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    • 专利摘要:
    "COMPOSITION OF ORAL HYGIENE". Oral care compositions are disclosed, for example, dentifrice compositions comprising an oral treatment composition comprising an orally acceptable carrier, metal oxide particles having an average particle size of no more than one of the dentin tubules and at least one amino acid capable of chelation of metal oxide. The composition may comprise an adherent polymeric material for adhering the metal oxide particles in the dentin tubule. The metal oxide particles have an average particle size of 5 micrometers or less, and may comprise zinc oxide.
    公开号:BR112012022935A2
    申请号:R112012022935-4
    申请日:2010-03-31
    公开日:2021-06-01
    发明作者:Venda Porter；Andre Morgan；Michael Prencipe
    申请人:Colgate-Palmolive Company；
    IPC主号:
    专利说明:

    ! 1/23 . The present invention relates to an oral hygiene composition, for example an o. dentifrice composition, for the improved release of an anti-plaque/anti-tartar agent on the oral surfaces of the oral cavity, and which can additionally treat or prevent hypersensitivity of the teeth. The present invention also relates to a method of releasing an anti-plaque/anti-tartar agent onto the oral surfaces of the oral cavity and simultaneously treating or preventing hypersensitivity of the teeth. The present invention has particular application in the treatment or prevention of tooth hypersensitivity by occluding the dentinal tubules.
    FUNDAMENTALS Dentin is a part of the tooth internal to enamel and cementum, which has a radially striated appearance due to a large number of channels or thin tubules known as the dentin tubules. The tubules extend from the pulp cavity to the periphery of the dentin and are usually around two micrometers in diameter at their base and a little narrower at their periphery. The 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. It is generally understood that partially or completely exposed tubules can lead to tooth sensitivity, an irritating and painful condition. In this theory, recession of the gum line exposes cementum to erosion. The corroded cementum in turn exposes the hollow tubules of the dentin. The exposed tubules cause the nerves inside the tooth to be excessively affected by external oral stimuli because the transfer of material and energy between the outside and the inside of the tooth is accelerated through the tubules. Common environmental stimuli such as heat, cold, chemicals and physical and mechanical pressure or stimuli such as brushing are capable of irritating the nerve through the open dentinal tubules and thus creating pain. Sensitive toothache appears to result from these stimuli, which apparently cause fluid movements in the dentinal tubules that activate the nerve endings in the pulp. Conventionally, two approaches have been taken to treat or improve . teeth sensitivity. Under one approach, the chemical environment near the nerve is . altered by the application of various agents in such a way that the nerve is not stimulated, or : . not stimulated so greatly. Known agents useful in this chemical approach include potassium salts (such as potassium nitrate, potassium bicarbonate, potassium chloride) and strontium, zinc salts and chloride salts. The second approach involves mechanically shielding the nerve by, for example, blocking the dentinal tubules completely or partially with “tubule blocking agents”. Agents that have been disclosed in the prior art include, for example, cationic alumina, clays, water-soluble or water-swellable polyelectrolytes, oxalates, amorphous calcium phosphate, hydroxyapatite, maleic acid copolymers and polyethylene particles.
    US-A1-2009/0186090 in the name of the present Applicant discloses the provision of an oral hygiene composition that reduces and/or eliminates the perception of tooth sensitivity. The composition includes an adherent material, and includes, in part, silica particles having a particle size of 2 to 5 micrometers.
    However, even though such an oral hygiene composition provides relief from clinical hypersensitivity, there is nevertheless still a need in the art for an oral hygiene composition, in particular a dentifrice, which, after use, provides prevention or reduction. tooth sensitivity and is not associated with the significant processing or formulation disadvantages.
    It is also known in the art to use zinc oxide as an anti-plaque/anti-tartar agent. The complex use of divalent or trivalent metal ions as anti-plaque agents is also known.
    It has been shown in the literature that the solubility of zinc can be improved. by forming a complex with a chelation molecule such as ethylenediamine tetraacetic acid or a bioactive molecule such as a cyclic α-hydroxyketone. For example, as disclosed in US-A-6287541, specific cyclic alpha-hydroxy ketones are used as complexing agents for bivalent copper, zinc, iron or tin and trivalent iron. S.Y.Gan, et al. “Antibacterial Activity of Zn-chelator Complexes.” IADR, March 2009, discloses the use of inert biocompatible chelators for zinc.
    However, the increased solubility does not guarantee an increase in anti-plaque, anti-gingivitis, hypersensitivity, and/or fresh breath efficacy. To provide these benefits, zinc must be released into the hard and/or soft tissues of the oral cavity.
    There is still a need for improved release of anti-plaque/anti-tartar agents to oral surfaces, particularly to the hard and/or soft tissue of the oral cavity): SUMMARY — In some embodiments, the present invention provides a composition of . oral hygiene which comprises an orally acceptable vehicle, a source of metal oxide steel particles having an average particle size of no more than one dentin tubule, and at least one amino acid capable of chelating the metal oxide particles.
    In some embodiments, the metal oxide particles can have an average particle size of 1 to 7 micrometers. In some embodiments, the metal oxide particles have an average particle size of 5 micrometers or g at least. The metal oxide typically comprises at least one metal oxide f. selected from zinc oxide, tin oxide, titanium oxide, calcium oxide, copper oxide and iron oxide or a mixture thereof.
    In other embodiments, the metal oxide is zinc oxide.
    Metal oxide particles can have a particle size distribution of 3 to 4 micrometers, a particle size distribution of 5 to 7 micrometers, a particle size distribution of 3 to 5 micrometers, a particle size distribution 2 to 5 micrometers, or a particle size distribution of 2 to 4 micrometers.
    The metal oxide particles may be present in an amount of up to 5% by weight, based on the total weight of the oral care composition, for example, in an amount of 0.5 to 2% by weight, based on the total weight of the oral hygiene composition.
    The metal oxide can be incorporated into the oral care composition in at least one form selected from a powder, a solution or suspension of nanoparticles, or encapsulated in a polymer or globule. Preferably, the at least one amino acid is selected from arginine, L-arginine, cysteine, leucine, isoleucine, lysine, L-lysine, alanine, asparagine, aspartate, phenylalanine, glutamate, glutamic acid, threonine, glutamine, tryptophan, glycine, valine, proline, serine, tyrosine and histidine, and mixtures thereof.
    Typically, the at least one amino acid is selected from L-arginine, cysteine, isoleucine, L-lysine, glutamic acid, serine, and mixtures thereof.
    DO More typically, the at least one amino acid comprises L-arginine.
    Optionally, the at least one amino acid is present in an amount of up to 5% by weight, further optionally from 0.5 to 5% by weight, even more optionally from 2.5 to 4.5% by weight, based on weight. total oral hygiene composition.
    The oral care composition may further comprise an adherent polymeric material for adhering the metal oxide particles in the dentin tubule.
    : In some embodiments, the metal oxide is encapsulated in a material. adherent polymeric. : : In some embodiments, the polymeric sticky material comprises at least one cellulose polymer.
    The at least one cellulose polymer can be one or more hydroxyalkyl cellulose polymer selected from hydroxypropylmethyl cellulose (HPMC), hydroxyethylpropyl cellulose (HepC), hydroxybutylmethyl cellulose (HBMC), and carboxymethyl cellulose (CMC).
