WO2018106666A1

WO2018106666A1 - Oral care copolymers and compositions and methods for use

Info

Publication number: WO2018106666A1
Application number: PCT/US2017/064672
Authority: WO
Inventors: Surya Kamin; Karyn B. Visscher; Sounak SARKAR; Fu Chen
Original assignee: Isp Investments Llc
Priority date: 2016-12-05
Filing date: 2017-12-05
Publication date: 2018-06-14

Abstract

The present invention provides copolymers for use in oral care. The invention further provides compositions and methods, employing the copolymers, for oral care treatment. The compositions and methods are especially useful for treating and protecting teeth against erosion. Specifically, the present invention provides random copolymers comprising (a) a first monomer comprising an acidic functionality; (b) a second monomer comprising a hydrophobic acrylate functionality; and (c) a third monomer comprising a compatibilizing agent. The copolymers may have the structure set out below: (i) wherein R, R₁, R₂, R₃, n, p, w, x, and y are defined herein. The present invention further provides compositions and methods, employing the copolymers, for treating and protecting teeth against erosion.

Description

ORAL CARE COPOLYMERS AND COMPOSITIONS AND METHODS FOR USE

FIELD OF THE INVENTION

[001] The present invention provides copolymers for use in oral care. The invention further provides compositions and methods, employing the copolymers, for oral care treatment. The compositions and methods are especially useful for treating and protecting teeth against erosion. Specifically, the present invention provides random copolymers comprising (a) a first monomer comprising an acidic functionality; (b) a second monomer comprising a hydrophobic acrylate functionality; and (c) a third monomer comprising a compatibilizing agent.

BACKGROUND OF THE INVENTION

[002] Dental erosion is the permanent loss of tooth material from the surface of the tooth caused by the action of chemicals such as harsh abrasives and acids. Teeth have an inner dentin layer and an outer protective hard enamel layer. This hard enamel layer is formed of porous hydroxyapatite mineral crystals. This porous hydroxyapatite mineral layer can be permeated by acidic substances to erode the teeth.

[003] Dental erosion may be caused by extrinsic or intrinsic factors. Extrinsic erosion is the result of oral consumption of dietary acids such as acidic beverages or fruit juices and environmental factors such as exposure to airborne contamination or acidic water. Intrinsic erosion is caused by endogenous acids produced in the stomach, which contact the teeth during the processes of vomiting, regurgitation, or reflux.

[004] Acidic beverages are the main cause in the initiation and progression of dental erosion.

[005] Oral care compositions are disclosed in CA 2,808, 332A1, U.S. patent no. 6,300,409B2, U.S. patent publication 2013/0059766A1, and Polymer, vol. 25, (1984) pp. 1600-1602.

[006] Accordingly, there is a continuing need for improved oral compositions and methods that provide immediate as well as sustained protection against dental erosion. SUMMARY OF THE INVENTION

[007] The present invention provides random copolymers comprising (a) a first monomer comprising an acidic functionality; (b) a second monomer comprising a hydrophobic acrylate functionality; and (c) a third monomer comprising a compatibilizing agent.

[008] The present invention also provides copolymers having the structure set out below:

[009] wherein R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; m ranges from 0 to 5; n ranges from 0 to about 23; and p is equal to or greater than 1 ; wherein w, x, and y are molar percentages, the sum of which is 100%.

[0010] The present invention also provides copolymers further comprising a fourth monomer comprising a vinyl or acrylate functionality and a primary, secondary, tertiary alkyl amine, or lactamic functionality.

[0011] The present invention also provides copolymers having the structure set out below:

[0012] wherein R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; R₄ is -O- or -NH; R5 is -2-pyrrolidone -CH(CH3)2 or -NR"₂, wherein R" is hydrogen, methyl, or ethyl; m ranges from 0 to 5; n ranges from 0 to about 23; p is >1; q ranges from 0 to 3; and wherein w, x, y, and z are molar percentages, the sum of which is 100%.

[0013] The present invention further provides compositions and methods, employing the copolymers, for treating and protecting teeth especially against erosion.

DETAILED DESCRIPTION OF THE INVENTION

[0014] The present invention provides random copolymers comprising (a) a first monomer comprising an acidic functionality; (b) a second monomer comprising a hydrophobic acrylate functionality; and (c) a third monomer comprising a compatibilizing agent. The present invention further provides compositions and methods, employing the copolymers, for treating and protecting teeth especially against erosion.

[0015] All percentages, parts, proportions, and ratios as used herein are by weight of the total composition, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level and therefore do not include solvents or by-products that may be included in commercially available materials, unless otherwise specified.

[0016] All references to singular characteristics or limitations of the present invention shall include the corresponding plural characteristics or limitations, and vice-versa, unless otherwise specified or clearly implied to the contrary by the context in which the reference is made.

[0017] Numerical ranges as used herein are intended to include every number and subset of numbers contained within that range, whether specifically disclosed or not. Further, these numerical ranges should be construed as providing support for a claim directed to any number or subset of numbers in that range.

[0018] All publications, articles, papers, patents, patent publications, and other references cited herein are hereby incorporated herein in their entireties for all purposes to the extent consistent with the disclosure herein.

[0019] As used herein, the following terms, unless otherwise stated, have the meanings set out below. [0020] The term "a" or "an", when used in conjunction with the term "comprising", may mean "one" but it is also consistent with the meaning of "one or more," "at least one," and "one or more than one." The use of the term "or" is used to mean "and/or" unless explicitly indicated to refer to alternatives only if the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and "and/or."

[0021] The term "about" refers to a difference of 10% from the value specified. Numerical ranges as used herein are meant to include every number and subset of numbers enclosed within that range, whether particularly disclosed or not. All percentages, parts, proportions, and ratios, as used herein, are by weight of the total composition, unless otherwise specified.

[0022] The term "acidic conditions" refers to conditions relating to the pH value of an aqueous solution. Pure water is considered to be neutral, with a pH close to 7.0 at 25°C. Solutions with a pH value less than 7 are considered to be acidic solutions.

[0023] The term "alkyl" refers to a functionalized or unfunctionalized monovalent straight- chain, branched-chain or cyclic C1-C60 group optionally having one or more heteroatoms. Particularly, an alkyl is a C1-C45 group and more particularly, a C1-C30 group. Particular, yet non-limiting examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, i<?ri-butyl, cyclobutyl, n-pentyl, isopentyl, cyclopentyl, n-hexyl, cyclohexyl, n- heptyl, cyclyheptyl, methylcyclohexyl, n-octyl, 2-ethylhexyl, i<?ri-octyl, ώο-norbornyl, n- dodecyl, i<?ri-dodecyl, n-tetradecyl, n-hexadecyl, n-octadecyl, and n-eicosyl.

[0024] The term "alkyl (alk) acrylate" refers to an alkyl ester of an acrylic acid or an alkyl acrylic acid.

[0025] The term "alkyl (alk) acrylamide" refers to an alkyl amide of an acrylic acid or an alkyl acrylic acid.

[0026] The term "alkylene" refers to a functionalized or unfunctionalized divalent straight- chain, branched-chain or cyclic C1-C40 group optionally having one or more heteroatoms. Particularly, an alkylene is a C1-C45 group and more particularly, a C1-C30 group. Particular, yet non-limiting examples of alkylene groups include -CH₂- -CH2-CH2-, -CH(CH3)-CH₂- -CH₂-CH(CH₃)-, -C(CH₃)2-CH₂-, -CH₂-C(CH₃)₂-, -CH(CH₃)-CH(CH₃)-, -C(CH₃)₂- C(CH₃)2- -CH₂-CH₂-CH₂- -CH(CH₃)-CH₂-CH₂- -CH₂-CH(CH₃)-CH₂- -CH2-CH2- CH(CH₃)-, -CH2-CH2-CH2-CH2-, -CH2-CH2-CH2-CH2-CH2-, -CH2-CH2-CH2-CH2- CH2-CH2-, -CH2-CH2-CH2-CH2-CH2-CH2-CH2-, cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, and the like.

