Non-halogenated phenyl substituted phenols, antimicrobial compositions containing the same, and methods of using the same

Abstract

A antimicrobial compound, compositions containing the same, and method of using the same for reducing the presence of microorganism on a substrate or in a fluid environment comprising an antimicrobial effective carrier and at least one antimicrobial compounds including non-halogenated phenyl substituted phenol compounds.

Description

FIELD OF THE INVENTION

[0002] The present invention relates to antimicrobial compounds and compositions containing such compounds, and more particularly to phenyl substituted phenol compounds exhibiting antimicrobial activity, antimicrobial compositions containing phenyl substituted phenol compounds, and methods of using such compositions.

BACKGROUND OF THE INVENTION

[0003] Recently, attention has focused on personal hygiene in light of mounting concerns about public health. There is a growing awareness of various microorganisms and microbial pathogens such as yeast, fungi, bacteria, molds and viruses, that can cause disease upon access and entry into the body such as through the eyes, ears, nose, mouth and skin. These microbes are generally transmitted from a source (e.g. a contaminated surface) by the hands to a person's body. Thus, a number of illnesses may easily be prevented by decontamination of the skin and the hands. In a related vein, the control of pathogenic or otherwise undesirable microbes is also a concern in promoting good oral hygiene, where reducing populations of microorganisms on the teeth, gums and tongue has been shown useful in controlling dental plaque accumulation, gingivitis, oral malodor, and other oral maladies.

[0004] It has been shown that at least 18 percent of the population is afflicted with some form of a microbial infection of the dermis. Although such infections are more common in third world areas, there is also a substantial incidence of the infections in developed areas where a high level of personal hygiene exists. Studies have further shown that the factors that contribute to rising incidence of such infections include longer lifespans, emerging resistance of microbes to antibiotics, increased use of antineoplastic agents, and a growing population of patients with some deterioration in their immune system.

[0005] Microbial infections and disease are caused by many types of microorganisms. Most infections are typically the result of microbial infection and/or the presence of microorganisms such as on the skin of the hand or foot, for example. Accordingly, it has been noted that effective treatments of such infections should also include proper preventive measures, specifically, thorough sanitization of the skin including the hands and contact surfaces to prevent further contamination and/or transmission to other individuals.

[0006] Treatment of infection typically includes the application of topical or systemic antibiotic/antifungal agents. Such therapies are disadvantageous because they exhibit a limited rate of success, are contraindicated and/or have undesirable drug interactions, produce elevated levels of toxicity, and/or are expensive. Additionally, the scientific and medical communities have moved away from the use of such systemic antimicrobial therapy for oral and general infection control due to an increase in the number of resistant strains of pathogenic microbes.

[0007] Antimicrobial cleansing compositions for use on the hands, skin, and scalp have used a variety of antimicrobial ingredients including anionic surface-active agent (e.g. sodium lauryl sulfate), coal tar, cationic antimicrobial agents such as chlorhexidine, and halogenated nonionic antimicrobial agents such as triclosan and hexachlorophene.

[0008] In addition to being present external to the body, microorganisms are also present in the oral cavity. Among undesirable microorganisms are Gram-positive and Gram-negative bacterial species associated with the formation of dental plaque (a dense, enamel-adherent biofilm consisting of microorganisms and their attendant extracellular matrix). Dental plaque is initially soft and removable by mechanical oral hygiene, but can undergo mineralization to form hard deposits of dental calculus. Although dental plaque may form on any part of the tooth surface, accumulation of plaque at the gingival margin is particularly implicated in the occurrence of gingivitis. Even with good oral hygiene, it has been shown that microorganisms (include those responsible for plaque formation) rapidly multiply and build up in the oral cavity, and many individuals have difficulty in maintaining good plaque control with brushing and flossing alone.

[0009] Specific areas, including periodontal and subgingival spaces, as well as interpapillary spaces of the tongue and tonsils provide a favorable environment for harboring bacteria and other microbes. Quite often the use of dentifrices such as toothpaste, and/or toothbrushes, dental flosses, and cosmetic mouthrinses, is insufficient to control the undesirable microorganisms. The persistence of these microorganisms in such environments greatly increases the risk of plaque and calculus build-up, which in turn presents a danger of gingival inflammation and more advanced forms of periodontal disease. In addition, the production of malodorous volatile compounds by accumulated populations of anaerobic microorganisms in dental plaque or on the tongue dorsum may lead to perceptible oral malodor.

[0010] Accordingly, it is highly desirable to include antimicrobial (antibacterial) agents in topical or oral compositions having biocidal and/or biostatic activity against a variety of microorganisms. Microorganisms of concern in hand and skin care include Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, Gram positive bacteria such as Staphylococcus aureus and Propionibacterium acnes, molds such as Aspergillus niger and Penicillium funiculosum, yeasts such as Candida albicans, Saccharomyces cerevisiae and Pityrosporum ovale, dermatophytic fungi such as Trichophyton rubrum, microalgae such as Chlorella spp. and Spyrogyra spp., and viruses such as Herpes virus and Picornavirus. Microorganisms of concern in dental plaque, gingivitis, malodor and other oral maladies in the oral cavity include Fusobacterium nucleatum, Prevotella intermedia, Actinomyces viscosus, Streptococcus sanguis, Streptococcus mutans, and Candida albicans.

[0011] One type of oral composition used as a standard in oral hygiene is mouthrinse. However, many mouthrinses have only been effective in masking halitosis. These include mouthrinses which comprise quaternary amines (e.g., combinations of ethanol and domiphen bromide and/or cetylpyridinium chloride) or mixtures of orally acceptable surface-active agents or surfactants. Several mouthrinses that have been marketed for the reduction of plaque and gingivitis generally rely on cationic agents such as chlorhexidine digluconate, metallic fluoride salts such as stannous fluoride, antimicrobial essential oils (e.g., thymol, eucalyptol, ethanol, menthol and methyl salicylate) and/or water-insoluble phenolic agents such as triclosan.

[0012] The cationic antimicrobial materials such as chlorhexidine, benzethonium chloride, and cetyl pyridinium chloride have been investigated as antimicrobial agents, for the control of gingivitis and/or oral malodor. The antimicrobial activity of these materials is theorized to be linked to the cationic charges of the molecule. This charge is attracted to negatively-charged moieties on the cell membrane or wall of the microorganism, and facilitates attachment to the surface of the microorganism. The attachment and subsequent interaction with the cell surface disrupts the cell membrane structure causing leakage of the intracellular fluids, eventually killing the microorganism. However, such materials are generally not effective when formulated in combination with anionic materials and when other cationic minerals and organic molecules present in hard water which may interfere with attraction and subsequent attachment of the cationic materials to the negatively-charged moieties. These chemical interactions may thereby reduce the overall antimicrobial efficacy of this class of compounds. Noncationic antimicrobial materials, on the other hand can be compatible with anionic components of an oral antimicrobial composition or other type of compositions containing an antimicrobial agent.

[0013] Halogenated hydroxydiphenyl ethers such as triclosan have been effectively employed in oral compositions as antimicrobial agents. However, halogenated compounds may present safety issues.

[0014] Alternatives to triclosan with similar antimicrobial activity have been the subject of continuing investigation. Alkyl substituted phenols, such as thymol (2-isopropyl-5-methyl phenol), are well known and widely used as antimicrobials. In combination with menthol, eucalyptol, and methyl salicylate, thymol is an active antimicrobial agent, for example, in commercial clinically effective anti-plaque/anti-gingivitis mouthrinse formulations. However, such essential oil formulations possess lower antimicrobial potency than those containing triclosan. Non-halogenated alternatives to triclosan with similar or improved antimicrobial activity have been the subject of inventors' investigation.

[0015] Accordingly, it would be a significant advance in the art of personal and dental hygiene to provide new non-halogenated, nonionic antimicrobial compounds and compositions containing such compounds which exhibit substantial antimicrobial effectiveness and yet do not possess the safety concerns often associated with halogenated compounds such as triclosan.

SUMMARY OF THE INVENTION

[0016] In accordance with the present invention, phenyl substituted phenol compounds exhibiting effective antimicrobial activity are disclosed. In one aspect of the invention, phenyl substituted phenol compounds are disclosed having the following formulas: 1

[0017] wherein

[0018] R1 and R2 are each independently selected from the group consisting of hydrogen, an alkyl group optionally substituted with a cycloalkyl group or an aryl group; an alkenyl group; an alkoxy group; a cycloalkenyl group; an aryl group; benzyl optionally substituted with an alkyl group; and a cycloalkyl group, wherein any one of which said groups can optionally be substituted with hydroxyl; and

[0019] R3 is selected from the group consisting of hydrogen, a hydroxyl group, an alkyl group optionally substituted with hydroxyl, an aryl group, a benzyl group, a benzyloxy group, an alkoxy group, and a cycloalkyl group optionally substituted with hydroxyl;

[0020] R4 is selected from the group consisting of hydrogen and an alkyl group optionally substituted with hydroxyl;

[0021] with the proviso that,

[0022] for compounds of Formula Ia, when R1 is a C1-8 n-alkyl group or a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group, and R2 is hydrogen, then R3 is not selected from the group consisting of a C1-8 n-alkyl group and a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group;

[0023] for compounds of Formulas Ia through Ic, when R1 and R2 and R4 are each hydrogen, then R3 is not selected from the group consisting of hydrogen, a 4-alkyl group, or a 2-benzyloxy group; and

[0024] for compounds of Formula Ic, wherein each of R1, R3 and R4 is hydrogen, then R2 is not selected from the group consisting of a methyl group, an ethyl group, or a tert-butyl group.

