Arthroscopic irrigation solution and method for peripheral vasoconstriction and inhibition of pain and inflammation

Patent metadata

Field	Value
Publication number	US-9254271-B2
Application number	US-38478109-A
Country	US
Kind code	B2
Filing date	Apr 8, 2009
Priority date	Oct 20, 1998
Publication date	Feb 9, 2016
Grant date	Feb 9, 2016

Abstract

A method and solution for perioperatively inhibiting a variety of pain and inflammation processes during arthroscopic procedures. The solution preferably includes a vasoconstrictor that demonstrates substantial agonist activity at alpha adrenergic receptors and that is selected for peripheral (local) vasoconstriction and one or more additional pain and inflammation inhibitory agents at dilute concentration in a physiologic carrier, such as saline or lactated Ringer's solution. The solution is applied by continuous irrigation of a wound during a surgical procedure for peripheral vasoconstriction and inhibition of pain and/or inflammation while avoiding undesirable side effects associated with systemic application of larger doses of the agents.

First claim

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A method of inhibiting pain and inflammation at a joint during an arthroscopic surgical procedure, comprising delivering to a joint during an arthroscopic procedure a solution comprising:
oxymetazoline,
at least a first pain/inflammation inhibitory agent comprising a cyclooxygenase inhibitor; and
a liquid carrier, wherein the solution is applied locally and perioperatively to the joint.

2. The method of claim 1 , further comprising at least a second pain/inflammation inhibitory agent selected from the group consisting of: a serotonin 2 receptor antagonist, a serotonin 3 receptor antagonist, a serotonin 1B receptor antagonist, a histamine receptor antagonist; a bradykinin receptor antagonist; a kallikrein inhibitor; a tachykinin receptor antagonist; a calcitonin gene-related peptide receptor antagonist; an interleukin receptor antagonist; a phospholipase inhibitor; a cyclooxygenase inhibitor; a lipoxygenase inhibitor; a prostanoid receptor antagonist; a leukotriene receptor antagonist; an opioid receptor agonist; a purinoceptor antagonist; an ATP-sensitive potassium channel opener; a mitogen-activated protein kinase (MAPK) inhibitor; a neuronal nicotinic acetylcholine receptor agonist; and a soluble receptor.

3. The method of claim 1 , wherein the first pain/inflammation inhibitory agent is ketoprofen.

4. The method of claim 1 , wherein the first pain/inflammation inhibitory agent comprises ketoprofen and the solution further comprises amitriptyline as a second pain/inflammation inhibitory agent.

5. The method of claim 1 , wherein the solution further comprises a second pain/inflammation inhibitory agent selected from the group consisting of serotonin receptor antagonists and histamine receptor antagonists.

6. The method of claim 5 , wherein the second pain/inflammation inhibitory agent functions as both a serotonin receptor antagonist and a histamine receptor antagonist.

7. The method of claim 1 , comprising continuously applying the solution to the joint.

8. The method of claim 7 , comprising continuously irrigating the joint with the solution.

9. The method of claim 1 , wherein the solution is applied by irrigation of the joint.

10. The method of claim 1 , wherein the solution is locally applied to the joint in the absence of metabolic transformation.

11. The method of claim 1 , wherein the perioperative application of the solution comprises intraprocedural application together with preprocedural or postprocedural application of the solution.

12. The method of claim 11 , wherein the perioperative application of the solution comprises preprocedural, intraprocedural and postprocedural application of the solution.

13. The method of claim 1 , wherein the oxymetazoline in the solution is delivered locally at a concentration of no greater than 300,000 nanomolar.

14. The method of claim 13 , wherein the oxymetazoline in the solution is delivered locally at a concentration of no greater than 75,000 nanomolar.

15. The method of claim 13 , wherein the first pain/inflammation inhibitory agent in the solution is delivered locally at a concentration of no greater than 500,000 nanomolar.

16. The method of claim 15 , wherein the first pain/inflammation inhibitory agent in the solution is delivered locally at a concentration of no greater than 100,000 nanomolar.

17. The method of claim 1 , wherein each of the agents in the solution is included at a concentration or dosage that is sufficient to provide a level of pain/inflammation inhibitory or vasoconstrictive effect at the joint when delivered locally to the joint and that results in a plasma concentration that is less than a plasma concentration that would be required to achieve the same level of inhibitory or therapeutic effect at the joint when delivered systemically.

18. The method of claim 1 , comprising intermittently applying the solution to the joint.

19. A method of inhibiting pain and inflammation at a joint of an extremity during an arthroscopic or open surgical procedure or other extremity procedure, comprising delivering to the surgical site during the procedure a solution comprising:
oxymetazoline,
at least a first pain/inflammation inhibitory agent comprising a cyclooxygenase inhibitor; and
a liquid carrier, wherein the solution is applied locally and perioperatively to the surgical site.

20. The method of claim 19 , wherein the solution further comprises at least a second pain/inflammation inhibitory agent selected to act on a different molecular target than oxymetazoline and the first pain/inflammation inhibitory agent.

21. The method of claim 19 , comprising continuously applying the solution to the surgical site.

22. The method of claim 19 , wherein the solution is applied by irrigation of the surgical site.

23. The method of claim 19 , wherein the perioperative application of the solution comprises intraprocedural application together with preprocedural or postprocedural application of the solution.

24. The method of claim 23 , wherein the perioperative application of the solution comprises preprocedural, intraprocedural and postprocedural application of the solution.

25. The method of claim 19 , wherein each of the agents in the solution is included at a concentration or dosage that is sufficient to provide a level of pain/inflammation inhibitory or vasoconstrictive effect at the surgical site when delivered locally to the surgical site and that results in a plasma concentration that is less than a plasma concentration that would be required to achieve the same level of inhibitory or therapeutic effect at the surgical site when delivered systemically.

26. The method of claim 19 , wherein the first pain/inflammation inhibitory agent is ketoprofen.

27. The method of claim 26 , wherein the solution further comprises amitriptyline as a second pain/inflammation inhibitory agent.

28. The method of claim 19 , wherein the procedure during which the solution is delivered comprises an open joint procedure.

29. The method of claim 28 , wherein the procedure during which the solution is delivered comprises a total joint replacement.

30. The method of claim 29 , wherein the solution is applied by intermittent irrigation during the procedure.

31. The method of claim 19 , comprising intermittently applying the solution to the joint.

32. A method of inhibiting pain and inflammation at a surgical or operative/procedural sites during an oral/dental surgery, ocular surgery or burn treatment procedures, comprising delivering to a site during an oral/dental surgery, ocular surgery or burn treatment procedure a solution comprising:
oxymetazoline,
at least a first pain/inflammation inhibitory agent comprising a cyclooxygenase inhibitor; and
a liquid carrier, wherein the solution is applied locally and perioperatively to the site.

33. The method of claim 32 , wherein the first pain/inflammation inhibitory agent is ketoprofen.

34. The method of claim 32 , wherein the first pain/inflammation inhibitory agent comprises ketoprofen and the solution further comprises amitriptyline as a second pain/inflammation inhibitory agent.

35. The method of claim 32 , wherein the so

Assignees

• Demopulos Gregory A
• Pierce Palmer Pamela
• Herz Jeffrey M
• Omeros Corp

Inventors

• Demopulos Gregory A
• Pierce Palmer Pamela
• Herz Jeffrey M

Classifications

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title

• A61K31/405

  Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin · CPC title

• A61K31/196

  the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil · CPC title

• A61K31/135

  having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} · CPC title

• A61K31/192

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title