MXPA99003759A - COMPOSITIONS TO CONTROL ORAL MICROBIAL OXIDATION-REDUCTION (Eh - Google Patents

Abstract

The present invention relates to an oral composition containing a zinc compound containing free available zinc ion and at least one stabilized or stable Eh raising compound distributed in an oral vehicle. The present invention further relates to a method of inhibiting the formation of sulfur containing anions and preventing a reduction in the Eh of the oral cavity. A method of reducing oral malodor and gingivitis and periodontitis is also provided by this invention.

Description

COMPOSITIONS TO CONTROL OXIDATION-REDUCTION (Eh) MICROBIAL ORAL LEVELS FIELD OF THE INVENTION The present invention provides oral compositions comprising a zinc compound containing free available zinc and at least one compound arising from stabilized or stable Eh distributed in an oral vehicle. The present invention is further directed to a method for inhibiting the formation of anionic sulfur species in the oral cavity and preventing the reduction of Eh from the oral cavity. A method to simultaneously reduce oral malodor, gingivitis and periodontitis by preventing or reducing oral putrefaction is also provided by this method. BACKGROUND OF THE INVENTION The hard and soft tissues of the mouth are covered with microbial populations that contain bacteria with different metabolic capacities. Gram-positive bacteria within these microbial populations readily catabolize carbohydrates to produce acids that attack the hard tissues of the oral cavity, resulting in the formation of dental caries lesions (cavities). In contrast, Gram-negative bacteria, especially anaerobes, readily metabolize several amino acids contained in saliva (and to a lesser degree than others) peptides and proteins in the oral cavity to form final products that favor the formation of bad odor and oral periodontitis. This process of the degradation of peptides, proteins and amino acids by oral bacteria is termed as oral bacterial putrefaction. The mixture of malodorous compounds produced by Gram-negative anaerobic bacteria during the degradation of putrefaction of proteins, peptides and amino acids, includes hydrogen sulfide, methyl mercaptan and dimethyl sulfide (formed of the sulfur containing the amino acids, cysteine, cystine and methionine); indole and skatole (formed during the metabolism of tryptophan); cadaverine and putrescine (produced from Usina and ornithine); and buti while and valerate (produced from the metabolism of other amino acids). The production of these malodour compounds in the oral cavity results in a condition commonly referred to as oral malodor. Hydrogen sulfide, methyl mercaptan, butyrate and propionate are final putrefaction products that also have cells and tissues that alter non-inflammatory roles in the periodontitis process. Methyl hydrogen sulfide and mercaptan are particularly effective compounds to facilitate the penetration capacity of oral toxins and other high molecular weight compounds produced by Gram negative bacteria to the oral epithelium and which leads to the characteristics of inflammation and degradation of gingivitis tissue. and periodontitis. Gingivitis is a condition in which the gingiva is red, swollen and bleeds. If left untreated, gingivitis can develop into periodontitis, a condition characterized by destruction of the periodontium, including loss of epithelial junction, destruction of membrane and periodontal ligaments, and loss of gingiva and alveolar bone. Severe periodontitis that results in deep periodontal pockets can eventually result in tooth loss. Previous studies have focused largely on the use of germicidal agents to treat gingivitis-periodontitis and oral malodor. Up to the findings of the present invention, previous studies had not recognized that gingivitis-periodontitis and oral malodor arise from a common process, oral bacterial putrefaction; also that this putrefaction can be inhibited by simultaneously decreasing the oral bacteria's ability to reduce the oxidation-reduction (Eh) potential of the oral cavity and at the same time, elevate the existing Eh to where the ambient environmental Eh environment does not lead to oral putrefaction and the production of oral disease. The metabolism and development of anaerobic bacteria in the oral cavity is favored when the Eh is decreased. The present invention has discovered that the oxidation-reduction potential (Eh) is a key regulatory factor in oral bacterial putrefaction. The decrease in Eh of the oral cavity has been found to occur in two steps, an oxygen suppression followed by the generation of electron-rich compounds. The present invention has discovered from studies on the isolation and catabolism by oral bacteria of nitrogenous substrates in human saliva that the main compounds responsible for the decrease of the Eh of the oral cavity are anions containing non-volatile sulfur derived in large part of cysteine and cystine (Table 1). These include the species of anionic sulfur, sulfur (S =), hydrogen sulfide (HS ") and methyl mercaptan (CH3S '). These anions favor the ecological environment for the reduction (lower Eh) that allows the anaerobic bacteria Gram Negative in the mouth, develop, which are involved in putrefaction and produce compounds rich in electrons leading to, and maintaining a prolonged decrease in the Eh of the oral cavity and the undesirable conditions of bad odor, gingivitis and periodontitis. lower favors the process of oral bacterial putrefaction while a higher Eh is inhibitory.

Table 1. Lower Eh reached with common amino acids when incubated with bacteria mixed in salivary sediment Eh (milivolts) Amino Acids Group A Group B Group C alanine 100 arginine 25 asparagine 70 aspartic acid 80 cysteine 20 cystine -10 glutamine 30 glutamine 100 histidine 70 isoleucine 115 leucine 110 95 methionine 95 ornithine 55 phenylalanine 100 proline 100 serine 115 threonine 110 tryptophan 85 tyrosine 40 valine 105 salivary supernatant -25; water control 142 The present invention provides compounds that simultaneously inhibit (i) the formation of these electron-rich compounds and thus prevent the Eh from decreasing to harmful levels and (ii) reacting with electron-rich compounds formed and neutralizing them thus , raise the Eh to safer levels, it has surprisingly been discovered according to the present invention that an oral composition containing a zinc compound capable of providing available free zinc and a stabilized or stable Eh raising compound can effectively prevent the decrease of Eh. This is crucial to avoid oral bacterial putrefaction, the metabolic processes that are the basis and which results in the development of oral malodor and gingivitis-periodontitis. The compounds of zinc, hydrogen peroxide and chlorine dioxide have each been used as therapeutic agents in oral compositions to destroy harmful bacteria implicated in oral malodor and gingivitis-periodontitis formation. Previous studies where zinc has been identified as having antimicrobial and anti-plaque effects have not made a distinction between zinc compounds where zinc is freely available and where it is not. (See for example, U.S. Patent No. 4,289,755 to Dhabhar). The zinc species is an important element of this invention, since the available free zinc (zinc ion) within the oral cavity is required to inhibit the Eh capacity of a pathogenic microbiota of putrefaction. The zinc compounds used in the described previously described compositions wherein zinc is not freely available. Zinc that binds or forms complexes with various ligands and zinc species that have a low solubility and form precipitates prevents that reaction with the enzymes that decrease the Eh and the products produced by the putrefactive microbiota and therefore are poorly adequate for the purposes of this invention.

