Methods for treating dental hypersensitivity

Abstract

Disclosed herein are methods of reducing or preventing dental hypersensitivity comprising providing an electrochemical oral care device comprising a flexible base substrate, a power source disposed on a side of the base substrate, a first electrode and a second electrode to a surface of the oral cavity of the subject; contacting an oral care composition for reducing or preventing dental hypersensitivity to the surface of the oral cavity of the subject and to the first electrode or the second electrode; and applying an electrical charge from the electrochemical oral device to the oral care composition. Also disclosed herein are kits comprising the electrochemical oral care device and the oral care composition.

Description

METHODS FOR TREATING DENTAL HYPERSENSITIVITYCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority from U.S. Provisional Patent Application No. 63 / 662,117, filed 20 June 2024, the contents of which are hereby incorporated herein by reference in their entirety.BACKGROUND

[0002] Exposure of dentin may occur, for example, from dental erosion or gingival recession. Gingival recession results in the exposure of increased tooth surface due to recession of the gum line. 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. Generally, saliva has a pH between 7.2 to 7.4. When the pH is lowered and the concentration of hydrogen ions becomes relatively high, the tooth enamel can become microscopically etched, resulting in a porous, sponge-like roughened surface that may cause dentin hypersensitivity, among other problems.

[0003] Dentin hypersensitivity is a painful response to a variety of stimuli, including thermal, tactile, evaporative, osmotic, and chemical stimuli. Dentin is a portion of the tooth internal to the enamel and cementum that has a radially striated appearance owing to a large number of fine canals or tubules known as dentin tubules. Dentin tubules run from the pulp cavity to the periphery of the dentin and are generally about two microns in diameter at their base and somewhat narrower at their periphery. Dentin tubules are not usually exposed to the environment in the oral cavity, as they are usually covered by enamel or cementum. The cementum in turn is often covered by the gums.

[0004] Exposure of the dentin, which is generally due to recession of the gums or loss of enamel, frequently leads to hypersensitivity. Changes in the flow of the plasma- like biological fluid present in the dentinal tubules can trigger mechanoreceptors present on nerves located at the pulpal aspect, thereby eliciting a pain response. This hydrodynamic flow can be increased by cold, air pressure, drying, sugar, sour (dehydrating chemicals), or forces acting onto the tooth. Hot or cold food or drinks, and physical pressure are typical triggers in those individuals with teeth sensitivity.

[0005] Conventionally, two approaches have been taken to treat or ameliorate tooth sensitivity. The first approach is to interfere with transmission of nerve impulses. Known desensitizing agentsare useful in this chemical approach and may include potassium salts (such as potassium nitrate, potassium bicarbonate, potassium chloride) and strontium, zinc salts, and chloride salts. The second approach involves the mechanical shield of the nerve by, e.g., blocking of the dentin tubules wholly or partially with dentin tubule occlusion agents. For example, arginine-calcium carbonate complexes plug dentinal tubules, providing immediate relief from dentinal hypersensitivity. For example, conventional oral care compositions, such as Colgate Sensitive Pro-Relief®, often include arginine and calcium carbonate as blocking agents to occlude the dentin and reduce sensitivity.

[0006] Nonetheless, there still exists a need in the art for enhanced prevention or reduction of tooth sensitivity wherein the application to the oral cavity is in a convenient form for providing substantially immediate relief over a period of time.BRIEF SUMMARY

[0007] This summary is intended merely to introduce a simplified summary of some aspects of one or more implementations of the present disclosure. Further areas of applicability of the present disclosure will become apparent from the detailed description provided hereinafter. This summary is not an extensive overview, nor is it intended to identify key elements of the present teachings, nor to delineate the scope of the disclosure. Rather, its purpose is merely to present one or more concepts in simplified form as a prelude to the detailed description below.

[0008] Aspects disclosed herein are directed to methods of reducing or preventing dental hypersensitivity in a subject in need thereof, the method comprising (1) providing an electrochemical oral care device comprising a flexible base substrate, a power source disposed on a side of the base substrate, a first electrode and a second electrode to an oral cavity of the subject; (2) contacting an oral care composition for reducing or preventing dental hypersensitivity to a surface of the oral cavity of the subject (e.g. the teeth) and to the first electrode or the second electrode; and applying an electrical charge from the electrochemical oral care device to the oral care composition.

[0009] In certain embodiments of the methods disclosed herein, the oral care composition is applied to the electrochemical oral care device prior to contacting the oral care composition to the surface of the oral cavity of the subject, and in certain embodiments, the oral care composition is applied to the oral cavity of the subject prior to contacting the oral care composition to the firstelectrode or the second electrode. According to certain embodiments, the electrochemical oral care device is in a mouth guard, a wand, or a tray designed to fit in the oral cavity of the subject.

[0010] According to various embodiments, the oral care composition comprises at least one occluding agent, and in certain embodiments, the at least one occluding agent is calcium carbonate. In certain embodiments, the oral care composition comprises at least one basic amino acid, and in certain embodiments, the at least one basic amino acid is selected from L-arginine or arginine bicarbonate. According to certain embodiments, the oral care composition disclosed herein comprises calcium carbonate and arginine bicarbonate.

[0011] In certain embodiments of the methods disclosed herein, the electrical charge is at least about 3 volts, preferably at least about 5 volts, and in certain embodiments, the electrical charge is less than about 10 volts, such as about 5 volts. In certain embodiments, the electrical charge is applied for at least about 5 minutes, preferably at least about 10 minutes. In certain embodiments, the electrical charge is about 5 volts and is applied for about 10 minutes. According to certain embodiments, the steps of the method are repeated at least twice.

[0012] In certain embodiments of the methods disclosed herein, the method occludes at least about 10% of exposed dentin tubules, such as at least about 15%, at least about 20%, or at least about 25% of exposed dentine tubules.

[0013] Also disclosed herein is a kit comprising (1) an electrochemical oral care device comprising a flexible base substrate, a power source disposed on a side of the base substrate, a first electrode and a second electrode; (2) an oral care composition for reducing or preventing dental hypersensitivity; and (3) instructions for use.

[0014] In certain embodiments of the kit disclosed herein, the oral care composition comprises at least one occluding agent, and in certain embodiments, the at least one occluding agent is calcium carbonate. According to certain embodiments of the kit disclosed herein, the oral care composition comprises at least one basic amino acid, and in certain embodiments, the at least one basic amino acid is arginine bicarbonate.

[0015] In certain embodiments of the kit disclosed herein, the electrochemical oral care device is in a mouth guard, a wand, or a tray designed to fit in the oral cavity of the subject and contact a surface of the oral cavity, such as the teeth. In certain embodiments, the first and second electrodes are designed to apply an electrical charge of at least about 3 volts, preferably at least about 5 volts.BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Implementation of the present technology will now be described, by way of example only, with reference to the attached figures. The features and advantages of the disclosure will be apparent from the following more detailed description of certain embodiments and as illustrated in the accompanying drawings in which:

[0017] FIG. 1 is a schematic view of an electrochemical oral care device according to an exemplary implementation of the disclosure.

[0018] FIG. 2 is a bar graph showing the percent tubule occlusion for dentin samples after application of 3 volts, 5 volts, and 7 volts of electric current from an electrochemical oral care device to an oral care composition, as described in Example 1.

[0019] FIG. 3 is a bar graph showing the percent tubule occlusion for dentin samples after application of 5 volts of current for 3 minutes and 10 minutes, as described in Example 1.

