MXPA94007195A - Composition containing phosphate derivatives - Google Patents

Abstract

The subject invention encompasses compositions in a form suitable for oral or topical administration comprising one or more phosphate derivatives, carrier materials and preferably a safe and effective amount of one or more actives.

Description

"C0MP0S1CI0NFS QÜF CQMPRFNDEN DFRIVADQS DE FOSFATO" lnventor (s): MICHAEL JOHANNES EIS, DENNIS GEORGE ANTHONY NELSON, JAMES EDWIN THOMPSON, JEFFREY CHARLES HAYES AND DOROTHY JEAN STUART the first American, the second New Zealander and the third to the fifth North Americans residing at 3841 Trevor Avenue, Cheviot, Ohio 45211; 8485 Rupp Farm Drive, West Chester, Ohio 45069; 11790 Tennyson Drive, Sharonville, Ohio 45241; 83 Bishops Gate Drive # 206. Cincinnati, Ohio 45246 and 1775 Leway Drive, Fairfield, Ohio 45014, E.U.A Causabiente: THE PROCTER & GAMBLE COMPANY, a North American company organized and existing according to the laws of the State of Ohio residing in One Procter & Gamble Plaza, Cincinnati, Ohio 45202, E.U.A.

SUMMARY The present invention comprises compositions in a form suitable for oral or topical administration comprising one or more phosphate derivatives, carrier materials, and preferably a safe and effective amount of one or more active ingredients.

ANTFCF? FNTF? F I A INVFN ION The present invention relates to compositions comprising one or more phosphate derivatives, and carrier materials wherein the compositions are in a form suitable for oral or topical administration. These compositions preferably contain a dry and effective amount of one or more active materials such as those that provide nutritional, therapeutic, antimicrobial, pharmaceutical, & Medicinal and / or aesthetic, and those that are commonly used in health care products. A wide variety of flavoring agents, refreshing agents, and sweeteners are currently used in products for consumer and health care. The aesthetic qualities of these compositions such as taste, odor, mouthfeel, and leave on the palate are important considerations for consumer acceptability. Products with bad taste, a bad taste on the palate or other negative aesthetic characteristics may initially limit or for a prolonged period of time the acceptability by the consumer, thus limiting the use by the consumer and compliance with the treatment regimes. An additional aspect of acceptability and compliance by the consumer is the consumer's perception of the product's effectiveness. The consumer's satisfaction with the product probably increases if there is some kind of sensory signal that reminds the consumer that the product is working after its ingestion, administration or expectoration. It has been found that phosphate derivatives comprising flavor components, refreshers, and / or sweeteners can be incorporated into oral or topical compositions to provide pleasing aesthetic characteristics and high consumer acceptability. It has also been discovered that these compositions for oral or topical administration can be formulated to include a safe and effective amount of one or more active ingredients. These compositions can provide a continuous refreshing, flavoring and / or sweetening activity, depending on the particular derivative that is used. These phosphate derivatives can also serve to improve the aesthetic characteristics of the compositions and provide a sensory signal to the user. Therefore, it is a purpose of the present invention to provide compositions that are aesthetically pleasing to the consumer. It is also an object of the present invention to provide compositions that provide a sensory signal to the user, and that preferably contain a safe and effective amount of one or more active ingredients. These and other purposes of the present invention will be more readily apparent from the following detailed description. All percentages and ratios that are used in the present invention, and all measurements are made at 25 ° C, unless otherwise specified. SUMMARY OF THE INVENTION The present invention relates to compositions comprising: (a) from 0.001% to 25%, approximately, of one or more phosphate derivatives having the formula: wherein R is selected from the group consisting of a cooling component, a sweetening component, and a flavor component; where R 'and R "are independently selected from the group consisting of R, an adherent component, M +, M ++, C +, and hydrogen, wherein X, X', and X" are independently selected from the group consisting of oxygen , nitrogen, and sulfur; where n is an integer from 1 to 3; and (b) from 75% to 99.999%, approximately, of vehicle materials; and wherein in addition the compositions are in a form suitable for oral or topical administration. DETAILED DESCRIPTION OF THE INVENTION The present invention relates to compositions comprising one or more phosphate derivatives, and carrier materials wherein the compositions are in a form suitable for oral or topical administration. These compositions also preferably contain a safe and effective amount of one or more active ingredients. The term "active", as used in the present invention, means an agent that provides a greater effect than an excipient such as agents that provide nutritional, therapeutic, antimicrobial benefits, W pharmaceutical, medicinal, and / or aesthetic, and those that are commonly used in health care products. The phrase "suitable for oral or topical administration", as used in the present invention, means any formulation that is suitable for the convenient administration of the composition according to which the composition is swallowed, chewed, swallowed, intentionally retained in The oral capidad during any period of time, is placed in contact with the internal mucous membranes of the body, such as those of the nose, mouth, or throat, either by direct or indirect application or inhalation to the nostrils or applied to the surfaces of the skin for therapeutic purposes or other reasons other than cosmetic benefits. The phrase "a safe and effective amount", as used in the present invention, means a sufficient amount of material to provide the desired benefit without unfavorable adverse side effects (such as toxicity, irritation or allergic response) provided at a reasonable ratio of advantage / risk when used in the manner of this invention. The specific safe and effective amount will vary with such factors as the particular condition being treated, the severity of the condition, the duration of the treatment, the physical condition of the patient, the nature of the concurrent therapy (if any), and the specific formulation and the optional components that are used. The components to be used in the present compositions and the preferred amounts to be used are described in detail later in the present invention. A- Phosphate Derivatives: The compositions of the present invention contain one or more phosphate derivatives. These compounds can be formulated by phosphorylation of at least one cooling, sweetening or flavor component. These compounds further include a linkage of at least one cooling, sweetening or flavor component to an adherent component via a phosphate bridge. In addition, the pyrophosphate and triphosphate groups can be replaced by the phosphate group. The refreshing, flavoring or adherent components can also be linked to phosphorus via two functional groups or fixing sites. In addition, the phosphate derivatives described above can be bound via a Coulomb interaction with charged compounds or materials, including polymers.