The solubility of zinc compounds varies as shown in the following table. Sol ubil ida d of selected zinc compounds Soluble Formula Compound (g / 1 00 cc) chlorine of zi nc ZnCl2 432 @ 25 ° C zinc citrate Zn3 (C6H5O7) 2 l slightly sun. zinc acetate Zn (C2H3O3) 2 30 @ 20 ° C zinc lactate Zn (C2H5O3) 2 5.7 @ 1 5 ° C zinc salicylate Zn (C7H6O3) 2 5 @ 20 ° C zinc sulfate ZnSO soluble zi nc oxide ZnO 0.00016 @ 29 ° C zinc nitrate ZnNO3) 2 infinitely soluble Data are from Handbook of Chemistry and Physics, Chemical R ubber Company, 67th Edition CRC Press, Boca Raton, Florida, 1986-87.

It is evident from this table that the amount of zinc that will be soluble and will be available in the oral cavity to control the pathogenic microbiota will vary considerably. Zinc compounds that provide low levels of zinc ions in solution, such as zinc oxide, are not suitable for the present invention. This distinction between the different zinc compounds was not recognized before this invention. In essence, in order to inhibit Eh from decreasing to harmful levels, it is essential that zinc ions are freely available. Previous studies have also identified hydrogen peroxide and chlorine dioxide as germicidal agents. Chlorine dioxide is usually derived from the chlorite ion. Hydrogen peroxide owes its germicidal activity to the release of oxygen and the formation of free radicals which provide chemical and mechanical mechanisms to kill anaerobic oral bacteria and clean wounds and remove tissue and other debris from inaccessible areas (such as between the teeth ). The release of oxygen from hydrogen peroxide is particularly pronounced in the presence of catalase, organic matter, metals and metal compositions. In this invention, this is inhibited by the use of chlorine ion, so that the peroxide will serve as a compound to raise the Eh rather than as a germicidal agent. The Patents of E. U.A. Nos. 5, 104, 644, 5, 174, 990 and 5,310,546 of Douglas, describe the use of hydrogen peroxide as a germicidal agent. Specifically in the oral composition described by Douglas, hydrogen peroxide releases molecular oxygen in the presence of catalase and tissue peroxidase to act against oral anaerobic bacteria. Previous studies do not stabilize hydrogen peroxide so it does not decompose. The oral composition described herein acts as a compound to raise the Eh from one that results in the formation of decomposition products. In this invention, the degradation of these species is prevented to produce a germicidal effect. The hydrogen peroxide in the composition described herein is stabilized using chloride ion, an acid pH and avoiding mixing thereof with the zinc ion until just before use. Chlorine dioxide is an oxyhalogen compound widely used in the industry to disinfect and control bacterial biofouling. It is also used to control the taste, odor, oxidation of metal ions and the removal of color in other applications. Several studies have described the use of chlorine dioxide as an antimicrobial agent in mouthwash applications. For example, the Patent of E. U .A. No. 4,696,81 1 of Ratcliff discloses a method and composition for destroying compounds that form smelling sticks; Patent No. U K 2290233A by Drayson and Butcher discloses compositions for whitening teeth. Others include inventions wherein the oxidation and germicidal capacities of chlorine dioxide are activated by forming chlorine dioxide just before use. The main reason that chlorine dioxide is generated in this way, is because chlorine dioxide is an unstable gas at room temperature (boiling point of 1 1 ° C) and is sensitive to decomposition by visible and ultraviolet light. In previous studies, chlorine dioxide is commonly generated from the chloride ion by acidification. Usually, it is provided as regulated sodium chlorite at a pH of about 7 to 8 and more, and as such, it is referred to as stabilized chlorine dioxide (U.S. Patent Nos. 4,689,215 and 4,837,009 to Ratcliff, Patent No. UK 2290233A by Drayson and Butcher and Patent No. WO 95/27472 by Richter). The dioxide similar to previous hydrogen peroxide is usually generated in order to kill oral bacteria. When chlorite acidification is carried out, the levels of chlorine dioxide produced are usually adequate for their germicidal purpose. But in compositions where chlorine dioxide is stabilized as sodium chlorite at a neutral or alkaline pH. Chlorine dioxide chlorite formation is a relatively slow process. Consequently, very little chlorine dioxide is available within the oral cavity as an antibacterial agent in these compositions. In contrast, in the present compositions, chlorite ions are not used as germicidal agents. Instead they are used as effective and stable Eh c lifting compounds, if their degradation to chlorine dioxide is prevented. In previous inventions, the use of chlorite ions involves provision (instead of removal) of electrons to allow the disproportionation of chlorite ion and formation of the bacteriocidal compound, chlorine dioxide, a process stimulated by the addition of acid. The oxidation-reduction change involves the change in the oxidation state from +3 to +4. On the other hand, when the chlorite acts as a compound that raises the Eh as in the present invention, its oxidation state decreases from +3 to -1. The reduction of chlorite ions to chloride ions after undergoing a series of reactions involving several intermediaries. What is evident from this analysis is that the chlorite ion is able to act as an oxidation or reduction agent depending on the reaction conditions. A few compounds show such effects of redox regulatory solution in multiple steps and therefore atypical. However, it is allowed to take into account or resist together with the zinc ion the kinds of changes in the level of Eh to allow rot to flower and be suitable for this invention. The use of sodium chlorite used as a compound to raise Eh rather than as a source of chlorine dioxide, is very important, since chlorine dioxide at high levels combine with certain amino acids to produce compounds that are potentially mutagenic. Therefore, the inhibition or prevention of significant chlorine dioxide formation from sodium chlorite is convenient and is preferred and is contraindicated if sodium chlorite is used to generate large amounts of chlorine dioxide therefrom with the chlorite. order to kill enough bacteria to have significant oral effects. A neutral and higher pH is essential for chlorite ion stability and to avoid the formation of chlorine dioxide. Also, the chloride ion is useful for the additional stabilization of sodium chlorite where there is a decrease in pH. This is because the chloride ion is produced when the chlorine becomes chlorous acid and disproportionation of the chlorous acid occurs. 5HCIO2? 4CIO2 + CI '+ H + + 2 H2O This reaction is inhibited by the massive action when chloride ion is supplied. Hydrogen peroxide such as sodium chlorite behaves as a compound to raise the Eh in that it also reacts easily as an oxidizing or reducing agent. An analogue to the chlorine dioxide / chlorite / chloride system is the molecular oxygen / hydrogen peroxide / water system wherein the chlorite ion and hydrogen peroxide are similarly placed as oxidation-reduction intermediates. In previous studies, peroxide is used to generate oxygen and / or reactive species with oxygen to kill oral bacteria involved in oral disease. As it is found for the chlorite ion, e! The peroxide in this invention functions as a compound for raising the Eh by removing the excess electrons from putrefaction and producing hydroxyl ions instead of supplying electrons and undergoing disproportionation as in the previous patents. The disproportionation reaction of hydrogen peroxide 2H2O2? 