The unpleasant taste can be decreased without the active ingredient having to impart a taste of its own. The active ingredient of the invention also decreases the perception of the bitter taste invoked by other active components of foods and other formulations that are placed in the oral cavity. The active ingredient may also be formulated in combination with other ingredients such as water alcohol, humectant, phenolic flavor, dental polishing agent, thickener and water.

RACXnROtINn OF THE INVENTION Previous inventions have focused on decreasing breath malodor by the addition of various ingredients to mouthwash, mouthrinse and dentifrice. The approach to addressing unpleasant taste in the oral cavity has been to overpower it with compounds that have a strong taste such as menthol. The applicant is not aware of any disclosure or suggestion in the art of using a compound that does not impart a strong taste to abrogate unpleasant taste in the oral cavity. The active ingredient whose use is herein claimed has been disclosed as having the property of

decreasing the perception of the bitter taste of various foods and pharmaceuticals when they are mixed with and administered contemporaneously with such foods and pharmaceuticals- (U. S. Serial Nos. 60/113,562 ; 09/865, 346.

The effect of these active ingredients on the bitter taste perception that has previously imparted by bitter taste moieties, has not been reported and could npot have been predicted, based on the prior art. As used herein the term"unpleasant taste"means a taste that a majority of a taste test panel of six randomly selected individuals will agree is a taste that lingers for 30 to 60 minutes after the ingestion of a food or beverage and is unacceptable.

Mouthwashes, mouthrinses, dentifrices and denture adhesives can elicit unpleasant taste in the oral cavity.

For example, a mouthwash or mouthrinse containing 0. 35% eucalyptus oil can be perceived as having a bitter or medicinal taste. Hussain and Barcelon (1991) proposed the use of 0.0025% fenchone, borneol or isoborneol to significantly suppress this off-taste. These, and other mentholated compositions appear to decrease perception of bitterness due to their cooling effect on the mouth.

Other mentholated compositions used to reduce bitter taste in mouthwash or mouthrinse are menthol, di-D- fructofuranose 1, 2' : 2,3'-dianhydride, anethole and menthofuran (Kondo and Nishimura, 1991; Ueki et al., 1993). Polygodial from plant extracts suppresses bitterness by a similar method of cooling (Ishikawa et al., 1995). Peppermint oil has been used as a bitterness blocker in mouthwash, mouthrinse and dentifrice to reduce the required amount of menthol (Hussein et al., 1994; Carlin et al., 1994). Sweeteners are also used to reduce bitterness of oral compositions (Peterson et al., 1994).

Accordingly it is an object of the invention to provide a formulation comprising an active ingredient that is capable of decreasing the perception of unpleasant

taste in the oral cavity, which has been caused by foods, pharmaceuticals or other compositions.

It is also an object of the invention to provide the active ingredient in an oral formulation which may be used as a mouthwash, mouthrinse, dentifrice or dental adhesive composition.

It is also an object of the invention to provide gums, tablets, lozenges, tooth powders, tooth hardeners, antitartar compositions and anticalculus compositions which contain the active ingredient in an amount that is effective to control unpleasant tastes in the oral cavity.

It is also an object of the invention to provide an active ingredient to control an unpleasant taste in the oral cavity wherein the active ingredient inherently has no significant taste.

These and other objects of the invention will become apparent from a review of the appended specification.

SUMMARY OF THE TNVRNTION The present invention relates to oral formulations which contain as an active ingredient, a effective amount of a nucleotide compound which contains a purine or pyrimidine group or derivative thereof which is bonded to a ribose or deoxyribose sugar moiety, or a derivative of ribose or deoxyribose and an ionizable phosphate. The term effective amount is used to describe the amount of the nucleotide compound which is effective to reduce unpleasant tastes in the oral cavity. The nucleotide compound may be incorporated as a component of a mouthwash, mouthrinse or dentifrice composition. These compositions may contain suitable vehicles and other conventional ingredients such as water, ethanol, humectants, flavors, dental polishing agents, thickeners, surfactants, biocides, fluorides etc. which are employed in such compositions in amounts which provide the desired form of a composition. The nucleotide compound is used at

a concentration that is effective to decrease the perception of an unpleasant taste in the oral cavity.

The amount of the nucleotide compound employed in the invention may comprise about 0. 0001% to 10% by weight and preferably between about 0. 0025% and 0. 5% by weight is used based on the total weight of the particular composition in which it is employed.

The present invention also provides for a method of decreasing unpleasant taste present in the oral cavity comprising administering a mouthwash, mouthrinse or dentifrice containing an effective amount of the nucleotide compounds according to the invention.

