Compositions for cleansing and targeted dissolution of bioceramic endodontic sealers from root canals during retreatment & their methods of use

Abstract

The present disclosure descries endodontic cleaning solutions and uses of the same. The composition are useful in endodontic procedures.

Description

COMPOSITIONS FOR CLEANSING AND TARGETED DISSOLUTION OF BIOCERAMICENDODONTIC SEALERS FROM ROOT CANALS DURING RETREATMENT & THEIRMETHODS OF USECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 515,786, filed July 26, 2023; the entire contents of this application is hereby incorporated by reference herein.BACKGROUND OF INVENTION

[0002] Human teeth are living structures comprised of both hard and soft tissues. The hard tissue consists of enamel (the hard exterior surface tissue of teeth), dentin (immediately below enamel and helps support enamel), and cementuni (a specialized hard tissue that covers the root of a tooth). The dental pulp, generally referred to as soft tissue, primarily resides within the pulp chamber. Pulp tissue consists of many types of cells and connective tissue but also includes blood vessels and nerves that enter the tooth from the apical foramen, which is a hole at the apex of a root canal. Generally, a tooth’s root canal system refers to the naturally occurring anatomical spaces within the root(s) of a tooth, including the pulp chamber, that contain the dental pulp.

[0003] The root canal system is complex and can become infected in several ways. Infection commonly occurs if dental caries is not treated before bacteria infiltrates the tooth’s pulp and root canal. Once a root canal system is infected, many treatment methods can be used depending upon the patient’s condition and practitioner’s preferred approach. Typically, an endodontic procedure called root canal therapy (RCT) is performed to cleanse the root canal system and remove infectious agents.

[0004] RCT usually involves three steps. The first step is called instrumentation and entails opening the tooth and widening the root canal system with a series of semi-rigid metal endodontic files, and often times with endodontic irrigants (e.g. sodium hypochlorite), to reduce the debris level created by the endodontic files. This step removes some organic and inorganic material, but its primary goal is to enlarge the root canal(s) to allow for the introduction of small cannulae used during irrigation. The second step is irrigation. Irrigation entails flushing of the root canal system using small cannulae (called irrigation needles) attached to syringes of various aqueous-based endodontic irrigants, including sodium hypochlorite. The goal of the irrigation step is to debridethe root canal system and to solubilize any remaining debris and smear layer introduced during instrumentation, as well as disinfection. The final step is called obturation, in which the root canal system is filled with various materials. After the endodontic procedure is finalized, a standard dental restorative procedure (e.g. composite filling or crown, among others) is used to complete the structure and aesthetics of the tooth.

[0005] Obturation is increasingly being performed with the use of sealers. In practice, use of sealers requires first filling the canal(s) with the sealer, followed by inserting a master gutta percha cone to a working length that helps physically push the sealer into dentinal tubules and canal complexities. Once in place, the sealers harden over time. Some sealers will harden or set via a chemical polymerization reaction, for example, from mixing two components together, or via a hydration reaction by extracting water present in the tooth and surrounding tissues. Currently, the most popular sealers are bioceramic sealers that offer some biocompatibility advantages. Bioceramic sealers may consist of MTA (mineral trioxide aggregate), calcium silicate cements, and calcium aluminate cements, among others, with cement-based sealer becoming the most common.

[0006] Although significant advancements have occurred in RCT, the potential for reinfection of the root canal space still exists, which necessitates retreatment or tooth extraction. The increasing commonality of bioceramic endodontic sealers creates a new challenge for retreatment of failed RCT. The bioceramic sealers cure as a hard cement-like or ceramic-like solid in the root canal and form a strong mechanical bond, and in some instances, a chemical bond to the dentin formed by calcium phosphate salts. The bioceramic sealer does not melt for removal, unlike gutta percha. Thus, the sealer needs to be cleaned out using dental files and instruments, essentially re-accessing the canal and increasing the canal preparation size, which can negatively impact the mechanical integrity of the tooth. Due to the cement or ceramic-like nature of the bioceramic sealers, much of the sealer is not removed even after physical instrumentation. Removal of all the bioceramic sealer material is crucial to expose and retreat any difficult to reach areas, such as lateral canals and isthmuses, where bacteria may have been missed and caused the RCT to fail after initial treatment. Therefore, there is a need in the art for methods and compositions to specifically remove the bioceramic sealer from the root canal system, while maintaining as much dentin and tooth integrity as possible, during these types of retreatment procedures.BRIEF SUMMARY