[0027] The term "amphiphilic" refers to chemical compounds possessing both hydrophilic (water-loving, polar) and hydrophobic (water repelling, fat-loving, lipophilic, non-polar) properties. Examples of charged hydrophilic groups include anionic groups (negatively charged) such as carboxylates, sulfates, sulfonates, and phosphates and cationic groups (positively charged) such as ammoniums. Examples of uncharged hydrophilic groups include alcohols with large alkyl groups such as diacyl glycerol and oligoethylene glycols. Amphiphilic compounds may have several hydrophilic and hydrophobic parts within the compound.

[0028] The term "aryl" refers to a functional group derived from an aromatic hydrocarbon. The aromatic hydrocarbon can be mononuclear or polynuclear. Examples of aryl group of the mononuclear type include phenyl, tolyl, xylyl, mesityl, cumenyl, and the like. Examples of aryl group of the polynuclear type include naphthyl, anthryl, phenanthryl, and the like. The aryl group can have at least one substituent selected from halogen, hydroxy, cyano, carboxy, carbamoyl, nitro, amino, aminomethyl, lower alkyl, lower alkoxy, mercapto, trichloroethyl, or trifluoromethyl. Examples of such substituted aryl groups include 2- fluorophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-methoxyphenyl, 4-hydroxyphenyl, and the like.

[0029] The term "branched and unbranched alkyl groups" refers to alkyl groups, which may be straight chained or branched. For example, the alkyl groups have from 1 to about 60 carbon atoms, more particularly, from 1 to about 30 carbon atoms, and yet more particularly from 1 to about 6 carbon atoms. Branched groups include isopropyl, feri-butyl, and the like.

[0030] The term "buffering agent" refers to a weak acid or weak base. Buffering agents are usually added to water to form a buffer solution, which only slightly changes its pH in response to other acids and bases being combined with it, particularly a strong acid or a strong base. Buffering agents have variable properties, some are more soluble than others; some are acidic while others are basic. As pH managers, they are important in many chemical applications, including agriculture, food processing, biochemistry, medicine, and photography.

[0031] The term "compatibilizing agent" refers to an agent that will, when added to an immiscible blend of monomers, increase their stability. Compatibilizing the polymers makes a more stable morphology by creating interactions between the two previously immiscible polymers. The respective portions of the copolymer are able to interact with the two phases of the blend to make the phase morphology more stable. The increased stability is caused by reducing the size of the phase-separated particles in the blend. The size reduction comes from the lower interfacial tension, due to accumulating block copolymers at the many interfaces between the two copolymers. These phase separated particles will not be as inclined to consolidate and grow because the interfacial tension is now much lower. This stabilizes the polymer blend to be a usable product. The compatibilizing agent is present in an amount sufficient to act as a synthesis and formulation aid and render solubility, dispersibility, and surface activity to the copolymer in aqueous and anhydrous environments.

[0032] The term "comprising" refers to optional compatible components that can be used provided that the important ingredients are present in the suitable form and concentrations. The term "comprising" thus encompasses and includes the more restrictive terms "consisting of" and "consisting essentially of" which can be used to characterize the essential ingredients such as cellulose ethers moieties, lactam moieties, linking groups and/or hybrid polymers.

[0033] The term "cycloalkyl group" refers to a non-aromatic mono- or multicyclo ring system having from about 3 to about 10 carbon atoms. The cycloalkyl group can be partially unsaturated. The cycloalkyl group can also be substituted with an alkyl group substituent as defined herein. The cycloalkyl chain may contain an oxygen, sulfur, or substituted or unsubstituted nitrogen atom, wherein the nitrogen substituent may be hydrogen, alkyl, substituted alkyl, aryl, or substituted aryl, thus providing a heterocyclo group. Representative monocyclo cycloalkyl rings include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like. Further, the cycloalkyl group can be substituted with a linking group, such as an alkyl group, alkylene group, and the like, to form cyclopropylmethyl group, cyclobutylmethyl group, and the like. The cycloalkyl group may also be a multicyclo cycloalkyl rings such as adamantyl, octahydronaphthyl, decalin, camphor, camphane, and noradamantyl.

[0034] The term "dental pellicle" refers to a protein film that forms on the surface enamel of teeth by selective binding of glycoproteins from saliva. The film prevents continuous deposition of salivary calcium phosphate. Dental pellicle forms quickly after a tooth is cleaned and after chewing. Dental pellicle protects the tooth from acids produced by oral microorganisms after consuming carbohydrates. Plaque is a biofilm composed of several different kinds of bacteria and their products that develop over the enamel on a layer known as pellicle. The process of plaque formation takes several days to weeks and will cause the surrounding environment to become acidic if not removed. The surface of enamel attracts salivary glycoproteins and bacterial products creating the pellicle layer. This thin layer forms on the surface of the enamel within minutes of its exposure.

[0035] The term "dentifrice" refers to a paste, gel, or liquid formulations unless otherwise specified. The dentifrice composition may be a single-phase composition or may be a combination of two or more dentifrice compositions. The dentifrice composition may be in any desired form, such as deep striped, surface striped, multi-layered, having the gel surrounding the paste, or any combination thereof. Each dentifrice composition in a dentifrice comprising two or more separate dentifrice compositions may be contained in a physically separated compartment of a dispenser and dispensed side -by-side.

[0036] The term "dispenser" refers to pump, tube, or container suitable for dispensing the oral care compositions.

[0037] The terms "effective amount" and "effective use level" of an agent refer to a sufficient amount of an agent employed to provide desired performance attributes, stability, efficacy, product aesthetics, and the like.

[0038] The term "free radical addition polymerization initiator" refers to a compound used in a catalytic amount to initiate a free radical addition polymerization, and is used herein as simply "initiator"". The term "free radical addition polymerization initiator" also refers to thermal and light activated initiators. The choice of "initiator" depends mainly upon its solubility and its decomposition temperature.

[0039] The term "functionalized" refers to the state of a moiety that has one or more functional groups introduced to it by way of one or more functionalization reactions known to a person having ordinary skill in the art. Particular, yet non-limiting examples of functionalization reactions include epoxidation, sulfonation, hydrolysis, amidation, esterification, hydroxylation, dihyroxylation, amination, ammonolysis, acylation, nitration, oxidation, dehydration, elimination, hydration, dehydrogenation, hydrogenation, acetalization, halogenation, dehydrohalogenation, Michael addition, aldol condensation, Canizzaro reaction, Mannich reaction, Clasien condensation, Suzuki coupling, and the like. Particularly, functionalization of a moiety replaces one or more hydrogens in the moiety with one or more non-hydrogen groups, for e.g. , alkyl, alkoxyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, and/or aryl groups. Particular, yet non-limiting examples of cycloalkyl groups include cyclopentane, cyclohexane, cycloheptane, and the like. Particular, yet non-limiting examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, and the like. Particular, yet non-limiting examples of aryl groups include benzenes, naphthalenes (2 rings), anthracenes (3 rings), and the like.

[0040] The term "halogen" refers to chloro, bromo, iodo and fluoro, and in one embodiment is fluoro, and/or chloro.

[0041] The term "heteroatom" refers to atoms such as oxygen, nitrogen, sulfur, silicon, phosphorous, and/or halogen. The heteroatom(s) may be present as a part of one or more heteroatom-containing functional groups and/or as a part of one or more heterocyclic rings. Non-limiting examples of heteroatom-containing functional groups include ether, hydroxy, epoxy, carbonyl, carboxamide, carboxylic ester, carboxylic acid, imine, imide, amine, sulfonic, sulfonamide, phosphonic, and silane groups.

