Methods and compositions for administration of oxybutynin

Abstract

The present invention is directed to methods and compositions for treating pulmonary disease comprising delivering directly to a patient's lungs a therapeutically effective amount of oxybutynin in combination with one or more pharmaceutically effective agents. Oxybutynin may be selected from the group consisting of, but not limited to, a xinafoate salt, a palmitate salt, a pamoic salt, a resonate salt, a laurate salt and other salts. The pharmaceutically effective agents comprise bronchodilators, antiinflammatories, corticosteroids, corticosteroid reversal agent or alveolar growth agents or other agents selected from proteinase or protease inhibitors.

We claim: 
     
         1 . A method for treating pulmonary disease comprising delivering directly to a patient's lungs a therapeutically effective amount of oxybutynin in combination with one or more pharmaceutically effective agents, wherein the oxybutynin is selected from the group consisting of a palmitate salt, a pamoic salt, and a resonate salt. 
     
     
         2 . The method according to  claim 1 , wherein oxybutynin is delivered in dry powder form. 
     
     
         3 . The method according to  claim 1 , wherein pharmaceutically effective agent is delivered in dry powder form. 
     
     
         4 . The method of  claim 1 , wherein the pharmaceutically effective agents comprise bronchodilators, antiinflammatories, corticosteroids, inhaled corticosteroid, corticosteroid resistance reversal agents, alveolar growth agents, proteinase inhibitors, or protease inhibitors. 
     
     
         5 . The method of  claim 4 , wherein the bronchodilators comprise long-acting beta agonists and short-acting beta agonists and derivatives or pharmaceutically acceptable salts thereof. 
     
     
         6 . The method of  claim 4 , wherein the antiinflammatories comprise inhaled corticosteroids, phosphodiesterase inhibitors or leukotriene receptor antagonists. 
     
     
         7 . The method of  claim 6 , wherein the corticosteroids comprise budesonide, fluticasone, beclomethasone, flunisolide, triamcinolone, ciclesonide, loteprednol, fluorometholone, and derivatives or pharmaceutically acceptable salts thereof. 
     
     
         8 . The method of  claim 4 , wherein the corticosteroid resistance reversal agent comprises vitamin D, synthetic vitamin D, vitamin D analogs, vitamin D receptor agonists, vitamin D receptor partial agonists, calcitriol, antioxidants, iNOS inhibitors, Phosphoinositide-3-kinase-delta inhibitors, p38 MAP kinase inhibitors, JNK inhibitors, MIF inhibitors, low-dose theophylline, p-glycoprotein inhibitors, macrolides, calcineurin inhibitors, statins and equivalents thereof. 
     
     
         9 . The method of  claim 4 , wherein the alveolar growth agent comprises vitamin A, All Trans Retinoic Acid (ATRA), retinoic acid receptor (RAR) agonists and RAR selective alveolar growth agents, RAR selective agonists, palovarotene and equivalents thereof. 
     
     
         10 . The method of  claim 5 , wherein the long-acting beta agonist comprises formoterol, salmeterol, odalaterol, carmoterol or vilanterol. 
     
     
         11 . The method of  claim 10 , further comprising an inhaled corticosteroid wherein the inhaled corticosteroid comprises budesonide, fluticasone, or mometasone. 
     
     
         12 . The method of  claim 11 , further comprising a selective agent selected from a soft steroid class, wherein the soft steroid class comprises ciclesonide or loteprednol. 
     
     
         13 . The method of  claim 10 , further comprising a corticosteroid resistance reversal agent, wherein the corticosteroid resistance reversal agent is selected from the group consisting of vitamin D, vitamin D analogs, synthetic vitamin D, vitamin D receptor agonists and antagonists, calcitol and equivalents thereof. 
     
     
         14 . The method of  claim 12 , further comprising a corticosteroid resistance reversal agent wherein the corticosteroid resistance reversal agent is selected from the group consisting of vitamin D, vitamin D analogs, synthetic vitamin D, vitamin D receptor agonists and antagonists, calcitol and equivalents thereof. 
     
     
         15 . The method of  claim 1 , wherein the pharmaceutically effective agents comprise
 a long-acting beta agonist comprising formoterol,   and an alveolar growth agent selected from the group consisting ATRA, cis-retionoic acid and palovarotene.   
     
     
         16 . The method of  claim 1 , wherein the pulmonary disease comprises asthma, atelectasis, bronchitis, chronic obstructive pulmonary disease, emphysema, lung cancer, pneumonia or pulmonary edema. 
     
     
         17 . The method of  claim 1 , wherein the pulmonary disease comprises chronic obstructive pulmonary disease,
 wherein the pharmaceutically effective agents comprise long acting muscarinic antagonists.   
     
     
         18 . The method according to  claim 1 , wherein oxybutynin and the pharmaceutically effective agent is delivered using a dry powder inhaler (DPI) or a metered dose inhaler (MDI) or liquid nebulizer. 
     
     
         19 . The method according to  claim 18 , wherein the dry powder inhaler includes a piezo vibrator. 
     
     
         20 . The method according to  claim 1 , wherein oxybutynin is delivered in dry powder form having a mass median aerodynamic particle size selected from the group consisting of 0.5-20 microns, 0.5-15 microns, 0.5-10 microns, or 0.5-5 microns. 
     
     
         21 . The method according to  claim 1 , wherein the dosage of the therapeutically effective amount of oxybutynin is within the range of 0.001 to 20 mg per day, 0.02 to 15 mg per day, or 0.05 to 10 mg per day administered as needed. 
     
     
         22 . A method for treating chronic obstructive pulmonary disease comprising delivering directly to a patient's lungs a therapeutically effective amount of oxybutynin in combination with one or more pharmaceutically effective agents, wherein oxybutynin is selected from the group consisting of a palmitate salt, a pamoic salt, and a resonate salt.