MXPA05001182A - Oral care composition comprising tropolone compounds and essential oils. - Google Patents

Abstract

The present invention relates to oral care compositions suitable for preventing or treating diseases or conditions of the oral cavity in warm-blooded animals including humans, comprising an oral care effective amount of at least one tropolone compound in combination with at least one essential oil, and a pharmaceutically acceptable oral carrier. This invention further relates to a method for preventing or treating diseases or conditions of the oral cavity in warm-blooded animals including humans, by applying an oral care effective amount of the oral care compositions to the oral cavity.

Description

COMPOSITIONS FOR MOUTH HYGIENE THAT INCLUDE COMPOUNDS OF TROPOLONE AND ESSENTIAL OILS AND METHODS TO USE THE SAME FIELD OF THE INVENTION The present invention relates in general to compositions for oral hygiene, more particularly to oral hygiene compositions comprising substituted tropoane compounds and essential oils and to methods for using same for oral hygiene.

BACKGROUND OF THE INVENTION The bad smell of the mouth, plaque, gingivitis, periodontal disease and discoloration of the teeth are all undesirable ailments that affect many people. The bad smell of the oral cavity is also known as halitosis or bad breath and it is generally estimated that in the United States it affects 20 to 90 million individuals. It is generally believed that the cause of this medical condition is due to the presence in the mouth of anaerobic bacteria, especially gram-negative anaerobic bacteria. Other oral ailments caused by microorganisms include periodontal disease, tooth decay, inflammation and the like.

Periodontal disease is a major cause of tooth loss in adults and can manifest as early as age 12. Periodontal disease affects the periodontium, which is the tissue that surrounds and surrounds a tooth (ie, the periodontal ligament, gum, and alveolar bone). Gingivitis and periodontitis are inflammatory disorders of the gum and the deeper periodontal tissues, respectively. Periodontal disease is usually associated with plaque buildup on the teeth. The teeth are coated with a proteinaceous salivary material (film) and then streptococci are attached to this coating. Gingivitis is usually caused by dental plaque and periodontitis is caused by infection that extends into the periodontal pocket or the space between the gum and the root of the teeth. Many of the current oral hygiene compositions that include toothpastes, mouthwashes, mouthwashes and dental gels are formulated to clean the oral cavity and kill pathogenic microbes. Such compositions for oral hygiene are typically formulated with one or more antimicrobial agents to destroy the microorganisms that contribute to the onset and progression of bad mouth odor, periodontal disease and other undesirable oral ailments. Current compositions for oral hygiene comprise antimicrobial agents and are formulated to maximize the kinetics of the antimicrobial agent. Antimicrobial agents dissolve to provide effective prevention of the disease encouragement, an eradication of oral microbes and penetration, reduction and elimination of plaque and gingivitis. A well-known antiseptic agent is thymol, also known as an essential oil that is used for its antimicrobial activity in a range of preparations for oral hygiene. In particular, thymol has been used in compositions for oral hygiene, such as mouth rinses, in amounts sufficient to provide the desired beneficial therapeutic effects. The LISTERINE® brand for mouth washing is a well-known antiseptic mouth rinse that has been used for more than a hundred years by millions of people and has proven effective in destroying microbes in the oral cavity, which are responsible for plaque, gingivitis and bad breath. Thymol and other essential oils, such as methyl salicylate, menthol and eucallptol, are active ingredients (ie, antimicrobial agents) in antiseptic mouth rinses, such as LISTERINE®. Even in small quantities, these essential oils are effective antimicrobial agents. Without being restricted to any specific theory, it is believed that the efficacy and taste of antiseptic mouth rinses, such as LISTERINE®, may be due to the dissolution and distribution kinetics of these four active agents. There is still a need to provide effective oral hygiene compositions and oral hygiene compositions, such as mouthrinses or mouthwashes containing them, having favorable antimicrobial kinetics showing chemical stability and favorable solubility for effective distribution and antiseptic efficacy. There is still a need to provide compositions and compositions for oral hygiene that are effective in preventing or treating diseases and diseases of the oral cavity in warm-blooded animals that include humans, eliminating or avoiding the presence of oral pathogenic microorganisms responsible for plaque, gingivitis and other undesirable oral complaints in the oral cavity.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to compositions for oral hygiene and methods for using same to prevent or treat diseases or diseases of the oral cavity in warm-blooded animals that include humans. Generally, the composition for oral hygiene contains substituted tropolone compounds together with one or more essential oils in effective amounts to avoid or eliminate the presence of pathogenic and harmful oral microorganisms in the oral cavity. The compositions for oral hygiene provide a high level of antimicrobial kinetics and a useful efficiency to prevent, among others, plaque, gum disease and the bad smell of the mouth. In addition, the composition for oral hygiene can be formulated in a range of products for oral hygiene that include but are not limited to toothpastes, gels dental, dental powders, mouth rinses, pills, chewing gums, tooth strips, dental floss, orally consumable film and oral nebulizers. In a particular aspect of the present invention, there is provided a composition for oral hygiene comprising: (a) an oral hygiene-effective amount of at least one compound of formula (I) wherein Ri, R2, R3, R4 and R5 are each independently selected from the group consisting of hydrogen, hydroxy, an alkyl group, a hydroxyalkyl group, an alkoxyalkyl group, an alkylene group, an alkenylene group, an alkaryl group, an aicycloaikyl group, an alkoxy group, an alkenyl group, an alkynyl group, an aryl group, a cycloalkyl group, a cycloalkenyl group, an aliphatic group optionally substituted with 1 to 3 halogens, an aromatic group optionally substituted with 1 to 3 halogens and a carbonyl group, and isomers and pharmaceutically acceptable salts thereof; (b) at least one essential oil; and (c) a pharmaceutically acceptable oral vehicle.

In a preferred embodiment of the present invention, the composition for oral hygiene comprises an oral hygiene-effective amount of at least one compound of formula (I), wherein R2, R3 and 5 are selected, each independently from the group consisting of hydrogen, an alkyl group having 1 to 6 carbons, a hydroxyalkyl group having 1 to 6 carbons and an alkoxyalkyl group wherein the "alkoxy" part and the "alkyl" part each have 1 to 6 carbons and R , and R4 are each hydrogen. The essential oil is preferably selected from the group consisting of thymol, eucalyptol, menthol, methyl salicylate and combinations thereof. In another aspect of the present invention, there is provided a method for preventing or treating diseases or diseases of the oral cavity, comprising administering an orally effective amount of the oral hygiene composition of the present invention to a warm-blooded animal. which includes human beings.

DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to compositions for oral hygiene with an antimicrobial efficacy against microorganisms, particularly oral microorganisms responsible for producing diseases or undesirable conditions in the oral cavity, including the bad odor of the mouth, the formation of plaque and the like, and the resulting dental and gum diseases that can follow next. The oral hygiene compositions may be in a form selected fromN. for example, mouthwashes, toothpastes, tooth powders, toothpastes, liquid dental flosses, gels, chewing gums, liquid filled gums, mint candies, lozenges, orally consumable films and the like. A preferred aspect of the present invention is directed to a composition for oral hygiene containing an effective amount of at least one substituted tropolone compound having antimicrobial activity together with one or more essential oils. In a particularly preferred aspect of the present invention, there is provided a composition for oral hygiene, preferably a mouthwash, containing an effective amount of at least one substituted tropolone compound, together with at least one essential oil. The essential oils are volatile aromatic oils which can be synthetic or can be obtained from plants by distillation, expression or extraction and which are generally carriers of the odor or flavor of the plant from which it was obtained. In the oral hygiene composition of the present invention, the essential oils provide an antiseptic activity. Some of these essential oils also act as flavoring agents. The essential oils of this invention include but are not limited to thymol, menthol, methyl salicylate (winter-green essence), eucalyptol, carvacrol, camphor, anethole, carvone, eugenol, isoeugenol, limonene, osimen, n-decyl alcohol, citronella, a-salpineol, methyl acetate, citronellyl acetate, methyl eugenol, cineole, linaiol, ethyl-linalaol, vanilla, peppermint essence, spearmint essence , lemon essence, orange essence, sage essence, rosemary essence, cinnamon essence, pepper essence, laurel essence, cedar leaf essence, gerianol, vebenona, anise essence, cherry laurel essence, benzaldehyde, essence of bergamot, bitter almond, chlorotimol, cinnamaldehyde, citronella essence, clove essence, mineral tar, eucalyptus essence, guaiacol, lavender essence, mustard essence, phenol, phenyl salicylate, pine essence, essence of pine, essence of sassafras, essence of lavender spica, storax, essence of thyme, balsam of tolu, essence of terpentine, and combinations thereof. Preferred essential oils are selected from thymol, methyl salicylate, eucalyptol, menthol and combinations thereof. The present invention is effective for cleaning the oral cavity and / or for treating diseases or diseases of the oral cavity including, but not limited to, gingivitis, periodontitis, bad odor of the mouth, dropping of the teeth and the like. The oral hygiene compositions of the present invention provide a high degree of antimicrobial efficacy against microorganisms, particularly pathogenic locus microorganisms, including but not limited to Fusobacterium nucleatum, Prevotella intermedia, Actinomyces viscosus, Campylobacter rectus, Porphyromonas gingivalis, Streptococcus sanguis. , Streptococcus mutans, Actinobacillus, Bacteroides, Capnocytophaga, Eikenella, Propionibacterium and Candida albicans, responsible for the bad odor of the mouth and the formation of plaque and stones and the resulting dental and gum diseases that can follow below. The present invention is also directed to methods for cleaning the oral cavity and / or for treating or preventing diseases or diseases of the oral cavity in warm-blooded animals including humans, by applying an orally effective amount to the oral cavity. of the composition for oral hygiene of the present invention. The term "diseases or diseases of the oral cavity" means in the present description, diseases of the oral cavity including, but not limited to periodontal disease, gingivitis, periodontitis, periodontosis, juvenile and adult periodontitis, and other inflammatory diseases of the tissues of the oral cavity in warm-blooded animals that include humans, more cavities, necrotizing ulcerative gingivitis and other ailments such as the bad smell of the mouth or unpleasant breath. The oral hygiene treatment compositions and methods provided by the present invention are particularly effective in preventing or treating periodontal disease (gingivitis and / or periodontitis) and the foul odor of the mouth in warm-blooded animals that include humans. humans. In a particular aspect of the present invention, there is provided a composition for oral hygiene comprising: (a) an oral hygiene-effective amount of at least one compound of formula (I) wherein Ri, R2, R3, R4 and R5 are each independently selected from the group consisting of hydrogen, hydroxy, an alkyl group, a hydroxyalkyl group, an alkoxyalkyl group, an alkylene group, an alkenylene group, an alkaryl group, an alcycloalkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an aryl group, a cycloalkyl group, a cycloalkenyl group, an aliphatic group optionally substituted with 1 to 3 halogens, an aromatic group optionally substituted with 1 to 3 halogens and a carbonyl group, and isomers and pharmaceutically acceptable salts thereof: (b) at least one essential oil; and (c) a pharmaceutically acceptable oral vehicle. In a preferred embodiment of the present invention, the composition for oral hygiene comprises an oral hygiene-effective amount of at least one compound of formula (I), wherein R2, R3 and R5 are each independently selected from the group consisting of in hydrogen, an alkyl group having 1 to 6 carbons, a hydroxyalkyl group having 1 to 6 carbons and an alkoxyalkyl group wherein the "alkoxy" part and the "alkyl" part each have 1 to 6 carbons and Ri and R are each hydrogen. The isomers of the compounds of formula (I) having the desired mixture thereof of antimicrobial activity are included in the scope of the present invention. In addition, hydrates and solvates with pharmaceutically acceptable organic solvents, as well as prodrugs of the compounds of the present invention, are also included in the present invention. In addition, the compounds of formula (I) or their pharmaceutically acceptable salts may be present in the form of addition products with water or various solvents, and these addition products are also included in the scope of the present invention. The term "pharmaceutically acceptable salts" refers to salts prepared from non-toxic, pharmaceutically acceptable bases or acids including inorganic or organic bases and inorganic or organic acids. They can be obtained from a variety of organic and inorganic cations well known in the art and including by way of example, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium and the like, and anions, such as hydrochloride, hydrobromide, tartrate. , mesylate, acetate, maleate, oxalate and the like. When the compound of the present invention is basic, salts can be prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids.