[0042] The term "homopolymer" refers to a molecule that comprises one type of monomer and the term "non-homopolymer" refers to a polymer that comprises more than one type of monomer and includes such polymers wherein a small amount of polymerization solvent may or may not be covalently bonded into the polymer. The non-homopolymer may be a copolymer, terpolymer, tetramer, or the like.

[0043] The term "hydrophilic-lipophilic balance" (HLB) refers to the degree to which a surfactant is hydrophilic or lipophilic, determined by calculating values for the different regions of the molecule.

[0044] The term "ionic" refers to compounds comprising ions held together by electrostatic forces.

[0045] The terms "linking group" and "spacer group" refer to a segment or group of molecules configured to connect two or more molecules to each another. When the linking group or spacer group is defined as being absent, the linking group or spacer group is replaced by a direct bond. [0046] The term "lozenge" refers to breath mints, troches, pastilles, microcapsules, and fast-dissolving solid forms including freeze dried forms (cakes, wafers, thin films, tablets) and compressed tablets. The term "fast-dissolving solid form" refers to the solid dosage form dissolves in less than 60 seconds, less than 15 seconds, less than 5 seconds, after placing the solid dosage form in the oral cavity.

[0047] The term "monomer" refers to the repeat units that comprise a polymer. A monomer is a compound that chemically bonds to other molecules, including other monomers, to form a polymer.

[0048] The term "multifunctional" refers to compounds having multiple or many functions or activities.

[0049] The term "multifunctional amphiphilic copolymer" refers to a polymer having multiple or many functions or activities and possessing both hydrophilic hydrophobic properties.

[0050] The term "non-ionic" refers to compounds not held together by electrostatic forces. These molecules are held together with covalent bonds.

[0051] The terms "one embodiment," "one aspect", "one version", and "one objective" of the invention include one or more such embodiments, aspects, versions, or objectives, unless the context clearly dictates otherwise.

[0052] The term "oral composition" refers to a product, which in the ordinary course of usage, is not intentionally swallowed for purposes of systemic administration of particular therapeutic agents, but is rather retained in the oral cavity for a time sufficient to contact substantially all of the dental surfaces and/or oral tissues for purposes of oral activity. The oral composition of the present invention may be in the form of a toothpaste, dentifrice, tooth powder, topical oral gel, mouth rinse, denture product, mouthspray, lozenge, oral tablet, or chewing gum.

[0053] The term "orally acceptable carrier" refers to any safe and effective materials for use in the compositions of the present invention. Such materials include fluoride ion sources, additional anticalculus agents, buffers, abrasive polishing materials, peroxide sources, alkali metal bicarbonate salts, thickening materials, humectants, water, surfactants, titanium dioxide, flavor system, sweetening agents, xylitol, coloring agents, and mixtures thereof.

[0054] The term "personal care composition" refers to such illustrative non-limiting compositions as skin, sun, oil, hair, and preservative compositions, including those to alter the color and appearance of the skin.

[0055] The term "pH" refers to a measure of the acidity or basicity of an aqueous solution. Pure water is considered to be neutral, with a pH of about 7.0 at 25 °C. Solutions with a pH less than 7 are considered to be acidic and solutions with a pH greater than 7 are considered to be basic or alkaline.

[0056] The terms "pharmaceutically acceptable" and "cosmetically acceptable" refer to molecular entities and compositions that are generally regarded as safe. Particularly, as used herein, the term "pharmaceutically acceptable" and "cosmetically acceptable" refer to approved by a regulatory agency of the appropriate governmental agency or listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly in humans.

[0057] The term "pharmaceutically acceptable excipient" refers to an additive included in a solid formulations in the form of powders, granules, capsules, pellets and tablets to increase the bulk of the desired formulation comprising present solid dispersion. The excipients may be added during or after the preparation of solid dispersion using spray drying or hot-melt extrusion or other methods.

[0058] The term "pharmaceutically active ingredient" refers to any ingredient considered to have a therapeutic effect when delivered to a subject in need thereof and further being regulated by drug authorities. Pharmaceutically active ingredients may act systemically upon oral consumption, or locally such as when present in the buccal cavity, on the skin, etc. They may also be delivered across the skin as in transdermal drug delivery systems.

[0059] The term "polymer" refers to both linear and branched polymers derived from one or more monomer units, which may or may not be crosslinked or grafted. Non-limiting examples of polymers include copolymers, terpolymers, tetramers, and the like, wherein the polymer is random, block, or alternating polymer. [0060] The term "poorly soluble" refers to slightly soluble or very slightly soluble compounds that require from about 100 or more parts of solvent for one part of solute. The poorly soluble compound means that the solubilization of the active pharmaceutical ingredient (API) compound becomes the rate-limiting step for absorption of such API compound.

[0061] The terms "preferred," "preferably", and variants thereof, refer to embodiments of the invention that afford certain benefits, under certain circumstances. However, 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 invention.

[0062] The terms "tartar" and "calculus" are used interchangeably and refer to mineralized dental plaque deposits.

[0063] The term "teeth" refers to natural teeth as well as artificial teeth or dental prosthesis.

[0064] The present invention provides random copolymers comprising (a) a first monomer comprising an acidic functionality; (b) a second monomer comprising a hydrophobic acrylate functionality; and (c) a third monomer comprising a compatibilizing agent.

[0065] Preferably, the present invention provides copolymers having the structure set out below:

[0066] wherein R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; m ranges from 0 to 5; n ranges from 0 to about 23; and p is equal to or greater than 1 ; wherein w, x, and y are molar percentages, the sum of which is 100%. [0067] The present invention also provides copolymers further comprising a fourth monomer comprising a vinyl or acrylate functionality and a primary, secondary, tertiary alkyl amine, or lactamic functionality.

[0068] Preferably, the present invention also provides copolymers having the structure set out below:

[0069] wherein R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; R₄ is -O- or -NH; R5 is -2-pyrrolidone -CH(CH3)2 or -NR"₂, wherein R" is hydrogen, methyl, or ethyl; m ranges from 0 to 5; n ranges from 0 to about 23; p is >1; q ranges from 0 to 3; and wherein w, x, y, and z are molar percentages, the sum of which is 100%.

[0070] The present invention further provides compositions and methods, employing the copolymers, for treating and protecting teeth especially against erosion.

[0071] Without wishing to be bound by theory, applicants believe that the first monomer, comprising an acidic functionality, in the copolymer provides functionalities that interact with the pellicle coated enamel surface of teeth to bind or anchor the copolymer to the teeth. The second monomer, comprising a hydrophobic acrylate functionality, in the copolymer provides a hydrophobic barrier on the teeth to protect the teeth and prevent softening and erosion from acidic substances, including foods and beverages. The third monomer, comprising a compatibilizing agent, in the copolymer is present in an amount sufficient to provide a synthesis and formulation aid and render solubility, dispersibility, and surface activity to the copolymer in aqueous and anhydrous environments. The exact type and amount of the appropriate compatibilizing agent depends upon many factors including the properties of the first monomer and the second monomer and the type of dental condition being treated. The optional fourth monomer comprises a vinyl or acrylate functionality for incorporation into the polymeric backbone and also a primary, secondary, tertiary alkyl amine, or lactamic functionality. When the copolymer is bound onto the enamel surface of the teeth, the alkyl amine or lactamic functionality in the fourth monomer can behave as a Lewis base or Bronstead base that can locally neutralize dietary acids in close vicinity to the enamel surface and buffer the local pH of the environment immediately surrounding the enamel surface to near neutral conditions. Unstimulated salivation in the mouth may reversibly convert the acidified alkyl amine or lactamic functionalities of the fourth monomer to their original basic state restoring their buffering capability. Alternatively, reapplication of a fresh amount of the acid barrier polymer through mouth rinse or dentifrice can replenish the enamel surface with a fresh consignment of the acid barrier polymer with the alkyl amine or lactamic functionality on the polymer in its native basic state.

