Priority

The present application is a non-provisional application that claims priority to U.S.

Provisional Application No. 61/637928, filed on April 25, 2012, the disclosure of which is hereby expressly incorporated by reference.

Field

[1] The present disclosure relates generally to an oral treatment. More specifically, the present disclosure relates to a varnish that provides for increased uptake of fluoride in enamel.

Background and Summary [2] Fluoride varnish is a highly concentrated form of fluoride which is applied to the tooth's surface, by a dentist, dental hygienist or other health care professional, as a type of topical fluoride therapy. It is not a permanent varnish but due to its adherent nature it is able to stay in contact with the tooth surface for several hours. It may be applied to the enamel, dentin or cementum of the tooth and can be used to help prevent decay, remineralize the tooth surface, and to treat dentine hypersensitivity.

[3] Fluoride-containing varnishes were originally developed some 50 years ago as a material for application by dentists to control dentinal hypersensitivity (i.e., pain to temperature changes and touch) in patients by occluding exposed dentinal tubules. In the 1960's scientists in Europe began adding 5% sodium fluoride to the varnishes to enhance their activity by

precipitating calcium fluoride on the exposed tubules along with the varnish. Additional clinical studies in Europe demonstrated that these fluoride-containing varnishes also were effective for the prevention of dental caries through the release of fluoride even though their retention on the enamel surface was generally less than 24 hours. As a result of these studies fluoride varnishes are now used throughout the world for both caries prevention and the treatment of dentinal hypersensitivity. [4] The effectiveness of a topical fluoride (such as a varnish) is primarily a function of the amount of fluoride uptake that can be achieved in previously demineralized areas.

Fluoride uptake is affected by the concentration of fluoride in the formula, the amount of time that the varnish is in contact with the demineralized area, and the ability of the varnish to induce migration of the fluoride from the varnish to the dental tissue.

[5] With respect to the concentration of fluoride in the varnish, increased

concentrations of fluoride also come with increased risks of dental fluorosis. This risk is especially pronounced and concerning for pediatric patients. Accordingly, simply providing a higher concentration of fluoride in the varnish is not always desired nor inherently superior.

[6] Fluoride varnish is composed of a high concentration of fluoride in a fast drying

(or curing), alcohol and resin based solution. Existing varnishes are known to have 5.0% sodium fluoride. The resin base is made of pine tree origin (e.g. colophonium or a derivative thereof). This resin provides allergic responses in some patients. Additionally, the resin has a yellow tint. When applied to teeth, this yellow tint is undesirable and unsightly. More recently derivatized (hydrogenated and other) versions have become readily available and used frequently. These varnishes have little color.

[7] Additionally, many existing varnishes, when applied, have a film thickness that is detectable to a patient. This thickness is noticeable and objectionable to the touch of the tongue. In addition, most existing varnishes are organoleptically unacceptable, especially for pediatric patients.

[8] Existing varnishes that contain sodium fluoride contain little or no water (<5%).

Since the fluoride is not easily soluble in these formulas, the fluoride normally settles and precipitates in these formulas. Sodium fluoride is an inorganic chemical compound that is soluble in water. Compositions such as consumer use dentifrices and oral rinses as well as professional use foams and gels containing fluoride contain water. These embodiments allow the fluoride to be evenly dispersed and therefore provide uniform deposition onto tooth surfaces. However, since these compositions begin breaking down immediately when introduced into the oral cavity, long term retention is not possible.

[9] The physical irritants of discoloration and objectionable feel are factors that tend to lead patients to reducing the amount of time that the varnish is permitted to act. In the case of the yellowing tint, this reduces patient likelihood to use the product in the first place and also increases the likelihood that the varnish will be prematurely removed. Similarly, the physical uncomfortability from film thickness increases the likelihood that the varnish will be removed prematurely, either voluntarily or through increased friction from being rubbed by the tongue.

[10] Existing varnishes also suffer from separation of their ingredients during storage.

