Aqueous oral care fluoride treatment compositions and methods

Abstract

Disclosed are aqueous oral care fluoride treatment compositions, methods for delivering fluoride to a patient's tooth surfaces, and methods for reducing the incidence of dental caries, the treatment compositions comprising 0.5% to 4.8% by weight of a water-soluble cationic N-containing polymer, a pharmaceutically acceptable buffer, 1.0% to 2.5% by weight of sodium fluoride, and at least 60% by weight of water, wherein the weight percentages are based on the total weight of the aqueous composition.

Description

[Background technology]

[0001] Fluoride treatment involves applying fluoride to the tooth surface to form fluorapatite and calcium fluoride.

[0002] Currently, two primary in-office fluoride treatment methods are in use. One treatment method uses a fluoride gel / foam in a tray. This method requires several grams of fluoride gel to be stored in a tray and then placed on the teeth in the patient's mouth. The tray is left in the mouth for 1 to 4 minutes, with the gel / foam in contact with the teeth. The gel / foam formulation is an aqueous system containing 2% sodium fluoride. This material requires the use of suction to draw excess gel from the mouth to avoid ingesting unnecessary large amounts of fluoride.

[0003] Another treatment method is dental fluoride varnish. Most fluoride varnishes on the market are rosin / ethanol-based formulations with hydrophobic properties. The varnish is applied to the teeth and left in place for several hours to allow the fluoride to be released from the composition. Dentists typically use fluoride varnish for in-office fluoride treatments. Most dental fluoride varnishes contain 5% sodium fluoride. The dose of the varnish is approximately 0.5 g. Dental varnishes place much less fluoride in the patient's mouth than fluoride gels / foams. Therefore, fluoride intake is lower with fluoride varnish. Furthermore, although fluoride varnishes are easier to apply because they are simply painted onto the patient's teeth, fluoride varnish treatments are more labor-intensive than gel treatments, and fluoride varnish treatments leave patients with an unpleasant "stained teeth" sensation.

[0004] A composition that is easy to apply to teeth as a varnish and has a short acting period similar to a gel / foam formulation is desirable. Summary of the Invention

[0005] The present disclosure provides aqueous oral care fluoride treatment compositions and methods of treatment (ie, methods of applying fluoride to a patient's tooth surfaces).

[0006] Such compositions can be used as in-office fluoride treatment compositions. They can be formulated into compositions that can be painted onto tooth surfaces, if desired. They can provide fluoride efficacy similar to that of varnishes, but for a shorter period of time than gel / foam formulations.

[0007] In one embodiment, the present disclosure provides an aqueous oral care fluoride treatment composition comprising: 0.5% to 4.8% by weight of a water soluble cationic nitrogen-containing (N-containing) polymer; a pharmaceutically acceptable buffer; 1.0% to 2.5% by weight of sodium fluoride; and at least 60% by weight of water, wherein the weight percentages are based on the total weight of the aqueous composition.

[0008] In another embodiment, the present disclosure provides a method of providing fluoride to a patient's dental surfaces, the method involving applying an aqueous oral care fluoride treatment composition disclosed herein to the patient's dental surfaces.

[0009] In another embodiment, the present disclosure provides a method for reducing the incidence of dental caries, the method involving applying an aqueous oral care fluoride treatment composition disclosed herein to a patient's dental surfaces.

[0010] The terms "polymer" and "polymeric material" include, but are not limited to, organic homopolymers, copolymers, such as block copolymers, graft copolymers, random copolymers, and copolymers, terpolymers, etc., as well as blends and modifications thereof. Furthermore, unless otherwise specifically limited, the term "polymer" is intended to encompass all possible geometric configurations of the material. These configurations include, but are not limited to, isotactic, syndiotactic, and atactic symmetries.

[0011] The terms "comprise" and variations thereof do not have a limiting meaning where these terms appear in the specification and claims. Such terms are understood to imply the inclusion of a recited step or element, or group of steps or elements, but not the exclusion of any other step or element, or group of steps or elements. "Consisting of" means inclusive of and limited to whatever follows the phrase "consisting of." Thus, the phrase "consisting of" indicates that the recited elements are necessary or mandatory, and that no other elements may be present. "Consisting essentially of" means including any elements listed after the phrase, and is limited to other elements that do not interfere with or contribute to the action or function specified in this disclosure for those recited elements. Thus, the phrase "consisting essentially of" indicates that the recited elements are necessary or mandatory, but that other elements are optionally included and may or may not be present depending on whether they materially affect the action or function of the recited elements.

[0012] The words "preferred" and "preferably" refer to embodiments of the present disclosure that may provide certain benefits, under certain circumstances, although other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the present disclosure.

[0013] In this application, terms such as "a," "an," and "the" are not intended to refer only to a singular entity, but are intended to include the general class of which a specific example may be used for illustration. The terms "a," "an," and "the" are used interchangeably with the phrases "at least one" and "one or more." The phrases "at least one of" and "including at least one of," following a list, refer to any one of the items in the list and any combination of two or more items in the list.

[0014] The term "or" is generally used in its ordinary sense, including "and / or," unless the content clearly dictates otherwise.

[0015] The term "and / or" means one or all of the listed elements or a combination of any two or more of the listed elements.

[0016] Further, all numbers herein are deemed to be modified by the term "about," and in certain embodiments, preferably, by the term "exactly." When used herein with respect to a measured quantity, the term "about" refers to the variation in the measured quantity that may be expected by one of ordinary skill in the art, exercising a degree of care commensurate with the measurement, the purpose of the measurement, and the precision of the measuring device used. As used herein, a "up to" number (e.g., up to 50) is inclusive of that number (e.g., 50).

