COMPOSITION AND METHOD FOR REMINERALIZATION OF TEETH

Abstract: This invention relates to non-aqeuous compositions and method utilizing same which are useful to remineralize subsurface dental enamel. More specifically, this invention relates to stable, single-part compositions containing calcium and phosphate salts which may be in a hydrophilic, non-aqueous vehicle and which when applied to lesions in dental enamel result in remineralization of subsurface dental enamel and/or mineralization of tubules in dentin thereby counteracting caries and/or hypersensitivity.

Description: It is suggested as.. Composition and Method For Remineralization of Teeth. BACKGROUND OF THE INVENTION 5 1. Field of the Invention This invention relates to non-aqueous compositions and processes utilizing same which are useful to remineralize subsurface dental enamel. More specifically, this Invention 10 relates to stable, single-part compositions containing calcium and phosphate salts which may be in a hydrophilic, non-aqueous vehicle and which when applied to lesions 1n dental enamel result 1n remineralization of subsurface dental 15 enamel and/or mineralization of tubules 1n dentln thereby counteracting carles and/or hypersensi tivity. 2. The Prior Art The primary component of the enamel 20 and dentln 1n teeth 1s calcium phosphate 1n the form of calcium hydroxyapatlte. This material is highly insoluble at normal oral pHs. However, carious lesions form 1n teeth, when they are subjected to acids produced from the glycolysis of sugars by the action of various oral bac¬ teria. This 1s because calcium phosphate salts are more soluble 1n acidic media. Saliva is supersaturated with respect to calcium and phosphate 1ons. Saliva therefore helps protect teeth against deml neral 1zat1on and can slowly remineralize teeth which have become de ineral 1 zed by acids. It 1s well known that the presence of fluoride Ions can enhance the natural remineralization process and this 1s one of the accepted mechanisms by which fluoride toothpastes and rinses protect against carles. The efficacy of fluoride containing toothpastes and rinses to remineralize teeth 1s limited by the modest levels of calcium and phosphate 1n saliva. It 1s evident from the prior art that 1t 1s highly desirable to Increase the available concentration of calcium and phosphate 1ons 1n the oral cavity to speed up the remineralization process. However, because of calcium phosphate's low solubility at the pH of saliva the addition of higher levels of dissolved calcium and phosphate Ions 1s not easily accomplished. Remineralization of dental enamel has been carried out experimentally both in vivo and 1n vitro. Some studies have concentrated on the remlneral 1 zing properties of saliva and synthetic solutions supersaturated with respect of hydroxyapatlte. Sucn studies comprise the subject matter of U.S. Patent Nos. 3,679,360 (Rubin) and 4,097,935 (Jarcho). Generally, the supersaturated solutions or slurries used 1n these patents for remineralization experiments have been prepared from a single form of calcium phosphate. When a carious lesion 1s flooded with one of these supersaturated solutions, the calcium and phosphate 1ons 1n the form of precipitated hydroxyapatlte remineralize the lesion. However, these solutions are impractical for use for several reasons. First, the amount of calcium and phosphate ions available for remineralization 1n these supersaturated solutions 1s too low. It is reported that 1t takes approximately 10,000 unit volumes of the usual supersaturated solution to produce one unit volume of mineral. Thus, remineralization by this method requires both an excessive volume of fluid and an excessive number of applications. The supersaturated solutions are Inherently limited 1n this respect because they cannot maintain their supersaturated state. When the hydroxyapatlte precipitates out to the point where the solution 1s no longer supersaturated, new supersaturated solution must be Introduced or the remineralization process stops. Another problem with single calcium phosphate slurries 1s that as the hydroxyapatlte precipitates out of solution, the pH of the solution changes. Unless the old solution 1s removed from contact with the tooth material , the solution may become too acidic or alkaline and damage the dental tissue. U.S. Patent No. 4,080,440 (Dlglullo et al ) discloses a metastable solution of calcium and phosphate 1ons at a low pH (between 2.5 to 4.0) underwhlch conditions the solubility of calcium phosphate salts 1s high. After penetration of the solution Into dem1 neral 1zed enamel , remineralization results from the precipitation of calcium phosphate salts when the pH rises. Fluoride 1ons can be included 1n the metastable solution. A significant disadvantage of the use of metastable solutions 1s that the relatively low pH might demineralize the dental enamel and/or Injure other tissue. U.S. Patent Nos. 4,177,258, 4,183,915 and 4,348,381 (Gaffar et al ) provide for a re lneral 1z1ng solution containing supersaturated concentrations of calcium Ions, phosphate ions and a fluoride source stabilized by the presence of an antlnucl eating agent such as dlamine tetramethyl enephosphonlc add, ethyl enedlamine tetramethyl enephosphonlc add and 2-phosphonobutane-tricarboxyl 1c add-1,2,4, or the water-soluble salts thereof. This solution is preferably adjusted to the neutral pH range where 1t 1s alleged to most effectively remineralize sub-surface lesions. Even though the antlnucl eating agent would be expected to stabilize the solution, equilibrium of the supersaturated concentrations 1s still found difficult to maintain and avoid precipitation of hydroxyapatlte and changes 1n the pH of the sol ut1 on . U.S. Patent Nos. 4,083,955 (Grabenstetter et al ) and 4,397,837 (Raaf et al ) provide a process for remlneral 1 zing demlneral 1zed enamel by the consecutive treatment of tooth surfaces with separate solutions containing calcium Ions and phosphate Ions. In this process fluoride Ions may be present in the phosphate solutions. It is immaterial which 1on1c solution 1s used to treat the teeth first. By sequentially applying calcium and phosphate Ions to the tooth surface high concentrations of the Ions are able to penetrate into lesions 1n solution form, where they precipitate as a calcium phosphate salt when Ions from the second treatment solution diffuse 1n. While apparently successful this method Involves the Inconvenience of a plurality of sequential applications which can also be found to be time consuming. Thus, the problem with known remineralization compositions and techniques 1s that there 1s not a one-part, stable remlneral 1 zing composition that may be suitably prepared as a mouthwash or rinse and can be Incorporated into other dentifrice compositions such as a toothpaste or gel , troche, chewing gum, lozenge and the like. There 1s a need for a method of remlneral 1 