The present compositions can provide the desired refreshing, flavoring and / or sweetening qualities by means of the action of the phosphate derivative itself. The compositions can also provide a sustained effect by releasing the refreshing, flavoring and / or sweetening component of the molecule after cleavage of the phosphate from the cooling component., flavor and / or sweetener by means of phosphatase enzymes. Phosphatase enzymes include but are not limited to acidic, basic phosphatases, and pyrophosphatases. The term "cooling component", as used in the present invention, refers to cooling components having a functionality of hydroxy, amino, or thiol which is capable of forming an ester, amido, or thioester bond with a phosphorus atom ( V). Preferred cooling components are selected from the group consisting of menthol, 3-1-menthoxypropane-1,2-diol ("TK-10"), menthone glycerol acetal ("MGA") and menthyl lactate. The term "mentor" and "menthyl" as used in the present invention include dextro- and levorotatory isomers of these compounds and racemic mixtures thereof The term "flavor component", as used in the present invention, refers to compounds of flavor having a functionality of hydroxy, amino, or thiol which is capable of forming an ester, mide, or thioester linkage with a phosphorus atom (V) .The preferred flavor compounds are selected from the group consisting of sodium salicylate. methyl, eugenol, vanillin, thymol, cinnamaldehyde glycerol acetal ("CGA"), and * linalool The term "sweetening component", as used in the present invention, refers to sweetening compounds having a functionality of hydroxy, amino, or thiol which is capable of forming an ester, amido, or thioester bond with a phosphorus atom ( V). The preferred sweetening components are saccharin, mannitol, sorbitol, glucose, sucrose, fructose, and neohesperidin dihydroxyachalcone. The term "adherent component", as used in the present invention, refers to monomers, oligomers, or polymers having hydroxy, amino, or thioester functionalities that are capable of forming ester, amido, or thioester bonds with atoms of phosphorus (V). Monomers, oligomers, or polymers may also possess additional hydroxy, amino, or thiol groups which may remain unsubstituted or be linked via ester, amido, or thioester linkages to a phosphorus atom (V) which is then also attached to a serving refreshing, flavorful, or active. Preferred compounds are selected from the group consisting of j- consists of C12-C18 diacylglycerol, hydrolyzed vinyl acetate / ethylene copolymer, cellulose; chitin, glucose, glucosamine, silica gel, glycerol, maleic acid-lower alkyl vinyl ether The terms "M +" and "M ++", as used in the present invention, refer to physiologically relevant metal cations. The phrase "physiologically relevant metal cations", as used in the present invention, refers to metal cations that are significant for the organic or bodily processes of a human or lower animal. The preferred "M +" cations are sodium and potassium. The preferred "M +" cations are calcium, zinc, magnesium, manganese, copper, and stannous. The term "C +", as used in the present invention, refers to an "organic" cation. An "organic" cation, as used in the present invention, refers to cations containing positively charged nitrogen, phosphorus, oxygen, or sulfur atoms. Such cations may contain more than one positively charged site and in the case of oligomers or polymers containing nitrogen, phosphorus, oxygen, or sulfur atoms, many positively charged centers may exist. Preferred "organic" cations include ammonium, protonated amines such as protonated glucosamine, and polymers containing partially or completely protonated amine such as protonated chitosan. The phosphate derivatives of this invention are represented by the following formula: In the above formula, R is selected from the group consisting of a cooling component, a sweetening component, and a flavor component; R 'and R "are independently selected from the group consisting of R, an adherent component, M +, M + +, C +, and hydrogen; X, X', and X" are independently selected from the group consisting of oxygen, nitrogen, and sulfur; and n is an integer from 1 to 3. Further, R 'may be equal to R ", preferably wherein R' and R" are selected from the group consisting of calcium, zinc, and magnesium, manganese, copper and tin. The derivatives Preferred phosphates have the formula: In the above formula: R is selected from the group consisting of menthol, TK-10, MGA, menthyl lactate, methyl salicylate, mannitol, sorbitol, glucose, sucrose, fructose, neohesperidin dihydrochalcone, eugenol, vanillin, thymol, CGA, and linalool; R 'and R "are independently selected from the group consisting of R, C12-C18 diacylglycerol, partially hydrolyzed vinyl acetate-ethylene copolymer, cellulose, chitin, glucosamine, silica gel, glycerol, maleic acid-lower alkyl vinyl ether, sodium, potassium, calcium, zinc, magnesium, manganese, copper and tin, ammonium, protonated amines, polymers containing partially or completely protonated amine, and hydrogen; X, X ', and X "are independently selected from the group consisting of oxygen, nitrogen, and sulfur, and n is an integer from 1 to 3., R 'can be equal to R ", preferably wherein R' and R" are independently selected from the group consisting of calcium, zinc, magnesium, manganese, copper and tin. The most preferred phosphate derivatives are menthyl