Method of synergistically enhancing the therapeutic efficacy and safety of medications through a combination therapy

Abstract

The present invention provides combinations, for treatment of subjects suffering from or at high risk of developing diseases and disorders involving expression of peroxisome proliferator-activated receptors (PPAR). The combinations include abscisic acid and one other bioactive agent, which together provide synergistic effects toward treatment or blocking of development of the disease or disorder. In exemplary embodiments, a combination of abscisic acid and a thiazolidinedione (TZD) is provided for increased insulin sensitivity and improved (i.e., reduced) obesity-induced inflammation.

1 . A composition for enhancing the efficiency of a an anti-diabetic compound, the composition comprising:
 abscisic acid;   an anti-diabetic compound; and   a carrier suitable for administration to a mammal.   
   
   
       2 . The composition of  claim 1 , wherein the anti-diabetic compound is a PPAR γ agonist, a glitazar, a conjugated linoleic acid, a dual PPAR α/γ agonist, a glucagon-like peptide 1 receptor agonist, or a biguanidine. 
   
   
       3 . The composition of  claim 2 , wherein the PPAR γ agonist is a thiazolidinedione. 
   
   
       4 . The composition of  claim 3 , wherein the thiazolidinedione is selected from rosiglitazone, pioglitazone and combinations thereof. 
   
   
       5 . The composition of  claim 2 , wherein the biguanidine is selected from metformin, glucophage and combinations thereof. 
   
   
       6 . The composition of  claim 1 , wherein the carrier is a pharmaceutically acceptable carrier. 
   
   
       7 . The composition of  claim 1 , wherein the carrier is a food, a nutritional supplement or a dietary aid. 
   
   
       8 . A composition for enhancing the efficiency of a cardioprotective compound, the composition comprising:
 abscisic acid;   a cardioprotective compound; and   a carrier suitable for administration to a mammal.   
   
   
       9 . The composition of  claim 8 , wherein the cardioprotective compound is selected from a PPAR α agonist, a guanylate cyclase activator, an angiotensin converting enzyme inhibitor, an angiotensin II type 1 blocker or a lipid-lowering drug. 
   
   
       10 . The composition of  claim 9 , wherein the PPAR α agonist is a fibrate. 
   
   
       11 . The composition of  claim 9 , wherein the lipid-lowering drug is a statin. 
   
   
       12 . The composition of  claim 11 , wherein the statin is atorvastatin calcium. 
   
   
       13 . The composition of  claim 8 , wherein the carrier is a pharmaceutically acceptable carrier. 
   
   
       14 . The composition of  claim 8 , wherein the carrier is a food, a nutritional supplement or a dietary aid. 
   
   
       15 . A composition for enhancing the efficiency of a an anti-inflammatory compound, the composition comprising:
 abscisic acid;   an anti-inflammatory compound; and   a carrier suitable for administration to a mammal.   
   
   
       16 . The composition of  claim 15 , wherein the anti-inflammatory compound is a conjugated linoleic acid, a non-steroidal anti-inflammatory drug or a steroidal anti-inflammatory drug. 
   
   
       17 . The composition of  claim 16 , wherein the non-steroidal anti-inflammatory drug is selected from acetylsalicyclic acid, acetaminophen, ibuprofen, paracetamol and combinations thereof. 
   
   
       18 . The pharmaceutical composition of  claim 16 , wherein the steroidal anti-inflammatory drug is selected from prednisone, predinsolone, cortisone and combinations thereof. 
   
   
       19 . The composition of  claim 15 , wherein the carrier is a pharmaceutically acceptable carrier. 
   
   
       20 . The composition of  claim 15 , wherein the carrier is a food, a nutritional supplement or a dietary aid. 
   
   
       21 . A method of enhancing the efficacy of one or more anti-diabetic compounds while maintaining or decreasing their doses, said method comprising: administering the anti-diabetic drugs in combination with abscisic acid. 
   
   
       22 . The method of  claim 21 , wherein the anti-diabetic compound is a PPAR γ agonist, a glitazar, a conjugated linoleic acid, a dual PPAR α/γ agonist, a glucagon-like peptide 1 receptor agonist, or a biguanidine. 
   
   
       23 . A method of enhancing the efficacy of cardioprotective compounds while maintaining or decreasing their doses, said method comprising: administering the drugs or compounds in combination with abscisic acid. 
   
   
       24 . The method of  claim 23 , wherein the cardioprotective compound is selected from a PPAR α agonist, a guanylate cyclase activator, an angiotensin converting enzyme inhibitor, an angiotensin II type 1 blocker or a lipid-lowering drug. 
   
   
       25 . A method of enhancing the efficacy of anti-inflammatory compounds while maintaining or decreasing their doses, said method comprising: administering the drugs or compounds in combination with abscisic acid. 
   
   
       26 . The composition of  claim 25 , wherein the anti-inflammatory compound is a conjugated linoleic acid, a non-steroidal anti-inflammatory drug or a steroidal anti-inflammatory drug. 
   
   
       27 . A method of altering the expression or activity of PPAR γ in a cell, the method comprising:
 contacting the cell with a combination of abscisic acid and a thiazolidinedione in a combined amount that is sufficient to alter the expression or activity of PPAR γ in the cell.   
   
   
       28 . The method of  claim 27 , which is a method of treating a subject having or having a predisposition to develop a disease or disorder involving expression or activity of PPAR γ. 
   
   
       29 . The method of  claim 28 , which is a prophylactic method that reduces or eliminates development of the disease or disorder in a subject not showing clinical signs of the disease or disorder. 
   
   
       30 . The method of  claim 27 , wherein the combination is a nutritional supplement, a functional food, or dietary aid. 
   
   
       31 . A method of increasing insulin sensitivity and improving obesity-induced inflammation in at least one cell of a mammal, the method comprising:
 contacting the cell with a combination of abscisic acid and a thiazolidinedione in a combined amount that is sufficient to alter the expression or activity of PPAR γ in the cell.   
   
   
       32 . The method of  claim 32 , wherein the abscisic acid and thiazolidinedione are the predominant biologically active agents contacted with the cell to result in increased insulin sensitivity and improved obesity-induced inflammation. 
   
   
       33 . The method of  claim 31 , which is a prophylactic method that reduces or eliminates development of a disease or disorder in a subject not showing clinical signs of the disease or disorder. 
   
   
       34 . The method of  claim 31 , wherein the combination is a nutritional supplement, a functional food, or dietary aid. 
   
   
       35 . A method for decreasing apoptosis of pancreatic beta cells in a mammalian subject, the method comprising administering to the subject the composition of  claim 1 . 
   
   
       36 . A method for increasing insulin secretion of pancreatic beta cells in a mammalian subject, the method comprising administering to the subject the composition of  claim 1 .