NEUTRAL TOPICAL SODIUM FLUORIDE GEL

Abstract: A neutral topical sodium fluoride gel is disclosed which comprises a thickened aqueous solution of sodium fluoride buffered to maintain a pH of from about 5 to 9.

Description: NEUTRAL TOPICAL SODIUM FLUORIDE CEL The invention relates to a neutral topical sodium fluoride gel composition useful for the control and prevention of dental caries when topically applied to erupted teeth. Background of the Invention Neutral aqueous solutions of sodium fluoride were first used in the prevention of dental caries about 40 years ago. The initial clinical studies using neutral sodium fluoride were carried out by Xnutson and Ar..strong(1) and by Bibby(2). In the early 1960's, acidulated phosphate fluoride ("APF") appeared to be a preferred material in that some laboratory tests by Brudevaid et al.(3) indicated that the APF System gave a higher fluoride uptake than neutral sodium fluoride. Therefore, the predominant fluoride material used by dentists, hygienists, and other dental technicians since then has been the APF material. In the late 1960's, the APF material was introduced in the form of a gel. One such formulation is described by Elbreder in U.S. Patent No. 3,337,412. Another APF gel is described by Weitzri.an et al., in U.S. Patent No. 4,267,167. As far as is known to the inventor, since the initial use of neutral aqueous sodium fluoride in dental caries prophylaxis, no one has proposed the use of an operatorapplied topical -"gel" or thickened aqueous solution thereof in dentistry. This is surprising, since, from the standpoint of clinical efficacy, it nmB is believed that (1) Public Health Rep. 52, 1701 (1943). {2) J. Am. Dent. Assoc. 31, 317 (1944). (3) Arch. Oral Biol. 2, 167 (1963). there is no difference between neutral sodium fluoride and APF(4), and yet there are some disadvantages to the use of the APF gel. For instance, APF has an acid etching potential for porcelain, polymer-glass composite materi- als, and for metal bridge-work and orthodontic brackets. This could lead to staining, weakening, and reduction of polish. Up to now, most professional fluoride "gel" treatments have been carried out on pre-teenage children. On these patients, the acid etching potential of APF gel is not a significant problem because they have a low incidence of porcelain, composites, metal bridgework, etc. However, the dental profession has come to. recognize that fluoride treatment would-beteneficial to many more patients than pre-teenagers. For instance fluoride treatment to control and/or prevent caries is useful for those undergoing orthodontic treatment, children as well as adults. Because of improved preventive and treatment measures, more adults are retaining their natural teeth; therefore, coronal and¯root dental caries is becoming a significant health problem in the adult population(5). Adult patients suffering from gum disease such as gingivitis and periodontal disease would benefit from fluoride treatment to retard the formation of caries in the portions of te roots of teeth that are becoming exposed because of receding gum lincs. Also, people who are handicapped, people with impaired salivary flow caused hy head and neck radia tion, and hemophiliacs can benefit from fluoride treatmen' to control dental caries. However, when fluoride gel treatment is extended to such patients, the acid etching potential of APF gel can become a significant concern. (4) For review, sec Ripa, Intl. Dent. J. 31, 105 (1981). (5) U.S. National Center for health Statistics data, 1971-1974. The present invention is based upon the discovery that a neutral sodium fluoride gel can be produced and used far caries prevention and control. Brief Summary of the Invention The invention provides a thickened or viscous aqueous solution of sodium fluoride containing sufficient sof fluoride for