2H2O2 + O2 It is very slow under ordinary conditions but rapid in the presence of enzymes, catalase and peroxidase, found in certain bacteria in the oral cavity. Again, hydrogen peroxide is a species such as chlorite ion that is thermodynamically unstable with respect to disproportionation and can function as an intermediate in oxidation-reduction reactions. In addition and again, the chloride ion inhibits the disproportionation of hydrogen peroxide but does so through the inhibition of catalase. The only oxygen-oxygen ligature in hydrogen peroxide in one of the weakest covalent bonds known. It breaks easily indicating that it readily accepts electrons and as a result, is capable of producing hydroxyl ions. Alternatively, the hydrogen peroxide is converted to the stable oxygen molecule. It has been shown in previous studies, that hydrogen peroxide marked with O18, that the oxygen produced is derived entirely from the peroxide species and not from the water. This suggests that the decomposition of peroxide does not involve the decomposition of the O-O bond but rather it provides electrons to an appropriate oxidizing agent. When H2O2 is used as a compound to raise the Eh, it is not used as a source for molecular oxygen. Recent studies by Douglas (Patents Nos. 5, 104,644, 5, 174, 990 and 5, 310, 546) have described oral compositions that combine zinc chloride and hydrogen peroxide to treat gingivitis-periodontitis. The Patent of E. U.A. No. 5, 174,990, describes a mouthwash containing zinc chloride and hydrogen peroxide. In these Douglas patents, it is necessary to take into account the instability before using the described formulations, which is caused in large part by the presence of the zinc metal. To help stabilize zinc, ligands are added to bind zinc well such as citrate and lauryl sulfate. However, these additions reduce the capacity of the free zinc, especially when these ligands are present at high ligand to zinc ratios. The mouth rinses in Patents Nos. 5, 174, 990 and 5, 310, 546, have a concentration of zinc chloride ranging from 0.005% to 0.1% and a concentration of hydrogen peroxide ranging from 0.25% to 0.65% . In the absence of ligands that bind to zinc, the zinc ion, in these zinc chloride levels, varies in concentration between 0.002% and 0.047%. In addition, recent studies have shown that hydrogen peroxide at the concentrations described herein is degraded by oral bacterial catalase and is not effective in vivo. Ryan and Kleinberg (1995) Archs. oral, Biol., 40, 753-763. Consequently, in order to decompensate the rapid decomposition of hydrogen peroxide by catalase, it is necessary to use higher concentrations of hydrogen peroxide (1% or greater). At concentrations of hydrogen peroxide above 3.0 to 3.5%, studies have shown that hydrogen peroxide can damage the soft tissues of the oral cavity. Therefore, for an oral composition containing hydrogen peroxide to be effective as a therapeutic and at the same time not to damage the soft or hard tissues of the oral cavity or to be harmful if ingested, its concentration needs to be between approximately 1% and 3% . In contrast, the oral compositions disclosed in this invention contain sufficient chloride ions to inhibit the hydrolysis of catalase from the peroxide, thus allowing the peroxide to remain intact even at lower levels of 1% peroxide and for the peroxide to serve as a compound for raise the Eh where the formation of toxic products from the peroxide is avoided. Many reactions involve hydrogen peroxide in solution, resulting in the production of free radical species, such as HO2 and OH. These are effective agents to kill bacteria and such formation is a basis for the use of hydrogen peroxide as a disinfectant. The decomposition catalyzed by transition metal ions of hydrogen peroxide can easily cause the formation of free radicals. The destabilizing effects of zinc are avoided in this invention using a two-compartment approach where the combination with the zinc compound is provided just before use to ensure maximum availability of the free zinc. The compositions described herein result in a synergism between the zinc ions, the peroxide used as a compound for raising Eh and the chloride ions. This two-compartment system is a more convenient and more effective approach than the oral compositions described previously. Methylene blue has been used as a compound to raise Eh. It easily accepts electrons and in this way helps to avoid the accumulation of electrons that produces lower Eh, which favors oral putrefaction. In the Patent of E. U.A. No. 5, 087,451 of Wilson and Harvery, methylene blue is used to inhibit periodontitis. The beneficial effect of methylene blue alone is significantly less than that achieved when used in conjunction with zinc ions as with the compositions of this invention. SUMMARY OF THE INVENTION The present invention is directed to oral compositions containing a zinc compound wherein the zinc ion is freely available and at least one stabilized or stable Eh raising compound is distributed in an oral vehicle. In one embodiment, the oral compositions contain a zinc compound containing freely available zinc ions, hydrogen peroxide and a compound containing chloride ions. In another embodiment, the composition contains a compound of zinc ions and an oxyhalogen compound. A further embodiment of this invention includes an oral composition containing a compound of zinc ions and methylene blue. The present invention is further directed to a method for inhibiting the formation of the anionic sulfur species and therefore preventing a decrease in the Eh of the oral cavity. Specifically, the method comprises delivering to the oral cavity a therapeutically effective amount of an oral composition containing a free available zinc compound and at least one stabilized or stable Eh elevation compound distributed in an oral vehicle. A further embodiment of the present invention is a method for reducing both oral malodor and gingivitis-periodontitis comprising supplying in the oral cavity a therapeutically effective amount of an oral composition containing a zinc ion compound and at least one compound that elevates stabilized or stable Eh. BRE VE DESCRIPTION OF THE INVENTION Figure 1 shows the relationship between the concentration of zinc ions and the rate at which oral bacteria are capable of producing volatile sulfur compounds and associated sulfur anions from cysteine. The inhibition is exponential and occurs as maximum once the concentration of zinc ion reaches approximately 0.2%. Figure 2, shows changes in Eh during an incubation of mixed oral bacteria and (i) salivary supernatant (ii) glucose (iii) salivary supernatant and glucose (iv) a water control. Figure 3 shows the changes in Eh during an incubation of mixture of oral bacteria and the salivary supernatant with (i) zinc chloride (ii) hydrogen peroxide and (iii) zinc chloride ion plus hydrogen peroxide. A control incubation containing oral bacteria mixed with salivary supernatant is also shown. Hydrogen peroxide itself loses some of its ability to inhibit the decrease in Eh due to the degradation of hydrogen peroxide by bacterial catalase during incubation. Figure 4 shows the mean Eh, odor index, level of volatile sulfur compound (CAV) and the level of indole / skatole produced in the samples formed at intervals over a period of 4 hours after rinsing with a mouthwash that They contain zinc chloride (0.08%), hydrogen peroxide (1%) and NaCl (2.9%). The CAV levels were measured with an instrument called Halimetro. Figure 5 shows the concentration of