MX2008007468A - Improved oral compositions comprising zinc citrate and/or tocopherol agents - Google Patents

Abstract

Methods and oral compositions for reducing one or more of plaque, tartar/ caries, dentinal sensitivity, malodor, and/ or inflammation are provided. The composition comprise an active ingredient that comprises a zinc salt.

Description

IMPROVED ORAL COMPOSITIONS COMPRISING ZINC AND / OR TOCOPHEROL CITRATE AGENTS CROSS REFERENCE TO RELATED REQUEST The present invention claims the benefit of United States Provisional Application No. 60 / 752,341 filed December 21, 2005, which is hereby incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION It is generally believed that plaque is formed as a byproduct of bacterial growth, and comprises a dense microbial layer containing a mass of microorganisms embedded in a polysaccharide matrix that adheres to the surfaces of the teeth and in the gingival margin. Periodontal diseases are inflammatory disorders that are the result of complex interactions between periodontal pathogens and the response of the host immune system. Gingivitis is inflammation or infection of the gums and alveolar bones that support the teeth, and is generally thought to be caused by bacteria in the mouth (particularly bacteria associated with plaque formation) and the inflammatory response triggered by the presence of bacteria / toxins of bacterial by-products. Periodontitis is a state of progressively worsened disease compared to gingivitis, in which inflamed gums begin to withdraw from the teeth, which can ultimately result in the destruction of the bone and periodontal ligament. Inflammation and chronic infection potentially results in the subsequent loss of teeth.

Additionally, bacteria generate acids as final products of the bacterial degradation of fermentable carbohydrates. These acids can dissolve the hydroxyapatite, which can result in the loss of cement and / or enamel potentially leading to the formation of dental caries or dentine hypersensitivity. Dentine hypersensitivity can occur when the enamel or protective cement that covers the dentin is lost, exposing the dentinal tubules to the oral environment. When the fluid filling the narrow dentinal tubules is exposed to the mouth, it allows the cold, tactile, evaporative and osmotic stimuli to be transmitted through the dentin to the pulp, which is then perceived as a sharp pain in the nerve fibers. . Dental caries causes the loss of enamel / cement, typically followed by enzymatic lysis of the underlying tissue, then the formation of cavities that can penetrate enamel, dentin and can reach the pulp, eventually leading to tissue necrosis.

There is a need for oral care compositions that effectively reduce the development or progression of oral disease, preferably containing an active ingredient that functions to decrease the effects of oral disease by preventing or reducing the multiple etiological factors that contribute to the oral disease. oral disease and / or exacerbate it. There is a continuing interest in the oral care field for oral care compositions that improve the treatment of plaque and tartar formation. Additionally, it would be convenient to have oral care compositions that provide multiple treatment benefits, such as those oral compositions that also reduce the sensitivity of dentine, the formation of caries and / or inflammation in the oral cavity.

BRIEF SUMMARY OF THE INVENTION In certain embodiments, the invention is directed to a method for treating an oral surface having dental sensitivity, comprising contacting the oral surface with an oral composition comprising a active ingredient comprising a zinc citrate agent and a potassium salt.

In certain embodiments, the present invention is directed to a method of reducing astringency, comprising contacting the oral surface with an oral composition comprising an active ingredient comprising a zinc citrate agent and a potassium salt.

In certain embodiments, the present invention is directed to a method for reducing plaque or tartar formation, caries or malodour, comprising contacting the oral surface with an oral composition comprising an active ingredient comprising a citrate agent. zinc and a potassium salt.

In certain embodiments, the present invention is directed to a method of treating inflammation in an oral tissue comprising: contacting the inflamed oral tissue with an oral composition comprising an active ingredient comprising a zinc citrate agent and a tocopherol agent.

In certain embodiments, the present invention is directed to an oral antiplaque and desensitizing composition, comprising: an active ingredient comprising a zinc citrate agent and a potassium citrate agent; Y a copolymer of maleic anhydride and polyvinyl methyl ether and a polyphosphate.

In certain embodiments, the present invention is directed to an oral composition, comprising: an active ingredient for oral care comprising a zinc citrate agent and a tocopherol agent, wherein the tocopherol agent comprises at least one compound selected from tocol (2-methyl-2- (4, 8, 12- trimethyltridecyl) -β-chromanol), α-tocopherol ((+) -2, 5, 7, 8-tetramethyl-2 - (4,8, 12 -trimethyltridecyl) -6-chromanol), β-tocopherol ((+) -2,5, 8 -trimethyl-2- (4,8, 12 -trimethyltridecyl) -6-chromanol),? -tocopherol ((+) -2, 7, 8 -trimethyl-2- (4,8, 12 -trimethyltridecyl) -6-chromanol), d-tocopherol ((+) - 8-methyl-2- (4,8, 12 -trimethyltridecyl) -6-chromanol), α-tocotrienol (2, 5, 7, 8- tetramethyl-2 - (4, 8, 12-trimethyl-3,7, 11-tridecatrienyl) -6-chromanol), β-tocotrienol (2,5, 8 -trimethyl-2- (4,8, 12 -trimethyl- 3, 7, 11-tridecatrienyl) -6-chromanol) or derivatives or mixtures thereof.

In certain embodiments, the present invention is directed to an oral composition comprising a zinc salt, a linear polyphosphate salt having an average chain length of 3 or less, and at least one of a potassium salt or a vitamin.

DETAILED DESCRIPTION OF THE INVENTION As used throughout the present description, the intervals are an abbreviated form to describe each and every one of the values that are within the range. Any value within the range can be selected as the interval limit. In addition, all references cited in the present description are incorporated by reference in their entirety. When there is a conflict between a definition in the present description and that of a cited reference, the present description prevails.

In several embodiments, the present invention provides methods for treating an oral cavity having an oral surface, and oral compositions comprising an active ingredient comprising a source of zinc ion.

In certain embodiments, the oral compositions reduce the formation of at least one of plaque and tartar, or both, on the oral surface. In certain embodiments, the oral composition reduces or mitigates gingivitis or periodontitis for patients who have symptoms of such disease. In certain embodiments, the oral compositions reduce the sensitivity in an oral surface, for example a tooth having dentin sensitivity. In other embodiments, oral methods and compositions reduce inflammation of oral surfaces, for example oral tissues.