[0017] Further, herein, the recitations of numerical ranges by endpoints include all numbers subsumed within that range, and those endpoints (eg, 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).

[0018] The term "room temperature" refers to a temperature of 20°C to 25°C, or 22°C to 25°C.

[0019] References throughout this specification to "one embodiment," "an embodiment," "particular embodiments," or "some embodiments" mean that a particular feature, structure, composition, or characteristic described in connection with an embodiment is included in at least one embodiment of the present disclosure. Thus, the appearances of such phrases in various places throughout this specification are not necessarily all referring to the same embodiment of the present disclosure. Furthermore, particular features, structures, compositions, or characteristics may be combined in any suitable manner in one or more embodiments.

[0020] The above summary of the present disclosure is not intended to describe each disclosed embodiment or every implementation of the present disclosure. The following description more particularly exemplifies exemplary embodiments. In several places throughout the application, guidance is provided through lists of examples, which examples can be used in various combinations. In each instance, the recited lists serve only as a representative group and should not be interpreted as an exclusive list. DETAILED DESCRIPTION OF THE INVENTION

[0021] The present disclosure provides aqueous oral care fluoride treatment compositions. The present disclosure also provides methods for delivering fluoride to a patient's tooth surfaces, as well as methods for reducing the incidence of dental caries. Such methods involve applying the aqueous oral care fluoride treatment compositions described herein to a patient's tooth surfaces.

[0022] In certain embodiments, applying the aqueous oral care fluoride treatment composition comprises painting the treatment composition onto the patient's tooth surfaces.

[0023] In certain embodiments, applying the aqueous oral care fluoride treatment composition comprises dispensing the treatment composition into a dental tray and attaching the tray with the treatment composition therein to the patient's tooth surfaces. In certain embodiments, the dental tray comprises an orthodontic aligner treatment tray.

[0024] The aqueous oral care fluoride treatment compositions of the present disclosure comprise at least 60%, at least 70%, or at least 80% by weight of water, based on the total weight of the aqueous composition. In certain embodiments, the treatment compositions comprise up to 96%, or up to 90% by weight of water, based on the total weight of the aqueous composition.

[0025] The treatment compositions of the present disclosure are aqueous compositions. While they may contain small amounts of organic solvents (e.g., a (C1-C4) alcohol such as ethanol), preferably they do not contain organic solvents that function as a liquid carrier (as opposed to organic solvents used as carriers / solvents for flavorings or sweeteners). For example, certain additives may be provided as a solution or dispersion in an organic solvent as a liquid carrier. If any organic solvent (that functions as a liquid carrier) is present in the aqueous oral care fluoride treatment compositions of the present disclosure, it is present in an amount of less than 5% by weight, based on the total weight of the aqueous composition.

[0026] The aqueous oral care fluoride treatment compositions of the present disclosure include a pharmaceutically acceptable buffering agent. The type and amount of such buffering agent are selected to provide the treatment composition with a pH of at least 6 or at least 6.5. In certain embodiments, the type and amount of such buffering agent are selected to provide the treatment composition with a pH of at most 8, at most 7.5, or at most 7. In certain embodiments, particularly in methods for reducing the incidence of dental caries, the type and amount of such buffering agent are selected to provide the treatment composition with a pH of 6.5 to 7.5, or a pH of 7.0, in accordance with the monograph entitled "Topical Fluoride Preparations for Reducing Incidence of Dental Caries" in the Federal Register, Vol. 39, No. 94, May 14, 1974.

[0027] Water-soluble polymers Although the aqueous oral care fluoride treatment compositions of the present disclosure contain water-soluble polymers, the compositions are typically not gels. Gels generally contain polymer chains that are chemically crosslinked and extended or swollen by a solvent (e.g., water). Thus, typically, the compositions of the present disclosure are not crosslinked, but they may contain polymer chains with chemically unbonded bonds that are extended in the presence of a solvent (e.g., water).

[0028] The aqueous oral care fluoride treatment composition of the present disclosure comprises a water-soluble cationic N-containing polymer. Typically, the water-soluble cationic N-containing polymer herein has a solubility in water at room temperature of greater than 1 g, greater than 2 g, greater than 3 g, greater than 4 g, or greater than 5 g per 100 g of water.

[0029] In certain embodiments, the aqueous oral care fluoride treatment composition of the present disclosure comprises the water-soluble cationic N-containing polymer in an amount of at least 0.5 wt.%, or at least 0.6 wt.%, or at least 0.9 wt.%, based on the total weight of the aqueous composition. In certain embodiments, the aqueous oral care fluoride treatment composition of the present disclosure comprises the water-soluble cationic N-containing polymer in an amount of up to 4.8 wt.%, or up to 4.0 wt.%, based on the total weight of the aqueous composition.

[0030] In certain embodiments, suitable water-soluble cationic N-containing polymers may be non-cationic, non-water-soluble, or neither prior to incorporation into the treatment composition. Such polymers are referred to herein as "polymer precursors." For example, a water-insoluble basic polymer (e.g., EUDRAGIT E100 poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate copolymer) can become cationic upon contact with an acidic aqueous solution. Typically, upon forming a cationic polymer, such a polymer has a solubility in water at room temperature of greater than 1 g per 100 g of water.

[0031] Examples of suitable classes of water-soluble cationic N-containing polymers or polymer precursors include (meth)acrylate copolymers containing dimethylaminoethyl side groups, such as copolymers derived solely from (meth)acrylate monomers or copolymers derived from (meth)acrylate monomers and other monomers, such as vinyl monomers; polyethyleneimine; and cationically modified polysaccharides. These polymers may contain nitrogen in the backbone and / or side groups. Various combinations of such polymers can be used if desired.