[0025] for compounds of Formula Ic, wherein each of R1, and R4 is hydrogen, and R3 is a 2-hydroxyl, then R2 is not a tert-butyl group.

[0026] In another aspect of the present invention, an antimicrobial composition comprising an effective amount of at least one antimicrobial compound such as a phenyl substituted phenol compound for reducing the presence of microorganisms on a substrate or in a fluid environment in combination with an antimicrobial effective carrier. In such aspect of the invention, there is provided an antimicrobial composition comprising an antimicrobial acceptable carrier and an antimicrobial effective amount of at least one antimicrobial compound selected from the following formulas: 2

[0027] wherein

[0028] R1 and R2 are each independently selected from the group consisting of hydrogen, an alkyl group optionally substituted with a cycloalkyl group or an aryl group; an alkenyl group; an alkoxy group; a cycloalkenyl group; an aryl group; benzyl optionally substituted with an alkyl group; and a cycloalkyl group, wherein any one of which said groups can optionally be substituted with hydroxyl; and

[0029] R3 is selected from the group consisting of hydrogen, a hydroxyl group, an alkyl group optionally substituted with hydroxyl, an aryl group, a benzyl group, a benzyloxy group, an alkoxy group, and a cycloalkyl group optionally substituted with hydroxyl;

[0030] R4 is selected from the group consisting of hydrogen and an alkyl group optionally substituted with hydroxyl;

[0031] with the proviso that,

[0032] for compounds of Formula IIa, when R1 is a C1-8 n-alkyl group or a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group, and R2 is hydrogen, then R3 is not selected from the group consisting of a C1-8 n-alkyl group and a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group; and

[0033] for compounds of Formulas IIa through IIc, when each of R1, R2 and R4 is a hydrogen, then R3 is not hydrogen.

[0034] In another aspect of the invention there is provided an oral antimicrobial composition comprising an effective antimicrobial amount of at least one antimicrobial compound including phenyl substituted phenol compounds for reducing the presence of microorganisms in an oral cavity in combination with an orally acceptable carrier.

[0035] In this aspect of the present invention, an oral composition comprises an orally acceptable carrier and an antimicrobial effective amount of at least one antimicrobial compound selected from the following formulas: 3

[0036] wherein

[0037] R1 and R2 are each independently selected from the group consisting of hydrogen, an alkyl group optionally substituted with a cycloalkyl group or an aryl group; an alkenyl group; an alkoxy group; a cycloalkenyl group; an aryl group; benzyl optionally substituted with an alkyl group; and a cycloalkyl group, wherein any one of which said groups can optionally be substituted with hydroxyl; and

[0038] R3 is selected from the group consisting of hydrogen, a hydroxyl group, an alkyl group optionally substituted with hydroxyl, an aryl group, a benzyl group, a benzyloxy group, an alkoxy group, and a cycloalkyl group optionally substituted with hydroxyl;

[0039] R4 is selected from the group consisting of hydrogen and an alkyl group optionally substituted with hydroxyl;

[0040] with the proviso that,

[0041] for compounds of Formula IIa, when R1 is a C1-8 n-alkyl group or a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group, and R2 is hydrogen, then R3 is not selected from the group consisting of a C1-8 n-alkyl group and a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group; and

[0042] for compounds of Formula IIa through IIc, when each of R1, R2 and R4 is a hydrogen, then R3 is not hydrogen.

[0043] In a further aspect of the invention, methods are provided for using the antimicrobial composition comprising at least one antimicrobial compound selected from Formulas IIa-IIc for reducing the presence of microorganisms on a substrate. The methods include treating the substrate with an effective amount of the antimicrobial composition containing the antimicrobial compounds selected from Formulas IIa-IIc.

[0044] In a still further aspect of the invention, methods are provided for using the oral composition comprising at least one antimicrobial compound selected from Formulas IIa-IIc for reducing the presence of microorganisms in an oral cavity of an individual. The methods include administering into the oral cavity an effective amount of the oral composition containing the antimicrobial compounds selected from Formulas IIa-IIc.

DETAILED DESCRIPTION OF THE INVENTION

[0045] The present invention is directed to phenyl substituted phenol compounds which exhibit effective antimicrobial activities in a variety of compositions and applications while maintaining a positive safety profile desirable for human use. The antimicrobial activity of the compounds of the present invention are much improved over those exhibited by prior art antimicrobial compounds. Since the novel compounds are composed entirely of hydrocarbon constituents with a hydroxyl substitutent, such compounds are significantly safer than prior art antimicrobial compounds such as halogenated phenoxyphenols, for example. More specifically, the novel compounds include at least one phenyl optionally substituted with an alkyl group substitutents which substantially improves overall antimicrobial activity for effectively reducing the presence of microorganisms.

[0046] The present invention is further directed to the antimicrobial composition which is effective in treating various substrate surfaces including the oral cavity that may contain microorganisms. The antimicrobial composition is especially effective against microorganisms residing in the oral cavity responsible for bad breath, plaque and/or calculus, and the resulting tooth and gum diseases that may be caused thereby. The antimicrobial composition is effective yet is safe to use and is available in a variety of forms and antimicrobial applications and uses.

[0047] Accordingly, the present invention provides for phenyl substituted phenol compounds exhibiting antimicrobial activities which are represented by one of the following formulas: 4

[0048] wherein

[0049] R1 and R2 are each independently selected from the group consisting of hydrogen, an alkyl group optionally substituted with a cycloalkyl group or an aryl group; an alkenyl group; an alkoxy group; a cycloalkenyl group; an aryl group; benzyl optionally substituted with an alkyl group; and a cycloalkyl group, wherein any one of which said groups can optionally be substituted with hydroxyl; and

[0050] R3 is selected from the group consisting of hydrogen, a hydroxyl group, an alkyl group optionally substituted with hydroxyl, an aryl group, a benzyl group, a benzyloxy group, an alkoxy group, and a cycloalkyl group optionally substituted with hydroxyl;

[0051] R4 is selected from the group consisting of hydrogen and an alkyl group optionally substituted with hydroxyl;

[0052] with the proviso that,

[0053] for compounds of Formula Ia, when R1 is a C1-8 n-alkyl group or a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group, and R2 is hydrogen, then R3 is not selected from the group consisting of a C1-8 n-alkyl group and a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group;

[0054] for compounds of Formulas Ia through Ic, when R1 and R2 and R4 are each hydrogen, then R3 is not selected from the group consisting of hydrogen, a 4-alkyl group, or a 2-benzyloxy group;

[0055] for compounds of Formula Ic, wherein each of R1, R3 and R4 is hydrogen, then R2 is not selected from the group consisting of a methyl group, an ethyl group, or a tert-butyl group; and

[0056] for compounds of Formula Ic, wherein each of R1, and R4 is hydrogen, and R3 is a 2-hydroxyl, then R2 is not a tert-butyl group.

[0057] The present invention further provides for preferred compositions comprising an antimicrobial acceptable carrier and an antimicrobial effective amount of at least one antimicrobial compound selected from the following formulas: 5

[0058] wherein

[0059] R1 and R2 are each independently selected from the group consisting of hydrogen, an alkyl group optionally substituted with a cycloalkyl group or an aryl group; an alkenyl group; an alkoxy group; a cycloalkenyl group; an aryl group; benzyl optionally substituted with an alkyl group; and a cycloalkyl group, wherein any one of which said groups can optionally be substituted with hydroxyl; and

[0060] R3 is selected from the group consisting of hydrogen, a hydroxyl group, an alkyl group optionally substituted with hydroxyl, an aryl group, a benzyl group, a benzyloxy group, an alkoxy group, and a cycloalkyl group optionally substituted with hydroxyl;

[0061] R4 is selected from the group consisting of hydrogen and an alkyl group optionally substituted with hydroxyl;

[0062] with the proviso that,

[0063] for compounds of Formula IIa, when R1 is a C1-8 n-alkyl group or a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group, and R2 is hydrogen, then R3 is not selected from the group consisting of a C1-8 n-alkyl group and a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group; and

[0064] for compounds of Formulas IIa through IIc, when each of R1, R2 and R4 are each hydrogen, then R3 is not hydrogen.

