MXPA00008179A - Antimicrobial denture adhesive composition - Google Patents

Abstract

Novel curable compositions are disclosed which include a water insoluble antimicrobial agent. The curable compositions are useful in inhibiting the growth of bacteria on the surface of the curable composition, within the curable compositions and in a volume adjacent to the curable composition.

Description

ANTIMICROBIAL COMPOSITION ADHESIVE FOR POSTZA DENTURE FIELD OF THE INVENTION The present invention relates to improvements in curable compositions intended for use or placement in direct contact with a biological surface. More specifically, the present invention describes curable compositions with antimicrobial properties, together with methods for their use, which are useful for preventing microbial growth on one or more surfaces of the curable composition, or within the curable composition or adjacent to the curable composition, after curing and subsequent contact with a biological surface.

BACKGROUND OF THE INVENTION Materials science has supplied us with a pletoria of compositions that can be transformed from an initial malleable state to a final non-malleable state, generally through the heating process, pressure application, and / or induction of polymerization. Said compositions provide us with a formation of materials that can be first molded into a desired shape, then subsequently induced to transform into an identical (or nearly identical) non-deformable final shape, up to the original molded shape. These processes can use heat or pressure (or both), to transforming the materials to a desired shape by manipulation of the physical properties of the material, or alternatively can use initiators and / or activators to begin a polymerization reaction throughout the mass formed. Alternatively, a healing process can occur simply as a composition that absorbs moisture from the surrounding environment. Said healing processes are observed in certain types of adhesives, such as retakes, based on urethanes and adhesives for dentures. The class of materials known as acrylics (which for the purpose of the present description should mean compositions comprised wholly or in part of acrylate and / or methacrylate monomers and / or polymers alone or in combination with one another and / or other compounds unsaturated and / or saturated), have gained acceptance since they are particularly suitable for the formation of prostheses to be placed in contact with the body. In particular, acrylics have been used to form dental restorative materials, dentures, temporary crown and bridge materials, and artificial nails, as well as have been used as adhesion promoters at the interface between a biological surface (here defined as any external or internal surface of a living organism) and a prosthesis (in order to provide the extended wear time required for, for example, a permanent dental restoration material). The curable acrylic compositions, when they are initiated and properly catalyzed, they undergo free radical addition reaction polymerization, which is exothermic in character (eg, generates heat). Since biological surfaces are invariably populated by a wide variety of microorganisms, inert objects (such as prostheses or adhesives), when placed in contact with such surfaces are subject to colonization on the surface and, often, to subsequent penetration by those same microorganisms. In addition, the infiltration of fluid in the interface between the biological and non-biological surfaces presents ideal conditions for the growth of microorganisms. In the absence of any protective mechanism to prevent such colonization, objects that are in contact with biological surfaces are often populated with a higher density of microorganisms than the original biological surface by itself. Therefore, a prosthesis can become a breeding base for potentially harmful microorganisms and subsequently can become a source of infection for adjacent living tissue. For example, the interphase or obstructed margin between an inert object and a biological surface, due to the accumulation of moisture (and often, the exclusion of oxygen, which results in an environment that leads to the growth of anaerobic microorganisms), may promote the development of microbial colonies in higher amounts than would the same biological surface, in an unobstructed state.

An example of this interfacial phenomenon is recurrent caries which is considered to be caused by the infiltration of microorganisms, particularly those responsible for tooth decay (tooth decay), in the interface margin between a restoration material dental (such as an amalgam or resin-based compound) and the surface of the natural tooth. In the preparation processes, the placement and completion of a dental restoration, the marginal adaptation of the restoration material, as well as the quality and strength of the union between the restoration surface and the surface of the natural tooth, is of vital importance for the duration of the restoration as a permanent prosthesis. If the adhesion of the restoration material is inadequate, or the shape of the restoration material is slightly non-conformant, oral fluids such as saliva, which constantly wet the restoration, have the ability to infiltrate the interface between the restoration material and the natural tooth. The microorganisms are transported together with the infiltration fluids and can colonize the marginal space. The metabolites of certain microorganisms, such as mutant species of streptococcus, are potentially harmful to the structure of natural teeth. Over time, erosion of the teeth at the interface (recurrent caries and possible failure of the restoration) may occur. It has been shown that recurrent cavities are a major cause in the failure of dental restorations. Is considered that the failure occurs due to the penetration of pathogenic organisms, such as S. mutants that are found within the structure of the teeth along the wall of the cavity through microfiltration and / or accumulation of bacteria at the margins, or interphase, between the restoration material and the teeth. The incidence of recurrent caries around enamel-containing restorations can be reduced by using fluoride-containing restorative materials. However, the amount of fluoride released has been shown to decrease significantly over time, and therefore the cariostatic capacity of these restoration materials is not clear for a long time. To overcome this disadvantage, attempts have been made to supplement the restoration materials with antimicrobial agents. The addition of chlorhexidine, as a water-soluble cationic antimicrobial agent for compounds of restorative materials, has not been successful due to loss of efficacy and deterioration of physical properties. Attempts have also been made to add other types of antimicrobial agents or restorative materials. Recently, Imazato and associated US Patent No. 5,733,949 inorated methacryloyloxydecylpyridinium bromide (MDPB) to experimental compounds and showed that the adhesion of S mutants to the surface of the restoration material was reduced. However, unlike chlorhexidine, a zone of inhibition was not evident through the disk diffusion method, indicating that the agent was not released in sub levels. M IC. This discovery suggests, that MDPD has a potential disadvantage, because it does not solve the problem of penetration of bacteria through the interfaces of restoration based on varnish, and the destruction of bacteria in the preparation of the cavity. The incidence of recurrent caries around restorations comprising enamel can be reduced by using fluoride-containing restorative materials. The purpose of fluoride is to convert hydroxyapatite to fluorapatite, which is more resistant to acid attack. The main disadvantage with the use of fluoride is that it does not have a significant antimicrobial activity and is easily washed or diffused, due to its high degree of solubility in the surrounding aqueous environment of the oral cavity. To overcome some of the disadvantages mentioned aboveAttempts have been made to add antimicrobial agents to dental materials that are more effective than fluoride against oral microorganisms, such as acrylics for dentures and soft coatings for dentures. Chlorhexidine and its acetate or gluconate salts are water-soluble cationic antimicrobial agents that have the ability to inhibit or kill a wide variety of oral pathogens. However, the incorporation of chlorhexidine salts into said compositions resulted in the rapid release of the highly water soluble antimicrobial agent and the subsequent deterioration of the physical properties of the cured material.