[0032] Typically, (meth)acrylate copolymers with dimethylaminoethyl side groups are the polymer precursors. The dimethylamidoethyl side groups of the (meth)acrylate copolymers can be reacted with other chemicals (e.g., acids such as citric acid, or buffers containing acidic components) to form cationic side groups. Evonik EUDRAGIT E100 poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate copolymer is an example of such a polymer. A copolymer of 2-dimethylaminoethyl (meth)acrylate (DMAEMA) and vinyl pyrrolidone (VP), available from Ashland Chemical as VP / DMAEMA copolymer 845G, is another example of this type of polymer.

[0033] Polyethylenimine polymers contain nitrogen atoms in both the polymer backbone and side groups. Polyethylenimine polymers can contain either linear or branched chains and can be converted into water-soluble cationic polymers. Typical examples of polyethyleneimine (PEI) are available from Polyscience.

[0034] Cationically modified polysaccharides contain cationic side groups attached to the polysaccharide. They are therefore cationic and water-soluble without further processing. A typical example of such a polymer is available from Colonial Chemical as PolysugaQuat-1218P.

[0035] Examples of suitable water-soluble cationic N-containing polymers or polymer precursors include: [ka] It is a (meth)acrylate copolymer containing dimethylaminoethyl side groups, where n represents the number of repeat units (typically n=50-2,000). (An example is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) with a 1:2:1 monomer molar ratio and an approximate average molecular weight (weight average) in the range of 5,000-500,000 g / mol, e.g., 47,000 g / mol.) [ka] It is a (meth)acrylate copolymer containing dimethylaminoethyl side groups, where x and y represent the number of repeat units (typically x=200-20,000, and y=200-20,000). (An example is VP / DMAEMA copolymer 845G from Ashland Chemical, which has an approximate average molecular weight (weight average) in the range of 700,000 g / mol to 1,200,000 g / mol.) [ka] This is polyethyleneimine, where n represents the number of repeating units (typically n=200 to 20,000). (An example is PEI, which has an approximate average molecular weight (weight average) in the range of 5,000 g / mol to 1,000,000 g / mol, e.g., 10,000.) [ka] It is a cationically modified polysaccharide, where n represents the number of repeating units (typically n=10-1000). (An example is PolySugaQuat-1218P from Colonial Chemical, which has a viscosity of 1300 CP at 30% solids in aqueous solution.) and any combination of the above.

[0036] In certain embodiments, the cationic polymer may have some hydrogen bonding interactions with the thickening agent (eg, hydroxyethyl cellulose) to form a sufficiently viscous aqueous composition.

[0037] Activator - Sodium Fluoride The aqueous oral care fluoride treatment composition of the present disclosure comprises sodium fluoride as an active agent. In certain embodiments, the treatment composition comprises at least 1.0 wt.% based on the total weight of the aqueous composition. In certain embodiments, the treatment composition comprises up to 2.5 wt.% based on the total weight of the aqueous composition.

[0038] During use, the fluoride-releasing composition can be applied to the oral cavity. In one embodiment, the fluoride-releasing composition is typically applied directly to one or more teeth. The fluoride-releasing composition is typically maintained in contact with the teeth for a time sufficient to release a therapeutically effective amount of fluoride. Fluoride release from the fluoride-releasing composition can be measured, for example, by the methods described in the Examples section of this disclosure. In certain embodiments, the treatment compositions of the present disclosure release at least 50% (or at least 55%, or at least 60%) of the sodium fluoride within 5 minutes. In certain embodiments, the treatment compositions of the present disclosure release at least 85% (or at least 90%, or at least 95%) of the sodium fluoride within 10 minutes. In certain embodiments, the treatment compositions of the present disclosure release at least 90% (or at least 95%, or at least 99%) of the sodium fluoride within 20 minutes.

[0039] In certain embodiments, the treatment compositions of the present disclosure release 90% or less (or 88% or less, or 70% or less) of the sodium fluoride within 1 minute or less. In certain embodiments, the treatment compositions of the present disclosure release 95% or less (or 92% or less, or 75% or less) of the sodium fluoride within 3 minutes or less. In certain embodiments, the treatment compositions of the present disclosure release 98% or less (or 95% or less, or 80% or less) of the sodium fluoride within 5 minutes or less.

[0040] In certain embodiments, the treatment compositions of the present disclosure release 100% (or up to 98%, or up to 90%) of the sodium fluoride within 10 minutes. In certain embodiments, the treatment compositions of the present disclosure release 100% (or up to 99%, or up to 95%) of the sodium fluoride within 15 minutes. In certain embodiments, the treatment compositions of the present disclosure release 100% (or up to 99%, or up to 98%) of the sodium fluoride within 20 minutes.

[0041] Further optional activators The aqueous oral care fluoride treatment compositions of the present disclosure may also contain one or more additional active agents in addition to sodium fluoride, which, if included, typically, but not always, include one or more active agents active in the oral cavity against disorders, diseases, or conditions of the teeth, gums, cheeks, tongue, palate, etc.

[0042] Examples of additional active agents that can be used include one or more whitening agents, anti-calculus agents, remineralization agents, stannous sources, antibacterial agents, antioxidants, saliva stimulants, breath fresheners, antiplaque agents, anti-inflammatory agents, H2 antagonists, desensitizing agents, nutrients, and proteins.If desired, various combinations of such additional active agents can be used.When used, one or more additional active agents will typically be used in an amount sufficient to achieve their intended effect.