[0020] FIG. 4 is a bar graph showing the percent tubule occlusion for dentin samples after application of 5 volts of current for ten minutes for a first, second, third, and fourth treatment cycle, as described in Example 1.DETAILED DESCRIPTION

[0021] For illustrative purposes, the principles of the present disclosure are described by referencing various exemplary embodiments thereof. Although certain embodiments of the disclosure are specifically described herein, one of ordinary skill in the art will readily recognize that the same principles are equally applicable to, and can be employed in other compositions and methods. Before explaining the disclosed embodiments of the present disclosure in detail, it is to be understood that the disclosure is not limited in its application to the details of any particular embodiment disclosed herein. The terminology used herein is for the purpose of description and not of limitation.

[0022] As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context dictates otherwise. The singular' form of any class of the ingredients refers not only to one chemical species within that class, but also to a mixture of those chemical species. The terms “a” (or “an”), “one or more” and “at least one” may be used interchangeably herein. The terms “comprising”, “including”, and “having” may be usedinterchangeably. The term “include” should be interpreted as “include, but are not limited to”. The term “including” should be interpreted as “including, but arc not limited to”.

[0023] As used throughout, ranges are used as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range. Thus, a range from 1-5, includes specifically 1, 2, 3, 4 and 5, as well as subranges such as 2-5, 3-5, 2-3, 2-4, 1-4, etc.

[0024] The term “about” when referring to a number means any number within a range of 10% of the number. For example, the phrase “about 2 wt.%” refers to a number between and including 1.8 wt.% and 2.2 wt.%.

[0025] 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.

[0026] The abbreviations and symbols as used herein, unless indicated otherwise, take their ordinary meaning. The abbreviation “wt%” means percent by weight with respect to the oral care composition. The symbol “°” refers to a degree, such as a temperature degree or a degree of an angle. The symbols “h”, “min”, “mL”, “nm”, and “pm” refer to hour, minute, milliliter, nanometer, and micrometer, respectively. The abbreviation “rpm” means revolutions per minute.

[0027] When referring to chemical structures and names, the symbols “C”, “H”, and “O” mean carbon, hydrogen, and oxygen, respectively. The symbols “=”, and “= ’ mean single bond, double bond, and triple bond, respectively.

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

[0029] The phrases, “a mixture thereof,” “a combination thereof,” or a combination of two or more thereof” do not require that the mixture include all of A, B, C, D, E, and F (although all of A, B,C, D, E, and F may be included). Rather, it indicates that a mixture of any two or more of A, B, C,D, E, and F can be included. In other words, it is equivalent to the phrase “one or more elements selected from the group consisting of A, B, C, D, E, F, and a mixture of any two or more of A, B,C, D, E, and F.” Likewise, the term “a salt thereof’ also relates to “salts thereof.” Thus, where the disclosure refers to “an element selected from the group consisting of A, B, C, D, E, F, a salt thereof, and a mixture thereof,” it indicates that that one or more of A, B, C, D, and F may be included, one or more of a salt of A, a salt of B, a salt of C, a salt of D, a salt of E, and a salt of F may be included, or a mixture of any two of A, B, C, D, E, F, a salt of A, a salt of B, a salt of C, a salt of D, a salt of E, and a salt of F may be included.

[0030] All components and elements positively set forth in this disclosure can be negatively excluded from the claims. In other words, the oral care compositions of the instant disclosure can be free or essentially free of all components and elements positively recited throughout the instant disclosure. In some instances, the oral care compositions of the present disclosure may be substantially free of non-incidental amounts of the ingredient(s) or compound(s) described herein. A non-incidental amount of an ingredient or compound is the amount of that ingredient or compound that is added into the oral care composition by itself. For example, an oral care composition may be substantially free of a non-incidental amount of an ingredient or compound, although such ingredient(s) or compound(s) may be present as part of a raw material that is included as a blend of two or more compounds.

[0031] Some of the various categories of components identified may overlap. In such cases where overlap may exist and the oral care composition includes both components (or the composition includes more than two components that overlap), an overlapping compound does not represent more than one component. For example, certain compounds may be characterized as both a polyol and a sweetener. If a particular oral care composition includes both a polyol and a sweetener, compound will serve only as either a polyol or a sweetener — not both.

[0032] For readability purposes, the chemical functional groups are in their adjective form; for each of the adjectives, the word “group” is assumed. For example, the adjective “alkyl” without a noun thereafter, should be read as “an alkyl group.”

[0033] As used herein, the term “subject” refers to individuals (e.g., human) to be treated by the methods or compositions of the present invention. Subjects include, but are not limited to, mammals (e.g., murines, simians, equines, bovines, porcines, canines, felines, and the like), and most preferably includes humans. In certain embodiments, the subject is a human experiencing dental hypersensitivity or a human at risk of developing dental hypersensitivity. Subjects that may experience dental hypersensitivity or subjects at risk of developing dental hypersensitivity mayinclude, for example, subjects of an increased age (e.g., adults or the elderly), subjects with preexisting oral disease (e.g., gingivitis, periodontitis), subjects with poor dental hygiene habits, subjects with poor dietary habits, subjects taking certain medications (e.g., medications that cause dry mouth); subjects who grind their teeth, smokers, and / or subjects with tooth decay, tooth erosion and / or fractured teeth.

[0034] As used herein, the term “in vitro” refers to an artificial environment and to processes or reactions that occur within an artificial environment. In vitro environments include, but are not limited to, test tubes and cell cultures. The term “in vivo” refers to the natural environment (e.g., an animal or a cell) and to processes or reaction that occur within a natural environment.

[0035] As used herein, the terms “prevention,” “preventing,” and the like refer to the prophylactic prevention of the incidence, recurrence, spread, onset or establishment of a disorder such as dental hypersensitivity. It is not intended that the present disclosure be limited to complete prevention or to prevention of establishment of any dental hypersensitivity. In some embodiments, the onset is delayed, or the severity or the chance of developing the disorder is reduced, and such constitute examples of prevention.

[0036] Disclosed herein are methods of reducing or preventing dental hypersensitivity comprising the application of an electrical current from an electrochemical oral care device, such as an electrochemical tray, that is in contact with an oral care composition comprising at least one dental occluding agent, e.g., calcium carbonate and optionally at least one basic amino acid, e.g., arginine bicarbonate, wherein the oral care composition is in contact with a surface of the oral cavity, such as the teeth.

[0037] In certain embodiments disclosed herein, the electrochemical oral care device is used to general an electric field through the oral care composition, which may allow the composition to act on the teeth and thereby avoid any rubbing on the tooth’s surface. Metal electrodes apply a voltage across the oral care composition, which is first applied to the teeth or first applied to the electrochemical oral care device and then applied to the teeth when the oral care device is inserted into the oral cavity. The voltage causes the active agents in the oral care composition, e.g., calcium carbonate and / or arginine bicarbonate, to move across the surface of the teeth, including inside exposed dentin tubules, thereby occluding the tubules. Electronically controlled movement of the occluding agents can ensure thorough and even application of the oral care composition to allsurfaces of the exposed dentin tubules in a controlled manner, offering advantages over physical application of the oral care composition, c.g., with a brush, wand, or fingers.

[0038] The present disclosure describes compact oral care devices that are effective and relatively simple to use. The methods described herein allow a user to apply the oral care composition evenly over surfaces of the oral cavity, including teeth having exposed dentin tubules, without the need for rubbing, brushing or other application to the tooth’s surface.Oral Care Compositions for Treating Dental Hypersensitivity

[0039] In embodiments of the disclosure, the methods disclosed herein may comprise use of an oral care composition comprising at least one dentin occluding agent, which agents act to physically occlude dentin tubules, thereby preventing or reducing dental hypersensitivity. In certain embodiments, the oral care composition is a composition as described in U.S. Patent Publication No. 2012 / 0141588 and / or U.S. Patent Publication No. 2015 / 0290112, both of which are incorporated by reference herein in their entireties.