[0007] The present disclosure provides cleaning compositions for an aqueous endodontic solution, or irrigant. The cleaning compositions disclosed herein are useful, without limitation, to aid in the removal of sealer material, and more specifically bioceramic sealer materials, in RCT retreatment procedures in vivo. Generally the cleaning solution is comprised of at least one acid, at least one surfactant, and at least one solvent. In certain embodiments, the composition can use an appropriate acid at a concentration and pH to selectively dissolve bioceramic and / or cement-based sealers while limiting damage to tooth material, such as dentin, which is primarily hydroxyapatite. Optionally the composition may contain one or more of the following: at least one chelating agent, at least one sequestrant, at least one hydrotrope, at least one builder, at least one antimicrobial agent, at least one lubricant, or at least one colorant. The present disclosure also teaches methods utilizing the disclosed cleaning composition. In yet another aspect, a product by process to create the cleaning solution is disclosed. In an even further aspect, kits containing the composition are disclosed.

[0008] In one aspect, an endodontic cleaning solution composition, includes: at least one acid selected from PBTC, citric acid, HEDP and mixtures of the same;at least one surfactant; and, water; wherein the cleaning solution composition has a pH between about 2 to 7. In some embodiments, the at least one acid is at a concentration between 5% and 35%. In some embodiments, the at least one acid chelates a metal ion. In some embodiments, the at least one acid consists of citric acid. In some embodiments, the composition also includes a builder. In some embodiments, the composition has a surface tension less than 40 dynes / cm. In some embodiments, the composition has a viscosity between IcP and 20cP at room temperature. In some embodiments, the at least one surfactant comprises a nonionic surfactant. In some embodiments, the at least one surfactant comprises an amine oxide. In some embodiments, the at least one surfactant consists of an amine oxide and a decyl octyl glycoside. In some embodiments, the composition includes at least one antimicrobial agent. In some embodiments, the composition includes at least one lubricant. In some embodiments, the composition includes at least one chelating agent. In some embodiments, the composition includes at least one chelating agent, wherein the at least one chelating agent is a polyacrylic acid. In some embodiments, the at least one acid consists of citric acid at a weight / weight (w / w%) concentration between 10% and 30%.

[0009] In another aspect, a method of retreating a failed root canal procedure, includes introducing an endodontic cleaning solution into a root canal or root canals to dissolve bioceramic sealer contained therein, wherein, the endodontic cleaning solution includes at least one acid selected from PBTC, citric acid, HEDP, polyacrylic acid, and mixtures of the same; at least one surfactant; and, water. In some embodiments, the cleaning solution composition has a pH between about 2 to 9. In some embodiments, the cleaning solution composition dissolves calcium silicate and calcium aluminate bioceramic sealer materials from the root canal during retreatment procedures. In some embodiments, the cleaning solution composition selectively dissolves bioceramic sealer materials but does not appreciably dissolve hydroxyapatite. In some embodiments, the cleaning solution composition dissolves and removes calcium hydroxide from the root canal spaces during RCT procedures.BRIEF DESCRIPTION OF THE DRAWINGS

[0010] FIG. 1 displays comparative testing data of sealer and hydroxyapatite (HA) disc dissolution of several compositions of different acids at specific pH values.

[0011] FIG. 2 displays comparative testing data of sealer and hydroxyapatite disc dissolution with a subset of acids compositions at specific pH values.

[0012] FIG. 3 compares normalized cured sealer dissolution results versus solution exposure (12mL) at room temperature for 30 minutes.

[0013] FIG. 4 cinoares normalized hydroxyapatite disc dissolution versus solution exposure (12mL) at room temperature for 30 minutes.DETAILED DESCRIPTION

[0014] The following paragraphs define in more detail the embodiments of the invention described herein. The following embodiments are not meant to limit the invention or narrow the scope thereof, as it will be readily apparent to one of ordinary skill in the art that suitable modifications and adaptations may be made without departing from the scope of the invention, embodiments, or specific aspects described herein.