See for example, J. McCourtie, and associates, Effect of Saliva and Serum on the Adherence of Candida Species to Chlorhexidine-treated Denture Acrylic in Journal of Medical Microbiology, Vol. 21, (1986), 209-203, in addition to M. Addy, In Vitro Studies into The Use of Denture Base and Soft Liner Materials as Carriers for Drugs in the Mouth in Journal of Oral Rehabilitation, Vol. 8, (1981), 131-142. Attempts have also been made to add other types of antimicrobial agents to the restorative materials Recently, Imazato et al., In US Pat. No. 5,733,949, incorporated methacryloyloxydecylpyridinium bromide (MDPB) into experimental compounds and showed that the adhesion of S mutants was reduced. . to the surfaces of the restoration material. However, unlike chlorhexidine, through the disc diffusion method, a zone of inhibition was not evident, indicating that the agent was not released or that it is released in sub. minimum levels of inhibition concentration (M IC). This discovery suggests that the MDPB has a potential disadvantage because it does not solve the problem of bacterial penetration through enamel-based restoration interfaces and the destruction of bacteria in the cavity preparation. It has been shown that the enamel surface enamel demineralization is caused by the production of acid from the S. mutants and from other cariogenic organisms, while the demineralization along the wall of the cavity is caused by a combination of acid attack on the surfaces of the Upper enamel and additional acid attack through the gaps or micro holes between the cavity wall and the restoration. Both types of acid attack can be avoided by cariostatic agents deposited on the outer surfaces, in the walls of the cavity and in the areas of the micro holes. Hence, the presence of cariostatic agents or antimicrobial agents can reduce or eliminate the formation of caries through the reduction of enamel solubility or through the inhibition of bacterial activity. Attempts have also been made to add water-soluble antimicrobial agents to the dental materials for the purposes of inhibition of growth on the surface. See, J. Osaka Univ. Dent. Sch, vol. 35, pp. 5-1 1, 1995. In JP Patent Application 3-1-18309, triclosan was added to the monomer of a highly curable composite material, and the material was subsequently cured with a curing light. The release of triclosan in the surrounding medium was extremely low (0.02 micrograms / ml) for most of the tested compositions. As a result, the researchers did not observe the reduction of bacteria around the disks made of various compositions impregnated with triclosan, until the concentration of triclosan was in an excess of 1% by weight namely 4% by weight. Only in 4% by weight of triclosan, there was a slight zone (<1 mm) of bacterial inhibition around the disk prepared from a light-cured composite restoration material. The cured composition was not effective in levels below 4% triclosan in inhibiting and destroying bacteria in the environment surrounding the restoration (eg, not in direct contact). Dental restorative materials, especially resin-based composites (which are generally composed of a fluid matrix transporter based on monomers and / or modified acrylic polymers, together with a dispersed inorganic phase composed of glass, silica, and others finely divided materials), have the ability to support the growth of microorganisms on surfaces exposed to the oral environment. Said surfaces are known to accumulate plaque and tartar to a degree, which is often greater than an exposed natural tooth surface. Once again, said accumulation can have an impact on the health of adjacent natural hard and soft tissue surfaces, for example, irritation of gingival tissues adjacent to a highly colonized restoration surface. Another example of this nterfacial phenomenon occurs in the art of artificial nails. Artificial nails are often formed by wetting an artist's brush in a liquid acrylic monomer, which contains a polymerization initiator (usually a tertiary mine such as dimethyl-p-toluidine). The wet brush is then contacted with a reservoir containing an acrylic polymer, which may also contain a polymerization initiator (such as benzoyl peroxide). The resulting paste of liquid and powder that adheres to the brush, is transferred to the The surface of the natural nail and the polymerization initiators interact to cause the polymerization of the paste into a hard mass within a period of about 3 to 7 minutes. Although the surface of the natural nail is usually prepared in such a way that it is intended to ensure the exclusion of microorganisms before placing the artificial nail paste, often the preparation procedure results in a surface of the natural nail not sterilized . Even if the sterile conditions on the surface of the natural nail were achieved in practice (which does not happen), insufficient bond strength between the polymerized artificial nail and the surface of the natural nail will result in the potential for infiltration of fluids in the interfacial space created by a partial separation. Said infiltration of fluids, can result, as in the dental restoration of the previous example, the colonization of the interface of the natural nail / artificial nail, through microorganisms derived from the exterior (such as Pseudomonas aeruginosa, which has been identified as the most common source of nail infection). Another example of the problems associated with colonization of the surface of acrylic prostheses is found in dentures. The extended wear time achieved by the most modern denture adhesive formulations has resulted in a longer residence time for the longer dentures, which are based on acrylic polymers. The Preparation of a denture is a process well known in the art, and is more fully described in references such as Phillip's Science of Dental Materials, K.J. Annsavice, ed. 10 th Edition, 1996 (W. B. Saunders &Co.). A typical denture is prepared by taking an impression of the edentulous arch, creating a dental mold from the impression, and subsequently creating a resin registration base on the casting. Subsequently, wax is added to the registration base and the artificial tooth is placed in the wax. A pressure container, called a "flask", is chosen, and the distribution of the finished teeth is covered in an inversion medium. Subsequently the flask is opened and the wax is removed. Subsequently, the base material of the denture is introduced into the mold cavity and the polymerized assembly is terminated through either a combination of heat and pressure or alternatively a chemical cure process. The flask is opened and the finished denture is removed. The extended denture retention time has resulted in a longer period during which oral microorganisms can use the denture adhesive composition, and subsequently enter by themselves on the denture surface as a means of growth. The growth of oral microorganisms within the denture adhesive compositions and on the denture surfaces has been identified as a cause of the disease Oral odor associated with the use of dentures. The growth of microorganisms in the denture can be promulgated by the adjacent growth in the denture adhesive. The papillary hyperplasia of inflammatory stomatitis (I PH) induced by false teeth (DIS), are known conditions to result from dentures with surfaces contaminated with microorganisms (see for example, E. Budtz-Jorgensen, and associates in Quantitative Relationship between Yeast and Bacteria in Denture-Induced Stomatitis, Scandinavian Journal of Dental Research, Vol. 91 (2) (1983 =, 134-142) In order to provide additional comfort to users of dentures, coating materials are often used soft ingredients to facilitate a better adaptation of the adhesion surface (generally in the region of the palate), and to provide a "damping" between the hard surface of the denture and the point of adhesion in the oral cavity. Soft coatings are often self-healing acrylic materials (autopolymerization), which use monomers and / or acrylic polymers with a relatively low glass transition temperature (Tg). Alternatively, plasticizers such as dibutyl phthalate are used to provide elasticity to the cured soft coating composition. The high flexibility and softness of said materials results in a higher degree of porosity, thereby increasing the probability of a microbial colonization. In particular, it has demonstrated that soft coating materials support the growth of Candida albicans, a fungal organism considered to be associated with denture stomatitis. Previous attempts have been made to limit the growth of microorganisms in the soft coating materials, through the inclusion of water-soluble antimicrobial agents, such as zinc undecylenate and undecylenic acid. The durability of the antimicrobial effect is relatively low in prior art compositions, which contain one or more water-soluble antimicrobial agents, primarily due to the rapid rate at which the agent is released from the material in the surrounding aqueous medium. More often, the presence of a water-soluble molecule within a cured composition will contribute to the deterioration of said physical properties of the composition; This is because the gaps left in the polymer structure of the composition cured by the solubilized antimicrobial may render the material unsuitable for its intended purpose. Therefore, there is a need for improved compositions and methods that address the problems associated with prostheses and acrylic adhesives contacted with a biological surface. In particular, there is a need for improved compositions and methods for their use to prevent the growth of microorganisms at the interface between a biological surface and a non-biological surface.

In addition, there is a need for improved curable compositions and methods for their use to inhibit or kill microorganisms in the surrounding medium in which they are placed.