monophosphate, monophosphate eugenyl, thymyl monophosphate, 1-mentyl diphosphate, bis-1-mentyl pyrophosphate, 1-mentyl triphosphate. The phosphate derivatives are used in the present invention at levels of from 0.001% to 25%, approximately, preferably from 0.01% to approximately 15%, by weight of the composition. Vehicle Materials: In formulating the compositions of this invention, the phosphate derivative is incorporated into a vehicle which may be completely inert or which may contain other active ingredients. The term "carrier materials", as used in the present invention, means one or more compatible substances suitable for administration to a human or lower animal. The term "compatible", as used in the present invention, means that the components of the compositions are capable of mixing with active phosphate derivatives, and with each other, such that there is no interaction that substantially reduces the effectiveness of the composition. the present compositions under ordinary conditions of use. The carrier materials must also be of sufficiently high purity and sufficiently low toxicity that they are suitable for administration to the human or lower animal being treated. A wide variety of vehicles will be suitable depending on the final use of the compositions. The phosphate derivatives can be incorporated into a variety of compositions that are generally divided into oral and topical compositions, the meaning of both terms being in their broadest possible sense. The oral compositions include not only foods and beverages that are taken by mouth and swallowed, but also orally ingested compositions that are put in the mouth for reasons other than maintenance. Such compositions include (but are not limited to) solid oral dosage forms such as tablets, tablet coatings, caplets, hydrogels, and liquid oral dosage forms such as syrups, emulsions and suspensions. Oral compositions also include those compositions that are put into the mouth but not necessarily swallowed, e.g., chewing gum. Topical compositions include compositions that are applied to, or which in normal use come into contact with, the internal membranes of the body such as those of the nose, mouth, or throat, either by direct or indirect application. Such compositions include (but are not limited to) nasal sprays, dentifrices, mouth rinses, lozenges, foams, gels, and throat sprays. The topical compositions can also be compositions that are applied to the external surfaces of the body for therapeutic reasons or different reasons than for a cosmetic benefit. Such compositions include ointments, lotions, gels, and creams. Preferred compositions of the present invention are health care compositions such as dentifrices, mouth rinses, liquid oral dosage forms, and nasal sprays. The present compositions preferably comprise about 75% to 99.999%, and preferably about 85% to 99.99%, by weight of the composition. The carrier materials suitable in the present invention, depending on the proposed end use, are selected from the group consisting of solvents, suspending agents, solubilizing agents, diluents, surfactants, regulators, lubricants, thickeners, emulsifiers, flavoring agents, colorants. , humectants, sweeteners, co-solvents, binders, disintegrating agents, flow-inducing agents, refreshers, plasticizers, wetting agents. antioxidants, stabilizers, and tabletting agents. Dentifrices The dentifrice compositions may be of the liquid, paste, powder, or gel type. These compositions will usually comprise a finely divided abrasive or polishing material, e.g., precipitated chalk, silica, magnesium silicate, calcium polymetaphosphate, aluminum hydroxide and other similar materials well known in the art. Abrasive materials are described in more detail in U.S. Patent 3,070,510, Cooley et al., December 25, 1962, which is incorporated herein by reference. The toothpaste compositions further contain a surfactant or foaming agent. Suitable surfactants are those which are reasonably stable and foam on a wide range of pH, including organic anionic, nonionic, cationic, zwitterionic and amphoteric non-soap synthetic detergents. These surfactants are disclosed by Gieske et al., In US Patent 4,051,234, issued September 27, 1977, which is also incorporated herein by reference. Water is also present in dentifrice compositions. The water used should preferably be deionized and free of organic impurities. The water generally comprises from 10% to 50%, approximately, and preferably from 20% to 40%, approximately, in mw weight of the compositions. These amounts of water include the free water that is added plus that which is introduced with other materials such as sorbitol. Optional ingredients in dentifrice compositions include flavoring agents, colorants, regulators, lubricants, thickeners, emulsifiers or plasticizers, and humectants. The dentifrice vehicle materials typically comprise about 50% to 94%, and preferably about 60% to 80%, W weight of the dentifrice compositions. Mouth Rinses Mouth rinses usually comprise an aqueous, alcoholic, or aqueous-alcoholic solution of an antiseptic that is sometimes colored or flavored to give a pleasant taste. Optional ingredients include humectants, surfactants, sweeteners, emulsifying agents, fluoride ion sources, dental tartar control, and anti plaque agents. Mouthwash products can also be formed by dissolving a powder or tablet containing stannous gluconate in water just before use.