As used herein, an "oral surface" includes the hard and soft tissues of the oral cavity. As used herein, "hard tissue" refers to tissues such as teeth and periodontal support in an oral cavity, such as that of a mammal. "Soft tissues" refers to tissues such as gums, tongue, surfaces of the oral cavity and the like. For example, the sensitivity of dentin is typically associated with hard tissue, i.e., a tooth, in particular, the dentin tissue in the root region covered by cement and / or dentin in the crown region of a tooth It is covered by enamel. In several embodiments, the methods and compositions of the present invention treat various oral surfaces in the oral cavity, and may include treatment of hard and soft tissues simultaneously, for example reducing inflammation in the oral cavity. soft tissues and preventing plaque, tartar, caries and / or sensitivity in hard tissues.

In various embodiments, the present oral compositions treat and / or inhibit various oral inflammatory conditions, such as gingivitis, periodontitis, oral lichen planus, Sjögren's syndrome and the like. The oral compositions may be present in several different forms, including a dentifrice, a paste, a gel, a medicament, a powder, an oral rinse, an oral wash, a hardener of the teeth, an oral film, a slurry, a solution injectable and a tablet, as well as any other form of oral care compositions known in the art.

In several embodiments, the oral composition comprises an active ingredient comprising a source of zinc ion. Examples of suitable sources of zinc ion to be used in the present incorporations include zinc salts such as, for example, zinc citrate, zinc sodium citrate, zinc acetate, zinc gluconate, zinc glycinate, zinc oxide, zinc sulfate, zinc bacitracin, zinc tribromosalicylanilide, zinc carbonate, zinc fluoride, zinc formate, zinc lactate, zinc oleate, zinc peroxide, zinc phosphate, zinc pyrophosphate, zinc silicate, zinc stearate, zinc tannate, zinc oxalate, zinc chloride or mixtures thereof.

In a particular embodiment, the zinc ion source is a zinc citrate agent. As used herein, the term "agent" refers to a composition that provides an active compound having the desired biological, physiological, chemical and / or mechanical effects. An agent can include precursors of the active compound that form the active compound in vivo or the agent can comprise the active compound and / or homologs, analogs or derivatives thereof. The agents may contain active compounds that are natural or synthetic. As will be appreciated by those skilled in the art, the agent may additionally comprise other components that do not decrease the effectiveness of the active compound, for example, buffers, diluents and impurities may be present in the agent.

In the context of the various embodiments, zinc citrate is useful as an active ingredient because it is particularly effective as an antibacterial, antiplaque, anti-chaff and anti-odor active agent. It is believed that, in addition to providing zinc ions in vivo, the citrate anion, in particular contributes to the antibacterial efficacy of the active ingredient, and thus is particularly effective in oral care compositions.

Thus, the zinc citrate agent can include an active compound of zinc citrate having the general formula Zn3 (C6H507) 2 • Zinc citrate can be provided in an analogous hydrated form, for example, it is commonly available as a trihydrate of zinc citrate Zn3 (C6H507) 2 • 3H20 or zinc citrate dihydrate Zn3 (C6H507) 2 • 2H20. Also, zinc citrate is sometimes provided as zinc sodium citrate Na2Zn2 (C6H507) 2 • The zinc citrate active compound can be provided in an oral composition in several ways; for example, citric acid and zinc chloride, zinc carbonate or other common zinc salts which combine with the citric acid to form the desired compound of zinc citrate can be formed from the precursors.

In certain embodiments, the invention provides oral compositions that treat an oral surface that has dentine sensitivity. The sensitivity of dentin (also known as dentine hypersensitivity) typically occurs when the enamel or protective cement that covers the dentine of a tooth is lost. For example, a cement opening typically occurs when there is a removal of gingival tissue that allows exposure of the cement to the oral cavity, thus making the cement susceptible to dissolution. The sensitivity of the dentin often causes pain when the exposed tooth area (ie, dentin) is put in contact with cold or hot temperatures, high concentrations of acids or sugars, or metals. Several methods to reduce tooth sensitivity have been employed. It is generally recognized that an effective treatment to treat the sensitivity of dentin is the effective and regular removal of plaque. Frequent and regular removal of the plaque allows remineralization of exposed dentinal tubules from salivary minerals, thus relieving much of the underlying cause of the pain. However, this method of treatment is not always an effective course of treatment in and of itself, as it is often not fast enough to relieve pain, or the plaque removal regimen is too rigorous or ineffective for a subject experience sensitivity of dentin.

Often, treatment for the sensitivity of dentine encompasses the application of an active ingredient comprising a desensitizing agent by means of an oral composition, such as a dentifrice or medicament. The use of desensitizing agents in oral compositions is known, including, by way of example, active ingredients such as tin and sodium fluoride, potassium nitrate, lithium or sodium, sodium fluoride, sodium monofluorophosphate, strontium chloride, potassium tartrate, potassium chloride, potassium sulfate, potassium and sodium citrate, and mixtures thereof.

In certain embodiments, the oral composition comprises an active ingredient comprising a desensitizing active agent in addition to the zinc citrate agent. In such oral compositions, the treatment may reduce the sensitivity of the oral surface, preferably that of the teeth. By reduction of sensitivity, it means that the pain and / or discomfort associated with the sensitivity of the dentine are markedly reduced and preferably are eliminated in such a way that the user has little or no perception of pain and / or discomfort. In certain embodiments, the desensitizing agent comprises an alkali metal or alkaline earth metal cation complexed with a citrate anion. The alkali metal or alkali metal citrate agents may include, for example, potassium citrate or sodium compounds.

In certain embodiments, a potassium citrate agent is used as a desensitizing agent in oral compositions. The potassium citrate compound has a general formula of K3C6H507, which may also be hydrated. Although not limiting for the present invention, it is believes that the alkali metal cations of citrate anions, in particular potassium cations, chemically interfere with the transmission of pain signals generated by the nerve fibers of the pulp of the exposed tubules. Additionally, as described above, it is believed that the citrate anion contributes to the antibacterial efficacy of the general active ingredient, thereby reducing plaque and tartar formation, among others, which when not decreased, may further contribute to the underlying etiology of the hypersensitivity of the dentin, especially the erosion of the mineralized layer on the dentin.

