Dentinal hypersensitivity treatment

Abstract

One method embodiment disclosed herein occludes exposed openings of dentin tubules. The method includes applying a debriding gel formulation to a surface of a tooth in order to coagulate and detach organic material from a surface of a dentin tubule opening, forming a debrided area. The method also includes rinsing the debriding gel formulation from the debrided area and at least partially drying the debrided area to form a dried debrided area. The method further includes applying an occluding gel formulation to the dried debrided area to form occluded tubules and rinsing the occluding gel from the occluded tubules. Both the debriding gel formulation and occluding gel include water. The water concentration in the debriding gel is about 10% to 30% of the water concentration of the occluding gel.

Description

DENTINAL HYPERSENSITIVITY TREATMENT Claim of Priority

[0001] This patent application claims the benefit of U.S. Provisional Patent Application No.63 / 644,762, filed May 9, 2024, which is incorporated by reference herein in its entirety. Field

[0002] Inventive embodiments disclosed herein relate to method embodiments for treating dentin hypersensitivity and formulation embodiments for occluding dentin tubules. Background

[0003] Dentin hypersensitivity, DHS, is manifested by a sharp pain experienced by dental patients and others. DHS occurs when effected teeth become hypersensitive to stimuli such as exposure to hot or cold, acidic or sweet foods, and air flow. This hypersensitivity and pain can impact eating, drinking, speaking and tooth brushing.

[0004] DHS is associated with conditions such as enamel attrition, erosion, corrosion, abrasion and abfraction. Peridontal tissue loss, gingival recession and other conditions leading to the exposure of dentin may also lead to the development of DHS. Even though up to about a third of people have experienced DHS, treatments for dentin hypersensitivity have not generally been successful. Summary

[0005] One method embodiment disclosed herein occludes exposed openings of dentin tubules. The method includes applying a debriding gel formulation to a surface of a tooth in order to coagulate and detach organic material from a surface of a dentin tubule opening, forming a debrided area. The method also includes rinsing the debriding gel formulation from the debrided area and at least partially drying the debrided area to form a dried debrided area. The method further includes applying an occluding gel formulation to the dried debrided area to form occluded tubules and rinsing the occluding gel from theoccluded tubules. Both the debriding gel formulation and occluding gel include water. The water concentration in the debriding gel is about 10% to 30% of the water concentration of the occluding gel.

[0006] Another method embodiment for treating dentin hypersensitivity includes applying a debriding gel formulation to a surface of a tooth in order to coagulate and detach organic material from a surface of a dentin tubule opening, forming a debrided area. The method also includes rinsing the debriding gel formulation from the debrided area and at least partially drying the debrided area to form a dried debrided area. The method additionally includes applying an occluding gel formulation to the dried debrided area to form occluded tubules and rinsing the occluding gel from the occluded tubules. Both the debriding gel formulation and occluding gel comprise include water. The water concentration in the debriding gel is about 10% to 30% of the water concentration of the occluding gel. Inventive embodiments also include a kit for treating dentin hypersensitivity. The kit includes a debriding formulation that includes one or more of phenolsulfonic acid, guaiacolsulfonic acid or ammonium phenolsulfonate in a concentration of at least about 50% by weight and water in a concentration of about 10% by weight. The kit also includes at least one occluding formulation comprising one or more of phenolsulfonic acid, guaiacolsulfonic acid, or ammonium phenolsulfonate in a concentration of at least about 5% by weight to about 20% by weight and a water concentration of at least about 70% by weight.

[0007] Description of Drawings

[0008] Figure 1 illustrates a schematic view of dentin tubules, tooth enamel, odenblasts and nerve fibers.

[0009] Figure 2 illustrates a Scanning Electron Micrograph, SEM, illustrating dentin tubule openings after exposure to 100% Occluding gel, Dentin tubule openings are clear.

[0010] Figure 3 illustrates a SEM illustrating dentin tubule openings after exposure to 30% Occluding gel. Dentin tubule openings are partially occluded by calcium sulfate salts.