Such acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethanesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, sedesic, lactic, maleic, malic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic acids , sulfuric, tartaric, p-toluenesulfonic, and the like. Particularly preferred are citric, hydrobromic, hydrochloric, maleic, phosphoric, sulfuric and tartaric acids. The salts obtained from inorganic bases include the aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic, manganese, potassium, sodium, zinc and the like salts. Particularly preferred are ammonium, calcium, magnesium, potassium and sodium salts. The salts obtained from pharmaceutically acceptable non-toxic organic bases include primary, secondary and tertiary amine salts, substituted amines including substituted amines present in nature, cyclic amines and basic ion exchange resins, such as arginine, betaine , caffeine, choline N'N-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethyl-morpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine and the like. Those skilled in the art will recognize a wide variety of non-toxic, pharmaceutically acceptable addition salts.

The term "alkyl" refers to monovalent linear and branched alkyl groups, preferably having from about 1 to 18 carbon atoms, more preferably from about 1 to 14 carbon atoms and even more preferably from about 1 to 6 carbon atoms. This term is exemplified by groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tere-butyl, n-heyl, n-oxtyl, tert-octyl and the like. The term "alkylene" refers to divalent alkylene groups preferably having from about 1 to 18 carbon atoms and more preferably from about 1 to 14 carbon atoms which may be linear or branched. The term is exemplified by groups such as methylene (-CH2 ~), ethylene (-CH2CH2-), propylene isomers (eg, -CH2CH2CH2- and -CH (CH3) CH2-) and the like. The term "alkenylene" refers to divalent alkenylene groups preferably having from about 2 to 18 carbon atoms and more preferably from about 2 to 14 carbon atoms which may be straight or branched chain and having at least 1 and preferably 1 to 2 sites of alkenyl unsaturation. This term is exemplified by groups such as ethenylene (-CH = CH-), the propenylene isomers (e.g., -CH = CHCH2- and -C (CH3) = CH- and -CH = C (CH3) -) and the like. The term "alkaryl" refers to alkylene-aryl groups preferably having from about 1 to 18 carbon atoms in the alkylene residue and from about 6 to 14 in the aryl moiety. Such alkaryl groups are exemplified by benzyl, phenethyl and the like. The term "alcycloalkyl" refers to alkylene-cycloalkyl groups preferably having from about 1 to 18 carbon atoms in the alkylene moiety and from about 3 to 14 in the cycloalkyl moiety. Such cycloalkyl groups are exemplified by -CH2-cyclopropyl, -CH2-cyclopentyl, -CH2CH2-cyclohexyl, and the like. The term "alkoxy" refers to the group "alkyl-O-". Alkoxy groups include, by way of example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy and the like, preferably having from about 1 to 6 carbon atoms. The term "alkoxyalkyl" refers to the groups "alkyl-O-alkyl-", preferably the alkyl part of the group has 1 to 6 carbon atoms and the alkoxy part of the group has 1 to 6 carbon atoms. The term "alkenyl" refers to alkenyl groups preferably having from about 2 to 18 and more preferably having from about 2 to 14 carbon atoms and having at least 1 and preferably 1 to 2 sites of alkenyl unsaturation. Such alkenyl groups are exemplified with ethenyl (-CH = CH2, n-propenyl (-CH2CH = CH2), isopropenyl (-C (CH3) = CH2) and the like. The term "alkynyl" refers to alkynyl groups preferably having about 2 to 18 carbon atoms and more preferably from about 2 to 14 carbon atoms and that they have at least 1 and preferably 1 to 2 sites of alkynyl unsaturation. Such alkynyl groups are exemplified by ethynyl (-CH / CH2), propargyl (-CH2CH / CH2) and the like. The term "aryl" refers to an unsaturated aromatic carbocyclic group, from about 6 to 18 carbon atoms having a single ring (e.g., phenyl) or condensed multiple rings (e.g., naphthyl or anthryl). Examples of arites include phenyl, naphthyl and the like. Unless otherwise restricted by the definition of the individual substituent, such aryl groups may be optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkoxy, acyloxy, hydroxy and the like. The term "cycloalkyl" refers to cyclic alkyl groups of about 3 to 18 carbon atoms having a single cyclic ring or multiple fused rings which may be optionally substituted with 1 to 3 alkyl groups. Such cycloalkyl groups include, by way of example, cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl, 1-methylcyclopropyl, 2-methylcyclopentyl, 2-methicyclooctyl and the like, or multi-ring structures such as adamantyl and the like. The term "cycloalkenyl" refers to cyclic alkenyl groups from about 4 to 18 carbon atoms having a single cyclic ring and at least one point of internal unsaturation which may be optionally substituted with 1 to 3 alkyl groups. Examples of cycloalkenyl groups Suitable include, for example, cyclopent-3-enyl, cyclohex-2-enyl, cyclooct-3-enyl, and the like. The preferred tropolone compounds of formula (I) for use in the oral hygiene compositions of the present invention include those selected from the group consisting of 2-hydroxy-7-methyl-2,4,6-cycloheptatrien-1. -one; 2-hydroxy-7-heptyl-2,4,6-cycloheptatrien-1 -one; 2-hydroxy-7- (methoxymethyl) -2,4,6-cycloheptatrien-1 -one; 2-hydroxy-4-methyl-2,4,6-cycloheptatrien-1-one; 2-hydroxy-4-dimethylethyl-2,4,6-cycloheptatrien-1-one; and 2-hydroxy-7- (hexyloxymethyl) -2,4,6-cycloheptatrien-1-one, and combinations thereof. It will be understood that some of the above compounds may be in the form of salts. In such cases, the compounds may be ionized and accompanied by a pharmaceutically acceptable anion or cation, as appropriate. Most generally, a cation is a monovalent material such as sodium, potassium or ammonium, but it can also be a multivalent cation together with a pharmaceutically acceptable monovalent anion, for example, calcium with a chloride, bromide, iodide, hydroxyl, nitrate, sulfonate, acetate, tartrate, oxalate, succinate, palmoate or similar anion; magnesium with such anions; zinc with such anions or the like. The term "oral hygiene composition" includes products that are retained in the buccal cavity long enough to contact the dental surfaces and / or tissues of the buccal mucosa and which exhibit the desired buccal activity. The expression "quantity effective for oral hygiene ", as used herein, means an amount of at least one compound of tropolone sufficient to prevent or treat diseases or ailments of the oral cavity or to significantly eliminate or at least destroy the presence of microorganisms unwanted in the oral cavity, without causing side effects, within the scope of accepted medical and dental criteria.The effective amount for oral hygiene of the tropolone compounds of the present invention may vary with the particular condition to be subjected to treatment (eg, for a disease of the oral cavity or bad smell), with the age and physical condition of the patient to be treated, the severity of the condition, the duration of the treatment, the nature of the concurrent therapy, the specific form (ie, salt) of the used tropolone compound and the particular vehicle with which the tropolone compound is applied. tropolone in the composition for oral hygiene of the present invention depends on the type of composition (e.g. eg, toothpaste, mouthwash and mouthrinse, lozenge, gum etc.) used to apply the tropolone compounds to the gingival / mucosal tissue and / or the teeth, due to the differences in efficacy of the compositions that come into contact with the tissue and teeth and also due to the amount of composition generally employed. Concentration may also depend on the diseases or ailments that are going to be treated.