zing dental enamel which employes a stable, single-part remlneral 1z1ng composition and does not require excessive amounts of solution and Inordinately long or frequent exposure times. It 1s the object of the present Invention to provide a single-part stable composition and process for the remineralization and the prevention of demlneral 1zat1 on of human teeth, which process and composition are capable of effectively incorporating calcium 1ons, phosphate Ions and fluoride Ions into the dental enamel , the composition also being easily usable by the consumer and not differing significantly, 1n flavor and appearance, from customary dental cosmetics . SUMMARY OF THE INVENTION In accordance with the present invention the problems of remineralization, without demlneral 1 zation are solved by applying to the teeth a stable, single-part composition which contains remineralization components which do not react with one another until Introduced Into the oral cavity. The composition contains at least one water-soluble caldum compound and at least one water-soluble Inorganic phosphate compound and, optionally, at least one water-soluble fluorine compound. In this way the 1ons which effect remineralization can be absorbed by the dental enamel and their subsequent reaction causes rehardenlng of demlneral 1 zed areas 1n the dental enamel . It has been found that effective remlneral 1 zing treatments can be prepared by providing non-aqueous solutions or preparations of soluble salts containing high concentrations of calcium, phosphate and, 1f desired, fluoride Ions and applying them to teeth at moderate pHs. However, the calcium ions must be prevented from reacting with the phosphate Ions or fluoride Ions until Immediately before use. In one embodiment of the invention, a non-aqueous toothpaste or gel Is provided comprising at least one water-soluble caldum salt, at least one water-soluble phosphate salt, 1f desired at least one water-soluble fluoride compound yielding fluoride Ions, and a hydrophilic, non-aqueous vehicle which 1s water soluble and wherein, when the composition 1s contacted with water, the resulting solution has a pH of between about 4.5 and 10.0. The stable, single-part system, in the form of toothpastes, gels, professional gels, i.e., those which are applied professionally or are obtained by a prescription, mouthwashes or rinses, troches, chewing gums, lozenges, and the like contain from about 0.05% to about 15% water-soluble calcium salt, from about 0.05% to 15% water-soluble phosphate salt, 1f desired from about 0.01% to 5.0% fl uorlde rel easing agent, and suitable pH adjusting compounds, I.e., adds or bases, such that the pH 1s between about 4.5 and 10.0, and preferrably between about 5.0 and 7.0. Compositions may be applied directly to the teeth and solubilized with saliva or are mixed with water, solubilized and Immediately applied to the teeth being treated. It has been found that such combinations produce rapid remineralization of lesions and are much more effective than conventional fluoride containing toothpastes 1n remi neral 1zing teeth. The stable, single-part system may also be 1n the form of a dry-mix concentrated product which may be diluted with water to prepare a mouthwash or otherwise treated or mixed to make other products. The dry-mix product may be 1n the form of a powder, granular material , flake, tablet or the like. This embodiment contains from about 1.0% to 80.0% of the caldum salt and the phosphate salt. Other adjuvants may, of course, be included. The compositions of the Invention give substantially improved remineralization and prevention of de i neral 1 zatlon of human teeth as compared with prior art compositions. The isadvantages of the prior art methods are overcome by the present Invention which effects subsurface remineralization rather than surface remineralization. Since dental carles begins as a subsurface demlneral 1zat1on of the dental enamel , subsurface remineralization arrests and repairs the carious lesion before any permanent structural damage to the tooth occurs. The present invention does not require preparation of the enamel surface, capping of the tooth, or removal of decay products. Further, the present invention may be conveniently practiced by the public without substantially changing their dental care habits. DESCRIPTION OF THE INVENTION The present Invention lies in the discovery that dental enamel may be re i neral 1 zed by the application of certain soluble salts yielding Ions which will react to form a desirable remlneral 1 zing precipitate. The crux of the Invention consists of the use of a stable, one-part system 1n the form of paste, gel , granules, powder, flakes, non-aqueous solution, etc, containing water-soluble salts which are placed in contact with the tooth surface. Saliva 1n the mouth causes dissolution of the soluble salts allowing the selected cations and anlons to diffuse through the tooth surface to the demlneral 1 zed subsurface with the cations and anlons forming a precipitate which 1s bound to the tooth structure. As a result, the tooth's subsurface 1s remlneral 1 zed when an effective amount of the remineralization system is ut111zed . As discussed above, the compositions of the Invention are preferably non-aqueous. By "non-aqueous" 1s meant that the compositions do not include water 1n such an amount that 1t will adversely affect the stability required by the remineralization composition of the invention, I.e., the components of the compositions of the invention do not contain significant quantities of free water. However, they may contain salts with water of hydratlon. Preferably, the compositions of the Invention Include either no water or only traces of water. By "effective amount of remlneral izlng system or agent" Is meant an amount when used 1n accordance with this Invention will bring about the remlneral 1 zing of teeth having carious lesions, or the mineralizing of normal teeth to prevent caries from forming and to Inhibit hypersensit1 v1ty by utilizing a toothpaste, gel , or mouthwash having the various components 1n the amounts set forth below. Concentrations of the soluble salt are from about 0.05 to 15% or the limit of solubility of the salt. Excess salt can be present, 1f desired. Concentrations from about 0.10% to 10% are preferred. The concentrations of the soluble salts containing the desired anlons are essentially the same as those for the water-soluble salts containing the desired cations . Although many precipitates are within the broad scope of this Invention, by depositing a precipitate less soluble than the original enamel , the remlneral 1 zed subsurface can be made to be more resistant to demlneral 1zat1on than was the original enamel. When a fluoride salt 1s utilized which yields fluoride 1ons, the remlneral 1 zed enamel is even more resistant to demlneral 1 zatl on than was the original enamel. The concentration