In several embodiments, the oral compositions may further comprise one or more additional desensitizing agents. In certain embodiments, such additional desensitizing agents (in addition to a potassium citrate agent) may include compounds known in the art, including those described above. In certain embodiments, the active ingredient comprises a potassium citrate agent and a second desensitizing agent selected from potassium tartrate, potassium chloride, potassium sulfate, potassium nitrate, sodium nitrate, sodium citrate or mixtures thereof.

In certain embodiments, the oral compositions comprise a zinc citrate agent and a potassium citrate agent, wherein the ratio of the zinc citrate agent to the potassium citrate agent is about 1: 1 to about 1: 5. . In some embodiments, the ratio of zinc citrate to potassium citrate agent is about 1: 2 to about 1: 3.

In several embodiments, the oral composition comprises an active ingredient wherein the zinc citrate agent is present in an amount of about 0.001% up to about 5% by weight of the oral composition, about 0.01 to about 3%, about 0.1 to about 3%, or about 1 to about 2% by weight of the oral composition.

In several embodiments, the potassium citrate agent is present in an amount of from about 0.001% to about 10% by weight of the oral composition, about 0.1 to about 7%, about 4 to about 6%, or about 5.5% by weight of the oral composition.

In several embodiments, a method for treating an oral surface having dentine sensitivity comprises contacting said surface with a composition. oral comprising an active ingredient comprising a zinc citrate agent and a potassium citrate agent. The particularly effective combination of the zinc citrate agent and the potassium citrate agent provides improved methods of treatment for sensitive teeth. For example, contacting the oral composition with the oral surface can reduce not only the sensitivity of the oral surface, but also the formation of plaque and / or tartar on the oral surfaces, which is believed to contribute to the conditions that cause and / or exacerbate the sensitivity of dentin.

Similarly, the combination of the zinc citrate agent and the potassium citrate agent in certain embodiments of the invention may result in an oral composition that has less astringency. Oral compositions comprising a source of zinc ion as an active ingredient which are highly astringent are known. To provide aesthetically desirable oral compositions, reduction and / or masking of such astringent properties is preferred. Additionally, according to certain additions, such as the amount of remaining citrate anion concentration thereof (contributed by both potassium citrate such as zinc citrate), the remaining antibacterial efficacy of a similar level compared to a comparative composition that it comprises only zinc citrate. Thus, the Relative concentration of zinc cations may be lower, thus reducing the astringency of the composition while still maintaining the desired antibacterial and desensitizing efficacy.

Additionally, according to certain embodiments, oral compositions comprising the source of zinc ion, for example, a zinc citrate agent, may further comprise certain components that reduce the astringency of the composition. Such components include a polyphosphate compound and / or a synthetic anionic linear carboxylate polymer. Methods for reducing astringency with these components are discussed in U.S. Patent No. 5,000,944 to Prencipe et al. And WO 02/45678 to Hoic et al.

It is believed that the astringency of completely or partially soluble zinc salts, such as zinc citrate and the like, is reduced by the formation of a complex of the polyphosphate compound with zinc ions. Additionally, the complex may further include a polycarboxylate polymer, as will be described in more detail below. In oral compositions, polyphosphates are described to provide benefits that include tartar inhibition, as well as the reduction of astringency-like aesthetic negatives associated with zinc. A molecularly linear dehydrated polyphosphate compound useful in the present invention comprises generally two or more condensed phosphate molecules. Cyclic polyphosphates are generally referred to as metaphosphates. The number of phosphorus atoms in the condensed phosphate molecules can range from two (usually referred to as a pyrophosphate) to infinity (ie, polyphosphates). The polyphosphate salts are generally used in the form of their completely or partially neutralized water-soluble alkali metal (for example, potassium, sodium or ammonium salts and any mixtures thereof). Examples of suitable polyphosphate compounds include sodium or potassium tripolyphosphates, sodium and potassium hexametaphosphates, disodium diacid pyrophosphate, tetrasodium pyrophosphate and tetrapotassium pyrophosphate in their non-hydrated as well as hydrated forms.

It is believed that a zinc / polyphosphate complex, for example, zinc / pyrophosphate complexes; zinc / tripolyphosphate; and zinc / hexametaphosphate, provide a combined anticalculus activity that is more effective than either single active ingredient alone (ie, Zn2 + and P207"4 (pyrophosphate) ions.) A range of polyphosphate ion to zinc ion in a molar ratio is, in several embodiments, about 1: 1 to about 5: 1, or about 2: 1 to about 5: 1. In several embodiments, the polyphosphate compound is optionally present in an amount of about 0.01 to about 5%, about 1 to about 4%, to about 1.5 to about 3% or about 2 to 2.5% by weight of the oral composition. In certain embodiments, the polyphosphate compound comprises tetrapotassium pyrophosphate (TKPP). In some embodiments, TKPP is present in an amount of from about 2 to about 3% by weight of the oral composition, for example about 2.5%.

The synthetic anionic linear polycarboxylates can complex with the complex of the polyphosphate and zinc compound, and are also known as efficacy enhancing agents for certain active ingredients for oral care, including antibacterial agents, anticalculus or other active agents within the composition oral.

Such anionic polycarboxylates are generally used in the form of their free acids, or water-soluble alkali metal salts partially neutralized or completely neutralized (for example potassium and preferably sodium) or ammonium. The terms "synthetic" and "linear" exclude known thickening or gel forming agents comprising carboxymethylcellulose and other cellulose derivatives and natural gums, and carbopoles having reduced solubility due to crosslinkers.

Preferred copolymers are 1: 4 to 4: 1 copolymers of maleic acid or anhydride with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether (methoxyethylene) having a molecular weight (MW) of about 30,000 to about 5,000,000. A useful copolymer is methyl vinyl ether / maleic anhydride. Examples of these copolymers can be obtained from ISP Corporation under the trade name GANTREZ®, for example AN 139 (MW 1,100,000), AN 119 (MW 200,000), S-97 Pharmaceutical Grade (MW 1,500,000), AN 169 (MW 2,000,000) and AN 179 (MW 2,400,000); wherein the preferred copolymer is S-97 Pharmaceutical Grade (MW 1,500,000). In several embodiments, a synthetic anionic polycarboxylate is included in the oral composition in an amount of about 0.001 to about 5% by weight, about 0.1 to about 2.0% by weight, or about 1.5% by weight.