In a preferred embodiment, the oral hygiene compositions of the present invention can include from about 0.001% to 10.0% by weight, based on the total weight of the oral hygiene composition, preferably from about 0.01% to 5.0% by weight , and more preferably from about 0.1% to 2.0% by weight of the tropolone compounds of the present invention, the remainder of the formulation being the essential oils, the carrier and other materials known in the art as components of oral hygiene compositions. . Such additional components may include buffers, surfactants, solubilizing agents, preservatives, emulsifiers, isotonisers, stabilizing agents, pH adjusters, sweeteners, similar coloring agents. The oral hygiene composition of the present invention contains an effective antimicrobial amount of an antimicrobial compound having a structure of formula (I) together with one or more effective antimicrobial essential oils, as active components. Such antimicrobially effective essential oils may include thymol, menthol methyl salicylate (wintergreen essence), eucalyptol, carvacrol, camphor, anethole, carvone, eugenol, isoeugenol, limonene, osimen, n-decyl alcohol, citronella, asalpineol, methyl acetate, citronellil acetate, methyl eugenol, cineole, linalool, ethyl-linalaol, vanilla, peppermint essence, mint essence, lemon essence, orange essence, sage essence, rosemary essence, cinnamon essence, essence of pepper, essence of laurel, essence of cedar leaf, gerianol, verbenone, anise essence, cherry laurel essence, benzaldehyde, bergamot essence, bitter almond, chlorotimol, cinnamaldehyde, citronella essence, clove essence, mineral tar, eucalyptus essence, guaiac, essence of lavender, mustard essence, phenol, phenyl salicylate, pine essence, pine needles essence, sassafras essence, spica lavender essence, storax, thyme essence, tolu balm, terpentine essence, and combinations thereof . The composition generally takes the form of a solution containing these components in water. The mixture by addition of the antimicrobial compounds of formula (I) and the antimicrobial essential oils, preferably those selected from the group consisting of thymol, menthol, eucalyptus, methyl salicylate and combinations thereof, provides a synergistic antimicrobial effect. In compositions for oral hygiene, essential oils are used in effective amounts to provide oral hygiene which includes the removal or destruction of oral microorganisms in the oral cavity. Generally, essential oils may be present in the oral hygiene composition of the present invention in an amount from about 0.001% to 8.0% by weight, based on the total weight of the composition; preferably in an amount from about 0.004% to 3.0% by weight; and more preferably in an amount from about 0.007% up to 2. 0% by weight. The amounts employed in the oral hygiene compositions may vary depending on how the composition can be determined by those skilled in the art. The compositions of the present invention generally contain thymol and / or one or more other essential oils. Preferably, the additional essential oils are eucalyptol, menthol or methyl salicylate, or mixtures thereof. It is most preferred that the composition contains these four essential oils. Thymol ((CH3) 2CHC6H3 (CH3) OH; isopropyl-m-cresol), also known by the chemical formula 5-methyl-2- (1-methylethyl) phenol, is an effective antimicrobial agent and is typically obtained from the essential oil of Thymus vulgaris Labiatae and Monarda punctata Labiatae. Thymol is a white crystalline powder with an aromatic odor and taste and is soluble in organic solvents but is only slightly soluble in deionized water. Thymol may be present in the oral hygiene composition of this invention in an amount from about 0.001% to 2.0% by weight based on the total weight of the composition; preferably in an amount from about 0.01% to 0.6% by weight; and more preferably in an amount from about 0.02% to 0.5% by weight. Menthol (CH3CsH9 (C3H7) OH; hexylhydroxythymol) also possesses antiseptic properties and provides a feeling of freshness and tingling. Menthol is isolated mainly from the essence of Mentha arvensis. In its commercial form, menthol is available as L-menthol crystals obtained from a procedure that involves a cooling of oil. Fractional distillation of the spearmint essence, which generally contains from about 40% to about 65% menthol, represents another important source of menthol. Synthetic sources of L-menthol are also available. Menthol may be present in the oral hygiene composition of the present invention in an amount from about 0.001% to 2.0% by weight based on the total weight of the composition; preferably in an amount from about 0.01% to 0.7% by weight; and more preferably in an amount from about 0.01% to 0.6% by weight. Eucalyptol (Ci0H18O; cineol), another essential oil with antiseptic properties, is obtained from the eucalyptus tree. Eucalyptol is a terpene ether that provides a refreshing, spicy taste and an antiseptic activity. By having a camphor smell and a refreshing taste, this essential oil is often combined with other essential oils such as menthol for the preparation of formulations to impart a medicinal effect. The use of menthol and eucalyptol combinations is widespread. Particularly preferred uses of the menthol-eucalyptol combination include, according to the present invention, toothpastes such as toothpastes dental gels. Eucalyptol may be present in the oral hygiene composition of the present invention in an amount from about 0.001% to 2.0% by weight based on the total weight of the composition; preferably in an amount from about 0.005% up to 0.5% by weight; and more preferably in an amount of about 0.007% up to 0.4% by weight. Methyl salicylate (C6H4OHCOOCH3), also known as wintergreen essence, is the main ingredient of many essential oils, constituting approximately 99% essence of wintergreen (Gaultheria procumbens) and sweet birch (Betula lento). Methyl salicylate having a distinctive refreshing aroma is widely used in mouthwashes, chewing gums and in other oral and pharmaceutical preparations. Methyl salicylate is able to provide flavor along with organoleptic flavor tones to the composition for oral hygiene, in addition to its antimicrobial function. Methyl salicylate may be present in the oral hygiene composition of the present invention in an amount from about 0.001% to 2.0% by weight based on the total weight of the composition; preferably in an amount from about 0.004% to 0.6% by weight; and more preferably in an amount from about 0.01% to 0.6% by weight. The oral hygiene composition of the present invention may contain the following essential oils in percentages by weight based on the total weight of the oral hygiene composition: (a) thymol from about 0.001% to 2.0% by weight; (b) menthol from about 0.001% to 2.0% by weight; (c) eucalyptol from about 0.001% to 2.0% by weight; and (d) methyl salicylate from about 0.001% to 2.0% by weight.

