Pharmaceutical formulations of nitrite and uses thereof

Abstract

The present invention relates to pharmaceutical compositions of nitrites such as inorganic nitrites, or any pharmaceutically acceptable salts, solvates, or prodrugs thereof, and the medical use of these compositions. The pharmaceutical compositions, which can be formulated for oral administration, can provide immediate release or extended release of the nitrite ion (NO 2 − ). The pharmaceutical compositions of the invention are useful, for example, for the treatment of chronic tissue ischemia.

What is claimed is: 
     
         1 - 18 . (canceled) 
     
     
         19 . A pharmaceutical composition for restoration of blood flow comprising:
 an effective amount of therapeutic, and   a pharmaceutically acceptable excipient,   wherein the therapeutic is inorganic nitrite, or a pharmaceutically acceptable salt, solvate, or prodrug thereof,
 administration of the pharmaceutical composition to a human results in a plasma concentration of nitrite ion that is maintained between 0.05 μM and 10 μM for up to 14 hours, 
 the pharmaceutical composition is administered in dosages of between 10 mg and 100 mg of therapeutic in a sustained release formulation. 
   
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein said plasma concentration is maintained between 0.05 μM and 1 μM. 
     
     
         21 . The pharmaceutical composition of  claim 19 , wherein the period of maintained plasma concentration occurs after the time of peak plasma concentration. 
     
     
         22 . The pharmaceutical composition of  claim 19 , wherein between 30-50% of a nitrite ion from the therapeutic is released in the first hour and the remainder of said nitrate ion is released in the following 2-14 hours. 
     
     
         23 . The pharmaceutical composition of  claim 19 , wherein said inorganic nitrite is administered at a dose that is between 0.05 mg-10 mg/kg weight of the human. 
     
     
         24 . The pharmaceutical composition of  claim 19 , wherein said pharmaceutical composition is formulated for oral administration. 
     
     
         25 . The pharmaceutical composition of  claim 19 , wherein the inorganic nitrite is administered at a dose that is between 0.05 mg-10 mg/kg weight of the human. 
     
     
         26 . The pharmaceutical composition of  claim 19  wherein the dosage of therapeutic is between 40 mg and 100 mg.
 is 
 
     
     
         27 . The pharmaceutical composition of  claim 19  wherein the dosage of therapeutic is between 50 mg and 100 mg. 
     
     
         28 . The pharmaceutical composition of  claim 19  wherein the dosage of therapeutic is 80 mg. 
     
     
         29 . A pharmaceutical composition for restoration of blood flow formulated for oral administration comprising:
 an effective amount of a therapeutic; and   a pharmaceutically acceptable enteric coating layer for delayed release of the inorganic nitrite, such that, when orally administered to a human subject, the inorganic nitrite is not substantially released in the stomach of said subject;   wherein the therapeutic is inorganic nitrite, or a pharmaceutically acceptable salt, solvate, or prodrug thereof;   administration of said pharmaceutical composition to a human results in a plasma concentration of nitrite ion that is maintained between 0.05 μM and 10 μM for up to 14 hours,   the pharmaceutical composition is administered in dosages of between 10 mg and 100 mg of therapeutic.   
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein the plasma concentration is maintained between 0.05 μM and 1 μM. 
     
     
         31 . The pharmaceutical composition of  claim 29 , wherein a period of maintained plasma concentration occurs after a time of peak plasma concentration. 
     
     
         32 . The pharmaceutical composition of  claim 29 , wherein between 30-50% of a nitrite ion of the therapeutic is released in a first hour and a remainder of the nitrate ion is released in a following 2-14 hours. 
     
     
         33 . The pharmaceutical composition of  claim 29 , wherein the inorganic nitrite is administered at a dose that is between 0.05 mg-10 mg/kg weight of the human. 
     
     
         34 . The pharmaceutical composition of  claim 29  wherein the dosage of therapeutic is between 40 mg and 100 mg. 
     
     
         35 . The pharmaceutical composition of  claim 29  wherein the dosage of therapeutic is between 50 mg and 100 mg. 
     
     
         36 . The pharmaceutical composition of  claim 29  wherein the dosage of therapeutic is 80 mg. 
     
     
         37 . A method for restoration of blood flow in a human, wherein said method comprises the administration of the pharmaceutical composition of  claim 19  to said human.