COMPOSITION, METHOD, AND KIT FOR ALPHA-1 PROTEINASE INHIBITOR
The present invention provides compositions comprising API and at least one amino acid, in particular a liquid API formulation comprising amino acids, and methods and kits related thereto. These amino acids when incorporated into the API composition afford stability to the API formulation.
1 . A composition comprising:
(a) an alpha 1-proteinase inhibitor (API); and
(b) at least one amino acid.
2 . The composition of claim 1 , wherein the at least one amino acid is present in the composition in a total amino acid amount sufficient such that the API retains at least 50% of its activity when the composition is exposed to a temperature for a period of time.
3 . The composition of claim 2 , wherein the temperature is about 5° C. to about 40° C.
4 . The composition of claim 2 , wherein the time is at least about 6 months.
5 . The composition of claim 1 , wherein the at least one amino acid is a neutral or a hydrophilic amino acid.
6 . The composition of claim 1 , wherein the at least one amino acid is selected from the group consisting of alanine, threonine, serine, hydroxyproline, glycine, proline, leucine, and histidine.
7 . The composition of claim 1 , wherein the amino acid is alanine.
8 . The composition of claim 1 , wherein the at least one amino acid is present in the composition in a total amino acid amount of about 0.01 M to about 3 M.
9 . The composition of claim 1 further comprising one or more excipients.
10 . The composition of claim 1 , wherein the one or more excipients is selected from the group consisting of: sucrose, mannitol, glycerol, sorbitol, dextran, trehalose, hydroxyethyl starch (HES), and 1,2-propanediol.
11 . The composition of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier.
12 . The composition of claim 1 , wherein the composition is suitable for intravenous administration to a subject.
13 . The composition of claim 1 , wherein the at least one amino acid is present in the composition in a total amino acid amount sufficient to maintain total protein aggregation at less than about 5% following exposure of the composition to a temperature for a period of time.
14 . The composition of claim 13 , wherein the temperature is about 25° C., wherein the period of time is about 6 months.
15 . The composition of claim 13 , wherein the temperature is about 5° C., wherein the period of time is about 6 months.
16 . The composition of claim 15 , wherein the at least one amino acid is present in the composition in a total amino acid amount sufficient to maintain total protein aggregation at less than about 2% following exposure of the composition to the temperature for the period of time.
17 . The composition of claim 13 , wherein the pH of the composition is about 6.3 to about 7.4.
18 . The composition of claim 13 , wherein the pH of the composition is about 6.7 to about 7.1.
19 . The composition of claim 1 , wherein the composition is in lyophilized form.
20 . A kit comprising the composition of claim 1 as a pharmaceutical composition suitable for intravenous administration.