DETAILED DRSCRTPTION OP THR TMVRNTTON Without being bound by any theory by which the present invention operates, it is believed that the nucleotide compounds described herein operate by blocking unpleasant tastes which may be present in the oral cavity of a human subjects.

The preferred nucleotides are soluble in water and may be prepared in water or water/alcohol mixtures. The unpleasant taste can be derived from recently eaten food or beverage products or from byproducts of bacterial metabolism in the oral cavity.

The oral formulation can be a simple aqueous solution of solvent and nucleotide. Alternatively, the oral formulation that the ingredient of the invention is added to may optionally include an anticaries agent such as sodium fluoride, potassium fluoride, stannous fluoride, sodium monofluorophosphate and sodium hexafluoride; antibacterial agent such as chlorhexidine, benzthonium chloride, cetyl pyridinium chloride and lupulones; alcohol such as ethanol and isopropanol; humectants such as glycerol, sorbitol, mannitol, polyethylene glycol and propylene glycol; surfactant such as sodium lauryl

sulfate, sodium dodecyl benzene sulfonate, sodium N-coco, N-methyl taurate and N-lauroyl sarcosine; antitartar agents such as tetrasodium pyrophosphate and sodium triphosphate; potassium chloride, potassium citrate and potassium nitrate to decrease teeth sensitivity; flavorings such as peppermint oil, wintergreen oil and eucalyptus oil; sweeteners such as sucrose, aspar. tyl phenyl alanine methyl ester and saccharin ; preservatives such as benzoate; polishing agents such as calcium carbonate, dicalcium phosphate and tricalcium phosphate; tooth hardeners; tooth whiteners; buffers ; anticalculus agents such as azacycloalkane diphosphonic acid; thickening agents such as carrageenan and hydroxymethyl cellulose; vitamins; coloring agents.

The orally acceptable vehicle for the compositions of the present invention when such compositions are mouthwashes or mouthrinses will normally be any which is employed in such compositions that do not contain the ingredient of the invention and will typically have a solvent base that is aqueous or aqueous alcoholic with the preferred alcohol being ethanol.

In preferred oral compositions that are in the form of mouthwashes or mouthrinses, there will also be present about 0-20wt% of alcohol, preferably ethanol, about 10- 50wt% of humectant, phenolic flavor in the range of about 0-lwt%, with the balance of the formulation comprising water at levels of up to about 90wt%.

The orally acceptable vehicle for the compositions of the present invention when such compositions are gums, tablets, lozenges, tooth powders, tooth hardeners, antitartar compositions, dental adhesives or anticalculus compositions will normally be any which is employed in such compositions that do not contain the nucleotide compound of the invention These formulations are exemplified in Remington 20th Ed., Mack Pub. Co. (2000).

In preferred oral compositions that are in the form

of gums, tablets, lozenges, tooth powders, tooth hardeners, antitartar compositions, dental adhesives or anticalculus compositions, there will also be present about 0-40wt% or 1-30wt% dental polishing agent, preferably finely divided silica, about 0-45wt% or 1- 35wt. % humectant, about 0. 5-10wt% thickener, about 0-20wt% or 1-20 of a sugar such as sucrose or lactose about 0-5wt% surfactant, and up to 90wt% water.

The ingredients, including the ingredient of the invention, are mixed and packaged by methods known to persons skilled in the art.

The nucleotide compounds are well known and comprise adenosine, guanine, cytosine, thymine, inosine and uracyl in chemical combination with a sugar and a phosphate. The preferred nucleotide compounds include, but are not limited to, adenosine 5'-monophosphate, inosine 5'- monophosphate, adenosine 3' : 5'-cyclic monophosphate, guanosine 2' : 3'-cyclic monophosphate, guanosine 3' : 5'- cyclic monophosphate, cytidine 5'-monophosphate, guanosine 2'-monophosphate, guanosine 3'-monophosphate, guanosine 5'-monophosphate, uridine 5'-monophosphate, 2'- deoxyadenosine 5'-monophosphate, 2'-deoxyadenosine 5'- triphosphate, 2'-deoxycytidine 5'-monophosphate, and 2'- deoxyguanosine 5'-monophosphate.

In specific, non-limiting embodiments, where adenosine 5'-monophosphate, inosine 5'-monophosphate, adenosine 3' : 5'-cyclic monophosphate, uridine 5'- monophosphate, 2'-deoxyadenosine 5'monophosphate, 2'- deoxyadenosine 5'-triphosphate or 2'-deoxyguanosine 5'- monophosphate is used to decrease unpleasant taste in the mouth an oral formulation comprising a concentration of the nucleotide of between about 0. 0001% and 10% by weight, preferably between about 0. 0025% and 0. 5% is used.