In certain embodiments, a method is provided for treating inflammation in oral tissue. In particular, the oral composition preferably reduces oral tissue inflammation by reducing one or more mediators of inflammation. Oral tissue inflammation generally refers to a localized protective response caused by injury or destruction of tissues, which serves to destroy, dilute or sequester both the injured agent and the injured tissue. In the acute form, it is characterized by pain, heat, redness, swelling and loss of function, where chronic inflammation is a slow process characterized mainly by the formation of new connective tissue. Chronic inflammation is often a continuation of acute inflammation or a prolonged form of low degree of inflammation (such as that associated with periodontitis or gingivitis) and usually causes permanent tissue damage. Histologically, inflammation involves a complex series of events, including dilation of arterioles, capillaries and venules, with increased permeability and blood flow; fluid exudation, including plasma proteins, and migration of leukocytes in the inflammatory site. The inflammation corresponds to increased levels of pro-inflammatory cell mediators (substances that are released from the cells), for example as the result of the interaction of an antigen with an antibody or by the action of an antigen with a sensitized lymphocyte.

Cytokines are proteins other than antibodies that are released by a cell population upon contact with a specific antigen and act as intercellular mediators to produce a response of a mammalian immune system. "Interleukin" is a term for a group of multifunctional cytokines that are produced by a variety of lymphoid and non-lymphoid cells. Examples of interleukin compounds generated by fibroblasts Gingivals include interleukin-lß, interleukin-6 and interleukin-8. Certain interleukin compounds appear to stimulate the production of arachidonic acid metabolites, such as prostaglandins, leukotrienes and thromboxanes, which are produced through the cyclooxygenase or lipoxygenase enzyme trajectories. These metabolites have been implicated as the main mediators in gingivitis, periodontitis, osteomyelitis and other inflammatory diseases.

Leukotrienes in particular appear to activate osteoblasts and inhibitors of osteoblast activity and promote bone resorption associated with periodontitis. Prostaglandins are localized and potent mediators of numerous different physiological processes and their production can be triggered by specific interleukin compounds. Tumor necrosis factor-alpha (TNF-a) is a cytokine produced by leukocytes during infection, and appears to play an important role in bone resorption during osteomyelitis. TNF-a appears to regulate bone resorption differently than arachidonic acid metabolites (such as prostaglandin E2 (PGE2) and leukotrienes).

Similarly, anti-inflammatory active ingredients for oral care can also play a role role in the reduction or scanning of reactive oxides species within the oral cavity. Reactive oxide species (ROS) are also proinflammatory mediators that are typically highly reactive products produced during various biochemical processes, and include superoxide anions (02 ~), hydrogen peroxide (H202) and hydroxyl radicals (-0H) ). ROS formation can occur as part of many cellular processes including mitochondrial respiration, immune cell responses, cell injury, heat, radiation of many origins, drug metabolism and other chemicals. It is thought that ROS are involved in almost all disease processes, as well as in the aging process. It is believed that increased ROS formation under pathological conditions causes cellular damage through the action of these highly reactive molecules by crosslinking proteins, mutagenized DNA and peroxidized lipids.

The suppression of one or more of the proinflammatory mediators described above prevents and / or treats tissue damage and / or tissue loss when the tissue is inflamed. Thus, the preferred active ingredients for oral care useful for oral compositions can serve as anti-inflammatory agents that suppress or reduce one or more mediators of inflammation. In certain embodiments, contacting the oral composition with the oral tissue inflammation also reduces the formation of plaque and / or tartar on an oral surface. Thus, a method for treating inflammation in an oral tissue comprises contacting an oral composition having an active ingredient comprising a tocopherol agent. In certain embodiments, the active ingredient further comprises a zinc citrate agent as described above. The tocopherol agent of the active ingredient can reduce and / or suppress the production of one or more proinflammatory mediators to reduce inflammation in oral tissue.

As used herein, a "tocopherol agent" refers to any tocopherol compound derived from a family of structurally similar 6-chromanol derivatives, enantiomers, racemates and other analogs, including synthetic and naturally derived compounds. Such compounds include α-tocopherol ((+) -2, 5, 7, 8-tetramethyl-2- (4,8,13-trimethyltridecyl) -6-chromanol), β-tocopherol ((+) -2,5, 8-trimethyl-2- (4, 8, 12-trimethyltridecyl) -6-chromanol),? -tocopherol ((+) -2,7,8-trimethyl-2- (4,8, 12-trimethyltridecyl) -6 -chromanol), d-tocopherol ((+) - 8-methyl-2- (4,8,12 -trimethyltridecyl) -6-chromanol), α-tocotrienol (2,5,7,8-tetramethyl -2 - ( 4,8, 12-trimethyl-3,7,11-tridecatrienyl) -6-chromanol), β-tocotrienol (2, 5, 8-trimethyl-2 - (4,8,13-trimethyl-3, 7, 11 -tridecatrienyl) -6-chromanol), and tocol (2-methyl-2- (4, 8, 12 -trimethyltridecl) -6-chromanol). Generally, the "Vitamin E" refers to biologically active compounds of the tocopherol family and may encompass a mixture of any two or more tocopherol and / or tocotrienol compounds listed above. Additionally, the tocopherol agent may comprise esterified and non-esterified forms of Vitamin E, for example, Vitamin E acetate (((+) -2, 5, 7, 8-tetramethyl-2 - (4,8, 12-trimethyltridecyl ) - 6-chromanol-acetate) or d-Vitamin E acetate (2, 5, 7, 8-tetramethyl-2 - (4, 8, 12-trimethyltridecyl) -6-chromanol-acetate) which are both derivatives of α-tocopheryl Although α-tocopherol is generally recognized as the most active form of Vitamin E, and is suitable for use in the present invention, in some embodiments, a mixture of different compounds of the tocopherol family is particularly effective.

