placement in an aqueous environment, dry hydrogels swell to the extent allowed by the degree of cross-linking.

[0089] “Phase” is traditionally defined as a homogeneous part of a heterogeneous system. Respectively, “phase separation” is the transformation of a homogeneous system to a heterogeneous one. Conventionally, the process of phase separation is accompanied with the formation of an interphase border between the phases of different composition. Typical examples of phase separation include sol-gel transition, precipitation in solution, or the spontaneous formation of a multi-layer (laminate) structure.

[0090] The terms “active agent,” “pharmacologically active agent” and “drug” are used interchangeably herein to refer to a chemical material or compound that induces a desired pharmacological, physiological effect, and include agents that are therapeutically effective, prophylactically effective, or cosmeceutically effective - as well as encompass pharmaceutically acceptable, pharmacologically active derivatives and analogs of those active agents specifically mentioned herein, including, but not limited to, salts, esters, amides, prodrugs, active metabolites, inclusion complexes, analogs, and the like. When the terms “active agent,” “pharmacologically active agent” and “drug” are used, it is to be understood that both the active agent per se as well as pharmaceutically acceptable, pharmacologically active salts, esters, amides, prodrugs, active metabolites, inclusion complexes, analogs, etc., are included.

[0091] The term “tooth whitening composition” refers to a composition that contains a hydrogel, as defined herein, and a whitening agent.Docket No. 941166-00- WO-Ol-OC

[0092] The term “effective amount” or “a cosmeceutically effective amount” of a cosmeceutically active agent means a nontoxic but sufficient amount of a cosmeceutically active agent to provide the desired cosmetic effect. The term “effective amount” or “a therapeutically effective amount” of a drug or pharmacologically active agent is intended to mean a nontoxic but sufficient amount of the drug or agent to provide the desired therapeutic effect. The amount that is “effective” will vary from subject to subject, depending on the age and general condition of the individual, the particular active agent or agents, and the like. Thus, it is not always possible to specify an exact “effective amount.” However, an appropriate “effective” amount in any individual case may be determined by one of ordinary skill in the art using routine experimentation. Furthermore, the exact “effective” amount of an active agent incorporated into a composition or dosage form of the invention is not critical, so long as the concentration is within a range sufficient to permit ready application of the formulation so as to deliver an amount of the active agent that is within a therapeutically effective range.

[0093] The term “surface” as in “oral cavity” surface or “body surface” is intended to include body surfaces such as skin, nails and mucosal tissue (e.g., sublingual, buccal, vaginal, rectal, urethral), as well as surfaces in and around the oral cavity (e.g., teeth, lips, gums, mucous membranes), as well as the surface of various skin wounds.

[0094] The terms “tack” and “tacky” are qualitative. However, the terms “substantially nontacky” “slightly tacky” and “tacky,” as used herein, may be quantified using the values obtained in a PKI or TRBT tack determination method, as follows. By “substantially nontacky” is meant a hydrogel composition that has a tack value that is less than about 25 g-cm / sec, by “slightly tacky” is meant a hydrogel composition that has a tack value in the range of about 25 g-cm / sec to about 100 g- cm / sec, and by “tack” is meant a hydrogel composition that has a tack value of at least 100 g- cm / sec.

[0095] The term “water-insoluble” refers to a compound or composition whose solubility in water is less than 5 wt. %, preferably less than 3 wt. %, more preferably less than 1 wt. % (measured in water at 20° C.). Similarly, the term “water-soluble” refers to a compound or composition whose solubility in water is greater than 5 wt. %, preferably greater than 3 wt. %, more preferably greater than 1 wt. % (measured in water at 20° C.).

[0096] The present invention is directed to an oral care composition. The oral care composition may be an oral care gel composition (also referred to as a “gel composition”).Docket No. 941166-00- WO-OLOC

[0097] The gel composition may comprise a plurality of polymers. The polymers may include poly ether polymers. The polymers may include poly acid polymers. In some embodiments, the plurality of polymers may comprise a first polymer, a second polymer, and a third polymer.

[0098] The first polymer may be a heat-sensitive polymer. The first polymer may be a gel-forming polymer. The first polymer may comprise a hydrophobic portion and a hydrophilic portion. The hydrophobic portion may comprise one or more hydrophobic segments. The hydrophilic portion may comprise one or more hydrophilic segments.