volatile sulfur compounds and Eh in vivo showing the elevation of cysteine (CAV and Eh responses) before and after a mouth rinse containing zinc chloride at 6 mM (0.08%). Figure 6 shows the concentration of volatile sulfur compounds and Eh in vivo after rinsing in cysteine (CAV and Eh responses) before and after a mouth rinse containing zinc chloride at 6 mM (0.08%), peroxide of hydrogen at 1% and sodium chloride at 500 mM (2.9%). Figure 7 shows the concentration of volatile sulfur compounds and the Eh in vivo after rinsing with cysteine (CAV and Eh responses) before and after a mouth rinse containing 0.5% sodium chlorite. Figure 8 shows the concentration of volatile sulfur compounds in vivo after rinsing with cysteine (CAV and Eh responses) before and after a mouth rinse containing 0.1% sodium chlorite. Figure 9 shows the concentration of volatile sulfur compounds in vivo after rinsing with cysteine (CAV and Eh responses) before and after a mouth rinse containing 0.1% sodium chlorite and 6 mM zinc chloride ( 0.08%). DETAILED DESCRIPTION OF THE INVENTION The essential components and their relevant proportions in the compositions of the invention are shown below. All patents, publications and test methods mentioned herein are incorporated herein by reference.

The present invention relates to an oral composition containing a zinc ion compound wherein a high concentration of available free zinc and at least one Eh rinse compound distributed in the oral vehicle is provided. A zinc ion compound as defined by the present invention is a compound of freely available zinc ions capable of inhibiting the decrease of Eh in the oral cavity. In this regard, it is important to inhibit the decomposition of cysteine or cystine from saliva, mucosal tissues (especially from the tongue) and food by oral bacteria. The freely available zinc ions are not bound. The zinc compounds present in the oral compositions of this invention include, for example, zinc chloride, zinc acetate, zinc lactate, zinc salicylate, zinc sulfate and zinc nitrate. In one embodiment of the present invention, the zinc compound is zinc chloride. The concentration of zinc ion in the oral composition can vary from about 0.02% to 0.2%. In a preferred embodiment, the concentration of zinc ion ranges from about 0.04% to about 0.12%. A stabilized Eh raising compound as defined herein is a compound capable of directly or indirectly elevating Eh from the oral cavity. Examples of compounds for raising Eh include, for example, hydrogen peroxide, oxyhalogen species such as sodium chlorite, and biologically compatible oxidation-reduction (redox) regulatory solutions such as methylene blue. Additional examples of compounds for raising Eh include fermentable common sugars such as glucose, galactose, fructose, maltose, lactose and sucrose. These compounds when metabolized by oral bacteria and in particular, oral streptococci, in the presence of oxygen produce, among other things, hydrogen peroxide. The concentration of the compound for raising Eh in the compounds of this invention may vary from about 0.1% to about 3.0% by weight of the composition. In a preferred embodiment, the concentration of the compound to raise the Eh is from about 0.1% to about 1.0%. When the compound for raising the Eh is hydrogen peroxide or a fermentable sugar, a compound containing chlorine ion is added to the oral composition in an amount sufficient to inhibit catalase in the oral cavity from the decomposition of hydrogen peroxide. The compound containing chlorine ions is a compound capable of inhibiting catalase activity in the oral cavity. Compounds containing the suitable chloride ion include alkali metal chloride salts and alkaline earth metal chloride salts such as, for example, NaCl and CaCl 2. In general, the concentration of the chloride ion-containing compound in the oral composition ranges from about 0.5% to about 2.5% by weight of the composition. Since some oral microbiota produce hydrogen peroxide in the presence of fermentable sugars, chloride ions are added to make it more effective. In one embodiment of this invention the zinc compound is zinc chloride, the compound for raising the Eh is hydrogen peroxide and the compound containing chloride ions is sodium chloride. In another embodiment of this invention, the oral composition containing zinc chloride, a fermentable sugar and sodium chloride. In a further embodiment of this invention, the oral composition contains zinc chloride and sodium chlorite oxyhalogen species and with or without sodium chloride. A further embodiment of the present invention consists of oral compositions containing zinc chloride and methylene blue with or without sodium chloride. We have discovered that the pH of the oral compositions of the present invention was specified for the zinc compound and the combination of Eh compounds used. When the compound to raise Eh is hydrogen peroxide, the preferred pH of the oral compositions generally ranges from about 3.0 to about 6.0. In one embodiment, the pH varies from about 3.5 to about 4.5. An acid pH has two convenient effects. First, an acidic pH ensures the availability of zinc ion since the zinc ion above a pH of about 6.0 is combined with the hydroxyl ions in solution to form poorly soluble zinc hydroxide, thus forming an unavailable zinc ion. Second, an acidic pH converts the sulfur anions to the acid forms that result in a higher Eh. In the case of hydrogen sulfide, because hydrogen sulfide is volatile, its formation serves as an effective means to mount the electrons carried by the sulfide ion that lead particularly to the decrease of Eh. Third, degradation of catalase from hydrogen peroxide is inhibited at an acidic pH. An acidic pH and the presence of chloride ion, ensures that the hydrogen peroxide in the composition does not degrade with storage and thus retains its effectiveness. On the other hand, when the compound of elevation of Eh is the oxychloride, sodium chlorite, a pH between about 3.0 and 6.0 is not suitable for the stability of sodium chlorite during storage. At acid pH, unstable and less convenient chlorine dioxide is produced. To be used for the purposes of this invention, the pH of sodium chlorite during storage needs to be between about 7.0 and about 8.5 where it is more stable. The instability of the zinc ion at a pH of 6.0 above the instability at a pH of about 6.0 and below it, necessitates that the two remain separated in a two-compartment system until ready to be used. When contacted with one another immediately before being used in admixture, the preferred pH is between about 5.5 and about 6.0. The addition of the chloride ion as sodium chloride and / or as part of zinc chloride provides stability along with synergistic activity. The pH of the oral compositions described herein can be controlled with acids such as hydrochloric and benzoic acid and with the base such as sodium hydroxide. In addition to the composition of zinc-peroxide-chloride ions, the zinc-oxyhalogen composition and the zinc-methylene blue composition, the oral compositions described according to the present invention may contain any conventional ingredient for the particular oral composition. . For example, liquid mouth rinses may contain a solvent such as distilled or deionized water and ethanol; a sweetening agent such as sorbitol, mannitol, xylitol, saccharin and aspartame; and a flavoring agent such as peppermint oil and spearmint oil. (See Patents of E. U.A. Nos. 4,226,851, 4,209, 754; 4, 289,755, and 5, 104, 644). Because the formulation difficulties associated with the instability of zinc ions at about 6.0 resulting from the formation of poorly