Compositions of exendin-4 derivatives

Abstract

In one aspect, exendin-4 derivative compositions are provided. In some embodiments, unit dose forms and kits containing such compositions are also provided. In some embodiments, such compositions are useful for treatment of hyperinsulinemic hypoglycemia.

1 .- 18 . (canceled) 
     
     
         19 . A pharmaceutical composition for treating hyperinsulinemic hypoglycemia, the pharmaceutical composition comprising an exendin-4 derivative or a pharmaceutically acceptable salt thereof, wherein the exendin-4 derivative is selected from the group consisting of exendin(3-39), exendin(4-39), exendin(5-39), exendin(6-39), exendin(7-39), and exendin(8-39). 
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein the exendin-4 derivative is pegylated. 
     
     
         21 . The pharmaceutical composition of  claim 19 , wherein the exendin-4 derivative is exendin(5-39). 
     
     
         22 . The pharmaceutical composition of  claim 19 , wherein the pharmaceutically acceptable salt is a sulfate salt, a hypochloride salt, a phosphate salt, a sulfamate salt, an acetate salt, a citrate salt, a lactate salt, a tartarate salt, a methanesulfonate salt, an ethanesulfonate salt, a benzensulfonate salt, a p-toluenesulfonate salt, a cyclohexylsulfamate salt, or a quinate salt. 
     
     
         23 . The pharmaceutical composition of  claim 19 , further comprising a solvent. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the solvent is selected from the group consisting of a vegetable oil, an aliphatic acid glyceride, a aliphatic acid ester, and an propylene glycol ester. 
     
     
         25 . The pharmaceutical composition of  claim 19 , further comprising a pharmaceutically acceptable diluent selected from the group consisting of water, saline, an isotonic buffer solution. 
     
     
         26 . The pharmaceutical composition of  claim 19 , further comprising a solubilizer, an isotonic agent, a suspending agent, an emulsifying agent, a stabilizer, a preservative, a tonicity-modifying agent, a pH adjustment agent, or combinations thereof. 
     
     
         27 . The pharmaceutical composition of  claim 19 , wherein the composition comprises an exendin-4 derivative concentration of 4-50 mg/mL. 
     
     
         28 . The pharmaceutical composition of  claim 19 , wherein the exendin-4 derivative is administered at a dose of about 0.01 mg to about 50 mg. 
     
     
         29 . The pharmaceutical composition of  claim 19 , wherein the exendin-4 derivative is administered in a total volume of 0.25-2 mL. 
     
     
         30 . The pharmaceutical composition of  claim 19 , wherein the composition is formulated for subcutaneous administration. 
     
     
         31 . The pharmaceutical composition of  claim 19 , wherein the composition is formulated for immediate release. 
     
     
         32 . The pharmaceutical composition of  claim 19 , wherein the composition is formulated for extended release. 
     
     
         33 . The pharmaceutical composition of  claim 19 , wherein the composition is formulated as a sterile isotonic solution in a unit or multi-dose vial or ampule. 
     
     
         34 . The pharmaceutical composition of  claim 19 , wherein the composition is formulated as a sterile isotonic solution in a cartridge pen-injector device. 
     
     
         35 . The pharmaceutical composition of  claim 19 , wherein the composition is formulated as a sterile isotonic solution in a single-dose pen, wherein the single dose pen optionally comprises a diluent and one or more needles. 
     
     
         36 . A unit dose form of the pharmaceutical composition of  claim 19 . 
     
     
         37 . A kit comprising at least one unit dose form of  claim 36 . 
     
     
         38 . The kit of  claim 37 , further comprising at least one delivery device. 
     
     
         39 . The kit of  claim 37 , wherein the kit comprises a plurality of individual injectable pen devices, optionally wherein the individual injectable pen devices are pre-programmed to deliver a fixed unit dose. 
     
     
         40 . A method of treating hyperinsulinemic hypoglycemia, the method comprising administering a therapeutically effective amount of the pharmaceutical composition of  claim 19  to a patient in need thereof. 
     
     
         41 . The method of  claim 40 , wherein the patient has previously had gastrointestinal surgery. 
     
     
         42 . The method of  claim 40 , wherein the patient has previously had bariatric surgery. 
     
     
         43 . The method of  claim 42 , wherein the bariatric surgery is selected from the group consisting of Roux-en-Y Gastric Bypass, Vertical Sleeve Gastrectomy, placement of an endosleeve device, duodenal mucosal resurfacing, partial bypass of the duodenum, vagal nerve blockade, and pyloroplasty. 
     
     
         44 . The method of  claim 40 , wherein the patient has congenital hyperinsulinemic hypoglycemia.