Mouthwash compositions are typically based on a water / ethanol solution having a water: ethanol ratio of about 20: 1 to 2: 1. Moisturizers, such as glycerin and sorbitol, are usually included to provide a moist sensation to the mouth. Conventional mouthwash compositions generally comprise, by weight of the composition, from 0% to 60%, approximately, ft of ethyl alcohol, 0% to 20% of a humectant, 0% to 2% of emulsifying agents, 0% a 0.5% sweetening agents, 0% to 0.3% flavoring agents and water balance. Liquid Forms of Oral Dosing Liquid forms of oral dosage include solutions, emulsions; pseudoemulsions, suspensions, and solutions and / or reconstituted suspensions of non-effervescent aqueous and non-aqueous granules. These dosage forms also contain solvents agents & emulsifiers, regulating agents, suspending agents, diluents, natural and artificial sweeteners, coloring agents, and suitable flavoring agents. Antioxidants may also be included such as butylated hydroxyanisole or butylated hydroxytoluene, and preservatives such as methyl- or propylparaben or sodium benzoate. Specific examples of vehicles and excipients that can be used to formulate oral dosage forms are described by Roberts, in US Patent 3,903,297, issued September 2, 1975, which is incorporated herein by reference.

In view of the fact that many of the active ingredients are generally used in the form of a water soluble salt, they can be easily incorporated into conventional aqueous base formulations. Water insoluble or sparingly soluble ingredients, generally in base form, can also be incorporated in orally acceptable water-based carriers such as dispersions, suspensions, oil-in-water emulsions and the like by means of dispersing, suspending or suspending agents. suitable emulsifiers, respectively, which are readily apparent to those skilled in the art of formulations. In preparing the liquid oral dosage forms, the active component is incorporated into an orally acceptable water-based carrier consistent with conventional practices. An "orally acceptable water-based carrier" is one in which the total or predominant solvent content is water. Typical vehicles include simple aqueous solutions, syrups, dispersions and suspensions, and water-based emulsions such as oil-in-water emulsions. The most preferred vehicle is a suspension or solution of the phosphate derivative and active in an aqueous vehicle containing a suitable suspending agent or solubilizing agent. Suitable suspending agents include celluloses, carboxymethylcellulose, and their salts, guar gum and the like. Suitable solubilizing agents include solutions of sucrose, ethanol, and surfactants such as polyoxyethylene derivatives of partial fatty acid esters of sorbitol anhydrides (eg , Polysorbate 80). Suspension systems, suspending agents and solubilizers, and methods for their use are described in M. Pernarowski, "Solutions, Emulsions and Suspensions", Reminqton's Pharmaceutical Sciences (A. Osol, editor, 15th Edition, 1975), which incorporated in the present invention as a reference. Even though the amount of water in the compositions of this invention may vary over a fairly wide range depending on the weight and total volume of the essential ingredients and other optional ingredients, the total water content will generally range from about 20% to 75%. , and preferably from 20% to 40%, approximately, by weight of the composition. Even though the water itself can make up the total vehicle, typical oral formulations also contain a cosolvent that includes but is not limited to alcohol, propylene glycol, glycerin, sorbitol solution, and the like, to aid in the solubilization and incorporation of insoluble ingredients in water, flavor oils and the like in the composition. In general, the compositions preferably contain about 10 to 20 volume percent / volume of the cosolvent. Nasal Atomizers The proper vehicles for nasal administration provide a product that is delivered to the nasal passages. Such vehicles can be, for example, aqueous or aerosol and are described in more detail in Reminqton's Pharmaceutical Sciences (17th Edition, 1985), which is incorporated herein by reference. Such product forms include (but are not limited to) nasal solutions for use as drops or as sprays, nasal suspensions, nasal ointments, nasal gels, or other vehicles suitable for oral administration. Preferred nasal dosage forms are solutions, suspensions, and gels, which normally contain sodium chloride in a larger amount of water (preferably purified water). Other ingredients include but are not limited to: pH adjusters such as sodium hydroxide, emulsifying or dispersing agents; regulatory agents such as sodium bicarbonate; preservatives such as benzyl alcohol, parabens, benzalkonium chloride, chlorhexidine gluconate and disodium EDTA; agents for regulating isotonicity such as sodium chloride, boric acid, potassium phosphate and propylene glycol; wetting agents; thickeners such as methylcellulose, carboxymethylcellulose, and carbomer; humectants such as sorbitol, propylene glycol, sorbitol, and glycerol; surfactants such as polyoxyethylene derivatives of partial fatty acid esters of sorbitol anhydrides; and mixtures thereof, may also be present. Solid Forms of Oral Dosing The present composition may also be in a solid oral dosage form. The tablets can be compressed, crushed, freeze dried, sugar coated, film coated or