[0043] When used, the brightener may be any suitable brightener. Brighteners include, for example, peroxide brighteners, non-peroxide brighteners, or both. Peroxide brighteners include hydrogen peroxide, alkali or alkaline earth metal peroxides, such as sodium peroxide, potassium peroxide, lithium peroxide, magnesium peroxide, calcium peroxide, barium peroxide, glyceryl hydrogen peroxide, alkyl hydrogen peroxide, dialkyl hydrogen peroxide, peroxy acids or peroxy acid salts, benzoyl peroxide, urea peroxide, and the like. Hydrogen peroxide is the most common. Non-peroxide brighteners include chlorine dioxide, chlorous acid, and hypochlorous acid. Chlorous acid and hypochlorous acid are typically in the form of alkali or alkaline earth metal salts, such as lithium, potassium, sodium, magnesium, calcium, or barium salts. Colorants, titanium dioxide, and hydroxyapatite may also be used.

[0044] If used, the anticalculus agent can be a variety of suitable anticalculus agents, including, for example, phosphates, polyphosphates, such as pyrophosphates, polyolefin sulfonates, polyolefin phosphates, diphosphonates, phosphonoalkanecarboxylic acids, and salts thereof, typically alkali metal or ammonium salts.

[0045] If used, the remineralizing agent can be a variety of suitable remineralizing agents, including, for example, materials that release calcium ions, phosphorus-containing ions, or both, such as calcium phosphates (e.g., monocalcium phosphate, dicalcium phosphate, and / or tricalcium phosphate), hydroxyapatite, calcium carbonate, and the like.

[0046] Examples of materials that release calcium ions include water-soluble calcium salts, such as calcium chloride, calcium nitrate, calcium gluconate, calcium lactate gluconate, calcium acetate, hydrates thereof, and combinations thereof. In certain embodiments, the calcium salt is selected from calcium chloride, calcium nitrate, hydrates thereof, and combinations thereof.

[0047] Calcium salts may also be used to modify the fluoride release profile.

[0048] In certain embodiments, the calcium salt is present in an amount of at least 0.5 wt.% based on the total weight of the aqueous composition, hi certain embodiments, the calcium salt is present in an amount of less than 3.0 wt.%, less than 2.0 wt.%, or less than 1.5 wt.% based on the total weight of the aqueous composition.

[0049] If used, the stannous ion source can be a variety of suitable stannous ion sources. Stannous ion sources include, for example, stannous halides, organic stannous carboxylic acid salts such as stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, and stannous citrate. When the fluoride source is stannous fluoride, it can also function as the stannous ion source.

[0050] When used, antibacterial agents include a variety of orally acceptable antibacterial agents, such as triclosan, 8-hydroxyquinoline, zinc ions, stannous ions, cupric compounds, phthalic acid and its salts, quaternary ammonium compounds, sanguinarine, salicylanilide, salicylic acid, thymol, eugenol, neomycin, kanamycin, clindamycin, amoxicillin, tetracycline, doxycycline, minocycline, metronidazole, and chlorhexidine.

[0051] When used, antioxidants can be a variety of orally acceptable antioxidants, examples of which include butylated hydroxyanisone, butylated hydroxytoluene, vitamin A, carotenoids, vitamin E, flavonoids, polyphenols, ascorbic acid or its salts, chlorophyll, melatonin, and the like.

[0052] If used, the saliva stimulant can be a variety of orally acceptable saliva stimulants, examples of which include citric acid, lactic acid, succinic acid, ascorbic acid, adipic acid, fumaric acid, and tartaric acid.

[0053] If used, the breath freshener can be a variety of orally acceptable breath fresheners, examples of which include zinc salts such as zinc gluconate, zinc citrate, and zinc chlorite, alpha-ionone, and the like.

[0054] If used, the antiplaque agent can be a variety of orally acceptable antiplaque agents. Examples include stannous salts, copper, magnesium, or strontium salts, dimethicone copolyols such as cetyl dimethicone copolyol, papain, glucoamylase, glucose oxidase, urea, calcium lactate, calcium glycerophosphate, strontium polyacrylate, and the like. Further examples of antiplaque agents include biofilm inhibitors, particularly those described in U.S. Pat. No. 8,968,709 (Yang et al.).

[0055] When used, anti-inflammatory agents can be a variety of orally acceptable anti-inflammatory agents, including steroids such as flucinolone and hydrocortisone, non-steroidal anti-inflammatory drugs such as ketorolac, flurbiprofen, ibuprofen, naproxen, indomethacin, diclofenac, etodolac, indomethacin, sulindac, tolmetin, ketoprofen, fenoprofen, piroxicam, nabumetone, acetylsalicylic acid, salicylic acid, diflunisal, meclofenamate, mefenamic acid, oxyphenbutazone, phenylbutazone, and the like.

[0056] If used, the H2 antagonist can be a variety of orally acceptable H2 antagonists, examples of which include cimetidine, ethinidine, ranitidine, tiotidine, rupitidine, denetidine, famotidine, roxatidine, pifatidine, ramutidine, zarutidine, nizatidine, mifentidine, lamixotidine, roxitidine, bisfentidine, safotidine, ebrotidine, impromidine, and the like.

[0057] If used, the desensitizing agent can be a variety of orally acceptable desensitizing agents, examples of which include potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate, strontium salts, arginine, acetylsalicylic acid or its salts, salicylic acid or its salts, codeine, acetaminophen, and the like.

[0058] When used, nutrients can be a variety of orally acceptable nutrients, such as vitamins, such as vitamin C, vitamin D, thiamine, riboflavin, folic acid, nicotinamide, niacin, pyridoxine, bioflavonoids, and supplements, such as amino acids, lipophilic substances, fish oils, polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid, coenzyme Q10, ubiquinone, and minerals, such as potassium.

