MXPA99007867A - Stannous fluoride gel with improved stand-up - Google Patents

Abstract

The present invention relates to a stannous fluoride-containing gel comprising from about 0.3%to about 1.0%(by weight) stannous fluoride, from about 1.0%to about 10%(by weight) silica thickening agent and anhydrous glycerin. Preferably, these gels also contain from about 0.01%to about 5%(by weight) of a gum system, e.g. hydroxyethyl cellulose. These gels exhibit very good ribbon stand-up qualities and excellent fluoride ion and stannous ion stability. Also, the present invention relates to an improved method for producing the above gels. This method uses mixing equipment commonly employed to manufacture dentifrices and provides a simplified processing scheme.

Description

STAINLESS FLUORIDE GEL WITH IMPROVED MAINTENANCE IN ITS FORM Ca po of the Invention This invention relates to a dental gel containing stannous fluoride and more particularly to a process for producing a stannous fluoride gel which has improved maintenance characteristics of the strip form when it is distributed from a tube. These gels exhibit a surprisingly good stability of the fluoride and io tin ion.

Background of the Invention Stannous fluoride (SnF2) has been reported to be an effective agent for the treatment of several oral conditions. The most important dental benefit imparted by stannous fluoride is the reduction of dental caries. Toothpastes sold by stockbrokers, which contain stannous fluoride, have been classified by the Food and Drug Administration of the U.S.A. (U.S. Food &Drug Administration) as therapeutic agents that provide protection Ref.031175 against the development of dental caries. The initial stannous fluoride toothpastes contained abrasive systems that reacted with fluoride, rendering these products ineffective in reducing tooth decay. Significant progress in the development of new abrasives has led to the development of stannous fluoride dentifrices with significantly improved fluoride ion availability. However, the antibacterial tin ion undergoes rapid hydrolysis and oxidation in water-based dentifrice, leading to a tin ion essentially not available. Now there are self-applied topical fluoride products based on 0.4% stannous fluoride but without the excipients of the formula that interact with fluoride and tin ions (eg, abrasives, water, surfactants, etc.). The main excipient of these "gels" of stannous fluoride is the glycerin humectant. The prior art clearly shows that the manufacturing method (eg, mixing times, temperature, manufacturing equipment) is critical to ensure the stability and availability of fluoride and tin ions. Actually the process described in U.S. Pat. Nos. 4,418,057 and 4,533,544 for a stannous fluoride gel, presents numerous challenges for manufacturing equipment. It requires the preparation of several lateral phases consisting of precise levels of stannous fluoride and glycerin. Mixing temperatures can vary up to 180 ° C, which are not easily achieved in most plants without special equipment. Another disadvantage of the gel preparations described in U.S. Pat. Numbers 4,418,057 and 4,533,544 is that the gels have a semi-liquid consistency, and when they are distributed over the bristles of a toothbrush, the gel immediately sinks through the bristles and escapes from the brush so that only a relatively small of the distributed product is retained on the toothbrush. Accordingly, SnF2 suspended in the thick anhydrous glycerin has not found wide acceptability as a home product due to the fact that the semifluid gel composition can not be controllably retained on the bristles of the toothbrush and then applied to the teeth for reliably supply SnF2 for the treatment of dental pieces. It is therefore an object of the present invention to provide a processing scheme for producing a stannous fluoride gel which avoids the disadvantages of the prior art.

It is also an object of the present invention to provide a stannous fluoride gel with good strip form maintenance qualities and a surprisingly good stability of the tin ion and the fluoride ion. These and other objects will be evident from the following.