[0099] The term “heat- sensitive” may refer to the polymer exhibiting a lower critical solubility temperature (“LCST”) - whereby above the LCST the hydrophilic portion(s) of the polymer associate in a micro-domain while the hydrophilic portion(s) remain in a polymer solution. The first polymer may form a gel in water - whereby the polymer is a liquid at lower temperatures and forms a gel as temperatures increase. In a non-limiting embodiment, the first polymer may exhibit a LCST ranging from about 19.5 °C to about 35.5 °C - including all temperatures and sub-ranges there-between. In some embodiments, the first polymer may exhibit a LCST of about 25 °C.

[0100] The first polymer may be present in the gel composition in an amount ranging from about 1.0 wt. % to about 20.0 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the first polymer may be present in the gel composition in an amount ranging from about 5 wt. % to about 10 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the first polymer may be present in the gel composition in an amount of about 6 wt. % to about 8.5 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between.

[0101] The heat- sensitive polymer may be a poly ether polymer. The hydrophobic portion of the first polymer may comprise blocks of polypropylene oxide. The hydrophilic portion of the first polymer may comprise blocks of polyethylene oxide. In some embodiments, the first polymer may comprise a linear PEG / PPG triblock copolymer and polypropylene glycol (PPG)-SMDI copolymer.

[0102] The first polymer is further described in, e.g., U.S. Pat. No. 7,339,013, the contents of which are hereby incorporated by reference in its entirety.

[0103] The second polymer may comprise a copolymer. The second polymer may comprise a polyacid polymer. The second polymer may comprise a copolymer of methyl vinyl ether andDocket No. 941166-00- WO-Ol-OC maleic anhydride. The second polymer may consist of a copolymer of methyl vinyl ether and maleic anhydride.

[0104] The second polymer may be present in the gel composition in an amount ranging from about 0.0 wt. % to about 10.0 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the second polymer may be present in the gel composition in an amount ranging from about 0.1 wt. % to about 6 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the second polymer may be present in the gel composition in an amount of about 0.33 wt. % to about 0.664 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between.

[0105] In alternative embodiments, the gel composition may be substantially free of the second polymer.

[0106] The third polymer may comprise a poloxamer. The term “poloxamer” or “poloxamer copolymer” refers to a polyethoxy / polypropoxy block copolymer, i.e., a nonionic triblock copolymer composed of a central hydrophobic chain of polyoxypropylene units (a.k.a. poly(propylene oxide) units) flanked by two hydrophilic chains of polyoxyethylene units (e.g., poly(ethylene oxide) units). Poloxamers have the following chemical structure:HO— [CH2CH2O] a[— CH(CH3)CH2O— ]b [CH2CH2O] a— H,

[0107] wherein a and b are integers, each typically between 10 and 200. Poloxamers are named according to common conventions based on their molecular weight and ethoxy content, and include poloxamer 407, poloxamer 338, poloxamer 237, poloxamer 188 and poloxamer 124. Poloxamers are distinguished from other polyethylene glycol / polypropylene glycol copolymers (PEG / PPG copolymers or EO / PO copolymers) which have a structure other than as a triblock structure, such as a random copolymer structure.

[0108] The third polymer may be present in the gel composition in an amount ranging from about 0.1 wt. % to about 20.0 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the third polymer may be present in the gel composition in an amount ranging from about 3 wt. % to about 7 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the third polymer may be present in the gel composition in an amount of about 5 wt. % - based on the total weight of the gel composition.Docket No. 941166-00- WO-Ol-OC

[0109] In some embodiments, the gel composition may comprise a fourth polymer. The fourth polymer may be a polyacid polymer. The fourth polymer may comprise polyacrylic acid. The fourth polymer may consist of a polyacrylic acid. The polyacrylic acid may be a homopolymer, a copolymer, and / or an interpolymer. The polyacrylic acid may be cross-linked.

[0110] The fourth polymer may be present in the gel composition in an amount ranging from about 0.0 wt. % to about 5.0 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there -between. In some embodiments, the fourth polymer may be present in the gel composition in an amount ranging from about 0 wt. % to about 0.6 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the gel composition is substantially free of the fourth polymer.