of salt containing fluoride 1on 1n the solution may be from about 0.01% to 5.0%, but from about 0.02% to 2.0% 1s preferred. In order to effect remineralization of the dental enamel , an effective amount of the desired cations and anlons must be employed 1n the oral cavity. The amount of solution 1n the mouth must contain at least 100 ppm of desired cations and 100 ppm of desired anlons and preferably contains more than 1,000 ppm of desired cations and 1,000 ppm of desired anlons. It is preferred to provide a level of fluoride Ions between about 20 ppm to 5,000 ppm 1n the oral cavity from the dentifrice or professionally applied or prescribed gel . While the length of time of contact between the dissolved salts and the tooth's surface is not critical , 1t 1s necessary for the length of time to be great enough to allow diffusion of the Ions through the tooth's surface to the demlneral 1 zed subsurface. It is submitted that at least ten seconds 1s required for this diffusion and preferably it should be greater than thirty seconds and even longer 1f possible. After dissolving 1n the saliva the solution should have a pH of from about 4.5 to 10.0 and preferably between about 5.0 and 7.0 before and after the precipitation reaction, and be otherwise compatible 1n the oral environment. While some precipitation may occur upon sol ub1l 1 zation or upon application to the teeth, not all of the 1ons should combine prematurely 1n the solution to form a precipitate, but must be able to diffuse through the surface of the tooth to a demlneral 1 zed subsurface area and be able to form an Insoluble salt with their respective counterlons. The compositions utilized and the insoluble precipitates must have acceptable levels of toxlcity (i.e., the particular Ions, in the amounts used 1n the remineralization process, must be non-tox1c). In a preferred embodiment of the present Invention, the stable, one-part, non-aqueous remlneral 1 zing composition contains about 0.05% to 15%, preferably about 0.10% to 10% of a water-soluble caldum salt yielding calcium Ions, from about 0.05% to 15%, preferably about 0.10% to 10%, of a water-soluble phosphate salt yielding phosphate 1ons and from about 0.01% to 5.0%, preferably from about 0.02% to 2.0%, of a soluble fluoride salt yielding fluoride ions in a hyrophlllc, non-aqueous vehicle which 1s water-soluble. The pH of the composition 1n the oral cavity 1s between about 4.5 and 10.0, preferably between about 5.0 and 7.0. The resulting precipitate 1s a caldum phosphate or hydroxyapatlte, the natural constituent of tooth enamel , with incorporated fluoride 1ons. Not only does this process result 1n remlneral 1 zed enamel , but the remi neral 1 zed enamel may be more resistant to subsequent demlneral 1 zati on than was the original enamel . As the caldum compound 1t 1s, 1n principle, possible to employ, 1n the preparations of the Invention, all water-soluble toxicol oglcal 1 y harmless cal um compounds. A compound 1s considered to be water-soluble when at least 0.25 gram thereof dissolves 1n 100 ml of H2O at 20° C. Suitable water-soluble caldum compounds are, for example, caldum chloride, caldum bromide, caldum nitrate, caldum acetate, caldum gluconate, caldum benzoate, caldum glycerophosphate , cal um formate, caldum fumarate, calcium lactate, calcium butyrate and calcium Isobutyrate, calcium malate, calcium aleate, caldum proplonate, calcium valerate or mixtures of water-soluble caldum compounds. Calcium nitrate 1s preferred. In the compositions of the Invention for the remineralization of human dental enamel , at least about 100 ppm of caldum Ions should be present; the upper limit 1s about 35,000 ppm of cal d urn Ions . Suitable water-soluble Inorganic phosphates within the scope of the present invention are, for example, alkali salts and ammonium salts of orthophosphoric add, such as potassium, sodium or ammonium orthophosphate , monopotass 1 urn phosphate, dipotasslum phosphate, tripotasslu phosphate, monosodlum phosphate, disodium phosphate and trisodium phosphate. The concentration of the phosphate Ions 1s preferably about 100 ppm to 40,000 ppm; solubility 1n water 1s defined as 1n the case of the caldum compounds. If desired, water-soluble salts yielding both calcium and phosphate Ions, such as monobas 1 c-cal c 1um orthophosphate, may be employed. The compositions of the Invention for the remineralization or prevention of demi neral 1zat1 on of human teeth preferably also contain water-soluble fluoride compounds, the carles-prophylactic activity of which has for a long time been considered to be established. Suitable fluoride compounds are the alkali fluorides such as sodium, potassium, lithium or ammonium fluoride, tin fluoride, indium fluoride, zirconium fluoride, copper fluoride, nickel fluoride, palladium fluoride, fl uorozi rconates such as sodium, potassium or ammonium fl uorozi conate or tin fl uorozirconate , f1 uorosll 1 cates , f1 uoroborates , f1 uorostannites . Organic fluorides, such as the known amine fluorides are also suitable for use 1n the compositions of the Invention. Water-soluble alkali metal monofluor- ophosphates such as sodium monof1 uorophosphate , lithium monof1 uorophosphate and potassium monof1 uorophosphate , preferably, sodium monof1 uorophosphate may be employed. In addition other water-soluble monof1 uorophosphate salts may be employed Including ammonium moπofluoro- phosphate aluminum monof1 uorophosphate , and the Hke. Suitable hydrophilic, non-aqueous vehicles for use 1n the present Invention Include polyalkylene glycols, the humectant polyols such as glycerine, propylene glycol, dlpropylene glycol and hexylene glycol. Glycerin, propylene glycol and polyethylene glycol are preferred. As used herein, "propylene glycol" Includes 1 ,2-propyl ene glycol and 1 ,3-propyl ene glycol. For a mouthwash ethyl alcohol could also be used as a vehicle. Such a product would be added to water immediately before being used. Non-ionic surfactants could be used as the hydrophilic, non-aqueous vehicle 1n the toothpaste or gel composition of the Invention Include materials such as polyoxyethyl ene sorbitan fatty add esters. Pol yoxyethyl ene fatty add esters are also suitable for use as the vehicle in the compositions of the Invention. Another suitable class of non-1onic surfactants for use in the vehicle 1n the present Invention are polyoxyethyne fatty ethers. The hydrophilic, non-aqueous, water-soluble vehicles preferably provide a viscosity for the composition suitable for Its use as a toothpaste or gel, e.g., between about 50,000 cps. to 600,000 cps. If the selected vehicle does not Itself provide the desired viscosity, viscosity modifiers, and/or other vehicle agents can be Included to provide such desired viscosity. The use of higher molecular weight polyethylene glycol such as Carbowax 8000 1s one preferred means of Increasing the viscosity of a non-aqueous system. Other