Treatment of Energy Utilization Disease

Abstract

Described are compositions comprising imino sugar acids for the treatment of energy utilization disease (e.g. metabolic syndrome, including any disease or disorder associated therewith, for example central obesity, elevated levels of triglycerides and diabetes, including type 1 diabetes, type 2 diabetes and insulin resistance), processes for producing said compositions from various plant sources, together with various products, compounds, compositions, medical uses and methods based thereon.

1 - 37 . (canceled) 
     
     
         38 . A method of treating diabetes, obesity or disorders associated with metabolic syndrome in a patient, the method comprising the administration to the patient of an isolated imino sugar acid, wherein the imino sugar acid does not inhibit disaccharidase activity, exhibiting an IC 50  value in the μM or mM range or greater. 
     
     
         39 . A method of treating diabetes, obesity or disorders associated with metabolic syndrome in a patient, which method comprises the administration to the patient of an imino sugar acid in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor. 
     
     
         40 . A method according to  claim 39  wherein:
 (i) the imino sugar acid is admixed, or physically associated within a single unit dose, with the dipeptidyl peptidase-4 (DPP-4) inhibitor; or 
 (ii) the imino sugar acid is co-packaged with the dipeptidyl peptidase-4 (DPP-4) inhibitor; or 
 (iii) the imino sugar acid is co-administered with the dipeptidyl peptidase-4 (DPP-4) inhibitor. 
 
     
     
         41 . The method of  claim 38  wherein the imino sugar acid is of a structural class selected from piperidine, pyrrolidine, pyrrolizidine, indolizidine and nortropane. 
     
     
         42 . The method of  claim 38  wherein the imino sugar acid is polyhydroxylated. 
     
     
         43 . The method of  claim 38  wherein the imino sugar acid is a piperidine imino sugar acid. 
     
     
         44 . The method of  claim 43  wherein the imino sugar acid is: (a) a pipecolic or hydroxypipecolic acid; (b) a piperidine ISA having at least 3 free hydroxyl (or hydroxyalkyl) groups on the ring system nucleus; or (c) N-acid derivatives of (a) or (b); or (d) a polyhydroxypipecolic acid having at least two (e.g. 3) free hydroxyl (or hydroxyalkyl) groups on the ring system nucleus. 
     
     
         45 . The method of  claim 38  wherein the imino sugar or imino sugar acid is of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is absent or is C 1 -C 6  alkyl; 
 the location of the carboxyl group may be switched from the ring carbon to the ring nitrogen to produce an N-acid analogue of the compound of formula (I); 
 or an acyl (e.g. O-acyl) derivative or dehydroxylated analogue in which one or more ring hydroxyl(s) are absent; 
 
       or a pharmaceutically acceptable salt or derivative thereof. 
     
     
         46 . The method of  claim 45  wherein the imino sugar or imino sugar acid is selected from the structures shown below: 
       
         
           
           
               
               
           
         
       
       or (a) N-acid analogues of the foregoing structures (G1)-(G4) in which the location of the carboxyl group is switched from the ring carbon to the ring nitrogen; (b) acyl (e.g. O-acyl) derivatives of the foregoing structures (or of the N-acid analogues of (a)); (c) dehydroxylated analogues of the foregoing structures (or of the N-acid analogues of (a) and (b)) in which one or more ring hydroxyl(s) are absent. 
     
     
         47 . A composition comprising an imino sugar acid combined with a dipeptidyl peptidase-4 (DPP-4) inhibitor. 
     
     
         48 . The composition of  claim 47  wherein the imino sugar acid is of a structural class selected from piperidine, pyrrolidine, pyrrolizidine, indolizidine and nortropane. 
     
     
         49 . The composition of  claim 47  wherein the imino sugar acid is polyhydroxylated. 
     
     
         50 . The composition of  claim 48  wherein the imino sugar acid is a piperidine imino sugar acid. 
     
     
         51 . The composition of  claim 50  wherein the imino sugar acid is: (a) a pipecolic or hydroxypipecolic acid; (b) a piperidine ISA having at least 3 free hydroxyl (or hydroxyalkyl) groups on the ring system nucleus; or (c) N-acid derivatives of (a) or (b); or (d) a polyhydroxypipecolic acid having at least two (e.g. 3) free hydroxyl (or hydroxyalkyl) groups on the ring system nucleus. 
     
     
         52 . The composition of  claim 47  wherein the imino sugar or imino sugar acid is of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is absent or is C 1 -C 6  alkyl; 
 the location of the carboxyl group may be switched from the ring carbon to the ring nitrogen to produce an N-acid analogue of the compound of formula (I); 
 or an acyl (e.g. O-acyl) derivative or dehydroxylated analogue in which one or more ring hydroxyl(s) are absent; 
 
     
     
         53 . The composition of  claim 52  wherein the imino sugar or imino sugar acid is selected from the structures shown below: 
       
         
           
           
               
               
           
         
       
       or (a) N-acid analogues of the foregoing structures (G1)-(G4) in which the location of the carboxyl group is switched from the ring carbon to the ring nitrogen; (b) acyl (e.g. O-acyl) derivatives of the foregoing structures (or of the N-acid analogues of (a)); (c) dehydroxylated analogues of the foregoing structures (or of the N-acid analogues of (a) and (b)) in which one or more ring hydroxyl(s) are absent. 
     
     
         54 . A method of treating diabetes, obesity or disorders associated with metabolic syndrome in a patient, which method comprises administering to the patient the composition of  claim 47 . 
     
     
         55 . A method of treating hyperglycaemia, glucose intolerance, hyperinsulinaemia, glucosuria, metabolic acidosis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, macular degeneration, glomerulosclerosis, diabetic cardiomyopathy, insulin resistance, impaired glucose metabolism, arthritis, hypertension, hyperlipidemia, osteoporosis, osteopenia, bone loss, brittle bone syndromes, acute coronary syndrome, infertility, short bowel syndrome, chronic fatigue, eating disorders or intestinal motility dysfunction in a patient, which method comprises administering to the patient an imino sugar acid as defined in  claim 38 . 
     
     
         56 . A method of treating or preventing type 2 diabetes in a patient, which method comprises administering to the patient the imino sugar acid of  claim 38 . 
     
     
         57 . A method according to  claim 39  wherein the imino acid sugar acid is selected from the structures shown below: 
       
         
           
           
               
               
           
         
       
       or (a) N-acid analogues of the foregoing structures (G1)-(G4) in which the location of the carboxyl group is switched from the ring carbon to the ring nitrogen; (b) acyl (e.g. O-acyl) derivatives of the foregoing structures (or of the N-acid analogues of (a)); (c) dehydroxylated analogues of the foregoing structures (or of the N-acid analogues of (a) and (b)) in which one or more ring hydroxyl(s) are absent.