[0011] Figure 4 illustrates a SEM illustrating dentin tubule openings after exposure to 20% Occluding gel. A majority of dentin tubule openings are occluded by calcium sulfate salts.

[0012] Figure 5 illustrates a SEM illustrating dentin tubule openings after exposure to 10% Occluding gel. Occlusion of dentin tubule openings by calcium sulfate salts is complete.

[0013] Figure 6 graphically illustrates changes in desiccation and tissue acidification activities of the phenol sulfonic acid ingredient of both the desiccating gel and occluding gel, hygroscopicity and acidification as a function of its concentration in water. Detailed Description

[0014] One method embodiment disclosed herein occludes exposed openings of dentin tubules. The method includes applying a debriding gel formulation to a surface of a tooth in order to coagulate and detach organic material from a surface of a dentin tubule opening, forming a debrided area. The method also includes rinsing the debriding gel formulation from the debrided area and at least partially drying the debrided area to form a dried debrided area. The method further includes applying an occluding gel formulation to the dried debrided area to form occluded tubules and rinsing the occluding gel from the occluded tubules. Both the debriding gel formulation and occluding gel include water. The water concentration of the debriding gel is about 10% to 30% of the water concentration of the occluding gel.

[0015] In describing and claiming inventive embodiments herein, the following terminology is used in accordance with the definitions set forth below. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the inventive embodiments herein.Specific and preferred values listed below for radicals, substituents, and ranges are for illustration only. They do not exclude other defined values or other values within defined ranges for the radicals and substituents. Definitions

[0016] As used herein, the articles “a” and “an” refer to one or to more than one, i.e., to at least one, of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0017] The term “about,” as used herein, means approximately, in the region of, roughly, or around. When the term “about” is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term “about” is used herein to modify a numerical value above and below the stated value by a variance of 20%.

[0018] The term “apply” or “application,” as used in reference to a composition, means to apply or spread the compositions of the present invention onto keratinous tissue such as the epidermis.

[0019] The terms “comprises,” “comprising,” and the like can have the meaning ascribed to them in U.S. Patent Law and can mean “includes,” “including” and the like. As used herein. “including” or “includes” or the like means including, without limitation.

[0020] As used herein, the terms “include”, “includes” and “including” are meant to be non-limiting.

[0021] For inventive embodiments herein, any numerical range recited herein is intended to include all sub-ranges subsumed therein. For example, a range of “1 to 10” is intended to include all sub-ranges between (and including) the recited minimum value of 1 and the recited maximum value of 10, that is, having a minimum value equal to or greater than 1 and a maximum value of equal to or less than 10.

[0022] The terms, percentage or percent as used herein refer to percentage or percent by weight.

[0023] Figure 1 illustrates a schematic view of dentin tubules 12 adjacent to tooth enamel 14. Odenblasts 16 and nerve fibers 18 oppose the tooth enamel 14 and are partially positioned within the dentin tubules 12.

[0024] The term, odenblast shown at 16 in Fig.1, as used herein, refers to a cell of neural crest origin that is part of an outer surface of the dental pulp, and whose biological function is dentinogenesis, which is the formation of dentin, the substance beneath the tooth enamel on the crown and the cementum on the root.

[0025] The term, dentin, as used herein refers to a calcified tissue, along with enamel, cementum, and pulp, and is one of the four major components of teeth. Dentin is usually covered by enamel on the crown of a tooth and cementum on the root of the tooth and surrounds the entire pulp. By volume, 45% of dentin consists of the mineral hydroxyapatite, 33% is organic material, and 22% is water. As used herein, the term “pulp” refers to a mass of connective tissue that resides within the center of a tooth, directly beneath a layer of dentin. As used herein, the term “cementum” refers to a specialized calcified substance covering the root of a tooth.

[0026] The term, dentin tubules, as used herein shown at 12 in Fig.1, refers to small, hollow microscopic channels that extend from the pulp inside of the tooth, through the dentin, ending adjacent to the enamel. Cross sections of dentin tubules are shown in a micrograph shown in Figure 2.