[0065] Compounds useful in the antimicrobial compositions of the present invention include, but are not limited to, 4-(tert-butyl)-2-(2-hydroxyphenyl)phenol, 4-ethyl-2-(2-hydroxyphenyl)phenol, 4-(4-hydroxybutyl)-2-(2-hydroxyphenyl)phenol, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)anisole, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)phenol, 2-(2-hydroxyphenyl)-4-benzylphenol, 4-ethyl-2-phenylphenol, 2-phenyl-4-propylphenol, 5-isopropyl-biphenyl-2-ol, 4-[4-(tert-butyl)phenyl]phenol, 4-(1,1-dimethylethyl)-phenylphenol, 3-(4-tert-butylphenyl)phenol, 2-(4-tert-butylphenyl)phenol, (2-,4-diphenyl)phenol, (4-tert-butyl, 2-phenyl)phenol, 2-(4-tert-butylphenyl)phenol, and 3-phenylphenol.

[0066] Preferred for use in the antimicrobial compositions are 4-(tert-butyl)-2-(2-hydroxyphenyl)phenol, 4-ethyl-2-(2-hydroxyphenyl)phenol, 4-(4-hydroxybutyl)-2-(2-hydroxyphenyl)phenol, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)anisole, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)phenol, 2-(2-hydroxyphenyl)-4-benzylphenol, 4-ethyl-2-phenylphenol, 2-phenyl-4-propylphenol, 5-lsopropyl-biphenyl-2-ol, and 4-[4-(tert-butyl)phenyl]phenol.

[0067] Particularly preferred for use in the antimicrobial compositions are 4-(tert-butyl)-2-(2-hydroxyphenyl)phenol, 4-ethyl-2-(2-hydroxyphenyl)phenol, 4-(4-hydroxybutyl)-2-(2-hydroxyphenyl)phenol, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)anisole, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)phenol, and 2-(2-hydroxyphenyl)4-benzylphenol.

[0068] The above antimicrobial compounds of Formulas IIa-IIc, are preferably incorporated in an antimicrobial composition of the present invention in an amount of about 0.0001 to 10%, more preferably from about 0.001 to 5% by weight.

[0069] The present invention also provides a method of reducing the presence of microorganisms on a substrate comprising treating the substrate with an effective amount of at least one antimicrobial compound selected from Formulas IIa-IIc.

[0070] The antimicrobial compositions of the present invention may be incorporated into food products for use as food preservatives. Such food preservative compositions may comprise at least one compound selected from Formulas IIa-IIc and an edible carrier, which may be added to food products to prevent or delay spoilage or discoloration caused by microorganisms. The composition may further include other food preservative agents including, but not limited to benzoic acid, sodium benzoate, and calcium propionate.

[0071] The antimicrobial compounds selected from Formulas IIa-IIc employed in this invention may also be incorporated into ophthalmic compositions suitable for topical administration. Such compositions may include topical ocular fluids comprising at least one antimicrobial compound suspended or dissolved in a sterile, isotonic, typically aqueous pharmaceutically acceptable ocular carrier or vehicle. The ophthalmic compositions may also be prepared in the form of ointments or salves. Such ointments or salves typically comprise at least one antimicrobial compound having Formulas IIa-IIc suspended or dissolved in a sterile, pharmaceutically acceptable ointment or salve base such as, for example, mineral oil/white petroleum base.

[0072] The liquid formulation of ophthalmic compositions typically requires the presence of water under isotonic conditions, and such compositions are intended for external application to the eye (i.e. eye drops). The antimicrobial compounds of Formulas IIa-IIc may be insoluble in water or dispersion medium, and may be suspended through use of suspending or dispersing agents. The compounds of the present invention may further be dispersed by means of emulsifying agents or other suitable stabilizers as known in the art.

[0073] The ophthalmic composition may include about 0.0001 to 10%, more preferably from about 0.001 to 5% by weight of the active antimicrobial compounds selected from Formulas IIa-IIc with the rest of the composition being the carrier and other materials known in the art as ophthalmological pharmaceutical ingredients or components. Such additional ingredients may include preservatives, solubilizers, emulsifying agents, surfactants, stabilizers, pH adjusting agents, buffers, isotonizers and the like. In ointment or salve compositions, anhydrous lanolin may also be included in the composition.

[0074] The antimicrobial compositions of the present invention may also be incorporated into products having a variety of vehicles for application to the skin or tissue surfaces including creams, lotions, foundations, cleansing lotions, soaps, shampoos, ointments, syrups and suspensions. Compositions may comprise, for example, aqueous or oily solutions or dispersions, oil-in-water or water-in-oil emulsions, pastes, gels or solids. Topically or orally acceptable carriers and excipients of use in such preparations will be well known to those skilled in the art.

[0075] The antimicrobial compositions of the present invention may further be included in products which are developed for the treatment of microorganism-induced conditions such as deodorant and/or antiperspirant preparations, antibacterial skin washes, anti-acne preparations, anti-athlete foot preparations, dental preparations, impregnated materials (e.g. wound dressings, sutures, and dental floss), pharmaceuticals, ophthalmic preparations and sterilants.

[0076] Typically, a deodorizing composition reduces or prevent body odor by reducing perspiration (e.g. often referred to as an antiperspirant composition) or the presence of microorganisms on the surface of the skin.

[0077] Antiperspirant compositions often comprise a metal salt, such as aluminum or zirconium salts which blocks the pores of the skin. Typically, such compositions, however, reduce perspiration by no more than 50%. It is well known that sweat is odorless until it has been degraded by the skin microflora. Typical deodorant compositions include ethanol and/or Triclosan (2′,4,4′-trichloro,2-hydroxy-diphenyl ether) which are a well known antimicrobial compounds. However, the deodorizing effect obtained with such deodorant compositions is transitory and shortly after application the concentration of microorganisms reaches previous levels.

[0078] The invention provides a deodorant composition for topical application to human skin comprising at least one antimicrobial compound selected from Formulas IIa-IIc in a cosmetically acceptable carrier in which the composition at least reduces the presence of microorganisms for a time greater than the transitory period.

[0079] Such deodorant compositions in addition to containing the composition of the present invention contain a low molecular weight aliphatic alcohol, preferably containing up to 4 carbons and especially a monohydric alcohol such as ethanol, which can act in combination with the antimicrobial compounds selected from Formulas IIa-IIc to provide an effective deodorant composition. The amount of the alcohol in the composition is typically selected within the range of from about 10 to 80% by weight, preferably from about 30 to 70% by weight.

[0080] The deodorant composition according to the present invention may also comprise other materials commonly found in deodorant or antiperspirant compositions. In practice, the present composition usually contains at least one cosmetically acceptable vehicle in addition to the antimicrobial compounds selected from Formulas IIa-IIc alone or in combination with an alcohol. The topically acceptable carrier may comprise a liquid vehicle such as an alcohol as described hereinbefore, in addition to, water, a hydrophobic vehicle which may for example be a volatile or non-volatile silicone oil, a liquid hydrocarbon, a water-insoluble alcohol, an aliphatic ether, an aliphatic or aromatic ester. The carrier is typically present in an amount of from about 10 to 80% by weight based on the total weight of the composition.

[0081] The composition of the present invention may contain one or more conventional deodorant active compounds as known to those of ordinary skill in the art, in an amount of from about 0 to 5% by weight. Other additives may include perfumes in an amount of from about 0 to 2% by weight, antiperspirant actives such as aluminum or zirconium compounds in an amount of from about 0 to 40% by weight, preferably from about 5 to 28% by weight, skin softening compounds such as silicone oils or solid silicone polymers, in an amount of from about 0 to 20% by weight, coloring compounds in an amount of from about 0 to 2% by weight, humectants, such as sorbitol or glycerol, in an amount of from about 0 to 10% by weight, thickening compounds such as starches or cellulose derivatives, in an amount from about 0 to 5% by weight, gellants such as dibenzoyl sorbitol, hydroxystearic acid, stearyl alcohol, or amide derivatives of tricarboxylic acids, in an amount of from about 0 to 15% by weight, suspension compounds, such as clays or silicas, in an amount of up to about 5% by weight, structurants such as silicone elastomers or silicone or hydrocarbon waxes, in an amount of about 0 to 15% by weight; propellants, such as hydrocarbons having a boiling point of below 10E C., e.g. butane and propane isomers, in an amount of from about 30 to 95% by weight, and other cosmetic adjuncts conventionally employed in such compositions. Where water and a hydrophobic material is present, the composition preferably contains an emulsifier/system such as polyethoxylate ethers or esters. The use of such substances and the proportions in which they are incorporated depend on the form of the composition which may be an aerosol, stick, roll-on, gel, lotion, cream, ointment, powder, suspension or soap.

