MXPA99003767A - Oral compositions containing zinc citrate salts - Google Patents

Abstract

Oral compositions containing an alkali metal or ammonium zinc citrate to provide protection against colds and flu.

Description

ORAL COMPOSITIONS CONTAINING ZINC CITRATE SALTS TECHNICAL FIELD The present invention relates to a method for preventing or controlling colds and similar diseases, such as influenza, by the use of an orai composition containing a zinc citrate of ammonium or alkali metal applied to the gingival tissue or of the oral mucosa. of the subject susceptible to suffer colds.

BACKGROUND OF THE INVENTION The common cold, although not usually a serious illness, is a highly frequent, troubling and annoying problem. The term "common cold" is applied to common respiratory diseases caused by several different respiratory viruses. Although rhinoviruses are the leading known cause of common colds, accounting for approximately 30% of colds in adults, viruses from several other groups are also important. Although immune responses occur, and infection by some respiratory tract viruses can thus be prevented by a vaccine, the development of a polytypic vaccine encompassing all possible agents is impractical. Thus, the problem of controlling acute upper respiratory diseases presents complex challenges, and the long-awaited discovery of a single cure for the common cold is an unreal expectation. In the case of rhinovirus infection, the symptoms of nasal discharge, nasal congestion and sneezing usually begin during the first day of the illness, and progress to a maximum severity around the second or third day. It is estimated that the costs to treat colds with cash medications in the United States are more than 1.5 billion dollars annually. It is estimated that the direct costs of treatment in outpatient clinics is almost 4 billion dollars. Indirect costs, based on the amount of loss in wages due to a restricted activity, are substantially higher. Currently, there is only symptomatic treatment for the common cold; Most drugs are taken orally. Examples of oral compositions of the prior art for the treatment of nasal symptoms and other symptoms of cold, influenza, allergy and sinus, as well as the discomfort, pain, fever and malaise associated therewith, generally contain an analgesic ( aspirin or acetaminophen) and one or more antihistamines, decongestants, cough suppressants, antitussives and expectorants. Other specific pharmaceutical active agents for nasal symptoms (e.g., congestion) generally contain oxymetazoline or phenylephrine. These active agents are usually supplied topically to the nasal mucosa by a nasal spray. For individuals with certain medical conditions such as heart disease, hypertension, diabetes or thyroid disorders, oral drugs such as decongestants may represent the risk of unfavorable interactions between drugs, and may cause an adverse reaction. Therefore, it would be highly desirable to provide relief of specific nasal symptoms by compositions without the need for such pharmaceutical active agents. It has been discovered that the topical application of zinc ammonium citrate or alkali metal citrate to the gingival or oral mucosa tissues of a subject susceptible to colds and / or influenza helps to reduce the incidence of said discomforts. Therefore, an objective of the present invention is to provide topical oral compositions that serve as a treatment to prevent colds and influenza.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to a method for reducing colds and symptoms similar to colds, such as influenza, in subjects susceptible to said discomforts, by applying a composition containing an effective amount of a zinc citrate of ammonium or alkali metal to the tissues gingival or oral mucosa.

DETAILED DESCRIPTION OF THE INVENTION The compositions of the present invention contain certain essential components, as well as non-essential components.

Zinc Ammonium or Alkali Metal Citrate The zinc salts found useful in the compositions used in the present method are described in the U.S. Patents. 4,289,754, September 15, 1981, and 4,325,939, April 20, 1982, both incorporated herein by reference in their entirety. The preferred compound is zinc citrate sodium. The amount of the zinc compounds used in the composition used in the method described herein is from about 0.1% to about 11%, preferably from about 0.1% to about 5%.

Acceptable vehicle The vehicle for the active components can be any vehicle suitable for use in the oral cavity. Such vehicles include the usual components of mouthwashes, toothpastes, tooth powders, prophylaxis pastes, lozenges, rubbers and the like, and are described in more detail below. The dentríficos and buccal washings are the preferred systems.