[0040] In certain embodiments, the oral care composition for use with the methods disclosed herein comprises at least one dentin occluding agent. In certain embodiments, the oral care composition for use with the methods disclosed herein comprises at least one dentin occluding agent together with a basic amino acid or salt thereof.

[0041] The at least one dentin occluding agent may be any dentin occluding agent known in the art. In certain embodiments, the oral care compositions for use in the methods disclosed herein comprises at least one dentin occluding agent selected from calcium carbonate and calcium silicate.

[0042] In certain embodiments, the oral care composition for relieving dentin hypersensitivity comprises particles of precipitated calcium carbonate. Optionally, the particles of precipitated calcium carbonate are present in the oral care composition in an amount of from about 10 wt% to about 50 wt%, such as from about 25 wt% to about 40 wt%, from about 30 wt% to about 36 wt%, from about 33 wt% to about 35 wt%, or about 34 wt%, based on the total weight of the oral care composition.

[0043] Optionally, the particles of precipitated calcium carbonate have an average particle size of no greater than a dentin tubule of a mammalian tooth. Typically, the particles of precipitated calcium carbonate have a particle size ranging from about 0.1 microns to about 13 microns.

[0044] In certain embodiments, the particles of precipitated calcium carbonate comprise a mixture of first particles having a particle size ranging from about 0.1 microns to about 13 microns and second particles having a particle size range of from about 1 to about 5 microns. In some embodiments, the first particles have a d50 of from about 2.5 to about 6 microns. In some embodiments, the first particles have a d50 of from 2.5 to 6 microns. In some embodiments, the second particles have a d50 from about 2.2 to about 2.6 microns. In some embodiments, the second particles have a d50 from 2.2 to 2.6 microns.

[0045] In certain embodiments, the first calcium carbonate particles are present in an amount of from about 5 to about 20 wt% based on the total weight of the oral care composition, and the second calcium carbonate particles are present in an amount of from about 5 to about 40 wt% based on the weight of the oral care composition. For example, in certain embodiments, the first calcium carbonate particles are present in an amount of from about 5 to about 15 wt% based on the weight of the oral care composition, and the second calcium carbonate particles are present in an amount of from about 20 to about 30 wt% based on the weight of the oral care composition.

[0046] In certain embodiments disclosed herein, the oral care composition may comprise calcium silicate, in addition to or instead of calcium carbonate. The calcium silicate is in the form of particles of a size such that they are effective to occlude dentinal tubules. Thus, the calcium silicate particles preferably have an average diameter of about 0.5 to about 10 microns, such as from about 1 to about 9 microns or about 2 to about 5 microns, with an average diameter below about 5 microns being most preferred. The calcium silicate may have a surface area of about 20 to about 400 m2 / g and a pore volume of 0.01 to 1 cc / g.

[0047] In oral care compositions disclosed herein that comprise calcium silicate particles, the calcium silicate particles may be present in any amount effective to occlude dentinal tubules. In certain embodiments, the calcium silicate particles are present in an amount of about 1 to about 20 wt%, such as about 5 to about 15 wt% or about 10 wt%, based on the total weight of the oral care composition.

[0048] Suitable calcium silicate particles can be obtained commercially or prepared by known methods. In certain embodiments, the calcium silicate has a high surface area. Although no phosphate pre-treatment is necessary, in certain embodiments, the calcium silicate may be pretreated with phosphate. High surface area calcium silicate may have a surface area greater than 20 m2 / g.

[0049] In addition to the at least one occluding agent selected from calcium carbonate and calcium silicate, which arc abrasives, the oral care composition may further comprise one or more additional abrasives, including but not limited to: a calcium phosphate abrasive (e.g., tricalcium phosphate (Ca3(PO4)2). hydroxyapatite (Caw(PO4)6(OH)2), dicalcium phosphate dihydrate (CaHPO42H2O, also sometimes referred to as DiCai) or calcium pyrophosphate; silica abrasives such as precipitated silicas having a mean particle size of up to about 20 mm (e.g., ZEODENT® 115, marketed by J. M. Huber); sodium metaphosphate; potassium metaphosphate; aluminum silicate; calcined alumina; and bentonite or other siliceous materials. In certain embodiments, the additional abrasive(s) may have an average diameter of about 0.1 to about 30 microns, such as about 5 to about 15 microns.

[0050] In certain embodiments, the oral care composition for use in the methods disclosed herein comprises at least one basic amino acid. In certain embodiments, the basic amino acid is incorporated into a dentifrice composition having a base formulation comprising calcium carbonate, and in particular precipitated calcium carbonate, as an abrasive. L-arginine and arginine salts such as arginine bicarbonate are themselves distinctly bitter in taste, and in aqueous solution can also impart a fishy taste. The addition of L-arginine or arginine salts to a base dentifrice formulation comprising calcium carbonate can provide a significant enhancement of taste and mouthfeel attributes to the dentifrice formulation and to an increase in the overall acceptance of the product to a consumer.

[0051] The basic amino acids that can be used in the compositions and methods disclosed herein include not only naturally-occurring basic amino acids, such as arginine, lysine, serine and histidine, but also any basic amino acids having a carboxyl group and an amino group in the molecule that are water-soluble and provide an aqueous solution with a pH of about 7 or greater.

[0052] Accordingly, basic amino acids suitable for use in the methods disclosed herein include, but are not limited to, arginine, lysine citrulline, ornithine, creatine, histidine, diaminobutanoic acid, diaminoproprionic acid, salts thereof or combinations thereof. In certain embodiments, the basic amino acids are selected from arginine, citrulline and ornithine, and in certain embodiments, the basic amino acid is arginine.

[0053] In certain embodiments, the basic amino acid comprises at least one intermediate produced in an arginine deiminase system. The intermediates produced in the arginine deiminase system may be useful in an oral care composition to provide plaque neutralization for caries control and / orprevention. Arginine is a natural basic amino acid that may be found in the oral cavity. Arginine in the mouth may be utilized by certain dental plaque bacterial strains such as .S'. sanguis, S. gordonii, S. parasanguis, S. rattus, S. milleri, S. anginosus, S. faecalis, A. naeslundii, A. odonolyticus , L. cellobiosus, L. brevis, L. fermenium, P. gingivalis, and T. denticola for their survival. Such organisms may perish in an acidic environment that may be present at areas close to the tooth surface where acidogenic and aciduric cariogenic strains may use sugars to produce organic acids. Thus, these arginolytic strains may break down arginine to ammonia to provide alkalinity to survive and, in addition, buffer the plaque and make a hostile environment for the cariogenic systems.

[0054] Such arginolytic organisms may catabolize arginine by an internal cellular enzyme pathway system called the “arginine deiminase system” whereby intermediates in the pathway are formed. In this pathway, L-arginine may be broken down to L-citrulline and ammonia by arginine deiminase. L-citrulline may then be broken down by ornithane trancarbamylase in the presence of inorganic phosphate to L-ornithine and carbamyl phosphate. Carbamate kinase may then break down carbamyl phosphate to form another molecule of ammonia and carbon dioxide and in the process also forms adenosine 5'-triphosphate (ATP). ATP may be used by the arginolytic bacteria as an energy source for growth. Accordingly, when utilized the arginine deiminase system may yield two molecules of ammonia. It has been found that, in certain embodiments, the ammonia may help in neutralizing oral plaque pH to control and / or prevent dental caries.

[0055] The oral care composition of certain embodiments disclosed herein may include intermediates produced in the arginine deiminase system, such as citrulline, ornithine and / or carbamyl phosphate.

