Arthroscopic Irrigation Solution and Method for Peripheral Vasoconstriction and Inhibition of Pain and Inflammation

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 exhibits alpha-adrenergic activity 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.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
         1 . A composition for use in the inhibition of pain and inflammation at a joint of an extremity or at a wound at an extremity, the composition comprising:
 an alpha-1 selective adrenergic receptor agonist; and   at least a first pain/inflammation inhibitory agent comprising a cyclooxygenase inhibitor.   
     
     
         2 . The composition of  claim 1 , further comprising amitriptyline. 
     
     
         3 . The composition of  claim 1 , wherein the cyclooxygenase inhibitor is selected from the group consisting of ketoprofen, diclofenac, naproxen, indomethacin, ibuprofen, and keterolac. 
     
     
         4 . The composition of  claim 1 , wherein the alpha-1 selective adrenergic receptor agonist is selected from the group consisting of phenylephrine, methoxamine and cirazoline. 
     
     
         5 . The composition of  claim 1 , further comprising a liquid carrier. 
     
     
         6 . The composition of  claim 5 , wherein the concentration of each agent within the composition is the concentration of that agent which is desired to be delivered locally to achieve a desired local level of therapeutic effect and results in a blood plasma level for the agent that is significantly less than the blood plasma level that would be required to achieve the same level of therapeutic effect. 
     
     
         7 . The composition of  claim 5 , wherein the alpha-1 selective adrenergic receptor agonist in the solution is delivered locally at a concentration of no greater than 300,000 nanomolar and the cyclooxygenase inhibitor in the solution is delivered locally at a concentration of no greater than 500,000 nanomolar. 
     
     
         8 . A composition for use in the inhibition of pain and inflammation at a joint of an extremity or at a wound at an extremity, the composition comprising:
 at least one alpha-1 selective adrenergic receptor agonist selected from the group consisting of phenylephrine, methoxamine and cirazoline; and   at least a first pain/inflammation inhibitory agent comprising a cyclooxygenase inhibitor.   
     
     
         9 . The composition of  claim 8 , further comprising a liquid carrier. 
     
     
         10 . The composition of  claim 9 , wherein the concentration of each agent within the composition is the concentration of that agent which is desired to be delivered locally to achieve a desired local level of therapeutic effect and results in a blood plasma level for the agent that is significantly less than the blood plasma level that would be required to achieve the same level of therapeutic effect. 
     
     
         11 . The composition of  claim 7 , wherein the concentration of each agent within the composition is the concentration of that agent which is desired to be delivered locally to achieve a desired local level of therapeutic effect and results in a blood plasma level for the agent that is significantly less than the blood plasma level that would be required to achieve the same level of therapeutic effect. 
     
     
         12 . The composition of  claim 8 , wherein the cyclooxygenase inhibitor is selected from the group consisting of ketoprofen, diclofenac, naproxen, indomethacin, ibuprofen, and ketorolac. 
     
     
         13 . The composition of  claim 8 , further comprising amitriptyline. 
     
     
         14 . A composition for use in the inhibition of pain and inflammation at a joint of an extremity or at a wound at an extremity, the composition comprising:
 at least one alpha-1 selective adrenergic receptor agonist selected from the group consisting of phenylephrine, methoxamine and cirazoline;   a cyclooxygenase inhibitor selected from the group consisting of ketoprofen, diclofenac, naproxen, indomethacin, ibuprofen, and ketorolac; and   amitriptyline.   
     
     
         15 . The composition of  claim 14 , further comprising a liquid carrier. 
     
     
         16 . The composition of  claim 15 , wherein the concentration of each agent within the composition is the concentration of that agent which is desired to be delivered locally to achieve a desired local level of therapeutic effect and results in a blood plasma level for the agent that is significantly less than the blood plasma level that would be required to achieve the same level of therapeutic effect. 
     
     
         17 . The composition of  claim 15 , wherein the alpha-1 selective adrenergic receptor agonist and amitriptyline are each in the solution for local delivery at a concentration of no greater than 300,000 nanomolar and the cyclooxygenase inhibitor in the solution for local delivery at a concentration of no greater than 500,000 nanomolar. 
     
     
         18 . A solution for use in the inhibition of pain and inflammation at a joint of an extremity during an arthroscopic or open surgical procedure or other extremity procedure, the solution comprising:
 an alpha-1 selective adrenergic receptor agonist;   at least a first pain/inflammation inhibitory agent comprising a cyclooxygenase inhibitor inhibitor; and   a liquid carrier, wherein each agent 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.   
     
     
         19 . The solution of  claim 18 , wherein the alpha-1 receptor selective agonist is selected from the group consisting of phenylephrine, methoxamine and cirazoline. 
     
     
         20 . The solution of  claim 18 , wherein the cyclooxygenase inhibitor is selected from the group consisting of ketoprofen, diclofenac, naproxen, indomethacin, ibuprofen, and keterolac. 
     
     
         21 . The solution of  claim 18 , wherein the solution further comprises amitriptyline as a second pain/inflammation inhibitory agent. 
     
     
         22 . The solution of  claim 18 , wherein the alpha-1 selective adrenergic receptor agonist in the solution is delivered locally at a concentration of no greater than 300,000 nanomolar. 
     
     
         23 . The solution of  claim 22 , wherein the alpha-1 selective adrenergic receptor agonist in the solution is delivered locally at a concentration of no greater than 75,000 nanomolar. 
     
     
         24 . The solution of  claim 18 , wherein the cyclooxygenase inhibitor in the solution is delivered locally at a concentration of no greater than 500,000 nanomolar. 
     
     
         25 . The solution of  claim 24 , wherein the cyclooxygenase inhibitor in the solution is delivered locally at a concentration of no greater than 200,000 nanomolar. 
     
     
         26 . The solution of  claim 18 , wherein the liquid carrier comprises a sustained release vehicle. 
     
     
         27 . The solution of  claim 26 , wherein the sustained release vehicle is selected from the group consisting of microparticles, microspheres, nanoparticles, proteins, liposomes, carbohydrates and gels.