[0072] In accordance with the present invention, random co-polymers have been developed which effectively protect tooth enamel surface when used in oral care compositions such as toothpaste and mouthwash. The copolymers are water-soluble upon dissolution and also have neutralizing properties. When applied during oral hygiene activities, these polymers can bind to and stay on a tooth surface to form a protective barrier polymer layer. The protective layer can protect teeth from dietary acids, through several mechanisms including, but not limited to, pH buffering (anionic or cationic components of the polymer absorbing protons), calcium stabilizing (calcium binding components such as carboxylic acid and phosphoric acid preventing calcium dissolution), diffusion barrier (hydrophobic components reduce acid contact with tooth surface), and remineralization. The protective effects of these polymers have been demonstrated using multiple in vitro methods.

[0073] The present invention provides random copolymers comprising (a) a first monomer comprising an acidic functionality; (b) a second monomer comprising a hydrophobic acrylate functionality; and (c) a third monomer comprising a compatibilizing agent.

[0074] In a preferred embodiment, the copolymer has the structure set out below:

[0075] wherein R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; m ranges from 0 to 5; n ranges from 0 to about 23; and p is equal to or greater than 1 ; wherein w, x, and y are molar percentages, the sum of which is 100%. Preferably R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; m ranges from 0 to 2; n ranges from 0 to about 10; and p is from 1 to about 8; wherein w, x, and y are molar percentages, the sum of which is 100%.

[0076] Preferably the first monomer is selected from the group consisting of carboxylic acids, oxoacids of phosphorus, oxoacids of sulfur, and mixtures thereof. More preferably, the first monomer is selected from the group consisting of vinyl phosphonic acid, itaconic acid phosphate, 3-hydroxyethyl methacrylate acid phosphate, 3-hydroxypropyl methacrylate acid phosphate, acrylic acid, methacrylic acid, vinyl sulfonic acid, vinyl benzene sulfonic acid, and mixtures thereof.

[0077] Preferably, the second monomer is selected from the group consisting of styrene, vinyl acetate, alkyl acrylates, alkyl methacrylates, isobutylene, 2,2,2-trifluoroethyl methacrylate, and mixtures thereof.

[0078] Preferably, the third monomer is selected from the group comprising of hydroxyl, alkyl, or phenyl terminated poly(propylene glycol) methacrylate, poly(ethylene glycol) methacrylate, and mixtures thereof.

[0079] Preferably, the copolymer is selected from the group consisting of (a) 2-hyroxyethyl methacrylate acid phosphate (HEMAP)/poly(propylene glycol) methacrylate (PPG- MA)/butyl methacrylate (BMA) terpolymer [HEMAP/PPG-MA/BMA] ; and (b) 2- hydroxyethyl methacrylate acid phosphate (HEMAP)/poly (propylene glycol) methacrylate/N-isopropylacrylamide (NIP AM) terpolymer [HEMAP/PPG-MA/NIPAM] .

[0080] Preferably, the first monomer is present in an amount ranging from about 10 mole% to about 80 mole%, the second monomer is present in an amount ranging from about 10 mole% to about 80 mole%, the third monomer is present in an amount ranging from about 10 mole% to about 80 mole%, of the total molar composition of the copolymer, wherein the sum of all mole% of the monomers in the copolymer is 100%. The molecular weight may range from about 2,000 to about 2,000,000 Daltons. [0081] The copolymer may further comprise a fourth monomer comprising a vinyl or acrylate functionality and a primary, secondary, tertiary alkyl amine, or lactamic functionality.

[0082] In a preferred embodiment, the copolymer has the structure set out below:

[0083] wherein R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; R₄ is -O- or -NH; R5 is -2-pyrrolidone -CH(CH3)2 or -NR"₂, wherein R" is hydrogen, methyl, or ethyl; m ranges from 0 to 5; n ranges from 0 to about 23; p is >1; q ranges from 0 to 3; and wherein w, x, y, and z are molar percentages, the sum of which is 100%.

[0084] Preferably, the fourth monomer is selected from the group consisting of N-isopropyl acrylamide, NN-dimethylaminoethyl methacrylate, NN-dimethylaminopropyl methacrylamide, hydroxyethyl pyrrolidone methacrylate, and mixtures thereof. Preferably, the first monomer is present in an amount ranging from about 10 mole% to about 80 mole%, the second monomer is present in an amount ranging from about 0 mole% to about 80 mole%, the third monomer is present in an amount ranging from about 10 mole% to about 80 mole%, and the fourth monomer is present in an amount ranging from 0 mole% to about 80 mole%, of the total molar composition of the copolymer, wherein the sum of all mole% of the monomers in the copolymer is 100%.

[0085] Preferably, the copolymer is 2-hydroxyethyl methacrylate acid phosphate (HEMAP)/butyl methacrylate (BMA)/poly (propylene glycol) methacrylate (PPG-MA) hydroxyethyl pyrrolidone methacrylate (HEPMA)/tetrapolymer [HEMAP/BMA/PPG- MA/HEPMA].

[0086] The present invention also provides oral care compositions comprising (1) a random copolymer comprising (a) a first monomer comprising an acidic functionality; (b) a second monomer comprising a hydrophobic acrylate functionality; and (c) a third monomer comprising a compatibilizing agent; and (2) an oral care additive.

[0087] Preferably, the copolymer has the structure set out below:

[0088] wherein R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; m ranges from 0 to 5; n ranges from 0 to about 23; and p is equal to or greater than 1 ; wherein w, x, and y are molar percentages, the sum of which is 100%.

[0089] The present invention also provides a method for protecting tooth enamel, wherein the method comprises contacting tooth enamel with an oral care composition; wherein the oral care composition comprises (1) a random copolymer comprising (a) a first monomer comprising an acidic functionality; (b) a second monomer comprising a hydrophobic acrylate functionality; and (c) a third monomer comprising a compatibilizing agent; and (2) an oral care additive.

[0090] Preferably, the copolymer has the structure set out below:

[0091] wherein R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; m ranges from 0 to 5; n ranges from 0 to about 23; and p is equal to or greater than 1 ; wherein w, x, and y are molar percentages, the sum of which is 100%.

[0092] In various embodiments, the oral compositions of the invention coat the teeth and act as a barrier to prevent or treat damage to the enamel of the teeth.

[0093] Further, the compositions have the ability to act as a carrier for oral care actives such as teeth whitening agents, antimicrobials, fluoride, desensitizing agents, and flavors to facilitate deposition and retention of these actives onto the oral surfaces where they can perform their intended function. The coating also acts as a protective barrier that retains the oral care active in close contact with the oral surface thereby ensuring that the activity lasts longer. Effective bleaching will remove stains and lead to whiter teeth. Enhanced retention of antimicrobials on the oral surfaces will result in reducing the oral microorganisms that are cause of dental diseases, including gingivitis, periodontal disease, and dental plaque.

[0094] The oral compositions of the invention may be in the form of a dentifrice, toothpaste, tooth powder, topical oral gel, mouthrinse, denture product, mouthspray, lozenge, oral tablet, or chewing gum. The oral composition may also be incorporated onto strips or films for direct application or attachment to oral surfaces.

[0095] The oral care compositions in aqueous form will optimally have a pH ranging from 4 to 10. In certain embodiments, the pH of the compositions ranges from 5 to 8. In addition to the components described above, the present oral care compositions may comprise additional components, which are described below.

[0096] Orally acceptable carriers include one or more compatible solid or liquid filler diluents or encapsulating substances, which are suitable for topical oral administration. "Compatible" means that the components of the composition are capable of being combined without interaction in a manner, which would substantially reduce the composition's stability and/or efficacy. The carriers or excipients of the invention can include the usual and conventional components of dentifrices (including non-abrasive gels and gels for subgingival application), mouth rinses, mouth sprays, chewing gums, lozenges, and breath mints.