Detailed description of the invention The present invention relates to a gel containing stannous fluoride, which comprises from about 0.3% to about 1.0% (by weight) of the stannous fluoride, from about 1.0% to about 10% (by weight) of silica thickening agent and an anhydrous base. Preferably, these gels also contain from about 0.01% to about 5% (by weight) of a gum system, for example hydroxyethyl cellulose. These gels exhibit very good strip-shape maintenance qualities and excellent stability of the fluoride ion and tin ion. Also, the present invention relates to an improved method for producing the above gels. This method uses the mixing equipment commonly used to make dentifrices and provides a simplified processing scheme. This method involves (a) dissolving about 0.01 to about 5.0 parts of the rubber system in an anhydrous base; (b) mixing from about 1 to about 10 parts of silica thickening agent; and (c) adding from about 0.36 to about 0.46 parts of stannous fluoride, wherein the anhydrous base is present in a sufficient amount such that the sum of all parts of the ingredients is 100. The present inventive improvement in maintenance of the gel form, the stability of the fluoride / tin ion and the processing techniques, is based on the incorporation into the gel of a silica thickening agent. All percentages and proportions used here are on a weight basis unless otherwise specified. When used herein, "holding" qualities of the strip form refers to a strip of gel which has an extrudable consistency such that the strip extruded from the gel, when distributed over the bristles of a toothbrush, it will remain on the upper surface of the bristles for a period of time sufficient to allow full application of the gel to the teeth, for example, a time interval of at least 0.5 to 1.0 minutes. The stannous fluoride-containing gel compositions of the present invention are generally comprised from about 0.3% to about 1.0% (preferably 0.36% to about 0.46%) of stannous fluoride, from about 1.0% to about 10.0% (preferably 3.0% to 8.0). %) of silica thickening agent and an anhydrous base. Preferably the anhydrous base is glycerin. In addition, the preferred gels of the present invention also include from about 0.1% to about 5% of a gum system, more preferably from about 0.3% to about 1.0% of a gum system. Thickening silica is used for three reasons. First, it increases the viscosity of the batch during processing by ensuring a good dispersion of the stannous fluoride (ie, it prevents the stannous fluoride from settling to the bottom of the tank). Second, it provides a strip with very good shape maintenance characteristics. Third, it has been observed that the resulting gel product exhibits a stability of the fluoride ion and the surprisingly good tin ion. The thickening silica used in the practice of the present invention is a colloidal or fuming silica. These silicas are in the form of finely divided particles, which typically have a particle size of less than about 4 microns. The fumed silica is typically made by the combustion of silicon tetrachloride in oxygen-hydrogen furnaces. The fumed silica is commercially available under the trade name Aerosil from Degussa Corporation and under the registered name Cab-O-Sil® from Cabot Corporation. A preferred fuming silica is Aerosil® 200 from Degussa Corporation, Ridgefield Park, NJ. As described in the literature of the manufacturers (Leaflet PT 6-50 1-694H), Aerosil 200 has the following properties: B BET surface area (DIN 66131) 200 + 25 m / g Average particle size 12 nm U Density in Sun. Standard shock absorber (DIN ISO 787 / X1, JIS K 5101/18) approx. 40 g / 1 Humidity (DIN ISO 787/11, ASTM D 280, JIS K 5101/21) < 1.5 ß pH (in 4% aqueous dispersion) 3.6-4.3 Si02 (based on a material burned for 2 hours at 1000 ° C) > 99.8% A rubber system may optionally be included in the SnF2 gels of the present invention at a concentration of from about 0.01% to about 5.0% by weight, preferably from about 0.3% to 1.0% by weight. The rubber systems used in the practice of the present invention are food grade gums. Suitable gums are selected from the group consisting of: hydroxyethylcellulose. A preferred hydroxyethylcellulose is Natrosol® 250 hydroxyethylcellulose manufactured by Aqualon Division of Hercules Inc., Wilmington, Delaware. The "LR" hydroxyethylcellulose, food grade, is the most preferred. The preferred hydroxyethyl cellulose has a molecular weight of about 9.0 x 104 as an estimate of the intrinsic viscosity measurements as provided by the manufacturer. Hydroxyethylcellulose has a low moisture content over a particle size such that at least 90% passes through a No. 40 mesh.