[0056] The oral care composition may include the above-described intermediates in an effective amount. In some embodiments the oral care composition includes about 1 mmol / L to about 10 mmol / L intermediate. In other embodiments, the oral care composition includes about 3 mmol / L to about 7 mmol / L intermediate. In other embodiments, the oral care composition includes about 5 mmol / L intermediate.

[0057] The oral care compositions disclosed herein are intended for topical use in the mouth; therefore, salts should be safe for such use, in the amounts and concentrations provided. Suitable salts include salts known in the art to be pharmaceutically acceptable salts are generally considered to be physiologically acceptable in the amounts and concentrations provided. Physiologicallyacceptable salts include those derived from pharmaceutically acceptable inorganic or organic acids or bases, for example acid addition salts formed by acids, which form a physiological acceptable anion, e.g., hydrochloride or bromide salt and base addition salts formed by bases which form a physiologically acceptable cation, for example those derived from alkali metals such as potassium and sodium or alkaline earth metals such as calcium and magnesium. Physiologically acceptable salts may be obtained using standard procedures known in the art, for example by reacting a sufficiently basic compound such as an amine with a suitable acid affording a physiologically acceptable anion. In certain embodiments, the basic amino acid is partially or wholly in a salt form selected from the group consisting of arginine bicarbonate, arginine hydrochloride, arginine phosphate and combinations thereof. Optionally, the basic amino acid in free or salt form is arginine bicarbonate.

[0058] In certain embodiments, the basic amino acid is present in the oral care composition in an amount of about 0.5 wt% to about 20 wt%, such as from about 5 wt% to about 25 wt%, about 10 wt% to about 25 wt%, about 15 wt% to about 25 wt%, about 18 wt% to about 22 wt%, about 20 wt%, or 19.6 wt%, based on the total weight of the oral care composition.

[0059] In certain embodiments, the oral care composition may include a chemical agent effective to treat or prevent tooth hypersensitivity, such as potassium salts (such as potassium nitrate, potassium bicarbonate, and potassium chloride), strontium salts, zinc salts, and chloride salts. In certain embodiments, such agents may be present in an amount of from about 0.01 to about 10 wt%, such as from about 1 to about 8 wt%, based on the total weight of the oral care composition.

[0060] The oral care compositions may further include one or more fluoride ion sources, e.g., soluble fluoride salts. A wide variety of fluoride ion-yielding materials can be employed as sources of soluble fluoride in the present compositions. Examples of suitable fluoride ion-yielding materials are found, for example, in U.S. Pat. No. 3,535,421, U.S. Pat. No. 4,885,155 and U.S. Pat. No. 3,678,154.

[0061] Representative fluoride ion sources may include, but are not limited to, stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium Iluorosilicate, amine fluoride, ammonium fluoride, and combinations thereof. In certain embodiments, the fluoride ion source includes at least one of stannous fluoride, sodium fluoride, sodium monofluorophosphate, or mixtures thereof.

[0062] In certain embodiments, the oral care composition may also contain a source of fluoride ions or fluorinc-providing ingredient in amounts sufficient to supply about 25-25,000 ppm of fluoride ions, generally at least about 500 ppm, e.g., about 500 to about 2000 ppm, e.g., about 1000 to about 1600 ppm, e.g., about 1450 ppm. The appropriate level of fluoride will depend on the particular application.

[0063] Fluoride ion sources may be added to the oral care composition at a concentration of about 0.01 wt% to about 10 wt%, such as about 0.03 wt% to about 5 wt%, or about 0.1 wt% to about 1 wt%, based on the total weight of the oral care composition. Weights of fluoride salts to provide the appropriate level of fluoride ion will obviously vary based on the weight of the counter ion in the salt. In certain embodiments, the oral care composition is free of or substantially free of a fluoride ion source. In certain embodiments wherein the oral care composition comprises calcium bicarbonate and a fluoride ion source, sodium monofluorophosphate may be preferred to sodium fluoride for stability reasons.

[0064] Another agent optionally included in the oral care composition disclosed herein is a surfactant or a mixture of compatible surfactants. Suitable surfactants are those which are reasonably stable throughout a wide pH range, for example, anionic, cationic, nonionic or zwitterionic surfactants. Non-limiting examples of suitable surfactants are disclosed, for example, in U.S. Pat. No. 3,959,458 to Agricola et al., U.S. Pat. No. 3,937,807 to Haefele, and U.S. Pat. No. 4,051,234 to Gieske et al.

[0065] In certain embodiments, the anionic surfactants useful herein include the water-soluble salts of alkyl sulfates having about 10 to about 18 carbon atoms in the alkyl radical and the water- soluble salts of sulfonated monoglycerides of fatty acids having about 10 to about 18 carbon atoms. Sodium lauryl sulfate, sodium lauroyl sarcosinate and sodium coconut monoglyceride sulfonates are examples of anionic surfactants of this type. Mixtures of anionic surfactants may also be utilized.

[0066] In another embodiment, cationic surfactants that may be used can be broadly defined as derivatives of aliphatic quaternary ammonium compounds having one long alkyl chain containing about 8 to about 18 carbon atoms, such as lauryl trimethylammonium chloride, cetyl pyridinium chloride, cetyl trimethylammonium bromide, di-isobutylphenoxyethyldimethylbenzylammonium chloride, coconut alkyltrimethyl-ammonium nitrite, cetyl pyridinium fluoride and mixtures thereof. Illustrative cationic surfactants include the quaternary ammonium fluorides described, forexample, in U.S. Pat. No. 3,535,421 to Briner et al. Certain cationic surfactants can also act as germicides in the oral care compositions.

[0067] Illustrative nonionic surfactants that can be used in the oral care compositions disclosed herein can be broadly defined as compounds produced by the condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound which may be aliphatic or alkylaromatic in nature. Examples of suitable nonionic surfactants include but are not limited to the PLURONICS® (BASF Corp.), polyethylene oxide condensates of alkyl phenols, products derived from the condensation of ethylene oxide with the reaction product of propylene oxide and ethylene diamine, ethylene oxide condensates of aliphatic alcohols, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides, and mixtures of such materials.

[0068] In certain embodiments, zwitterionic synthetic surfactants useful in the oral care compositions can be broadly described as derivatives of aliphatic quaternary ammonium, phosphonium and sulfonium compounds, in which the aliphatic radicals can be straight chain or branched, and wherein one of the aliphatic substituents contains about 8 to about 18 carbon atoms and one contains an anionic water- solubilizing group e.g., carboxy, sulfonate, sulfate, phosphate or phosphonate. Illustrative examples of the surfactants suited for inclusion in the oral care composition include, but are not limited to, sodium alkyl sulfate, sodium lauroyl sarcosinate, cocoamidopropyl betaine and polysorbate 20, and combinations thereof.

[0069] The surfactant or mixtures of compatible surfactants can be present in the oral care compositions in an amount of about 0.1 to about 5.0 wt%, such as about 0.3 to about 3.0 wt% or about 0.5 to about 2.0 wt%, based on a total weight of the oral care composition.

[0070] The oral care compositions disclosed herein may also include at least one flavoring agent. Flavoring agents that may be used in the practice of the methods disclosed herein may include, but are not limited to, essential oils as well as various flavoring aldehydes, esters, alcohols, and similar materials. Examples of the essential oils include oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Other exemplary flavoring agents may include such chemicals as menthol, carvone, and anethole. Certain embodiments employ the oils of peppermint and spearmint.

[0071] The flavoring agent may be incorporated in certain embodiments of the oral care composition at a concentration of about 0.1 to about 5 wt%, such as about 0.5 to about 1.5 wt%,based on the total weight of the oral care composition. The dosage of flavoring agent in the individual oral care composition dosage (i.c., a single dose) may range from about 0.001 to about 0.05 wt%, such as from about 0.005 to about 0.015 wt%, based on the total weight of the oral care composition.