In a preferred embodiment of the oral hygiene composition of the present invention, the oral hygiene composition may contain the following essential oils in percentages by weight based on the total weight of the composition for oral hygiene: (a) thymol from about 0.01% up to 0.6% by weight; (b) menthol from about 0.01% to 0.7% by weight; (c) eucalyptol from about 0.005% to 5% by weight; and (d) methyl salicylate from about 0.004% to 0.6% by weight. In a more preferred embodiment of the oral hygiene composition of the present invention, the oral hygiene composition may contain the following essential oils in percentages by weight based on the total weight of the composition for oral hygiene: (a) thymol from about 0.02% to 0.5% by weight; (b) menthol from about 0.01% to 0.6% by weight; (c) eucalyptol from about 0.007% to 0.4% by weight; and (d) methyl salicylate from about 0.01% to 0.6% by weight. The oral hygiene compositions of the present invention containing tropolone compounds of formula (I) and thymol and / or at least one other essential oil, provide an effective antimicrobial activity. The oral hygiene compositions may comprise other antimicrobial agents if desired. Such exemplary antimicrobial agents include chlorhexidine, chitosan, triclosan, cetylpyridium chloride, domiphene bromide, and the like. The amount of such antimicrobial agents used in the composition of this invention can be easily determined by those skilled in the art. The vehicle for the oral hygiene compositions of the present invention and, particularly, for the essential oils containing the compositions, can be aqueous medium. The aqueous medium can be a water-alcohol mixture, generally a water-ethanol or water-1-propanol mixture. The level of ethanol content may be from about 0.01% to 70% by weight based on the total weight of the composition to solubilize and deliver the antimicrobial agents and to provide a clear, aesthetically attractive liquid medium. A favorable amount of ethanol for improving the organoleptic signals of the oral hygiene compositions, specifically the mouthwash compositions, may be in the range of from about 0.1% to 30% by weight, more preferably from about 20% to 30% by weight although smaller quantities may be used if desired. Alternatively, the aqueous medium is water. The compositions for oral hygiene can be selected, for example, from the group consisting of mouthwashes or mouthwashes, toothpastes, tooth powders, toothpastes, dental flosses, liquids, gels, chewing gums, liquid-filled gums , mint candies, pills, toothpastes that form oral films, orally consumable films and the like. The oral hygiene compositions of the present invention comprise a pharmaceutically acceptable oral carrier in a adequate amount to accommodate the other components of the formulation. The term "pharmaceutically acceptable oral vehicle" refers to a vehicle capable of being mixed with the active components to be delivered to the desired target in an oral cavity and causing no harm to warm-blooded animals, including humans. Oral vehicles may include components of the composition that are capable of being mixed without interacting in a manner that would substantially reduce the stability of the composition and / or efficacy for oral hygiene, including the prevention or treatment of diseases or conditions of the oral cavity in warm-blooded animals that include humans, according to the compositions and methods of the present invention. Pharmaceutically acceptable oral vehicles of oral hygiene compositions may include one or more compatible fillers., solids or liquids, or encapsulated substances that are suitable for oral administration. The vehicles or excipients of the present invention may be in any form suitable for the mode of delivery, for example, solutions, colloidal dispersions, emulsions, suspensions, mouthwashes, gels, foams, powders, solids and the like, and may include the components conventional and conventional toothpastes (which include gels and gels for subgingival application), rinses and mouthwashes, mouth foggers, chewing gums, orally consumable films and pills (which include breath mints). Suitable vehicles for the preparation of the compositions of the present invention are well known in the art. Their selection will depend on secondary considerations such as taste, cost and storage stability, etc. The types of vehicles that can be included in the oral compositions of the present invention are abrasives, fluoride ions, thickening agents, humectants, flavoring and sweetening agents, anti-calculus agents, alkali metal bicarbonate salts, surfactants including nonionic surfactants and amphoteric and anionic surfactants, and mixing vehicles such as water, titanium dioxide, anti-inflammatory agents and the like. Preferred compositions of the present invention are mouthwash, mouthwash and mouth foggers. The components of such mouthwash, mouthwash and mouthwash typically include water that is present in an amount of from about 45% to 95% by weight and one or more ethanol up to 70%, a wetting agent up to 50%, a surfactant from about 0.01. % to 7%, a flavoring agent from about 0.04% to 2%, a sweetening agent from about 0.1% to 3%, and a coloring agent from about 0.001% to 0.5%. Such mouthwash, mouthwash and mouthwash may also include one or more anti-caries agents from about 0.05% to 0.3% (eg, fluoride ion) and an anti-calculus agent from about 0.1% to 3%.

Other preferred compositions of the present invention are dental solutions. The components of such dental solutions include water from about 90% to 99% by weight based on the total weight of the oral hygiene composition and one or more preservatives from about 0.01% to 0.5%, a thickener up to 5%, an agent Flavoring from about 0.1% to 3% and a surfactant up to 5%.

