Administration of capsaicinoids

Abstract

Disclosed in certain embodiments is a method for relieving pain at a site in a human or animal in need thereof, comprising administering by injection or infiltration, a dose of a capsaicinoid and coadministering an effective amount of a NSAID to decrease an undesired effect of the capsaicinoid.

What is claimed is:  
     
         1 . A method for relieving pain at a site in a human or animal in need thereof, comprising: 
 administering at a discrete painful site in a human or animal in need thereof a single injectable or implantable dose of a capsaicinoid in an amount effective to denervate said discrete site without eliciting an effect outside the discrete location and to attenuate pain emanating from said site, said effective dose being from about 1 μg to about 5000 μg of capsaicin or a therapeutically equivalent dose of a capsaicinoid other than capsaicin; and coadministering an effective amount of a non-steroidal anti-inflammatory agent to decrease an undesired effect of the capsaicinoid.    
     
     
         2 . The method of  claim 1 , wherein the NSAID is in the same formulation as the capsaicinoid.  
     
     
         3 . The method of  claim 1 , wherein the NSAID is in a different formulation than the capsaicinoid.  
     
     
         4 . The method of  claim 1 , wherein the NSAID is administered by a different route than the capsaicinoid.  
     
     
         5 . The method of  claim 1 , wherein the NSAID is administered by the same route as the capsaicinoid.  
     
     
         6 . The method of  claim 1 , wherein the NSAID is administered orally, via implant, parenterally, sublingually, rectally, topically, or via inhalation.  
     
     
         7 . The method of  claim 3 , wherein the administration of the capsaicinoid and the coadministration of the NSAID have overlapping durations of effect.  
     
     
         8 . The method of  claim 1 , wherein the NSAID is selected from the group consisting of aspirin, ibuprofen, diclofenac, naproxen, benoxaprofen, flurbiprofen, fenoprofen, flubufen, ketoprofen, indoprofen, piroprofen, carprofen, oxaprozin, pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid tolfenamic acid, diflurisal, flufenisal, piroxicam, sudoxicam or isoxicam, pharmaceutically acceptable salts thereof, and mixtures thereof.  
     
     
         9 . The method of  claim 1 , wherein the NSAID is selected from the group consisting of rofecoxib, celecoxib, DUP-697, flosulide, meloxicam, 6-MNA, L-745337, nabumetone, nimesulide, NS-398, SC-5766, T-614, L-768277, GR-253035, JTE-522, RS-57067-000, SC-58125, SC-078, PD-138387, NS-398, flosulide, D-1367, SC-5766, PD-164387, etoricoxib, valdecoxib and parecoxib or pharmaceutically acceptable salts thereof.  
     
     
         10 . The method of  claim 8 , wherein the NSAID is administered orally.  
     
     
         11 . The method of  claim 9 , wherein the NSAID is administered parenterally.  
     
     
         12 . The method of  claim 1 , wherein the NSAID is in an effective amount to reduce pain and/or inflammation at the site of administration of the capsaicinoid.  
     
     
         13 . The method of  claim 1 , further comprising administering a local anesthetic to the human or animal.  
     
     
         14 . The method of  claim 1 , wherein said dose of capsaicin is from about 10 to about 3000 μg.  
     
     
         15 . The method of  claim 1 , wherein said dose of capsaicin is from about 300 to about 1200 μg.  
     
     
         16 . The method of  claim 1 , wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle for injection or implantation.  
     
     
         17 . The method of  claim 16 , wherein said pharmaceutically acceptable vehicle is an aqueous vehicle is selected from the group consisting of Sodium Chloride Injection, Ringers Injection, Isotonic Dextrose Injection, Sterile Water Injection, Dextrose, Lactated Ringers Injection and any combinations or mixtures thereof.  
     
     
         18 . An injectable or implantable pharmaceutical composition for attenuating pain at a site in a human or animal in need thereof, comprising from 1 μg to 5000 μg of a capsaicinoid, an effective amount of an NSAID to decrease an undesired effect of the capsaicinoid, and a pharmaceutically acceptable vehicle for injection or implantation.  
     
     
         19 . The composition of  claim 18 , wherein the NSAID is selected from the group consisting of aspirin, ibuprofen, diclofenac, naproxen, benoxaprofen, flurbiprofen, fenoprofen, flubufen, ketoprofen, indoprofen, piroprofen, carprofen, oxaprozin, pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid tolfenamic acid, diflurisal, flufenisal, piroxicam, sudoxicam or isoxicam, pharmaceutically acceptable salts thereof, and mixtures thereof.  
     
     
         20 . The composition of  claim 18 , wherein the NSAID is selected from the group consisting of rofecoxib, celecoxib, DUP-697, flosulide, meloxicam, 6-MNA, L-745337, nabumetone, nimesulide, NS-398, SC-5766, T-614, L-768277, GR-253035, JTE-522, RS-57067-000, SC-58125, SC-078, PD-138387, NS-398, flosulide, D-1367, SC-5766, PD-164387, etoricoxib, valdecoxib and parecoxib or pharmaceutically acceptable salts thereof.  
     