[0097] The choice of a carrier to be used is determined by the way the composition is to be introduced into the oral cavity. If a toothpaste (including tooth gels, etc.) is to be used, then a "toothpaste carrier" is chosen comprising e.g., abrasive materials, sudsing agents, binders, humectants, flavoring and sweetening agents, etc. If a mouth rinse is to be used, then a "mouth rinse carrier" is chosen comprising, e.g., water, flavoring, and sweetening agents, etc. Typical oral carriers include mouth spray carrier, lozenge carrier, chewing gum carrier, sachet carrier, subgingival gel carrier, and biphasic dentifrice formulations. Carriers suitable for the preparation of compositions of the present invention are well known in the art.

[0098] The compositions of the invention may be in the form of non-abrasive gels, including subgingival gels, which may be aqueous or non-aqueous. Aqueous gels generally include a thickening agent (from 0.1 % to 20%), a humectant (from 10% to 55%), a flavoring agent (from 0.04% to 2%), a sweetening agent (from 0.1 % to 3%), a coloring agent (from 0.01 % to 0.5%), and the balance water. The compositions may comprise an anticaries agent (from 0.05% to 0.3% as fluoride ion), and an anticalculus agent (from 0.1 % to 13%).

[0099] Compositions of the invention may also be in the form of dentifrices, such as toothpastes, tooth gels, and tooth powders. Components of toothpaste and tooth gels generally include one or more of a dental abrasive (from 5% to 50%), a surfactant (from 0.5% to 10%), a thickening agent (from 0.1 % to 5%), a humectant (from 10% to 55%), a flavoring agent (from 0.04% to 2%), a sweetening agent (from 0.1 % to 3%), a coloring agent (from 0.01 % to 0.5%), and water (from 2% to 45%). Such toothpastes or tooth gels may also include one or more of an anticaries agent (from 0.05% to 0.3% as fluoride ion) and an anticalculus agent (from 0.1 % to 13%). Tooth powders, of course, contain substantially all non-liquid components.

[00100] Other compositions of the subject invention are mouthwashes including mouth sprays. Components of such mouthwashes and mouth sprays typically include one or more of water (from 45% to 95%), ethanol (from 0% to 25%), a humectant (from 0% to 50%), a surfactant (from 0.01 % to 7%), a flavoring agent (from 0.04% to 2%), a sweetening agent (from 0.1 % to 3%), and a coloring agent (from 0.001 % to 0.5%). Such mouthwashes and mouth sprays may also include one or more of an anti caries agent (from 0.05% to 0.3% as fluoride ion) and an anticalculus agent (from 0.1 % to 3%).

[00101] Other compositions of the invention are dental solutions including irrigation fluids. Components of such dental solutions generally include one or more of water (from 90% to 99%), preservative agent (from 0.01 % to 0.5%), thickening agent (from 0% to 5%), flavoring agent (from 0.04% to 2%), sweetening agent (from 0.1 % to 3%), and surfactant (from 0% to 5%).

[00102] Chewing gum compositions typically include one or more of a gum base (from 50% to 99%), a flavoring agent (from 0.4% to 2%), and a sweetening agent (from 0.01 % to 20%).

[00103] Water employed in the preparation of commercially suitable oral compositions can be of low ion content and free of organic impurities. Water generally comprises 5% to 80%, and 20% to 50%, by weight of an aqueous composition herein. These amounts of water include the free water, which is added plus that which is introduced with other materials, such as with sorbitol. Emulsifying agents may be used in the present compositions.

[00104] Titanium dioxide may also be used in the present composition. Titanium dioxide is a white powder, which adds opacity to the compositions. Titanium dioxide generally comprises from 0.25% to 5%, by weight of the dentifrice compositions.

[00105] The pH of the present compositions is adjusted through the use of buffering agents. Non-chelating buffering agents and systems, as used herein, refer to agents that can be used to adjust the pH of the compositions to a range of pH 4 to pH 10. Buffering agents include monosodium phosphate, trisodium phosphate, sodium hydroxide, sodium carbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium tartarate, and linear and cyclic polyphosphates. Buffering agents can be administered at a level of from 0.5% to 10%, by weight of the present compositions. The pH of dentifrice compositions is measured from a 3: 1 aqueous slurry of dentifrice, for example, 3 parts water to 1 part dentifrice.

[00106] The compositions of the invention can include a dental abrasive. Dental abrasives useful in the compositions of the invention include many different materials. The material selected is compatible within the composition of interest and does not excessively abrade dentin. Suitable abrasives include silicas, including gels and precipitates, insoluble sodium polymetaphosphate, hydrated alumina, calcium carbonate, dicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate, and resinous abrasive materials such as particulate condensation products of urea and formaldehyde. Mixtures of abrasives can be used. The total amount of abrasive in dentifrice compositions of the subject invention is 6% to 70%, by weight. Toothpastes can contain from 10% to 50% of abrasives, by weight of the composition. Solution, mouth spray, mouthwash and non- abrasive gel compositions of the subject invention typically contain no abrasive.

[00107] The compositions of the invention can include a surfactant, including sarcosinate surfactants, isethionate surfactants, and taurate surfactants. Other surfactants include alkali metal or ammonium salts of these surfactants and the sodium and potassium salts of lauroyl sarcosinate, myristoyl sarcosinate, palmitoyl sarcosinate, stearoyl sarcosinate, and oleoyl sarcosinate. The surfactant can be present in the compositions of the invention in an amount of 0.1% to 2.5%, 0.3% to 2.5% or 0.5% to 2% by weight of the total composition.

[00108] The compositions of the invention can include an anticalculus agent, such as synthetic anionic polymers, including polyacrylates and copolymers of maleic anhydride or acid and methyl vinyl ether, polyamino propane sulfonic acid, zinc citrate trihydrate, polypeptides such as polyaspartic and polyglutamic acids, and mixtures thereof.

[00109] The compositions of the invention can include a chelating agent such as tartaric acid. Chelating agents are able to complex calcium found in the cell walls of the bacteria. Chelating agents can also disrupt plaque by removing calcium from the calcium bridges, which help hold this biomass intact. The chelating agent must not have an affinity for calcium that is too high, since this may result in tooth demineralization from the chemically reactive and friable acid eroded dentition surface. Chelating agents include alkali metal salts of tartaric acid, disodium tartrate, dipotassium tartrate, sodium potassium tartrate, sodium hydrogen tartrate, and potassium hydrogen tartrate. The amounts of chelating agent suitable for use in the invention are 0.1 % to 2.5%, 0.5% to 2.5% and 1% to 2.5%. The tartaric acid salt chelating agent can be used alone or in combination with other optional chelating agents. The chelating agents have a calcium binding constant of 10¹ to 10⁵ to provide improved cleaning with reduced plaque and calculus formation. [00110] The compositions of the invention can include a water-soluble fluoride compound present in dentifrices and other oral compositions in an amount sufficient to give a fluoride ion concentration in the composition at 25 °C, and/or when it is used of from 0.0025% to 5% by weight, from 0.005% to 2% by weight, to provide additional anti caries effectiveness.

[00111] The compositions of the invention can include bleaching agents, teeth whitening agents, and teeth color modifying substances. These substances are suitable for modifying the color of the teeth to satisfy the consumer. These substances comprise particles that when applied on the tooth surface modify that surface in terms of absorption and, or reflection of light. Such particles provide an appearance benefit when a film containing such particles is applied over the surfaces of a tooth or teeth. The levels of colorants are generally used in the range of 0.05% to 20%, 0.10% to 15% or 0.25% to 10% of the composition.

