STABLE GLUCAGON FORMULATIONS FOR THE TREATMENT OF HYPOGLYCEMIA
The delivery of biopharmaceutical and other therapeutic agents parenterally to an animal via a minimally invasive, low pain administration is provided. The agents are delivered to the patient via, e.g., the epidermal, dermal, or subcutaneous layer of the skin in a concentrated form of injectable glucagon that is dissolved in a pharmaceutically acceptable carrier.
1 . A stable glucagon composition, said composition comprising: glucagon or a glucagon analog that has been dried with a carbohydrate and a buffer having a pH of about 2.0 to about 3.5.
2 . The stable glucagon composition of claim 1 , wherein said glucagon composition is reconstituted with a pharmaceutically acceptable carrier.
3 . The stable glucagon composition of claim 2 , wherein said pharmaceutically acceptable carrier is an aqueous carrier.
4 . The stable glucagon composition of claim 2 , wherein said pharmaceutically acceptable carrier is a non-aqueous carrier selected from the group consisting of lipids, aryl benzonates, alkyl benzonates and triacetin.
5 . The stable glucagon composition of claim 3 , wherein said aqueous carrier is water.
6 . The stable glucagon composition of claim 2 , wherein said glucagon composition is mixed with said pharmaceutically acceptable carrier to form a suspension.
7 . The stable glucagon composition of claim 2 , wherein said glucagon composition is mixed with said pharmaceutically acceptable carrier to form a paste.
8 . The stable glucagon composition of claim 4 , wherein said non-aqueous carrier is selected from the group consisting of triacetin, benzyl benzoate, miglyol, palm oil and mineral oil.
9 . The stable glucagon composition of claim 1 , wherein said buffer has a pH of about 3.0.
10 . The stable glucagon composition of claim 1 , wherein said buffer is selected from a glycine buffer, a citrate buffer, a phosphate buffer and mixture thereof.
11 . The stable glucagon composition of claim 10 , wherein said buffer is a glycine buffer.
12 . The stable glucagon composition of claim 10 , wherein said buffer is a citrate buffer.
13 . The stable glucagon composition of claim 1 , wherein said carbohydrate is selected from the group consisting of sugars and starches.
14 . The stable glucagon composition of claim 13 , wherein said carbohydrate is selected from the group consisting of trehalose, hydroxyethyl starch (HES), dextran and mixtures thereof.
15 . The stable glucagon composition of claim 14 , wherein said carbohydrate is trehalose.
16 . The stable glucagon composition of claim 14 , wherein said carbohydrate is hydroxyethyl starch (HES).
17 . The stable glucagon composition of claim 14 , wherein said carbohydrate is a mixture of trehalose and hydroxyethyl starch (HES).
18 . The stable glucagon composition of claim 1 , further comprising a surfactant.
19 . The stable glucagon composition of claim 18 , wherein said surfactant is polysorbate 20 (Tween® 20).
20 . The stable glucagon composition of claim 1 , further comprising an antioxidant.
21 . The stable glucagon composition of claim 20 , wherein the antioxidant is selected from the group consisting of ascorbic acid, cysteine, methionine, monothioglycerol, sodium thiosulphate, sulfites, BHT, BHA, ascorbyl palmitate, propyl gallate, and Vitamin E.
22 . The stable glucagon composition of claim 1 , further comprising a chelator.
23 . The stable glucagon composition of claim 22 , wherein the chelator is selected from the group consisting of EDTA, tartaric acid and salts thereof, glycerin, and citric acid and salts thereof.
24 . The stable glucagon composition of claim 1 , further comprising a preservative.
25 . The stable glucagon composition of 24 , wherein in the preservative is selected from the group consisting of benzyl alcohols, methyl parabens and propyl parabens.
26 . A stable pharmaceutical formulation for parenteral injection, said pharmaceutical formulation comprising: glucagon or a glucagon analog that has been dried with a carbohydrate and a buffer having a pH of about 2.0 to about 3.5, and a pharmaceutically acceptable carrier or diluent.
27 . A method for treating a disease, condition or disorder that may be treated, alleviated or prevented by administering to a subject the pharmaceutical formulation of claim 26 in an amount effective to treat, alleviate or prevent the disease, condition or disorder.
28 . The method of claim 27 , wherein the disease, condition or disorder comprises hypoglycemia.
29 . The method of claim 27 , wherein said administration is accomplished via use of a pen injection device.
30 . The method of claim 27 , wherein said administration is accomplished via use of an auto-injector device.
31 . The use of the pharmaceutical formulation of claim 26 for the treatment of a disease, condition or disorder that may be treated, alleviated or prevented by administering a glucagon or glucagon analog.
32 . The use of claim 31 , wherein the disease, condition or disorder is hypoglycemia.
33 . The use of any one of claims 31 , wherein the administration is parenteral administration.
34 . The use of claim 31 , wherein said administration is accomplished via use of a pen injection device.
35 . The use of claim 31 , wherein said administration is accomplished via use of a auto-injector device.
36 . A stable pharmaceutical formulation for parenteral injection, said pharmaceutical formulation consisting essentially of glucagon or a glucagon analog that has been dried with a carbohydrate and a buffer having a pH of about 2.0 to about 3.5, and a pharmaceutically acceptable carrier or diluent.
37 . A method for treating hypoglycemia in a subject in need thereof, said method comprising administering to said subject the pharmaceutical formulation of claim 26 in an amount effective to treat hypoglycemia.