Summary of the Invention. The present invention describes curable compositions with antimicrobial properties, together with methods for their use as or in conjunction with prostheses put in contact with a biological surface. Said biological surface is a potential source of microbial contamination, and the compositions and methods of the present invention are useful for substantially inhibiting the colonization of microorganisms on the surface, as well as colonization within the curable composition. Prosthesis materials formed from the compositions of the present invention which include an antimicrobial agent not soluble in water, and which are contacted with a potential source of microorganisms in an aqueous environment, have been unexpectedly shown to substantially prevent growth of adjacent microorganisms in it. In addition, prosthetic materials formed from the compositions of the present invention have been further shown to conveniently and substantially prevent the growth of microorganisms within a volume surrounding the prosthesis material. In the present invention, said volume is referred to as a "zone of inhibition" and is defined as the volume immediately adjacent to the material of prosthesis, and extends far from the prosthesis material, enough to inhibit the growth of microorganisms within the area. The zone of inhibition is determined in part by the degree of crosslinking of the curable composition, the concentration of the water-insoluble antimicrobial agent within the cured composition and the release of the non-water-soluble antimicrobial agent from the cured composition when it is placed in a watery environment. The zone or volume of inhibition is characterized by a concentration gradient of the antimicrobial agent not soluble in water, extending beyond the cured composition. This aspect of the present invention is particularly advantageous since the cured compositions of the materials for prostheses or adhesives, do not only prevent the colonization of microorganisms from the surface, but also prevent the colonization of microorganisms in places far from the prosthesis material, such as bonding material, biological contact, or prosthesis, or spaces between the compositions of the present invention and the biological or adjacent prosthesis material. A wide variety of compositions are available, for example those formed of materials known as acrylics, projected to be placed and used within the oral cavity for extended periods of time. For the purpose of the present description, the term acrylic should be interpreted as any monomeric or polymeric compound or mixture of compounds, having at least one unsaturated portion having the ability to pass through a polymerization reaction that produces a higher molecular weight compound. The polymeric materials resulting from the aforementioned polymerization reaction are also referred to as acrylics. The unsaturated portions include acrylate, and / or vinyl groups many of these compositions form prostheses, such as dentures and temporary restoration materials and must be formed so that when forming the individual's teeth or mouth, they allow comfortable use after periods of prolonged time. In order to achieve this goal, many of these compositions are provided in a curable form, so that after being formed for the needs of an individual, a chemical reaction can be initiated which will become a malleable mass once in a composition that Resist a change in shape and size. In accordance with the present invention, one or more water soluble antimicrobial agents can be included within the ingredients forming the curable composition, and subsequently the ingredients can be cured to form the prosthesis or adhesive of the present invention. The antimicrobial agents remain inert to the monomers or prepolymers that can be used to produce the cured composition. According to one embodiment, an antimicrobial agent is mixed together with one or more of the ingredients of the composition. Once all the projected ingredients are mixed or otherwise combined, the monomers or prepolymers are polymerized to produce a cured composition which incorporates the antimicrobial agent. In this way, the The cured composition includes an antimicrobial agent and additionally includes a zone or volume of inhibition surrounding the cured composition within which the growth of the microorganism is inhibited. The compositions of the present invention are curable through a variety of polymerization reactions that can be initiated, for example, by heat, light, and / or chemical catalysts. Cured compositions, when placed in an oral cavity, are unique in their ability to allow the antimicrobial agent to inhibit microbial growth in or within the cured composition and within a volume or zone of inhibition of the cured composition after being placed in the oral cavity, and according to one embodiment of the present invention, in concentrations of the antimicrobial agent of less than 4% by weight of the curable composition. In general, the class of antimicrobials broadly described as non-cationic antibacterial agents not soluble in water have utility in the compositions and methods of the present invention. More specifically, useful antimicrobial agents are selected from the group consisting of alogenated diphenyl ethers, allogenated salicynols, benzoic esters, allogenated carbanalides, and phenolic compounds. Most of the preferred antimicrobial agents are substantially non-water soluble members of either the allogenated diphenyl ether group or the phenolic group, in particular those compounds described in detail in the US Pat.

North American No. (s) 4,894,220 and 5,800,803 which are incorporated herein by reference. A preferred antimicrobial compound is triclosan. It is clear that the present invention is not intended to be limited to the specific antimicrobial agents described therein, and in U.S. Patent Nos. 4,894,220 and 5,800,803 incorporated herein by reference, if not that one skilled in the art would readily identify the useful antimicrobial agents based on the description of the present invention. In general, the concentration of antimicrobial compound not soluble in water is given at least 0.10% by weight of the ingredients of the curable composition as a whole, depending on the solubility of the antimicrobial compound in the curable composition. However, any concentration of an antimicrobial agent substantially not soluble in water that provides for the inhibition of microorganisms on the surface of, and at some finite distance from, a cured composition contacted with a biological surface, is contemplated to be within range of the present invention.

It is clear that different curable compositions will have an effect on the release range of the antimicrobial agent, and as such, the carrier of the curable composition and the antimicrobial agent are interrelated with respect to the concentration of the required antimicrobial agent. Therefore, it is an object of the present invention to provide improved acrylic compositions and methods for their use that can limit or avoid the growth of microorganisms on one or more of their surfaces over a prolonged period of time. It is further an object of the present invention to provide improved curable acrylic compositions and methods for their use that can limit or prevent the growth of microorganisms on one or more of their surfaces when exposed or in contact with a potentially ineffective biological surface. . It is still another object of the present invention to provide antimicrobial acrylic compositions which can be formed and substantially cured in situ on a biological surface. It is still another object of the present invention to provide antimicrobial acrylic compositions that can be formed and subsequently cured before being contacted with a biological surface. It is still a further object of the present invention to provide compositions and methods for their use for the purpose of preventing microbial contamination at the interface between a biological surface and a non-biological surface, which are in contact with each other. Other objects, features and advantages of certain embodiments of the present invention will be fully appreciated from the following description taken in conjunction with the Claims and accompanying figures.