Other preferred compositions of the present invention are orally consumable thin films or strips. Orally consumable films comprise a thin film carrier based on polymers which are not self-adhesive and which dissolve easily. Such compositions are typically administered in the oral cavity where it dissolves rapidly after coming into contact with the saliva and provide a rapid distribution of the active ingredients. Products in LISTE INE® POCKETPAKS ™ oral hygiene strips manufactured by PFIZER, Inc. of Morris Plains, New Jersey, are perhaps the most successful examples of an edible film composition effective for delivering therapeutic agents in particular antimicrobial agents in the form of LISTERINE® essential oils in the oral cavity. The components of such compositions generally include water in an amount of up to 75% by weight, a polymer that forms a water-soluble film that includes, but is not limited to, puyulin, in an amount of up to 25%, a flavoring agent in an amount of approximately 0.01% to 10%, a surfactant in an amount of up to 5% and, optionally, copper salts in an amount from about 0.01% to 5%. Other preferred compositions of the present invention are in the form of dentifrices such as toothpastes, dental gels and dental powders. The components of such toothpastes and dental gels generally include one or more dental abrasives, generally from about 10% to 50% by weight, a surfactant such as an anionic, nonionic or ionic hybrid detergent from about 0.5% to 10%, a thickening agent from about 0.1% to 5%, a humectant from about 10% to 55%, a flavoring agent from about 0.04% to 2%, a sweetening agent from about 0.1% to 3%, a coloring agent from 0.01% a 0.5% and water from approximately 2% to 45%. Such toothpastes or dental gels may also include one or more of an anti-caries agent from about 0.05% to 0.3% (eg, fluoride ion) and an anti-calculus agent from about 0.1% to 13%. Liquids and solids are provided to form a creamy or gelled mass that can be extruded from a pressure vessel or from a collapsible tube. Dental powders, of course, contain substantially all non-liquid components. Other preferred compositions of the present invention are in microcapsule form or more generally known as gel beds which generally comprise a flavoring agent in an amount of about 0.1% to 10% by weight, a lipophilic charge in an amount of about 1% to 60%, an emulsifier in an amount of about 0.1% to 5%, and a sweetening agent in an amount of about 0.1% to 3%. The chewing gum compositions typically include one or more gum bases from about 50% to 99% by weight, a flavoring agent from about 0.4% to 2% and a sweetening agent from about 0.01% to 5%. The term "lozenge", as used herein, includes: breath mints, tablets, lozenges, microcapsules and solid fast-dissolving forms including spray-dried forms (pastes, wafers, thin films) and tablets) and solid forms of rapid dissolution including tablets. The term "solid form of rapid dissolution", as used herein, means that the solid dosage form dissolves in less than about 60 seconds, preferably less than about 15 seconds, most preferably less than about 5 seconds. , after placing the solid dosage form in the oral cavity. The lozenges include disc-shaped solids comprising a therapeutic agent in a flavorant base. The base can be a hard candy of sugar, glycerinated gelatin or a combination of sugar with enough mucilage to shape it. The tablet compositions for sucking (of the compressed type) typically includes one or more fillers (compressible sugar), flavoring agents and lubricants. The surfactants can be employed in the composition of the present invention. There are organic materials that aid in the complete dispersion of the components including the active agents and flavor oils throughout the solution, as well as the dispersion of the preparation throughout the oral cavity and allow the compositions to have a clear and uniform appearance that is aesthetically more attractive. Preferably, the surfactant employed in the compositions of the present invention is a nonionic surfactant or an anionic surfactant employed in an amount sufficient to help solubilize the active components. Sufficient amount means that the surfactant is present in an amount that effectively aids the solubilization and kinetics of the distribution system of the tropolone compounds and essential oils. Additional components may be added, such as those known to those skilled in the art. For example, acidic preservatives such as sorbic or benzoic acid can be added to reduce the pH levels. Buffer systems may be necessary to control the pH of the composition to optimum levels. This is usually done by the addition of a weak acid and its salt or a weak base and its salt. Useful systems have been found in sodium benzoate and benzoic acid in amounts from about 0.01% to 4.0% by weight and sodium citrate and citric acid in amounts from about 0.001 to 0.2% by weight.

Preferably, the buffers are incorporated in amounts that maintain the pH at levels from about 3.5 to 9.0 and more preferably from about 4.0 to 7.0. In another embodiment of the present invention, there is provided a method for preventing or treating diseases or ailments of the oral cavity in warm-blooded animals including humans, by applying an effective amount for oral hygiene of the composition for oral hygiene of the present invention in the oral cavity. The effective amount for oral hygiene of the oral care compositions of the present invention is preferably applied to the mucosal tissue of the oral cavity, to the gingival tissue of the oral cavity and / or to the surface of the teeth. , to treat or prevent the diseases or ailments mentioned above, according to one or more conventional ones. For example, the gingival or mucosal tissue can be rinsed with a solution (eg, mouthwash or mouthwash) containing the composition of the present invention.; if a toothpaste (eg toothpaste, tooth gel or dental powder) is used, the gingival / mucosal tissue or the teeth can be bathed in the liquid and / or the foam generated by brushing the teeth; for a sufficient time, preferably from about 10 seconds to 10 minutes, more preferably from about 30 seconds to 60 seconds. The method of the present invention generally involves the expectoration of most of the composition after said Contact. The frequency of such contact is preferably from about once a week to about four times a day, more preferably from about 3 times a week to three times a day, even more preferably from one to two times a day. The period of said treatment is generally in the range from about one day to all of life. For diseases or particular ailments of the oral cavity, the duration of treatment depends on the severity of the disease or oral affliction to be treated, the particular form of administration used and the patient's response to treatment. If administration in the periodontal pockets is desirable, such as in the treatment of periodontal disease, a mouthwash or mouth rinse may be administered to the periodontal pocket using a syringe or an injection device with water, for example. After the irrigation, the patient can shake the washing liquid in the mouth to cover also the dorsal part of the tongue and other gingival / mucosal surfaces. In addition to toothpaste, with a non-abrasive gel, a dental gel, etc., you can brush the surface of the tongue and other gingival tissues and the mucosa of the oral cavity. Other non-limiting examples include chewing gum containing the composition of the present invention, chewing or sucking a bad breath pill or tablet. Preferred methods for applying the oral hygiene compositions of the present invention, on the gingival / mucosal tissue and / or on the teeth, include washing with a solution of a mouthwash or mouthwash and brush with a toothpaste. Other methods for applying the present composition to the gingival / mucosal tissue and the surface of the teeth are apparent to those skilled in the art. The present substituted tropolone compounds of formula (I), employed in the present invention can be prepared from readily available starting materials, employing the following general methods and procedures. It will be understood that where typical or preferred process conditions are indicated (i.e., reaction temperatures, times, molar ratios of the reagents, solvents, pressures, etc.) other conditions of the process may also be used, unless otherwise indicated else. Optimal reaction conditions may vary with the particular reagents or solvents employed, although such reaction conditions may be determined by one of ordinary skill in the art by routine optimization procedures.

SCHEME 1 The compounds of formula (I) can be prepared as shown in scheme 1, by reacting dichloroacetyl chloride with a substituted cyclopentadiene compound in R2, in the presence of a base such as triethylamine, to provide a cycloaduct of formula ( III). The cycloaduct of formula (III) is then treated with an acid such as acetic acid and a base such as triethylamine to provide the desired final product, a 4-alkyltropolone compound. When R2 is isopropyl, the resulting compound is hinokitiol which is used as the starting material in Scheme 2.