prophylactic treatment of the teeth, said thickened solution having a pH within the range of fro about 5 to about 9. Detailed Description of The Invention The neutral topical sodium fluoride gel of the invention is actually a thickened solution, and is not a true el. However, because the word "gel" is widely employed in the dental profession to refer to such materials, it will be used herein, with the understanding that the invention actually relates to a thickened solution and not to a true crosslinked "gel". The gel of the invention includes water, sodium fluoride1 thickener, and a buffer to maintain the prl between about 5 and 9, and preferably between about 6 and 8. Optionally, the composition will also contain flavoring agents, sweeteners, preservatives, and coloring agents at levels necessary to achieve the desired effects. Thus, typical ranges of proportions of the ingredients are shown in the following Table I: Table I Basic Formulation Ingredient % (wiz) Water 75.2 - 96.1 Sodium Fluoride 1.0 - 5.0 Thickener 1.0 - 20.0 Buffer 0.5 - 1.5 Flavor Sweetener 0.1 - 0.3 Preservatives 0.15 - 0.35 Coloring . 0.05 - 0.15 The thickeners that are employed in the invention include water soluble thickening materials such as natural guns, --cellulose derivatives -such as sodium carboxymethyl cellu lose, hydroxyethyl cellulose, and the like, polyacrylic acid polymers, inorganic thickeners such as colloidal silica medium molecular weight alkylene oxide polymers such as ethylene oxide/propylene oxide polymers or polyethylene oxides, and modified starch. The thickeners must be safe for human ingestion (FDA approved for internal use), must not bind fluoride ion or in any way significantly affect its bioavailability, and must provide the desired flow characteristics to the products of this invention. The thickener is added in a proportion sufficient to achieve a solution viscosity adequate to maintain a gel in an inverted mouthpiece tray applicator for up to about four minutes (typical tine For a professionally applied fluoride treatment), and yet be fluid enough to have acceptable handling characteristics for the dental operator (e.g., when dispensing into a gel tray applicator). The thickening agent, therefore, must impart a certain degrce of thixotropy to the neutral sodium fluoride formulation such that at rest the product has a thick, gel-like consistency, but under a shearinj force, resulting perhaps from simple agitation, the sodium fluoride gel thins or undergoes a reversible transition to a more fluid condition. Routine experimentation will suffice to determine the exact proportion of thickener needed to impart the above characteristics. The Examples below illustrate typi¯l proportions for the particular thickeners used. The preferred formulation for use in the invention is shown below in Table II: Table II Preferred Formulation for the Neutral Sodium Fluorice "Gel" Composition Inqredient % (w/w ) Water 87.7 Sodium Fluoride 2.0 Carbopol 934P {Polyacrylic acid) 1.2 Xanthan Gum 1.2 Sodium Hydroxide, 100 [aqueous] 6.5 Disodium Phosphate, Anhydrous 0.7 Flavor 0.3 Sodium Saccharin 0.1 Sodium Benzoate 0.2 Methyl Paraben 0.05 Coloring Solution 0.05 100.00 pH = 7.0 VISCOSITY = 85 poises at 60 RPM and 25 C. Carbopol 934P is polymerized acrylic acid. The aqueous sodiun hydroxide is added to neutralize this material to form the sodium salt thereof. The pH of the gel can be adjusted to the desired range by adding acids or bases such as phosphoric acid, hydroehlor ic acid, or sodium hydroxide, which form salts that are safe to ingest, or by the addition of ingestible buffering agents such as sodium phosphates. Disodium phosphate and monosodium phosphate are the preferred buffers. The buffer is preferred in order to maintain the pH within the desired neutral range, since absorption of carbon dioxide from air could reduce