[0015] For a bioceramic sealer dissolving solution to be effective, it must soften or dissolve the sealer to a degree that significantly aids in its removal in bulk particles and coatings from the root canal system during retreatment, while at the same time not significantly causing damage to theremaining tooth structure (dentin; hydroxyapatite(HA)). Bioceramic and / or cement-based sealers can be dissolved using a variety of acids, but many of these acids also dissolve the tooth structure to a significant degree by solubilizing hydroxyapatite, which is the primary mineral apatite of dentin. The present disclosure identifies certain acids that are efficient at dissolving bioceramic sealers without dissolving tooth structure when prepared at certain concentrations and pH values. In other words, the disclosed compositions can be used to selectively remove bioceramic sealer material from the root canal space during certain procedures while simultaneously acting gently on hydroxyapatite. Said in yet another way, the disclosed compositions have been developed for targeted dissolution of bioceramic sealer materials without chemically engaging or appreciably reacting with hydroxyapatite. Furthermore, the present disclosure shows that additives including surfactants, among other chemicals, can further benefit and enhance the results of the cleaning solution, all while minimizing damage to the tooth structure. In certain embodiments, the disclosed cleaning solution selectively targets the chemical bonds of calcium silicate hydrate molecules, calcium aluminate hydrate molecules or other cement-specific bonds. It may also be advantageous to simultaneously or alternatively chemically target filler molecules within the bioceramic and / or cement-based sealers to cause or hasten the sealer’s dissolution and solubilization. For example, zinc oxide is a radiopacifier that is commonly used in bioceramic and / or cement-based sealers at concentrations between 20% - 50% or more and may be chemically targeted in certain embodiments. It may be possible, therefore, to dissolve and solubilize the sealer material by chemically targeting certain chemical bonds of the sealer’s cementitious material or filler material.

[0016] In some embodiments, the cleaning solution composition includes at least one acid dissolved in an aqueous carrier, the acid comprising an organic acid or inorganic acid or combinations thereof. In certain embodiments, the acid may be a monoprotic acid or a polyprotic acid that is capable of losing more than a single proton per molecule in acid-base reactions. Polyprotic acids have various pKa values where the molecule is at a 50% / 50% balance between its protonated and deprotonated state for the proton in question. When polyprotic acids contain both protonated and deprotonated acid groups, they are referred to as “partially neutralized.” In further embodiments, the acid may be partially neutralized, thereby offering free acidity (i.e. the ability to protonate other chemical or molecules, or react with water molecules to form hydronium ions) while simultaneously maintaining a negative charge (i.e. anionic), which may be useful in chelating cationic ions present within the aqueous environment. Said differently, the acid, orcombination of acids, may protonate certain molecules within the bioceramic sealer, promoting its dissolution and liberating free metal cations into the aqueous environment that may then be chelated or sequestered by the acid or combination of acids (or other chelators present in the cleaning composition). Thus, the acid may promote bioceramic sealer dissolution through both acid attack and metal chelation. The pH of the cleaning solution composition may be modified accordingly to provide these types of characteristics in various preferences and balances.

[0017] The partially neutralized acid may also chelate free metal cations present in the aqueous environment (due to an equilibrium being established between cured bioceramic sealer and water). This chelation activity may promote continued dissolution of the sealer by forcing the equilibrium to dissolution. In such situations, the acid and metal cation have a Logio stability constant between 5 and 45. In some embodiments, the Logio stability is between 10 and 30. In certain embodiments, the Logio stability is between 10 and 20. In certain embodiments, the partially neutralized acid has a strong affinity for divalent and trivalent cations. In certain embodiments, the partially neutralized acid has a strong affinity for calcium, aluminum, zinc, and magnesium cations, among others. Although a single partially neutralized acid is referenced herein, more than one partially neutralized acid may be used in the cleaning composition.

[0018] Furthermore, as there are multiple bioceramic sealers on the market that are comprised of different cement-based materials (e.g. calcium silicate, other metal silicates, calcium aluminate, etc.), the disclosed cleaning solution may comprise at least two different acids that target the different base materials for these various bioceramic sealers. However, it may be possible to have one acid that effectively works on all bioceramic sealers on the market. Such a cleaning solution would simplify dental professional workflows and inventory management as one cleaning solution could be used for all different types of bioceramic sealers regardless of their composition. Furthermore, multiple acids can be selected such that the composition can be used to dissolve bioceramic sealers during retreatment procedures while also providing calcium chelating ability to be used during conventional RCT. Such a cleaning solution would simplify dental professional workflows and inventory management as one cleaning solution can be used for all endodontic procedures (conventional RCT and retreatment procedures) to remove bioceramic sealer and dentin smear layer created during RCT instrumentation. Additionally, the cleaning solution could be used to help remove intracanal medicaments, such as calcium hydroxide, during two-visit endodontic procedures.