[0027] The inside of a tooth is fed by blood vessels, but the outer layers of teeth don't contain blood vessels or nerves. Dentinal tubules function in a manner like blood vessels by carrying the pulp chamber's nutrients and fluids to the dentin layer.

[0028] The term, “debriding gel,” as used herein refers to a formulation that delivers a desiccating action to the surface of the dentin which coagulates any pathogenic organic material on the surface of the dentin and helps detach the pathogenic organic material from the surface. This action removes any debris from the opening of the dentin tubules and surrounding surface area.

[0029] Both debriding gel embodiments and occluding gel embodiments include a sulfonic acid bonded to a ring system such as benzene or phenol. Debriding gel formulation embodiments include active agents such as hydroxybenzene sulfonic acid, hydroxymethoxy benzosulfuricacid, and guaiacol sulfonic acid. Examples of debriding gel embodiments are presented herein.

[0030] The debriding gel includes a topical liquid that has been gelled and that is applied to a surface of a tooth and produces an aqueous extraction that detaches organic material such as necrotic debris and senescent cells, bacteria, yeast, fungi, and proinflammatory factors from dentin tubules. While gels are generally disclosed herein, it is understood that debriding formulations that are not gels may be usable herein.

[0031] The chemical process of the debriding gel works on a unique non- biologic platform; mechanical, cellular, and molecular. Mechanism of action centers around rapid extraction of water from the dentin tubule area forming a coagulum that harbors necrotic tissue and senescent cells, biofilm, and proinflammatory factors. This rapid desiccation process takes less than a minute and is selective to diseased tissue, leaving normal, living tissue unharmed.

[0032] The term, “occluding gel,” as used herein refers to a debriding gel that is diluted with water to 10% to 30% of its original strength rendering the occluding gel unable to extract water from the tooth surface when it makes contact. Instead, the occluding gel provides an acidification action within the tubule opening. This acidification triggers the formation of insoluble calcium salts within the dentin tubules by the combination of sulfuric and sulphonic acid components of occluding gel with calcium from the dentin mineral within walls of the tubules. Examples of occluding gels are presented herein.

[0033] A graph, shown in Figure 6, illustrates changes in desiccation and tissue acidification activities of the phenol sulfonic acid ingredient of both the desiccating gel and occluding gel, hygroscopicity and acidification as a function of its concentration in water. On the right side of graph in Figure 6, minimally diluted phenol sulfonic acid formulation embodiments displayed high levels of water absorption, as measured by a standardized hygroscopicity assay (green line), and a low level of tissue surface acidification, as measured by calcium ion release in a bovine enamel erosion assay (red line).

[0034] At 5% phenol sulfonic acid formulation embodiments, concentration in water, shown at the left side of the chart, the hygroscopicity activity is negative, but at the same time tooth surface acidification activity is at its peak as measured by calcium release. This supports a conclusion that the mode of action of undiluted phenol sulfonic acid formulations, upon contact with a tissue surface, involve macromolecular denaturation by water extraction and not by tissue acidification.

[0035] For method embodiments disclosed herein, dessication of the dentin tubules is followed by occluding the dentin tubules with calcium sulfate crystals. For some embodiments, the occluding gel includes the same ingredients as the dessicating gel but in different concentrations. Ingredients that act as dessicants in the dessicating gel are present in lower concentrations than in the dessicating gel. Water in the occluding gel has a concentration of 70% or more water. Water in the dessicating gel is present in a concentration of 30% percent or less.

[0036] The dessicant gel and the occluding gel both include a phenolsulfonic acid. The phenolsulfonic acid in the occluding gel reacts with calcium from the dentin tubules and other calcium-containing dessicated areas to form calcium salts that occlude the opening of the dentin tubules. These occlusions aid in the reduction of tooth sensitivity by blocking environmental factors from further irritation of the pulp nerves through the tubules.

[0037] The term “phenolsulfonic acid” as used herein, refers to any or all of hydroxybenzene sulfonic acid, hydroxymethoxy sulfonic acid, phenol sulfonic acid, and guaiacolsulfonic acid.