[00112] The compositions of the invention can include thickening materials to provide a desirable consistency of the composition, to provide desirable active release characteristics upon use, to provide shelf stability, and to provide stability of the composition, etc. Thickening agents include carboxyvinyl polymers, carageenans, hydroxyethyl cellulose, laponite and water-soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Nonionic charged polymers such as hydrophobically modified starch, polyethyleneoxide, natural gums such as aloe, vora hyaluronic acid glucan, gum karaya, xanthan gum, gum arabic, and gum tragacanth can also be used. Colloidal magnesium aluminum silicate or finely divided silica can be used as part of the thickening agent to further improve texture. Thickening agents in an amount of 0.1 % to 15%, 2% to 10%, or 4% to 8%, by weight of the total toothpaste or gel composition, can be used. Higher concentrations can be used for chewing gums, lozenges (including breath mints), sachets, non-abrasive gels and subgingival gels.

[00113] The compositions of the invention can include a humectant. Humectants serve to keep toothpaste compositions from hardening upon exposure to air, to give compositions a moist feel to the mouth, and, for particular humectants, to impart desirable sweetness of flavor to toothpaste compositions. The humectant, on a pure humectant basis, generally comprises 0% to 70%, 5% to 25%, by weight of the compositions herein. Suitable humectants for use in compositions of the subject invention include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, butylene glycol, polyethylene glycol, and propylene glycol, especially sorbitol and glycerin.

[00114] The compositions of the invention can include flavoring agents. Suitable flavoring agents include oil of wintergreen, oil of peppermint, oil of spearmint, clove bud oil, menthol, anethole, methyl salicylate, eucalyptol, cassia, L-menthyl acetate, sage, eugenol, parsley oil, oxanone, alpha-irisone, marjoram, lemon, orange, propenyl guaethol, cinnamon, vanillin, thymol, linalool, cinnamaldehyde glycerol acetal, and mixtures thereof. Flavoring agents are generally used in the compositions at levels of 0.001 % to 5%, by weight of the composition.

[00115] The compositions of the invention can include sweetening agents. Sweetening agents include sucrose, glucose, saccharin, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol, saccharin salts, thaumatin, aspartame, D- tryptophan, dihydrochalcones, acesulfame and cyclamate salts, sodium cyclamate and sodium saccharin, and mixtures thereof. A composition contains o.l% to 10% of these agents, or 0.1% to 1%, by weight of the composition.

[00116] The compositions of the invention can include coolants, salivating agents, warming agents, and numbing agents as optional ingredients in compositions of the present invention. These agents are present in the compositions at a level of 0.001 % to 10%, or 0.1% to 1 %, by weight of the composition. The coolant can be any of a wide variety of materials including carboxamides, menthol, ketals, diols, and mixtures thereof. Coolants in the compositions include the paramenthan carboxyamide agents such as N- ethyl-p-menthan-3-carboxamide, N,2,3-trimethyl-2-isopropylbutanamide, and mixtures thereof. Additional coolants are selected from the group consisting of menthol, 3,1- menthoxypropane-l,2-diol, menthone glycerol acetal, and menthyl lactate. The terms menthol and menthyl as used herein include dextro- and levorotatory isomers of these compounds and racemic mixtures thereof. Warming agents include capsicum and nicotinate esters, such as benzyl nicotinate. Numbing agents include benzocaine, lidocaine, clove bud oil, and ethanol.

[00117] The compositions of the invention can include an alkali metal bicarbonate salt. Alkali metal bicarbonate salts are soluble in water and unless stabilized, tend to release carbon dioxide in an aqueous system. Sodium bicarbonate is an alkali metal bicarbonate salt. The composition may contain 0.5% to 30%, 0.5% to 15%, or 0.5% to 5% of an alkali metal bicarbonate salt.

[00118] Other active agents include antimicrobial agents, water insoluble noncationic antimicrobial agents such as halogenated diphenyl ethers, phenolic compounds including phenol and its homologs, mono and poly-alkyl and aromatic halophenols, resorcinol and its derivatives, bisphenolic compounds and halogenated salicylanilides, benzoic esters, and halogenated carbanilides. The water soluble antimicrobials include quaternary ammonium salts and bis-biquamide salts, among others. Triclosan monophosphate is an additional water soluble antimicrobial agent. The quaternary ammonium agents include those in which one or two of the substitutes on the quaternary nitrogen has a carbon chain length (typically alkyl group) from 8 to 20, typically from 10 to 18 carbon atoms while the remaining substitutes (typically alkyl or benzyl group) have a lower number of carbon atoms, such as from 1 to 7 carbon atoms, typically methyl or ethyl groups. Dodecyl trimethyl ammonium bromide, tetradecylpyridinium chloride, domiphen bromide, N-tetradecyl-4-ethyl pyridinium chloride, dodecyl dimethyl (2phenoxyethyl) ammonium bromide, benzyl dimethylstearyl ammonium chloride, cetyl pyridinium chloride, quaternized 5-amino-l, 3-bis(2-ethyl-hexyl)-5-methyl- hexahydropyrimidine, benzalkonium chloride, benzethonium chloride and methyl benzethonium chloride are exemplary of typical quaternary ammonium antibacterial agents. Other compounds are bis[4-(R-amino)-l-pyridinium]alkanes. Other antimicrobials such as copper bisglycinate, copper glycinate, zinc citrate, and zinc lactate may also be included. Enzymes are another type of active that may be used in the present compositions. Useful enzymes include those that belong to the category of pro teases, lytic enzymes, plaque matrix inhibitors and oxidases: Proteases include papain, pepsin, trypsin, ficin, bromelin; cell wall lytic enzymes include lysozyme; plaque matrix inhibitors include dextranases; mutanases; and oxidases include glucose oxidase, lactate oxidase, galactose oxidase, uric acid oxidase, peroxidases including horse radish peroxidase, myeloperoxidase, lactoperoxidase, chloroperoxidase. The oxidases also have whitening/cleaning activity, in addition to antimicrobial properties. Other antimicrobial agents include chlorhexidine, triclosan, triclosan monophosphate, and flavor oils such as thymol. These agents, which provide anti- plaque benefits, may be present at levels of from 0.01% to 5%, by weight of the dentifrice composition. [00119] The invention also provides methods for treating or preventing damage to the enamel of a tooth surface, cleaning and polishing teeth, and reducing the incidence of stain, plaque, gingivitis, and calculus on dental enamel. The method of use comprises contacting a subject's dental enamel surfaces and oral mucosa with the oral compositions according to the invention. The method of use may be by brushing with a dentifrice, rinsing with a dentifrice slurry or mouthrinse, or chewing a gum product. Other methods include contacting the topical oral gel, mouthspray, or other form such as strips or films with the subject's teeth and oral mucosa. The composition may be applied directly to the teeth, gums, or other oral surface with a brush, a pen applicator, or the like, or even with the fingers.

[00120] The dentifrice compositions of the invention include (a) a first monomer comprising an acidic functionality; (b) a second monomer comprising a hydrophobic acrylate functionality; and (c) a third monomer comprising a compatibilizing agent, and combinations thereof, that are useful in treating or preventing various disorders of the oral cavity, for example, enamel remineralization, incipient caries remineralization, carious dentin remineralization, caries prevention, arresting decay, reversing decay, anti-caries, pit and fissure sealants, prophylactic pastes, fluoride treatments, dentinal sealants, and combinations thereof.

[00121] In one embodiment, a method of cleaning hypersensitive teeth includes contacting the teeth or a tooth surface of a subject in need thereof with a dentifrice composition of the invention. In another embodiment, the invention encompasses a method of treating dental hypersensitivity including contacting the teeth or a tooth surface of a subject in need thereof with a dentifrice composition of the invention.