    Typically, the polymeric sticky material comprises a mixture of two
    O, . hydroxyalkyl cellulose polymers having different molecular weight and the metal oxide comprises zinc oxide which is encapsulated in the mixture of two hydroxyalkyl cellulose polymers.
    In other embodiments, the polymeric sticky material comprises at least one polymer selected from polymers of poly(ethylene oxide), linear polyvinylpyrrolidone (PVP) and cross-linked polyvinylpyrrolidone (PVP), polyethylene glycol (PEG) / polypropylene glycol (PPG) copolymer ), ethylene oxide (EO)-propylene oxide (PO) block copolymers, ester gum, shellac, pressure sensitive silicone adhesives, methacrylates, or mixtures thereof.
    Preferably, the oral care composition is a dentifrice composition, such as a toothpaste or a gel.
    Alternatively, the oral care composition is formulated in a form selected from a mouthwash solution, a chewing gum, a soluble lozenge, and a soluble film. The present invention further provides a method of reducing tooth sensitivity which comprises applying to the surface of a mammalian tooth an oral hygiene composition of the present invention. The present invention further provides a method for protecting dental surfaces from acid-mediated degradation, which comprises applying to the surface of a mammalian tooth an oral hygiene composition of the present invention.
    The present invention further provides a method of maintaining or increasing the systemic health of a mammal which comprises applying a composition to an oral surface of a mammal at least once a day for a period of time, wherein the composition comprises: a . a hygiene composition now! of the present invention, and b. an agent selected from triclosan, triclosan monophosphate; chlorhexidine; alexidine; hexetidine; sanguinarine; benzalkonium chloride; salicylanilide; domifen bromide; cetylpyridinium chloride (CPC); tetradecylpyridinium chloride (TPC); N-tetradecyl-4-ethylpyridinium chloride (TDEPC); octenidine; delmopinol; octapinol; nisin, ion agent: zinc; copper ion agent, essential oils; furanones; bacteriocins, arginate. ethylauroyl, magnolia extracts, a source of metal ions, fluoride, tin ions, | .: arginine bicarbonate, honokiol, magonol, ursolic acid, ursic acid, morin, i and sea buckthorn extract, a peroxide, an enzyme, an extract of Camellia, a flavonoid, an as flavan, halogenated diphenyl ether, creatine and propolis .
    The present invention also provides a method of occluding a tubule of dentin within the surface of a mammalian tooth which comprises applying to the tooth surface a composition according to the present invention.
    The compositions may contain additional therapeutic and non-therapeutic components, and may also be used in the practice of various methods, which are. included within the scope of the invention. Compositions and methods within the scope of the invention may be useful, for example, in reducing or eliminating tooth sensitivity in a mammal, improving/maintaining systemic health, and/or occluding dentinal tubules. The present invention is based on the discovery by the present inventors that charged amino acids and peptides have an affinity for soft and/or hard tissue in the oral cavity, and are also able to chelate a metal oxide such as zinc oxide , tin oxide, or copper oxide, which has anti-plaque/anti-tartar efficacy when present in a therapeutically effective amount. Upon introduction of such a complex into the oral cavity, for example, by brushing the teeth, the amino acid/peptide can act to release the metal oxide at the desired location in the mouth. For example, if zinc oxide is released into dentin, the zinc oxide amino acid complex can occlude the dentin tubules and provide relief from hypersensitivity. Metal oxide can further provide anti-plaque/anti-tartar treatment or prevention. - The present inventors have found in particular that the release of zinc oxide from dentifrice on a hydroxyapatite surface can be increased with the addition of an amino acid such as L-arginine. including, but not limited to, powder, nanoparticle solution, and the encapsulation of zinc oxide by a polymer film or bead.
    BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 depicts a comparison of the incidence of occlusion resulting from treating a mammalian tooth dentin substrate with an Example of an oral hygiene composition of the invention versus a Comparative Example, the substrates being shown untreated, after treatment by brushing, and after treatment through a first acid test.
    DETAILED DESCRIPTION It is to be understood that the detailed description and specific examples, although . o indicating embodiments of the invention, are intended only for the purposes of . illustration and are not intended to limit the scope of the invention. : The following non-limiting definitions and guidelines should be considered in reviewing the description of this invention herein. The topics (such as "Fundamentals of the Invention" and "Summary") and subtopics (such as "Compositions") used herein are intended only for general organization of topics within the disclosure of the invention, and are not intended to limit the disclosure of the invention or any of its aspects. In particular, the subject matter disclosed in the "Fundamentals of the Invention", may include aspects of technology within the scope of the invention, and may not constitute a recitation of the prior art. The subject matter disclosed in the “Summary” is not an exhaustive or complete disclosure of and the entire scope of the invention or any of its embodiments. The classification or discussion of a material within a section of this descriptive report as having a particular utility (for example, as being an "active" or "carrier" ingredient) is done for convenience and no interference should be established in which the material should necessary or solely to function in accordance with its included classification when used in any given composition.
    Citation of references herein does not constitute an admission that such references are of the prior art or have any relevance to the patentability of the invention disclosed herein. Any discussion of the content of references cited in the Background of the Invention is intended only to provide a general summary of the assertions made by the authors of the references, and does not constitute an admission as to the accuracy of the content of such references. Any and all references cited herein are hereby incorporated by reference in their entirety.
    The description and specific examples, while indicating the embodiments of the invention, are intended for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, the recitation of multiple embodiments and having the mentioned aspects is not intended to exclude other embodiments having additional aspects, or other embodiments that incorporate different combinations of the mentioned aspects. Specific Examples are provided for purposes of illustration of how to prepare and use the compositions and methods of this invention and, unless explicitly mentioned otherwise, are not intended to be a representation that the provided embodiments of this invention were or were not made or tested.
    As used herein, the words "preferred" and "preferably" refer to embodiments of the invention that provide 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 not if . is intended to exclude other embodiments from the scope of the invention. Furthermore, the compositions and methods may comprise, consist essentially of, or consist of the elements described herein.
    As used herein, the word "include", and its variants, are intended to be non-limiting, such that the recitation of items from a list is not to exclude other similar items that may also be useful in the materials. , compositions, devices and methods of this invention.
    As used herein, the term "about" when applied to the value for a parameter of a composition or method of this invention, indicates that the calculation or measurement of the value allows for some slight inaccuracy without having a substantial effect on the chemical attributes or composition or method. If, for some reason, the imprecision given by "about" is not otherwise understood in the art with this usual meaning, then "about" as used herein indicates a possible variation of up to 5% of the value.
    As noted herein, all compositional percentages are by weight of the total composition, unless otherwise specified.
    The invention described herein includes an oral hygiene composition which contains at least (a) an amino acid and (b) a metal oxide particle. The metal oxide particle may have an average particle size of no more than one dentin tubule or, alternatively, may have an average particle size of 5 micrometers or less.
    In some embodiments, the oral care composition comprises at least one amino acid capable of chelating the metal oxide. The at least one amino acid can be selected from arginine, L-arginine, cysteine, leucine, isoleucine, lysine, L-lysine, alanine, asparagine, aspartate, phenylalanine, glutamate, glutamic acid, threonine, glutamine, . tryptophan, glycine, valine, praline, serine, tyrosine and histidine, and mixtures thereof. Typically, the at least one amino acid is selected from L-arginine, cysteine, : isoleucine, L-lysine, glutamic acid, serine, and mixtures thereof.
    More typically, the at least one amino acid comprises L-arginine.