soluble zinc hydroxide and the instabilities of many Eh-raising compounds such as sodium chlorite and hydrogen peroxide, the two compartment systems wherein the zinc ion compound and the Eh elevation compound are in respective compartments but can be mixed immediately before use are preferred. An example of a two-compartment composition for zinc chloride and sodium chlorite is shown in Table 2. The dentifrices may contain, for example, a conventional abrasive such as calcium pyrophosphate, aluminum hydroxide, resins, alkali metal metaphosphate. insoluble and silica in a normal amount of 20-60% by weight; a binder such as hydroxyethyl cellulose, xanthine gum and sodium carboxymethyl cellulose in a normal amount of 0.5-5.0% by weight; a foaming agent such as sodium lauryl sulfate, coconut sodium sodium monoglyceride sulfonate-N-methyl-N-palmitoyl tauride in a normal amount of 0.5-3.0% by weight; a flavoring agent; a sweetening agent, an antiseptic agent and any other ingredient required for the particular formulation. (See Patent of E. U.A. No. 5, 372, 802). Two-compartment supply systems are preferred. The tablets and powders may contain, for example, a carrier such as lactose or mannitol; a binder such as corn starch or carboxymethyl cellulose; and a disintegrator, once again in two-compartment supply systems. The present invention is also directed to a method for inhibiting the formation of sulfur-containing anions in the oral cavity and preventing a decrease in the Eh of the oral cavity by supplying it in the oral cavity with a therapeutically effective amount of an oral composition containing a compound of zinc ion and at least one compound to elevate the Eh distributed in an oral vehicle. As defined by the present invention, sulfur-containing anions include, for example, sulfur (S =), hydrogen sulfide anion (HS ") and methyl mercaptan anion (CH3S"). A therapeutically effective amount of the oral composition is an amount sufficient to inhibit the formation of sulfur-containing anions and prevent a decrease in the Eh of the oral cavity. For example, a therapeutically effective amount of the oral composition in a dentifrice or mouthwash may vary from about 0.5% to about 5% by weight and preferably from 2% to 3% by weight of the composition. Acceptable oral vehicles include, for example, any conventional oral delivery system, such as dental care products, food products and chewing gum. Examples of dental care products include, for example, dentifrices, topical solutions or pastes, mouth rinses in the form of liquids, powders, gels or tablets and dental threads. Examples of food products containing the oral compositions described herein include, for example, troches and sweets. The present invention is further directed to a method for reducing oral malodor, gingivitis and periodontitis by delivering in the oral cavity a therapeutically effective amount of an oral composition containing a zinc ion compound and at least one Eh elevation compound. distributed in an acceptable oral vehicle. As defined by the present invention, a therapeutically effective amount of an oral composition is an amount sufficient to raise the Eh of the oral cavity to normal levels and prevent or reduce oral malodor., gingivitis and periodontitis. A therapeutically effective amount of the oral composition is an amount sufficient to reduce or prevent the formation of malodor producing compounds such as hydrogen sulfide and the growth of harmful gram-positive anaerobic bacteria that gingivitis and periodontitis can cause. A therapeutically effective amount of the oral composition in a dentifrice or mouthwash may range from about 0.5% to about 5% by weight and preferably from about 2% to about 3% by weight of the composition. The present invention further provides an article of manufacture comprising a packaging material and the oral compositions described herein contained within the packaging material, wherein the oral composition is effective to prevent and / or reduce any decrease in Eh, oral putrefaction and development of bad odor, gingivitis and periodontitis and where the packaging material contains a label indicating that said oral composition is effective to elevate the Eh, and reduce oral putrefaction, oral malodor, gingivitis and periodontitis. The packaging material used to contain the oral compositions may contain glass, plastic, metal or any other suitable inert material. For example, a dentifrice containing the oral composition of the present invention can be contained in a collapsible tube, usually aluminum, lined lead or plastic or a squeezable, pumping or pressurized dispenser for measuring the contents or in a tearable bag. In order to illustrate the present invention, the experiments described in the following examples were carried out. It should be understood that the invention is not limited to the specific examples or the details described herein. The results obtained from the experiments described in the examples are shown in the table and annexed figures. Example / This Example demonstrates the ability of the salivary supernatant to decrease Eh and the ability of glucose to act as a compound to raise Eh in order to raise the Eh in the salivary sediment system model is developed by Kleinberg (1967 and 1970) Archs. oral Biol., 72: 1457- 1473; Advances oral Biol. (Volume 4) New York, NY Academic Press pages. 49-50 (See Figure 2). This model uses the mixed oral bacteria collected in the salivary sediment obtained from all the saliva by centrifugation. Extensive studies have shown that this system behaves metabolically like dental plaque (Singer et al., (1983) Archs oral Biol. 28: 29-35; Wijeyeweera and Kleinberg (1989 a and b) Archives oral Biol. 40: 743- 752). This model is recognized in the art as an effective model to study the microbial and related metabolic biochemical processes of the oral cavity. The ability of the different available amino acids of salivary peptides and proteins to decrease Eh in the salivary sediment system is shown in Table 1. To collect the salivary sediment and the salivary supernatant for analysis, the saliva stimulated by chewing paraffin wax was It was expelled in test tubes cooled in crushed ice. The donors had not brushed their teeth for 24 hours before collection. Donors were also fasted for at least 13 hours before providing full stimulated saliva containing a minimum level of endogenous carbohydrate (Kleinberg and Jenkins (1964) Arch. Oral Biol., 9: 493-516). After recovery, the saliva was centrifuged at 1740 X g for 15 minutes and the supernatant was subsequently removed by pipette and kept on ice until the analysis was carried out. Next, the pellet was washed three times with distilled water cooled in ice to remove any residual salivary supernatant. The washed salivary sediment was cooled in crushed ice until the analysis was carried out. Before incubating the samples and carrying out the analysis, the washed salivary sediment was re-suspended in distilled water at a final concentration of 50 percent (V / V). To analyze the capacity of several amino acids and salivary supernatant in order to produce a decrease in Eh, the incubation tubes were prepared containing the following: 16.7% (V / V) of salivary sediment, 60 mM of phosphate buffer and 33.3% (V / V) salivary supernatant or 3 mM amino acids. A control tube contained sediment and water. All preparations of the incubation mixture were made with the test tubes cooled in crushed ice until they were transferred to a water bath for incubation at 37 ° C for 24 hours. Measurements were taken in the following time intervals: 0 and 30 minutes and 1, 2, 3, 8 and 24 hours.