[0082] More preferred compositions include those represented for use in an oral cavity comprising an orally acceptable carrier and an antimicrobial effective amount of at least one antimicrobial compound selected from the following formulas: 6

[0083] wherein

[0084] R1 and R2 are each independently selected from the group consisting of hydrogen, an alkyl group optionally substituted with a cycloalkyl group or an aryl group; an alkenyl group; an alkoxy group; a cycloalkenyl group; an aryl group; benzyl optionally substituted with an alkyl group; and a cycloalkyl group, wherein any one of which said groups can optionally be substituted with hydroxyl; and

[0085] R3 is selected from the group consisting of hydrogen, a hydroxyl group, an alkyl group optionally substituted with hydroxyl, an aryl group, a benzyl group, a benzyloxy group, an alkoxy group, and a cycloalkyl group optionally substituted with hydroxyl;

[0086] R4 is selected from the group consisting of hydrogen and an alkyl group optionally substituted with hydroxyl;

[0087] with the proviso that,

[0088] for compounds of Formula IIa, when R1 is a C1-8 n-alkyl group or a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group, and R2 is hydrogen, then R3 is not selected from the group consisting of a C1-8 n-alkyl group and a C3-6 cycloalkyl group, each being optionally partially or fully substituted with a C3-6 cycloalkyl group or a C1-7 side chain alkyl group; and

[0089] for compounds of Formula IIa through IIc, when each of R1, R2 and R4 is a hydrogen, then R3 is not hydrogen.

[0090] Compounds useful for oral compositions include, but are not limited to, 4-(tert-butyl)-2-(2-hydroxyphenyl)phenol, 4-ethyl-2-(2-hydroxyphenyl)phenol, 4-(4-hydroxybutyl)-2-(2-hydroxyphenyl)phenol, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)anisole, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)phenol, 2-(2-hydroxyphenyl)-4-benzylphenol, 4-ethyl-2-phenylphenol, 2-phenyl-4-propylphenol, 5-lsopropyl-biphenyl-2-ol, 4-[4-(tert-butyl)phenyl]phenol, 4-(1,1-dimethylethyl)-phenylphenol, 3-(4-tert-butylphenyl)phenol, 2-(4-tert-butylphenyl)phenol, (2-,4-diphenyl)phenol, (4-tert-butyl, 2-phenyl)phenol, 2-(4-tert-butylphenyl)phenol, and 3-phenylphenol.

[0091] Preferred for use in oral compositions are 4-(tert-butyl)-2-(2-hydroxyphenyl)phenol, 4-ethyl-2-(2-hydroxyphenyl)phenol, 4-(4-hydroxybutyl)-2-(2-hydroxyphenyl)phenol, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)anisole, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)phenol, 2-(2-hydroxyphenyl)-4-benzylphenol, 4-ethyl-2-phenylphenol, 2-phenyl-4-propylphenol, 5-isopropyl-biphenyl-2-ol, and 4-[4-(tert-butyl)phenyl]phenol

[0092] Particularly preferred for use in oral compositions are 4-(tert-butyl)-2-(2-hydroxyphenyl)phenol, 4-ethyl-2-(2-hydroxyphenyl)phenol, 4-(4-hydroxybutyl)-2-(2-hydroxyphenyl)phenol, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)anisole, 4-(hydroxymethyl)-2-(2-hydroxyphenyl)phenol, and 2-(2-hydroxyphenyl)-4-benzylphenol.

[0093] The antimicrobial compounds selected from Formulas IIa-IIc may be present in an oral composition of the present invention preferably in an amount of from about 0.0001 to 10%, more preferably from about 0.001 to 5% by weight.

[0094] The present invention further provides a method of reducing microorganisms in an oral cavity which comprises administering to the oral cavity an oral composition having an effective amount of at least one antimicrobial compound selected from Formulas IIa-IIc.

[0095] The use of the antimicrobial compositions according to the invention in oral composition is particularly advantageous because they provide effective results against a broad range of microorganisms known to be present in the oral cavity. The oral compositions may take the form of bulk liquid solutions or suspensions, or bulk powders for convenient application to the surface of the oral cavity.

[0096] Oral compositions which contain antimicrobial compounds of the present invention may be in the form of mouthwashes, gargles, dentifrices, dispersible oral films, film-forming dentifrices, anti-plaque compositions and as general antiseptic compositions, for example, in the form of denture cleansing tablets or solutions. The oral compositions of the present invention may, if desired, further comprise at least one additional active ingredient and formulations containing such, as conventionally used in the art. These include, for example, anti-plaque agents such as bromochlorophene, triclosan, cetylpyridinium chloride, chlorhexidine salts, and essential oils such as thymol, menthol, and the like, fluoride ion sources such as sodium fluoride, sodium monofluorophosphate and amine fluorides, anti-tartar compounds such as zinc salts, preferably zinc citrate, and water soluble pyrophosphate salts, preferably alkali metal pyrophosphates, and desensitizing agents which reduce tooth sensitivity including potassium salts such as potassium nitrate and potassium chloride and strontium salts such as strontium chloride and strontium acetate.

[0097] One particular formulation comprising essential oils is sold commercially as LISTERINE® which composition is exemplified in Pan et al. (U.S. Pat. No. 6,121,315), and which reference includes effective essential oil formulations having anti-plaque activity. The contents of U.S. Pat. No. 6,121,315 is hereby incorporated by reference in its entirety. The essential oil formulation, optionally contained in the oral compositions of the present invention, preferably comprises from about 0.005% to 0.5% by weight of thymol, from about 0.005% to 0.5% by weight of menthol, from about 0.005% to 0.5% by weight of eucalyptol, and from about 0.005% to 0.5% by weight of methyl salicylate.

[0098] The compositions according to the invention may alternatively be provided in concentrated in form, for example as a powder, anhydrous solution or effervescent tablet formulation, suitable for dilution in water prior to use as a sterilant of, for example, dental instruments. One preferred use of the anti-microbial compositions of the invention is as toothbrush sanitizers, designed to reduce microbiological contamination of toothbrush heads, for example by overnight soaking as needed, typically every 1 to 14 days of use. A substantial reduction in microorganism contamination may be achieved in this way without significant adverse effects on the toothbrush or other dental instrument.

[0099] Antimicrobial enhancing agent(s) may be included in the oral compositions of the present invention. Incorporating such antimicrobial enhancing agent into compositions containing antimicrobial compounds are known in the art, as described for example in U.S. Pat. No. 5,188,821 and 5,192,531. The term “antimicrobial enhancing agent” as used herein refers to organic compounds which contains a delivery-enhancing group and a retention-enhancing group which together act to improve the sanitizing effectiveness of the antimicrobial agent. As used herein, the delivery-enhancing group refers to one which attaches or substantively, adhesively, cohesively or otherwise bonds the antimicrobial enhancing agent (carrying the antimicrobial agent) to oral surfaces such as tooth and gum, thereby “delivering”) the antimicrobial agent to such surfaces. The retention-enhancing group, generally hydrophobic, attaches or otherwise bonds the antimicrobial agent to the antimicrobial enhancing agent, thereby promoting retention of the antimicrobial agent to the antimicrobial enhancing agent and indirectly on the oral surfaces. The active retention of the antimicrobial agent on the oral surfaces enhances the disinfecting effect on oral surfaces.

[0100] In the preferred form, the antimicrobial enhancing agent includes an anionic polymer comprising a chain or backbone containing repeating units each preferably containing at least one carbon atom and preferably at least one directly or indirectly pendent, monovalent delivery-enhancing group, and at least one directly or indirectly pendent, monovalent retention-enhancing group geminally, vincinally, or less preferably otherwise bonded to atoms, preferably carbon, in the chain.

[0101] The antimicrobial enhancing agent may be a simple compound such as a polymerizable monomer, or more preferably a polymer including oligomers, homopolymers, copolymers of two or more monomers, ionomers, block copolymers, graft copolymers, cross-linked polymers and copolymers, and the like. The antimicrobial enhancing agent may be natural or synthetic, and water-insoluble or preferably water soluble or swellable, having an average molecular weight of from about 100 to 5,000,000, preferably from about 1,000 to 1,000,000, more preferably from about 25,000 to 500,000.

[0102] Preferable antimicrobial enhancing agents for use in the practice of the present invention include a natural or synthetic anionic polymeric polycarboxylate having a molecular weight of from about 1,000 to 5,000,000, preferably from about 30,000 to 500,000. Synthetic anionic polymeric polycarboxylates are generally employed in the form of their free acids or preferably partially or more preferably fully neutralized water soluble alkali metal such as potassium and sodium, or ammonium salts. Preferred are 1:4 to 4:1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether/maleic anhydride having a molecular weight of from about 30,000 to 1,000,000, most preferably from about 30,000 to 500,000. These copolymers are available, for example, as GANTREZ®, AN 139 (molecular weight 500,000), AN 119 (molecular weight 250,000), and preferably S-97 Pharmaceutical Grade (molecular weight 700,000), from ISP Technologies, Inc., Bound Brook, N.J. 08805.