[0038] The debriding gel formulation contacts the surface of a tooth for 3- to 6- seconds. The occluding gel formulation contacts the surface of the tooth for 2 to 3 minutes. Some method embodiments also include applying a sealant to the treated area. Some method embodiments include sequentially applying two or more occluding formulations.

[0039] The cause or causes of DHS are not well understood. One explanation has been a hydrodynamic theory that proposes that external stimuli, such as thermal, mechanical, evaporative and osmotic, lead to the movement of fluid within the dentinal tubules and this movementindirectly stimulates the pulp nerve ends, causing a painful sensation. For DHS to occur, the dentin must be exposed, either by loss of enamel or gingival recession, and the dentin tubules must be permeable both to the oral cavity and to the pulp.

[0040] Formulation embodiments usable as a debriding gel are provided herein as follows: Debriding Gel Formulation 1: Phenolsulfonic acid – 36% -37 by weight; Guaiacolsulfonic acid – 23% -24 by weight; Sulfuric Acid – 28%-29 by weight; Water – 10% by weight; and Colloidal Silica – 3% by weight. Debriding Gel Formulation 2: Benzenesulfonic acid – 43-45% by weight; Phenolsulfonic acid – 38-40% by weight; Water – 15% by weight. Colloidal Silica – 5% by weight.

[0041] The additive concentration of each ingredient adds up to 100% for the formulation.

[0042] The mechanism of action is believed to be the following: Application of a formulation embodiment disclosed herein acts as both a mechanical debridement and a chemical debridement. The mechanical debridement action derives from an elevated viscosity and density that allows the formulation to deliver a higher level of mechanical pressure and shear stress across a surface. The chemical debridement derives from a desiccating action of the formulation embodiment which acts to destabilize the cohesion of necrotized tissues and microbial biofilm so that they are more easily carried away by the mechanical action.

[0043] Debriding formulation embodiments not only absorb water mechanically, i.e. absorb water that is adhered to microbes and biofilm within and proximal to a wound, but also absorb water that is electrostatically bonded, i.e. hydrogen bonded, with structuralcomponents of bacteria and other microbes in wounds, thereby desiccating bacterial structure and destroying bacterial structural integrity. Formulation embodiments also desiccate any residual necrotic tissue.

[0044] Once structural integrity is destroyed, the microbes die and the biofilm is disrupted. Bacteria, and other pathogens exposed to formulation embodiments disclosed herein do not develop a resistance to the formulations. Formulation and method embodiments disclosed herein are effective against all bacteria, biofilm, prions and other infectious agents.

[0045] Additionally, debriding formulation embodiments disclosed herein prevent damage done by a destructive inflammation immune response initiated by necrotizing tissue by eliminating the necrotizing tissue before the response is prompted. Elimination of the necrotic tissue prevents the body from initiating a destructive inflammatory immune response.

[0046] Formulation embodiments that include free sulfuric acid have the free sulfuric acid component because sulfonation of the phenol and guaiacol or benzene performed does not remove residual sulfuric acid remaining at the conclusion of the sulfonation reactions. In order to drive the sulfonation reaction to completion so that all of the phenol and guaiacol or benzene molecules become sulfonated, excess sulfuric acid is added to a reaction mixture in a ratio of approximately 1:4:1, phenolsulfonic acid to guaiacolsulfonic acid or benzenesulfonic acid to sulfuric acid, so that there is an excess of sulfuric acid when the reaction is completed. The excess sulfuric acid is referred to as “free sulfuric acid” because it is not conjugated to a phenol or guaiacol.

[0047] The debriding formulation embodiments that do not contain any free sulfuric acid are blended from a purified sulfonated aromatic that is obtained already in sulfonated form. Any residual or excess free sulfuric acid is removed, so that when blending is completed, there is substantially zero free sulfuric acid in the blend.