compressed in multiple ways. The tablets may contain binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, preservatives and agents that induce flow. In general, vehicle materials suitable for the preparation of unit dosage forms for oral administration are well known in the art. Their selection will depend on secondary considerations such as taste, cost, shelf stability, which are not critical for the purposes of the present invention, and can be manufactured without difficulty by a person skilled in the art. The techniques and compositions for making solid oral dosages are described in Marshall, "Solid Oral Dosing Forms," Modern Pharmaceutics. volume 7, (Banker and Rhodes, editors), 359-427 (1979), which is incorporated herein by reference. The techniques and compositions for making tablets, capsules, and lozenges are described in Reminqton's Pharmaceutical Sciences (Arthur Osol, ed.), 1553-1593 (1980), which is incorporated herein by reference. Pills and Chewing Gums Other embodiments of the present invention include pills and chewing gums. The tablet compositions comprise a tablet vehicle (i.e., a candy base). Candy bases are disclosed in U.S. Patent 4,472,373, Ryan, issued September 18, 1984; and Patent US 4,083,955, Grabenstetter et al., issued April 11, 1978. The compositions of chewing gum comprising a chewing gum vehicle such as those that are disclosed in the same patent, these two patents they are incorporated in the present invention as a reference. The chewing gum carriers may comprise, for example, a gum base, flavoring agents, and sweetening agents. Other Vehicles The compositions of the invention can be formulated with a wide variety of carrier materials in addition to those that have already been disclosed. Some examples of substances that can serve as carrier materials are sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, cellulose acetate; powdered tragacanth; malt; jelly; talcum powder; stearic acid; magnesium stearate; Dicalcium phosphate; calcium sulfate; mineral oil and vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil, and theobroma oil; ^ silicones such as siloxanes, oils, fluids, gums and silicon greases, and ft Vulcanizable at 1 or 2 parts Ambient Temperature; polyols such as propylene glycol, glycerin, sorbitol, mannitol, polyethylene oxide, polyethylene glycol; agar, karaya gum; alginic acid; as well as other non-toxic compatible substances used in fomulations for consumption or health care. Refreshing materials can also be included as carrier materials in the compositions of the invention. The preferred cooling agents in the present invention are the paramentane agents P carboxyamide such as N-ethyl-p-menthane-3-carboxyamide (commercially known as "WS-3"), and 3-1-menthoxypropane-1,2-diol (commercially known as "TK-10"), and mixtures of these. These refreshing agents are described in the PCT Patent Application Publication WO 92-17164, to Upson et al., Published October 15, 1992. TK-10 is also described in U.S. Patent 4,459,425 a Amano et al., Issued July 10, 1984; and WS-3 and other parmenter carboxyamide agents are described in U.S. Patent 4,136,163 to Watson et al., issued January 23, 1979. Disclosures of all these patent publications are incorporated by reference in the present invention in its entirety. When desired or necessary, binders, lubricants, and suitable disintegrating agents can also be incorporated into the compositions. Suitable binders include starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums such as acacia sodium alginate, carboxymethylcellulose, cellulose ? microcrystalline, polyethylene glycol and waxes. Lubricants may include, for example, starch, methylcellulose, agar, bentonite, guar gum, etc. Wetting agents such as sodium lauryl sulfate, as well as coloring agents, flavoring agents, sweetening agents, excipients, tableting agents, stabilizers, antioxidants, and preservatives may also be present. Active: The compositions of the invention may also contain a safe and effective amount of one or more active ingredients. Some assets that are ™ useful in these compositions include (but are not limited to) antimicrobial agents such as iodine, sulfonamides, mercurials, bisbiguanides, or phenolics; antibiotics such as tetracycline, neomycin, kanamycin, metronidazole, or clindamycin; anti-inflammatory agents such as aspirin, acetaminophen, naproxen, ibuprofen, flurbiprofen, indomethacin, eugenol, or hydrocortisone; immunosuppressive or stimulatory agents such as methotrexate or levamisole; dentin desensitizing agents such as potassium nitrate, strontium chloride or sodium fluoride; Odor-absorbing agents such as peppermint oil or chlorophyll; reagents such as immunoglobulins or soluble antigens; local anesthetic agents such as lidocaine or benzocaine; nutritive agents such as amino acids, essential fats, vitamins and minerals; antioxidants such as thymol, alpha-tocopherol and butylated hydroxytoluene; lipopolysaccharides; complexing agents such as polymyxin; quaternary ammonium compounds such as benzalkonium chloride and cetylpyridinium chloride; aromatics such as camphor, eucalyptus oil, and aldehyde derivatives such as benzaldehyde, dental plate adhesives such as maleic acid-lower alkyl vinyl ether or copolymers of anhydrides and their salts; cooling agents that have therapeutic efficacy such as menthol; or peroxides such as urea peroxide.

