Compositions Comprising Oxo-Derivatives of Fatty Acids and Methods of Making and Using Same

Abstract

The present disclosure provides 15-oxo-EPA and 15-oxo-DGLA, compositions comprising 15-oxo-EPA and/or 15-oxo-DGLA, and methods of treating and/or preventing fibrosis, skin disorders, inflammation, kidney disease or renal dysfunction in a subject in need thereof by administering 15-oxo-EPA and/or 15-oxo-DGLA.

What is claimed is: 
     
         1 . (5Z,8Z,11Z,13E,17Z)-15-oxoicosa-5,8,11,13,17-pentaenoic acid (“15-oxo-EPA”). 
     
     
         2 . A composition comprising about 0.1g to about 4g of (5Z,8Z,11Z,13E,17Z)-15-oxoicosa-5,8,11,13,17-pentaenoic acid (“15-oxo-EPA”). 
     
     
         3 . A pharmaceutical composition comprising (5Z,8Z,11Z,13E,17Z)-15-oxoicosa-5,8,11,13,17-pentaenoic acid (“15-oxo-EPA”) and a pharmaceutically acceptable excipient. 
     
     
         4 . (8Z,11Z,13E)-15-oxoicosa-8,11,13-trienoic acid (“15-oxo-DGLA”). 
     
     
         5 . A composition comprising about 0.1g to about 4g of (8Z,11Z,13E)-15-oxoicosa-8,11,13-trienoic acid (“15-oxo-DGLA”). 
     
     
         6 . A pharmaceutical composition comprising (8Z,11Z,13E)-15-oxoicosa-8,11,13-trienoic acid (“15-oxo-DGLA”) and a pharmaceutically acceptable excipient. 
     
     
         7 . A method of treating and/or preventing fibrosis, inflammation, kidney disease or renal dysfunction in a subject in need thereof, the method comprising administering to the subject a compound, composition, or pharmaceutical composition of any preceding claim. 
     
     
         8 . The method of  claim 7 , wherein the fibrosis is associated with an organ or tissue selected from the group consisting of: lung, liver, heart, mediastinum, bone marrow, retroperitoneaum, skin, intestine, joint, a reproductive organ, and a combination thereof. 
     
     
         9 . The method of  claim 7  or  claim 8 , wherein the fibrosis is liver fibrosis. 
     
     
         10 . The method of any one of  claims 7  to  9 , wherein the fibrosis is associated with non-alcoholic fatty liver disease (NAFLD). 
     
     
         11 . The method of any one of  claims 7  to  10 , wherein a NAFLD activity score (NAS) is reduced in the subject after administration of the composition, optionally:
 wherein the NAS is reduced in the subject compared to baseline, or 
 wherein the subject is on fibrosis therapy and the NAS is reduced in the subject in comparison to a second subject who has not been administered the composition, wherein the second subject optionally has been administered a placebo, and/or wherein the second subject is optionally on fibrosis therapy, and
 optionally wherein the fibrosis therapy is continued during administration of the compound, composition, or pharmaceutical composition. 
 
 
     
     
         12 . The method of  claim 11 , wherein the fibrosis therapy comprises administration of a hepatitis C virus (HCV) non-antiviral agent, an HCV antiviral agent, a hepatitis B virus (HBV) non-antiviral agent, an HBV antiviral agent, a primary biliary cirrhosis agent, an alcoholic hepatitis agent, a primary sclerosing cholangitis agent, a NASH agent, an autoimmune hepatitis agent, a pulmonary fibrosis agent, a cystic fibrosis agent, a renal fibrosis agent, a skin fibrosis agent, a myelofibrosis agent, an eosinophilic esophagitis agent, an anti-TGF-β agent, an anti-CTGF agent, a recombinant human serum amyloid P agent, an anti-IL-4 agent, an anti-IL-5 agent (e.g., mepolizumab), an anti-IL-13 agent, a neurochemical receptor agent, an anti-IL-17A agent, a Hh or Hh(R) SMO antagonist, a CCR5 antagonist, a CCR4 cell recruitment inhibitor, a CXCR4 antagonist, an anti-CXCR4 agent, a CXCR3 antagonist, an anti-CCL17 agent, a NOX inhibitor, copaxone, adiponectin, an AMPK agonist, Y-box binding protein-1, a myofibroblast recruitment inhibitor, an anti-Th17 MMP inducer, an anti-extracellular matrix deposition compound, an adenosine receptor antagonist, a micro-RNA (miR) agent, a stem cell, tenofovir, an anti-collagen crosslinking agent (e.g., simtuzumab, mogamulizumab), or an angiotensin II receptor blocker (ARB) selected from the group consisting of: valsartan, telmisartan, losartan, irbesartan, azilsartan, eprosartan, olmesartan, or a combination of any of the foregoing. 
     
     
         13 . The method of any one of  claims 7  to  12 , wherein the 15-oxo-EPA, the composition comprising 15-oxo-EPA, the pharmaceutical composition comprising 15-oxo-EPA, the 15-oxo-DGLA, the composition comprising 15-oxo-DGLA, or the pharmaceutical composition comprising 15-oxo-DGLA is orally administered. 
     
     
         14 . The method of any one of  claims 7  to  13 , wherein the 15-oxo-EPA or the 15-oxo-DGLA is the only active ingredient in the composition. 
     
     
         15 . The method of any one of  claims 11  to  13 , wherein the composition further comprises an additional agent for affecting the fibrosis therapy. 
     
     
         16 . The method of any one of  claims 7  to  15  further comprising identifying the subject as having fibrosis before administering the 15-oxo-EPA, the composition comprising 15-oxo-EPA, the pharmaceutical composition comprising 15-oxo-EPA, the 15-oxo-DGLA, the composition comprising 15-oxo-DGLA, or the pharmaceutical composition comprising 15-oxo-DGLA. 
     
     
         17 . The method of any one of  claims 7  to  16  further comprising identifying the subject as having an increased risk of developing fibrosis before administering the 15-oxo-EPA, the composition comprising 15-oxo-EPA, the pharmaceutical composition comprising 15-oxo-EPA, the 15-oxo-DGLA, the composition comprising 15-oxo-DGLA, or the pharmaceutical composition comprising 15-oxo-DGLA. 
     
     
         18 . The method of  claim 16  or  claim 17 , wherein the step of identifying comprises determining a NAS associated with the subject, optionally wherein the NAS associated with the subject is at least 3. 
     
     
         19 . The method of any one of  claims 16  to  18 , wherein the step of identifying comprises screening for a genetic mutation in a nucleic acid molecule associated with the subject. 
     
     
         20 . The method of any one of  claims 16  to  19 , wherein the step of identifying comprises obtaining an analysis of blood and/or serum associated with the subject.