Incretin analog-containing compositions and uses thereof
A composition is provided that includes an incretin analog having activity at each the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors (i.e., tri-receptor agonist) and one or more additional agents such as a tonicity agent and a preservative. Methods also are provided for treating diseases such as type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and obesity with the composition.
1 . A pharmaceutical composition comprising:
an incretin analog comprising SEQ ID NO:1, or pharmaceutically acceptable salt thereof at a concentration from about 1 mg/mL to about 30 mg/mL;
a tris(hydroxymethyl)aminomethane (TRIS) buffer at a concentration from about 10 mM to about 100 mM;
mannitol at a concentration from about 10 mg/mL to about 100 mg/mL; and
an optional preservative selected from the group consisting of m-cresol and phenol;
wherein the pharmaceutical composition has a pH of about 6.5 to about 7.5.
2 . The pharmaceutical composition of claim 1 , wherein the mannitol is at a concentration of about 48 mg/mL.
3 . The pharmaceutical composition of claim 1 , wherein the optional preservative is m-cresol and is at a concentration of from about 1 mg/mL to about 10 mg/mL.
4 . The pharmaceutical composition of claim 3 , wherein the m-cresol is at a concentration of 3.15 mg/mL.
5 . The pharmaceutical composition of claim 1 , wherein the optional preservative is phenol and is at a concentration of from about 1 mg/mL to about 10 mg/mL.
6 . The pharmaceutical composition of claim 5 , wherein the phenol is at a concentration of 5 mg/mL.
7 . The pharmaceutical composition of claim 1 , wherein the incretin analog is at a concentration selected from the group consisting of 1 mg/mL, 2 mg/mL, 3 mg/mL, 4 mg/mL, 5 mg/mL, 6 mg/mL, 8 mg/mL, 9 mg/mL, 12 mg/mL, 18 mg/mL, 24 mg/mL and 30 mg/mL.
8 . The pharmaceutical composition of claim 1 , wherein the TRIS buffer is at a concentration of about 10 mM.
9 . The pharmaceutical composition of claim 1 further comprising ethylenediaminetetraacetic acid (EDTA) at a concentration of 0.3 mg/mL.
10 . The pharmaceutical composition of claim 1 , wherein mannitol is at a concentration of 48 mg/mL.
11 . The pharmaceutical composition of claim 10 , wherein the incretin analog or pharmaceutically acceptable salt thereof is at a concentration selected from the group consisting of 1 mg/mL, 2 mg/mL, 3 mg/mL, 4 mg/mL, 5 mg/mL, 6 mg/mL, 8 mg/mL, 9 mg/mL, 12 mg/mL, 18 mg/mL, 24 mg/mL and 30 mg/mL.
12 . The pharmaceutical composition of claim 1 further comprising a preservative selected from the group consisting of m-cresol and phenol, wherein the preservative is at a concentration of about 1 mg/mL to about 10 mg/mL.
13 . The pharmaceutical composition of claim 1 further comprising a pharmaceutically acceptable carrier, diluent or excipient.
14 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable salt is a sodium salt.
15 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable salt is a tetra sodium salt.
16 . A method of treating diabetes comprising the step of:
administering to an individual in need thereof an effective dose of the pharmaceutical composition of claim 1 .
17 . The method of claim 16 , wherein the effective dose is administered using an automatic injection apparatus.
18 . The method of claim 16 , wherein the effective dose is administered once weekly.
19 . A method of treating obesity comprising the step of:
administering to an individual in need thereof an effective dose of the pharmaceutical composition of claim 1 .
20 . The method of claim 19 , wherein the effective dose is administered using an automatic injection apparatus.
21 . The method of claim 19 , wherein the effective dose is administered once weekly.
22 . An article of manufacture comprising the pharmaceutical composition of claim 1 , wherein the article of manufacture is selected from a multiuse vial, a reusable pen injector, a pre-filled disposable pen, an autoinjector, and a pump.
23 . The method of claim 21 , wherein the volume of the pharmaceutical composition administered is about 0.5 mL.
24 . A pharmaceutical composition comprising:
an incretin analog comprising SEQ ID NO:1, or pharmaceutically acceptable salt thereof at a concentration from about 1 mg/mL to about 30 mg/ml;
a tris(hydroxymethyl)aminomethane (TRIS) buffer at a concentration of about 10 mM;
mannitol at a concentration of about 48 mg/mL; and
an optional preservative selected from the group consisting of m-cresol and phenol;
wherein the pharmaceutical composition has a pH of about 7.5.
25 . A pharmaceutical composition comprising:
an incretin analog comprising SEQ ID NO:1, or pharmaceutically acceptable salt thereof, at a concentration from about 1 mg/mL to about 30 mg/ml;
a tris(hydroxymethyl)aminomethane (TRIS) buffer at a concentration of about 10 mM;
mannitol at a concentration from about 10 mg/mL to about 100 mg/ml; and
phenol at a concentration of about 5 mg/ml;
wherein the pharmaceutical composition has a pH of about 7.5.