    The at least one amino acid is present in an amount sufficient to effectively chelate the metal oxide, and typically may be present in an amount of up to 5% by weight, optionally further from 0.5 to 5% by weight, even more optionally from 2.5 to 4.5% by weight, based on the total weight of the oral care composition.
    Metal Oxide Particles The metal oxide particles may be present in an amount of up to 5% by weight, preferably up to 2% by weight, more preferably from 0.5 to 2% by weight, even more preferably from 1 at 2% by weight, the weight being based on the total weight of the oral care composition.
    .: The metal oxide can comprise one or more metal oxides selected from . zinc oxide, tin oxide, titanium oxide, calcium oxide, copper oxide and iron oxide. Mixtures of such metal oxides can be used. However, zinc oxide is most preferred. Zinc oxide is known in the art to act as an anti-plaque and anti-calculus agent when used in oral care compositions. Consequently, when zinc oxide is used in the oral care compositions of the preferred embodiments of the present invention, zinc oxide can have a dual function, i.e. occlusion of dentin tubules and provide an anti-plaque/anti-tartar effect.
    The. In some embodiments, the source of metal oxide particles is selected from a powder, a solution or suspension of nanoparticles, a capsule and a globule.
    Therefore, embodiments of the invention include metal oxide, preferably zinc oxide, particles of a particular particle size, the particle size being selected to achieve occlusion of the dentin particles.
    Particle Size and Distribution In this specification, the particle size distribution was measured using a Malvern Particle Size Analyzer, Model Mastersizer 2000 (or comparable model) (Malvern Instruments, Inc., Southborough, Mass.), in which a beam of Helium-neon gas laser is projected through a transparent cell that contains silica, such as, for example, silica hydrogel particles suspended in an aqueous solution. The light rays that hit the particles are scattered through angles that are inversely proportional to the particle size. The recognized photodetector measures the amount of light at various predetermined angles. The electrical signals proportional to the measured values of light flux are then processed by a microcomputer system against a predicted dispersion pattern from theoretical particles as defined by the refractive indices of the sample and aqueous dispersant to determine 7 2O the distribution of the particle size of metal oxide. It should be understood that other methods of measuring particle size are known in the art, and based on the disclosure presented herein, the skilled artisan will understand how to calculate mean particle size, mean particle size, and/or distribution the particle size of metal oxide particles of the present invention.
    In one aspect, suitable metal oxide particles such as zinc oxide particles for oral care compositions of the invention have, for example, a particle size distribution of 3 to 4 micrometers, or alternatively, a size distribution. particle size of 5 to 7 micrometers, alternatively a particle size distribution of 3 to 5 micrometers, alternatively a particle size distribution of 2 to 5 micrometers, or alternatively a distribution of . “the particle size of 2 to 4 micrometers. Oral compositions within the scope of the invention include oxide particles | . metal such as zinc oxide that have an average particle size that is not greater than the average diameter of a mammalian dentin tubule, such that one or more particles are able to become lodged within the tubule, thereby effecting a reduction or elimination of tooth sensitivity observed. Suitable particles may have, for example, an average particle size of 8 micrometers or less, alternatively an average particle size of 3 to 4 micrometers, alternatively an average size
    7 particle size of 5 to 7 micrometers, alternatively, an average particle size of 3 to micrometers, alternatively, an average particle size of 2 to 5 micrometers, or alternatively, an average particle size of 2 to 4 micrometers . In one aspect of the invention, metal oxide particles such as Zinc Oxide have a particle size which is an average particle size. In another aspect, this particle size is an average (median) particle size. In one embodiment, the average particle comprises at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% of the total metal oxide particles in an oral hygiene composition of the invention.
    In one aspect of the invention, metal oxide particles such as zinc oxide have a particle size characterized by the parameters of an average particle size of about 2 µm to about 4 µm, a di10 of about 0. 5 um to about 45 um, and a d90 from about 5 um to about 10 um. As used herein, d10 refers to particles having a diameter that is 10% of the limit of the sample population (i.e., 10% of the population is equal to or less than the value of di10), and d90 refers to particles by having . a diameter that is 90% of the sample population boundary (that is, 90% of the population is equal to or less than the value of d980). In another aspect, a metal oxide such as Y DO zinc oxide has a particle size characterized by an average particle size from about 3 µm to about 5 µm, a d10 from about 1.5 µm to about of 3 um, and a d90 of about 6 um to about 11 um.
    The metal oxide particle can be prepared by any means known or developed in the art, and can be surface modified, if desired, to enhance the particle's ability to adhere to a tooth surface.
    Abrasive Particles The oral compositions may further comprise, in addition to the metal oxide dentin tubule occluding particles, one or more abrasive particles. Any abrasive particulates can be used and can be selected from sodium bicarbonate, calcium phosphate (for example dicalcium phosphate dihydrate), calcium sulfate, . precipitated calcium carbonate, silica (eg hydrated silica), iron oxide, aluminum oxide, perlite, plastic particles, eg polyethylene, and combinations thereof. In particular, the abrasive can be selected from a calcium phosphate (eg dihydrate: dicalcium phosphate), calcium sulfate, precipitated calcium carbonate, silica (eg hydrated silicas), calcium pyrophosphate and combinations . Any type of silica can be used, such as precipitated silicas or silica gels.
    In one embodiment, the oral hygiene composition comprises a silica having a particle size and an amount and distribution in the composition of
    You have oral hygiene so that silica has a dual function, and functions not only as a dentin tubule occluding particulate, but also as an abrasive particulate.
    Such a dual function particulate can be provided by a commercially available silica such as INEOS AC43, commercially available from Ineos Silicas, Warrington, UK, as described elsewhere herein.
    In one embodiment, such silica has an average particle size of 3 µm to 5 µm, as described elsewhere in detail herein.
    Various abrasives can be used in accordance with the present invention.
    One class of abrasives comprises silica particles as presented in detail here.
    Another class of abrasives are powdered silicas, in particular silica xerogels as defined in US-B-3,538,230. Additionally, as shown in US-B-4358437, powdered forms of calcium carbonate in an abrasive form is another class of abrasives.
    The compositions of the present invention may further comprise an optional abrasive 1s useful, for example, as a polishing agent.
    Any orally acceptable abrasive can be used, but the type, fineness, (particle size) and amount of abrasive must be selected so that tooth enamel is not excessively affected. worn out in normal use of the makeup.
    Suitable optional abrasives include silica, for example, in the form of precipitated silica or as a mixture with alumina, insoluble phosphates, calcium carbonate, and mixtures thereof.
    Among the insoluble phosphates useful as abrasives are orthophosphates, polymetaphosphates, and pyrophosphates.
    Illustrative examples are dicalcium orthophosphate dihydrate, calcium pyrophosphate, calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate and insoluble sodium polymetaphosphate.
    Polymers and Adhesive Materials The oral compositions of the invention may also include a polymeric adhesive material.
    The polymer can aid in the retention of metal oxide particles within the dentin tubules under saliva flow and during exposure to acidic foods and beverages.
    The polymeric sticky material can be any known or developed in the art that binds to the surface of a mammalian tooth and/or to the heterogeneous biofilm. which can also be present on the tooth surface.
    Fixation can occur by any means, such as ionic interaction, van der Waals forces, interactions : . hydrophobic-hydrophilic, etc.
    The adherent material can be, for example, any: homopolymers or copolymers (hereinafter collectively referred to as "polymers") which adhere to the surface of a tooth.