suitable thickening agents are water-soluble salts of cellulose ethers, such as sodium carboxymethyl cellulose, hydroxy methyl cellulose, hydroxypropyl cellulose, and hydroxyethyl cellulose. Natural gums such as gum karaya, gum arable, carrageenan and gum tragacanth, can also be used. Colloidal magnesium aluminum silicate, s111ca aerogels, silica xerogels, fumed silica, or other finely divided s11 lea can be used as part of the thickening agent for further Improved texture. Typically, hydrophilic, non-aqueous, water-soluble vehicles employed 1n the toothpaste or gel compositions of the Invention are present 1n an amount of from about 20% to 80%. Preferably, the vehicles are present 1n an amount of from about 30% to 70%. The amount of hydrophilic, non-aqueous, water-soluble vehicle employed 1n liquid formations, e.g., outhwashes, rinses, sprays, and the like 1s from about 50% to 95%. In addition to the remlneral 1 zing ingredients of the Invention, suitable non-aqueous toothpastes and gels can be made by employing 1n the toothpaste or gel , from about 0.5% to 50%, preferably from about 5% to 40%, of an abrasive, from about 0.2% to 5% of a sudsing agent, from about 0.1% to 5% of a binding agent, and the balance, hydrophilic, non-aqueous vehicle and minors, such as flavor, sweetner, coloring, etc. The pH of a of the toothpaste or gel containing the active catlonlc ingredients must have a pH of from about 4.5 to about 10.0 and, preferably, between about 5.0 and 7.0 when dissolved 1n saliva. Suitable abrasives Include s111 ca xerogels. Other conventional toothpaste abrasives can be used 1n the compositions of this invention, and Include beta-phase caldum pyrophosphate , dicalclum phosphate dlhydrate, anhydrous caldum phosphate, calcium carbonate, zironlum silicate, and thermosettlng polymerized resins. S111 ca aerogels and the Insoluble metaphosphates such as Insoluble sodium metaphosphate can be used. Mixtures of abrasives can be also be used. S111 ca xerogel abrasives are preferred. Suitable sudsing agents are those which are reasonably stable and form suds throughout the period of application. Preferably, non-soap anionic or nonionic organic synthetic detergents are employed. Examples of such agents are water-soluble salts of alkyl sulfate having from 10 to 18 carbon atoms 1n the alkyl radical , such as sodium lauryl sulfate, water-soluble salts of sulfonated monoglycerides of fatty acids having from 10 to 18 carbon atoms, such as sodium monoglyceride sulfonate, salts of C10-C18 fatty add amides of taurlne, such as sodium N-methyl taurate, salts of c 10~ c 18 fatty add esters of 1seth1onic add, and substantially saturated aliphatic acyl amides of saturated monoaminocarboxyl 1c adds having 2 to 6 carbon atoms, and 1n which the acyl radical contains 12 to 16 carbon atoms, such as sod1um-N-l auryl sarcoslde. Mixtures of two or more sudsing agents can be used. Toothpaste or gel compositions may also contain flavoring agents such as dl of wlntergreen, oil of pepperment, oil of spearmint, oil of sassafras, and oil of clove. Toothpaste or gel compositions may also contain sweetening agents such as saccharin, dextrose, levulose, sodium cyclamate, and aspartame Mixtures of sugar with a sweetner, e.g., sucralose, are contemplated. It 1s, of course, also possible to manufacture the dentifrice composition 1n the form of a transparent or translucent gel . This 1s accomplished by matching the refractive Index of the vehicle with the abrasives or Inorganic thickeners, 1f used. The non-aqueous remlneral 1 zing systems herein can also be provided 1n the form of a mouthwash or similar product e.g., a mouthrlnse product. The mouthwash can be made in accordance with the following. Mouthwashes generally comprise an alcohol , e.g., ethyl alcohol and flavoring materials. The alcohol provides an antibacterial effect, solubilizes the flavoring materials and provides a pleasant mouth feeling. Alcohol-free mouthwashes are now, however, gaining in popularity. An alcohol-free mouthwash would best be provided 1n the form of a dry powder or tablets which are added to water immediately before use. Such a product would contain 10 to 95% remlneral 1 zing salts and the balance would be flavors, sweeteners, and optionally antibacterial , efferveslng agents etc. Examples of suitable flavoring agents include hellotropyl nltrlle, wlntergreen oil (methyl salicylate), oil of peppermint, oil of assia, oil of anise, oil of cinnamon, and mixtures thereof. Suitable sweetening agents Include saccharin, glycerine, sorbltol , levulose, and 6-( tr1 bl uoro ethyl )-tryptophane and aspartyl phenyl al anlne methyl ester. It has been found that with the non-aqueous systems used 1n the present Invention some reaction between the caldum and phosphate Ions may, 1π fact, take place and cause some formation of Insoluble calcium phosphate, etc. during storage. The present Invention optionally overcomes this problem by Including suitable stabilizers which prevent reaction of the calcium Ions with the phosphate Ions and also with the fluoride 1ons 1f they are present. Any orally acceptable material that stabilizes one or more of the caldum, phosphate and/or fluoride salts during storage of the non-aqueous composition 1n a closed container can be employed 1n the present composition. Examples of suitable stabilizing agents include desslcatlng agents, coating or encapsulating materials and mixtures of such stabilizing agents . Examples of suitable desslcatlng agents Include magnesium sulfate, sodium sulfate, caldum sulfate, caldum chloride and colloidal silica, e.g., colloidal silica particles sintered together 1n chainlike formations having surface areas of from about 50 to about 400 square meters per gram such as materials sold under the trademark Cab-0-SH by Cabot Corp. It 1s believed that such materials act 1n stabilizing the compositions of the Invention by, for example, absorbing any existing water either present 1n or contacted with the composition so as to prevent reaction of the caldum, phosphate and/or fluoride salts. The stabilizing material 1s Included in the composition of the Invention in an amount effective so as to Inhibit reaction between the caldum, phosphate and/or fluoride salts in the composition during storage 1n a closed container, but so as to allow release of sufficient calcium phosphate and/or fluoride Ions when the composition 1s contacted with saliva, e.g., during brushing of teeth. Typically, the stabilizing material is included 1n the compositions of the present Invention in an amount of up to about 7.5%, preferably from about 0.1% to 5.0%. In an embodiment of this Invention there 1s provided a stable single-part non-aqueous dentifrice product for remi neral 1z1ng dental enamel comprising: (1) from about 0.05% to 15.0%, preferably about 0.10% to 10.0%, water-soluble cal um salt; (11) from about 0.05% to 15.0%, preferably about 0.10% to 