Detailed Description of the Invention. The principles of the present invention can be applied with particular advantage to obtain curable compositions and methods useful for inhibiting the growth of microorganisms in or within a volume surrounding a prosthesis designed to be placed adjacently or to make contact with biological tissue. . Applications of the present invention include prostheses projected to be placed within an oral cavity, adhesives used to secure dental prostheses, as well as, cosmetic prostheses such as artificial nails and adhesives related thereto. According to one embodiment of the present invention, the curable compositions of the present invention can be prepared according to methods well known in the art, using commercially available curable compositions intended for use in oral cavities, such as Herculite XRV (Kerr Corporation , Orange, CA). Although any commercially available curable composition designed to be placed in the oral cavity is contemplated, to be within the scope of the present invention, the curable antimicrobial compositions described therein preferably are of the class of (meth) acrylate monomers and polymers, which contain free radical polymerization initiators suitable for the desired mode of curing (heat, light, etc.) According to the present invention, the compositions cure in such a way that a matrix is produced which allows the activity of antimicrobial agent out of the cured composition. This can occur through release mechanisms such as elusion, diffusion or other release mechanisms that have first, second or third order kinetic release ranges. Although not intended to be bound by any particular scientific theory, it is believed that the compositions are cured in such a way that a cross-linked polymer system is produced which allows the sustained and sustained release of the antimicrobial agent. The curable compositions used as materials for dentures, materials for coating dentures (both hard and soft), denture adhesives, permanent restoration materials, adhesion promoting agents, construction cements and cavity coaters, are considered to unexpectedly benefit by the inclusion of non-water soluble antimicrobial compounds of the present invention, in a manner that is produced a volume or zone of inhibition within which the growth of the previous one is inhibited. The commercially available curable compositions used as resins of dental compounds and compositions for artificial nails, generally consist of a polymerizable number such as a species of acrylate or prepolymer, a filler in the form of a powder and a polymerization initiator and / or catalyst species. It is possible to formulate the compositions of the present invention in one part, or forming a single compound, or alternatively compositions may be provided which include components separately, for example, as a liquid and a powder or alternatively as two pastes. The two components are projected to be mixed together before the projected polymerization reaction takes place. Additional components may also be included, such as cross-linking comonomers, polymerization initiators, polymerization accelerators, photoinitiators, ultraviolet light absorbers, inks and the like. It is clear that the embodiments of the present invention are not limited to any particular curable composition, but that one skilled in the art will identify suitable curable compositions based on the description of the present invention. Specific monomers useful in the above applications include, but are not limited to methyl methacrylate, ethyl methacrylate, n-propyl methacrylate, isopropyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, propylene glycol monomethacrylate. , poly (ethylene glycol) methacrylate, isobornyl acrylate, isobomyl methacrylate, methoxyethoxyethyl methacrylate, ethoxyethoxyethyl methacrylate, tetrahydrofurfuryl methacrylate, methoxyethyl methoxylate and other monofunctional methacrylate and acrylate compounds and the like. The prepolymers, which in the present invention are defined as polymerizable compounds having one or more polymerizable groups in addition to having a molecular weight in excess of about 300 daltons, are selected from the group including, but not limited to dimethacrylate A 2,2-bis [4, - (3"-methacryloyl-2" h id roxy propoxy ) phenyl] propane (bis-GM A), ethoxylatebisphenol and dimethacrylate urethane (the reaction product of one mole of isosinate 2,2,4-trimethylhexamethylene with 2 mols of hydroxyethyl methacrylate) and the like. Cross-linked comonomers include ethylene glycol dimethacrylate, dimethylacrylate glycol diethylene, dimethacrylate glycol triethylene, trimethacrylate trimethylpropane, dimethacrylate 1,4-butamediol, dimethacrylate 1,6-hexanediol, dimethacrylate 1, 12-dodecanediol, polyethylene glycol dimethacrylate, and the like . Suitable fillers include powders, granules, particulates or other finely divided inorganic materials such as quartz, colloidal silica, alumina, hydroxyapatite, fluoroaluminium silicate glass, titanium dioxide, fumed silica, precipitated silica, and a variety of glasses and / or ceramics which optionally contain small amounts of heavy metals (barium, strontium, zirconium, etc.), as well as powders, granules, particulates and other finely divided organic materials, including polymers such as poly (methacrylate), poly (methacrylate butyl), poly (methacrylate) co-methyl), poly (methyl vinyl ether-co-maleic anhydride), poly (acrylic acid), poly (methacrylic acid), poly (pyrrolidone vinyl), poly (butyryl vinyl), polyethylene, polypropylene, polytetrafluoroethylene and the like. Inorganic fillers they can be modified on their surface, for example with a methacrylate-functional silane compound, in order to improve the compatibility after the polymerization of the inorganic filler with the matrix of the surrounding organic fluid. Polymerization initiators can be conveniently employed in the compositions of the present invention, in a concentration from about 0.1% to 5.0% by weight and include peroxides such as benzoyl peroxide and lauroyl peroxide in addition to barbituric acid 5-binyl-acid barbituric 1-benzyl-5-phenyl and other 5-alkyl or 5-aryl barbituric acid compounds and the like. One or more polymerization accelerators working in conjunction with the initiator to promote or improve the polymerization rate may conveniently be included in the compositions of the present invention in a concentration of from about 0.1% to 7.0% by weight. Accelerators such as N are particularly useful in this respect., N-dimethyl-p-toluidine, N, N-dihydroxyethyl-p-toludine, ethyl-p-dimethylamine benzoate, dimethylaminoethyl methacrylate, N- (2-cyanoethyl) -N-methyl aniline, and other aminofunctional compounds and the like. In order to achieve a normal level of storage stability, especially for compositions that are cured through a free radical healing mechanism, it may be desirable to include a conventional polymerization inhibitor. Examples of such inhibitors include ether monomethyl hydroquinone (M EHQ) and 2,6-di-tert-butyl-4-methylphenol (BHT or butylated hydroxytoluene) and the like. Some of the non-cationic non-water soluble antimicrobial agents described in the present invention, for example, the compounds containing the phenolic group, may have further utility in this regard, for example, both as an antimicrobial agent and as a polymerization inhibitor. . Polymerization inhibitors may be included up to and include about 1.0% of the weight of the composition. The compositions may additionally contain one or more photoinitiators, in order to render the combined liquid and solid components of the composition sensitive to light, thereby effecting polymerization by actinic energy at a wavelength or wavelength corresponding to the spectrum of said photoinitiators. Examples of useful photoinitiators include camphorquinone, benzyl, 2-hydroxy-2-methyl-1-phenyl-propane-1-one (Darocure 1 173, EM Chemicals, Hawthorne, NY), and 1-hydroxycyclohexyl phenyl ketone (Irgakure 184, Ciba- Geigy Corporation, Hawthorne, NY) and the like. The above photoinitiators may be included in the composition from about 0.1% by weight to about 6.0% by weight. In order to prevent degradation of the polymer and yellowing from ultraviolet light after the polymerization process has been completed, an ultraviolet light absorber can be included in the composition at a about 0.1% by weight to about 3.0% by weight. Examples of suitable ultraviolet light absorbers, considered to be of use in the compositions of the present invention, are benzotriazole 2 (2'-hydroxy-5'-methylphenyl) (Tinuvin P, Ciba-Geigy Corporation, Hawthorne, NY), 2-hydroxy-4-methoxybenzophenone and 2-cyano-3,3'-diphenylacrylic acid 2'-ester ethylexyl (Uvinul M40 and Uvinul N539, respectively, BASF, Ludwigshafen, Germany) and the like. The compositions of the present invention may also contain from about 0.5% to about 5.0% of a pigment or ink in order to adjust the color of the resulting polymerized composition. For example, a red lacquer pigment and titanium dioxide are added to a base denture polymer composition in order to provide a pigmentation that matches that of the oral mucosa. Suitable pigments and inks, include but are not limited to titanium dioxide, zinc oxide, nonsoluble lacquers, and soluble inks and the like. Pigments based on, for example, barium may be added in order to make the resulting polymerized composition radiopaque to x-rays. Other radiopairing fillers may also be conveniently included. In accordance with the present invention, an antimicrobial agent not soluble in water is included within the curable composition to not only inhibit the growth of both gram negative bacteria and gram positive bacteria on the surface and within the composition cured in an aqueous environment, if not also to inhibit the growth of gram-negative bacteria as gram positive bacteria within a volume surrounding the composition, in the present description termed as "zone of inhibition". The zone of inhibition is used to define the area immediately adjacent and outward radially or perpendicularly (in the case of a round object), of an object, in which the growth of a particular microorganism (or mixture thereof) is inhibited. microorganisms). When an object that processes antimicrobial properties is placed in or within a growth medium that has been inoculated with a microorganism, it is observed that the organisms will grow only in areas at a certain distance from the object. This is due to a concentration gradient of the antimicrobial compound that extends out from the object, decreasing in amount the extra movement away from the object. The ability of antimicrobial compounds and objects containing such compounds to inhibit the growth of microorganisms at some distance from the surface of the release substrate, can be determined using a disk diffusion assay, such as a Kirby-Bauer test. It is a convenient and relatively simple test procedure for the antimicrobial release capabilities of the curable compositions of the present invention. The ability of the curable composition of the present invention to inhibit the growth of bacteria in an aqueous environment in places far from the curable composition, since the antimicrobial agent of the present invention is not soluble in water, compared to the use of antimicrobial agents soluble in water or slightly soluble in water. The non-water soluble antimicrobial compounds useful in the present invention can be selected from the following group, which includes halogenated diphenyl ethers, halogenated salicylanilides, benzoic esters, halogenated carbanalides, and phenolic compounds. Most of the preferred antimicrobial agents are substantially water-insoluble members of either the halogenated diphenyl ether or phenolic group, in particular those compounds described in detail in U.S. Patent Nos. 4,894,220 and 5,800,803 which are incorporated herein by reference. incorporated herein by reference. The most preferred non-water soluble antimicrobial agent (in the present invention defined as an antimicrobial compound having a solubility in distilled water at 25 ° C of less than 1000 ppm) is triclosan (trade name Irgasan DP300). Triclosan (ether 2,4,4, -trichloro-2'-hydroxypropyl, CAS No. 338034-5) is a broad spectrum antimicrobial with a molecular weight of 289.5, having a very limited solubility in water at physiological temperatures (20). ppm in distilled water at 20 ° C and 40 ppm in distilled water at 50 ° C). The safety and use of triclosan in oral care products, mainly toothpastes passed in water in which triclosan has been established, has been established. solubilized, usually in a concentration of approximately 0.30% by weight. Therefore, in one embodiment of the present invention, the concentration of the antimicrobial compound not soluble in water will be at least about 0.10% by weight of the ingredients that formulate the curable composition, depending on the solubility of the antimicrobial compound in the ingredients. According to an alternative embodiment, the concentration of the antimicrobial agent is less than 4%, including 3%, 2%, and 1%. More preferably, the concentration of anitmicrobial compound not soluble in water will be in the range of between about 0.25% and about 5.0%, and more preferably in the range of from about 0.3% to about 1.0%. In the broadest sense, the concentration of an individual antimicrobial compound may vary from about 0.01% to about 10% by weight of the cured composition, in accordance with a particular intended use or purpose of the composition. The physical properties of the composition before curing (such as a solvent content which, due to evaporation, will not be part of the composition after being placed on a biological substrate) and in a cured form (determined by the degree of bonding) crossed), can affect the amount of antimicrobial compound required. In addition, the cured compositions include a volume or zone of inhibition surrounding the cured composition within which inhibits the growth of bacteria. It is recognized, and in some cases it is desirable that the curable composition be manipulated in its ability to release the antimicrobial compound in the surrounding medium. Said manipulation can be carried out by increasing or decreasing the amount of, for example, crosslinking in the cured composition, to prevent the antimicrobial compound from being released out into the environment very quickly. Since there are differences in the water solubility of the antimicrobial compounds, some compounds may be conveniently included in compositions which, when cured, release said antimicrobial in the surrounding medium in various ranges. In this form, the cured composition becomes a partial determinant of the range of antimicrobial diffusion in the surrounding volume, similar to a controlled release device (such as an encapsulating or transdermal patch). In the broadest sense, the level of antimicrobial compound optimally included in a particular composition of the present invention, is the minimum concentration which, over a prolonged period of time, will prevent the growth of microorganisms on the surface of and within a limited area around of the cured composition. A prolonged period of time in the present invention is defined as the amount of time during which the cured composition is in contact with the biological surface, and during which the cured composition is exposed to the potential colonization of one or more microorganisms.