In certain embodiments, an oral composition comprises a tocopherol agent comprising at least two compounds other than the tocopherol family. Thus, in certain embodiments, an active ingredient comprises at least two different tocopherol compounds selected from tocol, α-tocopherol, β-tocopherol, β-tocopherol, d-tocopherol, α-tocotrienol, β-tocotrienol or derivatives or mixtures thereof. the same. In other embodiments, the tocopherol agent comprises at least two compounds selected from α-tocopherol, β-tocopherol, β-tocopherol or d-tocopherol. Such product is commercially available from Riken Vitamin Co. , Ltd. (Tokyo, Japan) as a mixed tocopherol product containing a, ß,? and natural and synthetic d-tocopherol. In other embodiments, the tocopherol agent comprises a mixture of α-tocopherol and α-tocopherol. A mixture of tocopherol compounds is particularly effective as an anti-inflammatory agent. For example, a mixture of α- and β-tocopherol compounds has been found to be particularly effective as an anti-inflammatory active ingredient for oral care, including high absorption in inflamed oral tissues, which has not been previously observed.

The tocopherol agent comprising the tocopherol compounds may be present in the oral compositions in an amount of from about 0.001% up to about 5%, for example about 0.1% up to about 2.5% or about 0.2% up to about 1% by weight of the total composition. For example, in several embodiments wherein the tocopherol agent comprises mixtures of tocopherols, such as at least two different tocopherol compounds, for example a and β -tocopherols, each respective tocopherol compound is present in an amount of about 0.1% to about 1%, about 0.2% to about 0.75%, or about 0.3% to about 0.6% by weight of the oral compositions.

Additional optional oral care compounds that can be included as active ingredients in any of the oral compositions described above include, for example, additional antibacterial agents, bleaching agents, anti-caries agents and additional tartar control agent, periodontal actives, abrasives, breath-freshening agents, agents that control odor, tooth desensitizers, salivary stimulants, bleaching agents and combinations thereof. Any given material can serve multiple purposes within two or more of such asset categories. Examples of active among those useful herein are described in U.S. Patent Nos. 4,894,220 to Nabi et al., 5,288,480 to Gaffar et al., U.S. Patent Publication No. 2003/0206874 to Doyle et al. as well as in U.S. Patent No. 6,290,933 to Durga et al. and U.S. Patent No. 6,685,921 to Lawlor.

The useful assets herein are optionally presented in the oral compositions in safe and effective amounts. A "safe and effective" amount in the present context is an amount sufficient to provide a desired benefit, for example a therapeutic, prophylactic, nutritional or cosmetic effect, when the composition is repeatedly used as described herein, without effects inappropriate side effects such as toxicity, irritation or allergic reaction, commensurate with a reasonable benefit / risk ratio. Such a safe and effective amount will usually fall, but not necessarily, within the intervals approved by the appropriate regulatory agencies. A safe and effective amount may depend on the particular benefit desired or the condition to be treated or that is to be prevented, the particular object use, or to be administered, the composition, the frequency and duration of use, etc. Assets are typically present in a total amount of about 0.01% to about 80%, for example about 0.05% to about 60%, about 0.1% to about 50%, or about 0.5% to about 40% by weight of the composition.

Specifically, useful additional oral care compounds include, for example, nonionic antibacterial agents, including phenolic and bisphenolic compounds, such as, for example, halogenated diphenyl ethers, including triclosan (2, 4, 4'-trichloro-2 '). -hydroxy-diphenyl ether), triclocarban (3,4,4-trichlorocarbanilide), as well as 2-phenoxyethanol, benzoate esters and carbanilides. Such additional antibacterial agents may be present in the oral care composition in an amount of from about 0.01 to about 5% by weight of the oral composition. Useful anticalculus agents in addition to zinc ion sources and the polyphosphates described above include tin ion sources, such as stannous fluoride, stannous chloride and tin pyrophosphate.

In some embodiments, the active ingredient may comprise a source of fluoride ions or fluorine-providing component, such as anticaries and / or anticalculus agents, in an amount sufficient to supply about 25 ppm up to 5,000 ppm fluoride ions. The fluoride ion sources comprise inorganic fluoride salts, such as soluble alkali metal salts; for example sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluorides, including olaflur (N '-octadecyltrimethylenediamine-N, N, N' -tris- (2-ethanol) -dihydrofluoride ), as well as tin fluorides, such as stannous fluoride.

The oral composition may optionally comprise a nutrient such as a vitamin, mineral, antioxidant and / or amino acid active compound. Useful nutrients include, without limitation, vitamins that include sources of vitamin C, including ascorbic acid; carotenoids, including retinol (vitamin A), retinal, retinoic acid, α-carotene, β-carotene, β-carotene, d-carotene, lutein, lycopene, licofilo, licoxanthin, rodoxanthin, astaxanthin and cryptoxanthin; sources of B vitamins, including thiamin (vitamin B?), riboflavin (vitamin B2), nicotinamide and nicotinic acid (both referred to as niacin), pantothenic acid (vitamin B5), pantothenol, pyridoxine (vitamin B6), pyridoxal, pyridoxamine, acid folic acid, dihydrofolic acid, cyanocobalamin (vitamin B? 2) and biotin; bioflavonoids, including rutin, hesperetin, hesperidin, eriodictyol, quercetin, quercetagenet and quercetagitrin; cofactors of quinone-type enzyme, including ubiquinone (coenzyme Qio) pyrroloquinoline quinone (PQQ), para-aminobenzoic acid; sources of a-lipoic acid; sources of vitamin D, including calciferol and colecalciferol; salts, esters (including phosphate, acetate and long chain esters, for example linoleate and palmitate), isomers, enantiomers, racemates and tautomers thereof. Nutritional supplements include amino acids (such as L-tryptophan, L-lysine, methionine, threonine, levocarnitine and L-carnitine), lipotropic (such as choline, inositol, betaine and linoleic acid), fish oil (including components thereof such as omega-3 (N-3), polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid), and mixtures thereof.

The nutrient component may be a multivitamin complex comprising, in addition to a tocopherol agent, a plurality of vitamins / vitaminoids selected from: (a) sources of vitamin C; (b) carotenoids; (c) sources of B vitamins; (d) bioflavonoids; (e) cofactors of the quinone-like enzyme; (f) sources of α-lipoic acid; or (g) sources of vitamin D.