[0111] The gel composition may comprise an active agent. In a non-limiting embodiment, the active agent may be selected from zinc salts, stannous salts, quaternary ammonium compounds, guanidines, amino acids, amino acid complexes, fluoride ion sources (also referred as a “fluoride source”), tetrahydrocurcumin, vitamins, antibacterial agents, antifungal agents, anti-sensitivity agents, anti-inflammatory agents, anesthetic agents (e.g., local anesthetics), essential oils, and combinations thereof.

[0112] In some embodiments, the active agent may be selected from zinc oxide, zinc citrate, zinc sulfate, zinc chloride, zinc phosphate, zinc lactate, zinc pyrophosphate, zinc salicylate, zinc picolinate, stannous chloride, stannous fluoride, stannous pyrophosphate, cetylpyridinium chloride, benzalkonium chloride, chlorhexidine (e.g., chlorhexidine gluconate), arginine (e.g., arginine carbonate, arginine bicarbonate, arginine hydrochloride), lysine, histidine, zinc- bislysine-chloride complexes, zinc-bisarginine-chloride complexes, sodium fluoride, sodium monofluorophosphate, amine fluorides, tetrahydrocurcumin, eugenol, nicotinamide, riboflavin, sodium nitrate, potassium nitrate, strontium nitrate, eucalyptol, thymol, menthol, hydrogen peroxide, doxycycline, minocycline, ketoconazole, or combinations thereof.

[0113] In some embodiments the active agent may comprise a fluoride source. The fluoride source may comprise one or more of stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, and combinations thereof. In some embodiments, the active agent may comprise sodium fluoride.Docket No. 941166-00- WO-Ol-OC

[0114] The active agent may be present in the gel composition in an amount ranging from about 0.01 wt. % to about 2.0 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the active agent may comprise sodium fluoride and be present in the gel composition in an amount of about 0.01 wt. % to about 1.0 wt. % - including all wt. % and sub-range there-between - based on the total weight of the gel composition. In some embodiments, the active agent may comprise sodium fluoride and be present in the gel composition in an amount of about 0.1 wt. % to about 0.5 wt. % - including all wt. % and sub-range there-between - based on the total weight of the gel composition. In some embodiments, the active agent may comprise sodium fluoride and be present in the gel composition in an amount of about 0.2 wt. % to about 0.3 wt. % - including all wt. % and sub-range therebetween - based on the total weight of the gel composition. In some embodiments, the active agent may comprise sodium fluoride and be present in the gel composition in an amount of about 0.243 wt. %, based on the total weight of the gel composition.

[0115] It has been surprisingly discovered that the combination of first polymer, second polymer and third polymer - along with fluoride source - provides an unexpected improvement in the retention and delivery of fluoride to a tooth surface.

[0116] It has been surprisingly discovered that the combination of first polymer, third polymer, and fourth polymer - along with fluoride source - provides an unexpected improvement in the retention and delivery of fluoride to a tooth surface.

[0117] The gel composition may comprise a liquid carrier. The liquid carrier may include water. In some embodiments, the liquid carrier may consist of water. The liquid carrier may be present in the gel composition in an amount ranging from about 50.0 wt. % to about 90.0 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the liquid carrier may be present in the gel composition in an amount ranging from about 72 wt. % to about 88 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the liquid carrier may be present in the gel composition in an amount ranging from about 78 wt. % to about 84 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between.

[0118] The gel composition may comprise one or more humectants. Non-limiting examples of humectant may include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, propyleneDocket No. 941166-00- WO-Ol-OC glycol as well as other polyols and mixtures of these humectants. In a non-limiting embodiment, the humectant comprises propylene glycol.

[0119] The humectant may be present in the gel composition in an amount ranging from about 0.0 wt. % to about 50.0 wt.% - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the humectant may be present in the gel composition in an amount ranging from about 1 wt. % to about 10 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the humectant may be present in the gel composition in an amount ranging from about 1 wt. % to about 4.5 wt. % - based on the total weight of the gel composition, including all wt. % and subranges there-between.