the pff of an unbuffered gel. The thickening agent, either alone or in combination, is employed in a proportion sufficient to impart a viscosity of from about 40 to about 200 poises to the solution tested by a Brookfield Viscometer at 60 rHn and 25 C., using Spindle No. 5. The degree of thixotropy of the gel is preferably such that the Brookfield viscosity measured at 1.5 rpm and 25 C., using Spindle No. 4, is within the range of from about 500 to about 4,000 poises. The following examples describe additional gels that can be enployed in accordance with the invention: Example 1 The following example represents a formulation using a modified cellulose thickener, sodium carboxymethyl cellulose, though any other cellulose ether would apply, e.g., hydroxypropyl cellulose, hydroxyethyl cellulose, or a combination thereof (an ionic and nonionic cellulose flke sodium carboxymethyl cellulose and hydroxypropyl cellulose). The range for such thickeners would be about 1 to 5% tw/w) Ingredient % (w/w) Water 93.8 Sodium Fluoride 2.0 Sodium carboxymethyl cellulose 2.5 Disodium Phosphate 0.95 Monosodium Phosphate 0.05 Flavor 0.3 Sodium Saccharin 0.1 Sodium Benzoate 0.2 Methyl Paraben 0.05 Coloring 0.05 100.00 pH = 7.0 VISCOSITY = 130 poises at 60 RPM and 250C. Example 2 This example illustrates the use of water soluble acrylic acid polymers (carbomers, USP), e.g., Carbopol 934 ana 943 at 1 to 5; (w/w). Ingredient % (w/w) Water 81.1 Sodium Fluoride 2.0 Carbopol 934P 2.5 Sodium Hydroxide, 10% 13.0 Disodium Phosphate 0.7 Flavor 0.3 Sodium Saccharin 0.1 Sodium Benzoate 0.2 ethyl Paraben 0.05 Coloring Solution 0.05 100.00 pH = 7.0 VISCOSITY = 85 poises at 60 RPM and 25 C. Example 3 This example illustrates the use of a natural polysaccharide, i.e., xanthan gum, which can be used alone, as here, or in combination with another gun such as guar gum or a derivitive of alginic acid. Ingredient % (w/w) Water 93.8 Sodium Fluoride ' 2.0 Xanthan Gum 2.5 Disodium Phosphate 0.95 Monosodium Phosphate 0.05 Flavor 0.3 Sodium Saccharin 0.1 Sodium Benzoate 0.2 Methyl Paraben 0.05 Coloring Solution 0.05 100.00 = = 7.0 VISCOSITY = 80 poises at 60 RPM and 250 C. Example 4 This example illustrates the use of an inorganic thickener, i.e., magnesium aluminum silicate, in total concentration of 2 to 15% (w/w). Fumed silica can also be used as the inorganic thickener. Ingredient % (w/1 Water 86.3 Sodium Fluoride 2.0 Colloidal Magnesium Aluminum Silicate 10.0 Phosphoric Acid 1.0 Flavor 0.3 Sodium Saccharin 0.1 Sodium Benzoate - 0.2 Methyl Paraben 0.05 Coloring 0.05 100.00 pH = 6.5 VISCOSITY = 120 poises at 60 RPM and 25 C. Example 5 This example illustrates the use of Guar Gun in the range of 1 to 5% (w/w). Ingredient % (w/w) Water 94.1 Sodium Fluoride 2.0 Guar Gum 2.2 Disodium Phosphate 0.95 Monosodium Phosphate 0.05 Flavor 0.3 Sodium Saccharin 0.1 Sodium Benzoate 0.2 Methyl Paraben 0.05 Coloring 0.05 100.00 pH = VISCOSITY = 100 poises at 60 RPM and 25 C. Example 6 This example illustrates the use of a copolyner condensate of ethylene oxide and propylene oxide at 3 to 20%. Ingredient % (w/w) Water 78.3 -Sodium Fluoride 2.0 Pluronic F108 (ethylene oxide/propylene 18.0 oxide block copolymer) Disodium Phosphate 0.95 Monosodium Phosphate 0.05 Flavor 0.3 Sodium Saccharin 0.1 Sodium Benzoate 0.2 Methyl Paraben 0.05 Coloring O.CD 100.00 pH = 7.1 VISCOSITY = 105 poises at SO RPM and 250C. Example 7 This example illustrates the use of an ethylene oxide polymer, Polyox 301. Ingredient % (w/w) Water 93.3 Sodiun Fluoride 2.0 Polyox 301 3.0 Disodiun Phosphate 0.8 Monosodiu: Phosphate 0.2 Flavor 0.3 Sodium Saccharin 0.1 Sodium Benzoate 0.2 Methyl Paraben 0.05 Coloring 0.05 100.00 pH = 7.3 VISCOSITY = 90 poises at 60 RPM and 250 C. Example 8 This exanple illustrates the use of a mixture of sodium carboxymethyl cellulose and finely divided magnesium aluminum