Preferred extended times include from a few days to a few weeks, up to a few months and even years. The examples that follow are established to be representative of the present invention. These examples are not construed as limiting the scope of the present invention, and this and other equivalent embodiments will be appreciated by one skilled in the art, from the present description, tables, figures and appended claims.

EXAMPLE 1 A commercially available permanent restoration material was modified to include an antimicrobial agent not soluble in water, as follows: Table 1 Ingredient Herculite percentage XRV 100 100 99.75 99.5 99 Triclosan 0 0 0.25 0.5 1 Total 100 100 100 100 100 In general, syringes were emptied from Herculite XRV (Kerr Corporation, Orange, CA) in a heavy plastic taring bowl (on a scale with an accuracy of up to 0.001 grams) under low light conditions (this material is a permanent restoration material activated by light sensitive light between wavelengths of 400 and 500 nanometers). The syringes to fill them after mixing with triclosan. The correct amount of triclosan was calculated and weighed on an analytical balance with precision up to O.OOOl grams. The triclosan was combined with the restoration material under the same low light conditions as described above, the mixing procedure consisting of a manual kneading, of the triclosan powder in the restoration material similar to putty. A total of 5 minutes of kneading was performed for each sample, after which the mixed restoration material was placed again carefully into the original storage syringe. The control sample (A) was also kneaded (AK) in the same way as the many samples containing triclosan, in order to maintain a consistency throughout the test. When required, compositions A, AK, B, C, and D were formed into discs and subsequently cured to reproduce representative examples of a dental prosthesis. The cured composition containing the antimicrobial agent was studied to determine if the antimicrobial agent was released from the cured composition at levels greater than the M IC (minimum inhibition concentration) for S mutants at a baseline and then two weeks of washing.

Specifically, the composite restoration material (Kerr, Herculite XRV ™) was obtained from Schein (Long Island, NY).

S. Mutants (ATCC25175) were purchased from American Type Culture Collection (Virginia). Brucella Broth (Difco) was obtained from VWR, NJ. The Triclosan (Irgasan DP300) was obtained from CIBA Specialty Chemicals Corp., High point, NC. Brusella Broth (Difco) was rehydrated with double distilled water (28 g / l) and heated until a clarified solution was obtained. Subsequently, the nutrient was sterilized for 15 minutes in a 15-LB pressure autoclave. The final broth pH was 7.00 at 25 ° C. The sterilized nutrient broth was used to grow the bacteria. The freeze-dried S. mutants were reconstituted in 5 ml sterile polyethylene tubes. Brusella broth rehydrated and incubated at 37 ° C for 2 days. After establishing the growth, the bacterium was inoculated into the agar plates by beteado in four quadrants and left for growth at 37 ° C. After testing for purity and growth establishment, 100 ul of reconstituted culture was diluted in one milliliter of sterile water and its optical density was measured at 600 nm. Based on the optical density, the appropriate dilutions were made and 102 CFU's were transferred onto the agar plates and dispersed evenly to establish a "turf". Subsequently, discs A, AK, B, C, and D (control, kneading control, 0.25% antibacterial agent, 0.5%, 1.0%) were placed on agar surfaces with a separation of approximately 4cm. Subsequently the bacteria was left for growth at 37 ° C for 48 hours. The disks were washed five times in 5ml of distilled water, to remove all the debris and continue with the washes for two weeks twice a day in 5ml of distilled water. During this period, the discs were stored in 5ml of distilled water at room temperature. To check whether the antimicrobial agent was present in these disks, the experiment was repeated as described above. A separate experiment was carried out using P. aeruginosa bacteria, which is the most common source of nail infections. As shown in Figures 1 and 2, it was observed that all samples containing triclosan resist microbial colonization on the surface of and in a well-delineated area around the cured discs of the restoration material, whereby samples of Cured control without triclosan exhibited a marked growth of microorganisms on its surface and in immediate contact with the discs. Figure 1 illustrates a zone of inhibition where the growth of S. mutants was inhibited after 48 hours at 37 ° C. Starting with the upper part of Figure 1 and moving in the clockwise direction, the disks are identified as follows: 1 .0% triclosan, 0.5% triclosan, 0.25% triclosan, 0.0% triclosan as a control and 0.0% triclosan as a control kneading. Figure 2 illustrates a zone of inhibition where the growth of P. aeruginosa was inhibited after 48 hours at 37 ° C. Starting at the top of Figure 2 and moving clockwise, the disks are identified as follows: 0.25% triclosan, 1.0% triclosan, 0.5% triclosan, 0.0% triclosan, as a control and 0.0 % triclosan as a kneading control.