10.0% water-soluble phosphate salt, optionally together with from about 0.01% to 10.0% and preferably from about 0.02% to 5.0% water-soluble fluoride salt, (111) from about 0 to 7.5% of an orally acceptable desslcatlng agent; and (1v) wherein when the salts are contacted with water or saliva the pH 1s between about 4.5 and 10.0 and preferably between about 5.0 and 7.0. Another method for Inhibiting premature reaction of the caldum, phosphate and/or fluoride salts in the dentifrice compositions of the present invention 1s to provide a coating on or encapsulation thereof, e.g., with an oleophilic or, preferably, a polymeric material , which prevents reaction between the active materials. The presence of the coating on the various salts 1n the compositions of the present Invention prevents reactions of the active material by other substances, for example, by traces of water in or absorbed Into the system. Preferably, the coating 1s an edible coating. Suitable encapsulating or coating materials include oleophilic and other materials such as conventional edible gums, polymers which exhibit proportion ranging from hydrophilic to hydrophobic (water-insoluble), resins, waxes and mineral oils. The coating 1s preferably rinsable from the mouth. In accordance with the Invention a polymer employed for coating the water-soluble caldum and/or phosphate salt particles and the like of the Invention 1s selected from hydrophilic organic polymers and hydrophobic (water-Insoluble) organic polymers and mixtures thereof. Polyvlnyl acetate is illustrative of a water-Insoluble polymer which can be Included as an additional coating component to moderate the hydrophil 1dty of a hydrophilic polymer coating. Suitable water- 1 nsol ubl e polymers, alone or 1n combination with one or more other components, for coating remlneral 1z1ng salt particles Include polyvlnyl acetate, polyacryl amide , polyvlnyl chloride, polystyrene, polyethylene, polyurethane , and the like. The application of the polymer coating to the blend of caldum, phosphate, and other salt particles of the Invention process 1s accomplished by conventional means such as pan coating, fluldized coating, centrifugal flu1d1zed coating, and the like. The coating polymer usually 1s dissolved in a suitable solvent such as water, methanol , ethanol , acetone, tetrahydrofuran , ethyl acetate, dimethyl formamlde , and the like, as appropriate for a selected polymer species. A coating polymer also can be applied 1n the form of an emulsion or suspension. After the coating medium 1s applied to the particles, the solvent medium 1s removed by evaporation, thereby forming a continuous film coating which encapsulates the discrete crystallite particles. The coating thickness on the surface of the salt typically will vary 1n the range between about 0.1-20 microns. The coating can consist of a single layer or multiple layers. The polymeric coating can constitute between about 5.0% to 50.0% of the total dry weight of the coated particles. For purposes of release of the core matrix remineral 1 zing cal um phosphate and, if desired, fluoride salts 1n the encapsulated particles when Introduced Into the aqueous environment, a surface coating of water- 1 nsol ubl e polymer of the oral cavity may have a content between about 5.0% to 30.0% weight percent of a partlculate water-extractabl e organic or Inorganic filler, such as sodium monosaccharlde or d1 saccharide , sorbltol powder, mannitol , and the like. The rate of release of remi neral 1z1ng salt core matrix content of the encapsulated particles under aqueous conditions can be controlled by the quantity and type of polymer coating on the particle surface. Low molecular weight hydrophilic polymers will release the particle core matrix content at a relatively fast rate 1n the presence of moisture. High molecular weight polymers which are less hydrophilic will release at a relatively slow rate. Additional rate control is obtained by employing mixtures of polymer components of varied hydrophi 11dty. Polyethylene glycol (M.W. of 4000) or polyvlnyl alcohol will release the particle core matrix content at a relatively fast rate. Polyethylene oxide (M.W. of 4,000,000) or partially hydrolyzed polyvlnyl acetate will release at a relatively slow rate. Polyvlnyl pyrrol 1done will release the particle core matrix content at an immediate rate, when the encapsulated particles Incorporated into a dentifrice, e.g., toothpaste or gel , are applied to the teeth. A present Invention encapsulated remi neral 1z1ng salt particle composition exhibits a unique combination of properties because of the novel physical form of the free-flowing, but substantially Inert, polymer-coated particles when utilized as an Ingredient 1n a dentifrice. Examples of suitable oleophilic coatings or enscapsul atlng materials Include paraffin, mineral oil , edible oils such as peanut oil, coconut oil , palm oil, or safflower oil, oleophilic organic esters such as isopropyl slloxaπe myrlstate or Isopropyl palmitate, edible polysl 1 oxanes , and the like. Encapsulating salts with a mixture of paraffin and waxes is also suitable. By employing mineral oil as an oleophilic coating material for the caldum, phosphate and/or fluoride salts 1n the compositions of the Invention, one other advantageous characteristic 1s provided. Specifically, oral bacteria known to be adversely affected by oleophilic materials. Thus, the mineral oil used 1n the compositions of the invention will help 1n removing undesired bacteria during the course of treatment. The coating should be of a thickness and composition so that 1t either readily dissolves, disperses or emulsifies 1n water, e.g., in the mouth during brushing, or disintegrates during such action to release the active materials, I.e., one or more salts. If the oleophilic material used for the coating 1s water insoluble, such as mineral oil , the coating phase can be pre-emul s1fled with a non-1onic, non-aqueous surfactant such as a hydrophilic ethoxylated sorbitan monooleate, e.g., the material sold under the trademark Tween. In this manner, when the composition 1s placed 1n water, the mineral oil or other olephilic coating on the particles 1s emulsified more readily than without the emul s1ficatlon agent being present. Other similar surfactants can be employed such as sodium lauryl sulfate and other non-ionic surfactants. In an embodiment of this Invention there 1s provided a stable single-part non-aqueous dentifrice product for remineral 1 zing dental enamel comprising: (1) from about 0.05% to 15.0%, preferably about 0.10% to 10.0%, water-soluble caldum salt; (11) from about 0.05% to 15.0%, preferably about 0.10% to 10.0% water-soluble phosphate salt, optionally together with from about 0.01% to 10.0% and preferably from about 0.02% to 5.0% water-soluble fluoride salt, (111) wherein there 1s an encapsulating coating on at least one of the water-soluble salts that either readily dissolves, disposes or emulsifies 1n water, e.g., saliva, and (1v) wherein when the salts are contacted with water and/or saliva the pH 1s between about 4.5 and 10.0 and preferably between about 5.0 and 7.0. In another embodiment of this Invention there is provided a stable, single-part non-aqueous product for remineralization which can be reconstituted into a mouthwash by addition of water or into other products from the concentrate-11 ke product. Accordingly the product comprises from about 1.0% to 80.0% of a caldum salt, from about 1.0% to 80.0% of a phosphate salt, from about 0.1% to 20.0% of a stabilizer comprising a material selected from at least one member of the group consisting of a desslcatlng agent and a coating of at least one of the water-soluble salts that either readily dissolves, disperses or emulsifies 1n water, from about 0.01% to 20.0% of a flavor, from about 0.01% to 30.