    Such polymers can include cellulose polymers, for example one or more hydroxyalkyl cellulose polymers such as hydroxypropylmethyl cellulose (HPMC), hydroxyethylpropyl cellulose (HEPC), hydroxybutylmethyl cellulose (HBMC), carboxymethyl cellulose (CMC).
    In one embodiment the polymeric sticky material comprises a mixture of cellulose materials, for example a mixture of two o-hydroxyalkyl cellulose materials having different molecular weight. The blend typically comprises a blend of two hydroxypropyl methyl cellulose materials of different molecular weight. In a particularly preferred embodiment, the two hydroxypropyl methyl cellulose materials comprise a blend of HPMC materials commercially available from the Dow Chemical Company under the tradenames Methocel E5 and Methocel ES0.
    Modification of the polymer system can increase the strength of the film matrix to support a high load of solids, especially zinc oxide. By rebalancing the polymer system, the present inventors have discovered a method in which more active ingredients can be loaded into the film than could be done previously. This creates a film with a higher concentration of zinc compound that can be released, and also reduces the amount of film needed to release these higher amounts. Improved higher charge zinc-containing film formula provides greater deposition on surfaces for superior effectiveness. Gives . Likewise, improving the film formulation to maintain a higher zinc compound load can reduce the total film amount needed in a product, n 20 while at the same time delivering the same effectiveness as with a lower film load. .
    Polymers may alternatively or additionally include poly(ethylene oxide) polymers (such as POLYOX from Dow Chemical), linear PVP and crosslinked PVP, PEG/PPG copolymers (such as BASF Pluracare L1220), ethylene oxide block copolymers (EO) - propylene oxide (PO) (such as polymers marketed under the trademark Pluronic available from BASF Corporation), ester gum, shellac, pressure sensitive silicone adhesives (such as BioPSA from Dow-Corning) , methacrylates, or mixtures thereof. In one embodiment, a copolymer comprises (PVM/MA). In one embodiment, a copolymer comprises poly(methylvinylether/maleic anhydride). In another embodiment, a copolymer comprises poly(methylvinyl ether/maleic acid). In another embodiment, a copolymer comprises poly | (methylvinylether / maleic acid). In another embodiment, a copolymer comprises ' . mixed salts of poly (methylvinylether / maleic acid). i: Polymers of any molecular weight can be used, including, for example, molecular weights from 50,000 to 500,000, 500,000 to 2,500,000 or 2,500,000 to 10,000,000” (calculated by number average or weighted average).
    In one embodiment, a copolymer of methyl vinyl ether and maleic anhydride can be used in a monomeric ratio of 1:4 to 4:1. Other polymers that can be used as tacky materials include those listed in US-A1-2006/0024246, the contents of which are incorporated herein by reference. "x Commercially available polymers may be used in the present invention. It is understood that over time, the exact size, weight and/or composition of a commercially available polymer may change. Based on the disclosure presented herein, the skilled artisan will understand how to determine whether such polymers are useful in the invention.
    Compositions o In one aspect of the invention, oral care compositions containing the metal oxide particle, which may optionally contain silica particles, can desensitize a tooth. In another aspect, such compositions of the invention provide tooth desensitization that is superior to conventional desensitizing dentifrices. By way of non-limiting example, a dentifrice containing metal oxide particles of the invention provides desensitization of teeth by providing greater desensitization than a conventional dentifrice or a conventional desensitizing dentifrice by providing desensitization faster than a conventional dentifrice or a conventional desensitizing dentifrice, or by a combination of greater desensitization and faster desensitization, among other 7 20 effects. In one embodiment, a composition containing metal oxide particles of the invention provides superior desensitization and/or desensitization in the absence of any other desensitizing agent. In another embodiment, a composition containing metal oxide particles of the invention provides superior desensitization and/or desensitization, and may contain one or more additional desensitizing agents, such as silica particles, as described elsewhere herein.
    The invention also encompasses methods for using and/or applying a desensitizing composition containing metal oxide particles, which may optionally contain silica particles. In one embodiment, such a composition containing metal oxide particles can be applied to the tooth by means of conventional brushing techniques (for example, the use of a toothbrush). In another. In one embodiment, such a metal oxide particle-containing composition may be applied to the tooth by a method different from the conventional techniques of: . brushing. Other application methods include manual application (eg BR applying a composition to a tooth using one or more fingers, rubbing the tooth surface, rubbing in a circular motion, etc...), or application using any known dental instrument or applicator. It is to be understood, based on the disclosure presented herein, that any method of covering with a composition on a tooth, optionally using varying degrees of physical pressure, is encompassed by the invention.
    . The desensitization of a tooth in accordance with the invention may be measured by any technique set forth herein, or any technique known to those skilled in the art. DA Application of the composition to the tooth surface results in the introduction of the composition into one or more tubules of the dentin. The composition is applied to teeth by any method disclosed herein or known in the art.
    In some embodiments, the oral hygiene composition may include any other therapeutic, cosmetic and/or aesthetic material as desirable. Examples include non-silica desensitizing agents (eg, a nitrate salt, an arginine ester, a bicarbonate salt, potassium nitrate, an arginine-bicarbonate-phytate complex, potassium citrate, and arginine, among others). chemical bleaching agent (such as a peroxide releasing compound), an opaque bleaching agent (such as hydroxyapatite) and an anticalculus agent. Other options for inclusion in the oral hygiene composition of the invention include triclosan; tin ion agents; chlorhexidine; 1s alexidine; hexetidine; sanguinarine; benzalkonium chloride; salicylanilide; domifen bromide; cetylpyridinium chloride (CPC); tetradecylpyridinium chloride (TPC); N-tetradecyl-4-ethylpyridinium chloride (TDEPC); octenidine; delmopinol; octapinol; nisin; ion agents - zinc; copper ion agents; essencial oils; furanones; bacteriocins, lauroyl ethyl arginate, magnolia extracts, a metal ion source, arginine bicarbonate, honokiol, magonol, ursolic acid, ursic acid, morin, sea buckthorn extract, an enzyme, an extract of Camellia, a flavonoid , a flavan, halogenated diphenyl ether, creatine, and propolis.
    The oral hygiene composition can in particular be a dentifrice composition which can be a toothpaste or a gel.
    The composition according to the present invention may comprise an antimicrobial agent which may be selected from halogenated diphenyl ether (triclosan), herbal extracts or essential oils (eg rosemary extract, thymol, menthol, eucalyptol, methyl salicylate), bisguanide antiseptics (eg, chlorhexidine, alexidine, or octenidine), phenolic antiseptics, hexetidine, povidone iodine, delmopinol, salifluor, sanguinarine, propolis, oxygenating agents (eg hydrogen peroxide, sodium peroxyborate buffered, or peroxycarbonate), cetyl pyridinium chloride, magnolia extract, magnolol, honokiol, butyl magnolol, propyl honokiol, and mixtures thereof. Anti-fixation agents such as Solrol may also be included, as may agents. plaque dispersants such as enzymes (papain, glucoamylase, etc.).
    The composition according to the present invention may also comprise one or more other agents typically selected from an anti-plaque agent, a bleaching agent, antibacterial agent, cleaning agent, a flavoring agent, a sweetening agent, tackifiers, surfactants, foam modulators, abrasives,
    O. pH modifying agents, humectants, mouthfeel agents, dyes, abrasives, tartar control agents (antitartar), fluoride ion source, saliva stimulating agent, nutrients and combinations thereof.