SCHEME 2 4-isopropyl-7-hydroxyalkyltrapone 4-isopropyl-7-alkyltropolone The compounds of formula (I) can be further prepared as shown in scheme 2 by treating hinokitiol with a carbonyl compound (¾¾ = 0, wherein R 6 is an alkyl group) such as formaldehyde, acetaldehyde, proprionaldehyde, butyraldehyde and similar, in the presence of a base such as potassium hydroxide, and then adding an acid such as hydrochloric acid to obtain a 4-isopropyl-7-hydroxyalkyl-tropolone compound. The 4-isopropyl-7-hydroxyalkyl-troponone compound is then treated with a chlorinating agent such as SOC, in the presence of a base such as pyridine, to provide a 4-isopropyl-7-chloroalkyl-troponone compound. The isopropyl-7-chloroalkyl troponone compound is reacted with an alcohol (R7OH, wherein R7 is an alkyl group) such as methanol, ethanol, propanol and the like in the presence of heat to achieve the corresponding 4-isopropyl-7-alkoxyalkyl-troponone compound.

SCHEME 3 4-isopropyl-7-hydroxy-4-isopropyl-7-formyltropolone methyltropolone tropolone 4-isopropyl-7-chloromethyl-4-isopropyl-7-methoxymethyl tropolone tropolone The compounds of formula (I) can be further prepared as shown in scheme 3, by reacting 4-isopropyl-7-hydroxymethyltropolone with an oxidizing agent such as Mn02 for obtain 4-isopropyl-7-formyltropolone. The starting compound, 4-isopropyl-7-hydroxy-methyl-troponone, can be prepared by reacting the hinokithiol with formaldehyde in the presence of a base such as potassium hydroxide and then treating the reaction with an acid, such as hydrochloric acid. The 4-isopropyl-7-formyltropolone is reacted with an alkylmagnesium bromide compound (RsMgBr; wherein F¾ is an alkyl group) and the reaction is quenched with a hydrochloric acid to provide a 4-isopropyl-7-hydroxymethyltropolone compound. The 4-isopropyl-7-hydroxymethyltropolone compound is treated with a reducing agent such as phosphorus, preferably red phosphorus, in the presence of an acid, such as acetic acid, after which an oxidizing agent such as iodine is added to the reaction. to obtain a final product of a 4-isopropyl-7-alkyltropolone compound. The following examples are offered only to illustrate the invention and should not be construed as limiting the invention. For example, optimal reaction conditions may vary with the particular reagents or solvents employed, although such reaction conditions may be determined by one of ordinary skill in the art by routine optimization procedures.

EXAMPLE 1 Mouthwash composition containing compounds of formula (I) and essential oils A mouthwash composition was prepared having the following components shown below in Table 1.

TABLE 1 The composition was prepared by adding the essential oils (thymol, methanol, methyl salicylate and eucalyptol) and the compound of formula (I), flavor oils, poloxamer 407 and benzoic acid to alcohol, followed by the addition of 250 ml of water. Sorbitol, saccharin and dye were added to the resulting mixture followed by the addition of water to provide a 100 ml sample of the mouthwash composition.

EXAMPLE 2 4-RETHYLTHROPROPON As illustrated in Scheme A, a solution comprising 25 ml of triethylamine and 100 ml of a mixture of hexanes was added dropwise to a solution containing 48.5 g of methylcyclopentadiene (prepared from cracking). of a methylcyclopentadiene dimer) and 22.5 g of dichloroacetyl chloride in 200 ml of a mixture of hexanes at 0 ° C. The mixture was stirred for about one hour and then poured into 150 ml of water at about 0 ° C. The layers were separated and the aqueous phase was extracted with two 75 ml portions of hexanes. The combined organic layers were washed twice with water, then dried over NaaSC and concentrated to obtain an oil. The fractional distillation was carried out under vacuum to obtain a cycloadduct from formula (III) that was dissolved in 80 ml of acetone. The resulting solution was then added to a solution containing 28.5 ml of acetic acid, 82.5 ml of triethylamine, 36 ml of water and 100 ml of acetone. The mixture was refluxed under nitrogen for about four hours. The ketone was removed from the mixture under reduced pressure. An additional 100 ml of water was added and the solution was then extracted three times, each time with 100 ml portions of ether. The combined organic extracts were washed with water and dried over gSO4. The final product, 4-methyltropolone, was recrystallized from hexanes to obtain a white solid.

EXAMPLE 3 Synthesis of 4-isopropyl-7-methoxymethyltropolone SCHEME B As illustrated in scheme B, a solution comprising 10 g of hinokitiol and 8.8 ml of 25% aqueous KOH was heated at 60 ° C under argon. Formaldehyde was added in 1 ml portions every 30 minutes, until a total of 10 ml was added. The reaction mixture was concentrated to a yellow paste and 300 ml of acetone was added. The resulting yellow solid was collected and washed with acetone. The solid was suspended in 250 ml of dichloromethane and 50 ml of HCL 2.0 was added. The aqueous layer was washed with dichloromethane and the combined organic layers were washed with water and then dried over Na2SO4. The solvent is it was removed under vacuum, leaving an oil that solidifies after triturating with petroleum ether. An ice cooled solution of 4.0 g of 4-isopropyl-7-hydroxymethyltropolone and 1.8 ml of pyridine in 100 ml of diethyl ether was stirred vigorously for two hours and a solution of SOC (2.5 ml) in 80 ml of ether was added. to the same. The resulting mixture was concentrated to a solid. Boiling petroleum ether was added to the solid. The resulting mixture was filtered and the filtrate was cooled to 4-isopropyl-7-chloromethyltropolone as a solid. The solid product was then refluxed in methanol under nitrogen for about two hours and then concentrated to obtain a golden oil. A stream of N2 gas was passed through the oil until solidified to obtain 4-isopropyl-7-methoxymethyltropolone as a pale yellow solid.