[0059] When used, proteins include a variety of orally acceptable proteins, including milk proteins, peroxide-generating enzymes, amylase, papain, glucoamylase, glucose oxidase, and the like.

[0060] buffer The aqueous oral care fluoride treatment compositions of the present disclosure include a pharmaceutically acceptable buffering agent. The type and amount of such buffering agent are selected to provide a treatment composition having a pH of at least 6 or at least 6.5. In certain embodiments, the type and amount of such buffering agent are selected to provide a treatment composition having a pH of at most 8, at most 7.5, or at most 7. In certain embodiments, the type and amount of such buffering agent are selected to provide a treatment composition having a pH of 6.5-7.5, or at most 7.0. A variety of suitable pharmaceutically acceptable buffering agents are included. Examples include acetate (e.g., sodium acetate), sodium carbonate, citrate (e.g., sodium citrate), tartrate, glycylglycine, histidine, glycine, lysine, arginine, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, tris(hydroxymethyl)-aminomethane, or mixtures thereof.

[0061] thickener In certain embodiments, the aqueous oral care fluoride treatment compositions of the present disclosure include a thickener to provide the composition with a suitable viscosity that allows for the desired application method. For example, a suitable thickener can be used in an amount sufficient to achieve a solution viscosity that is suitable for maintaining the composition in an inverted mouthpiece tray applicator for up to about 4 minutes (a typical time for professionally applied fluoride treatments), yet is sufficiently fluid to have acceptable handling characteristics for a dental technician (e.g., when dispensed into a dental tray applicator). Alternatively, a suitable thickener in an amount sufficient to achieve a solution viscosity suitable for painting onto a tooth surface can be used.

[0062] In certain embodiments, the type and amount of thickening agent is selected to provide the treatment composition with a viscosity of at least 0.5 Pascal-seconds at a shear rate of 1.0 sec / s, hi certain embodiments, the type and amount of thickening agent is selected to provide the treatment composition with a viscosity of up to 100 Pascal-seconds at a shear rate of 1.0 sec / s.

[0063] In certain embodiments, the thickening agent is present in the treatment composition in an amount of less than 2.5% by weight based on the total weight of the aqueous composition, hi certain embodiments, the thickening agent is present in an amount of at least 0.5% by weight based on the total weight of the aqueous composition.

[0064] Suitable thickening agents are typically those that are generally safe for human consumption (FDA approved for internal use), that do not bind fluoride ions, and that do not significantly affect the bioavailability of fluoride ions.

[0065] In certain embodiments, the thickening agent is selected from natural gums, non-acid cellulose derivatives (e.g., hydroxyethyl cellulose), inorganic fillers (e.g., colloidal silica, fumed silica, alumina, titania, and zinc oxide), alkylene oxide polymers (e.g., polyethylene glycol, polypropylene glycol, and copolymers of polyethylene glycol and polypropylene glycol), non-acid modified starches, and combinations thereof.

[0066] Optional Additives In certain embodiments, the aqueous oral care fluoride treatment compositions of the present disclosure include one or more optional additives, including flavoring agents (i.e., flavoring agents) and sweeteners. Various combinations of such materials can be used if desired.

[0067] In certain embodiments, the aqueous oral care fluoride treatment compositions of the present disclosure include a sweetener. A variety of orally acceptable sweeteners can be used. Common sweeteners include xylitol, sorbitol, sucralose, aspartame, saccharin, usually sodium saccharin, and the like. When present, the sweetener can be used in any suitable amount, most often an amount sufficient to impart a pleasant sweetness to the composition. The suitable amount is typically 0.5% to 15% by weight, based on the total weight of the aqueous composition.

[0068] In certain embodiments, the aqueous oral care fluoride treatment composition of the present disclosure includes a flavoring agent. A variety of orally acceptable flavoring agents can be used. Common flavoring agents include peppermint oil, spearmint oil, cherry flavor, citric acid, orange flavor, vanilla, strawberry flavor, coconut flavor, and bubblegum flavor. When present, the flavoring agent can be used in any suitable amount, most often an amount sufficient to impart a pleasant flavor to the composition. The suitable amount is typically 1% to 4% by weight based on the total weight of the aqueous composition.

[0069] Illustrative Embodiments Embodiment 1 is an aqueous oral care fluoride treatment composition comprising 0.5% to 4.8% by weight of a water soluble cationic N-containing polymer, a pharmaceutically acceptable buffer, 1.0% to 2.5% by weight of sodium fluoride, and at least 60% by weight of water, where the weight percentages are based on the total weight of the aqueous composition.

[0070] Embodiment 2 is the treatment composition of embodiment 1, wherein the water soluble cationic N-containing polymer comprises a cationic N-containing polymer having a solubility in water of greater than 1 g, greater than 2 g, greater than 3 g, greater than 4 g, or greater than 5 g per 100 g of water.

[0071] Embodiment 3 is a treatment composition according to embodiment 1 or 2, wherein the water-soluble cationic N-containing polymer is present in an amount of 0.6% to 4.0% by weight.

[0072] Embodiment 4 is the treatment composition of embodiment 3, wherein the water-soluble cationic N-containing polymer is present in an amount of 0.9% to 4.0% by weight.

[0073] Embodiment 5 is a treatment composition according to any one of embodiments 1-4, wherein the water-soluble cationic N-containing polymer is derived from a polymer precursor that is not cationic prior to incorporation into the treatment composition.