In certain embodiments, where the active ingredient comprises a tocopherol agent, the active ingredient may also comprise pantothenic acid / pantothenol (vitamin B5) or orally acceptable salts or esters thereof. The total concentration of vitamin B5 sources in the oral composition can be, in several embodiments, about 0.005% up to about 1%, about 0.01% up to about 0.5%, about 0.03% up to about 0.1%, or around 0.05%.

In certain embodiments, the present invention is directed to an oral composition comprising a zinc salt, a linear polyphosphate salt having an average chain length of 3 or less, and at least one of a potassium salt or a vitamin. The vitamin may be any known in the art, including those listed in the current description, and the potassium salt may be any potassium salt known in the art, including those listed in the current description. In certain embodiments, the linear polyphosphate salt is pyrophosphate, a tripolyphosphate or a tetrapolyphosphate.

The oral compositions can be provided in an orally acceptable carrier or vehicle. The carrier can be a liquid, semi-solid or solid phase, in the form of an oral rinse, a dentifrice (including toothpastes, dental powders and prophylactic pastes), candies (including tablets and chewing gum), a medicament, a film or any other way known to someone experienced in the art. The selection of the specific carrier components depends on the desired product form.

In several embodiments, the oral composition has an orally acceptable vehicle having a pH of about 6 to 10, or about 7 to 9. This is particularly desirable in embodiments wherein the oral composition comprises the components to reduce the agent's astringency of zinc citrate as previously described, such as the polyphosphate compound. A decrease in pH of less than about 6 can potentially result in the precipitation of zinc citrate, particularly when complexed with the polyphosphate salt and / or the polycarboxylate polymer. Certain components serve to raise the pH of the oral composition. Such compounds include buffer solutions and conventional salts, as well as chemicals such as linear polycarboxylates. anionic (described above) and polyacrylates such as those available from B.F. Goodrich of Cleveland, Ohio, sold under the trade name CARBOPOL®, which has been shown to raise the pH when present in oral compositions.

Conventional ingredients can be used to form the carriers listed above. The oral compositions may include other materials in addition to those components previously described, including for example, surface active agents, such as surfactants, emulsifiers and foam modulators, viscosity modifiers and thickeners, humectants, diluents, agents that modify the additional pH, emollients, humidifiers, oral sensing agents, sweetening agents, flavoring agents, colorants, preservatives, solvents such as water and combinations thereof. Any given material can serve multiple purposes within two or more of such material categories. Preferably, such carrier materials are selected for their compatibility and stability with all constituents of the active ingredient.

Useful surface active agents are described in the aforementioned patent references and discussed above, including the United States of America Patent No. 4,894,220. Surface active agents are generally an important aspect of the oral composition, since they can function as surfactants, emulsifiers, foam modulators and / or active ingredient dispersing agents. Thus, its selection for compatibility with the constituents of the active ingredient is important. For example, in embodiments wherein the oral composition has an active ingredient comprising a cationic antibacterial agent, it is preferred that the carrier comprises surfactants that are not strongly anionic, since such anionic compounds can bind to the cationic active ingredient potentially reducing its bioavailability.

Suitable surface active agents are those that are reasonably stable and foam in a wide range of pH. These compounds are known in the art, and include non-soap anionic detergents (e.g., sodium lauryl sulfate (SLS), N-myristoyl and N-palmitoyl sarcosine), nonionic (e.g. Polysorbate 20 (sorbitan monolaurate polyoxyethylene 20, TWEEN® 20) and Polysorbate 80 (polyoxyethylene 20 sorbitan monooleate, TWEEN® 80), Poloxamer 407, available under the tradename PLURONIC® F127 from BASF Corporation), cationic, suteionic (for example cocoamidopl betaine and lauramido pl) betaine) and amphoteric organic synthetics. In several embodiments, one or more active surface agents are present in the composition oral in the range of about 0.001% to about 5%, or about 0.5% to about 2.5%. In embodiments wherein the oral composition comprises an active ingredient comprising lipophilic active compounds, the amount of surface active agent is increased to allow sufficient emulsification of the active ingredients within the carrier of the oral composition. The carrier is typically aqueous. For example, in embodiments in which the tocopherol agent is present in an aqueous carrier, the amount of surface active agent (such as SLS) present may be from about 1 to about 3% by weight of the oral composition, for example to around 1.5%.

In embodiments where the oral composition is in the form of an oral rinse, an example of a carrier is substantially liquid. The term "oral rinse" includes oral washes, sprays and the like. In such a preparation the orally acceptable carrier typically has an aqueous phase comprising water, or a mixture of water and alcohol. Additionally, in several embodiments, the oral carrier typically contains a humectant, a surfactant and a pH buffering agent.

The oral composition may optionally comprise a flavoring agent. Examples of flavoring substances they are known to one skilled in the art, and may be present in certain embodiments at a concentration of about 0.05% by weight to about 5% by weight.

In embodiments where the oral composition is in the form of a confection, an example of a carrier can be substantially solid or semi-solid. Candies carriers are known in the art. For a tablet, the carrier typically comprises a tablet-based material (eg, comprising a non-cariogenic polyol and / or sugar / starch derivative), an emulsifier, a lubricant, a flavoring agent, a thickener and optionally a material of coating. The chewing gum carriers generally have a chewing gum base, one or more plasticizing agents, a sweetening agent and a flavoring agent.

In embodiments where the oral composition is in the form of a film, an example of a carrier is substantially solid or semi-solid. Generally, such film carriers comprise a water soluble or dispersible film forming agent, such as a hydilic polymer. Optionally, the film carrier may also comprise hydobic film-forming polymers, such as a removable liner layer, or mixed with a hydilic film-forming polymer. The film carriers comprise optionally plasticizers, surface active agents, fillers, volume agents and agents that modify the viscosity.

In embodiments where an oral composition is in the form of a dentifrice, an example of a carrier is substantially semi-solid or a solid. The dentifrices typically contain surface active agents, humectants, viscosity modifying agents and / or thickeners, abrasives, solvents such as water, flavoring agents and sweetening agents.

In certain embodiments where an oral composition is in the form of a medicament, such as a non-abrasive gel or ointment that can be applied to the gingival margin and can be used in conjunction with wound dressings, gauze, films and the like. Such gels can include both aqueous and non-aqueous gels. Aqueous gels generally comprise a polymer base, a thickener, a humectant, a flavoring agent, a sweetening agent and a solvent, typically including water.