Fluoride particles settle out of the mixture creating a non-homogeneous paste. U.S. Patent No. 7,563,833 to Orlowski recognizes the difficulty in retaining fluoride salts in suspension in dental varnish. Typically, fluoride varnishes are now marketed in unit dose packages that are mixed by stirring and immediately applied with a small brush covering all of the tooth surfaces. This mixing is required due to the settling out of the ingredients. Patients are instructed not to brush their teeth for at least 4 hours (to prolong retention of the varnish) and are advised that the varnish will be gone within 24 hours or less.

[11] Accordingly, what is needed is a varnish that does not induce a pine allergy, does not impart an unsightly yellow tint to the dental tissue, has acceptable taste properties, is of a thickness that is unnoticeable, has a fluoride concentration that reduces likelihood of dental fluorosis, has a prolonged retention time on the dental tissue, resists settling out of ingredients, and provides superior fluoride release and uptake in tooth tissue.

[12] Additional features of the present disclosure will become apparent to those skilled in the art upon consideration of the following detailed description of the presently perceived best mode of carrying out the disclosure.

Detailed Description

[13] According to one exemplary embodiment of the present disclosure, a varnish is provided that is made up of:

[14] 30% Bleached dewaxed shellac (from insect-derived lac);

[15] 2.5 % Sodium Fluoride;

[16] 58.8% Ethanol;

[17] 1% Citric Acid;

[18] 3% Flavoring;

[19] 2% Ammonium Phosphate; [20] 2% Xylitol;

[21] 0.6% Sodium Saccharin; and

[22] 0.10% Hydroxyapatite/Calcium Phosphate.

[23] While the above formulation lists specific quantities, it should be appreciated that embodiments are anticipated where deviations on the percentages of each ingredient are made. One of skill in the art will recognize that such deviations in percentages or additions of other ingredients in small amounts are within the scope of the disclosure.

[24] In one embodiment, the varnish is provided in a flow-through unit-dose applicator such as an ampule having a brush applicator present at an egress point thereof. One such applicator is described in U.S. Patent Number 5,716,104. The ampule is illustratively constructed from pliable plastic. Squeezing the ampule provides for egress of the varnish from the ampule and into the brush. The brush is then put into contact with dental tissue (enamel) to apply the varnish thereto. It should be appreciated that the varnish is of a suitable viscosity to allow movement through the brush and to be responsive to the applied squeezing pressure. As will be discussed below, the reduced viscosity of the varnish is achieved through certain ingredient choices.

[25] The Sodium Fluoride is provided having an average particle size (diameter) of less than 50 micrometers (microns). Further embodiments are provided where at least 80% of the particles have a diameter of less than 16 microns. The fluoride is milled to obtain these particle sizes. Tight tolerances on the particle size provide for consistent fluoride release properties. Furthermore, smaller fluoride particles decrease the likelihood of the particles settling out of solution. Additionally, smaller fluoride particles provide for increased ease of re- suspension thereof when some fluoride does happen to settle out. In addition to formulations having 2.5% sodium fluoride, embodiments are envisioned having greater amount of sodium fluoride, such as 5%. Indeed, formulations are envisioned having l%-7.5% fluoride by weight.

[26] As previously noted, traditional varnishes have relied on pine tree resin base. In order to remove the potential for pine allergy, the present varnish uses the bleached dewaxed shellac (lac). This shellac is a non- water soluble dewaxed, bleached shellac. This shellac, when applied, is colorless or clear such that no color is applied to the teeth thereby. Accordingly, the present varnish does not present an unsightly appearance. Ethanol is provided as a solvent for the lac. Embodiments having between 5-40% shellac (by weight) have been formulated that provide usable varnishes. Embodiments having 10-40% (more specifically 25-35%) shellac have exhibited more desirable properties. Whereas too great of a shellac content creates a thick and noticeable coating, too low of a shellac content imparts low viscosity which can allow the varnish to migrate off the tissue to which it is applied and onto surrounding tissues, such as gingival tissues. Furthermore, the viscosity is chosen to allow the varnish to respond to pressure applied to the flow-through unit dose ampule and impregnate brush while also allowing the varnish to release from brush onto enamel. A varnish of 30% shellac is found to sufficiently inhibit undesired varnish migration to the surrounding tissues. The present formulation has a viscosity of 30-60 centipoise. Embodiments are envisioned having a viscosity of less than 100 centipoise and more specifically less than 75 centipoise.

