Compositions and Methods for the Treatment of Diseases Related to the Renin-Angiotensin-System

Abstract

The present invention relates to pharmaceutical compositions, kits and methods for the treatment of diseases related to the renin-angiotensin system (RAS), such as e.g. hypertension. The pharmaceutical compositions according to the invention comprise at least one aspartyl aminopeptidase inhibitor and at least one angiotensin-converting-enzyme (ACE) inhibitor, or at least one aspartyl aminopeptidase inhibitor and at least one chymase inhibitor.

1 .- 18 . (canceled) 
     
     
         19 . A pharmaceutical composition comprising:
 at least one aspartyl aminopeptidase inhibitor and at least one angiotensin-converting-enzyme (ACE) inhibitor; or   at least one aspartyl aminopeptidase inhibitor and at least one chymase inhibitor.   
     
     
         20 . The pharmaceutical composition of  claim 19 , further defined as comprising at least one aspartyl aminopeptidase inhibitor, at least one angiotensin-converting-enzyme (ACE) inhibitor, and at least one chymase inhibitor. 
     
     
         21 . The pharmaceutical composition of  claim 19 , wherein:
 the at least one aspartyl aminopeptidase inhibitor and the at least one ACE inhibitor; or   the at least one aspartyl aminopeptidase inhibitor and the at least one chymase inhibitor; or   the at least one aspartyl aminopeptidase inhibitor and the at least one ACE inhibitor and the at least one chymase inhibitor;   are combined in a single molecule.   
     
     
         22 . The pharmaceutical composition of  claim 19 , wherein the aspartyl aminopeptidase inhibitor is not a selective aminopeptidase A inhibitor. 
     
     
         23 . The pharmaceutical composition of  claim 19 , wherein the aspartyl aminopeptidase inhibitor is a selective DNPEP inhibitor. 
     
     
         24 . The pharmaceutical composition of  claim 19 , wherein the aspartyl aminopeptidase inhibitor is Amastatin or a derivative thereof. 
     
     
         25 . The pharmaceutical composition of  claim 19 , wherein the aspartyl aminopeptidase inhibitor is not Amastatin. 
     
     
         26 . The pharmaceutical composition of  claim 19 , wherein the ACE inhibitor is Lisinopril and/or Captopril. 
     
     
         27 . The pharmaceutical composition of  claim 19 , further defined as having a pharmacologic effect that is mediated by affecting Renin-Angiotensin system (RAS). 
     
     
         28 . The pharmaceutical composition of  claim 19 , wherein the composition is adapted for systemic administration. 
     
     
         29 . The pharmaceutical composition of  claim 28 , wherein the composition is adapted for oral administration. 
     
     
         30 . A method of treating a disease related to Renin-Angiotensin system (RAS) comprising:
 obtaining a pharmaceutical composition of  claim 19 ; and   administering the pharmaceutical composition to a subject;   wherein a disease related to RAS is treated in the subject.   
     
     
         31 . The method of  claim 30 , wherein the disease related to the RAS is a hyperplastic disease, a neoplastic disease, and/or a cardiovascular disease. 
     
     
         32 . The method of  claim 31 , wherein the cardiovascular disease is hypertension and/or heart failure. 
     
     
         33 . The method of  claim 31 , wherein the neoplastic disease is cancer. 
     
     
         34 . The method of  claim 33 , wherein the cancer is characterized by an increased Ang II level and/or in which an increase in the Ang 1-7 level is advantageous. 
     
     
         35 . The method of  claim 30 , wherein a pharmacologic effect of the composition is mediated by affecting the RAS. 
     
     
         36 . The method of  claim 30 , wherein the composition is administered systemically. 
     
     
         37 . The method of  claim 30 , wherein the composition is administered orally. 
     
     
         38 . A kit of parts comprising:
 a pharmaceutical composition comprising an aspartyl aminopeptidase inhibitor and a pharmaceutical composition comprising an angiotensin-converting-enzyme (ACE) inhibitor; or   a pharmaceutical composition comprising an aspartyl aminopeptidase inhibitor and a pharmaceutical composition comprising a chymase inhibitor; or   a pharmaceutical composition comprising an aspartyl aminopeptidase inhibitor and a pharmaceutical composition comprising an angiotensin-converting-enzyme (ACE) inhibitor and a pharmaceutical composition comprising a chymase inhibitor.   
     
     
         39 . The kit of  claim 38 , wherein:
 the at least one aspartyl aminopeptidase inhibitor and the at least one ACE inhibitor; or   the at least one aspartyl aminopeptidase inhibitor and the at least one chymase inhibitor; or   the at least one aspartyl aminopeptidase inhibitor and the at least one ACE inhibitor and the at least one chymase inhibitor;   are combined in a single molecule.