    Various components that can be added to the composition include, for example, a sweetening agent such as saccharin or sodium saccharin, alcohols such as ethanol, fluoride ion sources such as sodium fluoride, as well as glycerin, sorbitol, propylene glycol, polyethylene glycols, Poloxomer polymers such as POLOXOMER 407, PLURONIC F108, (both available from BASF Corporation), alkyl polyglycoside (APG), polysorbate, PEGA40, castor oil, menthol, and more.
    Flavorants among those useful in this invention include any material or mixture of materials operable to improve the flavor of the composition.
    Any orally acceptable natural or synthetic flavoring can be used, such as aromatic oils, aromatic aldehydes, esters, alcohols, similar materials, and combinations thereof.
    Flavorings include vanillin, sage, marjoram, parsley oil, spearmint oil, cinnamon oil, oil of wintergreen (methyl salicylate), peppermint oil, clove oil, laurel oil, anise oil, oil of eucalyptus, citrus oil, fruit essences and oils including those derived from lemon, orange, lime, grapefruit, apricot, banana, grape, apple, strawberry, cherry, - pineapple, etc., flavors derived from beans and nuts such as coffee, cocoa, cola, peanuts, almonds, etc., adsorbed and encapsulated flavorings, and their mixtures.
    Also included: 20 inside flavorings here are ingredients that provide fragrance and/or other sensory effects in the mouth, including cooling or warming effects.
    Such ingredients include menthol, menthyl acetate, menthyl lactate, camphor, eucalyptus oil, eucalyptol, anethole, eugenol, cassia, oxanone, [alpha]-irisone, propenyl guayetol, thymol, linalool, benzaldehyde, cinnamaldehyde, N-ethyl -p-menthan-3-carboxamine, N,2,3-trimethyl-2-isopropylbutanamide, 3-1-menthoxypropane-1,2-diol, cinnamaldehyde glycerol acetal (CGA), glycerol methone acetal (MGA), and its mixtures.
    One or more flavorings are optionally present in a total amount of from about 0.01% to about 5%, optionally in various embodiments from about 0.05 to about 2%, from about 0.1% to about 2.5%, and from about 0.1 to about 0.5%. Sweetening agents among those useful herein include dextrose, polydextrose, sucrose, maltose, dextrin, dry invert sugar, mannose, xylose, ribose, fructose, levulose, galactose, corn syrup, partially hydrolyzed starch, starch hydrolyzate. hydrogenated, sorbitol, mannitol, xylitol, maltitol, isomalt, aspartame, neotame, saccharin and its . salts, sucralose, intense sweeteners based on dipeptide, cyclamates, dihydrochalcones, and mixtures thereof.
    Mouthfeel agents include materials that impart a desirable texture or other feel during use of the composition.
    Colorants among those useful in this invention include pigments, dyes, varnishes, and agents that impart a particular shine or reflectivity such as beading agents. In various embodiments, the dyes are operable to provide a white or light colored coating on a tooth surface, to act as an > indicator of locations on the tooth surface that have actually been brought into contact by the composition, and/or to modify the appearance, in particular the color and/or opacity, of the composition to enhance the attractiveness to the consumer. Any orally acceptable colorant can be used, including FD&C dyes and pigments, talc, mica, magnesium carbonate, calcium carbonate, magnesium silicate, magnesium aluminum silicate, silica, titanium dioxide, zinc oxide, red, yellow , iron oxide brown and black, ferric ammonium ferrocyanide, manganese vilolette, ultramarine, titanium-submitted mica, bismuth oxychloride and mixtures thereof. One or more dyes are optionally present in a total amount of from about 0.001% to about 20%, for example from about 0.01% to about 10% or from about 0.1% to about 5% . The compositions of the present invention optionally comprise a tartar control (anti-calculus) agent. Tartar control agents among those useful in this invention include the salts of any of these agents, for example, their salts. alkali metal and ammonium: phosphates and polyphosphates (eg pyrophosphates), polyaminopropanesulfonic acid (AMPS), polyolefin sulfonates, polyolefin phosphates, r 20 diphosphonates such as azacycloalkane-2,2-diphosphonates (eg azacycloheptane acid-2, 2-diphosphonic acid), N-methyl azacyclopentane-2,3-diphosphonic acid, ethane-1-hydroxy-1,1-diphosphonic acid (EHDP) and ethane-1-amino-1,1-diphosphonate, phosphonoalkane carboxylic acids and salts of useful inorganic phosphate and polyphosphate include monobasic, dibasic and tribasic sodium phosphates, sodium tripolyphosphate, tetrapolyphosphate, mono-, di-, tri- and tetrasodium PB pyrophosphates, sodium trimetaphosphate, sodium hexametaphosphate and mixtures thereof.
    The compositions of the present invention optionally comprise a fluoride ion source and are useful, for example, as an anti-caries agent. Any orally acceptable particulate fluoride ion source can be used, including potassium, sodium and ammonium fluorides and monofluorophosphates, stannous fluoride, indium fluoride, amine fluorides such as olaflur (N'-octadecyltrimethylendiamine-N,N,N'- tris(2-ethanol)-dihydrofluoride), and or mixtures thereof. One or more sources of fluoride ions are optionally present in an amount that provides a clinically effective amount of fluoride ion soluble in the | . oral composition. . The compositions of the present invention optionally comprise a saliva stimulating agent useful, for example, in improving dry mouth. Any orally acceptable saliva stimulating agent can be used, including without limitation food acids such as citric, lactic, malic, succinic, adipic, fumaric and tartaric ascorbic acid, and mixtures thereof. One or more saliva-stimulating agents are
    "and optionally present in total amount effective for saliva stimulation.
    Compositions of the present invention optionally comprise a nutrient.
    Ts Suitable nutrients include vitamins, minerals, amino acids, and mixtures thereof.
    Vitamins include vitamins C and D, thiamine, riboflavin, calcium pantothenate, niacin, folic acid, nicotinamide, pyridoxine, cyanocobalamin, para-aminobenzoic acid, bioflavonoids, and mixtures thereof.
    Nutritional supplements include amino acids (such as L-tryptophan, L-lysine, methionine, threonine, levocarnitine and L-carnitine), lipotropics (such as choline, inositol, betaine, and linoleic acid), and mixtures thereof.
    The dentifrice composition according to the present invention comprises an orally acceptable carrier in a product such as a toothpaste or a gel.
    As used herein, an "orally acceptable carrier refers to a material or combination of materials that are safe for use in the compositions of the present invention, compatible with a reasonable benefit/risk ratio. 1s Preferably, the specific materials and compositions to be used in this invention are, therefore, pharmaceutically or cosmetically acceptable, clinically effective, and/or clinically effective.
    As used herein, such a component - "*pharmaceutically acceptable" or "cosmetically acceptable", "clinically effective" and/or "clinically effective" is one that is suitable for use with humans and/or animals and is provided in an appropriate amount (a clinically effective amount) to provide the desired therapeutic, prophylactic, sensory, decorative or cosmetic benefit without undue adverse side effects (such as toxicity, irritation and allergic response) commensurate with a reasonable benefit/risk ratio.
    The oral hygiene compositions described herein can be formulated in any form of release that allows the contact of the metal oxide particles and the amino acid, and ° when the polymeric adhering material is present, to the surface of the teeth.
