Human Growth Hormone Formulations

Abstract

Formulations containing complexed human growth hormone crystals are described. Also described are needleless injection systems for crystalline proteins.

1 .- 26 . (canceled) 
     
     
         27 . A hGH preparation comprising:
 poly-arginine complexed recombinant human growth hormone or human growth hormone derivative (hGH) crystals;   a buffer at a pH between about 6.1 to about 6.8;   a sodium salt; and   a suspending agent.   
     
     
         28 .- 29 . (canceled) 
     
     
         30 . A human growth hormone (hGH) preparation comprising:
 a suspension of hGH crystals coated with a polyelectrolyte;   a biologically compatible buffer having a pH range from about 5.0 to about 8.0;   a crystallinity promoting agent in an amount sufficient to maintain crystallinity of said hGH crystals; and   a tonicity modifier allowing for total osmolality of said preparation in the range of about 250 mOsm/kg to about 450 mOsm/kg.   
     
     
         31 . The hGH preparation of  claim 30 , further comprising a preservative. 
     
     
         32 . The hGH preparation of  claim 31 , wherein said preservative is phenol. 
     
     
         33 . The hGH preparation of  claim 32 , wherein said phenol is at a concentration of 0.2-0.3% w/v. 
     
     
         34 . The hGH preparation of  claim 30 , further comprising a chemical stabilizer. 
     
     
         35 . The hGH preparation of  claim 30 , wherein said a biologically compatible buffer has a buffer salt concentration in the range of 1 to 150 mM. 
     
     
         36 . The hGH preparation of  claim 35 , wherein said buffer salt is selected from the group consisting of acetate, triethanolamine, imidazole, phosphate, citrate, and Tris-HCl. 
     
     
         37 . The hGH preparation of  claim 30 , wherein said biologically compatible buffer comprises at least one of sodium phosphate and sodium citrate. 
     
     
         38 . The hGH preparation of  claim 30 , wherein said biologically compatible buffer comprises sodium phosphate. 
     
     
         39 . The hGH preparation of  claim 30 , wherein said crystallinity promoting agent comprises at least one of Sodium acetate and polyethylene glycol (PEG). 
     
     
         40 . The hGH preparation of  claim 30 , wherein said crystallinity promoting agent comprises PEG at about 1% w/v to about 25% w/v. 
     
     
         41 . The hGH preparation of  claim 30 , wherein said crystallinity promoting agent comprises phenol. 
     
     
         42 .- 48 . (canceled) 
     
     
         49 . The preparation of  claim 30 , further comprising hyaluronic acid. 
     
     
         50 .- 125 . (canceled) 
     
     
         126 . The hGH preparation of  claim 30 , wherein said crystallinity promoting agent comprises a suspending agent at about 2.5% to about 20%. 
     
     
         127 . The hGH preparation of  claim 126 , wherein said suspending agent comprises one or more of PEG, mannitol, glycine and sucrose. 
     
     
         128 . The hGH preparation of  claim 30 , wherein said polyelectrolyte is at least one of polyarginine, polylysine, and polyornithine. 
     
     
         129 . The hGH preparation of  claim 30 , wherein said tonicity modifier is selected from the group consisting of a neutral salt, sodium chloride, sodium acetate, Tris-HCL, a buffer salt outside of its working buffering pH range, a salt of an amino acid in the pH range outside its buffering pH range, glycine sodium salt, a polyol, and a polyethylene glycol. 
     
     
         130 . The hGH preparation of  claim 30 , wherein the crystalline hGH concentration is about 5 mg/ml to about 100 mg/mL. 
     
     
         131 . The hGH preparation of  claim 30 , wherein the preparation is disposed in a container containing at least one dose. 
     
     
         132 . The hGH preparation of  claim 27 , comprising said suspending agent at about 2.5% to about 20%. 
     
     
         133 . The hGH preparation of  claim 27 , wherein said suspending agent comprises one or more of PEG, mannitol, glycine and sucrose. 
     
     
         134 . The hGH preparation of  claim 27 , wherein said buffer is a phosphate buffer. 
     
     
         135 . The hGH preparation of  claim 27 , wherein said sodium salt comprises at least one of sodium chloride and sodium acetate at 60-200 mM. 
     
     
         136 . The hGH preparation of  claim 27 , wherein the crystalline hGH concentration is about 5 mg/ml to about 100 mg/mL.