Two-component pharmaceutical composition for the treatment of pain

Abstract

The present invention is directed to a pharmaceutical composition that includes a combination of about 2-5 milligrams of a non-steroidal anti-inflammatory drug and from about 2-30 milligrams of an opioid analgesic in a single pharmaceutical dosage unit that can provide effective chronic pain management with the added benefit of reduced side effects such as withdrawal and gastrointestinal disorders. The non-steroidal anti-inflammatory drug may be piroxicam and the opioid analgesic may be buprenorphine. The present invention also provides for a method of managing pain in a patient that includes administering the pharmaceutical composition previously described. The pharmaceutical composition previously described may be administered in a single or multiple dosage regimen.

What is claimed is: 
     
         1 . A pharmaceutical dosage unit comprising about 2-5 milligrams of a non-steroidal anti-inflammatory drug and about 2-30 milligrams of an opioid analgesic. 
     
     
         2 . The pharmaceutical dosage unit of  claim 1 , wherein the non-steroidal anti-inflammatory drug is present in an amount of about 2-3 milligrams. 
     
     
         3 . The pharmaceutical dosage unit of  claim 1 , wherein the non-steroidal anti-inflammatory drug is present in an amount of about 2 milligrams. 
     
     
         4 . The pharmaceutical dosage unit of  claim 1 , wherein the non-steroidal anti-inflammatory drug comprises aspirin, acetaminophen and phenacetin ibuprofen, diflunisal, diclofenac, naproxen, benoxaprofen, flurbiprofen, fenoprofen, flubufen, flurbiprofen, ketoprofen, indoprofen, piroprofen, carprofen, oxaprozin, pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen, tiaprofenic acid, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid tolfenamic acid, diflunisal, flufenisal, piroxicam, meloxicam, sudoxicam, sulindac, isoxicam, and mixtures thereof. 
     
     
         5 . The pharmaceutical dosage unit of  claim 1 , wherein the opioid analgesic is present in an amount of about 2-15 milligrams. 
     
     
         6 . The pharmaceutical dosage unit of  claim 1 , wherein the opioid analgesic is present in an amount of about 2 milligrams. 
     
     
         7 . The pharmaceutical dosage unit of  claim 1 , wherein the opioid analgesic comprises alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacyl morphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propiram, propoxyphene, sufentanil, tramadol, tilidine, salts thereof and mixtures thereof. 
     
     
         8 . The pharmaceutical dosage unit of  claim 1 , wherein the pharmaceutical dosage unit is delivered by sublingual, mucosal, parenteral, intravenous, intramuscular, transdermal administration and combinations thereof. 
     
     
         9 . The pharmaceutical dosage unit of  claim 1 , wherein the dosage unit manages chronic pain with reduced side effects in a subject in need thereof. 
     
     
         10 . The pharmaceutical dosage unit of  claim 9 , wherein the side effect is gastrointestinal ulceration, abdominal pain, cramping, nausea, gastritis, kidney disease, angiodema, pancreatitis, gastrointestinal bleeding, liver toxicity, or combinations thereof. 
     
     
         11 . The pharmaceutical dosage unit of  claim 9 , wherein the side effect is opioid withdrawal. 
     
     
         12 . A pharmaceutical combination dosage unit comprising a low effective amount of non-steroidal anti-inflammatory drug and a high effective amount of an opioid analgesic-for management of chronic pain or reducing dependency on pain killers in a subject with reduced side effects. 
     
     
         13 . The pharmaceutical combination dosage unit of  claim 12 , wherein the side effect is gastrointestinal ulceration, abdominal pain, cramping, nausea, gastritis, kidney disease, angiodema, pancreatitis, gastrointestinal bleeding, liver toxicity, or combinations thereof. 
     
     
         14 . The pharmaceutical combination dosage unit of  claim 12 , wherein the pharmaceutical combination dosage unit is delivered by sublingual, mucosal, parenteral, intravenous, intramuscular, transdermal administration and combinations thereof. 
     
     
         15 . A method of treating chronic pain in a patient comprising administering, in a single or multiple dosage regimen, a pharmaceutical dosage unit, the dosage unit including about 2-5 milligrams of piroxicam in combination with about 2-30 milligrams of buprenorphine. 
     
     
         16 . The method of  claim 15 , piroxicam is present in an amount of about 2-3 milligrams and buprenorphine is present in an amount of about 2-15 milligrams. 
     
     
         17 . The method of  claim 15 , wherein piroxicam is present in an amount of about 2.5 milligrams and buprenorphine is present in an amount of about 2 milligrams. 
     
     
         18 . The method of  claim 15 , wherein the pharmaceutical dosage unit is delivered by sublingual, mucosal, parenteral, intravenous, intramuscular, transdermal administration and combinations thereof. 
     
     
         19 . The method of  claim 15 , wherein the pharmaceutical dosage unit manages pain with reduced side effects. 
     
     
         20 . The method of  claim 19 , wherein the side effect is gastrointestinal ulceration, abdominal pain, cramping, nausea, gastritis, kidney disease, angiodema, pancreatitis, gastrointestinal bleeding, liver toxicity, or combinations thereof. 
     
     
         21 . The pharmaceutical dosage unit of  claim 1 , wherein the pharmaceutical dosage unit is absorbed through mucous membranes in a subject's mouth. 
     
     
         22 . The pharmaceutical dosage unit of  claim 1 , wherein the pharmaceutical dosage unit is in sublingual form. 
     
     
         23 . The pharmaceutical dosage unit of  claim 1 , wherein the pharmaceutical dosage unit is in transdermal form. 
     
     
         24 . The pharmaceutical dosage unit of  claim 1 , wherein the pharmaceutical dosage unit is in sublingual form and the opioid analgesic dosage is from 2 mg to 8 mg. 
     
     
         25 . The pharmaceutical dosage unit of  claim 1 , wherein the pharmaceutical dosage unit is in sublingual form for administration under the tongue of a subject. 
     
     
         26 . The pharmaceutical dosage unit of  claim 1 , wherein the pharmaceutical dosage unit is in sublingual form and dissolves rapidly once in the mouth of a subject. 
     
     
         27 . The pharmaceutical dosage unit of  claim 1 , wherein the unit further comprises one or more of binders, fillers, disintegrants, sustained-release agents, diluents, anti-adherents, glidants, flow aids, sweeteners, flavoring and color agents. 
     
     
         28 . The pharmaceutical dosage unit of  claim 1 , wherein the unit comprises a sustained-release form upon administration to a subject. 
     
     
         29 . The pharmaceutical dosage unit of  claim 28 , wherein the unit non-steroidal anti-inflammatory drug and the opioid analgesic are released simultaneously. 
     
     
         30 . The pharmaceutical dosage unit of  claim 28 , wherein the unit non-steroidal anti-inflammatory drug and the opioid analgesic are released sequentially. 
     
     
         31 . The pharmaceutical dosage unit of  claim 1 , wherein the unit comprises a sustained-release oral mucosal patch upon administration to a subject.