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US-20260124120-A1 - STABILIZED AQUEOUS COMPOSITIONS CONTAINING HYDROXYAPTITE AND FREE IONS FOR IN VIVO REMINERALIZATION OF CALCIFIED TISSUE & THEIR METHODS OF USE

US20260124120A1US 20260124120 A1US20260124120 A1US 20260124120A1US-20260124120-A1

Abstract

Aqueous-based compositions for remineralizing dentinal tissues in vivo are disclosed to arrest demineralization and early-stage caries, treat dentin/tooth sensitivity, fix white spot lesions, and strengthen dentinal hard tissues (enamel, dentin, cementum), among others. Methods utilizing the remineralizing composition are also disclosed.

Inventors

  • Alexander D. Johnson
  • Khongchee XIONG

Assignees

  • INTER-MED, INC.

Dates

Publication Date
20260507
Application Date
20260105

Claims (20)

  1. 1 . A dental remineralizing composition, comprising: at least two inorganic salts, at least one bioactive material, at least one buffering agent, at least one solvent, and, free potassium ions at a concentration between 100 ppb and 10 ppm; wherein at least a first inorganic salt yields free calcium (Ca 2+ ) ions in water, wherein at least a second inorganic salt yields free phosphate ions in water; wherein the bioactive material is formed in situ during manufacturing; wherein the composition contains free calcium and phosphate ions in equilibrium with suspended and stabilized hydroxyapatite; wherein the remineralizing solution exhibits a gel-like consistency.
  2. 2 . The composition of claim 1 , further comprising one or more of a thickener, a flavorant, a sweetener, a surfactant, a hydrotrope, a colorant, an antimicrobial agent, a preservative, a prebiotic, a probiotic, an antioxidant, a chelator, or a sequestrant.
  3. 3 . The composition of claim 1 , wherein the bioactive material's particle size is less than one micron in size.
  4. 4 . The composition of claim 1 , wherein the buffering agent is either TRIS or HEPES.
  5. 5 . The composition of claim 1 , wherein the thickening agent is poloxamer 407.
  6. 6 . The composition of claim 1 , wherein the composition has less than about 10 ppm fluoride.
  7. 7 . The composition of claim 1 , wherein the composition has a pH between 4 and 8.
  8. 8 . The composition of claim 1 , wherein the at least one bioactive material is formed in situ and is comprised of at least one apatite precursor, at least one apatite, and combinations thereof.
  9. 9 . The composition of claim 1 , wherein the ratio between the first inorganic salt that yields free calcium (Ca 2+ ) ions in water, and the second inorganic salt yields free phosphate ions in water is between 1.5:1 and 2:1.
  10. 10 . The composition of claim 1 , wherein the at least one bioactive material is formed in situ and is at a weight/weight concentration (w/w %) between 1% and 10%.
  11. 11 . The composition of claim 1 , further comprising at least one antimicrobial agent.
  12. 12 . The composition of claim 1 , further comprising at least one antimicrobial agent wherein the at least one antimicrobial agent is selected from sodium benzoate, potassium sorbate, sodium methylparaben, sodium propylparaben, or combinations thereof.
  13. 13 . The composition of claim 1 , further comprising at least one antioxidant.
  14. 14 . The composition of claim 1 , further comprising at least one antimicrobial agent consisting of hydrogen peroxide at a weight/weight concentration (w/w %) between 0.1% and 2.5%.
  15. 15 . A method of treating tooth sensitivity in vivo, comprising: introducing a remineralizing composition of claim 1 onto a tooth surface or surfaces, maintaining contact of the remineralizing composition with the tooth surface for a designated period of time, and removal of the remineralizing composition from the tooth surface, wherein the remineralizing composition remineralizes hydroxyapatite present within the teeth.
  16. 16 . The method of claim 15 , wherein the designated period of time of contact of the composition with the tooth surface is between 30 seconds and 30 minutes.
  17. 17 . The method of claim 15 , wherein the remineralizing composition is applied in vivo using a custom dental tray or appliance.
  18. 18 . The method of claim 15 , wherein the remineralizing composition occludes dentinal tubules in vivo.
  19. 19 . The method of claim 15 , wherein the remineralizing of hydroxyapatite present within teeth occurs to a depth of 100 microns.
