KR20000052736A - Oral compositions containing stannous gluconate - Google Patents

Abstract

PURPOSE: An use of an oral composition containing stannous gluconate applied to the gingival or oral mucosal tissue of the subject susceptible to colds, prevents or controls colds and similar maladies, such as flu. CONSTITUTION: A method of reducing the incidence of colds and similar maladies, such as flu, in animals susceptible to colds comprises applying to the gingival and/or oral mucosal tissue of said animal an effective amount of a composition containing an effective amount of stannous gluconate.

Description

Oral composition containing stannous gluconate {ORAL COMPOSITIONS CONTAINING STANNOUS GLUCONATE}

Common cold is not usually a serious illness, but it is a very common, uncomfortable and painful disease. The term "common cold" is used for minor respiratory diseases caused by various various respiratory viruses. Rhinoviruses are the major known cause of common colds, accounting for about 30% of adult colds, but several other groups of viruses are also important. While an immune response occurs and infection by some respiratory tract viruses can be prevented by the vaccine, the development of multiple types of vaccines that can cover all possible agents is impractical. Thus, the problem of inhibiting significant upper respiratory disease has become a complex challenge problem, and the development of a long-awaited, general cold single remedy is an unrealistic expectation.

With rhinovirus infection, symptoms of nasal discharge, nasal congestion, and sneezing usually begin on the first day of illness and become maximal on days 2-3. In the United States, the cost of treating colds with over-the-counter medications (over-the-counter sales) is estimated at more than $ 1.5 billion annually. The cost of direct treatment at an outpatient clinic is estimated at nearly $ 4 billion. Indirect costs due to reduced wages due to limited activity are substantially greater.

At present, only symptomatic treatment is useful for a common cold; Most of these drugs are taken by mouth. Typical prior art oral compositions for treating the nose and other colds, flu, allergies and sinus symptoms, discomfort, pain, fever and general discomfort associated therewith are generally analgesics (aspirin or acetaminophen) and one The above-mentioned antihistamine, congestion inhibitor, cough suppressant, antitussives (cough medicine), and expectorant are contained. Other specific pharmaceutical actives for nasal symptoms (eg, nasal congestion) generally contain oxymethazolin or phenylephrine. This active is usually delivered topically to the nasal mucosa via a nasal spray. For individuals with certain medical conditions, such as heart disease, high blood pressure, diabetes or thyroid disorders, oral medications, such as congestive medications, may pose a risk of undesirable drug interactions and may cause adverse reactions. Therefore, stable delivery from certain nasal symptoms through the composition is highly desirable without the need for such pharmaceutically active agents.

Topical application of stannous gluconate to gums or oral mucosal tissues of subjects prone to cough and / or flu has been found to help reduce the incidence of such diseases.

It is therefore an object of the present invention to provide a topical oral composition which provides a treatment method for preventing colds and flu.

[Overview of invention]

The present invention relates to a method of reducing said diseases in a subject susceptible to colds and similar symptoms, such as the flu, by applying a composition containing an effective amount of stannous gluconate to gum or oral mucosal tissue. .

The present invention provides for preventing or inhibiting similar diseases such as colds and flu, such as colds and flu, by using a composition for oral administration containing stannous gluconate applied to gums or oral mucosal tissue of a subject susceptible to colds. It is about a method.

The composition of the present invention contains certain essential ingredients as well as non-essential ingredients.

Stannous gluconate

Stannous gluconate is an essential component of the composition. This material is a known stannous chelate and can be provided to the composition as a chelate or as a separate soluble stannous and gluconate salt and a chelate formed in situ. Such salts include stannous chloride and sodium gluconate. Stannous gluconate is present in the composition at a level of about 0.1 to about 11%, preferably about 0.2 to about 4%.

Acceptable carrier

The carrier for the active ingredient (s) can be any excipient suitable for use in the oral cavity. Such carriers include conventional ingredients such as mouthwash, gargle, paste toothpaste, powder toothpaste, prophylactic paste, lozenge tablets, gums and the like, and are described in more detail below. Toothpaste and mouthwashes are preferred systems.

