Preparation of formulations of angiotensin II AT1 receptors antagonists for the treatment of arterial hypertension, other cardiovascular illnesses and its complications

Abstract

Preparation of AT1 receptors antagonists formulations using the cyclodextrins, their derivatives and/or biodegradable polymers for the treatment of arterial hypertension, other cardiovascular disease and their complications. Until now, no applications using the AT1 1 receptor antagonists and cyclodextrins or derivatives and/or biodegradable polymers for the treatment of arterial hypertension, other cardiovascular diseases and their complications, was found in the technical state of art. The present invention is characterized by the combination of two different technologies: one is the molecular encapsulation of AT1 1 receptor antagonists in cyclodextrins and the other is the microencapsulation in biodegradable polymers. It also comprises the increase of the effectiveness of the AT1 1 receptor antagonists as well as an increase in their bio-availability. The present invention comprises a new more effective alternative for the treatment of arterial hypertension, other cardiovascular diseases and their complications.

1 - 13 . (canceled)  
     
     
         14 . A composition comprising an inclusion compound consisting essentially of: (a) an Angiotensin II AT1 receptor antagonist or salt thereof and (b) a cyclodextrin.  
     
     
         15 . The composition according to  claim 14 , wherein the composition is a controlled-release system.  
     
     
         16 . The composition according to  claim 14 , wherein the Angiotensin II AT1 receptor antagonist or salt thereof is chosen from valsartan, telmisartan, irbersartan, candesartan, or eprosartan.  
     
     
         17 . The composition according to  claim 14  wherein the Angiotensin II AT1 receptor antagonist is angiotensin (1-7).  
     
     
         18 . The composition according to  claim 14 , wherein the cyclodextrin has six, seven, or eight units of glucopyranose.  
     
     
         19 . The composition according to  claim 14 , wherein the cyclodextrin is β-cyclodextrin.  
     
     
         20 . The composition according to  claim 14 , wherein the cyclodextrin is hydroxyalkylated cyclodextrin.  
     
     
         21 . The composition according to  claim 20 , wherein the hydroxyalkylated cyclodextrin is hydroxypropyl-β-cyclodextrin.  
     
     
         22 . A pharmaceutical composition comprising the composition as claimed in  claim 14  and a pharmaceutical acceptable carrier, diluent, excipient, or combination thereof.  
     
     
         23 . The pharmaceutical composition according to  claim 23 , wherein the composition is for oral, intramuscular, intravenous, subcutaneous or inhalation administration.  
     
     
         24 . The composition according to  claim 14 , wherein the composition further comprises a biodegradable or biocompatible polymer.  
     
     
         25 . The composition according to  claim 24 , wherein the polymer has a degradable surface.  
     
     
         26 . The composition according to  claim 25 , wherein the polymer is chosen from poly(2-hydroxyethyl methacrylate), polyacrilamide, poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-glycolic acid) (PLGA) and poly(anhydrides).  
     
     
         27 . The composition according to  claim 24 , wherein the composition is a controlled-release system.  
     
     
         28 . A pharmaceutical composition comprising the composition as claimed in  claim 24  and a pharmaceutical acceptable carrier, diluent, excipient, or combination thereof.  
     
     
         29 . The pharmaceutical composition according to  claim 28 , wherein the composition is for oral, intramuscular, intravenous, subcutaneous or inhalation administration.  
     
     
         30 . A process for the preparation of a composition comprising an inclusion compound consisting essentially of: (a) an Angiotensin II AT1 receptor antagonist or salt thereof and (b) a cyclodextrin, comprising forming an inclusion compound between an Angiotensin II AT1 receptor antagonist and a cyclodextrin.  
     
     
         31 . The process of  claim 30  further comprising the encapsulation of the inclusion compound with a biodegradable or biocompatible polymer.  
     
     
         32 . The process of  claim 31 , wherein the polymer has a degradable surface.  
     
     
         33 . The process according to  claim 32 , wherein the polymer is chosen from poly(2-hydroxyethyl methacrylate), polyacrilamide, poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-glycolic acid) (PLGA) and poly(anhydrides).  
     
     
         34 . A method of treating arterial hypertension comprising administering to a patient in need thereof a therapeutically effective amount of at least one pharmaceutical composition of  claim 22 .  
     
     
         35 . A method of treating arteriosclerosis associated with arterial hypertension comprising administering to a patient in need thereof a therapeutically effective amount of at least one pharmaceutical composition of  claim 22 .  
     
     
         36 . A method of treating stroke associated with arterial hypertension comprising administering to a patient in need thereof a therapeutically effective amount of at least one pharmaceutical composition of  claim 22 .  
     
     
         37 . A method of treating arterial hypertension comprising administering to a patient in need thereof a therapeutically effective amount of at least one pharmaceutical composition of  claim 28 .  
     
     
         38 . A method of treating arteriosclerosis associated with arterial hypertension comprising administering to a patient in need thereof a therapeutically effective amount of at least one pharmaceutical composition of  claim 28 .  
     
     
         39 . A method of treating stroke associated with arterial hypertension comprising administering to a patient in need thereof a therapeutically effective amount of at least one pharmaceutical composition of  claim 28.