The compositions of the present invention may also contain an effective amount of a flavoring component which does not interfere with the stability of tin ions and fluoride ions. The flavoring ingredient typically constitutes from about 0.05% to about 2.0% (preferably from about 0.1 to about 1.5%) of the gel composition. Suitable flavoring constituents are the flavoring oils, for example, the oils of spearmint, mints, wintergreen, clove, methyl salicylate, cinnamic aldehydes and menthol. The compositions of the present invention may also contain other typical toothpastes and gel-like additives as long as they do not interfere with the stability of the tin ions and the fluoride ions in the gel. These compositions are free of adhesives. The gel compositions of the present invention are prepared by (a) dissolving about 0.01 to about 5.0 parts of the gum system in an anhydrous base; (b) mixing it in from about 1 to about 10 parts of the silica thickening agent; and (c) adding from about 0.36 to about 0.46 parts of stannous fluoride, wherein, the anhydrous base is present in a sufficient amount such that the sum of all parts of the ingredients is 100. Preferably, the gum is hydroxyethylcellulose, the anhydrous base is glycerin (99.5%) and the silica thickening agent is silica. Also, step (a) is carried out at a temperature above 120 ° C, typically approximately 150 ° C. Optionally, the manufacturing method also includes a step of adding an additional seasoning (d) which involves mixing from about 0.05 to about 2.0 parts of a seasoning component that does not interfere with the stability of the tin ions or the ions of fluoride in the resulting composition. Preferably, the composition is cooled to a temperature below 40 ° C prior to step (d). The most preferred method uses from about 0.1 parts to about 2.0 parts of hydroxyethylcellulose, from about 3 to about 8 parts of the formed silica and from about 0.1 to about 1.5 parts of the flavor or seasoning.

The following examples are further illustrative of the present invention, but it is understood that the invention is not limited thereto.

EXAMPLES Briefly, the following method for producing a batch of stabilized stannous fluoride gel uses the mixing equipment commonly used to make toothpastes. The main batch tank is a Nauta mixer. What is also required is a small side or secondary phase tank, equipped with a submersion heater and a top Cowles blade or blade. The following procedure was used to prepare the gel described in Table 1: I. Preparation of the Rubber Phase (Phase A): B Add the majority of the amount of the glycerin formula of the Phase (99.5%) (See Sno. 010 in the table of the formula below) in the tank of the phase lateral or secondary equipped with a submersion heater and top mixer with a Cowles blade or blade.

Start of mixing. Adjust the weight and speed of the mixer to obtain a good swirl movement. Slowly add the amount of the hydroxyethylcellulose formula (Sno. 020) in the vortex. It is stirred continuously until it disperses well. Start heating and heat the stage to a minimum of 130 ° C. Continue mixing while heating, adjust the speed of the mixer to avoid splashing, when the phase becomes less viscous during heating. Turn off the heater when the batch temperature reaches 130 ° C and continue mixing for 15 minutes. Stop mixing and evaluate the batch to verify the presence of gum particles. If the particles are observed, mix for an additional 15 minutes, or until they are are scattered. Add the remaining amount of glycerin (Sno. 030) in the batch and continue mixing and start cooling with the water jacket until the batch temperature is lowered below 45 ° C.

B Continue agitating the solution at a low speed until the phase is transferred to the main batch tank.

II. Preparation of the Main Phase (Phase B): Transfer the gum phase (Phase A) to the Nauta mixer. Activate or turn on the fragment breakers, start the course with the auger in the down position. Weigh the amount of the remaining glycerin formula (Sno. 040) into the pot or cauldron of the side or secondary phase and transfer it to the Nauta mixer, so which raises the phase in the tank and the hoses. Turn off fragment breakers. Close and seal the Nauta tank and adjust the vacuum to 66 cm (26") of Hg Disconnect the vacuum 20 Using the feed opening, slowly extract the amount of the Formula of the smoking silica Aerosil 200 mark (Sno. 050) Stop the addition when the vacuum is reduced to 38.1 cm (15") of Hg. Continue mixing under a closed vacuum until the entire Aerosil is mixed or combined in the batch. Restore the vacuum to 66 cm (26") of Hg, and then disconnect the vacuum Repeat the previous steps until the entire Aerosil has been mixed in the batch Start the cooling Continue the cooling during the subsequent steps until the Batch temperature is below 40 ° C. 10 Start vacuum and mixing under vacuum open conditions for 15 minutes Release the vacuum and open the manhole of the mixer Stop the run or sweep near the inlet to man, activate or operate the auger in the downward position. Start or light the lump fragmenters. Slowly add the amount of the stannous fluoride formula (Sno. 060). Close and seal the mixer. Start the tour and mix under open conditions under vacuum for 10 minutes. Release the vacuum and stop the fragmenters of lumps. Recirculate the batch and remove four cubes of the batch from the lower opening and add them to the top part of the tank.

B Mix under open vacuum conditions during minutes. B Close the gap.

