Vasopressin formulations for use in treatment of hypotension

Abstract

Provided herein are peptide formulations comprising polymers as stabilizing agents. The peptide formulations can be more stable for prolonged periods of time at temperatures higher than room temperature when formulated with the polymers. The polymers used in the present invention can decrease the degradation of the constituent peptides of the peptide formulations.

1 - 15 . (canceled) 
     
     
         16 . A method for increasing blood pressure in a subject in need thereof, the method comprising
 a) providing a pharmaceutical composition comprising:
 20 units/mL vasopressin, or a pharmaceutically acceptable salt thereof; 
 a pharmaceutically acceptable excipient which is acetic acid, acetate, or a combination thereof; 
 optionally chlorobutanol; and 
 water, 
 wherein the pharmaceutical composition is at a pH of about 3.5 to about 4.1, and 
 the purity of vasopressin is at least 97% by HPLC; 
   b) diluting the pharmaceutical composition with a diluent to provide a concentration from 0.1 units/mL to 1 unit/mL vasopressin, or a pharmaceutically acceptable salt thereof, wherein the diluent is about 0.9% sodium chloride or about 5% dextrose;   c) intravenously administering the diluted pharmaceutical composition to the subject.   
     
     
         17 . The method of  claim 16 , wherein the purity of vasopressin in the pharmaceutical composition is at least 98% by HPLC. 
     
     
         18 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 2 at an amount of about 0.1% by mass of vasopressin. 
     
     
         19 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 2 at an amount of about 0.2% by mass of vasopressin. 
     
     
         20 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 2 at an amount of about 0.5% by mass of vasopressin. 
     
     
         21 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 2 at an amount of about 0.6% by mass of vasopressin. 
     
     
         22 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 2 at an amount of about 0.7% by mass of vasopressin. 
     
     
         23 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 2 at an amount of about 0.8% by mass of vasopressin. 
     
     
         24 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 4 at an amount of about 0.1% by mass of vasopressin. 
     
     
         25 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 4 at an amount of about 0.5% by mass of vasopressin. 
     
     
         26 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 4 at an amount of about 0.6% by mass of vasopressin. 
     
     
         27 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 4 at an amount of about 0.7% by mass of vasopressin. 
     
     
         28 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 4 at an amount of about 0.8% by mass of vasopressin. 
     
     
         29 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 4 at an amount of about 0.9% by mass of vasopressin. 
     
     
         30 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 3 at an amount of less than about 0.1% by mass of vasopressin. 
     
     
         31 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 3 at an amount of about 0.1% by mass of vasopressin. 
     
     
         32 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 3 at an amount of about 0.2% by mass of vasopressin. 
     
     
         33 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 7 at an amount of about 0.2% to about 0.3% by mass of vasopressin. 
     
     
         34 . The method of  claim 16 , wherein the pharmaceutical composition further comprises a peptide of SEQ. ID. NO.: 10 at an amount of about 0.3% to about 0.4% by mass of vasopressin. 
     
     
         35 . The method of  claim 16 , wherein the pharmaceutical composition is at a pH of about 3.5. 
     
     
         36 . The method of  claim 16 , wherein the pharmaceutical composition is at a pH of about 3.6. 
     
     
         37 . The method of  claim 16 , wherein the pharmaceutically acceptable excipient in the pharmaceutical composition is acetic acid. 
     
     
         38 . The method of  claim 16 , wherein the pharmaceutically acceptable excipient in the pharmaceutical composition is acetate. 
     
     
         39 . The method of  claim 16 , wherein the pharmaceutically acceptable excipient in the pharmaceutical composition is a combination of acetic acid and acetate. 
     
     
         40 . The method of  claim 16 , wherein the subject has a hypotension associated with vasodilatory shock. 
     
     
         41 . The method of  claim 40 , wherein the vasodilatory shock is post-cardiotomy shock or septic shock. 
     
     
         42 . The method of  claim 16 , wherein the intravenous administration provides to the subject from about 0.01 units/minute to about 0.1 units/minute vasopressin, or a pharmaceutically acceptable salt thereof. 
     
     
         43 . The method of  claim 42 , wherein the intravenous administration further comprises titrating up by 0.005 units/minute vasopressin, or a pharmaceutically acceptable salt thereof, at 10- to 15-minute intervals before achieving a target blood pressure response. 
     
     
         44 . The method of  claim 42 , wherein the intravenous administration further comprises attaining a target blood pressure in the subject and continuing the administration for a period of about 8 hours. 
     
     
         45 . The method of  claim 44 , wherein the intravenous administration further comprises, after the period of about 8 hours, reducing the administration by about 0.005 units/minute vasopressin, or a pharmaceutically acceptable salt thereof.