    For example, the compositions can be formulated in a mouthwash, a paste, a gel, a tablet (soluble or chewable), a spray, a chewing gum, and a film (totally or partially soluble or insoluble). The composition may contain any of the conventional excipients or carriers, although these will vary depending on the dosage form or dosage medium selected.
    Excipients or carriers can include, for example, humectants, colorants, flavors, glycerin, sorbitol, xylitol, and/or: . propylene glycol, water or other solvents, gum bases, thickening agents, surfactants, carrageenan (rich moss), xanthan gum and sodium carboxymethyl cellulose, starch, polyvinyl pyrrolidone, hydroxyethyl propyl cellulose, hydroxybutyl methyl cellulose, hydroxypropyl bimethyl cellulose, and hydroxyethyl cellulose and amorphous silicas.
    Surfactants can be included if desired.
    Examples of suitable surfactants include water soluble salts of higher fatty acid monoglyceride monosulfates, such as the monosulfated monoglyceride sodium salt of hydrogenated coconut oil fatty acids; higher alkyl sulfates such as sodium lauryl sulfate; alkyl aryl sulfonates such as sodium dodecyl benzene sulfonate; higher alkyl sulfoacetates such as sodium lauryl sulfoacetate; higher fatty acid esters of 1,2-dihydroxypropane sulfonate, and the substantially saturated higher aliphatic acyl amides of lower aliphatic amino carboxylic compounds, such as those having from 12 to 16 carbon atoms in the fatty acid, alkyl or acyl radicals; and others more. Examples of the last mentioned amides include N-lauryl sarcosine, and the sodium, potassium and ethanolamine salts of N-lauryl, N-myristoyl or N-palmitoyl sarcosine. Others include, for example, nonionic polyoxyethylene surfactants such as Polyoxamer 407, Steareth 30, Polysorbate 20, and castor oil; and amphoteric surfactants such as cocamidopropyl betaine (tegobaine) and cocamidopropyl betaine lauryl glycoside; condensation products of ethylene oxide with various hydrogen-containing compounds that are reactive with them and have long hydrocarbon chains (eg, aliphatic chains of 12 to 20 carbon atoms), whose condensation products (ethoxamers) contain hydrophilic polyoxyethylene components , such as the condensation products of poly-(ethylene oxide) with fatty acids, fatty alcohols, fatty amides and other fatty components, and with propylene oxide and polypropylene oxides.
    . In one embodiment, the oral composition includes a surfactant system that is sodium lauryl sulfate (SLS) and cocamidopropyl betaine.
    The oral hygiene composition of the invention can be prepared by any means known in the art. For example, methods of preparation for dentifrices are well known, for example as described in US-B-3966863, US-B-3980767, US-B-4328205 and US-B-4358437, the contents of which are incorporated herein by reference. . In general, any humectant (for example, glycerine, sorbitol, propylene glycol and/or polyethylene glycol) is dispersed in water with a conventional mixer under agitation. Within this dispersion are added thickeners such as carboxymethyl cellulose (CMC), carrageenan, or xanthan gum; any anionic polycarboxylate; any salts such as sodium fluoride anticaries agents; and any sweeteners.
    The resulting mixture is stirred until a homogeneous gel phase forms. In the gel phase any pigments used such as TIO are added, and additionally any acid or base required to adjust the pH of the composition. These ingredients are mixed until a homogeneous phase is obtained.
    The mixture is then transferred to a high speed/vacuum mixer, where surface active ingredients are added to the mixture. The metal oxide particles and any silica particles used are added subsequently. Any water-insoluble agents, such as triclosan, are solubilized in the flavoring oils to be included in the dentifrice, and this solution is added along with the surfactants into the mixture, which is then mixed at high speed in the range of 5 to 30 minutes, under a vacuum of 20 to 50 mm Hg. The resulting product is a homogeneous, semi-solid, extrudable paste or gel product.
    Methods of use The oral hygiene composition, e.g., dentifrice, according to the present invention can be administered or applied to a human or other animal subject. The composition is suitable for administration or application to the oral cavity of a human or animal subject.
    The invention also includes within its scope several related methods. For example, the invention includes within its scope methods of reducing and methods of occluding a tubule of dentin in a mammalian tooth, methods of protecting dentin against acid-mediated degradation, and methods of reducing tooth sensitivity.
    1 Each of these methods includes the steps of applying any of the compositions described above to the tooth surface. Application can be carried out by any method, as long as the adherent material and particles are brought into contact with the tooth surface. Application can be performed by brushing, flossing, prophylaxis, irrigation, scrubbing, rinsing (washing of the oral cavity), application of f 20 foam / gel and tray, chewing, spraying, brushing, etc., or applied by film or ribbon.
    Tooth sensitivity can be reduced in accordance with a method of the invention by applying a composition of the invention to a tooth surface. A composition can be applied using a traditional process, as described in detail elsewhere in this document, or through any instrument or applicator, whether or not typically associated with dental use. In one embodiment, one or more human fingers is used to apply a tooth sensitivity reducing composition to one or more teeth. A finger can be used to coat the composition on the surface of a tooth, or otherwise apply the composition to the surface of SD of a tooth.
    Alternatively, the invention includes methods of enhancing or maintaining the systemic health of a mammal by applying a composite to an oral surface: (both hard and soft tissues of the oral cavity). The composition for use in this method can be any of those described above, provided that it contains at least one of triclosan; triclosan monophosphate; chlorhexidine; alexidine; hexetidine; sanguinarine; benzalkonium chloride; salicylanilide; domiphen bromide; cetylpyridinium chloride (CPC); tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC); octenidine; delmopinol; octapinol; nisin; zinc ion agent, copper ion agent; essencial oils; furanones; bacteriocins, ethyl lauroyl arginate, magnolia extracts, a metal ion source, arginine bicarbonate, honokiol, magonol, ursolic acid, ursic acid, morin, sea buckthorn extract, a peroxide, an enzyme, an extract of Camellia , a flavonoid, a flavan, halogenated diphenyl ether, creatine, and propolis. The application can be at least once a day, although up to five times a day may be preferable, and it can be carried out over a period of time, for example, a week, up to a year, up to three years, or over a period of time. all life. Various embodiments will now be described with reference to the following non-limiting examples.
    EXAMPLES Example 1 A dentifrice composition having the formula in Table 1 was prepared. The compositions used in Examples and Comparative Examples had varying amounts of zinc oxide (ranging from 0 to 2% by weight) and amino acids (ranging from 0 to 5% by weight). For Example 1, the dentifrice composition comprises 1% by weight of zinc oxide powder, the ZnO being encapsulated, at a load of 50% by weight, in a polymer film, in particular in a polymer film which comprises a combination of two different molecular weight HPMC materials comprising Methocel E5 and oO Methocel E50. The combined zinc oxide/polymer film comprises 1% by weight ZnO and 1% by weight polymer film, each weight being based on the total weight of the composition. For Example 1, the dentifrice composition also comprises 4.3% by weight of L-arginine. Table 1: Composition of Toothpaste
    BR OO OO : een Aa TERA o tado [Areia Tama
    To measure the release of zinc to hydroxyapatite, the dentifrice was diluted 1 part by weight of dentifrice to 2 parts by weight of water and stirred to disperse the dentifrice.
    Then, a saliva coated hydroxyapatite disc was added to this slurry.
    The disc was slurried for 10 minutes and then rinsed three times with five ml of water.
    The disc was then digested with nitric acid and total zinc measured by atomic absorption spectroscopy.
