Human Growth Hormone Formulations
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.