[00122] The random copolymers, compositions comprising the random copolymers, and methods for using the random copolymers are set in the examples below. The examples are presented for purposes of demonstrating, but not limiting, the preparation of the hybrid polymers of this invention. EXAMPLES Example 1

Synthesis of HEMAP/PPG-MA/BMA (40/20/40)- Copolymer 1

[00123] Feed one is prepared with 35.15g poly(propylene glycol) methacrylate (PPG- MA; Mn = 375); 39.38g 2-hydroxyethyl methacrylate acid phosphate (HEMAP); 26.66g butyl methacrylate (BMA) and 54.09g isopropanol. Add 166g isopropanol into the reactor and commence purging of the reaction vessel with nitrogen. Heat the reaction flask containing isopropanol to reflux - approximately ~78C. In a separate vessel prepare a mixture of Triganox 25C 75 (l.Og) and isopropanol (20g). Label this vessel "Triganox Solution". When the reaction flask has reached reflux temperature, begin adding Feed 1, drop-wise, in to the reaction vessel over a period of 180 minutes. After 15 minutes of monomer feed, add 2g of the Triganox Solution into the reactor. Continue the drop-wise addition of Feed 1 over a period of approximately 165 minutes. While the monomers are feeding into the reactor, after 30 minutes charge 2.0g of the Triganox solution. After 45, 60, 75, 90, 105 and 120 minutes, charge 2.0g Triganox solution into the reactor. After 150 minutes, charge 2.0g Triganox solution into the reactor. At the completion of the monomer feeds, charge the reaction vessel with the remainder of the Triganox solution. The reaction vessel is allowed to heat at reflux for an additional 180 minutes. Note: during the initiator shots, additional isopropanol was added to replace any that has volatilized. Cool the reaction vessel and leave the material in the reactor. This is the end of 'day one'. On 'day two', heat the vessel to reflux and charge with 2.5g Triganox 25C 75. Hold for 2 hours. Add additional 2.5g Triganox 25C 75. Hold for 5 hours then cool reaction mixture.

Example 2

Synthesis of HEMAP/PPG-MA/NIPAM (40/20/40)- Copolymer 2

[00124] Feed one is prepared with 24.75g poly(propylene glycol) methacrylate (PPG- MA; Mn = 375); 27.72g 2-hydroxyethyl methacrylate acid phosphate (HEMAP); and 38.07g isopropanol. Feed two is prepared with 14.94g N-isopropylacrylamide and 38.07g isopropanol. Add 186.14g isopropanol into the reactor and commence purging of the reaction vessel with nitrogen. Heat the reaction flask containing isopropanol to reflux, ~78°C. In a separate vessel prepare a mixture of Triganox 25C 75 (l.Og) and isopropanol (20g). Label this vessel "Triganox Solution". When the reaction flask has reached reflux temperature, begin adding Feeds 1 and 2, drop-wise, in to the reaction vessel over a period of 180 minutes. After 15 minutes of monomer feed, add 2g of the Triganox Solution into the reactor. Continue the drop-wise addition of Feed 1 over a period of approximately 165 minutes. While the monomers are feeding into the reactor, after 30 minutes charge 2.0g of the Triganox solution. After 45, 60, 75, 90, 105 and 120 minutes, charge 2.0g Triganox solution into the reactor. After 150 minutes, charge 2.0g Triganox solution into the reactor. At the completion of the monomer feeds, charge the reaction vessel with the remainder of the Triganox solution. The reaction vessel is allowed to heat at reflux for an additional 180 minutes. Note: during the initiator shots, additional isopropanol was added to replace any that has volatilized. Cool the reaction vessel and leave the material in the reactor. This is the end of 'day one'. On 'day two', re-heat the vessel to reflux and charge with 2.5g Triganox 25C 75. Hold for 2 hours. Add an additional 2.5g Triganox 25C 75. Hold for 5 hours then cool reaction mixture.

Example 3

Synthesis of HEPMA/HEMAP/PPG-MA/BMA (20/20/20/40)- Copolymer 3

[00125] Feed one is prepared with 35.28g poly(propylene glycol) methacrylate (PPG- MA; Mn = 375); 19.76g 2-hydroxyethyl methacrylate acid phosphate (HEMAP); 26.76g butyl methacrylate (BMA); 18.53g hydroxyethylpyrrolidine methacrylate (HEPMA) and 54.28g isopropanol. Add 166g isopropanol into the reactor and commence purging of the reaction vessel with nitrogen. Heat the reaction flask containing isopropanol to reflux - approximately ~78C. In a separate vessel prepare a mixture of Triganox 25C 75 (l.Og) and isopropanol (20g). Label this vessel "Triganox Solution". When the reaction flask has reached reflux temperature, begin adding Feed 1, drop-wise, in to the reaction vessel over a period of 180 minutes. After 15 minutes of monomer feed, add 2g of the Triganox Solution into the reactor. Continue the drop-wise addition of Feed 1 over a period of approximately 165 minutes. While the monomers are feeding into the reactor, after 30 minutes charge 2.0g of the Triganox solution. After 45, 60, 75, 90, 105 and 120 minutes, charge 2.0g Triganox solution into the reactor. After 150 minutes, charge 2.0g Triganox solution into the reactor. At the completion of the monomer feeds, charge the reaction vessel with the remainder of the Triganox solution. The reaction vessel is allowed to heat at reflux for an additional 180 minutes. Note: during the initiator shots, additional isopropanol was added to replace any that has volatilized. Cool the reaction vessel and leave the material in the reactor. This is the end of 'day one'. On 'day two', re-heat the vessel to reflux and charge with 2.5g Triganox 25C 75. Hold for 2 hours. Add an additional 2.5g Triganox 25C 75. Hold for 5 hours then cool reaction mixture.

Example 4

Anti-demineralization Performance

[00126] High density hydroxyapatite (HAP) disks were pre-treated with 1% citric acid pH 3.8 for 15 minutes at 37 degrees C and 100 rpm and rinsed in deionized water. The disks were immersed in phosphate buffer solution (PBS) for 5 minutes at 37° C and 100 rpm. Disks were then treated for 2 minutes with model toothpaste treatment solution (described in Table 1) at 37° C and 100 rpm. Disks were immersed for 5 minutes in PBS solution at 37 degrees C and 100 rpm, rinsed in deionized water then placed in 2 ml citric acid (pH 3.8) for 15 minutes at 37° C and lOOrpm. Citric acid was collected and analyzed for calcium concentration by inductively coupled plasma mass spectrometry (ICP-MS). Average values from six disks were reported. A lower calcium concentration indicates better anti- demineralization performance. Effect of addition of copolymer on calcium dissolution was evaluated in commercial mouthwash and model toothpaste formulations. The results are shown in Table 2 and 3 below.

Model Toothpaste Composition Table 1

[00127] There is significant reduction in calcium dissolution when 2% w/w copolymer 1 was added to commercial mouthwash without fluoride. A commercial mouthwash containing fluoride (without co-polymer 1) was used for comparison (Table 2).

Table 2

[00128] All the copolymers showed reduction in calcium dissolution at 2% w/w in model toothpaste formula with fluoride. A commercial toothpaste containing fluoride diluted one part of toothpaste to two parts deionized water was used for comparison (Table 3).

Table 3

ND = Not Determined

Example 5

Surface Microhardness Measurement

[00129] Mounted polished bovine teeth specimen were pre treated in 1% citric acid (pH adjusted to 3.8) at room temperature for 2 min and rinsed in tap water prior to measuring initial surface microhardness with a Tukon 2500 Knoop hardness tester. A treatment/acid challenge cycle was carried out as follows. Specimen were placed in artificial saliva at 37°C and 50 RPM for 30 min and rinsed in tap water. One half of the specimen was covered with tape (side used as negative control) then treated with treatment solution with or without copolymer at 37°C, 100 rpm for 2 min. Specimen were rinsed in tap water, tape was removed and specimen were placed in artificial saliva at 37°C, 50 rpm for 30 min followed by acid challenge with 1% citric acid (pH adjusted to 3.8) at 37°C, 50 rpm for 5 min. Specimen were rinsed and placed in artificial saliva at 37 C and 50 RPM for 30 min. The above treatment/acid challenge cycle was repeated one more time. Surface microhardness of both treated side and the untreated side (negative control) was measured. Retention of hardness over initial hardness was calculated for each side of the specimen. % retention of hardness over negative control was determined. Average value from four specimens was reported. Effect of addition of copolymer on surface microhardness was evaluated in model full toothpaste formulations. Model full toothpaste with and without polymer were diluted 1 part of toothpaste to two parts water prior to use. Results are shown in Table 5 below. Higher retention of Knoop hardness indicates better protection of enamel from acid erosion.