[0103] Other useful polymeric polycarboxylates containing or modified to contain retention-enhancing groups include the 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being available, for example, as Monsanto EMA® No. 1103 (molecular weight 10,000), and Grade 61, and 1:1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl methacrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone. Additional polycarboxylate compounds containing or modified to contain retention-enhancing groups include copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic, polyitaconic and polymaleic acids, and sulfonacrylic oligomers with a molecular weight as low as 1,000 available as UNIROYAL® ND-2.

[0104] Also useful in the practice of the present invention are the so-called carboxyvinyl polymers, commercially available, for example, under the trademarks CARBOPOL® 934, 940, and 941 from B.F. Goodrich, Cleveland, Ohio 44131, these polymers consisting of a colloidally water-soluble polymer of polyacrylic acid crosslinked with from about 0.75% to about 2.0% of polyallyl sucrose or polyallyl pentaerythritol as a crosslinking agent, often with molecular weights of up to 4-5 million or more.

[0105] Polysiloxanes containing or modified to contain pendent delivery-enhancing groups and retention-enhancing groups such as liquid silicone oils such as diphenyl or di(C1-C4)alkyl polysiloxanes and particularly dimethyl-polysiloxane, may also be employed in the practice of the present invention.

[0106] Also effective herein are ionomers containing or modified to contain delivery- and retention-enhancing groups, lonomers are described on pages 546-573 of the Kirk Othmer Encyclopedia of Chemical Technology, Third Edition, Supplement Volume, John Wiley & Sons, copyright 1984, which description is incorporated herein by reference. Also effective herein, provided that contain or are modified to containing retention-enhancing groups, are polyesters, polyurethanes, and synthetic and natural polyamides including proteins and proteinaceous materials such as collagen, poly(arginine) and other polymerized amino acids.

[0107] The antimicrobial enhancing agent, when employed, is incorporated in the compositions of the present invention in weight amounts of from about 0.05 to about 5%, preferably from about 0.1 to 3%.

[0108] Fluoride ions may also be included in the oral compositions of the present invention. Fluoride ions are implicated in the prevention of dental caries and may also serve as a tooth-hardening agent. An amount of fluoride ions suitable for use in an oral composition of the present invention is from 25 ppm to 5,000 ppm.

[0109] Fluoride ion producing compounds vary in degree of water solubility. They release fluoride ions in water and do not generally react with other compounds of the oral composition. Among the fluoride ion producing compounds are inorganic fluoride salts, such as soluble alkali metal, alkaline earth metal salts, for example, sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, cuprous fluoride, zinc fluoride, barium fluoride, sodium monofluorophosphate, aluminum mono-and di-fluorophosphate and sodium calcium fluorophosphate. Alkali metal and tin fluorides, such as sodium and stannous fluorides, sodium monofluorophosphate (MFP) and mixtures thereof, are preferred.

[0110] The amount of fluoride ion producing compound is dependent upon the type of compound, its solubility in water, and the type of oral composition. A non-toxic amount of such compound is generally in the range from about 0.0005 to 3.0% by weight based on the total weight of the oral composition. Any suitable minimum amount of such compounds may be used, but it is preferable to employ a sufficient amount of the fluoride ion producing compounds to provide from about 300 to 2,000 ppm, more preferably from about 800 to about 1,500 ppm of fluoride ion to the oral cavity.

[0111] Typically, for sodium fluoride, the desired amount up to about 2% by weight, based on the total weight of the composition, and preferably in an amount of from about 0.05 to 1%, more preferably from about 0.2 to 0.35% by weight. Typically for sodium monofluorophosphate, the compound is desirably present in an amount of from about 0.1 to 3%, more preferably about 0.76% by weight.

[0112] The oral composition of the present invention may be in the form of a solution such as a mouthrinse, in the form of a solid or semi-solid such as a toothpaste, a gel dentifrice (which may contain from about 0 to 75% by weight of a polishing agent), a chewing gum, a dispersible oral film, a film-forming dentifrice, a solid lozenge, or the like.

[0113] Oral gel preparations typically contain a siliceous polishing material including crystalline silica having particle sizes of up to 5 microns, silica gel, colloidal silica or complex amorphous alkali metal aluminosilicate or combinations thereof. When visually clear or opacified gels are employed, a polishing agent of colloidal silica or alkali metal aluminosilicate complexes (that is, silica containing alumina combined in its matrix) are particularly useful, since they are consistent with gel-like texture and have refractive indices close to the refractive indices of gelling agent-liquid (including water and/or humectant) systems commonly used in dentifrices.

[0114] Where the oral composition of the present invention is a gel or paste, an orally acceptable carrier, including a water-phase with humectant which is preferably glycerine or sorbitol or an alkylene glycol such as polyethylene glycol or propylene glycol is present. Where water is typically present in an amount of from about 15 to 40% by weight and glycerine, sorbitol and/or the alkylene glycol (preferably propylene glycol) are preferably in an amount of from about 20 to 75% by weight, preferably about 25 to 60% by weight based on the total weight of the composition.

[0115] When the oral composition is substantially semi-solid or pasty in character, such as a toothpaste (dentifrice), the orally acceptable carrier of the dentifrice may contain a dentally acceptable polishing material such as sodium bicarbonate, sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated dicalcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, calcium carbonate, aluminum silicate, hydrated alumina, silica, bentonite, and mixtures thereof alone or with minor amounts of hard polishing material such as calcined alumina and/or zirconium silicate. Preferred polishing materials include sodium bicarbonate, silica, sodium metaphosphate, dicalcium phosphate, calcium pyrophosphate and hydrated alumina.

[0116] The polishing material is generally present in the oral composition in an amount of from about 10% to 75% by weight, preferably from about 10% to 30% by weight in a gel, and preferably from id& about 25% to 75% by weight in a cream or paste.

[0117] Toothpastes or dental cream dentifrices as well as gel dentifrices typically contain a natural or synthetic thickener or gelling agent in an amount of from about 0.1 to 10% by weight, preferably from about 0.5 to 5% by weight.

[0118] Suitable thickeners or gelling agents include Irish moss, iota-carrageenan, kappa-carrageenan, gum tragacanth, starch, polyvinylpyrrolidone, hydroxyethyl propyl cellulose, hydroxybutyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose and sodium carboxymethyl cellulose.

[0119] Where the oral composition is a liquid such as a mouthwash or rinse, the liquid carrier is typically a water-alcohol mixture. Generally, the weight ratio of water to alcohol is in the range of from about 3:1 to 10:1 and preferably from about 4:1 to 6:1. The alcohol is a non-toxic alcohol such as ethanol or isopropanol. A humectant such as glycerin, sorbitol or an alkylene glycol such as polyethylene glycol or preferably propylene glycol may be present in an amount of from about 10 to 30% by weight. Mouthrinses typically contain about 50 to 85% of water, from about 0 to 20% by weight of a non-toxic alcohol and from about 10 to 40% by weight of a humectant.

[0120] Organic surface-active agents may be used in the compositions of the present invention to achieve increased antimicrobial action and assist in achieving thorough and complete dispersion of the antimicrobial compounds of Formulas IIa-IIc throughout the oral cavity. The organic surface-active material is preferably anionic, nonionic or ampholytic in nature, and imparts to the composition detersive and foaming properties. Suitable examples of anionic surfactants are water-soluble salts of higher fatty acid monoglyceride monosulfates, such as the sodium salt of the monosulfated monoglyceride of hydrogenated coconut oil fatty acids, higher alkyl sulfates such as sodium lauryl sulfate, alkyl aryl sulfonates such as sodium dodecyl benzene sulfonate, higher alkyl sulfoacetates, higher fatty acid esters of 1,2-dihydroxy propane sulfonate, and the substantially saturated higher aliphatic acyl amides of lower aliphatic amino carboxylic acid compounds, such as those having 12 to 16 carbons in the fatty acid, alkyl or acyl radicals and alkoyl taurines, and the like. Examples of such compounds include N-lauroyl sarcosine, and the sodium, potassium and ethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoyl sarcosine which are substantially free from soap or similar higher fatty acid material as well as N-methyl-N-cocoyl (or oleoyl or palmitoyl) taurines. The use of sarcosinate compounds in the oral compositions of the present invention is typically advantageous since these materials exhibit a prolonged and marked effect in the inhibition of acid formation in the oral cavity due to carbohydrate breakdown in addition to exerting some reduction in the solubility of tooth enamel in acid solutions.

[0121] Examples of water-soluble nonionic surfactants are condensation products of ethylene oxide with various reactive hydrogen-containing compounds reactive therewith having long hydrophobic chains (e.g. aliphatic chains of about 12 to 20 carbon atoms), which condensation products (“ethoxamers”) contain hydrophilic polyoxyethylene moieties, such as condensation products of poly (ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g. sorbitan monostearate) and polypropyleneoxide.