It is recognized that in certain forms of therapy, combinations of these agents in the same delivery system may be useful in order to obtain an optimal effect. Thus, for example, an antimicrobial agent and an anti-inflammatory agent can be combined in an individual delivery system to provide a combined effectiveness. w Preferred assets are nutritious, therapeutic, medicinal, pharmaceutical, and those that are commonly used in health care products. Preferred formulations for the compositions of the present invention comprising one or more active ingredients are dental care preparations such as toothpastes and oral rinses, and cough / flu preparations in liquid oral dosage forms. Assets commonly used in cough / flu preparations include but are not limited to decongestants such as pseudoephedrine hydrochloride, phenylpropanolamine hydrochloride, and ephedrine hydrochloride.; antitussives such as dextromethorphan, clofedianol, carbetapentane, noscapine, codeine, hydrocodone, hydromorphone; analgesics such as acetaminophen and ibuprofen; expectorants and mucolytics such as glyceryl guaiacolate, guaiacolate, terpine hydrate, ammonium chloride, N-acetylcysteine and ambroxol; antihistamines such as chlorpheniramine maleate, azatadine, doxylamine sucinate, brompheniramine maleate and diphenhydramine hydrochloride; and non-sedating antihistamines such as astemizola, acrivastine, ketotifen, and terfenadine. These compounds as well as others are described in the following: U.S. Patent 4,619,934, to Sunshine et al., Issued October 28, 1986; and U.S. Patent 4,783,465, to Sunshine et al., issued November 8, 1988, which are incorporated by reference in the present invention. Bronchodilators are also useful, such as theophylline and albuterol; and stimulants such as caffeine. The oral forms of the cough / flu preparations comprise a safe and effective amount of one or more of the active components. The solid oral dosage forms preferably contain about 5% to 95%, more preferably about 10% to 95%, and more preferably about 25% to about 95% of the active components. The liquid oral dosage forms preferably contain from about 1% to 50%, more preferably from about 1% to about 25%, and more preferably from about 3% to about 10% of the active components. Preparations for dental care typically comprise a source of soluble floride ion as one of the active. The source of soluble fluoride ion is used in an amount sufficient to provide from 10 to 5000 pp, approximately, of fluoride ion. The preferred fluorides are sodium fluoride, stannous floride, nitrogen fluoride, and sodium monofluorophosphate. Norris et al., U.S. Patent 2,946,735, issued July 26, 1960; and Widder et al., U.S. Patent 3,678,154, issued July 18, 1972, discloses such salts as well as others. These two patents are incorporated herein by reference in their entirety. Various polymers and mixtures thereof are also useful in preparations for dental care. These polymers can be synthetic anionic polymeric polycarboxylates and their complexes and / or carboxyvinyl polymers. The polymers useful in the present compositions are disclosed in U.S. Patent 4,906,456, to Gaffer et al., Issued March 6, 1990, which is incorporated herein by reference in its entirety. The pyrophosphate salts are pharmaceutical active ingredients that can also be included in dental care preparations. Any of the alkali metal pyrophosphate salts can be used in their hydrated or unhydrated forms. Specific salts include alkali metal tetrapyrophosphate, diacalchal metal diacid pyrophosphate, triálcali metal monoacid pyrophosphate, and mixtures thereof, wherein the alkali metals are preferably sodium or potassium. The pyrophosphate salts are described in more detail in Kirk & Othmer, Encvclopedia of Chemical Technology. Second Edition, Volume 15, Interscience Publishers (1968) which is incorporated herein by reference in its entirety. The amount of the pyrophosphate salt is any effective amount and is generally sufficient to provide at least 1.0% P2O7"4, preferably from 1.5% to 6%, and more preferably from 0.5% to 6%. It should be noted that the level of P2? y4 can be provided to the composition (ie, the theoretical amount at an appropriate pH) and that other forms of pyrophosphate (eg, HP2O7"3) may be present. when the final product is established. Anti-plaque and anti-gingivitis pharmaceutical active ingredients can also be included in dental preparations. These active ingredients include quaternary ammonium compounds or bis-biguanides such as chlorhexidine and stannous ion in the form of a combination of stannous floride and stannous gluconate. Oral compositions comprising stannous ion are fully described in U.S. Pat., 004,597, to Majeti et al., Issued April 2, 1991, which is incorporated in the present invention as a reference in its entirety. Disinfectants such as triclosan and antiseptic agents such as thymol can also be included in dental preparations. Pharmaceutical active ingredients that are commonly used in gastrointestinal products are those agents that are safe and effective when administered orally to treat disorders of the upper gastrointestinal tract that result in symptoms of discomfort of the upper intestinal tract. Compositions for alleviating gastrointestinal distress may include antacid agents, agents that prevent the secretion of the acid, other pharmaceutical actives and mixtures thereof. Antacid agents include aluminum carbonate, aluminum hydroxide, aluminum phosphate, aluminum hydroxycarbonate, sodium aluminum dihydroxycarbonate, aluminum magnesium glycinate, aluminum dihydroxyaminoacetate, aluminum dihydroxyaminoacetic acid, calcium carbonate, calcium phosphate, hydrated sulfates of aluminiomagnesium, magnesium aluminate, aluminomagnesium silicates, magnesium carbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, magnesium trisilicate, sucralfate, sodium