  20. 20 . The method of claim 15 , wherein the remineralizing composition is applied in vivo following the application of a bioactive peptide.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of International Application No. PCT/US2025/035955, filed Jun. 30, 2025, which claims the benefit of U.S. Provisional Application No. 63/666,880, filed Jul. 2, 2024; the entire contents of those applications are hereby incorporated by reference herein. BACKGROUND OF INVENTION 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 cementum (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. Demineralization is a process where minerals are gradually lost from dentinal hard tissues due to factors including oral bacteria, acidic foods, and inadequate saliva. This demineralization can lead to increased tooth sensitivity, visible white spots, and ultimately the development of dental caries, which necessitates dental treatment to restore the destroyed or decayed tooth structure. In an effort to arrest demineralization before it progresses, several treatment modalities exist. The most common treatment is the application of a fluoride-containing material, such as a fluoride varnish or fluoride gel/paste, to the treatment site which helps strengthen the enamel and dentin through the formation of fluorapatite that is more resistant to acidic attack. However, excessive fluoride application can lead to unsightly fluorosis spots on teeth, and in extreme cases, fluorosis can weaken the tooth. An alternative material, called MI Paste, utilizes a milk-derived protein to help bind, adhere and release calcium, phosphate and fluoride to the tooth surface to treat sensitivity and demineralization. MI Paste exhibits limitations and potential disadvantages related to excessive fluoride application while also being a potential allergen due to the inclusion of a milk-derived protein. Furthermore, the inclusion of calcium and fluoride within the same chemistry may result in the precipitation of calcium fluoride, which is insoluble in aqueous media and renders calcium and fluoride ions useless for remineralization. U.S. Pat. No. 9,724,542 describes a composition containing remineralizing ingredients, including fluoride, in an aqueous-free emulsion that forms mucoadhesive gels when in contact with tooth surfaces and saliva. U.S. Pat. No. 10,279,203 describes a composition containing remineralizing ingredients that rely on delivery via pores contained with silicon dioxide microparticles. Therefore, there is a need in the art for methods and compositions to remineralize dentinal hard tissues in vivo that is appreciably fluoride free and does not include the use of animal or synthetically derived peptides or proteins. BRIEF SUMMARY The present disclosure provides aqueous-based compositions for remineralizing dentinal tissues in vivo. The remineralizing compositions disclosed herein are useful, without limitation, to arrest demineralization and early-stage caries, treat dentin/tooth sensitivity, fix white spot lesions, and strengthen dentinal hard tissues (enamel, dentin, cementum), among others. Although the disclosure is generally geared towards dental use, one skilled in the art can appreciate how the disclosed inventions may be applicable to other medical and orthopedic applications where remineralization of bone or other tissues is clinically advantageous. The present disclosure also teaches methods utilizing the remineralizing composition. In yet another aspect, a product by process to create the remineralizing composition is disclosed. In an even further aspect, kits containing the composition are disclosed. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows calcium phosphate precipitation and remineralization of hydroxyapatite powder overtime when exposed to an embodiment of the application. FIG. 2 shows in situ bioactive material formation within the remineralization composition (Formula A) versus different pHs. FIG. 3 shows laser microscope images at 50× of dentin tubules post seven-day treatment protocol. Nearly all of tubules are open within the negative control image which corresponds to a grading score of “0”. Conversely, ˜100% of the tubules are closed within the Formula A image which corresponds to a grading score of “4” and illustrates how an embodiment of the application effectively remineralizes dentin and occludes dentinal tubules, thereby eliminating patient sensitivity. Approximately 25% of the tubules appear closed within the SuperSeal image which corresponds to a grading score of “1”. FIG. 4 shows bioactive material formation (apatites and apatite precursors) versus remineralizing so