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 at an anatomic site that can be adapted for local delivery to the anatomic site during an operative, therapeutic or diagnostic procedure, the composition comprising:
 oxymetazoline;   a cyclooxygenase inhibitor; amitriptyline; and   a pharmaceutical carrier, 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, and wherein the composition is suitable for adding to an irrigation solution for local delivery at the anatomic site.   
     
     
         2 . The composition of  claim 1 , wherein the cyclooxygenase inhibitor comprises ketoprofen. 
     
     
         3 . The composition of  claim 1 , wherein the pharmaceutical carrier comprises a liquid irrigation carrier. 
     
     
         4 . A solution formulated for use in the inhibition of pain at an anatomic site that can be adapted for local delivery to the anatomic site during an operative, therapeutic or diagnostic procedure, the solution comprising:
 oxymetazoline and amitriptyline in a pharmaceutical carrier, wherein the composition is suitable for adding to an irrigation solution for local delivery at the anatomic site.   
     
     
         5 . The solution of  claim 4 , wherein the solution further comprises an additional pain/inflammation inhibitory agent. 
     
     
         6 . The solution of  claim 4 , wherein the concentration of each agent within the solution 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 . A solution formulated for use in the inhibition of pain at an anatomic site that can be adapted for local delivery to the anatomic site during an operative, therapeutic or diagnostic procedure, the solution comprising:
 at least one vasoconstrictive agent that is an α-adrenergic receptor agonist selected from the group consisting of oxymetazoline, p-aminoclonidine, naphazoline, tetrahydrozoline, anatazoline, tramazoline, monoxidine, apraclonidine, guanfacine, guanabenz and xylazine;   at least a first pain/inflammation inhibitory agent selected to act on a different molecular target than the α-adrenergic receptor agonist; amitriptyline; and   a liquid carrier, wherein the concentration of each agent within the solution 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, and wherein the solution is suitable for adding to an irrigation solution for local delivery at the anatomic site during the procedure.   
     
     
         8 . A composition for use in the inhibition of pain at an anatomic site that can be adapted for local delivery to the anatomic site during an operative, therapeutic or diagnostic procedure, the composition comprising:
 oxymetazoline;   at least a first pain/inflammation inhibitory agent selected to act on a different molecular target than a α-adrenergic receptor, wherein the first pain/inflammation inhibitory agent is selected from the group consisting of cyclooxygenase inhibitors, serotonin receptor antagonists and histamine receptor antagonists; amitriptyline; and   a pharmaceutical carrier, 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, and wherein the composition is suitable for adding to an irrigation solution for local delivery at the anatomic site.   
     
     
         9 . The solution of  claim 4 , wherein the anatomic site is a joint of an extremity, and wherein the solution comprises oxymetazoline, amitriptyline and ketoprofen in a liquid carrier.