bicarbonate, and mixtures thereof. Agents for the prevention of acid secretion include cimetidine, ranitidine, famotidine, omeprazole, and mixtures thereof. Other useful pharmaceutical actives include antiflatulent agents such as simethicone and bismuth-containing agents such as bismuth subsalicylate, bismuth aluminate, bismuth citrate, bismuth subcitrate, bismuth nitrate, bismuth subcarbonate, bismuth subgalate, and mixtures thereof. . The pharmaceutical actives comprise from 1% to 99%, approximately, and preferably from 25% to 60%, approximately, by weight of the composition. The one or more active compounds are used in the present compositions at levels of from 0.001% to 99%, and preferably from approximately 0.01% to 90%, by weight of the compositions. The following examples further describe and demonstrate embodiments within the scope of the present invention. These examples are presented for purposes of illustration only and should not be construed as limitations of the present invention since many variations thereof are possible without departing from the spirit and scope of the present invention. The percentages are by weight unless otherwise specified. EXAMPLE I Composition of Toothpaste A toothpaste composition according to the present invention having the following components is prepared: Component% by weight Eugenol Monophosphate 0.300 Purified Water 10.422 Sorbitol 60.565 Sodium Floride 0.243 Saccharin 0.130 Coloring 0.500 Silica 20,000 Mint flavor 0.500 Carbopol 0.300 Xanthan Gum 0.475 Trisodium Phosphate 1, 450 Monosodium Phosphate 0.590 Alkyl Sulfate Solution 4,000 Sodium (27.9% in H2O) Titanium Dioxide 0.525 Add sorbitol to the water and mix. Dissolve the salts, eugenol monophosphate, sodium fluoride, saccharin, trisodium phosphate, monosodium phosphate, and then add the dye. Adjust to pH 7.0-8.5. Combine separately the silica, carbopol, and xanthan gum, and then slowly add this mixture to the composition while mixing continuously. Add the sodium alkyl sulphate. Add the mint flavor. Mix for 10 or more minutes. EXAMPLE II Composition of Oral Mouthwash An oral mouthwash composition according to the present invention is prepared having the following components: Component% by weight Thymol monophosphate 0.300 Ethanol (normal gradation 190) 16.250 Polysorbate 80 0.120 Glycerin 10,000 Purified water 73.1218 Benzoic acid 0.0045 Cetylpyridinium Chloride 0.045 Domiphene Bromide 0.005 Sodium Saccharin 0.060 Dye 0.040 Sodium Benzoate 0.0537 Add all the ingredients except thymol monophosphate to ethanol and mix for 5 minutes. Add the thymol monophosphate last and then adjust the pH of the composition to pH 6, 5-8.5.

Example lll Liquid Oral Dosing Form A liquid oral dosage composition according to the present invention is prepared having the following components: Component% by weight Menthyl Trifosphate 0.300 Sucrose (granulated extra fine) 51, 000 Polysorbate 80 0.020 ~ Glycerin 2,000 Propylene Glycol 15,000 Sodium Citrate, Dihydrate 0,522 Citrus Acid 0,338 Potassium Sorbate 0, 100 Dextromethorphan Hydrobromide 0, 133 Guaifenesin 1, 333 Taste 0,300 Distilled Water 18,954 ™ Alcohol 10,000 Mix together the sucrose and 1/3 of the amount of water and Heat at about 60 ° C until the sucrose dissolves. Mix in polysorbate 80 and glycerin. Mix separately the propylene glycol, sodium citrate dihydrate, menthyl monophosphate, citric acid and about 1/3 of the amount of water. Add the flavor. Mix together the sucrose solution with the propylene glycol solution. Mix together this solution and the potassium sorbate solution.

Finally, add the flavor solution. Adjust the water level to the appropriate size of the batch. Adjust the pH to 6.5-8.5 approximately. Mix for 30-35 minutes. EXAMPLE IV Chewable Tablet A chewable tablet composition according to the present invention having the following components is prepared: Component% by weight Carbonate of Calcium and Mannitol 88.0 (weight ratio 50:50) Mannitol powder 5,085 Aspartame 0.178 Sodium Saccharin 0,092 3-1 -mentoxypropane-1, 2-diol 0,300 N-ethyl-p-menthane-3-carboxamide 0,025 Menthol Monophosphate (a) 0,300 Mint Flavor 0,400 Vanilla Flavor 0,300 Tail Flavor 0,070 Blue Particles 0,750 Talc 2,000 Stearate of Magnesium 2,500 (a) is prepared as described below. Grind the N-ethyl-p-menthane-3-carboxamide to ensure that it is in powder form. Dry mix all ingredients, except magnesium stearate, until uniformly mixed. Add the magnesium stearate and mix for 1-2 minutes. Press the desired amount into a tablet (the target is 550mg / tablet). Preparation of Menthyl Monophosphate In a two-liter three-neck flask cooled in an ice / water bath and equipped with a mechanical stirrer and a feed funnel, 153 mL of triethylamine is added to 157 g. of 1 -mentol in 186 mL of phosphorus oxychloride. After allowing the stirred suspension to warm to room temperature for 1 hour, the mixture is again cooled to 0 ° C, 500 mL of ether is added, and the mixture is carefully hydrolyzed with 500 mL of water. After 1.5 hours at 0 ° C, the mixture is allowed to warm to room temperature overnight. The aqueous layer is then extracted with diethyl ether (3 x 500 mL) and the combined ether layers are extracted with a solution of 1-N-sodium hydroxide (4 x 1 L). After extracting back the combined basic extracts with more ether (2 x 500 mL), the basic solution is acidified with a solution of concentrated hydrochloric acid at pH 0. An oily yellow product is removed and the remaining aqueous layer is extracted with three 1 liter portions of ether. The oil is dissolved in the combined ether extracts, the ether solution is dried with sodium sulfate, the mixture is filtered, and the solution is concentrated under vacuum to give a viscous syrup. After drying the product further in a vacuum oven, a white powder is obtained which can be purified by crystallization of an acetone / water mixture.