[0074] Embodiment 6 is a treatment composition according to embodiment 5, wherein the water-soluble N-containing polymer or polymer precursor is selected from (meth)acrylate copolymers with pendant dimethylaminoethyl groups, polyethyleneimines, cationically modified polysaccharides, and combinations thereof.

[0075] Embodiment 7 is a method for preparing a water-soluble cationic N-containing polymer or polymer precursor comprising: [ka] (In the formula, n=50~2,000) [ka] (wherein x = 200 to 20,000, and y = 200 to 20,000) [ka] (wherein n=5,000 to 1,000,000), and [ka] (In the formula, n=10~1,000) The treatment composition of embodiment 6 is selected from:

[0076] Embodiment 8 is a treatment composition according to any one of embodiments 1 to 7, wherein the water-soluble cationic N-containing polymer comprises a mixture of water-soluble cationic N-containing polymers.

[0077] Embodiment 9 is a treatment composition according to any one of embodiments 1 to 8, further comprising a thickening agent.

[0078] Embodiment 10 is a treatment composition according to embodiment 9, wherein the thickener is present in an amount sufficient to provide the composition with a viscosity of 0.5 to 100 Pascal-seconds at a shear rate of 1.0 Pa / sec.

[0079] Embodiment 11 is a treatment composition according to embodiment 9 or 10, wherein the thickening agent is present in an amount of at least 0.5% and less than 2.5% by weight.

[0080] Embodiment 12 is a treatment composition according to any one of embodiments 9-11, wherein the thickening agent is selected from natural gums, non-acid cellulose derivatives, inorganic fillers, alkylene oxide polymers, non-acid modified starches, and combinations thereof.

[0081] Embodiment 13 is a treatment composition according to any one of embodiments 1 to 12, further comprising a calcium salt.

[0082] Embodiment 14 is a treatment composition according to embodiment 13, wherein the calcium salt is present in an amount less than 3.0% by weight (or less than 2.0% by weight, or less than 1.5% by weight).

[0083] Embodiment 15 is a treatment composition according to embodiment 13 or 14, wherein the calcium salt is present in an amount of at least 0.5% by weight.

[0084] Embodiment 16 is a treatment composition according to any one of embodiments 13-15, wherein the calcium salt is selected from calcium chloride, calcium nitrate, calcium gluconate, calcium lactate gluconate, calcium acetate, hydrates thereof, and combinations thereof.

[0085] Embodiment 17 is a treatment composition according to embodiment 16, wherein the calcium salt is selected from calcium chloride, calcium nitrate, hydrates thereof, and combinations thereof.

[0086] Embodiment 18 is a treatment composition according to any one of embodiments 1 to 17, having a pH of 6 to 8, or a pH of 6.5 to 7.5.

[0087] Embodiment 19 is a treatment composition according to embodiment 18, having a pH of 6-7, or a pH of 7.0.

[0088] Embodiment 20 is a treatment composition according to any one of embodiments 1 to 19, comprising less than 5% by weight of an organic solvent acting as a carrier liquid (e.g., ethanol).

[0089] Embodiment 21 is a treatment composition according to any one of embodiments 1 to 20, which releases at least 50% (or at least 55%, or at least 60%) of the sodium fluoride in 5 minutes or less.

[0090] Embodiment 22 is a treatment composition according to any one of embodiments 1 to 21, which releases at least 85% (or at least 90%, or at least 95%) of the sodium fluoride in 10 minutes or less.

[0091] Embodiment 23 is a treatment composition according to any one of embodiments 1 to 22, which releases at least 90% (or at least 95%, or at least 99%) of the sodium fluoride in 20 minutes or less.

[0092] Embodiment 24 is a treatment composition according to any one of embodiments 1 to 23, which releases at least 90% or less (or 88% or less, or 70% or less) of the sodium fluoride in 1 minute or less.

[0093] Embodiment 25 is a treatment composition according to any one of embodiments 1 to 24, which releases 95% or less (or 92% or less, or 75% or less) of the sodium fluoride in 3 minutes or less.

[0094] Embodiment 26 is a treatment composition according to any one of embodiments 1 to 25, which releases 98% or less (or 95% or less, or 80% or less) of the sodium fluoride in 5 minutes or less.

[0095] Embodiment 27 is a treatment composition according to any one of embodiments 1 to 26, which releases 100% (or up to 98%, or up to 90%) of the sodium fluoride in 10 minutes or less.

[0096] Embodiment 28 is a treatment composition according to any one of embodiments 1 to 27, which releases 100% (or up to 99%, or up to 95%) of the sodium fluoride in 15 minutes or less.

[0097] Embodiment 29 is a treatment composition according to any one of embodiments 1 to 28, which releases 100% (or up to 99%, or up to 98%) of the sodium fluoride in 20 minutes or less.

[0098] Embodiment 30 is a treatment composition according to any one of embodiments 1 to 29, comprising at least 70% (or at least 80%) water by weight.

[0099] Embodiment 31 is a treatment composition according to any one of embodiments 1 to 30, comprising up to 96% (or up to 90%) water by weight.

[0100] Embodiment 32 is a treatment composition according to any one of embodiments 1 to 31, wherein the water-soluble N-containing polymer is not chemically crosslinked.

[0101] Embodiment 33 is a treatment composition according to any one of embodiments 1 to 32, comprising one or more active agents in addition to sodium fluoride.

[0102] Embodiment 34 is a treatment composition according to embodiment 33, wherein the one or more active agents comprise a whitening agent, anticalculus agent, remineralization agent, stannous source, antibacterial agent, antioxidant, saliva stimulant, breath freshener, antiplaque agent, anti-inflammatory agent, H2 antagonist, desensitizing agent, nutrient, protein, or combinations thereof.