[0072] The oral care compositions disclosed herein also may optionally include one or more chelating agents able to complex calcium found in the cell walls of the bacteria. Binding of this calcium weakens the bacterial cell wall and augments bacterial lysis.

[0073] A group of compounds suitable for use as chelating agents in the oral care compositions disclosed herein are the soluble pyrophosphates. The pyrophosphate salts used in the present compositions can be any of the alkali metal pyrophosphate salts. In certain embodiments, salts include tetra alkali metal pyrophosphate, dialkali metal diacid pyrophosphate, trialkali metal monoacid pyrophosphate and mixtures thereof, wherein the alkali metals are sodium or potassium. The salts may be useful in both their hydrated and unhydrated forms. An effective amount of pyrophosphate salt useful in the present composition is generally enough to provide at least about 1.0 wt% pyrophosphate ions, e.g., about 1.5 to about 6 wt% or about 3.5 to about 6 wt% of such ions, based on the total weight of the oral care composition.

[0074] The oral care compositions disclosed herein may also optionally include one or more polymers such as polyethylene glycols, polyvinylmethyl ether maleic acid copolymers, and polysaccharides (e.g., cellulose derivatives, such as carboxymethyl cellulose or polysaccharide gums, for example xanthan gum or carrageenan gum). 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.

[0075] Certain embodiments may include 1:4 to 4:1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, for example, methyl vinyl ether (methoxyethylene) having a molecular weight (M.W.) of about 30,000 to about 1,000,000.

[0076] Suitable generally, are polymerized olefinically or ethylenically unsaturated carboxylic acids containing an activated carbon-to-carbon olefinic double bond and at least one carboxyl group, that is an acid containing an olefinic double bond which readily functions in polymerization because of its presence in the monomer molecule either in the alpha-beta position with respect to a carboxyl group or as part of a terminal methylene grouping.

[0077] Illustrative of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, bcta-acryloxy propionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styryl acrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic, 2-benzyl acrylic, 2- cyclohexylacrylic, angelic, umbellic, fumaric, maleic acids and anhydrides. Other different olefinic monomers copolymerizable with such carboxylic monomers include vinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymers contain sufficient carboxylic salt groups for water- solubility.

[0078] A further class of polymeric agents includes a composition containing homopolymers of substituted acrylamides and / or homopolymers of unsaturated sulfonic acids and salts thereof, in particular where polymers are based on unsaturated sulfonic acids selected from acrylamidoalykane sulfonic acids such as 2-acrylamide-2-methylpropane sulfonic acid having a molecular weight of about 1,000 to about 2,000,000, described for example in U.S. Pat. No. 4,842,847 to Zahid.

[0079] Another useful class of polymeric agents includes polyamino acids, particularly those containing proportions of anionic surface-active amino acids such as aspartic acid, glutamic acid and phospho serine, as disclosed in U.S. Pat. No. 4,866,161 to Sikes.

[0080] In preparing oral care compositions, it is sometimes preferable to add some thickening material to provide a desirable consistency or to stabilize or enhance the performance of the formulation. In certain embodiments, the thickening agents may be selected from carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose, and water soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums such as karaya, gum arabic, and gum tragacanth can also be incorporated. Colloidal magnesium aluminum silicate or finely divided silica can be used as component of the thickening composition to further improve the composition’s texture. In certain embodiments, thickening agents in an amount of about 0.1 to about 10.0 wt%, such as about 0.5 to about 5.0 wt%, based on the total weight of the oral care composition, may be used.

[0081] Water may also be present in the oral care compositions disclosed herein. Water employed in the preparation of commercial oral care compositions may be deionized and free of organic impurities. Water may make up the balance of the oral care composition and may constitute about 5 wt% to about 90 wt%, such as about 20 wt% to about 60 wt% or about 10 wt% to about 30 wt%, by weight of the oral care composition. This amount of water includes the free water which isadded plus that amount which is introduced with other materials such as with sorbitol or any components of the composition.

[0082] Within certain embodiments of the oral care compositions, it is also possible to incorporate a humectant to prevent the composition from hardening upon exposure to air. Certain humectants can also impart desirable sweetness or flavor to oral care compositions. The humectant, on a pure humectant basis, may comprising about 15 to about 70 wt%, such as about 30 to about 65 wt% of the oral care composition, by weight based on the total weight of the oral care composition.

[0083] Suitable humectants include edible polyhydric alcohols, such as glycerine, sorbitol, xylitol, propylene glycol, as well as other polyols and mixtures of these humectants. Mixtures of glycerin and sorbitol may be used in certain embodiments as the humectant component of the oral care composition disclosed herein.

[0084] The oral care compositions disclosed herein may be made according to methods and procedures known to those skilled in the art.

[0085] In one illustrative embodiment, the oral care composition is made by neutralizing or partially neutralizing arginine in a gel phase with an acid, e.g., phosphoric acid, hydrochloric acid or carbonic acid, and mixing to form a first mixture. Actives such as, for example vitamins, CPC, fluoride, abrasives (including occlusive agent(s)), and any other desired active ingredients are added to a first mixture and mixed to form a second mixture. Where the final product is an oral care composition such as a dentifrice, a dentifrice base, for example, dicalcium phosphate precipitated calcium carbonate and / or silica, may be added to the second mixture and mixed. The final slurry is formed into an oral care composition product.Electrochemical Oral Care Device

[0086] In embodiments disclosed herein, there is provided an electrochemical oral care device, such as an electrochemical tray, designed for use in the methods disclosed herein. In certain embodiments, the oral care devices disclosed herein may be embodied as strips or patches capable of being completely retained within the oral cavity to provide a benefit to the oral cavity, such as preventing or reducing dental hypersensitivity. In certain exemplary embodiments, the oral care device may be a device such as those disclosed in U.S. Patent Publication No. 2017 / 0189153, the entire contents of which are incorporated herein by reference.

[0087] Figure 1 illustrates an exemplary oral care device 100 or a section of an oral care device according to implementations of this disclosure. More specifically, FIG. 1. is a schematicillustration of a plurality of layers or substrates that are stacked or otherwise disposed together to form the device 100. In embodiments of this disclosure, the device 100 is embodied as a strip or patch sized for placement in the oral cavity, although it is understood that the device 100 may take the form of a tray, a mouth guard, a wand, or any other form suitable for use according to the methods disclosed herein. The device 100 is illustrated in FIG. 1 as having a generally rectangular shape, but this disclosure is not limited to rectangular forms. For example, the size and / or shape of the footprint of the device 100 may be varied depending upon such factors as the application, desired aesthetics, or manufacturability concerns. In certain embodiments, the strip may be between about 1 mm and about 5 mm thick, such as about 1.5 mm to about 3 mm thick. The reduced thickness may result in more comfort for a user of the device, and may promote flexure or bending of the device, e.g., to better conform to the contours of the oral cavity.

[0088] As illustrated, the oral care device 100 includes a base layer 102, a power source 104, and an electrode layer 106. An optional active layer 112, an adhesive layer 114 and a release layer 116 also are illustrated in phantom lines in FIG. 1. One or more of these layers may be included in various embodiments of this disclosure.