[0122] Examples of polyoxamers useful in the practice of the present invention include block copolymers of polyoxyethylene and polyoxypropylene having an average molecular weight of from about 3000 to 5000 and a preferred average molecular weight of from about 3500 to 4000, and containing from about 10 to 80% by weight of hydrophilic polyoxyethylene groups of the block copolymer.

[0123] Natural and artificial sweeteners may be used in the oral compositions. The sweetener may be selected from a wide range of well known materials including naturally occurring water-soluble sweeteners, artificial water-soluble sweeteners and modified water-soluble sweeteners derived from naturally occurring water-soluble sweeteners. Artificial water-soluble sweeteners include, but are not limited to, soluble saccharin salts, e.g., sodium or calcium saccharin salts, cyclamate salts, the sodium, ammonium or calcium salt of 3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-dioxide, the potassium salt of 3,4-dihydro-6-methyl-1,2,3-oxathiazine4-one-2,2-dioxide (Acesulfame-K), the free acid form of saccharin and dipeptide based sweeteners, such as L-aspartic acid derived sweeteners. Dipeptide sweeteners include L-aspartyl-L-phenylalanine methyl ester (Aspartame) and materials described in U.S. Pat. No. 3,492,131, L-alpha-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alaninamide hydrate (Alitame), methyl esters of L-aspartyl-L-phenylglycerine and L-aspartyl-L-2,5-dihydrophenylglycine, L-aspartyl-2,5-dihydro-L-phenylalanine and L-aspartyl-L-(1-cyclohexene)-alanine. Naturally occurring water-soluble sweeteners include, but are not limited to, sugar alcohols, including sorbitol as 70% sorbitol solution, mannitol, xylitol, maltitol, hydrogenated starch hydrolysates and mixtures thereof.

[0124] Water-soluble sweeteners derived from naturally occurring water-soluble sweeteners include, but are not limited to, chlorinated derivatives of sucrose, known, for example, under the product designation of Sucralose, and protein-based sweeteners such as thaumaoccous danielli (Thaumatin I and III).

[0125] Sorbitol solution supplies sweetness and body to the composition and gives a desirable mouth feel. Sorbitol solution also enhances flavor, prevents harsh taste and provides a fresh and lively sensation in the mouth. It also adds body and serves as a humectant.

[0126] In general, an effective amount of sweetener is utilized to provide the level of sweetness desired in any particular embodiment of the oral compositions according to the present invention. This amount will vary with the sweetener selected and the final form of the oral composition. The amount of sweetener normally present is from about 0.0025% by weight to about 60% by weight of the oral composition. The exact range of amounts for each type of sweetener in an oral composition is readily determined by those skilled in the art.

[0127] The flavors that may be used in the invention include natural and artificial flavors known in the art. Suitable flavors include, but are not limited to, mints, such as peppermint, citrus flavors such as orange and lemon, artificial vanilla, cinnamon, various fruit flavors, flavoring oils, e.g. oil of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, cinnamon, lemon, and orange, methyl salicylate, and the like. Anethole (or anise camphor, p-propenyl anisole) is a flavor constituent of anise and fennel oils that are used widely as flavoring agent and antiseptic and was found useful in masking the harsh taste of thymol.

[0128] The amount of flavor is normally a matter of preference subject to the type of final oral composition, the individual flavor employed and the strength of flavor desired. The flavors are preferably utilized in amounts that may range of from about 0.01% to about 6% by weight of the oral composition.

[0129] Coloring agents are used in amounts effective to produce an oral composition of the desired color. These coloring agents may be incorporated in amounts up to about 3% by weight of the oral composition. The coloring agents may also include natural food colors and dyes suitable for food, drug and cosmetic applications. These coloring agents are known as FD & C dyes and lakes. The coloring materials are preferably water-soluble. Illustrative nonlimiting examples include the indigoid dye known as FD & C Blue No. 1, and D & C Yellow No. 10. A full recitation of all FD & C colorants and their corresponding chemical structures may be found in the Kirk-Othmer Encyclopedia of Chemical Technology, 3rd Edition, in volume 5 at pages 857-884. A preferred opacifier, titanium dioxide, may be incorporated in amounts up to about 2.0% by weight, preferably less than about 1.0% by weight based on the total weight of the composition and most preferably less than about 0.4% by weight.

[0130] Desensitizing agents used to diminish teeth sensitivity such as strontium chloride, potassium nitrate and potassium citrate may also be included in the oral compositions of the present invention at concentrations of from about 0.1 to 10% by weight.

[0131] Various other materials may be incorporated in the oral compositions of the invention including whitening agents such as urea peroxide and hydrogen peroxide, preservatives, such as sodium benzoate, chlorophyll compounds and/or ammoniated compounds such as urea, diammonium phosphate, and mixtures thereof. These adjuvants, when present, are incorporated in the compositions in amounts which do not substantially adversely affect the desired properties.

[0132] The oral compositions of the present invention may be prepared by suitably mixing the ingredients. By way of example, in the preparation of a mouthrinse, the antimicrobial compound of Formulas IIa-IIc may be dispersed in a mixture containing for example, alcohol, humectant, surfactant, and salts such as sodium fluoride and potassium phosphate, and a flavoring is then added and the resulting combination mixed thoroughly. Dentifrices are prepared in a similar manner with the addition, typically, of a thickener and a polishing agent.

[0133] The oral compositions of the present invention may be incorporated into lozenges, dispersible oral films, film forming dentifrices, chewing gum or other products, e.g. by stirring into a warm gum base or coating the outer surface of a gum base, illustrative of which may be mentioned jelutone, rubber latex, vinylite resins, and the like, desirably with conventional plasticizers or softeners, sugar or other sweeteners or carbohydrates such as glucose, sorbitol and the like.

[0134] Oral film forming dentifrices include materials that may be applied to dental and/or oral surfaces in a manner to form a film or coating for reducing physical access to such surfaces by microorganisms, acid, food residues, debris, and the like, and for preventing growth of harmful microorganisms. The resulting oral film thus provides a protective physical barrier and enhances delivery of antimicrobial agents for minimizing attachment, propagation, growth or colonization of bacteria on the dental surfaces. Such compositions may be water-soluble. Suitable oral film forming substances include silicone compounds, aminoalkyl silicones, organopolysiloxanes, dimethyl polysiloxanes, alkyl-dimethicone copolyols, alkoxy-dimethicone copolyols, cyclic siloxane polymers and like substances.

[0135] The vehicle or carrier for a tablet or lozenge is desirably a non-cariogenic solid water-soluble polyhydric alcohol (polyol) such as mannitol, xylitol, sorbitol, malitol, a hydrogenated starch hydrolysate, Lycasin, hydrogenated glucose, hydrogenated disaccharides or hydrogenated polysaccharides, in an amount of from about 90 to 98% by weight. Solid salts such as sodium bicarbonate, sodium chloride, potassium bicarbonate or potassium chloride may totally or partially replace the polyol carrier.

[0136] Tableting lubricants, in minor amounts of from about 0.1 to 5% by weight, may be incorporated into the tablet or lozenge formulation to facilitate the preparation of both the tablets and lozenges. Suitable lubricants include vegetable oils such as coconut oil, magnesium stearate, aluminum stearate, talc, starch and Carbowax.

[0137] Lozenge formulations contain about 2% gum as a barrier agent to provide a shiny surface as opposed to a tablet which has a smooth finish. Suitable non-cariogenic gums include kappa carrageenan, carboxymethyl cellulose, hydroxyethyl cellulose, and the like.

[0138] The lozenge or tablet may optionally be coated with a coating material such as waxes, shellac, carboxymethyl cellulose, polyethylene/maleic anhydride copolymer or kappa-carrageenan to further increase the time it takes the tablet or lozenge to dissolve in the mouth. The uncoated tablet or lozenge is slow dissolving, providing a sustained release rate of active ingredients of about 3 to 5 minutes. Accordingly, the solid dose tablet and lozenge composition of this invention affords a relatively longer time period of contact of the teeth in the oral cavity with the active ingredients.

[0139] Dispersible oral film formulations contain an antimicrobial compound of Formula (IIa-IIc) in a carrier comprising one or more water-soluble polymers in combination with certain ingredients and provides a therapeutic and/or cosmetic effect. The film is coated and dried utilizing existing coating technology and exhibits instant wettability followed by rapid dissolution/disintegration upon administration in the oral cavity.

[0140] The foregoing discussion discloses and describes merely exemplary embodiments of the present invention. One skilled in the art will readily recognize from such discussion that various changes, modifications and variations can be made therein without departing from the spirit and scope of the invention as defined in the following claims.

EXAMPLE 1

Mouthrinse Composition Containing Antimicrobial Compounds of Formulas IIa-IIc

[0141] A mouthrinse composition containing the ingredients and the amounts shown in Table 1 is prepared by mixing the alcohol soluble ingredients 2 and 3 with ethanol. Water is added to the mixture. Water soluble ingredients 4 through 9 are then added and blended thoroughly to the mixture. About 1000 ml of water is then added to the mixture to adjust the final volume to yield the mouthrinse composition.