The oxidation-reduction potential (Eh) was determined in each incubation mixture using a platinum electrode and a potassium chloride salt source leading to a calomel reference electrode connected to a pH meter used as a millivoltimeter. All measurements of Eh were related to the normal hydrogen electrode adding the value of 242 millivolts to the reading made with this electronic system. The lowest Eh reached with each amino acid is shown in Table 1. The corresponding Eh levels achieved with the salivary supernatant and the water control are shown in the lower part of the table. The Eh with supernatant decreases Eh lower and only, is equated by the amino acid, cystine. From the different amino acids tested, the amino acids containing sulfur, cystine, cysteine and methionine (Group C) showed lower E h; arginine, glutamic, ornithine and tyrosine (Group B) showed the following lower Eh; and the rest (Group A) showed higher Eh levels. The salivary supernatant fractionation experiments identified small peptides with cysteine as the constituent responsible mainly for decreasing the lower Eh activity of salivary supernatant. Example // A similar type of in vitro experiment as in Example 1 was carried out to analyze the capacity of (i) zinc chloride, (ii) hydrogen peroxide and (iii) zinc chloride and hydrogen peroxide, for avoid a fall in the Eh of the oral cavity. Incubation tubes were prepared containing 16.7% sediment, 60 mM phosphate buffer solution, and (i) zinc chloride at a concentration of 6.0 mM (0.08%), (ii) hydrogen peroxide at a concentration of 0.5% or (iii) zinc chloride at a concentration of 6.0 mM and hydrogen peroxide at a concentration of 0.5%. A tube containing salivary sediment and salivary supernatant alone (water control) was prepared. Figure 2 shows the Eh of the mixtures during the incubation at 37 ° C for a time of 24 hours. As shown in Figure 3, zinc chloride and hydrogen peroxide alone, or in combination, significantly raised the Eh of the incubation mixture compared to the salivary supernatant plus the salivary sediment control. The control incubation mixture containing only sediment and supernatant showed a rapid and extensive decrease in Eh. The incubation mixtures with zinc chloride alone and hydroxyl peroxide alone, showed some decrease in Eh. Hydrogen peroxide only progressively loses some of its capacity to reduce Eh since chloride was present, unlike zinc chloride, which inhibits its degradation by catalase. When zinc chloride and hydrogen peroxide were combined in the incubation, only a slight decrease in Eh occurred. The results in this example demonstrated the ability of a composition containing zinc chloride and hydrogen peroxide to reduce the decrease in Eh and thus reduce oral putrefaction that leads to the development of bad odor, gingivitis and periodontitis. Example J I ± This example shows the ability of the zinc ion peroxide-chloride ion compositions of the present invention to retard or reduce the ability of the oral bacteria to lower the Eh and their ability to produce a foul odor. As shown in Example I I, hydrogen peroxide may have an inhibitory effect on odor production by the mixed bacteria comprising the microflora of the salivary sediment system. However, it will be difficult for the peroxide to persist in this system or in the dento-gingival or in situ tongue since its microfloras contain bacteria that exceptionally have high activities of catalase and peroxidase. (Ryan and Kleinberg (1995) Archives oral Biol. 40: 743-752). Consequently, for the peroxide to be effective in the mouth, it is necessary to inhibit this catalase activity. Otherwise, peroxide levels above 1% may be necessary to produce oral malodor and its concentration may be harmful to oral soft tissues. An agent currently documented to be inhibitor of catalase activity is chloride ion. This analysis examined the effects to rise with a combination of ZnCI2, H202 and NaCl in the Eh and the activity to produce odor of the oral bacterium. The oral rinse consisted of ZnCI2 at 6 mM (0.08%), NaCl at 500 mM (2.9%) and H202 at 1%.