In specific, non-limiting embodiments, where guanosine 2' : 3'-cyclic monophosphate, guanosine 3' : 5'-

cyclic monophosphate, cytidine 5'-monophosphate, guanosine 2'-monophosphate, guanosine 5'-monophosphate, 2'- deoxycytidine 5'-monophosphate or guanosine 3'- monophosphate is used to decrease unpleasant taste in the mouth an oral formulation comprising a concentration of the nucleotide of between about 0.001% and 10% by weight, preferably between about 0. 025% and 0. 5% by weight based on the total weight of composition is used.

The preferred embodiment of the invention is such that the compounds claimed to decrease unpleasant taste are nucleosides in the form of adenosine, inosine, guanosine, cytosine, thymine, uracyl, 5-methylcytosine, thiouracil, bromothymine, azaadenines, azaguanosine, xanthine, hypoxanthine, 8-bromoguanine, 8-chloroguanine, 8-aminoguanine, 8-hydrazinoguanine, 8-hydroxyguanine,- 8methylguanine, 8-thioguanine, 2-aminopurine, 2,6- diaminopurine, 5-ethylcytosine, 5-methylcytosine, 5- bromouracil, 5-iodouracil, 5-ethyluracil, 5-propyluracil, 5-vinyluracil, and 5-bromovinyluracil combined with ribose or deoxyribose sugar, or derivative thereof, and contain an ionizable phosphate or similar anionic organic molecule. The compositions containing the nucleotide are in a pharmaceutically acceptable matrix in which the matrix has a composition such that the pH range is between 3.0 and 11-0 when placed in a suitable aqueous environment at a concentration of 1% by weight. The expression "pharmaceutically acceptable matrix"includes liquid carriers, liquid sprays, gels, solid tablets, chewable matrices such as gums, fast dissolving matrices and semi solid granules. These matrices are prepared by utilizing any one of a wide variety of different prior art methods well known to one of ordinary skill in the art.

The compositions as described above are sufficient to block unpleasant tastes present in the mouth of human subjects as determined by subjective determination of the taste intensity.

DESCRIPTION OF THE PREFERRED EMBODIMENTS EXAMPLE 1 A mouth wash formulation is prepared as follows: adenosine 5'-monophosphate 2. 0g ethanol 1. 5g glycerin 2. 0g purified water qs 100. ou EXAMPLE 2 A mouthwash formulation is prepared as follows: Adenosine 5'-monophosphate 2. 0g Sorbitol lOg Glycerine lOg Betaine 0. 5g Ethanol lOg Propylene glycol 7. 0g Phenolic flavors 0.15g purified water qs 100g EXAMPLE 3 A dentifrice formulation is prepared as follows: Adenosine 5'-monophosphate 2. 0g Glycerine lOg Glycine 0. 2g Sodium fluoride 0. 25g Xanthum gum 0. 5g Sodium lauryl sarcosinate lg Silica 20g purified water qs 100g EXAMPLE 4 A dentifrice formulation is prepared as follows:

Adenosine 5'-monophosphate 2. 0g Sodium fluoride 0. 25g Hydrated silica 25g Xanthum gum 0. 6g Sodium alkyl sulfate l. 0g Titanium dioxide l. Og Sodium saccharin 0. 13g purified water qs 100g EXAMPLE 5 A gum formulation is prepared as follows: Adenosine 5'-monophosphate 2. 0g Estergum lOg Coumorone resin 15g Dry latex 5g Sucrose 50g Glycine 0.02g Flavor 1. 5g Corn Syrup qs 100g EXAMPLE 6 A sugar-free gum formulation is prepared as follows: Adenosine 5'-monophosphate 2. Og Estergum lOg Coumorone resin 15g Dry latex 5g Sorbitol 49. 75g Saccharin 0. 25g Glycine 0. 02g Flavor 1. 5g Corn syrup qs 100g EXAMPLE 7

A lozenge formulation is prepared as follows: Adenosine 5g-monophosphate 2. 0g Sorbitol 17. 59 Mannitol 17. 5g Starch 15g Glycine 0. 02g Saccharin 0. 2g Flavor 1. 5g Corn syrup qs 100g EXAMPLE 8 A dental adhesive formulation is prepared by adding Adenosine 5'-monophosphate 2. 0g to any commertcially available denture adhesive.

EXAMPLE 9 A tablet formulation is prepared which has Adenosine 5'-monophosphate 2. 0g with or without suitable excipients.

EXAMPLE 10 The in vivo assay may be carried out as follows: 4 Subjects consumed 10 grams of onion. After 10 minutes, the unpleasant taste is graded on a scale from 1 to 10 (10 being the most unpleasant). Each subject then rinsed with 15 mL of a 10 mM AMP solution. Forty-five minutes after consumption of the onions, each subject rinsed with 15 mL of a 20 mM AMP solution.