% of a sweetener, from 0 to about 10.0% of a fluoride salt, from 0 to about 5.0% of a surfactant and wherein when the concentrate 1s mixed with water the pH of the resulting mixture 1s between about 4.5 and 10.0. In still another embodiment of this invention there 1s provided a stable single-part non-aqueous product for remlneral 1 zing dental enamel comprising: (1) from about 0.05% to 15.0%, preferably about 0.10% to 10%, water-soluble caldum salt; (11) from about 0.05% to 15.0%, preferably about 0.10% to 10% water-soluble phosphate salt, optionally together with from about 0.01% to 10.0% and preferably from about 0.02% to 5.0% fluoride releasing agent, (111 ) from about 0 to 7.5% of an orally acceptable desslcating agent; (1v) a hydrophilic, non-aqueous vehicle which is water-soluble and (v) wherein when the salts are contacted with water or saliva the pH 1s between about 4.5 and 10.0 and preferably between about 5.0 and 7.0. A plurality of packaging methods may be employed 1n order to contain or store the components and provide effective dispensing thereof Into the oral cavity. Thus, the components of a toothpaste, gel , cream, or the like, may be simultaneously dispensed from separate collapsible tubes preferably made of plastic, a plastic and metal laminate, etc. The tubes of the above embodiments are usually filled from the bottom and are subsequently sealed together by conventional techni ques. Another alternative packaging arrangement comprises of a pressurized container which 1s provided with a compartment and a spout. The internal pressure of the compartment is maintained by a pressurized gas, I.e., nitrogen, at the bottom of the compartment. Operation of a mechanical actuator actuates a valve which releases the contents of the compartment through the spout causing discharge of the paste or gel components onto a brush. The mouthwash or rinse and similar liquid embodiments are maintained 1n a manner similar to the pastes or gels 1n that during storage, each of the components are stabilized with regards to one another to prevent premature reaction. Upon dispensing, the components mix and react 1n the oral cavity to effect remineralization of dental enamel . The liquid components can therefore be stored 1n the compartment of a dispenser. The dispenser usually Includes a closure system comprising for example, an Inclined crown portion, a pouring spout extending upwardly from an upper surface of the crown portion and a cover for securement to the crown portion. The cover 1s provided with closure means, for example, depending plugs, to close the closure. The pouring spout 1s preferably provided with a vent opening 1n addition to a product orifice 1n the spouts. Transparent containers have proven to be the most satisfactory. Transparency aids a person's ability to accurately and controllably dispense relatively exact volumes from a dispenser. Transparent walled containers also serve as a window function for gauging the amounts of liquid remaining 1n the dispenser. The walls of the containers can be scribed or otherwise calibrated to assist in dispensing the correct remlneral 1 zing amount of product. While applicants do not wish the scope of the present invention to be limited by theory, 1t 1s believed that the caldum, phosphate, and fluoride ions diffuse through the tooth surface to the demlneral 1 zed subsurface and precipitate 1n the demlneral 1 zed subsurface where they remineralize the tooth structure. This 1s surprising because sufficient cal um, phosphate, and fluoride Ions remain soluble for a period of time sufficient to permit their diffusion into the demlneral 1 zed subsurface of the dental enamel . This 1s accomplished by allowing the product to mix with saliva when applied to the teeth or by combining the particular 1ons just prior to their application to the teeth in a solution having a pH of about 4.5 to 10 and preferably from about 5.0 to 7 at which pH enough of the caldum, phosphate, and fluoride ions remain soluble for the period of time required to remineralize the lesions of the dental enamel . As hereinbefore described, salts yielding the calcium Ions, phosphate Ions, and 1f desired, fluoride Ions are stored 1n a hydrophilic, non-aqueous vehicle and/or are stabilized against reaction to avoid the premature precipitation of caldum phosphate. Chemically equivalent concentrations are not necessary as long as the molar ratio of caldum and phosphate Ions 1n the mixture is from about 0.01 to up to 100 to 1. It 1s preferred that the ratio 1s from about 0.2 to 1 up to 5 to 1, and 1t is most preferred that the ratio is between about 1 to 1 and 1.67 to 1; the ratio of caldum to phosphate in Insoluble caldum phosphate salts. With regard to the length of time of exposure to the teeth of the solutions applied to, or formed 1n, the oral cavity 1t 1s necessary that the period of time be great enough to allow diffusion of the Ions into the demi neral 1 zed subsurface. At least about ten seconds are required for this diffusion. The paste, gel , or aqueous solution 1s preferably applied to the teeth for from about 10 seconds to about 5 minutes. The pH of the solution remains relatively constant after Its Introduction Into the oral cavity. Calcium phosphate may precipitate at this pH, but most surprisingly while some of the precipitation may occur Immediately and some small amount even before application to the teeth, sufficient calcium, phosphate and fluoride Ions remain 1n solution to diffuse Into the teeth and remineralize the demlneral 1 zed dental enamel . It 1s believed that the ability of the solutions to provide 1ons for remineralization 1s greatest upon their first Introduction into the oral cavity, thereafter decreasing. With a toothpaste, gel , and the like, mixing is achieved on the surface to the teeth while brushing and with a liquid non-aqueous mouthwash upon Introduction into the oral cavity. The essence of the present Invention lies with the stable, single part product; 1n the mixing of the