TABLE 1
Ingredients                      % by weight
1) Alcohol, USP                  15
2) Antimicrobial Agents of Formula (II) 0.05
3) Flavoring oil                 0.1
4) Glycerine                     3
5) Sodium lauryl methyl cocoyl taurate 0.3
6) Sodium citrate                0.08
7) Citric acid                   0.02
8) Saccharin sodium              0.1
9) FD&C Green #3                 0.0002
10) Water, USP                   QS to 100

EXAMPLE 2

Dentifrice Composition Containing Antimicrobial Compounds of Formulas IIa-IIc

[0142] A dentifrice composition containing the ingredients and the amounts shown in Table 2 is prepared by combining water, a portion of the humectant, the sweetener, the fluoride, and the water soluble buffers together. The remainder of the humectant is separately combined with the gum and then added to the initial mixture. Titanium oxide and silicas are blended and then added to the mixture. The colorant, flavor oil, antimicrobial compounds of Formulas IIa-IIc and the surfactant are added and blended with the mixture to yield the dentrifice composition.

TABLE 2
Ingredients                      % by weight
1) Glycerine                     6
2) Sodium carboxymethylcellulose 1.2
3) Sorbitol                      40
4) Sodium monofluoriphosphate, USP 0.76
5) Saccharin sodium              1
6) Sodium phosphate, dibasic     0.03
7) Sodium phosphate, monobasic   0.25
8) Silicon dioxide, hydrated     15
9) Titanium dioxide              0.2
10) Flavor oil                   2
11) Antimicrobial Agents of Formula (II) 0.5
12) FD&C Green #3                0.0002
13) Water, deionized             QS to 100

EXAMPLE 3

Deodorant Composition Containing Antimicrobial Compounds of Formulas IIa-IIc

[0143] A deodorant composition containing the ingredients and the amounts shown in Table 3 was prepared by mixing together the polar solvent, volatile nonpolar solvent, and the antimicrobial compounds of Formulas IIa-IIc. Gellants was added and agitated. The mixture was heated to a temperature in the range from about 75E to 100E C. until the gellants melted and formed a substantially clear and translucent liquid. The resulting liquid mixture was slightly cooled prior to adding the fragrance. The resulting liquid mixture was poured into a suitable container and cooled thus yielding a solid form deodorant composition.

TABLE 3
Ingredients                      % by weight
1) Propylene glycol              30
2) Glycerine                     2.5
3) Butyl stearate                20
4) Antimicrobial Agents of Formula (II) 0.5
5) Propylene glycol monostearate 15
6) Water                         32

EXAMPLE 4

Antibacterial Soap Composition Containing Antimicrobial Compounds of Formulas IIa-IIc

[0144] An antibacterial soap composition containing the ingredients and the amounts shown in Table 4 is prepared by agitating and mixing the ingredients for thorough blending.

TABLE 4
Ingredients                      % by weight
1) Sodium lauryl sulfate         67
2) Cocamidopropyl betaine        15
3) Glycerine                     1
4) Propylene glycol              1
5) Antimicrobial Agents of Formula (II) 1
6) Fragrance                     0.2
7) Water                         QS to 100

EXAMPLE 5

Antibacterial Cream or Ointment Composition Containing Antimicrobial Compounds of Formulas IIa-IIc

[0145] An antibacterial cream or ointment composition containing the ingredients and amounts shown in Table 5 is prepared by dissolving the antimicrobial compounds of Formulas IIa-IIc into the solvent and surfactant ingredients. The hydrophobic ingredients are then added to the resulting mixture and blended. The resulting mixture forms an emulsion having a uniform creamy consistency.

TABLE 5
Ingredients                      % by weight
1) Glycerine                     6
2) Propylene glycol              5.5
3) Sodium lauryl sulfate         1
4) Cetyl alcohol                 4.5
5) Cetyl palmitate               4
6) Steric alcohol                4.5
7) Steric acid                   4
8) White petrolatum              5
9) Antimicrobial Agents of Formula (II) 1
10) Water, deionized             64.5

Claims

1. A compound selected from the following formulas:

2. The compound of claim 1 wherein each of R1 and R2 is independently selected from the group consisting of straight or branched alkyl groups.

3. The compound of claim 1, wherein each of R1 and R2 is a cycloalkyl group.

4. An antimicrobial composition comprising an antimicrobial acceptable carrier and an effective antimicrobial amount of at least one compound selected from the following formulas:

5. The antimicrobial composition of claim 4 wherein the antimicrobial effective carrier is selected from the group consisting of water, saline, alcohol, glycerin, propylene glycol, mineral oil, petrolatum and mixtures thereof.

6. The antimicrobial composition of claim 4 wherein the compound has the Formula IIa wherein each of R2 and R3 is hydrogen, and R1 is selected from the group consisting of an alkyl group substituted with an aryl group; a cycloalkenyl group; benzyl substituted with an alkyl group; a cycloalkyl group optionally substituted with hydroxyl; and an aryl group optionally substituted with an alkyl group.

7. The antimicrobial composition of claim 6 wherein R1 is selected from the group consisting of 1-phenylethyl, cyclohex-2-enyl, 3-methylbenzyl, phenyl, phenyl substituted with tert-butyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, and 4-hydroxycyclohexyl.

8. The antimicrobial composition of claim 4 wherein the compound has the Formula IIa wherein R2 is hydrogen, and R3 is tert-butyl, and R1 is selected from the group consisting of hydrogen and phenyl.

9. The antimicrobial composition of claim 4 wherein the compound has the Formula IIa wherein each of R1 and R2 is hydrogen, and R3 is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with hydroxyl.

10. The antimicrobial composition of claim 9 wherein R3 is selected from the group consisting of tert-butyl, cyclohexyl, cyclopentyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.

11. The antimicrobial composition of claim 4, wherein the compound has the Formula IIc wherein each of R1, R3 and R4 is hydrogen and R2 is selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or a hydroxyl group; benzyl; an alkoxy group; a cycloalkenyl group; a cycloalkyl group optionally substituted with a hydroxyl group.

12. The antimicrobial composition of claim 11 wherein R2 is selected from the group consisting of tert-butyl, benzyl, hexyloxy, cyclohex-2-enyl, cyclohexyl, 2 cyclohexylethyl, 1-methyl-1-ethylpropyl, ethyl, propyl, 5-hydroxypentyl, isopropyl, 1,1-dimethylpropyl, cyclopentyl, 1-methylbutyl, 2-hydroxycyclopentyl and 3-hydroxycyclopentyl.

13. The antimicrobial composition of claim 4 wherein the compound has the Formula IIc wherein each of R1, R2 and R4 is hydrogen, and R3 is selected from the group consisting of a benzyloxy group or an alkyl group.

14. The antimicrobial composition of claim 13 wherein R3 is tert-butyl or a benzyloxy group.

15. The antimicrobial composition of claim 4 wherein the compound has the Formula IIc wherein each of R1 and R4 is hydrogen, and R3 is a hydroxyl, and R2 is selected from the group consisting of a benzyl group or an alkyl group optionally substituted with a hydroxyl group.

16. The antimicrobial composition of claim 15 wherein R2 is selected from the group consisting of tert-butyl, ethyl, isopropyl, benzyl, 4-hydroxybutyl, or hydroxymethyl.

17. The antimicrobial composition of claim 4 wherein the compound has the Formula IIc wherein each of R1 and R2 is hydrogen, R3 is an alkoxy group, and R4 is an alkyl group optionally substituted with hydroxyl.

18. The antimicrobial composition of claim 17, wherein R3 is a methoxy group and R4 is a hydroxymethyl group.

19. The antimicrobial composition of claim 4 wherein the compound has the Formula IIb wherein each of R1 and R2 is hydrogen, R3 is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with hydroxyl.

20. The antimicrobial composition of claim 19 wherein R3 is selected from the group consisting of tert-butyl, cyclohexyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyclopentyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.

21. The antimicrobial composition of claim 4 wherein the antimicrobial effective amount is from about 0.0001 to 10% by weight of the total weight of the antimicrobial composition.

22. The antimicrobial composition of claim 21 wherein the antimicrobial effective amount is from about 0.001 to 5% by weight of the total weight of the antimicrobial composition.

23. An oral composition comprising an orally acceptable carrier and an effective antimicrobial amount of at least one compound selected from the following formulas:

24. The oral composition of claim 23 wherein the orally acceptable carrier is selected from the group consisting of water, saline, alcohol, glycerin, propylene glycol, and mixtures thereof.

25. The oral composition of claim 23 wherein the compound has the Formula IIa wherein each of R2 and R3 is hydrogen, and R1 is selected from the group consisting of an alkyl group substituted with an aryl group; a cycloalkenyl group; benzyl substituted with an alkyl group; a cycloalkyl group optionally substituted with hydroxyl; and an aryl group optionally substituted with an alkyl group.

