Methods for rapidly treating severe hypoglycemia
View Patent ↗Disclosed is a method for treating or preventing hypoglycemia in a patient comprising administering an effective amount of a composition comprising a glucagon peptide which has been dried in a non-volatile buffer, and wherein the glucagon peptide has a pH memory that is about equal to the pH of the glucagon peptide in the non-volatile buffer, and an aprotic polar solvent, wherein the moisture content of the formulation is less than 5%, and wherein the dried glucagon peptide maintains the pH memory that is about equal to the pH of the glucagon peptide in the non-volatile buffer when the dried glucagon peptide is reconstituted in the aprotic polar solvent, wherein the patient has been diagnosed as having a blood glucose level between 0 mg/dL and less than 50 mg/dL or has an indication of impending hypoglycemia based on a blood glucose monitoring device before administration of the composition, and wherein the patient has a blood glucose level greater than 50 mg/dL to 180 mg/dL within 1 to 20 minutes after administration of the composition.
1. A method for treating hypoglycemia in a patient comprising administering an effective amount of a composition consisting essentially of:
(a) about 0.45 wt. % of a glucagon peptide which has been dried in a non-volatile glycine buffer, and wherein the glucagon peptide has a pH memory that is about equal to the pH of the glucagon peptide in the non-volatile buffer, wherein the pH memory is between 2.5 to 3.5;
(b) about 92 wt. % to 96 wt. % of an aprotic polar solvent, wherein the peptide is solubilized in the aprotic polar solvent, and wherein the aprotic polar solvent is dimethyl sulfoxide (DMSO);
(c) about 3 wt. % to 7 wt. % of trehalose;
(d) about 0.01 wt. % of glycine; and
(e) optionally hydrochloric acid,
wherein the moisture content of the composition is less than 5 wt. %.
2. The method of claim 1 , wherein the pH memory of the glucagon peptide is about 3.0.
3. The method of claim 1 , wherein the composition is administered in an amount that provides from about 0.5 mg/mL to about 100 mg/mL of glucagon to the patient.
4. The method of claim 1 , wherein the patient's blood glucose level is between from 50 mg/dL to 70 mg/dL during administration of the composition.
5. The method of claim 1 , wherein the patient's blood glucose level is between from 50 mg/dL to 180 mg/dL within 1 to 10 minutes after administration of the composition.
6. The method of claim 5 , wherein the patient's blood glucose level is between from 50 mg/dL to 180 mg/dL within 1 to 5 minutes after administration of the composition.
7. The method of claim 1 , comprising administering the composition with a syringe.
8. The method of claim 1 , comprising administering the composition with a pen injection device, an auto-injector device, or with a pump.
9. The method of claim 1 , comprising administering the composition parenterally.
10. The method of claim 1 , comprising administering the composition intravenously.
11. The method of claim 1 , wherein the patient has Type I, Type II, or gestational diabetes.
12. The method of claim 1 , wherein the glucagon is not complexed with a metal ion.
13. The method of claim 12 , wherein the metal ion is a zinc cation.
14. The method of claim 1 , wherein the composition consists essentially of:
(a) about 0.45 wt. % of the glucagon peptide;
(b) about 94.54 wt. % of DMSO;
(c) about 5 wt. % % of trehalose;
(d) about 0.01 wt. % of glycine; and
(e) optionally hydrochloric acid.
15. The method of claim 14 , wherein the composition has hydrochloric acid.
16. The method of claim 1 , wherein the composition consists of:
(a) about 0.45 wt. % of the glucagon peptide;
(b) about 94.54 wt. % of DMSO;
(c) about 5 wt. % % of trehalose;
(d) about 0.01 wt. % of glycine; and
(e) optionally hydrochloric acid.
17. The method of claim 16 , wherein the composition has hydrochloric acid.