Specifically, after two days at 37 ° C, the disk agar diffusion test showed a concentration that depends of the zones of inhibition before and after two weeks of washing. This indicates that the antimicrobial agents are still active after healing and continue to be released at higher levels of M IC of S. mutants after a washout period of two weeks. The control specimens showed no zones of inhibition, confirming that the antimicrobial activity was due to the antimicrobial agent and not to the constituents of the compound. The size of the "halos" that identify the zones of inhibition are similar before and after washing, suggesting that the release range is similar before and after washing. The zone of inhibition of the control and kneaded samples was calculated to be 0. In contrast, the prewashed discs containing .025% of antimicrobial agent showed an average zone of inhibition of 3.34mm. The samples washed during two weeks showed an area of inhibition. of inhibition of 3.1 mm. Similarly, discs containing 0.5% antimicrobial agent showed 3.81 mm and 3.92 mm inhibition zones for the prewashed and post-washed specimens respectively. Discs containing 1.0% antimicrobial agent showed average inhibition zones of 5.1 1 (prewashed) and 6.1 mm (post-washed). These data are shown in tables 3 and 4 below.

TABLE 3 Zones of inhibition (mm) Sample Disc 1 seo 2 Means Control 0 0 0 Control (Kneaded) 0 0 0 0. 0025 3.32 3.36 3.34 0. 005 3.83 3.8 3.81 0. 01 5.1 5.12 5.11 TABLE 4 Inhibition zones (mm) after 2 weeks of washing Sample Disc 1 Disc 2 Means Control 0 0 0 Control (Kneaded) 0 0 0 0. 25% 3.1 3.1 3.1 0. 50% 4.03 3.81 3.92 1. 00% 5.6 6.6 6.1 In this example, an antimicrobial agent was mixed with ingredients of a composition prior to polymerization. At least a portion of the antimicrobial agent was inert to the polymerization ingredients, meaning that at least a portion of the antimicrobial agent does not react with the polymerization ingredients and remains bound within the cure composition. Instead, the antimicrobial agent established a concentration gradient within a zone of inhibition surrounding the cured composition. Other means of incorporating the antimicrobial agent into the material of the compound were anticipated, for example, by dissolving the agent in the fluid monomer phase of the material of the compound before the addition of the inorganic filler, to provide the same properties as described in this. example.

The results of Example 1 indicate that the antimicrobial agent is released into the surrounding medium in concentrations high enough to inhibit the growth of S. and Aeruginosa P mutants. The studies of the zone of inhibition showed a concentration that depends on the zone of inhibition for both washed and unwashed samples. In addition, the zones of inhibition were similar, both in the samples washed for two weeks and in the unwashed samples, suggesting that the antimicrobial agent is slowly and constantly released into the surrounding medium in concentrations high enough to inhibit the growth of the organisms tested. . Based on the results shown in Tables 3 and 4, the highest concentrations of triclosan (such as above 4%) may exhibit zones of inhibition larger than those shown in the tables.The zones of inhibition within the meaning of the present invention, include those calculated to be greater than 1mm, within the range of about 1mm to 10mm, between about 1mm and up to about 7mm, or between about 1mm to about 6mm.The zones of inhibition greater than 10mm or less 1 mm are also considered within the embodiments of the present invention, therefore, embodiments of the present invention include the use of curable antimicrobial compositions in the form of dental restoratives to gradually release one or more antimicrobial agents at the interface. of natural teeth / restoration, to inhibit the growth of S mutants at the interface and in the preparation of the cavity. In addition, the antimicrobial agent is expected to have additional benefits, by destroying the residual S. mutants in the cavity preparation. In addition, the embodiments of the present invention include the use of an antimicrobial curable composition in the form of an artificial nail to gradually release one or more antibiotic agents at the interface of the natural nail / artificial nail to inhibit the growth of Aeruginosa P. at the interface. The antimicrobial compositions of the present invention, in the form of dentine and enamel adhesives "primers" based on acrylic monomers that promote adhesion, are useful to avoid interfacial infiltration of microorganisms and the subsequent recurrent caries associated therewith. According to an alternative embodiment of the present invention, the antimicrobial compositions are used to reduce the hypersensitivity of the teeth since it is related to the presence of S. mutants and to the production of acid therein. Hence, it is possible that the present invention can help in the prevention of hypersensitivity of the teeth, by inhibiting the S. mutants in restorations in the root or in the vicinity of the cement enamel junction. According to said embodiment, a curable composition that includes an antimicrobial agent is inserted into a desired tooth cavity, and it is left to inhibit the growth of S. mutants in a manner that reduces the hypersensitivity of the teeth.

EXAMPLE II Physical properties of the compositions of the present invention. Color stability The physical properties of the modified composite restoration materials were evaluated, including color stability, compression strength and dentin binding strength. Surprisingly, there was a distinct tendency especially a dentin binding strength, towards the improved physical properties for the composite material containing increasing levels of triclosan. Triclosan and composite restorative material (Kerr, Herculite XRV ™) were obtained commercially. The syringes of the compound were emptied and the antimicrobial was incorporated into the compound, kneading as described above in concentrations of 0.25%, 0.5% and 1% by weight. Subsequently the material of the compound was repackaged in the original syringes and coded so that the researchers did not know about the contents of the syringes. Prior to the color measurement studies, the syringes were stored at room temperature for two weeks. After this period, 3X15mm discs were prepared for each sample and the material was lightly cured for 30 days. seconds using a commercial healing light. The baseline color of the discs was subsequently measured using a color meter with 45 ° / 0o illumination / observation geometry (Minolta ™ CR221), and the color parameters were recorded in the L * color space, a *, b * tristimulus. Six readings were taken for each disc at random locations. The discs were then placed in a Sun Lamp color stability box, as specified in the Amarican Dental Association Specification # 27 and exposed for 24 hours to the ultraviolet. Subsequently the color was determined by visual checks and by the CR221 color meter. The color meter readings were taken at 6 random locations. The change in color was evaluated, averaging the color parameters L * a * b * tristimulus and comparing the CIELAB color scale results (International Commission of L'Eclairage, Recommendations regarding uniform color spaces, color difference equations , and psychometric color terms, Supplement 2 for the publication CI É 15 (E-13.1) 1971 (TC-1 .3), 1978, Paris: Beaurea Central of the CI É, 1978). E = [(L *) 2+ (a *) 2+ (b *) 2] 1/2 The visual evaluation of the color change according to ADA specifications showed insignificant color changes indicating that the antimicrobial can be added to the formulations of normal restoration material without altering the color. These results were confirmed by the measurements of the color. As shown in Table 3, the average color or E (E (initial)) of the control sample (without the antimicrobial agent) was calculated at 57.50. The average E of the sample kneaded at 56.64 was calculated. The value of the average color or E for the sample containing 0.25% by weight of antimicrobial was calculated at 55.17. The average color values for the spots containing 0.5% and 1.0% antimicrobial were calculated at 57.26 and 55.31 respectively. The statistical analyzes by means of the F-test (variation of two populations of numbers) did not show significant differences between the groups, thus providing additional evidence that the addition of antimicrobial to the restoration material under review will not cause a significant alteration in the the color. After exposure to ultraviolet light (E (Final)), the color values for the untreated and kneaded controls were calculated to be 57.14 and 56.45 respectively. The E values for 0.25%, .05% and 1% were calculated to be 54.42, 57.27, and 55.26 respectively. The statistical analysis for the F test showed a maximum significance level of p = 0.01 1 for the controls (kneaded) against 1% antimicrobial agent strongly suggesting that a larger sample would produce a significant statistical difference, and therefore The antimicrobial agent can increase the color stability and prevent the discoloration induced by ultraviolet light. The general change in color (change in E) (baseline against exposure to light), was calculated using the equation of color difference of the Commission Internationale de L 'Eclairage. The change in E for the control was calculated, the samples kneaded the triclosan at 0.25%, 0.5% and 1.0% and is shown in table 4 below. Table 4 Sample E (lnicial) E (Final) Change in E Control 57.5 57.14 -0.36 Control Amazed 56.64 56.45 -0.18 + 0.25% p / p triclosan 55.17 54.42 -0.75 + 0.50% p / p triclosan 57.26 57.27 0.01 + 1.00% p / p triclosan 55.31 55.26 -0.05 Collectively, the results shown above indicate that the addition of antimicrobial agent to the tested restoration material will not cause a color alteration. In fact, the results suggest that the antimicrobial agent will cause an improvement in color stability after exposure to ultraviolet light.