    Zinc absorption data from the dentifrice formula of Example 1 containing L-arginine and zinc oxide released from a polymer film, when Oo used as a slurry, is given in Table 2. It can be seen from Example 1 that zinc absorption was significant.
    Table 2: Zinc absorption into hydroxyapatite from a dentifrice slurry.
    Comparative Example 1 For Comparative Example 1, the dentifrice composition having the formula of Table 1 was prepared which comprises (as in Example 1) 1% by weight of ZnO encapsulated in a polymer film, but was modified compared to the Example 1, in which no chelation molecule, such as L-arginine, was present.
    The result is also shown in Table 2. It can be seen from Comparative Example 1 that zinc absorption was significantly lower, almost an order of magnitude lower than for Example 1. Comparison of Example 1 and Example Comparative 1 demonstrates that the chelating agent enhances the release of zinc oxide on the dentin surface, in particular * when used in combination with a polymeric film. . 25 Examples 2 to 7 and Comparative Example 2 . Example 1 was repeated except that for Example 2 a different amount of L-arginine was used and for Examples 3 to 7 different amounts of different amino acids were used.
    Furthermore, for Examples 2 to 7 all formulas contained 1% ZnO as a powder, and no polymer film as for Example 1 was present.
    Examples 2 to 7 employed a 1.4:1 molar ratio of the respective amino acid in the ZnO powder.
    For Comparative Example 2, again no amino acid was present and ZnO was present as a powder.
    The results of the zinc absorption test as described above in relation to Example 1 are summarized in Table 3. The zinc absorption data of the dentifrice formulas of Examples 2 to 7 containing zinc oxide powder and a variety of amino acids are presented. in Table 3, as is the result of Comparative Example 2 Table 3: Zinc absorption in hydroxyapatite of a paste | Zinc Absorption: A comparison of Examples 1 and 2 in both Tables 2 and 3 confirms that zinc absorption is significantly increased by the addition of L-arginine in the : 10 toothpaste and the effect is observed whether zinc oxide is added to dentifrice encapsulated in a polymeric film (Example 1) or as a powder (Example 2). Table 3 shows that zinc absorption can be increased by a variety of amino acids.
    The results of these Examples and Comparative Examples demonstrate that the 1st amino acids can improve the release of insoluble zinc oxide on a surface similar to that found in the oral cavity.
    The increased release of zinc oxide should improve the antibacterial benefits associated with an increase in zinc.
    These Examples highlight several amino acids that appear to be able to release zinc on surfaces of the oral cavity.
    Additional amino acids such as leucine, lysine, alanine, asparagine, aspartate, phenylalanine, glutamate, threonine, glutamine, tryptophan, . glycine, valine, praline, tyrosine, and histidine can also be used.
    The release of other metal oxide particles, such as tin or copper oxide, on the surfaces of the oral cavity can also be improved by combining with amino acids.
    Example 3 Example 3 was carried out to evaluate the occlusion effectiveness of a dentifrice formula including an amino acid as a chelator for zinc oxide.
    For Example 3, a dentifrice composition having the formula in Table 1 was prepared which comprised 1% by weight of zinc oxide powder (as in Example 2) and
    3% by weight amino acid, which comprised L-arginine. To assess the occlusion effectiveness of dentifrice formulas, dentin discs were prepared from human molars. The molars were cut, filed and polished. Finally, the discs were lined with 6 wt% citric acid and sonicated to open the tubules on the dentin surface. Each disc was brushed for 1 minute and 30 seconds with a mechanical toothbrush and a slurry of water and dentifrice 1:2 by weight. After brushing, the disc was rinsed for 15 seconds with water and then stored in a phosphate buffer solution for 15 minutes. This treatment cycle was repeated 7 times per disc. After the seventh treatment, the discs were examined using a confocal microscope to image the degree of surface coverage by the dentifrice product. The discs were then exposed to 1 min acid tests. (using a commercial carbonated cola drink) and examined after each treatment to assess the amount of product remaining in the 1 tubules of dentin. The results of this study are shown in Figure 1. It can be seen from Example 3 that after 7 brushing cycles there was good occlusion of the dentin tubules. After 12 subsequent cycles of acid testing using glue, there was still good occlusion of the dentin tubules. Comparative Example 3 . For Comparative Example 3, a dentifrice composition having the formula of Example 3 (i.e., 1 wt% ZnO powder), but omitting the L-arginine, was prepared. This dentifrice was subjected to the same occlusion effectiveness test as in Example 3, and the result is also shown in Figure 1. It can be seen for Comparative Example 3 that after 7 brushing cycles there was poor occlusion of the dentin tubules. After 12 subsequent cycles of acid testing using glue, there was even worse occlusion of the dentin tubules.
    A comparison of Example 3 and Comparative Example 3 shows that metal oxide particles, in particular zinc oxide particles, provide good dentin occlusion when used in combination with an amino acid such as L-arginine So as a chelator. Without being bound by any theory, it is believed that the amino acid is likely to improve the adhesion of ZnO within the dentin tubules, and on other surfaces of the ' . oral cavity, through the formation of a bridge between zinc oxide and dentin. The negatively charged carboxylate group on the amino acid is suspected to bind zinc oxide (due to the existence of a positive zeta potential at pH < 9 for zinc oxide, as disclosed in an article titled “The effect of pH on the corrosion inhibition of zinc pigments by phenol derivatives”, by at B. Muller and W. Klager, Corrosion Science, 38 (1996), pages. 1869-1875), with the positively charged group that correspondingly binds to the dentin surface.
    All amino acids are zwitterionic at physiological pH, and so it is believed that the amino acid may be able to bind to a charged particle on charged surfaces in the oral cavity.
    The charge and functionality of the amino acid R group varies among amino acids; however from current studies by the inventors, the charge/functionality in the R group does not appear to have a significant impact on zinc absorption on hydroxyapatite surfaces, as evidenced by the results in Table 3. As shown in Figure 1, it was observed by the present inventors that the increased release of zinc oxide to dentin by L-arginine provides occlusion of dentin tubules that is more resistant to acid attack than zinc oxide alone.
    This is an additional potential benefit provided by the zinc oxide/amino acid system as the occlusion of dentin tubules is associated with the relief of hypersensitivity.
    权利要求:
    Claims (26)
    [1]
    1. Oral hygiene composition, characterized by the fact that it comprises: an orally acceptable vehicle; a source of metal oxide particles, wherein said metal oxide particles have an average particle size of 1 to 7 micrometers; and one or more amino acids.
    [2]
    2. Oral hygiene composition according to claim 1 or claim 2, characterized in that the metal oxide comprises at least one metal oxide selected from zinc oxide, tin oxide, titanium oxide, calcium oxide, copper oxide and iron oxide or a mixture of these.
    [3]
    3. Oral hygiene composition according to claim 2, characterized in that the metal oxide comprises zinc oxide.
    [4]
    4. Oral hygiene composition according to any one of claims 1 1s to 3, characterized in that the metal oxide particles have a particle size distribution of 3 to 4 micrometers, a particle size distribution of 5 to 7 micrometers, a particle size distribution of 3 to 5 : micrometers, a particle size distribution of 2 to 5 micrometers, or a particle size distribution of 2 to 4 micrometers.
    [5]
    . 20 5. Oral hygiene composition according to any one of claims 1 to 4, characterized in that the metal oxide particles are present in an amount of up to 5% by weight, based on the total weight of the composition of oral hygiene.