[27] Monobasic ammonium phosphate (MAP) was added and resulted in enhanced fluoride release and enhanced fluoride uptake by the underlying enamel. MAP is an inorganic phosphate. While MAP is specifically discussed, other embodiments that use other inorganic phospates are anticipated. Traditional varnishes have included an organic system including colophonium and alcohol in which traditional water-soluble inorganic ortho-phosphates (such as MAP), are totally (or nearly totally) insoluble. Similarly, dibasic sodium and potassium phosphates are only slightly soluble in alcohol while other water soluble phosphates such as sodium and potassium pyrophosphates, sodium glycerophosphate and sodium

hexametaphosphate are also insoluble in alcohol. The present varnish is similarly an organic system in which MAP is only slightly soluble. Accordingly, it was surprising that the addition of phosphate to an organic product would provide any benefit to the non-aqueous varnish.

However, it was consistently demonstrated that the presence of phosphate significantly increased the amount of fluoride released when immersed in an aqueous environment (such as a mouth). Testing shown in Table 1 shows that a concentration of somewhere between 1-3% resulted in the greatest fluoride release properties.

[28] Table 1

Ammonium Phosphate percent Fluoride Release (micrograms F/grams varnish) 0.0 4,384 ± 114

1.0 5,072 ± 387

2.0 5,518 ± 314

3.0 4,646 ± 108

[29] MAP presents slight solubility in ethyl alcohol and acidic pH. Embodiments are envisioned where sodium and potassium salts are used instead of MAP.

[30] Additionally, the inclusion of MAP also had the unexpected result of aiding in the re-suspension of settled sodium fluoride. In the absence of the phosphate, the sodium fluoride settles to the bottom or sides of the delivery ampule over a period of several hours and became very difficult to re-suspend. This settling out of the fluoride is exacerbated by the relatively low viscosity of the varnish. The presence of MAP facilitated the re-suspension of the sodium fluoride within 10 seconds of reasonable manual shaking of the ampule.

[31] Citric Acid was added to enhance the retention of the varnish by slightly etching sound enamel on which the varnish is applied. Citric Acid is a carboxylic acid. Areas having sensitivity problems due to exposed dentinal tubules and areas having demineralization provide suitable bonding sites for the varnish. However, sound enamel surfaces are more challenging on which to achieve suitable bonding for the varnish. The slight etching of the enamel by the citric acid improves adherence (retention) of the varnish, including on areas of sound enamel.

Increased adherence (retention) results in increased caries-preventive effects. Embodiments having 5% or less citric acid have been formulated that provide usable varnishes. Embodiments having 1-3% citric acid have exhibited suitable properties. Embodiments are envisioned where other carboxylic acids are used in place of the citric acid.

[32] Hydroxyapatite/Tricalcium Phosphate enhances the deposition of fluoride and the remineralization of demineralized enamel for so long as the fluoride does not react with the calcium prior to delivery to the enamel surface. As previously noted, the varnish presents a nonaqueous mixture. The non-aqueous mixture keeps the fluoride separated from the calcium within the varnish. Accordingly, the provided combination of elements causes the fluoride to remain in a non-dissolved/non-dissociated form prior to application. Once applied, the aqueous environment of the mouth allows interaction between the fluoride and the calcium with the tooth surfaces.

[33] Various taste additives (xylitol, sodium saccharin, and flavoring) were added to increase the taste appeal, particularly for children.

[34] The above embodiment includes 58.8% Ethyl Alcohol. Embodiments are envisioned where at least 38% of the varnish is Ethyl Alcohol. More specifically, embodiments of up to 90% alcohol are envisioned. This concentration of alcohol allows the varnish to be a liquid mixture. Traditional varnishes have been pastes and not water soluble.

[35] The above varnish was tested along with the leading commercially available varnishes. The above varnish formulation having 5% sodium fluoride exhibited 13,205 ± 197 micrograms of fluoride release per gram of varnish. The largest amount of fluoride release of the other tested varnishes was 11,480 ± 286 micrograms of fluoride per gram of varnish.

[36] While this disclosure has been described as having an exemplary design, the present disclosure may be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this disclosure pertains.