The oral rinse was tested for its effects to decrease En and the odor-forming activity of oral bacteria. The oral malodor formation was evaluated organoleptically, measuring CAV using a Halimetro (Model RH-17A Interscan Portable Analyzer) and measuring the indole / skatole formation using the Kovac method. Gadebusch H. and Gabriel S. (1956) "Modified Stable Kovac's Reagent for the Detection of Idol", Amer. J. Clin. Path. 26., 1373-1375. Organoleptic measurements were made by having a trained individual return the odor produced and the odor regime on a scale of 0-4, zero indicating no odor and four indicating a strong odor. In the Kovac method, Kovac reagent (P-Dimethylaminobenzaldehyde dissolved in amyl alcohol and acidified with HCl) was added for each test sample and the bluish / red color was measured at 567 nm in a spectrophotometer. The experiments were carried out on subjects who fasted and who did not have oral hygiene during the last 12 hours. The test began between approximately 9 a. m. and 10 a. m. For the sample of the base line, the subject expelled saliva from the mouth by a moderate expectoration and rested for 2 minutes to allow the collection of fresh saliva. This saliva was then placed in an ice-cooled test tube. If the saliva recovered was less than 750 ml, an additional period of 2 minutes was used for recovery. After collection of the base line, the subject rinsed his mouth with 5 ml of test solution for 20 seconds and collected a saliva sample as before. Harvesting once again stronger for a period of 2 minutes. Saliva samples were also collected in different types up to four hours after rinsing. 750 ml of each saliva sample were immediately incubated in a water bath at 37 ° C and Eh, odor index and volatile sulfur compounds (CAV) in each sample were determined at 0, 15 and 30 minutes and at 1, 2, 3, 4, 8 and 24 hours; these values were averaged to give an analysis of average values of each parameter in each sample. The subjects were tested on three different days. Day one was without the use of a rinse, day two with an aqueous rinse and day three with a rinse of zinc-peroxide-chloride ions. Figure 4 shows the results after rinsing zinc-hydrogen peroxide-chloride ions. As shown by this figure, the zinc-hydrogen peroxide-chloride ion composition of the present invention favored a more positive Eh level and its effect on odor was dramatic. The production of organoleptically determined odor and by indole / skatole formation was almost completely retarded and CAV production was significantly reduced. The new change of the base line (LB) was observed when the water was the rinsing solution or rinsing was not performed. The oral composition of the present invention affected the Eh positively and suppressed the odor parameters even after 4 hours after the rinse. Only the indole / skatole formation started to return after 4 hours. These results demonstrate the ability of the oral compositions described herein to reduce oral malodor by preventing the ability of oral bacteria to reduce Eh from the oral cavity. Example IV The ability of a zinc chloride rinsing solution to reduce or prevent the formation of volatile sulfur compounds (CAV) in vivo after successive confrontations with a cysteine rinse was studied in this Example. The rinse solution consisted of zinc chloride at 6 mM (0.08%). The experiments were carried out on subjects who fasted and did not perform oral hygiene for at least 12 hours. The subject rinsed his mouth with 5 ml of a 6 mM solution of cysteine for 30 seconds to stimulate substantial CAV production by oral bacteria. This test is analogous to the use of glucose as a comparison substrate to determine the glycol activity of dental plaque bacteria (Stephan, R. M. 1944. J. dent Res. 23, 257) or ingestion of a fixed amount of glucose as a comparison by analyzing the activity of diabetes. Before and after rinsing, a Halimetro instrument was used to measure the volatile sulfur compounds (CAV) produced. Simultaneously, a platinum electrode was placed on the posterior dorsal surface of the tongue, just before the circumvallating papillae to measure Eh. After 20 minutes, the subject rinsed his mouth in 5 ml of zinc chloride solution for 30 seconds. Again, the air CAVs of the subject's mouth and the Eh were measured. The subject was then rinsed successively with 6 mM of the cysteine solution at 40, 60, 140, 320 and 380 minutes and the CAV and Eh of the subject's oral cavity were re-measured each time (see Figure 5) using the Halometer and the platinum electrode. As shown in Figure 5, zinc chloride rinsing reduced the ability of oral bacteria to produce the CAV response to cysteine rinsing and to slow the production of the CAV response to subsequent cysteine rinses for approximately 5 hours after. The same figure also shows the response of Eh that occurs coincidently with the response of CAV after the confrontation with cysteine. The Eh rose to a small degree during rinsing with the zinc chloride solution. The elimination of cysteine by saliva and the rapid use of cysteine by oral bacteria facilitates the removal of cysteine and the return of CAV to its respective base line during each episode of confrontation with cysteine. As demonstrated by this in vivo analysis, zinc chloride is a compound that is capable of reducing the ability of oral bacteria to generate volatile sulfur compounds. This contributes to the activity of reduced oral putrefaction and in turn to the production of reduced oral malodor and gingivitis-periodontitis. EXAMPLE V The ability of the zinc-hydrogen peroxide-salt composition to reduce or prevent the formation of CAV in vivo after successive confrontations with a cysteine rinse was studied in this Example in the same manner as in Example IV. The oral rinse consisted of zinc chloride at 6 mM (0.08%), hydrogen peroxide at 1% and sodium chloride at 500 mM (2.9%). As before, 5 mL of the zinc / peroxide / chloride ion composition of this invention was applied as a rinse for 30 seconds. Measurements of CAV and Eh were also carried out as before and the results are shown in Figure 6. The zinc-peroxide-chloride ions rinse of this invention showed greater inhibition of CAV production and for a longer time than in Example IV zinc chloride without peroxide and chloride ion was tested. The Eh rose strongly and more than with the chloride-peroxide-sodium chloride composition after its application than with the zinc chloride alone in Example IV and the subsequent Eh responses were initially inhibited and the return to the response of the base line was delayed. This example shows that the oral composition of the present invention can significantly inhibit CAV production of cysteine and its ability to decrease Eh and has the ability to raise Eh when introduced in vivo. EXAMPLE VI The ability of the zinc-chloride-sodium chlorite composition to reduce or prevent the formation of CAV in vivo after successive confrontations with a cysteine rinse was studied in this Example in the same manner as in Examples IV and V. The oral rinse consisted of zinc chloride at 6 mM (0.08%) and sodium chlorite at 0.5%. As before, 5 ml of the zinc / peroxide / chloride ion composition of this invention was applied as a rinse for 30 seconds. The CAV and Eh measurements were also carried out as before and the results are shown in Figure 7. The zinc chloride-zinc chlorite rinse of this invention was shown as in Example V, greater inhibition of CAV production and for a longer time than in Example IV where zinc chloride was tested without sodium chlorite. The Eh rose strongly and more with the zinc chloride-sodium chlorite composition after its application than with the zinc chloride alone in Example IV; Subsequent Eh responses were initially inhibited and the return to the base line response was delayed. This example shows that the oral composition of the present invention can significantly inhibit the production of CAV of cysteine and its ability to decrease Eh and has the ability to raise the Eh by introducing it into the oral cavity. Example VII The capabilities of rinsing solutions of 0.1% sodium chlorite, one sin and one with sodium chloride at 6 mM (0.08%) were compared in this Example for their ability to reduce or prevent the formation of CAV in vivo after of successive confrontations with a cysteine rinse as before. The oral rinse consists of the application of 5 ml for 30 seconds of 0.1% sodium chlorite solution or 0.1% sodium chlorite solution to which 0.08% zinc chloride was added. Measurements of CAV and Eh were carried out as before and the results are shown in Figures 8 and 9. Sodium chlorite showed no inhibition of CAV production (Figure 8) while the zinc chloride-chlorite combination sodium was inhibitory and more than that observed for zinc chloride alone (Figure 5) in Example IV. This Example shows that combining the zinc chloride and sodium chlorite can produce an effect greater than the expected effect of the simple addition of their individual effects.

Claims (39)

1. REVIVAL DICATIONS 1. An oral composition comprising a zinc compound containing freely available zinc ions, wherein the concentration of freely available zinc ions ranges from about 0.02% to about 0.2% and at least one stabilized Eh elevation compound, in where the concentration of the Eh elevation compound varies from about 0.1% to about 3.0%, distributed in an oral vehicle, wherein the zinc compound and the Eh elevation compound are stored separately and mixed before use the oral composition.
