Opioids for the treatment of the chronic obstructive pulmonary disease (copd)

Abstract

The present invention relates to an opioid controlled release oral dosage form comprising at least one opioid for the manufacture of a medicament to treat patients with Chronic Obstructive Pulmonary Disease (COPD).

1 - 13 . (canceled) 
     
     
         14 . A method of treating Chronic Obstructive Pulmonary Disease (COPD) comprising administering to a patient in need thereof a controlled release oral dosage form comprising an opioid agonist. 
     
     
         15 . The method of  claim 14 , wherein the dosage form provides an effective treatment when administered every 12 hours at steady state. 
     
     
         16 . The method of  claim 14 , wherein the dosage form provides an effective treatment when administered every 24 hours at steady state. 
     
     
         17 . The method of  claim 14 , wherein the dosage form is administered to the patient twice daily. 
     
     
         18 . The method of  claim 14 , wherein the opioid agonist is selected from oxycodone, hydromorphone, propoxyphene, nicomorphine, dihydrocodeine, diamorphine, papaveretum, codeine, ethylmorphine, phenylpiperidine, methadone, dextropropoxyphene, buprenorphine, pentazocine, tilidine, tramadol, hydrocodone, meperidine, oxymorphone, alphaprodine, anileridine, dextromoramide, metopone, levorphanol, phenazocine, etoheptazine, propiram, profadol, phenampromide, thiambutene, pholcodeine, codeine, dihydrocodeinone, fentanyl, 3-transdimethylamino-4-phenyl-4-trans-carbethoxy-Λ′-cyclohexene, 3-dimethylamino-O-(4-methoxyphenyl-carbamoyl)-propiophenone oxime, (−)-β-2′-hydroxy-2,9-dimethyl-5-phenyl-6,7-benzomorphane, (−)-2′-hydroxy-2-(3-methyl-2-butenyl)-9-methyl-5-phenyl-6,7-benzomorphane, pirinitramide, (−)-α-5,9-diethyl-2′-hydroxy-2-methyl-6,7-benzomorphane, ethyl 1-(2-dimethylaminoethyl)-4,5,6,7-tetrahydro-3-methyl-4-oxo-6-phenyl-indol-2-carboxylate, 1-benzoylmethyl-2,3-dimethyl-3-(m-hydroxy-phenyl)-piperidine, N-allyl-7α(1-R-hydroxy-1-methylbutyl)-6,14-endo-ethanotetrahydronororipavine, (+2′-hydroxy-2-methyl-6,7-benzomorphane, noracylmethadol, phenoperidine, α-dl-methadol, α-l-methadol, β-dl-acetylmethadol, α-l-acetylmethadol, β-l-acetylmethadol, and sufetanil, and pharmaceutically acceptable salts thereof. 
     
     
         19 . The method of  claim 18 , wherein the opioid agonist is selected from oxycodone, hydromorphone, propoxyphene, nicomorphine, dihydrocodeine, diamorphine, papaveretum, codeine, ethylmorphine, phenylpiperidine, methadone, dextropropoxyphene, buprenorphine, pentazocine, tilidine, tramadol, and hydrocodone, and pharmaceutically acceptable salts thereof. 
     
     
         20 . The method of  claim 18 , wherein the opioid agonist is selected from oxycodone, hydrocodone, hydromorphone, methadone, oxymorphone, fentanyl, and sufentanil, and pharmaceutically acceptable salts thereof. 
     
     
         21 . The method of  claim 14 , wherein the dosage form further comprises an opioid antagonist. 
     
     
         22 . The method of  claim 21 , wherein dosage form is configured to release the opioid agonist and the opioid antagonist in an independent and invariant manner. 
     
     
         23 . The method of  claim 21 , wherein the opioid antagonist is selected from naltrexone, naloxone, nalmefene, nalorphine, nalbuphine, naloxoneazinen, methylnaltrexone, ketylcyclazocine, norbinaltorphimine, naltrindol, 6-β-naloxol, and 6-β-naltrexol, and pharmaceutically acceptable salts thereof. 
     
     
         24 . The method of  claim 23 , wherein the opioid antagonist is selected from naltrexone, nalmefene, and naloxone, and pharmaceutically acceptable salts thereof. 
     