[0089] The base layer 102 is preferably a thin, flexible substrate. As used herein, the term flexible means capable of being bent, without breaking, by manual manipulation to conform to various features of a user’s oral cavity. The substrate may be made from any number of orally acceptable materials, including but not limited to, textiles, cloth, wood composite, resin, elastomer, paper, insoluble or less soluble cellulose derivatives such as ethyl cellulose and cellulose acetate, polyvinyl chloride, wax, PARAFILM®, polyethylene, polyvinyl alcohol, TEFLON®, polyvinyl chloride, polyvinyl acetate and their derivatives. In some instances, the flexible substrate may also or alternatively include a water-soluble polymer to promote adhesion of the device 100 to the teeth or gums. For example, the base layer 102 may include hydrophilic cellulose ethers (e.g. carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose), polyvinyl acetates, carbomers (e.g., CARBOPOL® 97 IP), polysaccharide gums (e.g., xanthan gum), modified food starches, gelatin (e.g., animal or fish-based gelatin), cross-linked carboxyvinyl copolymers, cross-linked polyvinylpyrrolidones, polyethylene oxide (e.g., Polyox), polyacrylic acids and poly acrylates, polyvinyl alcohols, alginate, casein, pullulan, and combinations thereof.

[0090] The power source 104 may be disposed on the base substrate 102, and may be a battery. The power source may be single use or rechargeable. Although several types of batteries, includingbutton and coin batteries, may be used in accordance with principles of this disclosure, in some embodiments the power source 104 comprises a flexible power source, such as a polymer battery . Polymer batteries may be preferred for their thin profile and / or their flexibility. For instance, polymer batteries may be as thick as 750 microns, or thinner. The power source 104 may be a printed battery such as a battery commercially available from Imprint Energy, Inc. of Alameda, Calif. The printed battery may include zinc screen-printed on a flexible substrate, for example.

[0091] In some embodiments, the power source 104 may be adhered to the base substrate using any known adhesive, epoxy, or the like. Alternatively, the power source 104 may include the base substrate 102. For example, some commercially available polymer batteries generally include components printed on a substrate. When such a commercially available battery is used in embodiments of this disclosure, the substrate of the battery may also act as the base substrate 102.

[0092] The electrode layer 106 generally includes a pair of electrodes 108 disposed on an electrode substrate 110. As illustrated, the electrodes 108 may include two spaced-apart conductive strips functioning as an anode and a cathode with applied current. The electrodes 108 are substantially parallel and extend generally longitudinally, i.e., parallel to a longitudinal axis 118 of the device 100. The electrodes are sufficiently thin that they can bend with, e.g., without delaminating from, the base layer 102 and the electrode substrate. The electrodes 108 may be printed or otherwise formed on the electrode substrate 110 and may comprise any number of materials including, but not limited to, tin, silver, copper, platinum, and the like. The materials comprising the electrodes may be chosen for their flexibility, as well as for their compatibility with the environs of the oral cavity. In some embodiments, at least one of the electrodes may be formed from a sacrificial material, such as a sacrificial metal. For example, an electrode made of zinc will oxidize upon application of current, thereby releasing Zn2+. These zinc ions are recognized as effective anti-bacterial agents.

[0093] The electrodes 108 are attached to terminals of the power source 104. In some embodiments, the electrode 108 may be connected to the power source 104 using leads or similar conductors. In still other embodiments, the electrode layer 106 may be affixed on the power source 104 in such a manner as to create an electrical communication between the electrode 108 and the power source 104. In still other embodiments, the power source 104 and the electrodes 108 may be disposed on a common substrate, such as the base substrate 102 or the electrode substrate 110.

[0094] Although two electrodes 108 are illustrated in FTG. 1 , additional electrodes 108 may also be provided. For example, the electrodes may be positioned and numbered generally to correspond with a location and number of a user’s teeth.

[0095] The device 100 comprising the base substrate 102, the power source 104, and the electrode layer 106 may form a complete oral care device 100. In operation, the oral care device 100 may be placed in a user’s oral cavity and current is passed through the electrodes 108 to provide an electrochemical benefit in the oral cavity. As discussed above, the benefit may constitute a reaction with an active agent or active substance also provided in the oral cavity, e.g., the oral care compositions as disclosed herein. In one example, the electrode may be used to activate the at least one occluding agent to move to exposed dentin tubules. The oral care composition disclosed herein comprises the active substance or active agent, e.g., at least one occluding agent, and may be in the form of a gel or paste comprising an electrically conductive medium to the teeth or otherwise in the oral cavity. For example, in some embodiments, an effective amount of an oral care composition comprising the at least one occluding agent and at least one basic amino acid in an electrically conductive medium may be applied to the teeth, and (just before or during application) the composition is exposed to an electric potential so as to facilitate movement of the at least one occluding agent (e.g., calcium carbonate) to exposed dentin tubules, thereby occluding the dentin tubules.

[0096] Carbonates, including calcium carbonate and arginine bicarbonate which may be present in the oral care composition disclosed herein, are one type of inert salts that can be activated by the electrical field in embodiments of this disclosure, e.g., to provide a benefit such as occluding dentin tubules. Other types of inert salts may include sulfates, chlorides, or phosphates.

[0097] While the device 100 may be complete with the base substrate 102, the power source 104 and the electrode layer 106, as illustrated in FIG. 1, one or more optional components may also be included. For example, the device 100 may further include the active layer 112. The active layer may include the oral care composition disclosed herein. Thus, while the user can apply the oral care composition separately, the active layer may incorporate the oral care composition into the device 100. The oral care composition may be applied to the electrode layer 106 directly, such as by deposition, printing, painting or other known techniques. Alternatively, the active layer 112 may further include an active layer substrate that is designed to hold the oral care composition. In some examples, the active layer substrate may be a water-soluble polymer, whichcarries the oral care composition and may promote adhesion of the oral care composition to other layers of the device.

[0098] The device 100 may also or additionally include an adhesive layer 114, to promote retention of the device 100 in a desired position in the oral cavity. The adhesive layer may include any conventional orally-compatible, releasable adhesive. For example, water-soluble polymers, noted above as an example of an active layer substrate, may also be used as an adhesive in the present disclosure. As illustrated in FIG. 1, the adhesive layer 114 may have the same general footprint as the other components making up the strip. As a result, the entire strip may include adhesive. In other embodiments, less adhesive may be included. For example, only portions of the footprint of the strip may be adhesive. For instance, adhesive may be provided only at longitudinal ends of the strip, with the strip being applied much like other commercially available bandages. In other implementations, adhesive may be applied about the periphery of the strip and in still other embodiments, the adhesive layer may include a plurality of adhesion points or regions.

[0099] The oral care device 100 may also include a release layer 116. The release layer 116 may be a removable member disposed over components of the device 100, for example to prevent contamination of the oral care device 100 prior to insertion into the mouth. The release layer 116 illustrated in FIG. 1 comprises a thin sheet of flexible material, e.g., a polymeric material, that a user peels off to reveal the electrode layer, active layer, and / or adhesive layer, depending upon the construction of the device 100. When the adhesive layer 114 is present, for example, the release layer will ensure that the adhesive remains tacky until the device 100 is to be used. Although the release layer 116 is shown as a single layer, in other embodiments the release layer may instead take the form of an envelope or complete package, e.g., for completely retaining the oral care device 100 therein.

[0100] In some embodiments, the release layer 116 may also control activation of the device 100. For example, the release layer may include a physical obstruction that prevents electrical communication between the power source 104 and the electrode 108. Removing the release layer will also remove this obstruction, thereby allowing current to flow from the power source to the electrode 108. In other implementations, removal of the release layer 116 may be detected, e.g., using a presence / absence sensor, and the output from that sensor may trigger powering-up of the device.

