Crystallized recombinant human growth factor formulations
Formulations containing complexed human growth hormone crystals are described. Also described are needleless injection systems for crystalline proteins.
1. An hGH pharmaceutical formulation comprising polyelectrolyte complexed crystallized recombinant hGH;
a biologically compatible buffer in the pH range of 5.4 to 7.0, selected from the group consisting of triethanolamine, imidazole, glycine, histidine, citrate, acetate, phosphate and tris, or a combination thereof, and
one or more additional components selected from the group consisting of a sodium salt having a sodium ion concentration in the range of 60-200 mM, a suspending agent, a chemical stabilizer, a surfactant, and a preservative, wherein the biologically compatible buffer and the one or more additional components are selected from the group consisting of:
10 mM Na Phosphate, 25 mM Tris, 100 mM NaAc, 5% PEG 6000, pH 6.5;
10 mM Na Phosphate, 0.25% Phenol, 150 mM NaCl, 5% PEG 6000, pH 6.0;
10 mM Na Citrate, 0,2% Tween 20, 0.25% Phenol, 150 mM NaCl, pH 6.0;
30 mM Triethanolamine, 100 mM Na Acetate, 5% PEG6000, pH 6.8;
25 mM Triethanolamine, 10 mM Methionine, 100 mM NaCl, 2% PEG3350, pH 6.8;
25 mM imidazole, 100 mM Na Acetate, 5% PEG6000, pH 6.5;
2 mM Na citrate, 8 mM Na phosphate, 120 mM NaCl, 0.3% Phenol, pH 6.0;
10 mM Na Phosphate, 100 mM Glycine, 0.3% phenol, pH 6.0;
10 mM Na Phosphate, 100 mM NaCl, 0.3% phenol, pH 6.0;
10 mM Na Phosphate, 100 mM Na acetate, 5% PEG 6000, pH 6.0;
10 mM Na Phosphate, 100 mM NaCI, 5% PEG 6000, pH 6.0;
10 mM Na Phosphate, 100 mM NaCl, 5% PEG 6000, pH 6.5;
2 mM Na citrate, 8 mM Na phosphate, 120 mM NaCI, 0.3% Phenol pH 5.4;
10 mM Na phosphate, 100 mM NaCl, 10% w/v PEG3350 pH 6.0;
10 mM Na citrate, 80 mM Na Glycine, 10% w/v PEG6000 pH 5.4; and
10 mM Na acetate, 120 mM NaCl, 10% w/v PEG6000 pH 5.6.
2. The hGH pharmaceutical formulation of claim 1 , further comprising a preservative.
3. The hGH pharmaceutical formulation of claim 2 , wherein the preservative is phenol, m-cresol, chlorobutanol, or benzyl alcohol.
4. The hGH pharmaceutical formulation of claim 1 , further comprising hyaluronic acid.
5. The hGH pharmaceutical formulation of claim 1 , further comprising an anti-microbial agent.
6. The hGH pharmaceutical formulation of claim 1 , further comprising a chemical stabilizer.