[0120] The gel composition may comprise one or more surfactants. The surfactant may be anionic, cationic, nonionic, or zwitterionic surfactants. The surfactant may be selected from cocamidopropyl betaine, sodium lauryl sulfate, sodium lauryl ether sulfate, ammonium lauryl sulfate, cocomonoethanolamide, cocodiethanolamide, laurylamidopropyl dimethylamine oxide, myristylamidopropyl dimethylamine oxide, decyl glucoside, sodium N-cocoyl-N-methyl taurate, sodium cocoyl isoethioniate, sodium dioctyl sulfosuccinate. In some embodiments, the surfactant comprises cocamidopropyl betaine.

[0121] The surfactant may be present in the gel composition in an amount ranging from about 0.0 wt. % to about 5.0 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the surfactant may be present in the gel composition in an amount ranging from about 0.1 wt. % to about 3 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the surfactant may be present in the gel composition in an amount of about 0.45 wt. % - based on the total weight of the gel composition.

[0122] The gel composition may further comprise hyaluronic acid or an alkali metal hyaluronate (e.g., sodium hyaluronate) polymer. The gel composition may have a total amount of hyaluronic acid and / or salts thereof (e.g., an alkali metal hyaluronate) of about 2 wt.% or less, about 1 wt.% or less, about 0.5 wt.% or less, about 0.1 wt.% or less, or about 0.05 wt.% or less, based on the total weight of the gel composition. In some embodiments, the gel composition is substantially free of hyaluronic acid. In some embodiments, the gel composition is free of hyaluronic acid. In some embodiments, the gel composition is substantially free of the alkali metal hyaluronate (e.g.,Docket No. 941166-00- WO-Ol-OC sodium hyaluronate). Tn some embodiments, the gel composition is free of the alkali metal hyaluronate. In some embodiments, the gel composition is substantially free of hyaluronic acid and / or salts thereof (e.g., an alkali metal hyaluronate). In some embodiments, the gel composition is free of hyaluronic acid and / or salts thereof (e.g., alkali metal hyaluronate(s)).

[0123] The gel composition may also have a reduced amount, be substantially free of, or free of carbomers. For example, the gel composition may have a total amount of carbomers of about 2 wt.% or less, about 1 wt.% or less, about 0.5 wt.% or less, about 0.1 wt.% or less, or about 0.05 wt.% or less, based on the total weight of the gel composition. Examples of carbomers that may be excluded from the gel composition include from Carbopol 2984, Carbopol 934, Carbopol Ultrez 10, Carbopol 940, Carbopol 941, Carbopol 956 Carbopol 981, Carbopol 2020, and a combination of two or more thereof.

[0124] The gel composition may further comprise one or more additional components - such as, but not limited to, preservatives (e.g., sodium benzoate), coloring agents, flavoring agents (e.g., eugenol, spearmint flavor), sweeteners, buffers (e.g., acids or bases, such as sodium carbonate or sodium bicarbonate), antioxidants (e.g., p-hydroxyacetophenone, ascorbic acid, beta-carotene, retinol, alpha-tocopherol, propyl gallate, tertiary butylhydroquinone, butylated hydroxyanisole, butylated hydroxy toluene), or other oral care ingredients.

[0125] The additional components may be present in the gel composition in an amount ranging from about 0.0 wt. % to about 2.0 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the additional components may comprise sodium benzoate in an amount ranging from about 0.1 wt. % to about 1.0 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between. In some embodiments, the additional components may comprise a flavorant - such as spearmint flavor - an amount ranging from about 0.1 wt. % to about 0.2 wt. % - based on the total weight of the gel composition, including all wt. % and sub-ranges there-between.

[0126] In an alternative embodiment, the gel composition may optionally comprise small amounts of additional polymers (e.g., 0.1-10 wt. %, or 0.1-5 wt. %, or 0.1 to 3 wt. %, or 0.1 to 1 wt. %, each of in the aggregate) to further adjust the viscosity of the formulations or to enhance the solubility or stability of an active agent or other component. Such additional polymers include polyethylene glycols, polypropylene glycols, polysaccharides (e.g., cellulose derivatives, for example carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethylDocket No. 941166-00- WO-Ol-OC cellulose, microcrystalline cellulose; or polysaccharide gums, for example xanthan gum, guar gum, or carrageenan gum, karaya gum); polyvinyl pyrrolidone (PVP), such as cross-linked PVP; synthetic anionic polymeric polycarboxylates. Acidic polymers, for example polyacrylate gels, may be provided in the form of their free acids or partially or fully neutralized water-soluble alkali metal (e.g., potassium and sodium) or ammonium salts. In one embodiment, the oral care composition may contain PVP. PVP generally refers to a polymer containing vinylpyrrolidone (also referred to as N- vinylpyrrolidone, N-vinyl-2-pyrrolidione and N-vinyl-2-pyrrolidinone) as a monomeric unit. The monomeric unit consists of a polar imide group, four non-polar methylene groups and a non-polar methane group.