EXAMPLE lll Compression resistance / bond strength. The example below demonstrates that no significant differences in compression strength were observed between the control and antimicrobial compound samples.

Triclosan was incorporated into Herculite XRV (Kerr) by emptying the syringes and kneading it in the dark in concentrations of 0.25%, 0.5% and 1% by weight. The composite material was subsequently repackaged in the original syringes and coded so that the researchers did not know about the contents of the syringes. Freshly extracted human molars were stored in a solution of thymol at 3 ° C. Before use, the enamel was removed using a low velocity diamond closure (Isomet, Beuhler) to obtain flat surfaces, and all samples were examined under a light microscope to ensure that all enamel was removed from the test areas . A standard cylindrical stainless steel die was used for the compression resistance measurements, which allowed healing in 3mm sections. To measure the compressive strength, the die was filled and compressed to a level of 3mm. This was cured with a standard light for 30 seconds, then a second section of 3mm was compressed in the cured section and again exposed to healing light for 30 seconds. This was repeated for the third section to obtain cylindrical specimens of 3 X 9mm. The specimens were subsequently stored at 37 ° C in a humidification chamber to obtain a complete cure. The compression resistance measurements were made using a head tension tester (MTS Model 810 Material Testing System) fitted to a N250 load. Three cylinders were prepared for each test sample.

The binding strength was measured by compressing the test samples in a gelatin capsule (4mm in diameter and 9mm in length). The capsules were placed on a glass sheet to obtain flat surfaces, and were cured for 1 minute using a standard dental cure light. After ensuring that all surfaces were flat, the cylinders were bonded to the surfaces of the strong water dentine, using the prime & bond ™ (Caulk) according to the manufacturer's instructions. Two samples were attached for each denture and for each sample, two teeth were used. Before measurements, the samples were stored in a humidification chamber at 37 ° C. The shear bond strength was measured, using an MTS system under travel control in a strain range of 0.02"/ min, ensuring that the end of the blade was placed in the dentin-restoration material interface. Compression resistance, are indicated in Table 5 and do not show significant differences between the samples of the control and antimicrobial compound TABLE 5 Sample Compression Resistance (Mpa) Control 50.03 (SD = 9.70) Control (Amazed) 48.90 (SD = 2.80) 0.25% Triclosan 48.87 (SD = 2.60) 0.50% Triclosan 48.24 (SD = 2.88) 1.00% Triclosan 52.05 (SD = 6.42) The binding resistance results for dentin are shown in Table 6 below. Table 6 Sample Union Resistance (Mpa) Control 9.74 (SD ± 3.30) Control (Amazed) 10.43 (SD ± 3.30) 0.25% Triclosan 10.53 (SD ± 4.16) 0.50% Triclosan 13.13 (SD ± 5.94) 1.00% Triclosan 14.13 (SD ± 6.22) Statistical analysis using ANOVA (variation analysis) showed no differences between the samples. However, the data review showed a directional improvement in the shear bond strength with an increase in antimicrobial agent concentration, for example, enamel-dentin binding strength control, was determined at 94.74 ± 4.37 MPa, while that the binding strength of the restoration material containing 1.0% antimicrobial agent was determined at 14.13 ± 6.22 MPa, which results in an improvement of 45%, demonstrating that the material of the antimicrobial compound of the present invention can to provide an improvement in the shear bond strength, when the curing is in contact with that of the stabilized dentin. The different adhesion promoters in primers and bonding agents used to increase the bond strength of restorative materials for dentine, are usually molecules of active surface that are applied to the structure of the teeth after strong water or conditioning. These agents are considered to provide adhesion, bridging the gap between the hydrophilic dentine surface and the matrix resin of the hydrophobic compound. Although not wishing to be bound by any particular theory, it is speculated that triclosan and other antimicrobial agents with similar molecular properties may in some way alter the tension of the interfacial surface between the stabilized dentin surface and the restorative material. of the compound. In addition, the above data suggest that triclosan may increase the color stability of a composite restoration material; the increase in bond strength may be a result of the free radical tempering capabilities of triclosan. Free-radical quenchers have been shown to reduce the branching of the growth polymer, during the reaction of polymerization additions, an effect which could result in the presence of a more linear interfacial polymer in the structure. The reduced branching and high linearity of the polymers can result in lower glass transition temperatures and increased tensile strength.

EXAMPLE IV Since the above results suggest that the inclusion of triclosan in a resin-based composite restoration material, it may increase the overall bond strength to the stabilized dentin, an adhesion promoting composition was prepared, as shown in Table 6 below, which would serve as binding agents between the surface of natural teeth (dentin and / or enamel) and a material Resin-based restoration. Other stabilization or binding agents that could benefit from the inclusion of the water-insoluble antimicrobial compounds described in the present invention are described in amounts different from the prior art compositions in US Patent No. (S) 4,514,527; 4,659,751; 5,270,351; , 5,276,068 and 4,966,934 each of which is incorporated in its entirety to the present invention as a reference. Table 6 Ingredient Percentage by weight Bis-GMA 70.00 Triethylene glycol dimethacrylate 29.55 Comforquinone 0.20 Dimethylaminoethyl methacrylate 0.15 Triclosan 0.10 TOTAL 100.00 The example shown in Table 6 is a resin cured by non-filled light which is used to bond resin-based composite restoration materials to strong water enamel surfaces. The porosity created in the enamel allows the penetration of the low viscosity resin in the enamel substructure. After curing by exposure to light energy in the range of 400 to 500 nm, the resulting bond is mainly mechanical in nature, through the formation of hard resin "tapes" that cure within the enamel substructure .

EJ EMPLO V In accordance with another embodiment of the present invention, a solvent-based adhesion promoter containing different levels of Triclosan was prepared and is useful for binding the compositions of the present invention to the surface of the natural nail, and was tested for adhesion duration compared to an adhesion control promoter withTriclosan. The Triclosan in the compositions of Table 7 below, at the level of 0.3 and 1.0% by weight of the non-volatile solids (for example, exclusive of the solvent transporter of ethyl acetate, which evaporates rapidly when stabilizing the contact of the composition with the surface of the nail).

Table 7 Ingredients P «Percent A B C Ethyl acetate 88.24 88.2 88.1 3 Methacryloyloxyethyl maleate 8.75 8.75 8.75 Hydroxyethyl methacrylate 2.92 2.92 2.92 Fluorad FC-430 0.08 0.08 0.08 Triclosan 0 0.03 0.12 TOTAL 1 00 1 00 100 Each of the above compositions was evaluated for their adhesion promotion properties in 40 individuals. None of the evaluators who participated in the study was informed of the compositions of the product, and each product found in Table 7 was coded in order to blind the study. A simple cover of each stabilizing agent was applied to the surface of the natural nail, followed by a medium abrasion of the nail plate with a nail file. All stabilizing agents were allowed to evaporate until the surface appeared to be dry. In each case, there was a residual gloss on the surface of the treated nail, followed by the evaporation of the ethyl acetate. After application of the stabilizing agent, an artificial nail that excludes Triclosan was "sculpted". The observations regarding the color of the artificial nails, adhesion to the nail plate and performance properties in general were accumulated during a period of 30 days. At the end of the evaluation period, there was a slight preference (although probably not significant) for the stabilizing agent corresponding to composition B of Table 7. In general, the performance of all the artificial nail stabilization agents was relatively the same, indicating that the presence of Triclosan in the composition does not affect the performance properties of this type of adhesion promoter, when present at the interface of the artificial nail / natural nail.