     
         25 . The method of  claim 24 , wherein the opioid antagonist is naloxone or a pharmaceutically acceptable salt thereof. 
     
     
         26 . The method of  claim 25 , wherein the naloxone or the pharmaceutically acceptable salt thereof is present in the dosage form in an amount range of 1 to 50 mg. 
     
     
         27 . The method of  claim 25 , wherein the opioid agonist is present in the dosage form in an amount that is therapeutically equivalent to an amount of oxycodone or a pharmaceutically acceptable salt thereof, and the amount of oxycodone or the pharmaceutically acceptable salt thereof is in excess relative to the amount of naloxone or the pharmaceutically acceptable salt thereof. 
     
     
         28 . The method of  claim 25 , wherein the opioid agonist is present in the dosage form in an amount that is therapeutically equivalent to an amount of oxycodone or a pharmaceutically acceptable salt thereof, and the amount of oxycodone or the pharmaceutically acceptable salt thereof is in a weight ratio to the naloxone or the pharmaceutically acceptable salt thereof ranging from 25:1 to 1:1. 
     
     
         29 . The method of  claim 28 , wherein the amount of oxycodone or the pharmaceutically acceptable salt thereof is in a weight ratio to the naloxone or the pharmaceutically acceptable salt thereof ranging from 5:1 to 1:1. 
     
     
         30 . The method of  claim 29 , wherein the amount of oxycodone or the pharmaceutically acceptable salt thereof is in a weight ratio to the naloxone or the pharmaceutically acceptable salt thereof of 5:1, 4:1, 3:1, 2:1, or 1:1. 
     
     
         31 . The method of  claim 30 , wherein the amount of oxycodone or the pharmaceutically acceptable salt thereof is in a weight ratio to the naloxone or the pharmaceutically acceptable salt thereof of 2:1. 
     
     
         32 . The method of  claim 14 , wherein the opioid agonist is present in the dosage form in an amount range that is therapeutically equivalent to 10 to 150 mg of oxycodone or a pharmaceutically acceptable salt thereof. 
     
     
         33 . The method of  claim 32 , wherein the opioid agonist is present in the dosage form in an amount range that is therapeutically equivalent to 10 to 80 mg of oxycodone or a pharmaceutically acceptable salt thereof. 
     
     
         34 . The method of  claim 21 , wherein the opioid agonist is present in the dosage form in an amount range that is therapeutically equivalent to 10 to 150 mg of oxycodone or a pharmaceutically acceptable salt thereof. 
     
     
         35 . The method of  claim 34 , wherein the opioid agonist is present in the dosage form in an amount range that is therapeutically equivalent to 10 to 80 mg of oxycodone or a pharmaceutically acceptable salt thereof. 
     
     
         36 . The method of  claim 25 , wherein the opioid agonist is present in the dosage form in an amount range that is therapeutically equivalent to 10 to 150 mg of oxycodone or a pharmaceutically acceptable salt thereof. 
     
     
         37 . The method of  claim 36 , wherein the opioid agonist is present in the dosage form in an amount range that is therapeutically equivalent to 10 to 80 mg of oxycodone or a pharmaceutically acceptable salt thereof. 
     
     
         38 . The method of  claim 31 , wherein the opioid agonist is present in the dosage form in an amount range that is therapeutically equivalent to 10 to 150 mg of oxycodone or a pharmaceutically acceptable salt thereof. 
     
     
         39 . The method of  claim 38 , wherein the opioid agonist is present in the dosage form in an amount range that is therapeutically equivalent to 10 to 80 mg of oxycodone or a pharmaceutically acceptable salt thereof. 
     
     
         40 . The method of  claim 14 , wherein the dosage form further comprises a sustained release matrix. 
     
     
         41 . The method of  claim 40  wherein the sustained release matrix comprises an alkyl cellulose or a hydroxyalkyl cellulose. 
     
     
         42 . The method of  claim 41 , wherein the sustained release matrix comprises an alkyl cellulose. 
     
     
         43 . The method of  claim 42 , wherein the alkyl cellulose is ethyl cellulose.