In addition to the active agent (s), the present compositions may be used for antiplaque / gingivitis agents such as quaternary ammonium compounds, water insoluble agents such as triclosan, tea (as described below), stannous salts and zinc salts It may contain. Formulations of this type are described in US Pat. No. 4,894,220 (Nabi et al., Jan. 16, 1990); US Patent No. 4,656,031 (Lane et al., April 7, 1987); And US Pat. No. 5,004,597 (Majeti et al., April 2, 1991). All of these are incorporated herein by reference in their entirety.

The abrasive polish material contemplated for use in the present invention may be any material that does not excessively wear dentin. These include, for example, silica, including calcium and precipitates, calcium carbonate, dicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalcium phosphate, calcium polymethaphosphate, insoluble sodum polymethaphosphate, hydrated alumina and resinous Abrasive materials such as particulate condensation products of urea and formaldehyde, and other materials disclosed in US Pat. No. 3,070,510 (Cooley et al., December 25, 1962), which are incorporated herein by reference. Mixtures of abrasives may also be used.

Various types of silica tooth abrasives can provide the inherent benefits of excellent tooth clean and gloss performance without undesirable tooth enamel or dentin wear. Silica abrasive materials are also highly compatible with soluble fluoride and polyphosphonate sources. For this reason, they are preferable to be used here.

Silica abrasive gloss materials useful herein, like other abrasives, generally have an average particle size of about 0.1 to 30 microns, preferably 5 to 15 microns. The silica abrasive may be precipitated silica or silica gel, such as silica zero gels described in US Pat. No. 3,538,230 (Pader et al., March 2, 1970) and US Pat. No. 3,862,307 (DiGiulio, June 21, 1975). Used herein for reference). Preferred are silica zero gels sold under the trade name "Syloid" (W. R. Grace & Company, Davison Chemical Division). Preferred precipitated silica materials include silica commercially available under the trade name "Zeodent" from J. M. Huber, preferably "Zeodent 119". This silica abrasive is described in US Pat. No. 4,340,583 (July 29, 1982), which is incorporated herein by reference.

The abrasive in the compositions described herein is present at a level of about 6 to about 70%, preferably about 15 to about 25%, if the toothpaste is a paste toothpaste. If the composition is a powdered toothpaste, levels as high as 90% can be used.

The compositions of the present invention may also contain soluble fluoride ion sources such as sodium, potassium, lithium fluoride, stannous fluoride and sodium monofluorophosphate, among others. The fluoride source should be sufficient to provide about 50 to about 3500 ppm of fluoride in a paste toothpaste or mouth rinse.

Flavoring agents may also be added to the dentifrice compositions. Suitable flavoring agents include, among others, presser foot oil, peppermint oil, sparemint oil and clove oil. Sweeteners that can be used include aspartame, acesulfame, saccharin, dextrose, levulose and sodium cyclamate. Flavoring and sweetening agents are generally used at levels of from about 0.005% to about 2% by weight in toothpaste.

Toothpaste compositions may also contain emulsifiers. Suitable emulsifiers are suitably stable emulsifiers and foams over a wide pH range, including non-soap anionic, nonionic, cationic, counterionic and zwitterionic organic synthetic detergents. Many of these suitable surfactants are disclosed in US Pat. No. 4,051,234 (Gieske et al., Sep. 27, 1977), which is incorporated herein by reference.

Water is also present in the paste toothpaste of the present invention. The water used to prepare commercial paste-type toothpastes should preferably be deionized and free of organic impurities. Water generally constitutes about 10-50% by weight, preferably about 20-40% by weight of the paste-like toothpaste composition herein. This amount of water includes free water added in addition to being introduced with other materials such as sorbitol.

In preparing paste toothpastes, it is necessary to add some thickening material to provide the desired hardness. Preferred thickeners are the carboxyvinyl polymers, xanthan gum, carrageenan, hydroxyethyl cellulose and water soluble salts of cellulose ethers, such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose, in the forms previously mentioned herein. Natural gums such as karaya gum, gum arabic and tragant gum can also be used. Colloidal magnesium aluminum silicate or finely divided silica can be used as part of the thickener to further enhance the texture. 0.5 to 5.0% by weight of thickener in the total composition can be used.

It is also desirable to include some wet material in the pasty toothpaste to prevent it from curing. Suitable humectants may include glycerin, sorbitol, xylitol and other edible polyhydric alcohols at levels of about 5 to about 70%.