26. The oral composition of claim 25 wherein R1 is selected from the group consisting of 1-phenylethyl, cyclohex-2-enyl, 3-methylbenzyl, phenyl, phenyl substituted with tert-butyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, and 4-hydroxycyclohexyl.

27. The oral composition of claim 23 wherein the compound has the Formula IIa wherein R2 is hydrogen, and R3 is tert-butyl, and R1 is selected from the group consisting of hydrogen and phenyl.

28. The oral composition of claim 23 wherein the compound has the Formula IIa wherein each of R1 and R2 is hydrogen, and R3 is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with hydroxyl.

29. The oral composition of claim 28 wherein R3 is selected from the group consisting of tert-butyl, cyclohexyl, cyclopentyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl and 3-hydroxycyclopentyl.

30. The oral composition of claim 23 wherein the compound has the Formula IIc wherein each of R1, R3, and R4 is hydrogen and R2 is selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or a hydroxyl group; benzyl; an alkoxy group; a cycloalkenyl group; a cycloalkyl group optionally substituted with a hydroxyl group.

31. The oral composition of claim 30 wherein R2 is selected from the group consisting of tert-butyl, benzyl, hexyloxy, cyclohex-2-enyl, cyclohexyl, 2 cyclohexylethyl, 1-methyl-1-ethylpropyl, ethyl, propyl, 5-hydroxypentyl, isopropyl, 1,1-dimethylpropyl, cyclopentyl, 1-methylbutyl, 2-hydroxycyclopentyl and 3-hydroxycyclopentyl.

32. The oral composition of claim 23 wherein the compound has the Formula IIc wherein each of R1, R2 and R4 is hydrogen, and R3 is selected from the group consisting of a benzyloxy or an alkyl group.

33. The oral composition of claim 32 wherein R3 is tert-butyl or a benzyloxy group.

34. The oral composition of claim 23 wherein the compound has the Formula IIc wherein each of R1 and R3 is hydrogen, and R2 is an alkyl group.

35. The antimicrobial composition of claim 34 wherein the alkyl group is tert-butyl.

36. The oral composition of claim 23, wherein the compound has the Formula IIc wherein each of R1 and R4 is hydrogen, and R3 is a hydroxyl, and R2 is selected from the group consisting of a benzyl group or an alkyl group optionally substituted with a hydroxyl group.

37. The oral composition of claim 36 wherein R2 is selected from the group consisting of tert-butyl, ethyl, isopropyl, benzyl, 4-hydroxybutyl, or hydroxymethyl.

38. The oral composition of claim 23 wherein the compound has the Formula IIc wherein each of R1 and R2 is hydrogen, R3 is an alkoxy group, and R4 is an alkyl group optionally substituted with hydroxyl.

39. The antimicrobial composition of claim 38, wherein R3 is a methoxy group and R4 is a hydroxymethyl group.

40. The oral composition of claim 23 wherein the compound has the Formula IIb wherein each of R1 and R2 is hydrogen, R3 is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with a hydroxyl.

41. The oral composition of claim 40 wherein R3 is selected from the group consisting of tert-butyl, cyclohexyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyclopentyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.

42. The oral composition of claim 23 wherein the compound has Formula IIb wherein R1 is hydrogen, R2 is phenyl, and R3 is an alkyl group

43. The oral composition of claim 42 wherein R3 is tert-butyl.

44. The oral composition of claim 23 wherein the antimicrobial effective amount is from about 0.0001 to 10% by weight of the total weight of the oral composition.

45. The oral composition of claim 44 wherein the antimicrobial effective amount is from about 0.001 to 5% by weight of the total weight of the oral composition.

46. The oral composition of claim 23 further comprising at least one essential oil.

47. The oral composition of claim 46 wherein the at least one essential oil is selected from the group consisting of thymol, menthol, eucalyptol, methyl salicylate, and combinations thereof.

48. The oral composition of claim 47, wherein the essential oil comprises: an amount of from about 0.005 to 0.5% menthol; an amount of from about 0.005 to 0.5% eucalyptol; an amount of from about 0.005 to 0.5% methyl salicytate; and an amount of from about 0.005 to 0.5% thymol.

49. A method of reducing the presence of microorganisms on a substrate comprising treating the substrate with an effective amount of the antimicrobial composition of claim 4.

50. The method of claim 49 wherein the antimicrobial effective carrier is selected from the group consisting of water, saline, alcohol, glycerin, propylene glycol, mineral oil, petrolatum, and mixtures thereof.

51. The method of claim 50 wherein the antimicrobial effective amount is from about 0.0001 to 10% by weight.

52. The method of claim 49 wherein the antimicrobial effective amount is from about 0.001 to 5% by weight.

53. The method of claim 49 wherein the antimicrobial composition is in the form of a member selected from the group consisting of a deodorant, a soap, an ointment, and a cream.

54. A method of reducing the presence of microorganisms in an oral cavity comprising administering into the oral cavity a microorganism-reducing effective amount of the oral composition of claim 23.

55. The method of claim 54 wherein the orally acceptable carrier is selected from the group consisting of water, saline, alcohol, glycerin, propylene glycol, and mixtures thereof.

56. The method of claim 54 wherein the compound has the Formula IIa wherein each of R2 and R3 is hydrogen, and R1 is selected from the group consisting of an alkyl group substituted with an aryl group; a cycloalkenyl group; benzyl substituted with an alkyl group; a cycloalkyl group optionally substituted with hydroxyl; and an aryl group optionally substituted with an alkyl group.

57. The method of claim 56 wherein R1 is selected from the group consisting of 1-phenylethyl, cyclohex-2-enyl, 3-methylbenzyl, phenyl, phenyl substituted with tert-butyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, and 4-hydroxycyclohexyl.

58. The method of claim 54 wherein the compound has the Formula IIa wherein R2 is hydrogen, and R3 is tert-butyl, and R1 is selected from the group consisting of hydrogen and phenyl.

59. The method of claim 54 wherein the compound has the Formula IIa wherein each of R1 and R2 is hydrogen, and R3 is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with hydroxyl.

60. The method of claim 59 wherein R3 is selected from the group consisting of tert-butyl, cyclohexyl, cyclopentyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.

61. The method of claim 54 wherein the compound has the Formula IIb wherein R1 is hydrogen, R2 is phenyl, and R3 is an alkyl group.

62. The method of claim 61 wherein the alkyl group is tert-butyl.

63. The oral composition of claim 54 wherein the compound has the Formula IIb wherein each of R1 and R2 is hydrogen, R3 is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with a hydroxyl.

64. The oral composition of claim 63 wherein R3 is selected from the group consisting of tert-butyl, cyclohexyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyclopentyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.

65. The method of claim 54, wherein the compound has Formula IIc wherein each R1, R3 and R4 is hydrogen and R2 is selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl or a hydroxyl; a benzyl, an alkoxy group; a cycloalkenyl group; a cycloalkyl group optionally substituted with a hydroxyl.

66. The method of claim 65 wherein R2 is selected from the group consisting of tert-butyl, benzyl, hexyloxy, cyclohex-2-enyl, cyclohexyl, 2 cyclohexylethyl, 1-methyl-1-ethylpropyl, ethyl, propyl, 5-hydroxypentyl, isopropyl, 1,1-dimethylpropyl, cyclopentyl, 1-methylbutyl, 2-hydroxycyclopentyl and 3-hydroxycyclopentyl.

67. The method of claim 54 wherein the compound has the Formula IIc wherein each of R1, R2 and R4 is hydrogen, and R3 is selected from the group consisting of benzyloxy or an alkyl group.

68. The method of claim 67 wherein R3 is tert-butyl or benzyloxy group.

69. The method of claim 54, wherein the compound has the Formula IIc wherein each of R1 and R4 is hydrogen, and R3 is a hydroxyl, and R2 is selected from the group consisting of a benzyl group or an alkyl group optionally substituted with a hydroxyl group.

70. The method of claim 69 wherein R2 is selected from the group consisting of tert-butyl, ethyl, isopropyl, benzyl, 4-hydroxybutyl, or hydroxymethyl.

71. The method of claim 54 wherein the compound has the Formula IIc wherein each of R1 and R2 is hydrogen, R3 is an alkoxy group, and R4 is an alkyl group optionally substituted with hydroxyl.

72. The method of claim 71, wherein R3 is a methoxy group and R4 is a hydroxymethyl group.

73. The method of claim 54 wherein the antimicrobial effective amount is from about 0.0001 to 10% by weight.

74. The method of claim 73 wherein the antimicrobial effective amount is from about 0.001 to 5% by weight.

75. The method of claim 54 wherein the oral composition is in the form of a member selected from the group consisting of a mouthrinse, a dentifrice, a chewing gum, a dispersible oral film, a lozenge, and an oral film forming dentifrice.