[0103] Embodiment 35 is a treatment composition according to any one of embodiments 1 to 34, further comprising a flavoring agent.

[0104] Embodiment 36 is a treatment composition according to any one of embodiments 1 to 35, further comprising a sweetener.

[0105] Embodiment 37 is a method of providing fluoride to a patient's dental surfaces, comprising applying to the patient's dental surfaces an aqueous oral care fluoride treatment composition of any one of embodiments 1-36.

[0106] Embodiment 38 is the method of embodiment 37, wherein applying comprises painting the treatment composition onto the patient's tooth surface.

[0107] Embodiment 39 is the method of embodiment 36, wherein applying comprises dispensing the treatment composition into a dental tray and attaching the tray with the treatment composition therein to the patient's tooth surfaces.

[0108] Embodiment 40 is the method of embodiment 39, wherein the dental tray comprises an orthodontic aligner treatment tray.

[0109] Embodiment 41 is a method of reducing the incidence of dental caries in a patient in need thereof, comprising applying to the patient's dental surfaces an aqueous oral care fluoride treatment composition of any one of Embodiments 1-39.

[0110] Embodiment 42 is the method of embodiment 41, wherein applying comprises painting the treatment composition onto the patient's tooth surface.

[0111] Embodiment 43 is the method of embodiment 41, wherein applying comprises dispensing the treatment composition into a dental tray and attaching the tray with the treatment composition therein to the patient's tooth surfaces.

[0112] Embodiment 44 is the method of embodiment 43, wherein the dental tray comprises an orthodontic aligner treatment tray. [Example]

[0113] The objects and advantages of this invention are further illustrated by the following examples, but the particular materials and amounts thereof recited in these examples, as well as other conditions and details, should not be construed to unduly limit this invention. These examples are for illustrative purposes only and are not intended to limit the scope of the appended claims. [Table 1]

[0114] Polymer Chemical Structure EUDRAGIT E100 polymer [ka] Polyscience Polyethyleneimine(PEI) [ka] Ashland VP / DMAEMA Copolymer 845 G [ka] Colonial PolySugaQuat-1218P [ka]

[0115] Visual inspection Any undesired precipitation or polymer / water phase separation was visually inspected. During the preparation of the composition, the liquid composition was visually inspected for phase separation and / or white precipitation. If polymer aggregates or sponge-like semi-solid gel formed due to the interaction between two different polymers in the composition were present, it meant that phase separation had occurred and a non-uniform composition was formed.

[0116] Fluoride Release Test Fluoride release was measured with a Mettler Toledo T70 titrator. A Cole Parmer fluoride electrode was first calibrated in parts per million (ppm) of fluoride using TISAB III prior to measuring samples for fluoride release each day (Total Ionic Strength Adjustment Buffer (TISAB III) concentrated solution is used with a fluoride ion-selective electrode, Sigma Aldrich). Each example composition was coated in a thin layer onto a RINZL Plastic microscope slide, with a coating area of ​​2.54 cm on each side of the slide. 2 The total weight of the coating was approximately 0.045 g. A fluoride meter titration cup was filled with 50 mL of a mixture of 45 mL of MilliQ DI water and 5 mL of TISAB III concentrate. A fluoride ion-selective electrode was placed in the titration cup of the diluted TISAB III solution, and the meter was allowed to equilibrate for 30 seconds before analyzing each sample. After 30 seconds, the clamped sample was reduced to 50 mL of diluted TISAB III solution. Fluoride release (mV) was measured at various time points during a 30-minute titration in a Mettler Toledo T70 titrator. Fluoride release was calculated against a fluoride standard calibration curve. The average of two titrations was reported for each example.

[0117] pH test The pH of the various compositions was measured using a Fisher Scientific Accumet Model 15 pH meter and a Fisher Scientific Accumet pH probe cat#13-620-291, SN 6153081P 15 pH probe. Prior to measurement, the meter was calibrated with standard pH solutions. pH values ​​were obtained by inserting the probe into the solution and waiting 2 minutes to obtain the pH value.

[0118] Viscosity Test The viscosity of the composition was measured at room temperature using a TA Instruments AR-G2 magnetic bearing rheometer equipped with a parallel plate fixture. Approximately 1.4 mL of the composition was placed between the plates, and the plate gap was set to 1 millimeter (mm) for room temperature measurements. The viscosity was recorded at a shear rate of 1.0 (1 / s). Two tests were performed for each sample, and the average was reported.

[0119] Preparation of Fluoride Treatment Compositions Preparation of cationic polymer stock solutions To convert the cationic polymer precursor to the cationic polymer, the following procedure was used.

[0120] A 162 g quantity of deionized (DI) water was added to a glass bottle, followed by 14 g of KH2PO4 and mixing thoroughly to dissolve the KH2PO4 in the water. 24 g of EUDRAGIT E100 polymer was then added, and the mixture was mixed with a magnetic stirrer for 24 hours (hours) to dissolve the polymer in water, forming a water-soluble cationic polymer. This was the cationic polymer stock solution for EUDRAGIT E100 polymer.

[0121] A 70 g quantity of DI water was added to a glass bottle, followed by 30 g of KH2PO4, and mixed thoroughly to dissolve the KH2PO4 in the water. Next, 10 g of PEI polymer was added, and the mixture was stirred with a magnetic stirrer for 24 hours to dissolve the polymer in water, forming a water-soluble cationic polymer. This was the cationic polymer stock solution for the PEI polymer.