[0048] Additional specific liquid and gel formulations usable for debriding include the following:Debriding Formulation 3: Contains Free Acid in a Gel Form Phenolsulfonic acid – 36% by weight Guaiacolsulfonic acid – 23% by weight Free Sulfuric Acid – 28% by weight Water – 10% by weight Colloidal Silica – 3% by weight Debriding Formulation 4: Contains no free acid, in a liquid form Benzenesulfonic acid – 45% by weight Phenolsulfonic acid – 40% by weight Water – 15% by weight Debriding Formulation 5: Contains no free acid, in a gel form Benzenesulfonic acid – 43% by weight Phenolsulfonic acid – 38% by weight Water – 14% by weight Colloidal Silica – 5% by weight

[0049] Other formulation embodiments are disclosed below: Debriding Formulation 6 Component Concentration Ranges Phenolsulfonic Acid 25-80% by weight Guaiacolsulfonic Acid 25-80% by weight Ammonium Phenolsulfonate 0-32% by weight Water 13-30% by weight

[0050] The additive concentration of each ingredient adds up to 100% for the formulation. Debriding Formulation 7: Component Concentration Ranges Phenolsulfonic Acid 25-80% by weight Guaiacolsulfonic Acid 25-80% by weight Ammonium Phenolsulfonate 0-5% by weight Water 13-30% by weight

[0051] Occluding gel formulations used herein include phenol sulfonic acid solutions that are about 30% or less than the concentration of the desiccating gel formulations used with the occluding gel formulations. Water concentration in occluding gel formulations include about 70% more water than the desiccating gel formulations.

[0052] Another inventive embodiment includes a kit for treating DHS. The kit includes a debriding gel having the ingredients and concentrations shown in Table 1. The phenol sulfonic acid concentration is 58.6%. The water concentration is 10.2%. The kit also includes a first occluding gel having a phenol sulfonic acid concentration of 17.6% and a water concentration of 70.7%. The kit additionally includes a second occluding gel having a phenol sulfonic acid concentration of 11.7% and a water concentration of 79.4%. The kit further includes a third occluding gel having a phenol sulfonic acid concentration of 5.8% and a water concentration of 88.1%.

[0053] The kit is used by adding the debriding gel to contact dentin tubules for 3- to 6- seconds. Following removal of the debriding gel, the occluding gels, 1, 2 and 3 are sequentially applied to the dentin tubules for 2 to 3 minutes. Some method embodiments also include applying a sealant to the treated. EXAMPLE

[0054] The figures 2-5 shown herein are Scanning Electron Micrographs, SEMs, of dentin surfaces that were exposed a desiccating gel for 3-6 seconds and then were exposed to serial dilutions of occluding gel for 2 minutes and were then washed and prepped for examination. The concentrations of ingredients for occluding gel strength applied are listed under each figure and range from 1% strength in Figure 2 to full 100% strength in Figure 11.

[0055] The figures show that application of the higher strength occluding gel solutions which act as desiccants, shown in Figures 8-10, lead to clean dentin tubule openings. The effect of applying occluding gel having phenol sulfonate acid at concentrations ranging from 10-30%, which no longer act by surface desiccation but rather by surface acidification,show a different change. At 30%, phenol sulfonate in Figure 6, some precipitation of material occurs in the openings of the dentin tubules.

[0056] At application of occluding gel 20% phenol sulfonic acid concentrations, the openings of the tubules appear to be completely occluded by formation of a crystalline material. At 10% phenol sulfonic acid occluding gel concentration, the formulation not only produces tubular occlusion, but also generates the formation of crystal structures extending beyond the openings and over the dentin surface outside the tubules. These crystalline materials were identified as calcium sulfate salt by reflectance spectroscopy.

[0057] Table 1:

[0058] While examples herein have been set forth for purposes of illustration, it will be apparent to those skilled in the art that the invention is susceptible to additional embodiments and that certain of the details described herein may be varied considerably without departing from the basic principles of the invention.