[0019] In certain embodiments, the pH of the cleaning solution is about equal to the pKa value of one of the polyprotic acids providing a balance between the deprotonated and protonated acid, thereby allowing it to simultaneously act as an acid and chelator effectively while also providing a buffering effect to mitigate swings in pH during bioceramic sealer dissolution. In certain embodiments, the pH of the cleaning solution is between 1 and 10. In some embodiments, the pH of the cleaning solution is between 2 and 8. In some embodiments, the pH of the cleaning solution is between 3 and 6. In some embodiments, the pH of the cleaning solution is between 3 and 10. In some embodiments, the pH is between 5 and 9.5. In some embodiments, the pH is between 6 and 9. In some embodiments, the pH is between 7 and 9. Generally, the cleaning solution pH is slightly acidic, neutral, or slightly basic. The pH of the composition can be optionally modified using pH modifiers (e.g., hydrochloric acid, sodium hydroxide) to achieve the target pH.

[0020] In certain embodiments, the at least one acid comprises carboxylic acid moieties, phosphonate moieties, sulfonate moieties, or combinations thereof. Non-limiting examples of acids include citric acid, 2-phosphonobutane-l,2,4-tricarboxylic acid (PBTC), 1- hydroxyethylidene-l,l-diphosphonic acid (HEDP; also called etidronic acid), formic acid, glycolic acid, maleic acid, phytic acid, acetic acid, lactic acid, phosphoric acid, sulfuric acid, and ethylenediaminetetraacetic acid (EDTA), a polyphosphate, and sodium tripolyphosphate (STPP), among others. In some embodiments, the at least one acid is at a concentration (weight concentration; % w / w) of 0.1% to 50%. In certain embodiments, the at least one acid is at a concentration of 1% to 25%. In certain embodiments, the at least one acid is at a concentration of 2.5% to 15%. In certain compositions, the at least one acid is selected from PBTC, HEDP, or citric acid. In some embodiments, the at least one acid consists of a combination of citric acid and PBTC. In some compositions, the at least one acid consists of a combination of citric acid and at least one other acid.

[0021] Additionally, at least one chelating agent may be optionally added to the composition to chelate free cations to promote and accelerate the dissolution and solubilization of the bioceramic and / or cement-based sealers. Through the addition of a chelating agent, the acids comprising the cleaning solution’s composition can continue to dissolve the sealer material without being consumed by chelation reactions. In such situations, the chelating agent and cation have a Logic stability constant between 5 and 45. In some embodiments, the Logic stability is between 10 and 30. In certain embodiments, the Logic stability is between 10 and 20. In certain embodiments, thechelating agent has a strong affinity for divalent and trivalent cations. The at least one chelating agent is at a concentration of between 1% - 30%. In some embodiments, the chelating agent is at a concentration between 2.5% - 20%. In some embodiments, the chelating agent is at a concentration between 5% - 10%. Example chelating agents include, but are not limited to ethylenediaminetetraacetic acid (EDTA), n-(2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), other EDTA derivatives, acrylic acid homopolymer (also called polyacrylic acid, e.g. Acusol 425, Acusol 445, Acusol 190k, or other Acusols), acrylic acid copolymers, diethylenetriaminepentaacetic acid (DTPA), dimercaprol, trientine, defarasirox, deferiprone, deferoxamine, succimer, nitrilotriacetic acid, trans- l,2-DiaminOcyclohexane-N,N,N',N'- tetraacetic acid (CyDTA), iminodiacetic acid (IDA), nitrilotrimethylphosphonic acid (NTP), nitrilotris(methylphosphonic acid) (NTPO), amongst others. In certain embodiments, sulfate or phosphate sequestrants are added to the composition.

[0022] The cleaning solution may also include surfactants to enhance wetting, solubilization (solubility, cleaning and bioceramic sealer removal), debris suspension, emulsification and metal ion suspension. Surfactants are important to help suspend and wash away debris, aggregates, and filler material from the bioceramic and / or cement-based sealer that are not appreciably chemically dissolved or solubilized. Examples of suitable wetting agents are surfactants such as alkyldiphenyloxide disulfonates, alkyl aryl sulfonates, sodium dodecylbenzene sulfonate, alkyl sulfates, alcohol ethoxylates, polyoxyethylene glycol octylphenol ethers, polyoxyethylene glycol alkylphenol ethers, polyoxyethylene glycol sorbitan alkyl esters, sorbitan alkyl esters, copolymers of polyethylene glycol and / or propylene glycol, poloxamers, sodium stearates, sodium lauryl ether sulfates, linear alkylbenzene sulfonates, amine oxides, betaines, sodium lauryl sulfate, and disulfonates, fluorosurfactants, among others. In some embodiments, the surfactants are nonionic, anionic or zwitterionic, although certain cationic surfactants can be employed. In certain embodiments, the surface tension of the cleaning solution is less than 100 dynes / cm. In some embodiments, the surface tension is less than 60 dynes / cm. In certain embodiments, the surface tension is less than 40 dynes / cm. In one embodiment, the concentration of the at least one surfactant is between 0.01% - 25%. In some embodiments, the concentration of the at least one surfactants is between 0.1% - 15%. In some embodiments, the concentration of the at least one surfactants is between 0.1% - 5%. In some embodiments, the at least one surfactant comprises anamine oxide. In other embodiments, the at least one surfactant comprises an amine oxide and a decyl octyl glucoside.

[0023] Hydrotropes can also be added to surfactants for formulation stability and to reduce phase separation. Certain hydrotropes that can be used in the cleaning solution include, but are not limited to, sodium xylene sulfonate (SXS), ethylhexyl sulfonate (EHS), and sodium cumene sulfonate (SCS), among others. In another aspect, the hydrotrope may be present in the cleaning solution without the surfactant. In some embodiments, antimicrobial agents may be added to the composition to promote disinfection of the root canal space during retreatment. Suitable antimicrobial agents can include, but are not limited to, chlorhexidine gluconate, iodine (I2), hypochlorous acid, hydrogen peroxide, sodium benzoate, ascorbic acid, potassium sorbate, amongst others. Furthermore, lubricants may be added to the composition to help promote introduction of mechanical tools (e.g., endodontic files or rasps) to the root canal space to help loosen and remove bioceramic sealer material in conjunction with the cleaning solution. Suitable lubricants can include, but are not limited to, propylene glycol, glycerin, and polyethylene glycol, amongst others. These additives (e.g. hydrotropes, antimicrobial agents, and lubricants) can be added to the composition at a concentration of between 0.01% - 20%. In some embodiments, these additives can be added to the composition at a concentration of between 0.1% - 10%. In some embodiments, these additives can be added to the composition at a concentration of between 0.5% - 5%.

[0024] Additional builders and sequestrants can be added to the composition for improved performance, such as polyacrylic acids, and hexametaphosphate (HMP), among others. The concentration of the at least one builder or at least one sequestrant is between 0.01% - 15%. In some embodiments, the concentration of the at least one builder or at least one sequestrant is between 0.1% - 10%. In some embodiments, the concentration of the at least one builder or at least one sequestrant is between 0.1% - 2.5%. It may be possible that one chemical satisfies multiple ingredient classifications within the disclosed cleaning solution composition. For example, polyacrylic acids (also called acrylic acid homopolymers) may be classified as a chelating agent or a builder. In some aspects, the cleaning solution composition includes a thixotropic or thickening agent. Examples of suitable thixotropic agents are fumed silica and metallic silicates. Examples of suitable thickening agents are polymers, such as polystyrene, polypropylene, polyethylene, polyacrylates, polyacrylamides, polyvinyl alcohol, and copolymersand surfactant combinations, such as an uncharged surfactant (amine oxide, betaine) combined with an anionic surfactant from the list of suitable anionic surfactants. At room temperature, the disclosed cleaning may have a viscosity of about 0.5 cP to 2000 cP. In some embodiments, the viscosity is about 1 cP to 20 cP. The cleaning solution has a viscosity allowing it to be easily introduced into the root canal for improved penetration into dentinal tubules and canal complexities for removal of bioceramic sealer contained therein. In certain aspects, the cleaning solution may be non-Newtonian or pseudoplastic.

[0025] In certain embodiments, the cleaning solution contains a colorant (e.g., a dye, pigment, or the like) to impart a visible color to the composition which may be helpful when used clinically in vivo for visualization, especially under a microscope. The colorant may additionally have an affinity for the bioceramic sealer, which would help identify residual sealer needing removal during the retreatment procedure. Alternatively, the colorant may be pH sensitive and may change color as bioceramic sealer is dissolved and removed.

[0026] In further aspects of the disclosure, the cleaning solution composition provides a suitable shelflife of about 6—48 months when stored at room temperature without displaying characteristics of chemical instability or significant decreased clinical efficacy. An example of chemical instability would be the formation of a precipitate, or significant phase separation, during storage that renders the composition less effective or useless.

[0027] In certain aspects, the cleaning solution composition may be packaged in various syringes or containers sized between 0.1 mL-5000 mL, and in some embodiments, bottles sized between 100 mL-1000 mL. In some embodiments of the invention, it may be beneficial to have the cleaning solution composition stored in separate containers (e.g. two separate bottles, dual barrel syringe, etc.) as two distinct components, which the user may mix immediately prior to use.

[0028] The packaging of the components must be compatible for long-term storage (months to years). Satisfactory plastic resins for the packaging material may include, but are not limited to, polypropylene, polycarbonate, polyethylene, styrene acrylonitrile, methyl methacrylate- acrylonitrile-butadiene-styrene, and poly-cyclohexylenedimethylene terephthalate glycol, among others.

[0029] In certain aspects, the cleaning solution is provided as an item within a kit. In some embodiments, the kit may comprise any one or more of the following components: application tips, application brushes, mixing tips, mixing vessels, empty syringes, an instructions for use,mixing wells or other single use vessels, a dental etchant or etchants, a dental adhesive or adhesives, a dental primer or primers, a dental composite or composites, a dental cement or cements, an endodontic irrigant or irrigants, an endodontic sealer or sealers, and endodontic file or files, among other common dental and endodontic products.

[0030] The method of using the cleaning solution in vivo typically includes introducing the cleaning solution into the root canal system through the use of various application tips (cannulas) attached to a syringe containing the solution therein. Depending on the amount of bioceramic sealer present in the canal, 0.5mL to 50mL (or more) of the cleaning solution can be utilized to remove the bioceramic sealer and this volume of solution can be delivered over the course of a few seconds to 20 minutes or more. Once all the bioceramic sealer has been appreciably removed, the cleaning solution may be removed by the dental professional using a water, saline, or other endodontic irrigant rinse, pressured air, vacuum, paper points, or other commonly used techniques. Depending on the cleaning solution’s composition, it may be useful in both conventional RCT as well as retreatment procedures. In certain embodiments, the cleaning solution is used along with common endodontic irrigating solutions such as sodium hypochlorite (NaOCl) and EDTA. In other embodiments, the cleaning solution is ultrasonically activated by ultrasonic dental devices to further promote the cleaning ability of the disclosed composition. In some situations, the cleaning solution may be used in conjunction with sonic, multisonic or laser activation devices to increase the efficiency of the sealer removal.

[0031] One embodiment of a method of manufacturing the cleaning solution is as follows: first placing water in a mixing vessel, then dissolving at least one acid. Next, the pH is modified to the desired target pH using hydrochloric acid or sodium hydroxide. Lastly, surfactants are added as well as any other ingredients. The product by process is necessary to follow so precipitates, or other symptoms of an incompatible formulation, do not occur during manufacturing that would render the cleaning solution useless.DEFINITIONS

[0032] For purposes of interpreting this specification, the following abbreviations, terms and definitions will apply and whenever appropriate, terms used in the singular will also include the plural and vice versa. In the event that any definition set forth below conflicts with any document incorporated herein by reference, the definition set forth below shall control.

[0033] The term “room temperature” or ambient temperature as used herein refers to common ambient temperatures ranging from about 18 °C to about 27 °C.

[0034] The term “treating” refers to administering a therapy in an amount, manner, or mode effective to improve a condition, symptom, or parameter associated with a disorder. In some aspects, treating refers to the treatment of a dental ailment such as an infected tooth.

[0035] The term “substantially” as used herein means to a great or significant extent, but not completely.

[0036] As used herein, “a”, “an”, “the”, “at least one”, and “one or more” are used interchangeably.

[0037] The terms “comprises” and variations thereof do not have a limiting meaning where these terms appear in the description and claims.

[0038] The term “patient” or “subject” refers to mammals and humans. Thus, in one aspect, the subject is a mammal, or a mammal in need thereof. In one aspect, the subject is a human, or human in need thereof. In one aspect, the human or human in need thereof is a medical patient. The subject can be from ~0 years of age to 99 years of age or older.

[0039] The term “in vivo” generally means in a living subject.

[0040] The term “composition” generally refers to the chemical makeup of certain embodiments of the disclosed invention and is synonymous with “formula”, “formulation” and the like.

[0041] The term “chemical stability” generally refers to a composition or formula that remains in chemical equilibrium for a period of time without significant reactivity. In some instances, this stability can be observed visually, for example, if there is not a change in the composition’s state, such as observing the formation of a visible solid precipitate over time or phase separation. Said differently, the observation of a visible precipitate or phase separation within a composition or formula over time would indicate the initial formula was chemically instable. The precipitate then formed due to the composition desiring to become more chemically and thermodynamically stable.

[0042] The term “endodontic” generally refers to inside the tooth. The term “endodontic procedure” is generally synonymous with “root canal therapy” (abbreviated as RCT), or “root canal procedure”, and refers to a treatment of an infected tooth to cleanse the root canal system and remove the infection.

[0043] When an initial root canal treatment fails, a retreatment procedure is needed where the tooth is re-accessed and cleansed again to remove the source of infection and failure. The term “retreatment” generally refers to this type of retreatment procedure.

[0044] The term “smear layer” is known to those of skill in the art of dentistry and refers to the complex accumulation of soluble and insoluble organic and inorganic debris resulting from the mechanical preparation of a tooth surface. The smear layer includes cutting debris, tooth particles, microorganisms, necrotic material, and other substances resulting from preparation, and can include a superficial layer on the surface of a prepared tooth along with a layer or layers that are packed into the adjacent dentinal tubules at varying depths.

[0045] The term “sealer” generally refers to materials that are used as part of the obturation step of an endodontic procedure to help seal the canal. This term is generally synonymous with “endodontic sealer” and includes bioceramic sealers and non-bioceramic sealers, with bioceramic sealers mainly being cement-based materials. Within this embodiment, “sealer” is generally used synonymously with “bioceramic sealers” and refers to sealer materials that are cement-based in their composition.

[0046] The term “root canal system” generally refers to the naturally occurring anatomical spaces within the root(s) of a tooth including the pulp chamber.

[0047] The term “chelating agent” generally refers to chemical compounds or molecules that complex with metal ions to form a stable, water-soluble complex. The term “chelating agent” is to be understood as synonymous with the terms “chelant,” “chelator,” “metal complexing agent,” “complexing agent,” “sequestrant,” and “sequestering agent”.

[0048] The abbreviation “EDTA” will be understood to refer to the chemical ethylenediaminetetraacetic acid, which is a chelating agent capable of binding a variety of metal ions, for example, calcium ions.

[0049] The abbreviation “HEDP” will be understood to refer to the chemical 1 -hydroxy ethylidene- 1,1-diphosphonic acid, which is a chelating agent capable of binding a variety of metal ions, for example, calcium ions.

[0050] The abbreviation “PBTC” will be understood to refer to the chemical 2-phosphonobutane- 1,2,4-tricarboxylic acid, which is a chelating agent capable of binding a variety of metal ions, for example, calcium ions.

[0051] The term “dentin” generally refers to a type of calcified tissue that is a major component of teeth. Hydroxyapatite is the main inorganic constituent of dentin and is a naturally occurring mineral from of calcium apatite with the formula Cas(PO4)3(OH).

[0052] The term “cleaning solution” generally refers to embodiments of the present disclosure that are generally used to remove bioceramic sealers from the root canal system during RCT and retreatment procedures in vivo (although its use is not restricted only to retreatment procedures). “Cleaning solution” is synonymous with “sealer dissolving solution”.

[0053] The term “cementation” generally refers to the process of a material containing cement to react with water to set or harden (i.e. via a hydration reaction). Specifically in the context of this disclosure, cement-based bioceramic sealers contain cement materials which react with water to transition from a fluid state to a rigid state via this hydration reaction. In the context of this disclosure, “cementation” is generally synonymous with “setting”, or “hardening” and these types of words are used interchangeably throughout the disclosure.

[0054] The term “polyprotic” generally refers to molecules that are able to donate more than one proton per acid molecule, in contrast to monoprotic acids that only donate one proton per molecule.

[0055] The above summary of the present invention is not intended to describe each disclosed embodiment or every implementation of the present invention. The description that follows more particularly exemplifies illustrative embodiments. In several places throughout the description, guidance is provided through lists of examples, which examples can be used in various combinations. In each instance, the recited list serves only as a representative group and should not be interpreted as an exclusive list.EXAMPLES

[0056] Table 1 summarizes the chemical constituents that comprise the disclosed cleaning solution. Additionally, Table 2 provides example formulas or compositions of the disclosure including the developed and tested PBTC blend formula. This blend is envisioned to be used in the cleaning solution regardless of the acid chosen. For example, PBTC can be readily replaced with HEDP for the formulations listed in Table 2, although additional builders, chelators, or surfactants may be necessary to stabilize the HEDP and ensure precipitates don’t form when HEDP chelates various metal cations. It is also conceivable that equivalent performance may be met by omitting one or more of the non-acid additives.Table 1 : Chemical constituents that comprise the cleaning solution.Table 2: Example formulas or compositions that comprise the cleaning solution.TESTING

[0057] Test #1. Preliminary testing investigated the ability of various acids at different concentrations and pHs to dissolve the calcium aluminate-based REGEN Bioactive EndoSealer (“sealer”, Inter-Med / Vista Apex, Racine, WI) and hydroxyapatite (HA) discs (Clarkson Chromatography Products, South Williamsport, PA). Approximately 0.65 - 0.75g samples of cured sealer were placed within 20g of acidic solution for 30 minutes at room temperature. After incubation, the sealer samples were removed from the acidic solution, rinsed with ~3mL deionized water, and then dried at 55C for 45 minutes. Final mass measurements were then taken to calculate sealer mass loss. An identical procedure was utilized for the HA discs which were all about 0.35g in mass, although exposure to the acidic solution was undertaken for five days.