product components in the mouth; and the quick and timely application of the resulting aqueous solution which will precipitate calcium phosphate, caldum fluoride, and calcium f1 uoro-apatl te 1n the subsurface enamel of the teeth. Before such precipitation occurs, the mixture comprising the aqueous solution must quickly be applied to the teeth. Surprisingly, the solution can have a pH of about 4.5 to 10, but preferably about 5.0 to 7 to achieve this result. At a pH below about 3, demlneral 1 zati on occurs rapidly. A pH below 2.5 1s generally undesirable from a safety standpoi nt . The pH of the solutions of the present Invention may be adjusted to the pH desired by methods well known 1n the art. The pH may be controlled by the addition of any add which 1s safe for use 1n the oral cavity and which yields the desired pH at the amount employed. Examples of suitable adds are acetic add, phosphoric add, hydrochloric add, citric add and malic add; by the addition of a base, for example, sodium hydroxide; or buffered, for example with sodium citrate benzoate, carbonate, or bicarbonate, disodium hydrogen phosphate, sodium dlhydrogen phosphate, etc. Preferably the remlneral 1 zing salts employed can be selected to obtain the desired pH. Usually a combination of monobasic, dibasic and/or trlbasic alkali metal phosphate salt 1s selected to provide the target pH. The following Examples Illustrate the Invention: In the Examples and elsewhere herein parts and percent are by weight unless otherwise stated . EXAMPLE 1 In this example a non-aqueous product for testing was prepared and mixed with water just previous to testing. The testing procedure was as follows: Artificial lesions, about 50 u deep, were formed 1n one surface of bovine enamel chips using a demlneral 1 zing Carbopol gel , which was used to treat the specimens for 72 hours. The surface hardness of the surface to be treated was then measured. The regimen cycle consisted of a 30 minute demlneral 1zat1on 1n a standard demlneral 1 zing solution followed by a 5 minute treatment of the test products diluted 1 part product to two parts human saliva, followed by a 60 minute remineralization 1n human saliva. Overnight, which was every fifth cycle, the specimens were kept with a layer of saliva and stored 1n a cold room. The test ran for three days, from a total of 15 demlneral Ization: treatment: remlneral ization cycles. For the treatment cycle, the remlneral 1 zing test agent of the example was diluted 1 part product to 2 parts saliva and mixed together Immediately before immersion of the enamel specimens. The non-aqueous oral remineral 1 zing test agent was prepared as follows: Caldum nitrate 4 Dlpotassium phosphate 8.00 Sodium fluoride 0.55 Glycerin 50 Acetic add To adjust pH of A & B mixture of 5.5 Immediately after mixing . The above product was then mixed with 137.45 parts of water to solubllize the salts and then was diluted with saliva as described above. HARDNESS INCREASE DUE TO TREATMENT (Vlckers Hardness Units) 1200 ppm Fl uorlde at Example 1 Crest PH 5.5 PI acebo cycles 17.0 + 1.9 11, 1.4 10 cycles 23.6 + 1.4 13, 3.6 13.7 + 2.3 3.9 + 0.7 15 cycles 34.8 + 2.8 11, 1.7 20 cycles 48.2 + 2.8 17.5 2.2 FLUORIDE INCREASE DUE TO TREATMENT (ug/cm3 ) 1200 ppm Fluoride at Example 1 Crest pH 5.5 PI acebo 5 cycles 2433 1879 10 cycles 3523 2082 2928 244 15 cycles 4431 2196 20 cycles 4749 2964 The results show much greater remineralization, as measured by hardness increase and fluoride uptake, due to treatment with the product of Example 1 than Crest, fluoride solution or pi acebo. EXAMPLES 2. 3. 4 and 5 Examples 2-5 Illustrate various embodiments of remlneral 1z1ng toothpaste formulation of the Invention as follows: Exam le Glycerin Carbowax 400 Propylene glycol Silica abrasive Silica thickener DCPDH* Caldum chloride Cal um glycerophosphate Disodium phosphate Sodium meta-phosphate Sodium lauryl sulfate Sodium fluoride Stannous fluoride Sodium MFP Flavor Saccharin 0.20 0.20 0.30 0.20 ♦ DCPDH * Dlcalciu phosphate dihydrate Example 6 Illustrates an embodiment of a remlnerali zing mouthwash formulation and Example 7 Illustrates a dry-mix concentrate suitable for dilution as follows: Example 7 Glycerin Ethanol Sodium MFP Cal um nitrate 50 Monopotasslum phosphate 41.725 Sodium fluoride 0.275 Spray dried flavor 5.0 Asparta e 3.0 Example 7 is diluted 5g to 100 g water before use. EXAMPLES 8-11 Example 8-11 Illustrate dry-mix concentrated formulations which can be diluted with water when they are to be employed. Example I I IP. li Caldum lactate pentahydrate 59.7 Caldum acetate anhydrous 40.0 Caldum gluconate Encapsulated* cal um nitrate 97% Magnesium chloride Monopotassiu phosphate 30.0 Dlpotasslum phosphate Monosodlum phosphate Disodium phosphate Sodium fluoride 0.3 Stannous fluoride Sodium MFP Flavor 6.0 Saccharin 3.0 Asparta e 20.0 ♦ Caclium nitrate encapsulated with water soluble ethyl cellulose encapsulent Usage Concentration 1.0 g 0.75 g 1.2 g 0.42g per oz per oz per oz per oz Examples 12-14 each illustrate a formulation which can be employed as an efferevercent mouthwash when dilutent with water. Example 12 11 14 Cal um acetate anhydrous 30.0 Encapsulated* cal um nitrate 97% 26.0 36.0 Monopotasslum phosphate 20.0 28.0 30.0 Malic add 16.0 17.0 11.0 Magnesium chloride 5.0 Sodium bicarbonate 10.0 15.0 10.0 Sodium fluoride 2.0 2.0 Flavor 6.0 5.5 4.0 Saccharin 4.5 2.0 Aspartame 20.0 ♦ Cal um nitrate encapsulated with water soluble ethyl cellulose encapsulent Usage Concentration 5.0 g 4.0 g 5.0 g per oz per oz per oz

Claims: WHAT IS CLAIMED IS: 1. A stable, single part, non-aqueous, dry-mix product which may be diluted with water to form an aqueous product for remineral 1 zing lesions in teeth comprising: (I) from about 1.0% to 80.0% of at least one water-soluble caldum salt; (II) from about 1.0% to 80.0% of at least one water-soluble phosphate salt; and (III) a stabilizer comprising a material selected from at least one member of the group consisting of from about 0.1% to 20.0% of a desslcatlng agent and a coating on at least one of the water-soluble salts that either readily dissolves, disperses or emulsifies 1n water; (1v) wherein when the components are diluted the pH of the aqueous product 1s between about 4.5 and 10.0. 2. The product according to claim 1 wherein the product contains up to about 10.0% of at least one water-soluble fluoride salt which yields fluoride Ions. 3. The product according to claim 1 wherein the product contains from about 0.10% to 20.0% of a flavor. 4. The product according to claim 1 wherein the product contains from about 0.10% to 30.0% of a sweetner. 5. The product according to claim 1 wherein the product contains up to about 5.0% of a surfactant. 6. The product according to claim 1 wherein the pH of the mixture is from about 5.0 to 7.0 upon diluting. 7. The product according to claim 1 wherein said product 1s 1n the form of a powder, granular material , flake, or tablet. 