GRAS COMPOSITION FOR INTRANASAL DELIVERY OF PARATHYROID HORMONE
What is described is an aqueous pharmaceutical composition for intranasal delivery of PTH, comprising a PTH molecule, and one or more excipients selected from the group consisting of a chelating agent, an alcohol, and a surface active agent, wherein the PTH molecule selected from the group consisting of SEQ NO: 1, SEQ NO: 2, and SEQ NO: 3.
1 . A pharmaceutical composition for intranasal delivery comprising an aqueous solution of a PTH, a polyoxyethylene sorbitan ester, a polyol, and chlorobutanol, wherein the composition has greater than about 6% bioavailability of the PTH upon intranasal administration of the composition to a human.
2 . The pharmaceutical composition of claim 1 , wherein the composition has greater than about 8% bioavailability of the PTH upon intranasal administration of the composition to a human.
3 . The pharmaceutical composition of claim 1 , wherein the PTH is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3.
4 . The pharmaceutical composition of claim 1 , wherein the polyoxyethylene sorbitan ester is polysorbate 80 or polysorbate 20.
5 . The pharmaceutical composition of claim 4 , wherein the polysorbate 80 is present at 1 mg/mL or lower in the composition.
6 . The pharmaceutical composition of claim 1 , wherein the polyol is selected from sucrose, mannitol, sorbitol, lactose, L-arabinose, D-erythrose, D-ribose, D-xylose, D-mannose, trehalose, D-galactose, lactulose, cellobiose, gentibiose, glycerin and polyethylene glycol.
7 . The pharmaceutical composition of claim 1 , wherein the composition has a pH of from about 3 to about 6.
8 . The pharmaceutical composition of claim 1 , wherein the composition is in the form of liquid droplets.
9 . The pharmaceutical composition of claim 8 , wherein the liquid droplets have an average volume-mean particle size (Dv,50) of from about 1 micron to about 1000 microns.
10 . The pharmaceutical composition of claim 8 , where in the liquid droplets have an average volume-mean particle size (Dv,50) of from about 5 microns to about 500 microns.
11 . The pharmaceutical composition of claim 8 , where in the liquid droplets have an average volume-mean particle size (Dv,50) of from about 10 microns to about 100 microns.
12 . A method for treating osteoporosis or osteopenia in a human subject comprising administering intranasally to the human a pharmaceutical composition of claim 1 .
13 . The method of claim 12 , wherein upon intranasal administration to the human subject the PTH has a maximum serum concentration, Cmax, of about 100 pg/mL or greater.
14 . The method of claim 12 , wherein the dose of PTH administered to the human subject is from about 1 microgram to about 2000 microgram.
15 . A method for preventing the onset of osteoporosis or osteopenia in a human subject comprising administering intranasally to the human a pharmaceutical composition of claim 1 .