Biocompatible dental putty formulations for controlled release of bupivacaine

• US 9,943,466 B1
• Filed: 06/14/2017
• Issued: 04/17/2018
• Est. Priority Date: 05/09/2017
• Status: Active Grant

• Current Assignee: Research Triangle Institute, University of North Carolina At Chapel Hill (University of North Carolina System)
• Original Assignee: Research Triangle Institute, University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Johnson, Leah Marie, Rothrock, Ginger Denison, Shepherd, Sarah Dorothy, O'Buckley, Sandra Cordel, Neely, Andrea Gail
• Primary Examiner(s): Azpuru, Carlos A
• Application Number:
  US15/622,238
• Time in Patent Office: 307 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 47/46 Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
• CPC Class Codes: A61K 6/15 Compositions characterised by their physical properties
• CPC Class Codes: A61K 6/69 Medicaments
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Abstract

The disclosure provides biocompatible dental material that is moldable and biodegradable and provides sustained and/or controlled delivery of one or more local anesthetics within a dental cavity or space. Such dental material is customizable for the size and shape needed for a particular patient or particular application. The dental material may also provide customizable sustained and/or controlled delivery of one or more local anesthetics.

Claims

1. A biocompatible dental putty comprising a biodegradable hemostatic matrix having biodegradable microparticles dispersed therein, said biodegradable microparticles encapsulating a local anesthetic agent, wherein the biodegradable microparticles upon biodegradation thereof release the local anesthetic agent into the biodegradable hemostatic matrix and wherein the biodegradable hemostatic matrix is permeable to diffusion therethrough of the released local anesthetic agent.

2. The biocompatible dental putty of claim 1, wherein the biodegradable hemostatic matrix comprises an absorbable gelatin material.

3. The biocompatible dental putty of claim 1, wherein the biodegradable hemostatic matrix comprises an absorbable porcine gelatin material.

4. The biocompatible dental putty of claim 1, wherein the biodegradable microparticles comprise a polymeric material capable of providing controlled release of the local anesthetic agent encapsulated therein.

5. The biocompatible dental putty of claim 3, wherein the biodegradable microparticles comprise (poly)lactic-co-glycolic acid).

6. The biocompatible dental putty of claim 5, wherein the local anesthetic agent comprises bupivacaine.

20. The biocompatible dental putty of claim 1, wherein the biodegradable microparticles contain the local anesthetic agent at a loading of from about 5% to about 25% by weight of the biodegradable microparticle.

21. The biocompatible dental putty of claim 1, wherein the biodegradable microparticles comprise (poly)lactic-co-glycolic acid having a molecular weight in a range of from 7 to 17 kDa.

22. The biocompatible dental putty of claim 21, wherein the (poly)lactic-co-glycolic acid is ester-terminated.

23. The biocompatible dental putty of claim 1, wherein the biodegradable microparticles contain the local anesthetic agent in a base form.

24. The biocompatible dental putty of claim 1, wherein the biocompatible dental putty provides a biphasic release of the local anesthetic agent.

25. The biocompatible dental putty of claim 1, wherein:

the biodegradable microparticles contain the local anesthetic agent at a loading of from about 5% to about 25% by weight of the biodegradable microparticle;

the biodegradable microparticles comprise ester-terminated (poly)lactic-co-glycolic acid having a molecular weight in a range of from 7 to 17 kDa;

the biodegradable microparticles contain the local anesthetic agent in a base form; and

the biocompatible dental putty provides a biphasic release of the local anesthetic agent.

7. A pain management system configured to be positioned in a dental extraction cavity in a patient after dental surgery comprising a biocompatible dental putty comprising a biodegradable hemostatic matrix having biodegradable microparticles dispersed therein, said biodegradable microparticles encapsulating a local anesthetic agent, wherein the biodegradable microparticles upon biodegradation thereof release the local anesthetic agent into the biodegradable hemostatic matrix and wherein the biodegradable hemostatic matrix is permeable to diffusion therethrough of the released local anesthetic agent.

8. The pain management system of claim 7, wherein the biodegradable hemostatic matrix comprises an absorbable porcine gelatin material, the biodegradable microparticles comprise (poly)lactic-co-glycolic acid), and the local anesthetic agent comprises bupivacaine.

9. A dental kit comprising one or more units of the pain management system of claim 7.

10. A method of providing controlled release of a local anesthetic at a tooth extraction site in a patient in need of said local anesthetic, comprising:

molding into a desired shape and size a biocompatible dental putty comprising a biodegradable hemostatic matrix having biodegradable microparticles dispersed therein, said biodegradable microparticles encapsulating a local anesthetic agent, wherein the biodegradable microparticles upon biodegradation thereof release the local anesthetic agent into the biodegradable hemostatic matrix and wherein the biodegradable hemostatic matrix is permeable to diffusion therethrough of the released local anesthetic agent; and

applying the biocompatible dental putty to the tooth extraction site in the patient.

11. The method of claim 10, wherein the biodegradable hemostatic matrix comprises an absorbable gelatin material.

12. The method of claim 10, wherein the biodegradable hemostatic matrix comprises an absorbable porcine gelatin material.

13. The method of claim 10, wherein the biodegradable microparticles comprise a polymeric material capable of providing controlled release of the local anesthetic agent encapsulated therein.

14. The method of claim 12, wherein the biodegradable microparticles comprise (poly)lactic-co-glycolic acid).

15. The method of claim 14, wherein the local anesthetic agent comprises bupivacaine.

16. The method of claim 14, wherein the biocompatible dental putty degrades in less than 7 days.

26. The method of claim 10, wherein the biodegradable microparticles contain the local anesthetic agent at a loading of from about 5% to about 25% by weight of the biodegradable microparticle.

27. The method of claim 10, wherein the biodegradable microparticles comprise (poly)lactic-co-glycolic acid having a molecular weight in a range of from 7 to 17 kDa.

28. The method of claim 27, wherein the (poly)lactic-co-glycolic acid is ester-terminated.

29. The method of claim 10, wherein the biodegradable microparticles contain the local anesthetic agent in a base form.

30. The method of claim 10, wherein the biocompatible dental putty provides a biphasic release of the local anesthetic agent.

17. A method of controlling pain in a patient after a tooth extraction comprising:

molding into a desired shape and size a biocompatible dental putty comprising a biodegradable hemostatic matrix having biodegradable microparticles dispersed therein, said biodegradable microparticles encapsulating a local anesthetic agent, wherein the biodegradable microparticles upon biodegradation thereof release the local anesthetic agent into the biodegradable hemostatic matrix and wherein the biodegradable hemostatic matrix is permeable to diffusion therethrough of the released local anesthetic agent; and

applying the biocompatible dental putty to the tooth extraction site in the patient.

18. The method of claim 17, wherein the biodegradable hemostatic matrix comprises an absorbable porcine gelatin material, the biodegradable microparticles comprise (poly)lactic-co-glycolic acid), and the local anesthetic agent comprises bupivacaine.

19. The method of claim 18, wherein the biocompatible dental putty degrades in less than 7 days.