    [6]
    6. Oral hygiene composition according to claim 6, characterized in that the meta oxide particles! they are present in an amount of 0.5 to 2% by weight, based on the total weight of the oral care composition.
    [7]
    7. Oral hygiene composition according to any one of claims 1 to 6, characterized in that the source of metal oxide particles is selected from a powder, a solution of nanoparticles; a suspension of nanoparticles; a capsule; and a globule.
    [8]
    8. Oral hygiene composition according to any one of claims 1 to 6, characterized in that at least one of said one or more amino acids is selected from arginine, L-arginine, cysteine, leucine, isoleucine, lysine , L-lysine, alanine, asparagine, aspartate, phenylalanine, glutamate, glutamic acid, threonine, glutamine, tryptophan, glycine, valine, praline, serine, tyrosine and histidine, and a combination of two or more of these.
    [9]
    9. Oral hygiene composition according to claim 8, characterized in that at least one of said one or more amino acids is selected from L-arginine, cysteine, isoleucine, L-lysine, glutamic acid, serine, and a combination of two or more of these.
    [10]
    10. Hygiene composition now! according to claim 9, characterized in that at least one of said one or more amino acids is L-arginine.
    [11]
    11. Oral hygiene composition according to any one of claims 1 to 10, characterized in that at least one of said one or more amino acids is present in an amount of up to 5% by weight, based on the total weight of the oral hygiene composition.
    [12]
    12. Oral hygiene composition according to claim 11, characterized in that at least one of said one or more amino acids is present in an amount of 0.5 to 5% by weight, based on the total weight of the composition of oral hygiene.
    [13]
    13. Oral hygiene composition according to claim 12, characterized in that at least one of said one or more amino acids is present in an amount of 2.5 to 4.5% by weight, based on the total weight of the oral hygiene composition.
    [14]
    14. Oral hygiene composition according to any one of claims 1 to 13, characterized in that it further comprises a polymeric adherent material.
    [15]
    15. Oral hygiene composition according to claim 14, characterized. in that the metal oxide source is a capsule, and the capsule comprises a polymeric sticky material.
    [16]
    20 16. Oral hygiene composition according to claim 14 or claim 15, characterized in that the polymeric sticky material comprises one or more cellulose polymers.
    [17]
    17. Oral hygiene composition according to claim 16, characterized in that at least one of said one or more cellulose polymers is a hydroxyalkyl cellulose polymer selected from hydroxypropylmethyl cellulose (HPMC), hydroxyethylpropyl cellulose (HEPC), hydroxybutylmethyl cellulose (HBMC), and carboxymethyl cellulose (CMC).
    [18]
    18. Oral hygiene composition according to claim 17, characterized in that the polymeric sticky material comprises a mixture of two hydroxyalkyl cellulose polymers having different molecular weights and the metal oxide comprises zinc oxide which is encapsulated in the mixture of two hydroxyalkyl cellulose polymers.
    [19]
    19. Oral hygiene composition according to any one of claims 14 to 18, characterized in that the polymeric adhesive material comprises one or more polymers selected from a polymer of poly (ethylene oxide), polyvinylpyrrolidone (PVP), copolymer polyethylene glycol (PEG) / polypropylene glycol (PPG), block copolymers of ethylene oxide (EO) - propylene oxide (PO), ester gum, shellac, pressure sensitive silicone adhesives, methacrylates, or its mixtures.
    [20]
    20. Oral hygiene composition according to any one of claims 1 to 19, characterized in that it is a dentifrice composition.
    [21]
    21. Oral hygiene composition according to claim 20, characterized in that it is a toothpaste or a gel.
    [22]
    22. Oral hygiene composition according to any one of claims 1 to 19, characterized in that the composition is formulated in a form selected from a mouthwash solution, a chewing gum, a soluble tablet, and a soluble film.
    [23]
    23. Method of reducing tooth sensitivity, characterized in that it comprises applying to the surface of a mammalian tooth an oral hygiene composition according to any one of claims 1 to 22.
    [24]
    24. Method of protecting dental surfaces from acid-mediated degradation, characterized in that it comprises the application to the surface of a mammalian tooth of an oral hygiene composition according to any one of claims 1 to 22.
    [25]
    5 25. A method of maintaining or increasing the systemic health of a mammal comprising applying a composition to an oral surface of a mammal at least once a day for a period of time, characterized in that the composition comprises: a . a hygiene composition according to any one of claims 1. 20 to 22e b. an agent selected from triclosan; triclosan monophosphate; chlorhexidine; alexidine; hexetidine; sanguinarine; benzalkonium chloride; salicylanilide; domifen bromide; cetylpyridinium chloride (CPC); tetradecylpyridinium chloride (TPC); N-tetradecyl-4-ethylpyridinium chloride (TDEPC); octenidine; delmopinol; octapinol; nisin, zinc ion agent; copper ion agent, essential oils; furanones; bacteriocins, ethylauroyl arginate, magnolia extracts, a source of metal ions, fluoride, tin ions, arginine bicarbonate, honokiol, magonol, ursolic acid, ursic acid, morin, sea buckthorn extract, a peroxide, an enzyme , an extract of Camellia, a flavonoid, a flavan, halogenated diphenyl ether, creatine and propolis.
    [26]
    26. Method of occluding a tubule of dentin within the surface of a mammalian tooth, characterized in that it comprises applying to the tooth surface a composition according to any one of claims 1 to 22.
    aaa io O comparative 3 SNS O 1% by weight of powder| RANA SO
    7 of ZnO + none | MA The amino acid A A 1% by weight of | OO PO podeznO+3% [NA O s by weight of L- ASSNANSS O arginine FS
    Figure 1
    类似技术:
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    RU2587058C2|2016-06-10|Oral care compositions
    BR112018009665B1|2021-05-18|oral care composition to reduce hypersensitivity on a tooth and use of chitosan and at least one small particle silica
    同族专利:
    公开号 | 公开日
    US9883995B2|2018-02-06|
    US8652495B2|2014-02-18|
    US20130017240A1|2013-01-17|
    WO2011123123A1|2011-10-06|
    CN102811698B|2016-01-13|
    ES2548988T3|2015-10-22|
    TW201204402A|2012-02-01|
    JP2013523730A|2013-06-17|
    RU2537035C2|2014-12-27|
    CA2792356C|2014-11-18|
    SG183905A1|2012-10-30|
    US9532932B2|2017-01-03|
    US20170100312A1|2017-04-13|
    AU2010349783A1|2012-09-20|
    MX2012010608A|2012-10-03|
    RU2012146347A|2014-05-10|
    US20140120041A1|2014-05-01|
    EP2552382A1|2013-02-06|
    PL2552382T3|2016-02-29|
    TWI406676B|2013-09-01|
    CN102811698A|2012-12-05|
    AU2010349783B2|2013-08-22|
    MY160776A|2017-03-15|
    CA2792356A1|2011-10-06|
    US20180116924A1|2018-05-03|
    EP2552382B1|2015-09-09|
    ZA201206666B|2016-09-28|
    JP5694506B2|2015-04-01|
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    法律状态:
    2021-06-08| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2021-06-15| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2021-09-14| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|
    2022-01-11| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    优先权:
    申请号 | 申请日 | 专利标题
    PCT/US2010/029472|WO2011123123A1|2010-03-31|2010-03-31|Oral care composition|
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