[0127] The gel composition may exhibit a pH ranging from about 3.5 to about 9.5 - including all pH values and sub-ranges there-bet ween. In some embodiments, the gel composition may exhibit a pH ranging from about 4.5 to about 6.5 - including all pH values and sub-ranges there-between.

[0128] The gel composition may exhibit a lower viscosity (also referred to as a first viscosity) ranging from about 1,000 mPa-s to about 100,000 mPa-s at room temperature - including all viscosities and sub-ranges there-between. In some embodiments, the gel composition may transition into a viscous gel at a temperature above the LCST resulting in an upper viscosity (also referred to as a gel viscosity or a second viscosity) ranging from about 100,000 mPa-s to about 5,000,000 mPa-s at - including all viscosities and sub-ranges there-between.

[0129] The first viscosity and the second viscosity may not be equal. The second viscosity may be greater than the first viscosity. A ratio of the second viscosity to the first viscosity is at least 3:1. In some embodiments, the ratio of the second viscosity to the first viscosity is at least 10:1. In some embodiments, the ratio of the second viscosity to the first viscosity is at least 20:1. In some embodiments, the ratio of the second viscosity to the first viscosity is at least 30:1. In some embodiments, the ratio of the second viscosity to the first viscosity is at least 40:1. In some embodiments, the ratio of the second viscosity to the first viscosity is at least 50:1.

[0130] The gel composition may be provided as part of a kit. The gel composition may be configured for delivery as an oral spray. In some embodiments, the aforementioned kit comprises such gel composition packaged into a container with a finger-tip actuated spray device, optionally with a long-tip for accurate delivery of the spray into small spaces within the oral cavity. In some embodiments, the gel composition is formulated for injection, e.g., into the periodontal pocket. In some embodiments, the gel composition may be packaged in a container or kit with a syringe andDocket No. 941166-00- WO-Ol-OC a needle (e.g., metal or plastic) suitable for injection of the hydrogel into the periodontal pocket. In some embodiments, the gel composition may be packaged in a tube (e.g., a squeezable tube) or in a single-use application for application to the tooth (e.g., to a damaged tooth) or the gums or to the oral mucosa or to the dental socket (e.g., following tooth extraction), such as, using an applicator (e.g., a plastic applicator or a cotton-tipped swab) or the tip of a finger (e.g., the patient's finger or a dentist's or dental hygienist's finger).

[0131] The gel composition may serve as a vehicle for controlled release of the active agent directly into the tissues / teeth of the oral cavity over an extended period of time without the interference caused by dilution by saliva. In some embodiments, such a composition may be administered into a periodontal pocket, completely or partially filling said pocket, whereupon the liquid will transition to a viscous gel that adheres and remains inside the inflamed pocket, releasing the therapeutic agent in a sustained release manner to thereby treat the underlying periodontal disease.

[0132] The terms “periodontal pocket,” “periodontal crevice,” “gingival pocket,” “gingival crevice,” and “dental pocket,” used herein interchangeably, refer to an abnormal space between the cervical enamel of a tooth and the overlying unattached gingiva, resulting from a chronic inflammatory response associated with untreated gingivitis or periodontitis, which leads to destruction and fracture of the bone and tissue supporting said tooth.