Another preferred embodiment of the present invention is a mouthwash composition. Conventional mouthwash composition components may contain a carrier of the active agent of the invention. Oral cleaning solutions generally contain a water / ethyl alcohol solution of about 20: 1 to about 2: 1, and preferably contain flavors, sweeteners, wetting agents and subsiding agents as mentioned in the toothpaste. do. Wetting agents, such as glycerin and sorbitol, give the mouth a moist feeling. Generally 0 to 60% (preferably 10 to 25%) of ethyl alcohol and 0 to 20% (preferably 5 to 20%) of humectant, 0 to 0, based on the weight of the mouthwash of the present invention 2% (preferably 0.01 to 0.15%) emulsifier, 0 to 0.5% (preferably 0.005 to 0.06%) sweetener, such as saccharin, 0 to 0.3% (preferably 0.03 to 0.3%) Flavor, and balance water.

Suitable lozenge tablets and chewing gum components are disclosed in US Pat. No. 4,083,955 (Grabenstetter et al., Apr. 11, 1978), which is incorporated herein by reference.

Other optional ingredients useful in the present invention are pyrophosphate salts, such as those described in US Pat. No. 4,515,772 (Parran et al., May 7, 1985), hereby incorporated by reference. Also useful are nonionic antibiotics, such as triclosan, described in US Pat. No. 4,894,220 (Nabi et al., Jan. 16, 1990), hereby incorporated by reference. Both patents are incorporated herein by reference.

Another agent that can be used in the present invention is an alkali metal bicarbonate such as sodium bicarbonate. These are commercially stable items and can be used with peroxide compounds in separate compartments, as disclosed in US Pat. No. 4,849,213 and US Pat. No. 4,528,180 (both of which are incorporated herein by reference).

Another preferred composition of the invention is a controlled-release drug delivery system for positioning in the periodontal pocket. Such systems include, but are not limited to, cellulose hollow fibers disclosed in US Pat. No. 4,175,326 (Goodson, Nov. 27, 1979); Ethylcellulose film disclosed in US Pat. No. 4,568,535 (Loesche, Feb. 4, 1986); Light absorbing putty materials disclosed in US Pat. No. 4,568,536 (Kronenthal, Maftei and Levy, Feb. 4, 1986); In vivo degradable microspheres and matrices disclosed in US Pat. No. 4,685,883 (Jernberg, Aug. 11, 1987); Microparticles or microcapsules disclosed in US Pat. No. 4,780,320 to Baker, Oct. 25, 1988; Polymeric elements disclosed in European Patent No. 0, 140,766 (Goodson, published May 8, 1985); And the lactide / glycolide executions described in US Pat. No. 5,198,220 (Damani, Mar. 30, 1993), which patents are incorporated herein by reference. Such controlled-release delivery systems generally consist mainly of polymeric materials and include a matrix that captures stannous gluconate, a solid matrix with one or more active agents. Typically, the active agent spreads from the solid material into the periodontal sac over time.

Preferred controlled-release drug delivery systems comprise from about 0.001 to about 50%, preferably from about 0.01 to about 25%, more preferably from about 0.1 to about 15%, even more preferably from about 1 to about 10% Monotin gluconate and a controlled-release carrier.

Preferred pH of the composition and / or pH in the mouth may be any pH that is safe for firm and flexible tissues of the mouth. Such pH is generally about 3 to about 10, preferably about 5 to about 9.

Manufacturing method

The carrier composition of the present invention can be prepared using a general method in the field of oral products.

For example, a paste-type toothpaste composition can be prepared by mixing the humectant portion with water and heating it to 66-71 ° C. The fluoride source, if present, is added with sweetening, whitening (opaque) agents and flavoring agents.

Use composition

The present invention in a method aspect comprises applying a safe effective amount of the composition to gums and / or oral mucosal tissue. Generally at least about 5 g of mouthwashes and at least about 0.5 g of paste or liquid toothpaste.