[0122] An 88 g quantity of DI water was added to a glass bottle, followed by 10 g of VP / DMAEMA copolymer 845. The mixture was mixed with a magnetic stirrer for 24 hours to dissolve the polymer in water, forming a water-soluble cationic polymer. This was the cationic polymer stock solution for the VP / DMAEMA polymer.

[0123] Preparation of pH 6-7 buffer stock solution A quantity of 3.84 g of citric acid was dissolved in 200 mL of DI water, and 14.2 g of NaHPO was dissolved in 500 mL of DI water. After both solutions were made, 465 mL of the NaHPO solution was added to 150 mL of the citric acid solution. The solutions were mixed well, and the pH of the final solution was measured. This is a pH buffer, and the pH was 7.0.

[0124] A quantity of 3.84 g of citric acid was dissolved in 200 mL of DI water, and 14.2 g of NaHPO was dissolved in 500 mL of DI water. After both solutions were made, 335 mL of the NaHPO solution was added to 150 mL of the citric acid solution. The solutions were mixed well, and the pH of the final solution was measured. The pH was 6.39.

[0125] Preparation of Fluoride Aqueous Coating Compositions Calcium chloride dihydrate was dissolved in DI water in a glass bottle. The cationic polymer stock solution, sodium fluoride, DI water, xylitol, and flavoring agent were added to a plastic bottle and mixed thoroughly to form a solution with magnetic stirring for 30 minutes. The calcium chloride solution was then slowly added to the fluoride solution with stirring for approximately 5 minutes. Further mixing was carried out for another 30 minutes. Any white precipitation was noted while the calcium chloride solution was added to the fluoride-containing composition. Other additives, such as calcium phosphate, were then added, if desired, and mixed thoroughly for 10 minutes. HEC NATROSOL 250HHX pharm thickener was then added and stirred for approximately 30 minutes. The sample was then placed on a Wheaton roller overnight with mixing at maximum speed to form a viscous aqueous coating composition. The samples were visually inspected for the formation of any polymer aggregates or sponge-like semi-solid gels that separated from the aqueous solution, which may result from interactions between the two different polymers in the composition.

[0126] The detailed mixing ratios are listed in the table below. [Table 2] [Table 3] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8] [Table 9]

[0127] The entire disclosures of the patents, patent documents, and publications cited herein are incorporated by reference in their entirety, as if each were individually incorporated. Various modifications and alterations to the present disclosure will become apparent to those skilled in the art without departing from the scope and spirit of the present disclosure. It is understood that the present disclosure is not intended to be unduly limited by the exemplary embodiments and examples set forth herein, and that such examples and embodiments are presented merely as examples within the scope of the present disclosure, which is intended to be limited only by the claims set forth herein as follows.

Claims

1. 1. An aqueous oral care fluoride treatment composition comprising: a water-soluble cationic N-containing polymer present in an amount of 0.9% to 4.0% by weight; sodium fluoride present in an amount of 1.0% to 2.5% by weight; a water-soluble calcium salt present in an amount of 0.5% to 3.0% by weight; Water present in an amount of at least 60% by weight; a pharmaceutically acceptable buffer; and wherein said weight percent is based on the total weight of said aqueous oral care fluoride treatment composition; An aqueous oral care fluoride treatment composition, wherein the aqueous oral care fluoride treatment composition does not phase separate and does not precipitate.

2. 10. The aqueous oral care fluoride treatment composition of claim 1, wherein said water-soluble cationic N-containing polymer is derived from a polymer precursor that is not cationic prior to incorporation into said aqueous oral care fluoride treatment composition.

3. 3. The aqueous oral care fluoride treatment composition of claim 1 or 2, wherein the water-soluble cationic N-containing polymer or polymer precursor thereof is selected from (meth)acrylate copolymers with pendant dimethylaminoethyl groups, polyethyleneimines, cationically modified polysaccharides, and combinations thereof.

4. The water-soluble cationic N-containing polymer or its polymer precursor is 【Chemical 1】 (in the formula, n=50 to 2000), 【Chemistry 2】 (Wherein, x = 200 to 20,000, and y = 200 to 20,000) 【Chemistry 3】 (In the formula, n=5,000 to 1,000,000) 【Chemistry 4】 (In the formula, n = 10 to 1,000), and any combination of the above 4. The aqueous oral care fluoride treatment composition of claim 3, selected from:

5. 4. The aqueous oral care fluoride treatment composition of claim 3, wherein the water-soluble cationic N-containing polymer or polymer precursor thereof is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) copolymer.

6. 6. The aqueous oral care fluoride treatment composition of any one of claims 1 to 5, further comprising a thickener present in an amount less than 2.5% by weight.

7. 7. The aqueous oral care fluoride treatment composition of any one of claims 1 to 6, wherein the water-soluble calcium salt is present in an amount of less than 2.0% by weight.

8. 8. The aqueous oral care fluoride treatment composition of any one of claims 1 to 7, wherein the water-soluble calcium salt is calcium chloride.

9. 9. The aqueous oral care fluoride treatment composition of any one of claims 1 to 8, having a pH of 6 to 8.

10. 10. The aqueous oral care fluoride treatment composition of any one of claims 1 to 9, comprising less than 5% by weight of organic solvent.

11. 11. The aqueous oral care fluoride treatment composition of any one of claims 1 to 10, comprising up to 96% by weight of water.

12. 12. An aqueous oral care fluoride treatment composition according to any one of claims 1 to 11 for delivering fluoride to a patient's tooth surfaces.

13. 13. The aqueous oral care fluoride treatment composition of claim 12 dispensed into a dental tray, wherein the dental tray comprises an orthodontic aligner treatment tray.

Images