Disorders implicating pufa oxidation

Abstract

Some aspects of the invention provide for a method of treating hepatic disorders, lipidemias and cardiac-related risk factors using polyunsaturated fatty acids which are modified in certain positions to attenuate oxidative damage by Reactive Oxygen Species (ROS) and/or suppress the rate of formation of reactive products and toxic compounds.

1 .- 30 . (canceled) 
     
     
         31 . A method of treating or preventing the progression of lipidemia or cardiac -related risk factors, comprising:
 administering an effective amount of a modified polyunsaturated fatty acid or fatty acid ester, or a combination thereof to a patient having one or more conditions selected from the group consisting of lipidemia, liporegulation disorders, lipotoxicity, ischemic heart disease, hypertension, atrial fibrillation, left ventricular hypertrophy, coronary artery disease and atherosclerosis and in need of treatment;   wherein the modified polyunsaturated fatty acid or fatty acid ester is incorporated into the patient's body following administration.   
     
     
         32 . The method of  claim 31 , wherein the subject has lipidemia or is susceptible to lipidemia. 
     
     
         33 . The method of  claim 31 , wherein the subject has atherosclerosis or is susceptible to atherosclerosis. 
     
     
         34 . The method of  claim 31 , wherein the amount of modified polyunsaturated fatty acid or fatty acid ester comprises between about 5% to about 75% of the total amount of the polyunsaturated fatty acids or fatty acid esters delivered to the patient's body. 
     
     
         35 . The method of  claim 31 , wherein the modified polyunsaturated fatty acid or fatty acid ester having the following formula: 
       
         
           
           
               
               
           
         
         wherein R is H or C 3 H 7 ; 
         R 1  is H or alkyl; 
         each Y is independently H, D, or F, wherein at least one Y is D or F; 
         n is 1 to 5; and 
         m is 1 to 10. 
       
     
     
         36 . The method of  claim 31 , wherein the modified polyunsaturated fatty acid or fatty acid ester comprises deuterated polyunsaturated fatty acid or deuterated fatty acid ester. 
     
     
         37 . The method of  claim 36 , wherein the modified polyunsaturated fatty acid or fatty acid ester is deuterated at one or more bis-allylic positions. 
     
     
         38 . The method of  claim 36 , wherein a cell or tissue of the patient maintains a sufficient concentration of the deuterated polyunsaturated fatty acid or fatty acid ester to reduce or prevent autoxidation of undeuterated polyunsaturated fatty acids or fatty acid esters, or cancel toxicity of undeuterated polyunsaturated fatty acid or fatty acid ester in the patient's body. 
     
     
         39 . The method of  claim 36 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is an omega-3fatty acid, an omega-6 fatty acid, an omega-3 fatty acid ester, or an omega-6 fatty acid ester. 
     
     
         40 . The method of  claim 36 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is a deuterated linoleic acid, a detuerated linoleinic acid, a deuterated arachadonic acid, a deuterated eicosapentaenoic acid, or a deuterated docosahexaenoic acid, or an ester of any of the foregoing. 
     
     
         41 . The method of  claim 36 , wherein the deuterated polyunsaturated fatty acid ester is selected from an alkyl ester, a triglyceride, a diglyceride, a monoglyceride, and combinations thereof. 
     
     
         42 . The method of  claim 36 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is selected from the group consisting of 11,11-D2-linolenic acid, 14,14-D2-linolenic acid, 11,11,14,14-D4-linolenic acid, 11,11-D2-linoleic acid, 14,14-D2-linoleic acid, 11,11,14,14-D4-linoleic acid, 11-D-linolenic acid, 14-D-linolenic acid, 11,14-D2-linolenic acid, 11-D-linoleic acid, 14-D-linoleic acid, and 11,14-D2-linoleic acid, and an ester of any of the foregoing, and combinations thereof. 
     
     
         43 . The method of  claim 42 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11-D2-linoleic acid or an ethyl ester thereof. 
     
     
         44 . The method of  claim 42 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11,14,14-D4-linolenic acid or an ethyl ester thereof. 
     
     
         45 . The method of  claim 36 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is further stabilized at a pro-bis-allylic position. 
     
     
         46 . The method of  claim 45 , wherein the further stabilization comprises replacing one or more hydrogens at a pro-bis-allylic position with deuterium or replacing one or more carbon atoms at a pro-bis-allylic position with  13 C. 
     
     
         47 . The method of  claim 31 , further comprising co-administering at least one antioxidant. 
     
     
         48 . The method of  claim 47 , wherein the antioxidant is selected from the group consisting of Coenzyme Q, idebenone, mitoquinone, mitoquinol, vitamin C, vitamin E, and combinations thereof. 
     
     
         49 . The method of  claim 36 , wherein the amount of deuterated polyunsaturated fatty acid or fatty acid ester administered to the patient is in the range of about 0.1 mg/kg to 100 mg/kg per day. 
     
     
         50 . A composition for treating or preventing the progression of lipidemia or cardiac-related risk factors, comprising deuterated polyunsaturated fatty acid or fatty acid ester at one or more bis-allylic position, or a combination thereof; wherein the deuterated polyunsaturated fatty acid or fatty acid ester is incorporated into a cell or tissue of the patient following administration and maintains a sufficient concentration to reduce or prevent autoxidation of undeuterated polyunsaturated fatty acids or fatty acid esters, or cancel toxicity of undeuterated polyunsaturated fatty acid or fatty acid ester in the patient.