In several embodiments, the methods of the invention promote oral health in the oral cavity and treat the plaque on an oral surface of a mammalian subject. In an embodiment, a method to provide one or more benefits of oral health to an oral cavity of a mammalian subject comprises preparing an oral composition as described herein, wherein an active ingredient comprises a zinc citrate agent and a second agent. The second agent is optionally potassium citrate or a tocopherol agent. The prepared oral composition is contacted with an oral surface within the oral cavity. The oral composition containing the active ingredient can provide multiple oral health benefits, such as anti-gingivitis, antiperiodontitis, anticaries, anti-jar, anti-inflammatory, analgesic, anti-aging and breath freshener.

Thus, any of the various embodiments of the oral care composition described above are contacted with or applied regularly to an oral surface, preferably at least once a day, more preferably in multiple days in a week, and more preferably on a long-term daily basis.

The oral composition of the present invention can be made by any of the methods known in the art by combining the ingredients to make oral care compositions. Examples of methods that can be used are set forth in: U.S. Patent No. 6,403,059 to Martin et al., Clinical Pharmacology for Dental Professionals (Mosby-Year Book, Inc., 3rd edition 1989); Mosby's Dental Hygiene: Concepts, Cases and Competencies (Daniel S. and Harfst S., eds., Elsevier Science Health Science Div. 2002) and Ernest W. Flick, Cosmetic and Toiletry Formulations, 2nd edition), whose contents are incorporated in the present for reference.

Toothpastes are typically prepared by adding various salts (including zinc and fluoride salts, when included in the composition) and sweeteners (eg, saccharin), and any compounds of the orally active, water-soluble active ingredients, where they are mixed. In another container, all humectants, gums and polymers are added together. The water-based mixture described above is added to the container with the humectants, gums and polymers. The combined ingredients are optionally heated to a temperature greater than about 40 ° C, for example from about 60 ° C to about 70 ° C, to disperse gums and polymers. The heated mixture is then cooled to less than about 38 ° C (about 100 ° F). The mixture is then combined with abrasives, where it is mixed at high speed under a vacuum for about 15 to about 20 minutes. Any of the lipophilic active ingredients are mixed in a flavor oil (and / or alcohol). This mixture is mixed with the water-based mixture above, where it is mixed under high speed and vacuum until dispersed enough. The surfactants are added and the mixture is mixed again to disperse it.

In certain embodiments, a method of making an oral composition comprises adding an additional active compound as part of the active ingredient to one or more carrier ingredients prior to mixing. In other embodiments, such additional active ingredients for oral care are added with lipophilic ingredients to the homogeneous mixture. If the additional oral care assets are added to one or more carrier ingredients prior to mixing to form a homogeneous mixture, or are added to the mixture with the lipophilic components after mixing, it depends on the nature of the additional active ingredient (e.g. , if it can withstand heating greater than or equal to around 40 ° C or if it is hydrophobic, hydrophilic, anionic, cationic or non-ionic). One skilled in the art can easily determine the appropriate point in the method for making the oral composition by adding the active ingredients, based on these considerations. For example, in certain embodiments, where the active ingredient for oral care comprises a source of soluble zinc ions and fluorine ions, soluble zinc salts and / or fluorine salts can be added to one or more ingredients carriers before mixing that are substantially soluble in water.

The present invention is further illustrated through the following non-limiting examples.

Example 1 The dentifrice compositions of the present invention are made by combining the following ingredients: The dentifrice 1 corresponds to an oral composition comprising the active ingredients including a zinc citrate agent, an a-tocopherol agent (Vitamin E), a panthenol agent (Vitamin B5) and a source that provides fluorine (sodium monofluorophosphate) (MFP for its acronym in English)), which provides an oral antiplaque, anti-caries, anti-caries and anti-inflammatory composition. The dentifrice 2 comprises an active ingredient comprising at least two tocopherol compounds, named an a-tocopherol agent (Vitamin E) and a mixed tocopherol agent comprising the compounds of a, β, d, β-tocopherol, as well as as a source that provides fluoride (sodium fluoride). The dentifrice 2 provides anti-inflammatory and anticaries benefits, among others. Toothpaste 3 is an oral composition comprising active ingredients including a zinc citrate agent, a potassium citrate agent and a source of Fluorine (sodium MFP), which provides a reduction in the sensitivity of dentine, an anti-plaque, anti-caries and anticaries benefit.

Claims (37)

1. A method for treating an oral surface having dental sensitivity comprising contacting the oral surface with an oral composition comprising an active ingredient comprising a zinc citrate agent and a potassium salt.

2. The method as claimed in clause 1, characterized in that the potassium salt is a potassium citrate agent.

3. The method as claimed in clause 1, characterized in that the zinc citrate agent comprises a compound having the general formula Zn3 (C6H507) 2.

4. The method as claimed in clause 2, characterized in that the potassium citrate agent comprises a compound having the general formula K3C6H507.

5. The method as claimed in clause 1, characterized in that the active ingredient further comprises a compound selected from potassium tartrate, chloride of potassium, potassium sulfate, potassium nitrate, sodium nitrate, sodium citrate or mixtures thereof.

6. The method as claimed in clause 1, characterized in that a ratio of the zinc citrate agent to the potassium salt is about 0.5: 1 to about 1: 0.5.

7. The method as claimed in clause 1, characterized in that the zinc citrate agent is present in an amount of about 0.001% up to about 5% by weight of the oral composition and the potassium salt is present in a amount of about 0.001% to about 10% by weight of the oral composition.

8. The method as claimed in clause 1, characterized in that the oral composition further comprises a copolymer of maleic anhydride and polyvinyl methyl ether.

9. The method as claimed in clause 1, characterized in that the oral composition further comprises a polyphosphate compound.

10. The method as claimed in clause 1, characterized in that the oral composition further comprises a copolymer of maleic anhydride and polyvinyl methyl ether and a polyphosphate agent.

11. A method for reducing astringency comprising contacting the oral surface with an oral composition comprising an active ingredient comprising a zinc citrate agent and a potassium salt.