Model Full Toothpaste Composition Table 4

[00130] Addition of 2% w/w copolymer to model full toothpaste increased retention of surface microhardness over negative control from 13% to 20%, whereas commercial toothpaste with 240 ppm fluoride showed 10% increase in surface microhardness over negative control (Table 5). Table 5

Example 6

Stain Prevention Test

[00131] Hydroxyapatite (HAP) discs were sintered at 800°C, cooled to room temperature and stored until use. HAP discs were incubated in saliva for 20 h @ 37°C. Pellicle coated discs were then treated in treatment test solution for 30 min and rinsed in deionized water. CIE L*a*b* color values were recorded before subjecting discs to tea stain treatment for 30 min. Discs were rinsed with deionized water and final CIE L*a*b* color values were recorded. Stain prevention efficacy was quantified by E which is the color tained background represented by the equation

where AL indicates the luminosity (whiteness) between stained discs and unstained background. An average of eight individual values were reported. Effect of addition of 2% w/w copolymer on stain prevention was evaluated in a commercial mouthwash without fluoride at pH 4.3. Results are shown in Table 6. Copolymer 1 in mouthwash formulation improved stain prevention efficacy.

Table 6

Commercial mouthwash^ without fluoride 36

with 2% Co-polymer 1

[00132] While this invention has been described in detail with reference to certain preferred embodiments, it should be appreciated that the present invention is not limited to those precise embodiments. Rather, in view of the present disclosure, which describes the current best mode for practicing the invention, many modifications and variations would present themselves to those skilled in the art without departing from the scope and spirit of this invention.

Claims

We claim.

1. A random copolymer comprising:

(a) a first monomer comprising an acid functionality;

(b) a second monomer comprising a hydrophobic acrylate functionality; and

(c) a third monomer comprising a compatibilizing agent.

2. The copolymer according to claim 1 , wherein the copolymer has the structure set out below:

wherein R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; m ranges from 0 to 5; n ranges from 0 to about 23; and p is equal to or greater than 1; wherein w, x, and y are molar percentages, the sum of which is 100%.

3. The copolymer according to claim 2, wherein R is hydrogen or methyl; Ri is hydrogen or -(CH₂CH₂0-)_mP03H₂; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; m ranges from 0 to 2; n ranges from 0 to about 10; and p is from 1 to about 8; wherein w, x, and y are molar percentages, the sum of which is 100%.

4. The copolymer according to claim 1, wherein the first monomer is selected from the group consisting of carboxylic acids, oxoacids of phosphorus, oxoacids of sulfur, and mixtures thereof.

5. The copolymer according to claim 4, wherein the first monomer is selected from the group consisting of vinyl phosphonic acid, itaconic acid phosphate, 3-hydroxyethyl methacrylate acid phosphate, 3-hydroxypropyl methacrylate acid phosphate, acrylic acid, methacrylic acid, vinyl sulfonic acid, vinyl benzene sulfonic acid, and mixtures thereof.

6. The copolymer according to claim 1, wherein the second monomer is selected from the group consisting of styrene, vinyl acetate, alkyl acrylates, alkyl methacrylates, isobutylene, 2,2,2-trifluoroethyl methacrylate, and mixtures thereof.

7. The copolymer according to claim 1, wherein the third monomer is selected from the group comprising of hydroxyl, alkyl, or phenyl terminated poly(propylene glycol) methacrylate, poly(ethylene glycol) methacrylate, and mixtures thereof.

8. The copolymer according to claim 1, wherein the first monomer is present in an amount ranging from about 10 mole% to about 80 mole%, the second monomer is present in an amount ranging from about 10 mole% to about 80 mole%, the third monomer is present in an amount ranging from about 10 mole% to about 80 mole%, of the total molar composition of the copolymer, wherein the sum of all mole% of the monomers in the copolymer is 100%.

9. The copolymer according to claim 1, wherein the molecular weight ranges from about 2,000 to about 2,000,000 Daltons.

10. The copolymer according to claim 1, further comprising a fourth monomer comprising a vinyl or acrylate functionality and a primary, secondary, tertiary alkyl amine, or lactamic functionality.

11. The copolymer according to claim 10, wherein the copolymer has the structure set out below:

wherein R is hydrogen or methyl; Ri is hydrogen or -(CfbCfhO- POsEh; R2 is hydrogen or -CX3, where X is hydrogen or a halogen; R3 is hydrogen or a C1-C10 alkyl group; R₄ is -O- or -NH; R5 is -2-pyrrolidone -CH(CH3)2 or -NR"₂, wherein R" is hydrogen, methyl, or ethyl; m ranges from 0 to 5; n ranges from 0 to about 23; p is >1 ; q ranges from 0 to 3; and wherein w, x, y, and z are molar percentages, the sum of which is 100%.

12. The copolymer according to claim 10, wherein the fourth monomer is selected from the group consisting of N-isopropyl acrylamide, NN-dimethylaminoethyl methacrylate, NN-dimethylaminopropyl methacrylamide, hydroxyethyl pyrrolidone methacrylate, and mixtures thereof.

13. The copolymer according to claim 10, wherein the first monomer is present in an amount ranging from about 10 mole% to about 80 mole%, the second monomer is present in an amount ranging from about 0 mole% to about 80 mole%, the third monomer is present in an amount ranging from about 10 mole% to about 80 mole%, and the fourth monomer is present in an amount ranging from 0 mole% to about 80 mole%, of the total molar composition of the copolymer, wherein the sum of all mole% of the monomers in the copolymer is 100%.

14. The copolymer according to claim 1, wherein the copolymer is selected from the group consisting of:

(a) 2-hyroxyethyl methacrylate acid phosphate (HEMAP)/poly(propylene glycol) methacrylate (PPG-MA)/butyl methacrylate (BMA) terpolymer [HEMAP/PPG-MA/BMA] ; and

(b) 2-hydroxyethyl methacrylate acid phosphate (HEMAP)/poly (propylene glycol) methacrylate/N-isopropylacrylamide (NIP AM) terpolymer [HEMAP/PPG-MA/NIPAM] .

15. The copolymer according to claim 10, wherein the copolymer is 2-hydroxyethyl methacrylate acid phosphate (HEMAP)/butyl methacrylate (BMA)/poly(propylene glycol) methacrylate (PPG-MA) hydroxyethyl pyrrolidone methacrylate (HEPMA)/tetrapolymer [HEMAP/BMA/PPG-MA/HEPMA] .

16. An oral care composition comprising: (1) a random copolymer comprising:

(a) a first monomer comprising an acidic functionality;

(b) a second monomer comprising a hydrophobic acrylate functionality; and (c) a third monomer comprising a compatibilizing agent; and (2) an oral care additive.

17. The oral care composition according to claim 16, wherein the copolymer has the structure set out below:

18. A method for protecting tooth enamel, wherein the method comprises contacting tooth enamel with an oral care composition; wherein the oral care composition comprises:

(1) a random copolymer comprising:

(a) a first monomer comprising an acidic functionality;

(b) a second monomer comprising a hydrophobic acrylate functionality; and

(c) a third monomer comprising a compatibilizing agent; and

(2) an oral care additive.

19. The method according to claim 18, wherein the copolymer has the structure set out below: