Composition and method for using medicament for endodontic irrigation, stem cell preparation and tissue regeneration

Abstract

A single intra-canal substance composition for tissue dissolution, disinfection, tissue degradation, tissue removal and disinfection is provided. The composition includes calcium hydroxide, sodium hydroxide, potassium thioglycolate or calcium thioglycolate, to form an effective single intra-canal substance capable of degrading a cell by disrupting its disulfide bonds. Further, the composition may incorporate mineral oil, urea, cetearyl alcohol, D&C yellow No. 8, chromium hydroxide, theobroma cocoa seed butter, iron oxides, fragrances, water fragrance, lanolin, and ceteareth-20 to enhance its functioning. Furthermore, the composition that is bactericidal against Enterococcus faecalis, Streptococcus mutans and Candida albicans, used in multiple applications in dentistry and medicine. Furthermore, the composition is a single intra-canal irrigant that eradicates microorganisms as it facilitates the chemo-mechanical debridement of the root canal system.

Claims

1. A method of treating a patient, the method comprising the steps of: (a) irrigating a pulpal cavity of a tooth with a composition comprising a hydroxide, a thioglycolate, and either of ceteryl alcohol or ceteareth-20; and (b) removing a pulpal tissue from the pulpal cavity.

2. The method of claim 1, wherein the step of irrigating the bony cavity includes flowing the composition into the bony cavity.

3. The method of claim 2, further comprising the step of providing a syringe having a barrel at least partially filled with the composition, wherein flowing the composition into the pulpal cavity includes expelling the composition from the syringe through an endodontic irrigation needle or syringe tip into the pulpal cavity.

4. The method of claim 1, wherein the step of irrigating the pulpal cavity includes coating a portion of a medical instrument with the composition and inserting the coated portion into the pulpal cavity.

5. The method of claim 1, wherein the composition is adapted to disrupt a disulfide bond in at least one of the pulpal tissue and a microbe.

6. The method of claim 1, wherein irrigating the pulpal cavity comprises degrading the pulpal tissue, thereby facilitating the step of removing the pulpal tissue from the pulpal cavity.

7. The method of claim 1, wherein the composition includes an hydroxide, a thioglycolate, and water.

8. The method of claim 7, wherein the hydroxide is present in the composition in an amount effective to deprotonate at least one of the thioglycolate and a biomolecule present in a soft tissue.

9. A method of treating a patient, comprising the steps of: irrigating a bony cavity with a composition comprising a compound comprising potassium thioglycolate, calcium thioglycolate, 2-mercaptoethanol, dithiothreitol, dithioerythritol, tris(2-carboxyethyl)phosphine, dithiobutylamine, and glutathione, thereby degrading at least one of a soft tissue and a microbe within the bony cavity.

10. The method of claim 9, wherein the bony cavity includes a pulpal cavity of a tooth and the soft tissue includes a pulpal tissue.

11. The method of claim 9, further comprising the step of removing from the bony cavity at least one of a tissue and a bacteria that has been degraded.

12. The method of claim 9, wherein the step of irrigating the bony cavity includes flowing the composition into the bony cavity.

13. The method of claim 12, further comprising the step of providing a syringe having a barrel at least partially filled with the composition, wherein flowing the composition into the bony cavity includes expelling the composition from the syringe through an endodontic irrigation needle or syringe tip into the bony cavity.

14. The method of claim 9, wherein the step of irrigating the bony cavity includes coating a portion of a medical instrument with the composition and inserting the coated portion into the bony cavity.

15. The method of claim 9, wherein the step of irrigating a bony cavity includes degrading at least one of a soft tissue and a microbe by contacting one or more of a prepared surface, an unprepared surface, and a biofilm.

16. The method of claim 9, wherein the step of irrigating a bony cavity includes contacting an abnormally growing tissue, thereby degrading it.

17. The method of claim 9, wherein the composition includes an hydroxide, a thioglycolate, water, fragrance, lanolin, mineral oil, urea, ceteryl alcohol and ceteareth-20.

18. The method of claim 9, wherein the bony cavity is formed by the operative treatment of a carious lesion in a tooth.

19. The method of claim 18, wherein the composition is a restorative rinse.

20. The method of claim 18, wherein the composition is effective to reduce a quantity of streptococcus mutans within the bony cavity by at about 99%.

21. A method of treating a patient, comprising the steps of: forming an opening for accessing a bony cavity within a tooth; irrigating the bony cavity with a composition comprising a reducing agent effective in disrupting disulfide bonds in proteins, wherein the composition comprising a hydroxide, a thioglycolate, and either of ceteryl alcohol or ceteareth-20; debriding the bony cavity; and rinsing the bony cavity, thereby removing the composition therefrom.

22. The method of claim 21, wherein the step of irrigating the bony cavity includes flowing the composition into the bony cavity.

23. The method of claim 22, further comprising the step of providing a syringe having a barrel at least partially filled with the composition, wherein flowing the composition into the bony cavity includes expelling the composition from the syringe through an endodontic irrigation needle or syringe tip into the bony cavity.

24. The method of claim 21, wherein the step of irrigating the bony cavity includes coating a portion of a medical instrument with the composition and inserting the coated portion into the bony cavity.

25. The method of claim 21, wherein the step of irrigating a bony cavity includes contacting a pulpal tissue or a microbe with the composition.

26. The method of claim 21, wherein the composition further includes water, fragrance, lanolin, mineral oil, urea, ceteryl alcohol and ceteareth-20.

27. The method of claim 21, wherein the step of irrigating the bony cavity includes contacting a surface of a pulp tissue or a biofilm within the bony cavity with the composition for 5 minutes or more.

28. The method of claim 21, wherein the bony cavity is formed by the operative treatment of a carious lesion in a tooth.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The above and still further features and advantages of the present invention will become apparent upon consideration of the following detailed description of embodiments thereof, especially when taken in conjunction with the accompanying drawings, and wherein:

(2) FIG. 1 is a cross sectional view of a tooth with tooth decay about to go under treatment in accordance with an embodiment of the present invention;

(3) FIG. 2 illustrates the tooth of FIG. 1 at a stage of treatment showing access to the pulpal chamber in accordance with an embodiment of the present invention;

(4) FIG. 3 illustrates the tooth of FIG. 1 at a further stage of treatment showing a composition being applied in accordance with an embodiment of the present invention;

(5) FIG. 4 illustrates the tooth of FIG. 1 at a further stage of treatment showing a composition accessing the cavity's floor in accordance with an embodiment of the present invention;

(6) FIG. 5 illustrates the tooth of FIG. 1 at a further stage of treatment showing a rinsing solution in accordance with an embodiment of the present invention;

(7) FIG. 6 illustrates the tooth of FIG. 1 at a further stage of treatment showing the tooth after rinsing and the empty root canal in accordance with an embodiment of the present invention;

(8) FIG. 7 is a flow chart depicting root canal treatment using a composition, in accordance with an embodiment of the present invention; and

(9) FIG. 8 illustrates structure of disulfide bonds in proteins according to an embodiment of the present invention.

(10) The headings used herein are for organizational purposes only and are not meant to be used to limit the scope of the description or the claims. As used throughout this application, the word “may” is used in a permissive sense (i.e., meaning having the potential to), rather than the mandatory sense (i.e., meaning must). Similarly, the words “include,” “including,” and “includes” mean including but not limited to. To facilitate understanding, like reference numerals have been used, where possible, to designate like elements common to the figures.

DETAILED DESCRIPTION

(11) The present invention will be illustrated below in conjunction with an exemplary application, e.g., root canal treatment. Although well suited for use with, e.g., a medical application having disulfide bonds and requiring breakage of disulfide bonds, the present invention is not limited to any particular type of medical application. Those skilled in the art will recognize the disclosed techniques may be used in any medical or non-medical application in which it is desirable to provide breakage of disulfide bonds.

(12) The phrases “at least one”, “one or more”, and “and/or” are open-ended expressions that are both conjunctive and disjunctive in operation. For example, each of the expressions “at least one of A, B and C”, “at least one of A, B, or C”, “one or more of A, B, and C”, “one or more of A, B, or C” and “A, B, and/or C” means A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B and C together.

(13) The term “a” or “an” entity refers to one or more of that entity. As such, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein. It is also to be noted the terms “comprising”, “including”, and “having” can be used interchangeably.

(14) The term “automatic” and variations thereof, as used herein, refers to any process or operation done without material human input when the process or operation is performed. However, a process or operation can be automatic, even though performance of the process or operation uses material or immaterial human input, if the input is received before performance of the process or operation. Human input is deemed to be material if such input influences how the process or operation will be performed. Human input that consents to the performance of the process or operation is not deemed to be “material.”

(15) The terms “determine”, “calculate” and “compute,” and variations thereof, as used herein, are used interchangeably and include any type of methodology, process, mathematical operation or technique.

(16) In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of embodiments or other examples described herein. In some instances, well-known methods, procedures, compositions, or components have not been described in detail, so as to not obscure the following description. Further, the examples disclosed are for exemplary purposes only and other examples may be employed in lieu of, or in combination with, the examples disclosed. It should also be noted the examples presented herein should not be construed as limiting of the scope of embodiments of the present invention, as other equally effective examples are possible and likely.

(17) FIG. 1 shows a cross-sectional view of a tooth 100 in accordance with an embodiment of the present invention. The tooth 100 includes tooth decay 101, as shown in the figure. Because of the tooth decay 101, the tooth 100 is under a treatment (i.e., root canal treatment). The tooth 100 further includes enamel 102, a pulpal calcification 103, a dentin 104, and a pulp 105. The tooth 100 further includes an apex 106 and a periodontal ligament 107. The purpose of the root canal treatment is to completely remove the pulp 105 (as it is infected or injured, and can infect surrounding teeth), and that includes removal of all tissues, debris and microorganisms from root canal area.

(18) Tissues of the pulp 105 differ from tissues of the enamel 102 and tissues of the dentin 104. Pulpal tissue is a highly vascular and soft tissue. On other hand, the dentin 104 and the enamel 102 are hard, calcified, and mineralized tissues. The enamel 102 and the dentin 104 include same type of inorganic materials, but differ in degree of calcification and mineralization of the inorganic material. Further, protein of the enamel 102 is resistant to enzymatic hydrolysis. The enamel 102 is more resistant to enzymatic digestion than skin. Therefore, the protein of the enamel 102 is not classified as a type of keratin and is not affected by actions of a chemical depilatory, if the chemical depilatory is applied. Further, chemical composition of the tissues of the pulp 105 is different than chemical composition of the dentin 104 and the enamel 102.

(19) According to an embodiment of the present invention, the pulp 105 includes disulfide bonds. The disulfide bond is a covalent bond that is derived by coupling of two thiol groups. The linkage is called an SS bond or disulfide bridge. The disulfide bonds are present in a plurality of living and non-living species. For example, disulfide bonds are present in bacteria as they serve as a protective role for bacteria. Further, in humans also, disulfide bonds are found in secretory proteins, lysosomal proteins, and exoplasmic domains of stability of proteins in extracellular tissue. Further, disulfide bonds are also found in nuerokeratin of the myelinated sensory nerve A fibers. Furthermore, disulfide bonds are present in HNGB1 (high-mobility group protein-1), which is a mediator of inflammation. According to an embodiment of the present invention, a method is provided for utilizing the disulfide Bond or S—S bond for cleaning out the pulp 105 and removing tissue.

(20) Tissues of the pulp 105 include disulfide bonds. Disulfide bonds acts like a glue and hold together molecules and proteins. If the disulfide bonds are broken, it may weaken and break down structure of the pulp 105 and facilitate removal of tissues from the pulp 105.

(21) FIG. 2 depicts the tooth 100, during the root canal treatment, according to an embodiment of the present invention. The pulpal chamber is accessed, as shown in the figure. FIG. 2 further depicts access to the cavity 108, and access to cavity walls 109.

(22) FIG. 3 depicts introduction of a composition 110 into the cavity 108, according to an embodiment of the present invention. The composition is placed into the cavity 108 by using a disposable needle 111.

(23) According to an embodiment of the present invention, the composition 110 is a chemical depilatory. The present invention utilizes the chemical depilatory as an endodontic intra-canal medicament for irrigation, disinfection, and lubrication to provide anti-microbial properties and further facilitate removal of smear layer. In an embodiment of the present invention, the composition 110 breaks the disulfide bonds of pulpal tissue. The breakage of the disulfide bonds degrades structure of the pulpal tissue in order to remove tissue.

(24) The chemical depilatories have been used for a wide variety of purposes. For example, chemical depilatories have been used for reducing microbial levels on the hide of an animal. Further, the chemical depilatories have been used in removal of hair from skin and outer extremities as from the arms, legs, face, and underarms. Furthermore, the chemical depilatories have been used to remove unwanted hairs from the external skin of both animals and humans. However, chemical depilatories have never been used in endodontics or in dentistry.

(25) Further, tissues of the pulp 105 and hair have a similar characteristic of containing disulfide bonds as both are derived from neural crest stem cells. The hair follicle bulge is derived from cranial neural crest, and similarly the dental pulp and periodontal ligament are derived from the neural crest. Chemical depilatories has been used in hair removal on humans and as an antimicrobial agent on hides of animals for years successfully, the present invention utilizes the chemical depilatories in a novel way for use in endodontic and for removal of tissue from a bony cavity.

(26) According to an embodiment of the present invention, the composition 110 includes active ingredients of calcium hydroxide, sodium hydroxide, and potassium thioglycolate. In an embodiment of the present invention, the composition 110 further includes mineral oil, urea, lanolin, water, fragrance, cetearyl alcohol and ceteth-20 for contributing to ability of the composition 110 to produce desired results.

(27) According to an embodiment of the present invention, the composition 110 is capable of dislodging calcifications that lie within root canal system by weakening attached connective tissue as well as removal of soft tissue from the cavity of a hard, bony tissue. In an embodiment of the present invention, the composition 110 provides a single endodontic irrigant composition that dissolves tissue, removes the smear layer, and includes antibacterial capability.

(28) Further, in an embodiment of the present invention, the composition 110 (or chemical depilatory) may be used by a dental professional in an unprepared as well as prepared root canal system in order to facilitate the instrumentation of root canal walls and pulpal chamber by dislodging calcifications, removing pulpal tissue and debris.

(29) The composition 110 may do multiple roles in the root canal treatment. For example, the composition 110 may act as an irrigant, disinfectant, conditioner, antimicrobial agent and lubricant for endodontic chemo-mechanical preparation of the root canal space, according to an embodiment of the present invention. The composition 110 includes calcium hydroxide, sodium hydroxide, and potassium thioglycolate in combination. Further, in an embodiment of the present invention, the composition 110 may include mineral oil, urea, cetearyl alcohol and ceteth-20 for use for irrigation, disinfection, lubrication, removing the smear layer, dissolving pulpal tissue and as an anti-bacterial agent. In an embodiment of the present invention, the composition 110 may be in the form of, for example, but in not restricted to, a lotion, a cream, a gel, a solution, and a paste. In another embodiment of the present invention, the composition 110 may be an emulsion, such as, micro-emulsion and macro-emulsion.

(30) Further, in an embodiment of the present invention, lanolin as used as an emollient. Furthermore, in an embodiment of the present invention, water is used for diluting. Further, in an embodiment of the present invention, the composition 110 may also include aloe barbadensis as an emollient.

(31) In an embodiment of the present invention, the composition 110 may be used in endodontic usages during intra-canal instrumentation in order to break disulfide bonds present in pulpal tissue, to remove the smear layer, and to be effective against bacteria present in the root canal system. According to an embodiment, the composition 110 may be used as a single endodontic irrigant on unprepared as well as prepared tooth surfaces in order to dissolve tissue, remove the smear layer, and be effective against bacteria. The composition 110 may further provide for removal of soft tissue inside of a hard, bony cavity. Further, according to an embodiment of the present invention, the composition 110 may provide preparation of regeneration and formation of mineralized and soft tissue in a hard bony cavity (e.g., a human or animal). Furthermore, the composition 110 may be used as intraosseous irrigant, and in medicine, for example, in long bones and in preparing skeletons for museums etc.

(32) FIG. 4 depicts the composition 110 accessing the cavity's floor 108 as well as the cavity walls 109. The composition 110 provides removal of soft, connective tissue (i.e., pulp tissues) from within a hard tissue cavity (i.e., enamel and dentin) and hard bony cavities. In an embodiment of the present invention, the composition 110 is a chemical depilatory that removes soft tissue, necrotic tissue, debris, and calcified tissue from within the hard tissue cavity. In an embodiment of the present invention, the composition 110 functions as an intra-canal medicament with properties of an irrigant, disinfectant, lubricant, antimicrobial agent, debriding agent, and cleansing agent (as it is capable of removing the smear layer). The composition 110 is further capable for chemo-mechanical cleansing and enlarging of the root canal system. Furthermore, the composition 110 is also capable of bleaching teeth.

(33) According to an embodiment of the present invention, the composition 110 includes active ingredients of calcium hydroxide, sodium hydroxide, and potassium thioglycolate, as discussed above.

(34) In one embodiment of the present invention, calcium hydroxide (present in the composition 110) creates an alkaline environment so that endodontic pathogens are not able to survive. Further, in an embodiment of the present invention, sodium hydroxide (which is a strong base) is used in tissue digestion by bleaching. Further, the sodium hydroxide breaks down chemical bonds in tissue as bone remains present.

(35) Further, in an embodiment of the present invention, potassium thioglycolate (present in the composition 110) breaks down sulfur bonds present in keratin protein of pulp. Potassium thioglycolate reacts with the cystine present in the protein. The reaction is following: 2SH—CH2-COOH (thioglycolic acid)+R—S—S—R (cystine=disulfide bridge)---->2R—SH+COOH CH2 SS CH2 COOH (dithiodiglycolic acid).

(36) Further, in an embodiment of the present invention the composition 110 may include one or more of following constituents including, but not limited to, water, mineral oil, urea, cetearyl alcohol, D&C yellow No. 8, chromium hydroxide, theobroma cocoa seed butter, iron oxides, fragrances, and ceteareth-20. According to an embodiment of the present invention, the mineral oil may fill surface cracks. Those skilled in the art will appreciate that the surface cracks if not filled, may harbor bacteria. Further, the mineral oil may act as a lubricant. Further, according to an embodiment of the present invention, the urea may retain moisture and function as a keratolytic emollient.

(37) Further, according to an embodiment of the present invention, the cetearyl alcohol may include a coconut oil. The cetearyl alcohol can emulsify with ceterth-20 can to form cetereth-20 and enhances viscosity of the lotion.

(38) Once, the pulp has been cleaned out and root canal area disinfected with help of the composition, a rinsing solution may be introduced, as shown in FIG. 5.

(39) FIG. 5 shows introduction of a rinsing solution 112 using a disposable needle 113 for applying the rinsing solution. FIG. 6 shows the tooth 100 after rinsing with an empty root canal system 114.

(40) According to an embodiment of the present invention, the composition 110 (i.e., the chemical depilatory) breaks the disulfide bonds in the pulpal tissues. Therefore, any pulp stones attached to weakened pulpal tissues can also be removed. The breaking of bonds aids in the removal of unwanted pulpal tissue and debris. The composition 110 further lubricates, irrigates, disinfects, dissolves, cleanses and removes the smear layer. Further, the composition 110 (or the chemical depilatory) provides antimicrobial protection against infections.

(41) The composition 110 includes chemicals (that breaks the disulfide bonds, e.g., calcium hydroxide, sodium hydroxide, and potassium thioglycolate) with other substances (that are needed to lubricate, dissolve, disinfect and remove pulpal debris, e.g., mineral oil, urea, cetearyl alcohol and ceteth-20). The disulfide bonds are present in myelinated sheath of nerves that enters the tooth via its apical opening. The composition 110 weakens portion of the myelinated sheath of an entering nerve within the root canal system, so that, it can be easily scraped off the inner root canal wall of the tooth. For example, the chemical depilatories removes the hair from the follicle by weakening it at the point that it emerges from the follicle, the present invention utilizes the chemical depilatories in weakening nerve's protection by breaking down the disulfide bond in the myelinated sheath that surrounds and protects the nerve.

(42) Further, the composition 110 provides cleansing and debriding the pulp chamber and root canal space. The composition 110 further removes smear layer by breaking the disulfide bonds present in glycosaminoglycans (GAG), which is the matrix of the inorganic layer. Furthermore, the composition 110 provides dislodging pulpal calcifications by breaking bonds within the tissue that surrounds the calcification.

(43) Hence, the composition 110 provides disinfecting, cleansing, irrigating and lubricating both prepared and unprepared tooth surfaces during dental procedures. The composition 110 may be used in endodontic during non-surgical root canal therapy during intra-canal chemo-mechanical preparation. Also, the composition 110 further may be used to remove the debris that is formed during dental procedure and dissolve proteins within the pulpal chamber.

(44) Further, according to embodiment of the present invention, the composition 110 may be used for cleaning, irrigating, disinfecting, etc. of inside of any bony cavity (e.g., a hard bony cavity, a bony cavity in canines). For example, the composition may be used for intra-medullary reaming and irrigating (e.g., to be used before a rod in orthopedics), maceration (e.g., cleaning animal skulls & bones used of preserving them), preparing a bony surface for stem cells, for a site for regeneration of new tissue, and for removing tissue from inside a bony cavity to allow for the mineralized tissue.

(45) Further, the composition 110 may be used for preparing a bony surface for cellular differentiation, tissue formation, and tissue regeneration. Those skilled in the art will appreciate that for making regeneration of stem cells successful, the diseased or unwanted cells must be removed as they damage the underlying tissues' ability to generate on its own new cells. In an embodiment of the present invention, the composition 110 removes the diseased or unwanted, infected or inflamed cells, and provides a clean area for regeneration of stem cells.

(46) Further, the composition 110 may assist a dentist to prepare the tooth surface to place stem cells inside the tooth for pulpal and tissue regeneration. The stem cells may be used within the pulpal chamber. For example, an embodiment of the present invention provides a root canal therapy whereby a root canal procedure will be cleaning the chamber/roots and then placing stein cells to re-grow pulpal and mineralized tissue. Those skilled in the art will appreciate that this can only be performed if the composition 110 as described here in above is first used to clean the inside of the tooth 100, and failure to clean the inside of the tooth 100 sufficiently will not provide a clean enough surface for the placement of stem cells. The composition 110, provided by the present invention, provides cleaning of the inside of the tooth 100 and provides a clean surface for placement of stem cells. Furthermore, according to an embodiment of the present invention, the composition 110 may also provide bleaching of teeth as it removes the dead blood which is dark in color from within the teeth that gives the tooth a dark shade.

(47) FIG. 7 is a flowchart of a method 700 for cleaning out pulp and disinfecting root canal area in a root canal treatment, according to an embodiment of the present invention. According to an embodiment of the present invention, the method 700 provides using a chemical depilatory as a composition in endodontic. The method 700 is effective due to disulfide bonds presence in pulpal tissue.

(48) At step 702, a chemical depilatory composition is dispensed into disposal tubes. Further, disposal needles may be attached to the disposable tubes. According to an embodiment of the present invention, the composition may include calcium hydroxide, sodium hydroxide, and potassium thioglycolate. In one embodiment of the present invention, calcium hydroxide (present in the composition) creates an alkaline environment so that endodontic pathogens are not able to survive. Further, in an embodiment of the present invention, sodium hydroxide (which is a strong base) is used in tissue digestion. Further, the sodium hydroxide breaks down chemical bonds and further keeps bones intact. Furthermore, in an embodiment of the present invention, potassium thioglycolate (present in the composition) breaks down sulfur bonds present in protein of pulp tissue. In another embodiment of the present invention, potassium thioglycolate is a thiol-based depilatory.

(49) In another embodiment of the present invention, the composition may further include mineral oil, urea, cetearyl alcohol, D&C yellow No. 8, chromium hydroxide, theobroma cocoa seed butter, iron oxides, fragrances, and ceteareth-20 to enhance its functioning, in addition to calcium hydroxide, sodium hydroxide, and potassium thioglycolate. According to an embodiment of the present invention, the mineral oil may act as a lubricant. Further, according to an embodiment of the present invention, the urea may retain moisture, prevent infections, treat inflammatory conditions, and function as a keratolytic emollient. Further, according to an embodiment of the present invention, the cetearyl alcohol can emulsify with ceterth-20 can to form cetereth-20 and enhances viscosity of the lotion. In an embodiment, the cetearyl alcohol may include a coconut oil. Furthermore, in an embodiment of the present invention, the fragrance acts as deodorizers.

(50) At step 704, a few drops of the composition are placed in a pulpal chamber to wet the floor with the disposable needle. At step 706, the composition or solution is placed it at opening of the canal for going inside the canal with help of an endodontic file/reamer/instrument of choice, coat the ‘file’ with the solution and. In an embodiment of the present invention, the opening of the canal may include, but is not restricted to, soft tissues. The solution is left there for about 1-3 minutes.

(51) At step 708, the composition or solution is rinsed with warm water. Further, in an embodiment of the present invention, the solution may also be rinsed with warm sodium hypochloride. In another embodiment of the present invention, the solution may also be rinsed with other commercial, conventional irrigants. Further, the pulp and pulpal debris is removed and irrigated out.

(52) At step 710, it is determined whether the pulpal calcifications or infected/damaged area of tooth has been completely removed and dislodged, and the canal area has been completely disinfected. In case, there are still some tissues of pulp remaining or infection remaining, flow of the method 700 returns to the step 702. Otherwise, the method 700 proceeds towards step 712, wherein the pulpal canal is prepared for obturation. In an embodiment of the present invention, a mechanical instrument procedure may be carried out for obturating the pulpal canal and then the method 700 concludes.

(53) FIG. 8 illustrates disulfide bonds in proteins according to an embodiment of the present invention. Disulfide bonds 802 present in tissue proteins of a human body may be considered as a framework for living cells. In an embodiment of the present invention, in a human body, let say, an infected area having neoplastic cells is present in tissue. By using the present invention the infected area of the human body may be treated by a chemical depilatory that can cause apoptosis in abnormal cells. The present invention applied to the infected area breaks disulfide bonds 802 present. When the disulfide bonds 802 are broken in the infected tissue, a doctor may prevent regeneration of the neoplastic cells in that area. Further, DNA, RNA or proteins are dependent upon the disulfide bonds 802 for their integrity and existence. Therefore, once the disulfide bonds 802 are broken, the cell loses its ability for functioning and regeneration. Cellular breakdown results in the prevention and arrest of abnormally growing cells.

(54) The foregoing disclosure has focused on exemplary depilatory compositions which disrupt disulfide bonds. These exemplary compositions are not intended to be limiting, however, and it should be appreciated that any composition or active pharmaceutical ingredient which effectively reduces such disulfide bonds can fall within the scope of the various systems and methods of the invention. Exemplary active ingredients suitable for use in the various embodiments of the invention include, without limitation, potassium thioglygolate, calcium thioglycolate, 2-mercaptoethanol, dithiothreitol, dithioerythritol, tris(2-carboxyethyl)phosphine, dithiobutylamine, and glutathione, as well as combinations of two or more of these ingredients.

(55) The various methods of the present invention generally involve the application of the compositions described above to contact materials in bony cavities such as the pulpal cavity of a tooth. These compositions are applied, in some cases, by irrigating the bony cavities with flowable compositions that can be delivered through syringes and irrigation needles or flexible tips familiar to those of skill in the art. In other cases, the compositions are pastes that are placed in bony cavities using a spatula and/or by coating an instrument such as an endodontic file with the paste and then using the instrument to mechanically debride the bony cavity. As the examples below demonstrate, the compositions can contact various surfaces within the cavity for intervals normally associated with endodontic irrigation and de-pulping, such as 5, 15 or 30 minutes.

(56) Compositions of the invention are delivered in any suitable format for use in an endodontic or general dental office. In one group of embodiments, a composition is provided in a pre-filled syringe which is optionally packaged with one or more irrigation needles or flexible tips and/or directions for use that set out one of the methods for irrigating a bony cavity discussed above.

(57) Although the foregoing disclosure has focused on examples in the endodontic setting, compositions according to various embodiments of the invention are useful in a variety of other settings. While not wishing to be bound by any theory, in general, compositions of the invention do not degrade “bony” tissues comprising hydroxyapatite (which lacks disulfide bonds), such as tooth or bone. However, non-bony tissues (“soft” tissues) and microbes are generally much more susceptible to disruption. Accordingly, in one group of preferred embodiments, compositions of the invention are disposed within body cavities which are at least partially defined by bony tissues (“bony cavities”). Bony cavities can be naturally occurring, such as the marrow cavity of a bone or the pulpal cavity of a tooth. Alternatively or additionally, bony cavities can be at least partially man made, for instance in the course of operative removal of a carious lesion from a tooth, or due to the resection of tumorous tissue from a bone. With respect to operative treatment for carious lesions in particular, it is believed that methods of the invention advantageously permit the disinfection of bony cavities before they are filled, thus reducing the risk of recurrence of the lesion or of other undesirable sequelae. As the following examples demonstrate, compositions of the invention are, advantageously, effective in reducing titers of streptococcus mutans, which is known to contribute to the formation of carious lesions in teeth.

(58) Compositions of the present invention are also useful for disinfecting bony cavities and surfaces for taxidermy or pathology purposes. In certain embodiments, for instance, a composition of the invention is applied to bony cavities in cadaver skeletons to prepare them for display.

(59) Test Results

(60) Test results will now be provided here to illustrate the above principles. The following example illustrates working of the present invention in accordance with an embodiment of the present invention. A person of ordinary skill in the art will appreciate the present invention may be performed for any medical use and is not limited to any particular medical application.

(61) Testing of the present invention's anti-microbial activity was done in an independent laboratory in accordance with the USFDA Regulations 21 CFR Part 58. The testing of the present invention was done under the supervision of a quality assurance supervisor and a study director. The study was done at an off-site laboratory that performed the tests under protocol that includes reproducibility of test results and details to allow for inspection. The laboratory keeps all the documentation and details on file.

(62) The testing of the test organism was done with contact time of 5 minutes, 15 minutes and 30 minutes. The time intervals were chosen so as to correspond to times that practitioners use in clinical practice. The maximum time was chosen as 30 minutes, since actual treatment time is approximately equal to 30 minutes. Keeping patient's mouth open for 30 minutes maximum for a procedure is reasonable. Time required for instrumentation for an endodontic procedure is estimated around 5 minutes. Fifteen minutes may be needed, when the practitioner uses the instrument before an obturation procedure in a second visit when two visits are needed for non-surgical root canal treatment. Recovery times were tested for bacteria using 2-5 days times and C. albicans with 2-5 days intervals. Recovery values are the colonies forming abilities.

(63) The plate counts are based on colony formation units (CFU)/plate for both bacteria and yeast. For bacteria and yeast, the 25-250 CPU/plate are statistically accurate range. For mold, 8-80 CFU/plate is statistically accurate range. Soybean Casein Digest Agar was used as the medium for plates of the test organism of S. mutans and E. faecalis. Sabouraud Dextrose Agar was used for C. albicans. All plates were handled under laboratory conditions with their controls.

(64) The test microorganisms (i.e., E. faecalis, C. albicans, and S. mutans) were picked because they are the prevalent organisms in Endodontic infections. Endodontic infections are mixed microorganisms or flora. Candida albicans, Streptococcus mutans and Enterococci faecalis are the microorganisms that have a major presence in the endodontic lesion, which all need to be eradicated. Candida albicans are typically opportunistic infections in humans. Candida albicans are yeasts a type of fungi that are in infections of root canals and cause oral candidiasis and are prevalent in HIV cases. The treatment of candidiasis is by the use of anti-fungal treatment and not by antibiotics. Streptococcus mutans, bacteria, have a large presence in dental caries and has the ability to dematerialize enamel by its ability to reach the critical pH that is needed. Furthermore, S. mutans has a significant presence in root canal infections, since it has the ability to survive levels of oxygen tension and absence of essential nutrients. S. mutans can maintain microbial growth and continue acid production at low pH values. Enterococcus faecalis, bacteria, is found most commonly in persistent radiographic lesions after root canal treatment. Due to the prevalence of E. faecalis in persistent endodontic infections, it is essential that the main persistent etiologic agent is eradicated during root canal instrumentation. Therefore, complete removal of irritants from the root canal system is best and most effective way to eradicate root canal infections.

(65) The test results describe procedure for evaluation of products for anti-microbial activity against selected organisms at representative contact times. Products are evaluated in a liquid matrix. The test organisms and contact times are chosen by sponsor. This is a quantitative test that allows the determination of the amount of organism reduction at pre-determined intervals. All test method acceptance criteria were met. The acceptance criteria were that negative controls should be negative for growth, positive controls should be positive for growth, and neutralization should be confirmed at ˜70% Specific criteria for pass/fail of the test article must be determined by the sponsor.

(66) Inoculum Preparation: Plates of Soybean Casein Digest Agar (SCDA) media were inoculated with stock cultures of the test organisms S. mutans and E. faecalis and incubated at 30-35° C. for 18-48 hours. Plates of Sabouraud Dextrose Agar (SDEX) media were inoculated with stock cultures of the test organism C. albicans and incubated at 20-25° C. for 44-52 hours. Growth was harvested from the surface using a sterile bent glass rod and Physiological Saline Solution 0.9% (PHSS).

(67) Where necessary, culture suspensions were adjusted for the test procedure with PHSS to approximately (˜) 10.sup.8 CFU/ml using visual turbidity.

(68) Test Article Preparation: Test articles were prepared according to the product label or sponsor instructions and were tested without any additional manipulation or dilution.

(69) Neutralization: A 0.1 ml aliquot of the test article was mixed with 9.9 ml Dey-Engley Neutralizer Broth (DEYE). An additional tube of 10 mL of DEYE was prepared as a titer control. The tubes were inoculated with 0.1 ml of a test organism suspension diluted to approximately ≦10,000 CFU/mL, then mixed thoroughly. Aliquots from each tube were plated in triplicate onto SCDA and incubated at 30-35° C. for 2-5 days for S. mutans and E. faecalis. Aliquots from each tube were plated in triplicate onto SDEX and incubated at 20-25° C. for 2-5 days for C. albicans.

(70) Controls: Positive control tubes containing 10 mL PHSS were prepared. A 0.1 mL aliquot of the test organism was added to each tube. The positive control was assayed at 0 hour and the longest tested time point. The negative control consisted of plating sterile aliquots of applicable liquid media in triplicate and incubating as described in the test procedure.

(71) Test Procedure: Tubes containing 10 mL of each test article were prepared and inoculated with 0.1 mL of the test organism to yield ˜10.sup.6 CFU/mL. The test articles were mixed thoroughly.

(72) At 5 minutes, 15 minutes and 30 minutes of exposure, 1.0 mL aliquots of the test suspension were removed and added to 9 mL of neutralizer and serially diluted to produce a 1:100 dilution of test suspension to neutralizer. The tubes were mixed thoroughly. Serial dilutions were made in the appropriate neutralizer and assayed using a standard spread plate method.

(73) All plating was performed in triplicate. Bacterial test articles were plated onto SCDA and incubated at 30-35° C. for 2-5 days. Yeast test articles were plated onto SDEX and incubated at 20-25° C. for 2-5 days.

(74) Quantitative analysis was used to study the anti-microbial activity of the present invention. The following formulas were used by the independent laboratory in preparing their report of the effectiveness of the present invention.

(75) Calculations: The log reduction values were calculated using the following formula:
log reduction=log.sub.10 U−log.sub.10 C

(76) Wherein, U=Average positive control titer, C=Average recovered counts

(77) The percent reduction values were calculated using the following formula:
% Reduction=[1− 1/10.sup.(log reduction)]×100

(78) The percent neutralization is obtained according to the following equation:
% Neutralization=[(Average Sample Count/Plate)/(Average Control Count/Plate)]×100

(79) Test Article—Enterococcus faecalis

(80) TABLE-US-00001 Average Control Average Test Percent Identifi- Exposure Titer Article Titer Reduction Log.sub.10 cation Intervals (CFU/ml) (CFU/ml) (%) Reduction Control 30 minutes 1.1 × 10.sup.7  1.0 × 10.sup.7 7 0.03  5 minutes <2.0 × 10.sup.2 >99.9982 >4.74 Sample 15 minutes 1.1 × 10.sup.7 <2.0 × 10.sup.2 >99.9982 >4.74 1 30 minutes <2.0 × 10.sup.2 >99.9982 >4.74

(81) Test Article—Candida albicans

(82) TABLE-US-00002 Average Control Average Test Percent Identifi- Exposure Titer Article Titer Reduction Log.sub.10 cation Intervals (CFU/ml) (CFU/ml) (%) Reduction Control 30 minutes 8.5 × 10.sup.6  1.0 × 10.sup.7 −32 −0.12  5 minutes <2.0 × 10.sup.2 >99.9976 >4.63 Sample 15 minutes 8.5 × 10.sup.6 <2.0 × 10.sup.2 >99.9976 >4.63 1 30 minutes <2.0 × 10.sup.2 >99.9976 >4.63

(83) Test Article—Streptococcus mutans

(84) TABLE-US-00003 Average Control Average Test Percent Identifi- Exposure Titer Article Titer Reduction Log.sub.10 cation Intervals (CFU/ml) (CFU/ml) (%) Reduction Control 30 minutes 4.1 × 10.sup.7  4.5 × 10.sup.7 −11 −0.05  5 minutes <2.0 × 10.sup.2 >99.99951 >5.31 Sample 15 minutes 4.1 × 10.sup.7 <2.0 × 10.sup.2 >99.99951 >5.31 1 30 minutes <2.0 × 10.sup.2 >99.99951 >5.31

(85) Neutralization

(86) TABLE-US-00004 Percent Average control Average test article Neutralization Organism counts (CFU) counts (CFU) (%) E. faecalis 40 41 103 C. albicans 36 46 128 S. mutans ~7 ~9 ~129

(87) The qualitative analysis, given here, confirms that the present invention is very useful and successful in its ability to disinfect the pulpal chamber from the test microorganisms (i.e., E. faecalis, C. albicans, and S. mutans). The qualitative analysis for all of the three test microorganisms at all of the time intervals had a greater than 99.9951% reduction of test microorganism. Neutralization of the microorganisms was successful because all of the percentage for neutralization was over 70% which was needed for confirmation. Furthermore, in the recovery testing, there were no colonies forming units in any of the plates with any of the test microorganisms. Therefore, the microorganisms did not regenerate and did not reappear. The lack of the microorganisms present in the recovery results proves that the present invention is able to eradicate all the test materials/microorganisms during the instrumentation.

(88) Above test results prove that the composition, as provided by the present invention, provides anti-microbial activity against above organisms (i.e., E. faecalis, C. albicans, and S. mutans). Further, the tests show that the present invention, composition, or chemical depilatory provides unexpected results proving its useful in endodontic usages for eradicating E. faecalis, C. albicans and S. mutans in a very short time. Furthermore, the test results prove that the present invention is able to prevent E. faecalis, C. albicans, and S. mutans from recovering. Therefore, these test results prove that the present invention is novel in its use and have the ability to eradicate microorganisms in endodontic therapies. Further, the test results prove that the present invention is a novel single intra-canal medicament and as an effective bactericidal agent that kills E. faecalis, S. mutans, and C. albicans. The present invention may be useful to eradicate the microorganisms from other bony cavities having infections due to one of the microbes (e.g., E. faecalis, S. mutans, and C. albicans). If a bacteremia resulted after a dental procedure, these microbes may appear in other bony cavities or on orthopedic prosthesis that may benefit from the present invention's bactericidal ability. In canines, their bony cavities in the middle and inner ear can be infected by bacteria (Streptococcus) and/or fungi (Candida). Both of these microorganisms can be killed by the present infection.

(89) Further, the test results prove that the present invention was successful in utilizing the chemical depilatory's ability to break disulfide bonds in bacteria and yeast to disrupt the functioning of the infected cells with the microbes. Therefore, disrupting the ability of the bacteria, yeast, and infected cells to function causes the cells to degrade facilitating the removal of tissues. Further, the test results prove that the present invention is able to disrupt the disulfide bonds in living cells and tissues.

(90) The exemplary systems and methods of this present invention have been described in relation to a root canal treatment and removal of tissue from within a hard bony structure. However, to avoid unnecessarily obscuring the present invention, the preceding description omits a number of known structures and devices. This omission is not to be construed as a limitation of the scope of the claimed invention. Specific details are set forth to provide an understanding of the present invention. It should however be appreciated that the present invention may be practiced in a variety of ways beyond the specific detail set forth herein.

(91) Also, while the flowcharts have been discussed and illustrated in relation to a particular sequence of events, it should be appreciated that changes, additions, and omissions to this sequence can occur without materially affecting the operation of the present invention.

(92) A number of variations and modifications of the present invention can be used. It would be possible to provide for some features of the present invention without providing others.

(93) While the foregoing is directed to embodiments of the present invention, other and further embodiments of the present invention may be devised without departing from the basic scope thereof. It is understood that various embodiments described herein may be utilized in combination with any other embodiment described, without departing from the scope contained herein. Further, the foregoing description is not intended to be exhaustive or to limit the present invention to the precise form disclosed. Modifications and variations are possible in light of the above teachings or may be acquired from practice of the present invention.

(94) Certain exemplary embodiments may be identified by use of an open-ended list that includes wording to indicate the list items are representative of the embodiments and the list is not intended to represent a closed list exclusive of further embodiments. Such wording may include “e.g.,” “etc.,” “such as,” “for example,” “and so forth,” “and the like,” etc., and other wording as will be apparent from the surrounding context.

(95) No element, act, or instruction used in the description of the present application should be construed as critical or essential to the present invention unless explicitly described as such. Also, as used herein, the article “a” is intended to include one or more items. Where only one item is intended, the term “one” or similar language is used. Further, the terms “any of” followed by a listing of a plurality of items and/or a plurality of categories of items, as used herein, are intended to include “any of,” “any combination of,” “any multiple of,” and/or “any combination of” multiples of the items and/or the categories of items, individually or in conjunction with other items and/or other categories of items.

(96) The present invention, in various embodiments, configurations, and aspects, includes components, methods, processes, systems and/or apparatus substantially as depicted and described herein, including various embodiments, sub-combinations, and subsets thereof. Those of skill in the art will understand how to make and use the present invention after understanding the present disclosure. The present invention, in various embodiments, configurations, and aspects, includes providing devices and processes in the absence of items not depicted and/or described herein or in various embodiments, configurations, or aspects hereof, including in the absence of such items as may have been used in previous devices or processes, e.g., for improving performance, achieving ease and/or reducing cost of implementation.

(97) The foregoing discussion of the present invention has been presented for purposes of illustration and description. The foregoing is not intended to limit the present invention to the form or forms disclosed herein. In the foregoing Detailed Description for example, various features of the present invention are grouped together in one or more embodiments, configurations, or aspects for the purpose of streamlining the disclosure. The features of the embodiments, configurations, or aspects of the present invention may be combined in alternate embodiments, configurations, or aspects other than those discussed above. This method of disclosure is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment, configuration, or aspect. Thus, the following claims are hereby incorporated into this Detailed Description, with each claim standing on its own as a separate preferred embodiment of the present invention.

(98) Moreover, though the description of the present invention has included description of one or more embodiments, configurations, or aspects and certain variations and modifications, other variations, combinations, and modifications are within the scope of the present invention, e.g., as may be within the skill and knowledge of those in the art, after understanding the present disclosure. It is intended to obtain rights which include alternative embodiments, configurations, or aspects to the extent permitted, including alternate, interchangeable and/or equivalent structures, functions, ranges or steps to those claimed, whether or not such alternate, interchangeable and/or equivalent structures, functions, ranges or steps are disclosed herein, and without intending to publicly dedicate any patentable subject matter.