silicate in a ratio of 1:2 to 1:9. Ingredient % (w/w) Water 86.6 Sodium Fluoride 2.0 magnesium Aluminum Silicate 8.5 Sodium CMC 1.2 Monosodium Phosphate 1.0- Flavor 0.3 Sodium Saccharin 0.1 Sodium Benzoate 0.2 Methyl Paraben 0.05 Coloring 0.0 PH = 7.3 100.00 VISCOSITY = 110 poises at 60 RPM and 250 C. Example 9 This example illustrates the use of an acid-modified starch in the range of 2 to 158 (w/w). Ingredient % (w/w) Water 88.S Sodium Fluoride 2.0 "Instant Clear Gel" (Starch-from National 7.5 Starch and Chemical Company) Disodium Phosphate 0.95 Monosodium Phosphate 0.05 Flavor 0.3 Sodium Saccharin 0.1 Sodium Benzoate 0.2 Methyl Paraben 0.05 Coloring O.C: 100.00 pH = 6.9 VISCOSITY = 150 poises at 60 RPM and 25 C. Example 10 This example illustrates the use of a hydrocolloid seaweed extract, carrageenan, at 0.5 to 4.0% (w/w). Ingredient % (w; Water 94.1 Sodium Fluoride 2.0 Carrageenan 2.2 Disodium Phosphate 0.95 ,onosodium Phosphate 0.05 Flavor 0.3 sodium Saccharin 0.1 Sodium Benzoate 0.2 Methyl Paraben 0.05 Coloring 0.05 100.00 pH = 7.1 VISCOSITY = 110 poises at 60 RPM and 250 C. The thickened neutral odium fluoride aqueous solutions of the invention are applied to the teeth by the dentist, hygienist, or technician in the conventional manner. This involves either a tray technique or a "paint on" technique. The tray technique is preferred becauseof the one venience and time-saving aspects of the tray application. In this method, a gel application tray is filled approximately one-third full with the gel product. After the teeth are thoroughly dried, the filled tray is inserted into the patient's mouth and is maintained there for four minutes. Tha tray is then removed and the patient expectorates any excess gel remaining in the mouth. For the "paint on" technique, the teeth are isolated with cotton rolls and dried thoroughly with air. A cotton applicator is then dipped into the gel and applied to the teeth, keeping the teeth covered with gel for four minutes. Once again, aEter the cotton rolls are removed, the patient expectorates excess gel.

Claims: CLAIMS: 1. A thickened sodium fluoride aqueous composition com- prising water, sodium fluoride in a proportion of fro about 1 to about 5 weight percent of the total composition, and thickener, wherein the pH of the composition is within the range of from about 5 to about 9. 2. The composition of Claim 1 wherein said composi'io-. contains a buffering agent. or Claim 2 3. The composition.of Claim 1/wherein said composition includes flavoring agents, preservatives, and coloring agents. or Claim 3 t. The composition of Claim 2/wherein the buffering agent is disodium phosphate, monosodium phosphate, or mixture thereof. 5. . The composition of Claim 1, 2, 3, or 4 wherein said composition has a viscosity of from about 40 to about 200 poisec-tested by a Brookfield viscometer at 60 RPM and 250 C, and a viscosity of 500 to 4000 poises tested by a Brookfield viscometer at 1.5 RPM and 25 C. any one of 9 to 6. The composition of/Claims/5 wherein the thickener is polyacrylic acid or sodium salt thereof, a natural gum, sodium carboxymethyl cellulose, hydroxyethyl cellulose, colloidal silica, starch, colloidal magnesium alulainu: silicate, a hydrocolloid seaweed extract, or mixtures thereof any one of 1 to 7. The composition of any one of 1 to Claims/ wherein the pi is within the range of Erom about 6 to about 8. 8. A composition according to any one of Claims 1 to 7 for use in controlling dental caries. 9. A method of preparing a composition according to any one of Claims 1 to 8 comprising mixing said ingredients in the specified proportions and, if necessary, adjusting the pH to the specified range.

Inventors: ZAHRADNIK, ROBERT THOMAS
Applicants: JOHNSON & JOHNSON DENTAL PRODUCTS COMPANY
Application year: 1983
Main classification: A61K6
IPC codes: A61K6, A61K8, A61Q11