Drug – bio-affecting and body treating compositions – Dentifrices
Reexamination Certificate
2001-05-03
2002-07-09
Rose, Shep K. (Department: 1614)
Drug, bio-affecting and body treating compositions
Dentifrices
C424S450000
Reexamination Certificate
active
06416745
ABSTRACT:
The present invention relates to compositions and methods for the treatment of dental hypersensitivity.
BACKGROUND OF THE INVENTION
Dentinal hypersensitivity is a temporary induced pain sensation produced when hypersensitive teeth are subjected to changes in temperature and/or pressure or to chemical action. Hypersensitivity may occur whenever the dentin of a tooth is exposed by attrition or abrasion, or when the tooth's finer root surface is exposed by periodontal disease. Dentin is a bone-like material in teeth that is usually covered by enamel above the gum line and cementum below the gum line. The enamel or cementum may be removed through decay, injury, disease or other causes, thereby exposing the dentin to external stimuli in the mouth. Dentin generally contains channels, called tubules, that allow material and energy transport between the exterior of the dentin and the interior of the tooth where the nerve is located. One theory of dentinal hypersensitivity, called the hydrodynamic theory, suggests that exposure of these tubules to external stimuli can cause irritation of the nerve and lead to the discomfort of hypersensitivity. The hydrodynamic theory suggests that hypersensitivity may be treated by making the nerve in the tooth less sensitive to stimuli, or by blocking or occluding the tubules to prevent or limit exposure of the nerve to external stimuli.
Many attempts have been made to control dentinal hypersensitivity. One approach is to reduce the excitability of the nerve in a sensitive tooth. This technique interferes with the ordinary triggering process of the nerve by altering the chemical environment of the nerve through the use of agents to make the nerve less sensitive. These agents are generally referred to as “nerve agents” or “nerve desensitizing agents”. The most well-known agent for this purpose is potassium nitrate, used in commercial dentifrices for sensitive teeth and discussed in U.S. Pat. No. 3,863,006. Examples of other agents known as nerve desensitizing agents are potassium salts such as potassium bicarbonate and potassium chloride and the like. Another approach to controlling dentinal hypersensitivity, as discussed above with regard to the hydrodynamic theory, is the use of agents to fully or partially occlude tubules. Examples of such “tubule blocking agents” include the following: charged polystyrene beads, U.S. Pat. No. 5,211,939; apatite, U.S. Pat. No. 4,634,589; a polyacrylic acid polymer having a typical molecular weight from about 450,000 to about 4,000,000, U.S. Pat. No. 5,270,031; and certain clays, U.S. Pat. No. 5,589,159. Still others have attempted to treat dentin sensitivity by inducing the growth of mineral inside the dentinal tubules. A further approach described in U.S. Pat. No. 5,735,942 to Litkowski and U.S. Pat. No. 5,891,233 to Salonen et al. is the use of bioactive glass to treat tooth sensitivity. In general, these inventions suffer from problems of fluoride compatibility and these inorganic solids are abrasive materials.
It is apparent that a considerable amount of work has been done with regard to the problem of dentinal hypersensitivity. Despite these efforts, however, there is still a need for an effective, improved dentinal formulation for treating dentinal hypersensitivity. In accordance with the present invention, it has been discovered that compositions containing certain liposomes are effective in treating hypersensitivity. The compositions of the present invention are unique in that they are capable of inducing mineral formulation in dentinal tubules thereby occluding the tubules. The subject compositions are further unique in that, in addition to providing tubule blocking, the liposomes themselves have the capability to deliver nerve desensitizing agents, thereby also acting to reduce the excitability of the nerve to external stimuli.
SUMMARY OF THE INVENTION
The present invention relates to an orally acceptable formulation for the treatment of dentinal hypersensitivity containing liposomes capable of inducing mineral formation in the dentinal tubules and which may carry a further therapeutic agent, such as a desensitizing agent, for reducing the sensitivity of the nerve to external stimuli. The present invention also encompasses methods for the treatment of dentinal hypersensitivity utilizing compositions containing certain liposomes.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a composition for treating hypersensitive teeth comprising a carrier suitable for oral health use and an effective amount of certain liposomes that have the capacity to induce mineral formation in the dentinal tubules thereby achieving tubule occlusion. Liposomes are well known materials as is their preparation from a wide variety of amphiphilic molecules. While liposomes have been utilized for a variety of applications in the health field, primarily as vehicles for various active substances, they have not been extensively used for dental preparations.
In those instances where liposomes have been proposed for used in dental preparations, it has been necessary to utilize a “target molecule” in order for them to adhere to dental hard tissue, such as enamel and dentin. The target functions like a tentacle that functions to anchor the liposome to dentin and enamel. For example, in U.S. Pat. No. 4,767,615, liposomes must be connected via chromium metal ions to another target molecule that has an affinity for hydroxyapatite.
Not all liposomes are effective at inducing mineral formulation. Therefore, the surface of the liposome is critical and it has been found in accordance with the present invention that the surface of the liposomes must be anionic. The anionic surface of these materials induces mineral formation by acting as a mineral template that attracts soluble mineral ions that are naturally present in the dentin tubular fluid and saliva. These liposome-surface-attracted soluble mineral ions precipitate from the dentin tubule fluid onto the liposome surface, which in turn, acts to nucleate mineral growth in the fluid. The mineral formed in the dentinal tubules will provide a massive insoluble plug, thereby restoring the tubules to their healthy, naturally impermeable state, blocking tubule fluid movement and insulating the dentinal nerves. The plugging action acts to impede subsequent transmission of material energy and pressure gradients through the dentin, and may also retard the penetration of oral bacteria or the by-products of bacterial metabolism, an added benefit.
Several investigations have shown that liposomes surfaces with phosphate groups neutralized with a monovalent metal ion, such as sodium or potassium, preferably the latter, have the requisite anionic surface and are effective in the present invention, while liposomes with a choline surface or inositol surface are not mineral-inducing. Preferably, the liposomes of the present composition are prepared from salts of diolylphosphatidic acid (DOPA, Avanti® Polar Lipids, Inc.). In order to penetrate and be retained in the dentinal tubules, the liposome diameter should not be greater than about 2 microns, preferably from about 0.1 to 1.5 microns, most preferably about 0.5 micron. Therefore, in a preferred embodiment, the present invention provides a dentifrice composition for treating hypersensitive teeth comprising an effective amount of a mineral-inducing liposome wherein the liposome is a potassium salt of DOPA, having a diameter not greater than 0.5 microns.
In addition to their capacity to function as tubule blocking agents as described above, the liposomes of the present invention provide a means of delivering additional agents, specifically nerve desensitizing agents into the dentinal tubules and releasing them therein in a controlled fashion. This is a significant advantage in that the overall effect of the subject preparations is enhanced by the action of two agents that function to treat dentinal hypersensitivity by two recognized mechanisms. Such nerve desensitizing agents include, for example, potassium salts such as nitrate, bicarbon
Fitz Benjamin D.
Markowitz Kenneth J.
Block Drug Company Inc.
Rose Shep K.
Stein-Fernandez Nora
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