In addition to the active agents, the present compositions may contain an antiplaque / antigingivitis agent, such as quaternary ammonium compounds, water insoluble agents such as triclosan, teas, as defined herein below, and stannous salts. These types of agents are described in the U.S. patent. 4,894,220, of January 16, 1990 to Nabi et al., Patent of E.U.A. 4,656,031, from April 7, 1987 to Lane and others; and patent of E.U.A. 5,004,597, from April 2, 1991 to Majeti et al., All incorporated herein by reference in their entirety. The abrasive polishing material contemplated for use in the present invention can be any material that does not excessively wear dentin. These include, for example, silicas including gels and precipitates, calcium carbonate, dicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate, insoluble sodium polymetaphosphate, hydrated aluminum dioxide, and resinous abrasive materials such as condensation in urea and formaldehyde particles, and other materials such as described by Cooley et al. in the US patent 3,070,510, of December 25, 1962, incorporated herein by reference. Mixtures of abrasives can also be used. Silica dental abrasives, of various types, can provide the unique benefits of exceptional polishing performance and dental cleaning without excessively abrading the enamel or dentin of the teeth. Silica abrasive materials are also exceptionally compatible with soluble fluoride and polyphosphonate sources. For these reasons, they are preferred for use herein. The useful abrasive polishing materials herein, as well as the other abrasives, generally have an average particle size ranging from about 0.1 to 30 microns, preferably from 5 to 15 microns. The silica abrasive can be precipitated or silica gels such as the silica xerogels described in Pader et al., U.S. Pat. No. 3,538,230, issued March 2, 1970, and DiGiulio, patent of E.U.A. No. 3,862,307, of June 21, 1975, both incorporated herein by reference. Preferred are silica xerogels marketed under the trade name of "Syloid" by W. R. Grace & Company, Davison Chemical Division. Preferred precipitated silica materials include those marketed by J. M. Huber Corporation under the tradename "Zeodent", particularly the silica having the designation "Zeodent 119". These silica abrasives are described in the US patent. No. 4,340,583, July 29, 1982, incorporated herein by reference. The abrasive in the compositions described herein is present at a level of from about 6% to about 70%, preferably from about 15% to about 25%, when the toothpaste is a toothpaste. Higher levels, as high as 90%, can be used if the composition is a dental powder.

The compositions of the present invention may also contain a fluorous ion source, such as sodium, potassium or lithium fluorides, stannous fluoride, and sodium monofluorophosphate, among many others. The fluoride source should be sufficient to provide from about 50 to about 3500 ppm of fluoride. Flavoring agents can also be added to the dentifrice compositions. Suitable flavoring agents include, among many others, pyrola oil, peppermint oil, spearmint oil and clove oil. Sweetening agents that can be used include aspartame, acesulfame, saccharin, dextrose, levulose, and sodium cyclamate. Flavoring and sweetening agents are generally used in dentifrices at levels of about 0.005% to about 2% by weight. The dentifrice compositions may also contain emulsifying agents. Suitable emulsifying agents are those which are reasonably stable and which foam over a wide pH range, including synthetic, nonionic, nonionic, cationic, switterionic and amphoteric soap organic detergents. Many of these suitable surfactants are described by Gieske et al. In the U.S. patent. No. 4,051, 234, of September 27, 1977, incorporated herein by reference in its entirety. Water is also present in the toothpastes of this invention. The water used in the preparation of commercially suitable toothpastes should preferably be deionized and free of organic impurities. Water generally comprises about 10% to 50%, preferably about 20% to 40% by weight, of the toothpaste compositions herein. These amounts of water include the free water that is applied, plus that which is introduced with other materials such as sorbitol. In the preparation of toothpastes, it is necessary to add some thickening material to provide a desired consistency. Preferred thickening agents are carboxyvinyl polymers of the type mentioned hereinabove, xanthan gum, carrageenan, hydroxyethylcellulose and water soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethylcellulose. Natural gums such as karaya gum, gum arabic and tragancanth gum can also be used. Magnesium-aluminum colloidal silicate or finely divided silica can also be used as part of the thickening agent to improve the texture. Thickening agents may be used in an amount of 0.5% to 5.0% by weight of the total composition. It is also convenient to include some moisturizing material in a toothpaste to prevent it from hardening. Suitable humectants include glycerin, sorbitol, xylitol, and other edible polyhydric alcohols at a level of about 5% to about 70%. Another preferred embodiment of the present invention is a mouthwash composition. The conventional components of the mouthwash composition may comprise the carrier for the active agents of the present invention. The buccal washes generally comprise from about 20: 1 to about 2: 1 of a water / ethyl alcohol solution, and preferably other ingredients such as flavoring, sweetening, wetting and foaming agents such as those mentioned above for the dientrifics. Moisturizers such as glycerin and sorbitol give a moist sensation to the mouth. Generally, on a weight basis, the buccal washes of the invention comprise from 0% to 60% (preferably from 10% to 25%) of ethyl alcohol, from 0% to 20% (preferably from 5% to 20%) of a humectant, from 0% to 2% (preferably from 0.01% to 0.15%) of emulsifying agent, from 0% to 0.5% (preferably from 0.005% to 0.06%) of sweetening agent such as saccharin, from 0% to 0.3% (preferably from 0.3% to 0.3%) of flavoring agent, and the water balance. Suitable tablet and chewing gum components are described in the US patent. No. 4,083,955, April 1, 1978 to Grabenstetter et al., Incorporated herein by reference. Other optional components useful in the present invention are pyrophosphate salts, such as those described in U.S. 4,515,772, May 7, 1985 to Parran et al., Incorporated herein by reference. Also useful are nonionic antimicrobials such as triclosan, described in U.S. 4,894, 220, of January 16, 1990 to Nabi et al. Both patents are incorporated herein by reference.