[0133] The terms “sustained-release,” “extended release,” and “controlled release,” used herein interchangeably, refer to the release of an active agent from a composition comprising it at predetermined intervals or gradually, in such a manner as to make the contained active agent available over an extended period of time, e.g., hours (e.g., up to 1, 6, 12, 18, 24, 36, or 48 hours), days (e.g., 1-30 days), or weeks (e.g., 1-4 weeks). The release profile of the active agent from the composition of the present disclosure, after turning into a gel, depends on various parameters such as the particular polymers used, and their amounts in the composition; and the ratio (by weight) between the various polymers.EXAMPLES

[0134] The following examples were performed to test adhesion and fluoride uptake performance of the oral care composition of the present invention. The oral care composition included the following components:Docket No. 941166-00- WO-Ol-OCPolymer 1 - heat-sensitive hydrophobic polypropylene oxide (POP) segments and hydrophilic polyethylene oxide (POE) portionsPolymer 2 - copolymer of methyl vinyl ether and maleic anhydridePolymer 3 - triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG)Polymer 4 - Poly(acrylic acid)Propylene Glycol - “PG”Surfactant - cocamidopropyl betaineFlavorant - spearmint flavorTable 1

[0135] As a threshold matter, the composition of Comp. Ex. 1-4 showed poor stability - especially at higher levels of NaF, whereby precipitate was observed. Below 1.0 wt. % NaF (i.e., Ex. 1-4) showed proper stability.

[0136] Each of the compositions of the Control and Examples 1-4 were evaluated for hard tissue adhesion, tested in vitro using bovine teeth that were warmed in an incubator at 37°C for 15 minutes. An amount of 200 pl. of each gel composition was added to the surface of the teeth and a circular 2.5 g copper weight 0.75 inches in diameter was pressed on top of the gel. Once all samples were prepared, the lid was propped up in the incubator at 37 °C, simultaneously starting a timer to track how long the penny remains adhered to the enamel. The results are shown in Table 2.Docket No. 941166-00- WO-Ol-OCTable 2

[0137] A subsequent test was performed to measure the amount of fluoride release and uptake. The compositions of Ex. 3 and Ex. 4 were compared against a number of comparative formulations. The compositions of Comparative Examples 5-7 are listed below:Comp. Ex. 5 - 0.243 wt.% NaF Toothpaste - with immediate rinse Comp. Ex. 6 - 0.243 wt.% NaF Toothpaste - with 30 rinse Comp. Ex. 7 - 0.05 wt.% NaF mouthwash

[0138] Fluoride uptake was assessed in vitro using bovine teeth that were rinsed with water. A respective set of bovine teeth were then contacted with the formulations of each of Ex. 3, Ex. 4, Comp. 5, Comp. 6, and Comp. Ex. 7. Specifically, Comp. Ex. 5 and 6 utilized 0.35 grams of the toothpaste and involved brushing the bovine teeth samples for 2 minutes. Comp. Ex. 7 submerged the bovine teeth in 10 mL of mouthwash and placed on a shaker for 1 minute.

[0139] Each sample tooth was then immersed in 1 M KOH followed by thoroughly rinsing with water and neutralized with 1 M HNO3 and TISAB-III was added. Fluoride levels were measured with an ion-selective electrode and normalized compared to the surface area of the bovine blocks.

[0140] Subsequently, the teeth were etched for 15 minutes with 0.1 M HCIO4 followed by TISAB- III being added to the solution and fluoride levels were measured with an ion-selective probe and normalized compared to the surface area of the bovine blocks. The results arc set forth below in Table 3.Table 3Docket No. 941166-00- WO-Ol-OC

[0141] As demonstrated by Table 3, the formulations of the present invention provide increased fluoride update by bovine enamel compared with the 0.24 wt.% of NaF Toothpaste with the 0.05 wt.% NaF mouthwash under condition simulating normal use.

Claims

Docket No. 941166-00- WO-Ol-OCCLAIMSWhat Is Claimed Is:

1. An oral care composition comprising: a fluoride source; a polymer blend comprising: a first polymer that is heat-sensitive and comprises a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a second polymer comprising a copolymer of methyl vinyl ether and maleic anhydride; a third polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the oral care composition is free of hyaluronic acid and / or a salt thereof and free of carbomer.

2. The oral care composition according to claim 1, wherein the fluoride source comprises sodium fluoride, the fluoride source being present in an amount from about 0.1 wt. % to about 1 wt. %, based on the total weight of the oral care composition.

3. The oral care composition according to any forgoing claim, wherein the first polymer is present in an amount ranging from about 1.0 wt. % to about 20.0 wt. %, based on the total weight of the oral care composition.

4. The oral care composition according to any foregoing claim, wherein the second polymer is present in an amount ranging from about 0.1 wt. % to about 6.0 wt. %, based on the total weight of the oral care composition.