EXAMPLE VI A number of liquid artificial nail binding compositions (similar to those described in US Pat. No. 5,738,843, incorporated in its entirety by reference to the present invention) were prepared containing various levels of Triclosan. The disks were prepared by combining a portion of each liquid linker, by weight, with two parts of a finely divided polymer consisting of a 70/30 molar ratio of poly (methacrylate-ethyl-co-methyl) copolymer containing approximately 1.2% by weight of benzoyl peroxide. The benzoyl peroxide in the powder, when combined with the liquid linker (which contains dimethyl-p-toluidine), initiates a free radical addition polymerization process that turns the liquid linker / powder into a hard mass fused in approximately 5 minutes. Very little, if any, difference in polymerization time was observed between the different mixtures prepared from the liquid binders found in Table 8 below, indicating that the inclusion of Triclosan did not inhibit the addition polymerization reaction in no significant way. This was somewhat unexpected, since the sensitivity of free acrylic mass radical polymerization reacts with the presence of aromatic alcohols such as BHT (butylated hydroxytoluene).

Table 8 Ingredients Percentage by weight A B C D Ethyl methacrylate 83.2 82.7 82.2 81.2 Ethylene glycol dimethacrylate 6 6 6 6 Isopropyl alcohol 10 10 10 10 Dimethyl-p-toluene 0.8 0.8 0.8 0.8 Triclosan 0 0.5 1 2 Total 100 100 100 100 EXAMPLE Vil Denture adhesives are usually composed of high molecular weight water soluble polymers dispersed in a hydrophobic transporter, such as petrolatum. When placed in the oral cavity at the interface between a denture and the soft tissue of the mouth, the water is absorbed by the dispersed polymer, which leads to an abrupt increase in the cohesion and viscosity of the composition. A denture adhesive can be described as curing, when a highly viscous and highly cohesive state is achieved. In Table 9 below, an example of a useful antimicrobial denture adhesive composition is provided: The above composition was prepared by dissolving Triclosan in the mineral oil petrolatum (to which red lacquer number 27 D &; C and sodium saccharin and has been completely dispersed), which was heated to 150 degrees Fahrenheit to liquefy the mixture. A dispersion mixer was used to sequentially mix the hydrous silica ell Gantrez MS-955 (IS), Wayne, NJ), and finally the cellulose gum in the above mixture. The mixing was continued to a smooth dispersion and the finished composition was obtained which was immediately filled into the sealed plastic-aluminum laminate tubes. In the prior art, similar types of formulations were found without adding the steps of including a substantially non-water-soluble non-cationic antimicrobial agent of the present invention (see for example U.S. Patent Nos. 5,424,058 incorporated in its entirety by reference herein). In general, said compositions they consist of (1) a transporter not soluble in water (2) one or more water-thickable polymers in a finely divided form, dispersed homogeneously in a carrier, and (3) various adjuvants, including pigments, inks, flavorings and preservatives. The portion of the non-water soluble carrier of the denture adhesive may be hydrophobic organic materials such as petrolatum, mineral oil, waxes and vegetable oils. Water-swellable polymers that have utility in denture adhesives include poly (ethylene oxide), carboxymethyl cellulose salts, methyl cellulose, hydroxypropyl cellulose, polymers of acrylamide, poly (vinylpyrrolidone), and partial salts of poly (methyl vinyl ether) -co-maleic) mixed and increase the non-viscosity and cohesion as a result of the absorption of water by the growth medium. Inhibition zone studies were carried out as described above in Example I. After 48 hours, the denture adhesive containing Triclosan above exhibited an inhibition zone of approximately 3-4mm, whereas a commercially available denture adhesive did not exhibit a zone of inhibition. In fact, the surface of the commercial denture adhesive was colonized by S mutants after a trial period of 48 hours. The addition of Triclosan from the above denture adhesive formulation resulted in a composition having the ability to inhibit microorganisms in the volume surrounding the mass of swollen or cured adhesive.

It is clear that the embodiments of the present invention have been described in the form of illustration of some of the applications of the principles of the present invention. Those skilled in the art can make numerous modifications based on the teachings presented in the present description, without departing from the spirit and scope of the invention.

Claims (14)

R E I V I N D I C A C I O N S Having described the present invention, it is considered as a novelty and, therefore, the content of the following CLAIMS is claimed as property.

1 .- An adhesive material for dentures to place it between a denture and an oral cavity, said material comprising: A transporter not soluble in water; One or more polymers swellable with water in a finely divided form dispersed through the carrier; An antimicrobial agent not soluble in water releasable from the material, such that a zone of inhibition is created within which the growth of bacteria is inhibited.

2. - A material as described in claim 1, further characterized in that the antimicrobial agent not soluble in water is provided in sufficient concentrations to substantially prevent bacterial growth in the material, when the material is brought into contact with the oral cavity.

3. - A material as described in Claim 1, further characterized in that the antimicrobial agent not soluble in water is selected from the group consisting of diphenyl ethers halogenated, halogenated salicylatenides, benzoic esters, halogenated carbanalides, and phenolic compounds.

4. - A material as described in Claim 1, further characterized in that the antimicrobial agent not soluble in water is provided in a concentration of between about 0.10% by weight and less than 4% by weight of the composition.

5. - A material as described in Claim 1, further characterized in that the antimicrobial carrier not soluble in water is Triclosan.

6. A method for forming a denture adhesive material to be placed between a denture and an oral cavity, said method comprising: Mixing a non-water soluble carrier, one or more polymers thickened in water in a finely divided form dispersed through of the conveyor; An antimicrobial agent not soluble in water releasable from the material in such a way that a zone of inhibition is created within which the growth of bacteria is inhibited.

7. - The method as described in claim 6, further characterized in that the antimicrobial agent is not soluble in Water is a selected member consisting of halogenated diphenyl ethers, halogenated salicylanilides, benzoic esters, halogenated carbanalides, and phenolic compounds.

8. The method as described in Claim 7, further characterized in that the antimicrobial agent not soluble in water is provided in a concentration of between about 0.10% by weight and less than 4% by weight of the composition.

9. - The method as described in Claim 8, further characterized in that the antimicrobial agent not soluble in water is Triclosan.

10. A method for inhibiting the growth of bacteria, between a denture and a human tissue, wherein said method comprises: molding a denture adhesive including an antimicrobial agent not soluble in water; Place the denture adhesive between a denture and a human tissue in an aqueous environment susceptible to bacterial growth;

Allowing the denture adhesive to establish a zone of inhibition in a manner that inhibits the growth of bacteria within the zone of inhibition. 1 - The method as described in Claim 10, further characterized in that, the bacterium is S mutants.

12. The method as described in Claim 10, further characterized in that the antimicrobial agent not soluble in water is initially present in an amount greater than 0.1% by weight of the denture adhesive.

13. The method as described in Claim 10, further characterized in that the antimicrobial agent not soluble in water is initially present in an amount between about 0.1% and 4% by weight of the denture adhesive.

14. The method as described in Claim 10, further characterized in that the antimicrobial agent not soluble in water is initially present in an amount of less than 4% by weight of the denture adhesive. R E S U M N A new curable compositions are described which include an antimicrobial agent not soluble in water. The curable compositions are useful for inhibiting the growth of bacteria on the surface of the curable composition, within the curable compositions and in a volume adjacent to the curable composition.