Claims

In the Claims What is claimed is:

1. A method for occluding exposed openings of dentin tubules, comprising: applying a debriding gel formulation to a surface of a tooth in order to coagulate and detach organic material from a surface of a dentin tubule opening, the debriding gel forming a debrided area; rinsing the debriding gel formulation from the debrided area and at least partially drying the debrided area to form a dried debrided area; and applying an occluding gel formulation to the dried treated area to form occluded dentin tubules wherein the occluding gel formulation has a water concentration that is about 70 percent by weight or greater than the water concentration in the debriding gel formulation and water in the desiccating gel is present in a concentration of about 30% or less than water concentration in the occluding gel.

2. The method of claim 1, for occluding exposed openings of dentin tubes further comprising rinsing the occluding gel from the occluded dentin tubules.

3. The method of claim 1, further comprising applying a sealant to the occluded dentin tubules.

4. The method of claim 1, wherein the debriding gel formulation contacts the surface of a tooth for 3- to 6- seconds.

5. The method of claim 1, wherein the occluding gel formulation contacts the surface of the tooth for 2 to 3 minutes.

6. The method of claim 1, wherein the debriding gel formulation comprises any or all of hydroxy-benzenesulfonic acid, hydroxymethoxy-benzenesulfonic acid, sulfuric acid and water.

7. The method of claim 1 wherein the debriding gel formulation comprises any or all of phenolsulfonic acid; guaiacolsulfonic acid; sulfuric Acid; and water.

8. The method of claim 1, wherein the occluding gel formulation comprises hydroxy benzenesulfonic acid; hydroxymethoxy benzene sulfonic acid; and water.

9. The method of claim 1, wherein the occluding gel formulation comprises phenolsulfonic acid, guaiacolsulfonic acid; ammonium phenolsulfonate; and water.

10. The method of claim 1, wherein the occluding gel formulation comprises hydroxy benzenesulfonic acid in a concentration ranging from 3.5 to 10.6% by weight.

11. The method of claim 1, wherein the occluding gel formulation comprises hydroxymethoxy benzenesulfonic acid in a concentration range of 2.3 to 7% by weight.

12. A method for treating dentin hypersensitivity, comprising: applying a debriding gel formulation to the dentin in order to coagulate and detach organic material from a surface of any dentin tubule opening, forming a debrided area of the dentin; rinsing the debriding gel formulation from the debrided area and at least partially drying the debrided area to form a dried debrided area of the dentin; applying an occluding gel formulation to the dried treated area of the dentin to form occluded dentin tubule openings; and rinsing the occluding gel formulation from the occluded dentin tube openings.

13. The method of claim 12, further comprising applying a sealant to the occluded dentin tubules.

14. The method of claim 12, wherein the debriding gel formulation contacts the surface of a tooth for 3- to 6- seconds.

15. The method of claim 12, wherein the occluding gel formulation contacts the surface of the tooth for 2 to 3 minutes.

16. The method of claim 12, wherein the debriding gel formulation comprises hydroxy-benzenesulfonic acid, hydroxymethoxy-benzenesulfonic acid, sulfuric acid and water.

17. The method of claim 12, wherein the debriding gel formulation comprises phenolsulfonic acid; guaiacolsulfonic acid; ammonium phenolsulfonate; and water.

18. The method of claim 12, wherein the occluding gel formulation comprises hydroxy benzenesulfonic acid in a concentration ranging from 3.5 to 10.6% by weight.

19. The method of claim 12, wherein the occluding gel formulation comprises hydroxymethoxy benzenesulfonic acid in a concentration range of 2.3 to 7% by weight.

20. The method of claim 12 wherein the debriding gel formulation comprises phenolsulfonic acid; guaiacolsulfonic acid; sulfuric Acid; and water.

21. The method of claim 12, wherein the debriding gel formulation comprises benzenesulfonic acid; phenolsulfonic acid; and water.

22. A kit, comprising: A debriding formulation comprising one or more of phenolsulfonic acid guaiacolsulfonic acid or ammonium phenolsulfonate in a concentration of at least about 50% by weight and a water concentration of about 10% by weight; and At least one occluding formulation comprising one or more of phenolsulfonic acid guaiacolsulfonic acid or ammonium phenolsulfonate in a concentration of at least about 5% by weight to about 20% by weight and a water concentration of at least about 70% by weight.

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