[0058] Test #1 data is summarized in Figure 1. For the cleaning solution to be most efficacious and advantageous, a high sealer mass loss and low HA disc mass loss is desirable. Several samples were identified as advantageous as they exhibited high sealer mass loss and little to no HA disc mass loss. These include 7% PBTC with additive blend at pH of 9 and 4.7 (“7% PBTC Blend from Table 1), 10% citric acid at pH of 8.3 and 6.3, and 10% HEDP at pH 8.3. These acid compositions are shown in Figure 2. The performance of citric acid and HEDP would likely be further improved using the same additives that were used with the PBTC blend. Interestingly, scaling up all ingredients approximately two-fold (13% PBTC blend) did not improve performance but actually seemed to inhibit sealer dissolution within this study. Therefore, total dissolved solids seems to be an important consideration of the disclosed cleaning solution composition. In certain embodiments, the concentration of water in the disclosed cleaning solution is at least 50%. In some embodiment, the concentration of water in the disclosed cleaning solution is at least 60%. In some embodiment, the concentration of water in the disclosed cleaning solution is at least 80%.

[0059] Test #2. A subsequent test was undertaken following a similar methodology to Test #1, however, the test methodology was updated to make the test more clinically relevant (i.e. the cured sealer and HA discs were exposed to 12mL of solution for 30 minutes). Normalized cured sealer dissolution results are shown in Figure 3 and normalized HA disc dissolution results are shown in Figure 4. The disclosed Blend B resulted in greater than 10 times the dissolution of cured sealer compared to standard endodontic irrigants (6% NaOCl and 17% EDTA), while dissolving less than 4% of the HA disc compared to 20% Citric Acid (Ultradent, South Jordan, UT). This test exemplifies the benefits of the disclosed cleaning solution compositions which selectively dissolvebioceramic / cement-based sealer materials without significant collateral damage or dissolution to dentin (i.e. hydroxyapatite).

Claims

CLAIMSWhat is claimed is:

1. An endodontic cleaning solution composition, comprising: at least one acid selected from PBTC, citric acid, HEDP and mixtures of the same; at least one surfactant; and, water; wherein the cleaning solution composition has a pH between about 2 to 7.

2. The composition of claim 1, wherein the at least one acid is at a concentration between 5% and 35%.

3. The composition of claim 1, wherein the at least one acid chelates a metal ion.

4. The composition of claim 1, wherein the at least one acid consists of citric acid.

5. The composition of claim 1, further comprising a builder.

6. The composition of claim 1, wherein the composition has a surface tension less than 40 dynes / cm.

7. The composition of claim 1, wherein the composition has a viscosity between IcP and 20cP at room temperature.

8. The composition of claim 1, wherein the at least one surfactant comprises a nonionic surfactant.

9. The composition of claim 1, wherein the at least one surfactant comprises an amine oxide.

10. The composition of claim 1, wherein the at least one surfactant consists of an amine oxide and a decyl octyl glycoside.

11. The composition of claim 1 further comprising at least one antimicrobial agent.

12. The composition of claim 1 further comprising at least one lubricant.

13. The composition of claim 1 further comprising at least one chelating agent.

14. The composition of claim 1 further comprising at least one chelating agent, wherein the at least one chelating agent is a polyacrylic acid.

15. The composition of claim 1, wherein the at least one acid consists of citric acid at a weight / weight (w / w%) concentration between 10% and 30%.

16. A method of retreating a failed root canal procedure, comprising:introducing an endodontic cleaning solution into a root canal or root canals to dissolve bioceramic sealer contained therein, wherein, the endodontic cleaning solution comprises: at least one acid selected from PBTC, citric acid, HEDP, polyacrylic acid, and mixtures of the same; at least one surfactant; and, water.

17. The method of claim 16, wherein the cleaning solution composition has a pH between about 2 to 9.

18. The method of claim 16, wherein the cleaning solution composition dissolves calcium silicate and calcium aluminate bioceramic sealer materials from the root canal during retreatment procedures.

19. The method of claim 16, wherein the cleaning solution composition selectively dissolves bioceramic sealer materials but does not appreciably dissolve hydroxyapatite.

20. The method of claim 16, wherein the cleaning solution composition dissolves and removes calcium hydroxide from the root canal spaces during RCT procedures.

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