Another agent that can be used in the present compositions is an alkali metal bicarbonate, such as sodium bicarbonate. These are stable articles of commerce and may be used together with a peroxide compound in separate compartments, as described in U.S. 4,849,213 and U.S. 4,528,180, both to Schaeffer, incorporated herein by reference in its entirety. Other preferred compositions of the present invention are controlled release drug delivery systems for placement in the periodontal pocket. Such systems include, but are not limited to, the hollow cellulose fibers described in the U.S.A. No. 4,175,326, issued to Goodson on November 27, 1979; the ethylcellulose films described in the U.S.A. No. 4,568,535 issued to Loesche on February 4, 1986; the absorbable material in the form of putty described in the patent of E.U.A. No. 4,568,536, issued to Kronenthal, Maftei and Levy on February 4, 1986; the biodegradable microspheres and matrix described in the US patent. No. 4,685,883, issued to Jemberg on August 11, 1987; the suspensions of microparticles or microcapsules described in the patent of E.U.A. No. 4,780,320, issued to Baker on October 25, 1988; the polymeric devices described in European Patent Application No. 0,140,766 to Goodson, published May 8, 1985; and the lactide / glycolide executions described in the US patent. No. 5,198,220, from March 30, 1993 to Damani; These patents are incorporated herein by reference. Such controlled release delivery systems generally include a solid matrix, usually of polymeric material, loaded with one or more active agents, the matrix containing stannous gluconate. Typically, the active agents diffuse over time from the solid material to the periodontal pocket. Preferred controlled release drug delivery systems comprise from about 0.001% to about 50%, more preferably from about 0.01% to about 25%, more preferably from 0.1% to about 15%, most preferably from about 1% to about 10%, of stannous gluconate and a controlled release vehicle. The pH of the present compositions and / or their pH in the mouth can be any pH that is safe for the hard and soft tissues of the mouth. Said pH's are generally from about 3 to about 10, preferably from about 5 to about 9.

MANUFACTURING METHOD The vehicle compositions used in the present invention can be manufactured using methods that are common in the area of oral products. For example, toothpaste compositions can be prepared by mixing part of the wetting agent and water and heating from 66 ° C to 71 ° C.

The fluoride source, if present, is then added together with the sweetener, the opacifier and the flavoring.

COMPOSITIONS OF USE The present invention in its method aspect involves applying to the gingival tissue and / or the oral mucosa, safe and effective amounts of the compositions (generally an amount of at least about 5 grams of a mouthwash, and at least about 0.5. grams of a toothpaste or liquid toothpaste). A preferred method of the present invention involves contacting a composition of the present invention with the soft tissue of the oral cavity for at least about 15 seconds, preferably about 20 seconds to about 10 minutes, more preferably about 30 minutes. seconds to approximately 60 seconds. The method often involves expectoration of most of the composition after said contact, preferably followed by rinsing, for example, with water. The frequency of said contact is preferably from about once a week to about five times a day, more preferably from about three times a week to about four times a day, most preferably still from about once a day to about three times a day. times a day. The period of such treatment typically varies from about a day to a lifetime.

