A pharmaceutical preparation for improving absorption and postprandial hypoglycemic action of insulin

Abstract

The present disclosure relates to compositions and combinations comprising one or more insulin(s) and one or more vasoactive agent(s), and use thereof for increasing subcutaneous insulin absorption and/or treating diabetes and/or treating or preventing hyperglycemia or complications in a patient in need thereof.

1 . A method for treating diabetes comprising simultaneously administering subcutaneously to the same site in a subject in need thereof, a therapeutically effective amount of one or more insulins and a subcutaneously effective amount of one or more vasoactive agents. 
     
     
         2 . The method of  claim 1 , wherein said insulin is transformed insulin. 
     
     
         3 . The method of  claim 2 , wherein said insulin is a short-acting insulin analogues (SAIA). 
     
     
         4 . The method of  claim 1 , wherein said insulin is insulin lispro, insulin glulisine or insulin aspart. 
     
     
         5 . The method of  claim 1 , wherein said vasoactive agent is a prostacyclin IP 1  receptor agonist, a purinergic class 2 receptor agonist, a tachykinin receptor agonist, a histaminergic class 2 receptor agonist, a kinin B 2  receptor agonist, a potassium channel opener, or a combination thereof; or
 a combination of a nitrogen oxide donor and inhibitors of cyclic guanosine monophosphate phosphodiesterases; or an analog of cAMP or cGMP.   
     
     
         6 . The method of  claim 5 , wherein said vasoactive agent is prostacyclin IP 1  receptor agonist. 
     
     
         7 . The method of  claim 1 , wherein said subject is a human Type 2 diabetes (T2D) patient. 
     
     
         8 . The method of  claim 1 , wherein said subject is an obese human Type 2 diabetes (T2D) patient. 
     
     
         9 . The method of  claim 1  further comprising administering a therapeutically effective amount of at least one or more therapeutic that is a sulfonylurea, a meglitinide, a biguanide, a thiazolidinedione, a dipeptidyl peptidase-4 inhibitor, a glucagon-like peptide analog, a gastric inhibitory peptide analog, an inhibitor of renal sodium-dependent glucose cotransporters, or a combination thereof. 
     
     
         10 . A pharmaceutical composition comprising a therapeutically effective amount of one or more insulin(s) and a subcutaneously effective amount of one or more vasoactive agents. 
     
     
         11 . The composition of  claim 10 , wherein said insulin is transformed insulin. 
     
     
         12 . The composition of  claim 11 , wherein said insulin is a short-acting insulin analogues (SAIA). 
     
     
         13 . The composition of  claim 10 , wherein said insulin is insulin lispro, insulin glulisine or insulin aspart. 
     
     
         14 . The composition of  claim 10 , wherein said vasoactive agent is a prostacyclin IP 1  receptor agonist, a purinergic class 2 receptor agonist, a tachykinin receptor agonist, a histaminergic class 2 receptor agonist, a kinin B 2  receptor agonist, a potassium channel opener, or a combination thereof; or
 a combination of a nitrogen oxide donor and inhibitors of cyclic guanosine monophosphate phosphodiesterases; or   an analog of cAMP or cGMP.   
     
     
         15 . The composition of  claim 14  wherein said vasoactive agent is prostacyclin IP 1  receptor agonist. 
     
     
         16 .- 26 . (canceled) 
     
     
         27 . A method for the treatment or prevention of hyperglycemia comprising simultaneously administering subcutaneously to the same site in a subject in need thereof, a therapeutically effective amount of one or more insulins and a subcutaneously effective amount of one or more vasoactive agents.