EXAMPLE 4 Synthesis of 4-isopropyl-7-hexyltro-copone SCHEME C. 4-isopropyl-7-hydroxy-methyl-troponone 4-isopropyl-7-formyl-troponone 4-sopropi l-7-hydroxyl hexyltropolone 4-isopropyl-7-hexyltropolone as illustrated in Scheme C, 4-isopropyl-7-methoxymethyltropolone as produced in Example 2, it was oxidized in the presence of MnO2 until 0.85 g of 4-isopropyl-7-formyltropolone was obtained. 4- Sopropil-7-formyltropolone was added to ether until a solution was obtained which was shaken under? at 0 ° C. 5 ml of a 2.0 M solution of pentylmagnesium bromide was added to the solution via syringe. The mixture was stirred for approximately 45 minutes and then cooled with 20 ml of water. 10 ml of 0.5 M HCL and 100 ml of ether were added to the mixture. The layers were separated and the organic layer was dried over Na2SO4. The solvent was removed and the resulting oil was triturated with petroleum ether to obtain 4-isopropyl-7-hydroxyhexyl-troponone as a yellow oil. The oil product was mixed in 2 ml of water, 1 g of red phosphorus and 15 ml of acetic acid. The mixture was stirred well and 1 g of 12 was added. The reaction mixture was refluxed for about one hour and then filtered. 150 ml of water was added to the filtrate. K2C03 was added to the mixture to generate a basic pH. The mixture was extracted with petroleum ether. The organic layer was washed with Na2S2C > 3 and then with water and dried over Na 2 SO 4 to obtain 4-isopropyl-7-hexyltropolone in the form of an oil. The above description describes and clarifies only exemplary embodiments of the present invention. One skilled in the art will readily recognize from this description and the appended claims that various changes, modifications and variations thereof may be made, without deviating from the spirit and scope of the invention, as described in the following claims.

Claims (1)

1. NOVELTY OF THE INVENTION CLAIMS 1. - A composition comprising: (a) an effective amount of at least one compound of formula (I) wherein R t, R 2, R 3, R 4 and 5 are each independently selected from the group consisting of hydrogen, hydroxy, an alkyl group, a hydroxyalkyl group, an alkoxyalkyl group, an alkylene group, an alkenylene group, an alkaryl group, an alcycloalkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an aryl group, a cycloalkyl group, a cycloalkenyl group, an aliphatic group optionally substituted with 1 to 3 halogens, an aromatic group optionally substituted with 1 to 3 halogens and a carbonyl group and pharmaceutically acceptable salts thereof; (b) optionally, at least one essential oil; and (c) optionally, a pharmaceutically acceptable oral vehicle. 2. The composition according to claim 1, further characterized in that the alkyl group has 1 to 6 carbon atoms, the hydroxyalkyl group has 1 to 6 carbon atoms and the alkoxy part and the alkyl part of the alkoxyalkyl group each have 1 to 6 carbon atoms. 3. The composition according to any one of the preceding claims, further characterized in that the effective oral amount of the compound of formula (I) is from 0.001% to 10% by weight based on the total weight of the composition. 4. The composition according to any one of the preceding claims, further characterized in that at least one essential oil is selected from the group consisting of thymol, menthol, methyl salicylate (wintergreen essence), eucalyptol, carvacrol, camphor, anethole. , carvone, eugenol, isoeugenol, limonene, osimen, n-decyl alcohol, citronella, a-salpineol, methyl acetate, citronellyl acetate, methyl-eugenol, cineole, linalool, ethyl-linalale, vanilla, essence of peppermint, essence mint green, essence of lemon, essence of orange, essence of sage, essence of rosemary, essence of cinnamon, essence of pepper, essence of laurel, essence of leaf of cedar, gerianol, verbenone, essence of anise, essence of laurel cherry , benzaldehyde, bergamot essence, bitter almond, chlorothimol, cinnamaldehyde, citronella essence, clove essence, mineral tar, eucalyptus essence, guaiacol, lavender essence, mustard essence, phenol, salicylate phenyl essence of pine, essence of pine needles, essence of sassafras, essence of lavender spica, storax, essence of thyme, balsam of tolu, essence of terpentine and combinations thereof. 5. The composition according to any one of the preceding claims, further characterized in that at least one essential oil is selected from the group consisting of thymol, eucalyptol menthol and methyl salicylate and mixtures thereof. 6. The composition according to any one of the preceding claims, further characterized in that the amount effective for oral hygiene of thymol is from 0.001% to 2.0% by weight based on the total weight of the composition. 7. The composition according to any one of the preceding claims, further characterized in that the effective amount for oral hygiene of eucalyptol is from 0.001% to 2.0% by weight based on the total weight of the composition. 8. The composition according to any one of the preceding claims, further characterized in that the amount effective for oral hygiene of methyl salicylate is from 0.001% to 2.0% by weight based on the total weight of the composition. 9. - The composition according to any one of the preceding claims, further characterized in that the effective amount for oral hygiene of menthol is from 0.001% to 2.0% by weight based on the total weight of the composition. 10. The composition according to any one of the preceding claims, further characterized in that at least one compound of the formula (I) is selected from the group consisting of 4- methyl-7-hydroxymethylpropolone, 4-methyl-7-methoxymethyltropolone, 4,7-dimethyltropolone, 7-methyl-4-isopropylthroponone, 7-hexyl-4-isopropylthroponone, 4-t-butyltropolone, 5-t-butyltroponone, 4-isopropylopropolone, 4-methyltolone, 7-methoxymethyl-4-isopropylthroponone, 7-hexoxymethyl-4-isopropyl troponone and combinations thereof. 11 - The composition according to any one of the preceding claims, further characterized in that the effective amount of at least one essential oil is from 0.001% to 8.0% by weight based on the total weight of the composition. 12. The composition according to any one of the preceding claims, further characterized in that the effective amount of at least one essential oil comprises 0.064% by weight of thymol, 0.092% by weight of eucalyptol, 0.060% by weight of methyl salicylate. and 0.042% by weight of menthol, each based on the total weight of the composition. 13. The composition according to any one of the preceding claims, further characterized in that it additionally comprises an alcohol in an amount from about 0.01% to 70% by weight based on the total weight of the composition. 14. The composition according to any one of the preceding claims, further characterized in that the alcohol is ethanol. 15. - The composition according to any one of the preceding claims, further characterized in that the effective amount of the compound of formula (I) is from about 0.03% to 2% by weight based on the total weight of the composition for oral hygiene and that of at least one essential oil is 0.064% by weight of thymol, 0.092% by weight of eucalyptol, 0.060% by weight of methyl salicylate and 0.042% by weight of menthol , each based on the total weight of the composition.