2. 2. The oral composition of claim 1, wherein the concentration of freely available zinc ranges from 0.04% to about 0.12% by weight.
3. 3. The oral composition of claim 1, wherein the concentration of the elevation compound ranges from about 0.1% to about 1.0% by weight.
4. The oral composition of claim 2, wherein the zinc compound containing freely available zinc ions is selected from the group consisting of zinc chloride, zinc sulfate, zinc acetate, zinc lactate, zinc salicylate and nitrate of zinc.
5. The oral composition of claim 1, wherein the elevation compound of Eh is selected from the group consisting of hydrogen peroxide, oxyhalogen, methylene blue and sodium chloride.
6. 6. The oral composition of claim 1, wherein e! zinc compound is zinc chloride and the Eh raising compound is hydrogen peroxide and the composition further comprises a chloride ion compound, wherein the concentration of chloride ions ranges from about 0.5% to about 2.5% by weight.
7. The oral composition of claim 6, wherein the pH of the zinc compound during storage ranges from about 3.0 to about 6.0 and the pH of the hydrogen peroxide during storage ranges from about 3.0 to about 6.0.
8. 8. The oral composition of claim 6, wherein the chloride ion compound is sodium chloride.
9. The oral composition of claim 1, wherein the zinc compound is zinc chloride and the compound of elevation of Hey, it's sodium chlorite.
10. The oral composition of claim 9, wherein the pH of the zinc compound during storage ranges from about 3.0 to about 6.0 and the pH of the sodium chlorite during storage ranges from about 7.0 to about 8.5. eleven .
11. The composition of claim 10, wherein the composition further comprises a chloride ion compound.
12. 12. The oral composition of claim 1, wherein the chloride ion compound is sodium chloride.
13. 13. The oral composition of claim 1, wherein the oral composition is a product for dental care, food products, troches, chewing gum or candy.
14. A method for inhibiting the formation of sulfur-containing anions in the oral cavity and preventing the decrease in the Eh of the cavity by delivering a therapeutically effective amount of an oral composition comprising a zinc compound containing zinc ions into the oral cavity. freely available having a concentration ranging from 0.02% to about 0.2% and at least one stabilized Eh elevation compound, wherein the concentration of the Eh elevation compound ranges from about 0.1% to about 3.0%, distributed in an oral vehicle, wherein the zinc compound and the Eh elevation compound are stored separately and mixed before using the oral composition.
15. 15. The method of claim 14, wherein the concentration of freely available zinc ion ranges from 0.04% to about 0.12% by weight.
16. 16. The method of claim 14, wherein the concentration of the elevation compound of Eh ranges from about 0.1% to about 1.0% by weight.
17. The method of claim 14, wherein the freely available zinc containing compound is selected from the group consisting of zinc chloride, zinc sulfate, zinc acetate, zinc lactate, zinc salicylate and zinc nitrate.
18. 18. The method of claim 14, wherein the elevation compound of Eh is selected from the group consisting of hydrogen peroxide, oxyhalogen, methylene blue and sodium chloride.
19. 19. The method of claim 14, wherein the zinc compound is zinc chloride and the elevation compound of Eh is hydrogen peroxide and the composition further comprises a chloride ion compound, wherein the concentration of chloride ions varies from about 0.5% to about 2.5% by weight.
20. The method of claim 19, wherein the pH of the zinc compound during storage ranges from about 3.0 to about 6.0 and the pH of the hydrogen peroxide during storage ranges from about 3.0 to about 6.0. twenty-one .
21. The method of claim 19, wherein the chloride ion compound is sodium chloride.
22. 22. The method of claim 14, wherein the zinc compound is zinc chloride and the elevation compound of Eh is sodium chlorite.
23. The method of claim 22, wherein the pH of the zinc compound during storage ranges from about 3.0 to about 6.0 and the pH of the sodium chlorite during storage ranges from about 7.0 to about 8.5.
24. 24. The method of claim 23, wherein the composition further comprises a chloride ion compound.
25. 25. The method of claim 24, wherein the chloride ion compound is sodium chloride.
26. 26. The method of claim 14, wherein the oral composition is a product for dental care, food products, troscos, chewing gum or candy.
27. 27. A method for reducing odor and gingivitis-periodontitis delivered in the oral cavity a therapeutically effective amount of an oral composition comprising a zinc compound containing freely available zinc ions having a concentration ranging from about 0.02% to 0.2% and at least one stabilized Eh elevation compound, wherein the concentration of the Eh elevation compound varies from about 0.1% to about 3.0%, distributed in an oral vehicle, wherein the zinc compound and the compound Eh elevation is stored separately and mixed before use to the oral composition.
28. 28. The method according to claim 27, wherein the concentration of freely available zinc ion ranges from 0.04% to about 0.12% by weight.
29. 29. The method according to claim 27, wherein the concentration of the Eh elevation compound ranges from about 0.1% to about 1.0% by weight.
30. 30. The method according to claim 27, wherein the freely available zinc containing compound is selected from the group consisting of zinc chloride, zinc sulfate, zinc acetate, zinc lactate, zinc salicylate and zinc nitrate.
31. 31 The method according to claim 27, wherein the elevation compound of Eh is selected from the group consisting of hydrogen peroxide, oxyhalogen, methylene blue and sodium chloride.
32. 32. The method according to claim 27, wherein the zinc compound is zinc chloride and the elevation compound of Eh is hydrogen peroxide and the composition further comprises a compound of chloride ions, wherein the concentration of chloride ions it varies from about 0.5% to about 2.5% by weight.
33. The method according to claim 27, wherein the pH of the zinc compound during storage ranges from about 3.0 to about 6.0 and the pH of the hydrogen peroxide during storage ranges from about 3.0 to about 6.0.
34. 34. The method according to claim 32, wherein the chloride ion compound is sodium chloride.
35. 35. The method according to claim 27, wherein the zinc compound is zinc chloride and the elevation compound of Eh is sodium chlorite.
36. 36. The method according to claim 35, where the pH of the zinc compound during storage varies from about 3.0 to about 6.0 and the pH of the sodium chlorite during storage varies from about 7.0 to about 8.5.
37. 37. The method according to claim 36, wherein the composition further comprises a chloride ion compound.
38. 38. The method according to claim 37, wherein the chloride ion compound is sodium chloride.
39. 39. The method according to claim 27, wherein the oral composition is a product for dental care, food products, troches, chewing gum or candy.