STABILIZED GLUCAGON SOLUTIONS
A formulation composed of a sugar such as glucose and a surfactant such as myristoyl lysophosphocholine (LMPC) has been designed to stabilize both hydrophilic and hydrophobic portions of the glucagon molecule, under prolonged physiological conditions, in a formulation that is sufficiently similar to the pH and osmolarity of plasma so as not to induce or to minimize site irritation. The combination of a simple sugar and an surfactant stabilizes the glucagon molecule in an aqueous solution for seven days at 37° C.
1 . A stabilized glucagon formulation comprising
Glucagon,
A surfactant, and
A mono or disaccharide,
Wherein the surfactant and saccharide are in an effective amount to stabilize the glucagon, and
Wherein the osmolarity is approximately 250 to 310 mOs and the pH 4-7.5.
2 . The formulation of claim 1 wherein the surfactant is a lysophospholipid, phospholipid, glycerophospholipid or amphilic block copolymer.
3 . The formulation of claim 2 wherein the surfactant is myristoyl lysophosphocholine
4 . The formulation of claim 1 wherein the sugar is a monosaccharide or diasaccharide with an alkyl chain length ranged from C8 to C12.
5 . The formulation of claim 4 wherein the sugar is selected from the group consisting of lactose, maltose and glucose.
6 . The formulation of claim 1 further comprising a preservative.
7 . The formulation of claim 1 wherein the concentration range for the glucagon is between 0.5 and 5 mg/mL; sugar is between 20 and 100 mg/mL; and surfactant is between 0.1 and 10 mg/mL.
8 . The formulation of claim 7 wherein the concentration range for the glucagon is between 0.8 and 1.5 mg/mL; sugar is between 36 and 72 mg/mL, and surfactant is between 0.5 and 5 mg/mL.
9 . The formulation of claim 1 comprising a preservative in a concentration of between 0.2 and 3 mg/mL.
10 . The formulation of claim 1 comprising a microemulsion or liposome.
11 . The formulation of claim 1 comprising a reconstitutable powder.
12 . The formulation of claim 11 wherein the glucagon is provided in a two vial kit with one vial containing glucagon and a second vial containing diluent, wherein the glucagon is reconstituted with diluent immediately before use.
13 . The formulation of claim 1 wherein the glucagon is administered in a pump.
14 . The formulation of claim 1 wherein the glucagon is provided in a single vial as a solution.
15 . The formulation of claim 1 wherein the pH of the glucagon is in the physiological range.
16 . The formulation of claim 1 wherein the pH of the glucagon is in the acidic range.
17 . A method of making a stable glucagon solution comprising providing the formulation of claim 1 .
18 . A method of treating a patient in need thereof comprising administering the glucagon of claim 1 .