Claims (25)

1. NOVELTY OF THE CLAIMS INVENTION A composition comprising: (a) from 0.001% to 25%, approximately, of one or more phosphate derivatives having the structure: wherein R is selected from the group consisting of a cooling component, a sweetening component, and a flavor component; wherein R 'and R "are independently selected from the group consisting of R, an adherent component, M +, M + +, C +, and hydrogen, wherein X, X', and X" are independently selected from the group consisting of oxygen, nitrogen, and sulfur; where n is an integer from 1 to 3; and (b) from 75% to 99.999%, approximately, of vehicle materials; and wherein in addition the composition is in a form suitable for oral or topical administration.
2. The composition according to Claim 1 wherein R -R ", preferably wherein R 'and R" are independently selected from the group consisting of calcium, zinc, magnesium, manganese, copper and stannous.
3. The composition according to Claim 1 further comprising a safe and effective amount of one or more active ingredients.
4. A composition comprising: (a) from 85% to 99.99%, approximately, of one or more phosphate derivatives having the structure: wherein R is selected from the group consisting of menthol, 3-1-menthoxy-propane-1,2-diol, menthone glycerol acetal, menthyl lactate, methyl salicylate, saccharin, mannitol, sorbitol, glucose, sucrose, fructose, dihydrochalcone of neohesperidin, eugenol, vanillin, thymol, cinnamaldehyde glycerol acetal, and linalool; wherein R 'and R "are independently selected from the group consisting of R, C12-C18 diacylglycerol, partially hydrolyzed vinyl acetate / ethylene copolymer, cellulose, chitin, glucosamine, silica gel, glycerol, maleic acid-vinyl ether of lower alkyl, M +, M ++, C +, and hydrogen, wherein X, X ', and X "are independently selected from the group consisting of oxygen, nitrogen, and sulfur; where n is an integer from 1 to 3; and (b) from approximately 1% to 99% of vehicle materials; and wherein in addition the composition is in the form suitable for oral or topical administration.
5. The composition according to Claim 4 wherein M + is sodium or potassium, M ++ is selected from the group consisting of calcium, zinc, magnesium, manganese, copper, stannous, and C + is selected from the group consisting of ammonium, protonated amines, and polymers which contain partially or completely protonated amines.
6. The compositions according to Claim 4 wherein R '= R ", preferably wherein R' and R" are selected from the group consisting of calcium, zinc, magnesium, manganese, copper and stannous.
7. The composition according to Claim 4 further comprising a safe and effective amount of one or more active ingredients.
8. A composition suitable for oral administration comprising: (a) from about 85% to 99.99% of one or more phosphate derivatives having the structure: wherein R is a cooling component that is selected from the group consisting of menthol, 3-1-methoxypropane-1,2-diol, menthone glycerol acetal, menthyl lactate; wherein R 'and R "are hydrogen, wherein X, X' and X" are oxygen; where n is an integer from 1 to 3; and (b) from approximately 1% to 99% of vehicle materials; and wherein the composition is furthermore in a form suitable for oral or topical administration.
9. The composition according to Claim 8 wherein R is menthol and n is 1.
10. The composition according to Claim 9 further comprising a safe and effective amount of one or more active ingredients.
11. The composition according to Claim 10 wherein the composition is in the form of a dentifrice.
12. The composition according to Claim 10 wherein the composition is in the form of an oral mouth rinse.
13. The composition according to Claim 10 wherein the composition is in the form of a chewable tablet.
14. The composition according to Claim 10 wherein the composition is in a liquid oral dosage form.
15. The composition according to Claim 10 wherein the composition is in the form of a nasal spray.
16. A composition comprising: (a) from 85% to 99.99%, approximately, of one or more phosphate derivatives having the structure: wherein R is selected from the group consisting of methyl salicylate, eugenol, vanillin, thymol, cinnamaldehyde glycerol acetal, and linalool; wherein R 'and R "are hydrogen, wherein X, X' and X" are O; where n is an integer from 1 to 3; and (b) from 1% to 99%, approximately of vehicle materials; and wherein in addition the composition is in a form suitable for oral or topical administration.
17. The composition according to Claim 16 further comprising a safe and effective amount of one or more active ingredients.
18. The composition according to Claim 17 wherein R is thymol and n is 1.
19. The composition according to Claim 17 wherein R is eugenol and n is 1.
20. The composition according to Claim 18 wherein the composition is in the form of an oral mouth rinse.
21. The composition according to Claim 18 wherein the composition is in the form of a dentifrice.
22. The composition according to Claim 18 wherein the composition is in a liquid oral dosage form.
23. The composition according to Claim 19 wherein the composition is in the form of an oral mouth rinse.
24. 24. The composition according to claim 19 wherein the composition is in the form of a dentifrice.
25. 25. The composition according to claim 19 wherein the composition is in a liquid oral dosage form. In testimony of which I sign the above in this city of Mexico, D.F. on the 19th day of the month of September 1994. By: THE PROCTER & GAMBLE COMPANY ATTORNEY P &G / mep