     
         21 . A method for attenuating pain at a surgical site or an open wound in a human or animal, comprising: 
 infiltrating a dose of a capsaicinoid in an amount effective to denervate a site selected from a surgical site or an open wound without eliciting an effect outside the site, said effective dose being from about 1 μg to about 15,000 μg of capsaicin or a therapeutically equivalent dose of a capsaicinoid other than capsaicin; and coadministering an effective amount of a non-steroidal anti-inflammatory agent to decrease an undesired effect of the capsaicinoid.    
     
     
         22 . The method of  claim 21 , wherein the NSAID is in the same formulation as the capsaicinoid.  
     
     
         23 . The method of  claim 21 , wherein the NSAID is in a different formulation than the capsaicinoid.  
     
     
         24 . The method of  claim 21 , wherein the NSAID is administered by a different route than the capsaicinoid.  
     
     
         25 . The method of  claim 21 , wherein the NSAID is administered by the same route as the capsaicinoid.  
     
     
         26 . The method of  claim 21 , wherein the NSAID is administered orally, via implant, parenterally, sublingually, rectally, topically, or via inhalation.  
     
     
         27 . The method of  claim 23 , wherein the administration of the capsaicinoid and the coadministration of the NSAID have overlapping durations of effect.  
     
     
         28 . The method of  claim 21 , wherein the NSAID is selected from the group consisting of aspirin, ibuprofen, diclofenac, naproxen, benoxaprofen, flurbiprofen, fenoprofen, flubufen, ketoprofen, indoprofen, piroprofen, carprofen, oxaprozin, pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid tolfenamic acid, diflurisal, flufenisal, piroxicam, sudoxicam or isoxicam, pharmaceutically acceptable salts thereof, and mixtures thereof.  
     
     
         29 . The method of  claim 21 , wherein the NSAID is selected from the group consisting of rofecoxib, celecoxib, DUP-697, flosulide, meloxicam, 6-MNA, L-745337, nabumetone, nimesulide, NS-398, SC-5766, T-614, L-768277, GR-253035, JTE-522, RS-57067-000, SC-58125, SC-078, PD-138387, NS-398, flosulide, D-1367, SC-5766, PD-164387, etoricoxib, valdecoxib and parecoxib or pharmaceutically acceptable salts thereof.  
     
     
         30 . The method of  claim 28 , wherein the NSAID is administered orally.  
     
     
         31 . The method of  claim 29 , wherein the NSAID is administered parenterally.  
     
     
         32 . The method of  claim 21 , wherein the NSAID is in an effective amount to reduce pain and/or inflammation at the site of administration of the capsaicinoid.  
     
     
         33 . The method of  claim 21 , further comprising administering a local anesthetic to the human or animal.  
     
     
         34 . The method of  claim 21 , wherein said dose of capsaicin is from about 600 to about 15,000 μg.  
     
     
         35 . The method of  claim 21 , wherein said dose of capsaicin is from about 600 to about 1000 μg.  
     
     
         36 . The method of  claim 21 , wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle for infiltration.  
     
     
         37 . The method of  claim 36 , wherein said pharmaceutically acceptable vehicle is an aqueous vehicle is selected from the group consisting of Sodium Chloride Injection, Ringers Injection, Isotonic Dextrose Injection, Sterile Water Injection, Dextrose, Lactated Ringers Injection and any combinations or mixtures thereof.  
     
     
         38 . An pharmaceutical composition for attenuating pain at a surgical site in a human or animal in need thereof, comprising a capsaicinoid selected from the group consisting of from 1 μg to 15,000 μg of capsaicin, a therapeutically equivalent amount of one or more other capsaicinoids, and therapeutically equivalent combinations thereof; an effective amount of an NSAID to decrease an undesired effect of the capsaicinoid; and from about 1 ml to about 100 ml of a pharmaceutically acceptable vehicle for infiltration.  
     
     
         39 . The composition of  claim 38 , wherein the NSAID is selected from the group consisting of aspirin, ibuprofen, diclofenac, naproxen, benoxaprofen, flurbiprofen, fenoprofen, flubufen, ketoprofen, indoprofen, piroprofen, carprofen, oxaprozin, pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid tolfenamic acid, diflurisal, flufenisal, piroxicam, sudoxicam or isoxicam, pharmaceutically acceptable salts thereof, and mixtures thereof.  
     
     
         40 . The composition of  claim 38 , wherein the NSAID is selected from the group consisting of rofecoxib, celecoxib, DUP-697, flosulide, meloxicam, 6-MNA, L-745337, nabumetone, nimesulide, NS-398, SC-5766, T-614, L-768277, GR-253035, JTE-522, RS-57067-000, SC-58125, SC-078, PD-138387, NS-398, flosulide, D-1367, SC-5766, PD-164387, etoricoxib, valdecoxib and parecoxib or pharmaceutically acceptable salts thereof