Generally, individuals can recognize that they will be exposed to a cold virus, and then they can use the products described here either before exposure, after exposure, or at the first signs of a cold. The compositions used in the present method can also be used by the subject as a gargle. Additionally, subjects who take large doses of vitamin C can obtain an improved benefit against colds by using the compositions described herein. The following examples describe and demonstrate in more detail the preferred embodiments within the scope of the present invention. The examples are given for illustrative purposes only, and are not intended to be limiting of this invention, since many variations thereof are possible without departing from their spirit and scope.

EXAMPLE I Toothpaste % by weight% by weight Water 13,017 12,500 Sorbitol 45,425 44,552 Glycerin 10,198 10,198 Titanium dioxide 0.525 0.525 Silica 20,000 20,000 Sodium carboxymethylcellulose 1.050 1.050 Magnesium-aluminum silicate 0.408 0.408 Sodium alkylsulfate (solution at 27.9%) 4.000 4.000 Na-Zn citrate Saccharin sodium 0.200 0.200 Flavoring 0.851 0.851 Blue # 1 of FD &C (1% solution) 0.051 0.051 Sodium monofluorophosphate 0.243 - Sodium hydroxide (50% solution) 0.500 0.395 PH 4.5 4.5 EXAMPLE II Mouth rinses % by weight% by weight Citrus of Na-Zn Glycerin 8,000 12,000 Sorbitol (aqueous solution at 70%) Ethanol 10,000 10,000 Polysorbate 80 0.300 0.300 Sodium saccharine 0.050 0.050 Flavor 0.150 0.150 Sodium hydroxide 0.020 0.020 Benzoic acid 0.0.50 0.050 Blue # 1 of FD &C (solution at 1%) 0.020 0.020 Sodium monofluorophosphate 0.183 - Water 80.187 77.850 EXAMPLE III Topical gels % by weight% by weight Na-Zn Glycerin Citrate 91,896 70,000 Sobitol (70% solution) - 21,765 Sodium carboxymethylcellulose 0.600 0.800 Hydroxyethylcellulose Flavoring 1.000 1.000 Sodium saccharin 0.200 0.200 Sodium alkylphosphate (27.9%) 2,000 2,000 Sodium monofluorophosphate 0.760 _ EXAMPLE IV Tablets for mouthwash % by weight% by weight Na-Zn Flavoring Citrate 0.150 g 0.150 g Sodium saccharin 0.050 g 0.200 g Mannitol 0.773 g-Sodium carboxymethylcellulose 0.050 g - Sodium benzoate 0.030 g 0.025 g Citric acid - 0.200 g Sodium carbonate - 0.100 g Sodium bicarbonate - 0.200 g Glycine - 0.050 g Sodium monofluorophosphate 0.183 q - Dissolve in Dissolve in 97.745 g 97.856 g of water water

Claims (10)

NOVELTY OF THE INVENTION CLAIMS

1. - A method for reducing the incidence of colds and similar ailments, such as influenza, in animals susceptible to colds, characterized in that it comprises applying to the gingival tissue and / or the oral mucosa of said animal, an effective amount of a composition containing a effective amount of a zinc ammonium or alkali metal citrate.

2. The method according to claim 1, further characterized in that said composition is in the form of a toothpaste.

3. The method according to claim 1, further characterized in that said composition is in the form of a mouthpiece.

4. The method according to claim 1, further characterized in that said composition is in the form of a site-specific delivery system.

5. The method according to claim 1, further characterized in that the concentration of a zinc citrate of ammonium or alkali metal is about 0.1% to about 11%.

6. - The method according to claim 2, further characterized in that said toothpaste contains a silica abrasive.

7. The method according to claim 6, further characterized in that the zinc salt is sodium zinc citrate.

8. The method according to claim 7, further characterized in that it contains a fluoride ion source.

9. The method according to claim 8, further characterized in that it contains an agent selected from the group consisting of surfactants, humectants, sweetening agents, and mixtures thereof.

10. The method according to claim 9, further characterized in that the humectant is selected from the group consisting of sorbitol, glycerin, xylitol, and mixtures thereof.