12. A method for reducing the formation of plaque or tartar, caries or bad odor, comprising contacting the oral surface with an oral composition comprising an active ingredient comprising a zinc citrate agent and a potassium salt.

13. The method as claimed in clause 1, characterized in that the oral composition further comprises a nonionic halogenated diphenyl ether.

14. The method as claimed in clause 1, characterized in that the oral composition further comprises a tocopherol agent.

15. The method as claimed in clause 1, characterized in that the oral composition has a pH of about 6 to about 10.

16. The method as claimed in clause 1, characterized in that the oral composition has a form of an oral rinse, a dentifrice, a confection, a medicament or a film.

17. A method for treating inflammation in an oral tissue comprising: contacting the inflamed oral tissue with an oral composition comprising an active ingredient comprising a zinc citrate agent and a tocopherol agent.

18. The method as claimed in clause 17, characterized in that the tocopherol agent comprises a compound selected from tocol (2-methyl-2- (4, 8, 12-trimethyltridecl) -6-chromanol), α-tocopherol ( (+) -2, 5, 7, 8-tetramethyl-2- (4, 8, 12-trimethyltridecyl) -6-chromanol), β-tocopherol ((+) -2,5,8-trimethyl-2- ( 4,8, 12-trimethyltridecyl) -6-chromanol),? -tocopherol ((+) -2,7, 8-trimethyl-2- (4,8, 12-trimethyltridecyl) -6-chromanol), d-tocopherol ((+) - 8 -methyl- 1- (4,8, 12-trimethyltridecyl) -6-chromanol), α-tocotrienol (2,5,7,8-tetramethyl -2- (4,8, 12 -trimethyl) -3, 7, 11-tridecatrienil) -6- chromanol), β-tocotrienol (2,5, 8-trimethyl-2- (4,8, 12-trimethyl-3,3,7,11-tridecatrienyl) -6-chromanol) or derivatives or mixtures thereof.

19. The method as claimed in clause 17, characterized in that the tocopherol agent comprises a-tocopherol ((+) -2, 5, 7, 8-tetramethyl-2- (4, 8, 12-trimethyltridecyl) -6 -chromanol) and? -tocopherol ((+) -2,7,8-trimethyl-2- (4,8, 12-trimethyltridecyl) -6-chromanol).

20. The method as claimed in clause 17, characterized in that the tocopherol agent is present in an amount of about 0.001% up to about 5%.

21. An oral antiplaque and desensitizing composition comprising: an active ingredient comprising a zinc citrate agent and a potassium citrate agent; Y a copolymer of maleic anhydride and polyvinyl methyl ether and a polyphosphate.

22. The composition as claimed in clause 21, characterized in that the zinc citrate agent it comprises a compound having the general nominal formula of Zn3 (C6H507) 2.

23. The composition as claimed in clause 21, characterized in that the potassium citrate agent comprises a compound having the general nominal formula of K3C6H507.

24. The composition as claimed in clause 21, characterized in that the active ingredient further comprises a compound selected from potassium tartrate, potassium chloride, potassium sulfate, potassium nitrate, sodium nitrate, sodium citrate or mixtures thereof. same.

25. The composition as claimed in clause 21, characterized in that a ratio of the zinc citrate agent to the potassium citrate agent is about 0.5: 1 to about 1: 0.5.

26. The composition as claimed in clause 21, characterized in that the zinc citrate agent is present in an amount of about 0.001% up to about 5% by weight of the oral composition and the potassium citrate agent is present in an amount of about 0.001% up to about 10% by weight of the oral composition.

27. The composition as claimed in clause 21, characterized in that the oral composition also comprises nonionic halogenated diphenyl ether.

28. The composition as claimed in clause 21, characterized in that the oral composition is in the form of an oral rinse, a dentifrice, a confection, a medicament or a film.

29. An oral composition comprising: an active ingredient for oral care comprising a zinc citrate agent and a tocopherol agent, wherein the tocopherol agent comprises at least one compound selected from tocol (2-methyl-2- (4, 8, 12- trimethyltridecl) -6-chromanol), α-tocopherol ((+) -2,5,7, 8-tetramethyl-2- (4,8, 12-trimethyltridecyl) -6-chromanol), β-tocopherol ((+) -2, 5, 8-trimethyl-2- (4,8, 12-trimethyltridecyl) -6-chromanol),? -tocopherol ((+) -2, 7, 8-trimethyl-2- (4, 8, 12 -trimethyltridecyl) -6-chromanol), d-tocopherol ((+) - 8-methyl-2- (4,8,13-trimethyltridecyl) -6-chromanol), α-tocotrienol (2, 5, 7, 8- tetramethyl-2- (4,8, 12-trimethyl-3, 7, 11-tridecatrienyl) -6-chromanol), β-tocotrienol (2,5, 8-trimethyl-2- (4,8, 12-trimethyl- 3, 7, 11-tridecatrienyl) -6-chromanol) or derivatives or mixtures thereof.

30. The composition as claimed in clause 29, characterized in that the tocopherol agent comprises a-tocopherol ((+) -2, 5, 7, 8-tetramethyl-2- (4, 8, 12-trimethyltridecyl) -6 -chromanol) and? -tocopherol ((+) -2,7,8-trimethyl-2- (4,8,13-trimethyltridecyl) -6-chromanol).

31. The composition as claimed in clause 29, characterized in that the tocopherol agent is present in an amount of about 0.001% up to about 5%.

32. The composition as claimed in clause 29, characterized in that the zinc citrate agent is present in an amount of from about 0.001% to about 5% by weight and the tocopherol agent is present in an amount of about 0.001% up to about 5% by weight of the composition.

33. The composition as claimed in clause 29, characterized in that the composition further comprises a copolymer of maleic anhydride and polyvinyl methyl ether and a polyphosphate agent to reduce the astringency of the zinc citrate agent.

34. The composition as claimed in clause 29, characterized in that the composition further comprises a nonionic halogenated diphenyl ether.

35. An oral composition comprising a zinc salt, a linear polyphosphate salt having an average chain length of 3 or less, and at least one of a potassium salt or a vitamin.

36. The oral composition as claimed in clause 35, characterized in that the linear polyphosphate salt is a pyrophosphate.

37. The oral composition as claimed in clause 36, characterized in that the linear polyphosphate salt is a tripolyphosphate.