8. A stable, single part, non-aqueous product for remlneral 1 zing lesions 1n teeth compri s1 ng : (I) from about 0.05% to 15.0% of at least one water-soluble caldum salt; (II) from about 0.05% to 15.0% of at least one water-soluble phosphate salt; and (III) a stabilizer comprising a material selected from at least one member of the group consisting of up to about 7.5% of a desslcatlng agent and a coating on at least one of the water-soluble salts that either readily dissolves, disperses or emulsifies 1n water; (iv) wherein when the components are mixed with water or saliva the pH of the mixture 1s between about 4.5 and 10.0. 9. The product according to claim 8 wherein the product contains from about 0.01% to 5.0% of at least one water-soluble fluoride salt which yields fluoride ions. 10. The product according to claim 8 wherein the product contains from about 0.10% to 10.0% of said caldum salt. 11. The product according to claim 8 wherein the product contains from about 0.10% to 10.0% of said phosphate salts. 12. The product according to claim 11 wherein the product contains from about 0.02% to 2.0% of said fluoride salt. 13. The product according to claim 8 wherein the pH of the mixture 1s from about 5.0 to 7.0 upon mixing . 14. The product according to claim 8 wherein the molar ratio of caldum and phosphate Ions 1n the two components is from about 0.01 to 1 up to 100.0 to 1. 15. The product according to claim 14 wherein the molar ratio of caldum and phosphate Ions 1n the two components 1s from about 0.2 to 1 up to 5.0 to 1. 16. The product according to claim 8 wherein said product is 1n the form of a powder, granular material , flake, or tablet. 17. The product according to claim 8 wherein the said product contains from about 100 ppm to 35,000 ppm caldum Ions and from about 100 ppm to 40,000 ppm phosphate Ions. 18. The product according to claim 8 wherein said product contains from about 20 ppm to 5,000 ppm fluoride ions. 19. A stable, single part, non-aqueous product for remi neral 1 zing lesions 1π teeth compri sing : (I) from about 0.05% to 15.0% of at least one water-soluble calcium salt; (II ) from about 0.05% to 15.0% of at least one water-soluble phosphate salt; (III) a hydrophilic, non-aqueous vehicle which 1s water-soluble; and (1v) wherein when the salts are contacted with water or saliva the pH of the mixture 1s between about 4.5 and 10.0. 20. The product according to claim 19 wherein said product contains from about 0.01% to 5.0% of at least one water-soluble fluoride salt which yields fluoride Ions. 21. The product according to claim 19 wherein the product contains from about 0.10% to 10.0% of said caldum salt. 22. The product according to claim 19 wherein the product contains from about 0.10% to 10.0% of said phosphate salt. 23. The product according to claim 22 wherein the product contains from about 0.02% to 2.0% of said fluoride salt. 24. The product according to claim 19 wherein the pH of the mixture 1s from about 5.0 to 7.0 upon mixing the two components. 25. The product according to claim 19 wherein the molar ratio of caldum and phosphate Ions is from about 0.01 to 1 up to 100.0 to 1. 26. The product according to claim 25 wherein the molar ratio of caldum and phosphate Ions 1s from about 0.02 to to 1 up to 5.0 to 1. 27. The product according to claim 19 wherein the product 1s a non-aqueous paste, a gel or a professional gel . 28. The product according to claim 19 wherein the product 1s a non-aqueous liquid mouthwash or rinse. 29. The product according to claim 19 wherein the product contains from about 100 ppm to 35,000 ppm caldum Ions and from about 100 ppm to 40,000 ppm phosphate Ions. 30. The product according to claim 19 whererin the product contains from about 20 ppm to 5,000 ppm fluoride Ions. 31. A method for remlneral 1 zing lesions 1n teeth comprising: (1) applying to the teeth a stable, single part, non-aqueous composition comprising from about 0.05% to 15.0% of at least one water-soluble calcium salt; from about 0.05% to 15.0% of at least one water-soluble phosphate salt; and a stabilizer comprising of a material selected from at least one member of the group consisting of up to about 7.5% of a desslcatlng agent and a coating on at least one of the water- soluble salts that either readily dissolves, disperses or emulsifies 1n water (II ) contacting the composition with an aqueous solvent for the salts comprised of water or saliva wherein the resulting mixture has a pH of from about 4.5 to 10.0; and (III) applying said mixture as an aqueous solution to the teeth for a sufficient time that the caldum and phosphate ions from each of the salts diffuse Into the subsurface of demi neral i zed enamel and subsequently precipitate to form hydroxyapatlte and remineralize the dental enamel. 32. The method according to claim 31 wherein the product 1s 1n the form of a powder, granular material, flake, or tablet. 33. The method according to claim 31 wherein the product contains a hydrophilic, non-aqueous vehicle which is water-soluble. 34. The method according to claim 33 wherein the product applied to the teeth 1s a non-aqueous paste, a gel , or a professional gel and 1s extruded onto a toothbrush. 35. The method according to claim 31 wherein the product applied to the teeth 1s a non-aqueous mouthwash or rinse. 36. The method according to claim 31 wherein the period of application of caldum and phosphate Ions to the teeth 1s from about 10 seconds up to 15 minutes. 37. The method according to claim 31 wherein the product contains from about 0.10% to 10.0% of said caldum salt. 38. The method according to claim 31 wherein the product contains from about 0.10% to 10.0% of said phosphate salt. 39. The product according to claim 31 wherein the product contains from about 0.01% to 4.0% of at least one water-soluble fluoride salt which yields fluoride ions. 40. The method according to claim 39 wherein the product contains from about 0.02% to 2.0% of said water-soluble fluoride salt. 41. The method according to claim 31 wherein the resulting dissolved product has a pH of from about 5.0 to 7.0. 42. The method according to claim 31 wherein the molar ratio of calcium and phosphate ions 1s from about 0.01 to 1 up to 100.0 to 1. 43. The method according to claim 42 wherein the molar ratio of caldum and phosphate Ions 1s from about 0.2 to 1 up to 5.0 to 1. 44. The method according to claim 31 wherein the product contains from about 100 ppm to 35,000 ppm caldum Ions and from about 100 ppm to 40,000 ppm phosphate Ions. 45. The method according to claim 31 wherein the product contain from about 20 ppm to 5,000 ppm fluoride ions.

Inventors: USEN NORMAN, WINSTON ANTHONY E, USEN, NORMAN, WINSTON, ANTHONY, E.
Applicants: ENAMELON INC, USEN NORMAN, WINSTON ANTHONY E, ENAMELON, INC., USEN, NORMAN, WINSTON, ANTHONY, E.
Application year: 1996
Main classification: A61K7
IPC codes: A61K8, A61Q11