5. The oral care composition according to any foregoing claim, wherein the third polymer is present in an amount ranging from about 3.0 wt. % to about 7.0 wt. %, based on the total weight of the oral care composition.Docket No. 941166-00- WO-Ol-OC6. The oral care composition according to any foregoing claim further comprising: a liquid carrier present in an amount ranging from about 72 wt. % to about 88 wt. %, based on the total weight of the oral care composition.

7. The oral care composition according to any foregoing claim further comprising: a surfactant present in an amount ranging from about 0.1 wt. % to about 5.0 wt. %, based on the total weight of the oral care composition.

8. The oral care composition according to claim 7, wherein the surfactant is selected from: cocamidopropyl betaine, sodium lauryl sulfate, sodium lauryl ether sulfate, ammonium lauryl sulfate, cocomonoethanolamide, cocodiethanolamide, laurylamidopropyl dimethylamine oxide, myristylamidopropyl dimethylamine oxide, decyl glucoside, sodium N-cocoyl-N-methyl taurate, sodium cocoyl isoethioniate, sodium dioctyl sulfosuccinate, and a combination of two or more thereof.

9. The oral care composition according to any foregoing claim further comprising: a humectant in an amount ranging from about 0.1 wt. % to 10.0 wt. %, based on the total weight of the oral care composition.

10. The oral care composition according to any foregoing claim, wherein the oral care composition is in the form of a gel or a paste.

11. The oral care composition according to any foregoing claim, wherein the oral care composition exhibits a first viscosity from about 1,000 mPa-s to about 100,000 mPa-s at temperature below 19 °C and a second viscosity from about 100,000 mPa-s to about 5,000,000 mPa-s at a temperature above 35 °C, the second viscosity being greater than the first viscosity.

12. An oral gel comprising: a fluoride source; a polymer blend comprising:Docket No. 941166-00- WO-Ol-OC a first polymer that is heat-sensitive and comprises a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a second polymer comprising polyacrylic acid; a third polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the oral gel is free of hyaluronic acid and / or a salt thereof and free of carbomer.

13. An oral gel comprising: a fluoride source; a polymer blend comprising: a first polymer that is heat-sensitive and has a lower critical solubility temperature of about 19.5 °C to about 35.5 °C, the first polymer comprising a linear PEG / PPG triblock copolymer and polypropylene glycol(PPG)-SMDI copolymer; a second polymer comprising polyacrylic acid; a third polymer comprising a triblock copolymer having a central hydrophobic block of polypropylene glycol with two end hydrophilic blocks of polyethylene glycol (PEG); and wherein the oral gel composition exhibits a first viscosity of about 1,000 mPa-s to about 100,000 mPa-s at temperature below the lower critical solubility temperature and a second viscosity of about 100,000 mPa-s to about 5,000,000 mPa-s at a temperature above the lower critical solubility temperature, the first and second viscosity not being equal.

14. The oral gel according to claim 13, wherein the fluoride source comprises sodium fluoride.

15. The oral gel according to any one of claim 13 or claim 14, wherein the fluoride source is present in an amount ranging from about 0.1 wt.% to about 1.0 wt.%, based on the total weight of the oral gel.Docket No. 941166-00- WO-Ol-OC16. The oral gel according to any one of claims 13 to 15, wherein the first polymer is present in an amount ranging from about 1.0 wt.% to about 20.0 wt.%, based on the total weight of the oral gel.

17. The oral gel according to any one of claims 13 to 16, wherein the second polymer is present in an amount ranging from about 0.1 wt.% to about 6.0 wt.%, based on the total weight of the oral gel.

18. The oral gel according to any one of claims 13 to 17, wherein the third polymer is present in an amount ranging from about 3.0 wt.% to about 7.0 wt.%, based on the total weight of the oral gel.

19. The oral gel according to any one of claims 13 to 18, wherein a ratio of the second viscosity to the first viscosity is at least 3:1.

20. A method of treating, preventing, inhibiting or ameliorating a symptom associated with, a disease, disorder or condition of the oral cavity comprising administering an oral care composition according to any one of claims 1 to 12, or an oral gel according to any one of claims 13 to 19, to an oral cavity surface of a subject in need thereof.

Images