Preferred methods of the present invention comprise contacting the composition of the present invention with oral cavity soft tissue for at least about 15 seconds, preferably from about 20 seconds to about 10 minutes, more preferably from about 30 seconds to about 60 seconds. This method often involves spitting out most of the composition after such contact, preferably after rinsing with water or the like. The frequency of such contacts is preferably about once per week to about five times per day, more preferably about three times per week to about four times per day, even more preferably about once to about three times per day. Such treatment period typically ranges from about 1 day to lifetime. In general, people may be exposed to cold viruses, so they may use the products described herein before, after exposure, or when the first signs of cough are seen.

The composition used in the process of the invention can also be used by the subject as a gargle. In addition, subjects who consume significant amounts of vitamin C may have improved relief from colds in the use of the compositions described herein.

The following examples further illustrate and demonstrate preferred embodiments within the scope of the present invention. Various modifications of the embodiments are possible without departing from the spirit and scope of the invention, which is intended to be illustrative only and not to be considered as a limitation of the invention.

Example I

Paste Toothpaste

Weight% 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

Na carboxymethyl cellulose 1.050 1.050

Magnesium Aluminum Silicate 0.408 0.408

Na Alkyl Sulfate (27.9% Solution) 4.000 4.000

Na Gluconate 1.738 3.476

Stannous chloride dihydrate 1.794 1.794

Na saccharin 0.200 0.200

Flavor 0.851 0.851

FD & C Blue # 1 (1% Solution) 0.051 0.051

Sodium Fluoride 0.243-

Na hydroxide (50% solution) 0.500 0.395

pH 4.5 4.5

Example II

Mouthwash

Weight% weight%

TiN Chloride Dihydrate 0.519 0.519

Sodium Gluconate 0.521 1.041

Glycerin 8.000 12.000

Sorbitol (70% aqueous solution)--

Ethanol 10.000 10.000

Polysorbate 80 0.300 0.300

Sodium Saccharin 0.050 0.050

Flavoring 0.150 0.150

Sodium hydroxide 0.020 0.020

Benzoic Acid 0.050 0.050

FD & C Blue # 1 (1% solution) 0.020 0.020

Sodium Monofluoro Phosphate 0.183-

Water 80.187 77.850

Example III

Topical gel

Weight% weight%

Stannous chloride dihydrate 1.794 2.153

Sodium Gluconate 1.750 2.082

Glycerin 91.896 70.000

Sorbitol (70% solution)-21.765

Sodium Carboxymethyl Cellulose 0.600 0.800

Hydroxyethyl cellulose--

Flavor 1.000 1.000

Sodium Saccharin 0.200 0.200

Sodium Alkyl Sulfate (27.9%) 2.000 2.000

Sodium Monofluoro Phosphate 0.760-

Example IV

Oral Rinsing Tablets

Stannous chloride dihydrate 0.519 g 0.519 g

Sodium Gluconate 0.50Og 0.700g

Flavor 0.150g 0.150g

Sodium Saccharin 0.050g 0.200g

Mannitol 0.773 g-

Sodium Carboxymethyl Cellulose 0.050g-

Sodium Benzoate 0.030g 0.025g

Citric acid-0.200 g

Sodium carbonate-0.100 g

Sodium bicarbonate-0.200 g

Glycine-0.050 g

Sodium monofluoro phosphate 0.01 g-

2.255g 2.144g

Water water

Of 97.745g Of 97.856g

Melt Melt

Claims (10)

Reducing the incidence of colds and similar diseases, such as the flu, in animals by applying an effective amount of a composition containing an effective amount of stannous gluconate to the gums and / or oral mucosal tissue of a susceptible animal How to let. The method of claim 1, wherein the composition is in the form of a paste toothpaste. The method of claim 1, wherein the composition is in the form of an oral rinse. The method of claim 1, wherein the composition is in the form of a delivery system with site-specificity. The method of claim 1 wherein the concentration of stannous gluconate is from about 0.1 to about 11%. A method according to claim 2, wherein the paste toothpaste contains a silica abrasive. 7. The method of claim 6, additionally containing another stannous salt. 8. Process according to claim 6 or 7, further containing a source of fluoride ions. The method according to claim 6, further comprising an agent selected from the group consisting of surfactants, wetting agents, sweeteners and mixtures thereof. The method of claim 6, wherein the humectant is selected from the group consisting of sorbitol, glycerin, xylitol, and mixtures thereof.