[0101] Although not illustrated, the device 100 may also include control circuitry or similar features to control the electrical circuit created by the power source 104 and the electrode 108. For example, the control circuitry may alternate the polarity of the electrodes during use. Alternating the polarity may prevent accumulation of charged particles or ions on the electrodes. The control circuitry may also be programmed to control an amount of current supplied to the electrode 108. The control circuitry may also include a power-up function, or the like, to activate the power source when the device is ready for use. The control circuitry may include a manual switch as part of the power-up function, such as a toggle or push button switch. Moreover, as discussed above, the release layer could also be integrated into the power-up function, e.g., such that removal of the release layer powers up the device. In other embodiments, the control circuitry may include sensor outputs. For example, a conventional presence / absence sensor could be disposed to be covered by the release layer, and detect removal of the release layer. This detection could then be used to turn on the device. In another embodiment, a water- or liquid moisture-detecting sensor may be provided. When the sensor comes in contact with saliva, i.e., upon being inserted into the mouth, the power source is turned on. The control circuitry could be provided on a separate layer, or could be integrated into another layer. For example, it may be desirable to incorporate the control circuitry into the electrode layer, the base layer, and / or the power source layer.

[0102] As will be appreciated, the oral care device 100 is generally a thin, flexible device capable of simple insertion into the oral cavity. Depending upon the benefit to be achieved from the device, the device may be placed over one or more teeth, on the gums, on the inside of the cheek, and / or on or under the tongue. In certain embodiments, it may be desirable to situate the electrodes as close to the teeth as possible. Because the device is flexible, in some examples the device can be folded, for example, proximate the longitudinal axis 118, such that device can be placed around one or more teeth with one of the electrodes 108 in front of the tooth / teeth and the other of the electrodes 108 disposed behind the tooth / teeth. In this manner, the electrical field generated at the electrodes 108 would pass through the tooth / teeth disposed between the spaced electrodes 108. This arrangement disposes the electrodes in intimate contact with the teeth. Such an arrangement may also be beneficial to drive ions, such as Fl- or Ca2+ions, into the tooth enamel.

[0103] Thus, in some embodiments, this disclosure provides a complete, electrode-based oral care device capable of providing benefit to the oral cavity without the need for external (to the oral cavity) components. The overall thickness of the device 100 is preferably less than about 2 mm.

[0104] Moreover, the flexible device described herein may be used in connection with an additional structure. For example, the device may be placed in a more rigid form, such as a tray or mouth guard. In certain embodiments, the device may be used in connection with a wand, such that the wand may be held by the user or by another individual (e.g., a dental professional) and applied to areas of the oral cavity in need to treatment. In certain embodiments, the tray, wand, or mouth guard may comprise two sections, with one designed to fit the bottom teeth and one designed to fit the top teeth. In certain embodiments, the tray, wand, or mouth guard may comprise a single section designed to fit top teeth or bottom teeth. In certain embodiments, the tray, wand, or mouth guard may be designed to fit the entirety of the top or the bottom teeth, and in certain embodiments, the tray, wand, or mouth guard may be design to fit only a portion, e.g., one half or one quarter of the top or the bottom teeth. In this manner, the device, in whatever form, may be kept in close proximity to the teeth, for example. The use of a tray, wand, or mouth guard may obviate the need for an adhesive in some instances.Methods

[0105] Disclosed herein are methods of using the oral care composition together with the electrochemical oral care device, e.g., in a method of reducing or preventing dental hypersensitivity. In certain embodiments, the method comprises applying an oral care composition as disclosed herein to a surface (e.g., the teeth) in the oral cavity and contacting the oral care composition with the electrochemical oral care device disclosed herein; then, an electrical current can be applied to the electrochemical oral care device to activate the oral care composition on the surface.

[0106] In certain embodiments, an electrochemical oral care device as disclosed herein is provided to a subject, e.g., a subject in need of treatment for dental hypersensitivity. The electrochemical oral care device is placed in the oral cavity of the subject, proximate a portion of the oral cavity to be treated. When reducing dental hypersensitivity is the desired objective, the device 100 is preferably placed in intimate contact with the tooth or teeth to be treated. The method may include bending or folding the electrochemical oral care device to promote this intimate contact, e.g., in the manner described above, or the method may include inserting a tray, wand, or mouth guard containing the electrochemical oral care device into the oral cavity of the subject. In certain embodiments, the adhesive layer 114 described above may be provided to promote placement and retention of the device 100 at the desired location in the oral cavity and / or in the tray, wand, ormouth guard. Next, the electrochemical oral care device is activated, to allow current to flow through the electrodes and obtain the desired electrochemical benefit.

[0107] In certain embodiments disclosed herein, when activated, the electrodes of the electrochemical oral care device apply a charge of less than about 20 volts, such as less than about 15 volts, or about 10 volts or less. In certain embodiments, the electrodes of the electrochemical oral care device apply a charge of greater than about 2 volts, such as about 3 volts, about 4 volts, about 5 volts, about 6 volts, about 7 volts, about 8 volts, about 9 volts, or about 10 volts. In certain embodiments, the electrodes of the electrochemical oral care device apply a charge ranging from about 2 to about 20 volts, such as from about 3 to about 15 volts or about 5 to about 10 volts.

[0108] In certain embodiments of the methods disclosed herein, the electrical charge from the electrochemical oral care device is applied to the oral care composition in contact with the oral cavity (e.g., the surface of the teeth) for at least about 3 minutes, such as at least about 4 minutes, at least about 5 minutes, at least about 6 minutes, at least about 7 minutes, at least about 8 minutes, at least about 9 minutes, or at least about 10 minutes. In certain embodiments, the electrical charge is applied for about 3 to about 20 minutes, such as from about 5 to about 15 minutes or about 10 minutes.

[0109] The methods disclosed herein may include additional steps, such as introducing the oral care composition into the oral cavity. The oral care composition may be provided as part of the device, or may be applied separately, as described herein. The steps of the methods disclosed herein may be repeated, in whole or in part, multiple times. For example, in certain embodiments, the steps of the method are repeated twice, three times, four times, or five times. In certain embodiments, the steps of the method are repeated more than five times. The steps of the method may be repeated multiple times over the course of one treatment, i.e., during the same hour or the same day. Alternatively or additionally, the steps of the method may be repeated multiple times over the course or multiple treatments. For example, in certain embodiments, the steps of them method are repeated twice over the course of a single treatment, e.g., within one hour. In certain embodiments, the method may be repeated for multiple treatments, e.g., wherein the treatment cycles are spaced apart by at least about 2 hours, such as at least about 8 hours, at least about 12 hours, at least about 24 hours, at least about 1 week, at least about 2 weeks, at least about 3 weeks, or at least about 1 month.

[0110] In certain embodiments of the methods disclosed herein, the method occludes at least about 5% of exposed dentin tubules, such as at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50% of exposed dentine tubules. In certain embodiments, the method occludes about 5% to about 50% of exposed dentin tubules, such as about 5% to about 45%, about 5% to about 40%, about 5% to about 35%, about 5% to about 30%, about 5% to about 25%, about 5% to about 20%; about 10% to about 50%, about 10% to about 45%, about 10% to about 40%, about 10% to about 35%, about 10% to about 30%, about 10% to about 25%, or about 10% to about 20%.

[0111] In certain embodiments of the methods disclosed herein, the method reduces dental hypersensitivity in the subject by at least about 5%, such as at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, or at least about 85%. Hypersensitivity or a reduction in hypersensitivity may be measured by any means known in the art, including known in vivo or in vitro methodologies.

[0112] Other modifications, combinations, enhancements and benefits will be appreciated by those having ordinary skill in the art, with the benefit of this disclosure.EXAMPLESExample 1

[0113] A gel formulation was prepared containing:2% hydroxyethylcellulose;34% calcium carbonate;19.6% arginine bicarbonate; and44.4% deionized water.