III. Lot Complement Continue mixing and cooling until the batch temperature is below 40 ° C. Empty the amount of the flavor or seasoning into the formula (Sno.070). Mix under closed vacuum for 5 minutes. Mix under open conditions under vacuum during minutes. Stop mixing. Release the vacuum and open the mixer cover.

The resulting product exhibits exceptional smoothness and clarity and is free of trapped air.

The accelerated stability of the batches prepared using the above method has been evaluated. The concentrations of the Tin ion and the Fluoride ion are available in percentages by weight. OR or C? ? n- rt F H s-i DJ 3 H- or P o > Analyzed by Time weeks at 8 weeks to 12 weeks at the following following IODs? o Zero conditions conditions conditions Dl-i 3 H- fD a (X H- or a or C? 3 ci > rt Or o? to ? TI Note: "RT" = Ambient Temperature or (r1 C? A rt C? C? It is noted that in relation to this date the best method known by the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, property is claimed as contained in the following

Claims (12)

1. A stannous fluoride gel composition exhibiting improved maintenance of its shape and good stability of the tin ion and the fluoride ion, characterized in that it comprises from about 0.3% to about 1.0% by weight of tin fluoride, about 1.0% up to about 10.0% silica thickening agent, optionally one or more of a gum system, a flavoring or flavoring component which does not significantly destabilize tin ions and fluoride ions, and gel or paste additives typical teeth which do not interfere with the stability of tin ions and fluoride ions; and the remainder being an anhydrous base, wherein the resulting gel provides an effective therapeutic amount of the tin ions and the fluoride ions.

2. The composition according to claim 1, characterized in that the anhydrous base is glycerin.

3. The composition according to claim 2, characterized in that the stannous fluoride is present in the composition at a concentration of about 0.36% up to about 0.46% by weight.

4. The composition according to claim 3, characterized in that the silica thickening agent is a colloidal silica or a fumed silica.

5. The composition according to claim 4, characterized in that it contains from about 3.0% to about 8% fumed silica.

6. The composition according to claim 5, characterized in that it also comprises a rubber system.

7. The composition according to claim 6, characterized in that the gum system is selected from the group consisting of hydroxyethylcellulose, xanthan gum and carrageenan.

8. The composition according to claim 7, characterized in that the rubber system is hydroxyethyl cellulose.

9. The composition according to claim 8, characterized in that the rubber system is present in the composition at a concentration of about 0.01 to about 5.00% by weight.

10. The composition according to claim 9, characterized in that it contains from about 0.3% to about 1.0% of the rubber system.

11. The composition according to claim 10, characterized in that it further comprises from about 0.05% to about 2.0% of a flavor component which does not significantly destabilize the tin ions and the fluoride ions. 12. The composition according to claim 11, characterized in that it contains from about 0.1% to 1.5% of the flavor or seasoning component. 13. A method for producing the compositions of the stannous fluoride gel, characterized in that it comprises the steps of: (a) dissolving about 0.01 to about 5.0 parts of the gum system in an anhydrous base; (b) mixing in from about 1 to about 10 parts of silica thickening agent; and (c) adding from about 0.36 to about 0.46 parts of the stannous fluoride wherein the anhydrous base is present in a sufficient amount such that the sum of all the ingredients parts is 100. 14. A method according to claim 13, characterized in that the gum system is hydroxyethyl cellulose, the anhydrous base is glycerin (99.5%) and the silica thickening agent is fumed silica. 15. A method according to claim 14, characterized in that step (a) is carried out at a temperature above 120 ° C. 16. A method according to claim 15, characterized in that step (a) is carried out at approximately 150 ° C. 17. A method according to claim 15, characterized in that it further comprises the additional step of: (d) mixing from about 0.05 to about 2.0 parts of a flavor component that does not interfere with the stability of tin ions and fluoride ions in the resulting composition. 18. A method according to claim 17, characterized in that the composition is cooled to a temperature below 40 ° C prior to step (d). 19. A method according to claim 18, characterized in that from about 0.1 part to about 2.0 parts of the hydroxyethyl cellulose are dissolved in step (a); from about 3 to about 8 parts of the fumed silica are mixed in step (b); and from about 0.1 to about 1.5 parts of the flavor or seasoning are mixed in step (d).

12. A method according to claim 19, characterized in that the composition of the resulting gel provides an effective therapeutic amount of the tin ions and the fluoride ions.