[0114] Experiments were then conducted to determine the optimal working conditions to minimize treatment time and maximize the percentage of occluded dentin tubules using the formulation together with an electrochemical tray device. First, dentin occlusion was measured after applying 3 volts, 5 volts, and 7 volts of current to the formulation for 10 minutes for one cycle. Next, another test was performed by applying 5 volts of current to the formulation for either 3 minutes or 10minutes. Finally, 5 volts of current was applied to the formulation for 10 minutes for a total of 4 treatment cycles.

[0115] Whole human molars were cut laterally to produce 700 pm thick slices. The slices were then polished, cleaned by sonication, and acid etched in a 1% citric acid solution for 30-45 seconds. The dentin slices were then sonicated in deionized water to clean the surfaces. The prepared dentin slices were imaged under a Leica confocal microscope to determine the baseline area of the open tubules.

[0116] The disks were then treated through the following steps. A fresh batch of the formulation containing arginine bicarbonate and calcium carbonate in HEC was made and placed into a tray. The slices of dentin were placed 2-4 mm away from the negatively charged stainless steel electrode with the desired treatment side facing the electrode. Depending on the test, a potential of either 3 volts, 5 volts, or 7 volts was applied for 3 minutes or 10 minutes before taking the dentin slices out and removing the formulation by gently rinsing the surface with deionized water. Once the gel was removed, the dentin was placed in a phosphate buffer solution and stirred for 15 minutes. The dentin was then rinsed again with deionized water and gently dried with a Kimwipe. The process was repeated for experiments with multiple treatment cycles. The dentin slices were imaged using the confocal microscope after the treatment to measure the percentage of dentin tubule occlusion.

[0117] Varying the voltage: For this experiment, two slices of dentin with a total of 10 sample areas were selected for samples tested at 3 volts (Dentin A and Dentin E); two dentin slices with 11 sample areas were used for testing at 5 volts (Dentin G and Dentin H), and three dentin slices with 18 sample areas were used for testing at 7 volts (Dentin J, Dentin K, and Dentin N). The percent occlusion across all the points were averaged for each group and are listed in Tables 1-3 below.

[0118] Table 1 - Occlusion at 3 volts

[0119] Table 2 - Occlusion at 5 volts

[0120] Table 3 - Occlusion at 7 volts

[0121] As shown in the data above and in the graph of Figure 2, when a lower voltage was applied (3 volts) for ten minutes, the average dentin occlusion was lower than when 5 volts was applied for the same period of time. Increasing the voltage from 3 volts to 5 volts increased the occlusion by a factor of about 4. However, as the voltage was increased further to 7 volts, there was not another significant increase in the measured occlusion. The occlusion of the dentin tubules at 5 volts and 7 volts remained similar at about 22% and about 21%, respectively. From these results, it is shown that a voltage tray may be set at about 5 volts to maximize the overall occlusion while minimizing the overall treatment time.

[0122] Varying the treatment time: Three dentin slices with a total of 16 sample areas and two dentin slices with a total of 11 different sample areas were imaged and processed for the 3 minute and 10 minute groups, respectively. The percent occlusion across all the points were averaged for each group and are listed in Tables 4 and 5 below.

[0123] Table 4 - Occlusion at 5 volts for 3 minutes

[0124] Table 5 - Occlusion at 5 volts for 10 minutes

[0125] Images were collected at each point after every treatment cycle using the Leica confocal microscope and the open tubule area was calculated to determine the occlusion percentage compared to the initial baseline. As shown in Figure 3, when the samples were treated at 5 volts for three minutes, the average dentin occlusion was measured at about 10%; however, when the treatment time was increased to 10 minutes, the occlusion across the samples increased to about 22%. Therefore, it can be concluded that the ability for the electrochemical tray to deposit the calcium carbonate from the formula into the dentin tubules is partially dependent on the overall treatment time.

[0126] Multiple treatment cycles: Two dentin slices with a total of 11 different sample areas were imaged and processed after each of four treatment cycles. The percent occlusion across the 11 sample areas was averaged for each cycle. The results from the first treatment cycle are shown above in Table 5, and the results from the second, third, and fourth treatment cycles are provided in Tables 6-8 below.

[0127] Table 6 - Occlusion at 5 volts for 10 minutes, Second treatment cycle

[0128] Table 7 - Occlusion at 5 volts for 10 minutes, Third treatment cycle

[0129] Table 8 - Occlusion at 5 volts for 10 minutes, Fourth treatment cycle

[0130] Images were collected at each point after every treatment cycle using the Leica confocal microscope, and the open tubule area was calculated to determine the occlusion percentage compared to the initial baseline. As shown in Figure 4, it was observed that the greatest increase in occlusion occurred after the initial treatment, from 0 to about 22%. Subsequent treatments lead to smaller increases of about 2-3% on top of the previous result. After 4 treatment cycles, the overall average occlusion was measured at about 29%. Using the electrochemical tray tray formultiple treatment cycles was shown to provide an average of about 29% occlusion on an exposed dentin surface.

Claims

CLAIMSWhat Is Claimed Is:

1. A method of reducing or preventing dental hypersensitivity in a subject in need thereof, the method comprising: providing an electrochemical oral care device comprising a flexible base substrate, a power source disposed on a side of the base substrate, a first electrode and a second electrode to a surface of the oral cavity of the subject; contacting an oral care composition for reducing or preventing dental hypersensitivity to the surface of the oral cavity of the subject and to the first electrode or the second electrode; and applying an electrical charge from the electrochemical oral device to the oral care composition.

2. The method of claim 1, wherein the oral care composition is applied to the electrochemical oral care device prior to contacting the oral care composition to the surface of the oral cavity of the subject.

3. The method of claim 1, wherein the oral care composition is applied to the oral cavity of the subject prior to contacting the oral care composition to the first electrode or the second electrode.

4. The method of any one of the preceding claims, wherein the oral care composition comprises at least one occluding agent.

5. The method of claim 4, wherein the at least one occluding agent is calcium carbonate.

6. The method of any one of the preceding claims, wherein the oral care composition comprises at least one basic amino acid.

7. The method of claim 6, wherein the at least one basic amino acid is arginine bicarbonate.

8. The method of any one of the preceding claims, wherein the electrochemical oral care device is in a mouth guard, a wand, or a tray designed to fit in the oral cavity of the subject.

9. The method of any one of the preceding claims, wherein the electrical charge is at least about 3 volts, preferably at least about 5 volts.

10. The method of any one of the preceding claims, wherein the electrical charge is less than about 10 volts, preferably about 5 volts.

11. The method of any one of the preceding claims, wherein the electrical charge is applied for at least about 5 minutes, preferably at least about 10 minutes.

12. The method of any one of the preceding claims, wherein the electrical charge is applied for about 10 minutes.

13. The method of any one of the preceding claims, wherein the steps of the method are repeated at least twice.14 The method of any one of the preceding claims, wherein the method occludes at least about 10% of exposed dentin tubules, such as at least about 15%, at least about 20%, or at least about 25% of exposed dentine tubules.

15. A kit comprising: an electrochemical oral care device comprising a flexible base substrate, a power source disposed on a side of the base substrate, a first electrode and a second electrode; an oral care composition for reducing or preventing dental hypersensitivity; and instructions for use.

16. The kit of claim 15, wherein the oral care composition comprises at least one occluding agent.

17. The kit of claim 16, wherein the at least one occluding agent is calcium carbonate.

18. The kit of any one of claims 15-17, wherein the oral care composition comprises at least one basic amino acid.

19. The kit of claim 18, wherein the at least one basic amino acid is arginine bicarbonate.

20. The kit of any one of claims 15-19, wherein the electrochemical oral care device is in a mouth guard, a wand, or a tray designed to fit in the oral cavity of the subject.

21. The kit of any one of claims 15-20, wherein the first and second electrode apply an electrical charge of at least about 3 volts, preferably at least about 5 volts.

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