Long-Acting Formulations of Insulin
The application relates to an aqueous pharmaceutical formulation comprising 200-1000 U/mL [equimolar to 200-1000 IU human insulin] of insulin glargine.
1 . An aqueous pharmaceutical formulation comprising 270-330 U/mL of insulin glargine [equimolar to 270-330 IU human insulin].
2 . The aqueous pharmaceutical formulation of claim 1 further comprising at least one excipient selected from the group consisting of zinc, m-cresol, glycerol, and polysorbate 20.
3 . The aqueous pharmaceutical formulation of claim 2 further comprising 90 μg/mL zinc, 2.7 mg/mL m-cresol, and 20 mg/mL glycerol 85%.
4 . The aqueous pharmaceutical formulation of claim 3 , wherein the zinc is present in the form of zinc chloride.
5 . The aqueous pharmaceutical formulation of claim 2 further comprising 90 μg/mL zinc, 2.7 mg/mL m-cresol, 20 μg/mL polysorbate 20, and 20 mg/mL glycerol 85%.
6 . The aqueous pharmaceutical formulation of claim 5 , wherein the zinc is present in the form of zinc chloride.
7 . The aqueous pharmaceutical formulation of claim 1 , wherein the pH of the aqueous pharmaceutical formulation is between 3.4 and 4.6.
8 . The aqueous pharmaceutical formulation of claim 7 , wherein the pH of the aqueous pharmaceutical formulation is 4.0.
9 . An aqueous pharmaceutical formulation comprising 270-330 U/mL of insulin glargine [equimolar to 270-330 IU human insulin] wherein the pH of the aqueous pharmaceutical formulation is between 3.4 and 4.6.
10 . The aqueous pharmaceutical formulation of claim 9 , wherein the pH of the aqueous pharmaceutical formulation is 4.0.
11 . The aqueous pharmaceutical formulation of claim 9 further comprising at least one excipient selected from the group consisting of zinc, m-cresol, glycerol, and polysorbate 20.
12 . The aqueous pharmaceutical formulation of claim 11 further comprising 90 μg/mL zinc, 2.7 mg/mL m-cresol, and 20 mg/mL glycerol 85%.
13 . The aqueous pharmaceutical formulation of claim 12 , wherein the zinc is present in the form of zinc chloride.
14 . The aqueous pharmaceutical formulation of claim 11 further comprising 90 μg/mL zinc, 2.7 mg/mL m-cresol, 20 μg/mL polysorbate 20, and 20 mg/mL glycerol 85%.
15 . The aqueous pharmaceutical formulation of claim 14 , wherein the zinc is present in the form of zinc chloride.
16 . An aqueous pharmaceutical formulation comprising 270-330 U/mL of insulin glargine [equimolar to 270-330 IU human insulin], 90 μg/mL zinc chloride, 2.7 mg/mL m-cresol, and 20 mg/mL glycerol 85%, wherein the pH of the aqueous pharmaceutical formulation is 4.0.
17 . An aqueous pharmaceutical formulation comprising 270-330 U/mL of insulin glargine [equimolar to 270-330 IU human insulin], 90 μg/mL zinc chloride, 2.7 mg/mL m-cresol, 20 μg/mL polysorbate 20, and 20 mg/mL glycerol 85%, wherein the pH of the aqueous pharmaceutical formulation is 4.0.
18 . An aqueous pharmaceutical formulation comprising 270-330 U/mL of insulin glargine [equimolar to 270-330 IU human insulin], wherein the pharmacokinetic profile and the pharmacodynamic profile of the 270-330 U/mL aqueous pharmaceutical formulation are flatter than the pharmacokinetic profile and the pharmacodynamic profile of an aqueous pharmaceutical formulation comprising 100 U/mL of insulin glargine, and wherein the pH of the 270-330 U/mL aqueous pharmaceutical formulation is between 3.4 and 4.6.
19 . The aqueous pharmaceutical formulation of claim 18 , wherein the pH of the aqueous pharmaceutical formulation is 4.0.
20 . The aqueous pharmaceutical formulation of claim 18 further comprising at least one excipient selected from the group consisting of zinc, m-cresol, glycerol, and polysorbate 20.
21 . The aqueous pharmaceutical formulation of claim 20 further comprising 90 μg/mL zinc, 2.7 mg/mL m-cresol, and 20 mg/mL glycerol 85%.
22 . The aqueous pharmaceutical formulation of claim 21 , wherein the zinc is present in the form of zinc chloride.
23 . The aqueous pharmaceutical formulation of claim 20 further comprising 90 μg/mL zinc, 2.7 mg/mL m-cresol, 20 μg/mL polysorbate 20, and 20 mg/mL glycerol 85%.
24 . The aqueous pharmaceutical formulation of claim 23 , wherein the zinc is present in the form of zinc chloride.
25 . An aqueous pharmaceutical formulation comprising 270-330 U/mL of insulin glargine [equimolar to 270-330 IU human insulin] providing a peakless long acting basal insulin, wherein the pH of the aqueous pharmaceutical formulation is between 3.4 and 4.6.
26 . An aqueous pharmaceutical formulation comprising 270-330 U/mL of insulin glargine [equimolar to 270-330 IU human insulin] exhibiting an extended duration of exposure of insulin glargine than an aqueous pharmaceutical formulation comprising 100 U/mL insulin glargine, wherein the pH of the 270-330 U/mL aqueous formulation is between 3.4 and 4.6.
27 . The aqueous pharmaceutical formulation of claim 1 further comprising an analogue of exendin-4.
28 . The aqueous pharmaceutical formulation of claim 27 , wherein the analogue of exendin-4 is selected from the group consisting of lixisenatide, exenatide, and liraglutide.
29 . The aqueous pharmaceutical formulation of claim 28 comprising 0.1 μg to 10 μg lixisenatide per Unit insulin glargine.
30 . The aqueous pharmaceutical formulation of claim 29 comprising 0.2 to 1 μg lixisenatide per Unit insulin glargine
31 . The aqueous pharmaceutical formulation of claim 30 comprising 0.25 μm to 0.7 g lixisenatide per Unit insulin glargine.
32 . A method of treating Type I or Type II Diabetes Mellitus in a patient in need thereof comprising subcutaneously administering to the patient an aqueous pharmaceutical formulation comprising 270-330 U/mL of insulin glargine [equimolar to 270-330 IU human insulin].
33 . The method of claim 32 , wherein the aqueous pharmaceutical formulation further comprises at least one excipient selected from the group consisting of zinc, m-cresol, glycerol, and polysorbate 20.
34 . A method of extending the duration of exposure of a long acting insulin in the treatment of Type I or Type II Diabetes Mellitus in a patient in need thereof comprising subcutaneously administering to the patient an aqueous pharmaceutical formulation comprising 270-330 U/mL insulin glargine [equimolar to 270-330 IU human insulin].
35 . The method of claim 34 , wherein the aqueous pharmaceutical formulation further comprises at least one excipient selected from the group consisting of zinc, m-cresol, glycerol, and polysorbate 20.
36 . A method of reducing the incidence of hypoglycaemia in the treatment of Type I or Type II Diabetes Mellitus in a patient in need thereof comprising subcutaneously administering to the patient an aqueous pharmaceutical formulation comprising 270-330 U/mL insulin glargine [equimolar to 270-330 IU human insulin].
37 . The method of claim 36 , wherein the aqueous pharmaceutical formulation further comprises at least one excipient selected from the group consisting of zinc, m-cresol, glycerol, and polysorbate 20.
38 . A method of providing a peakless long acting basal insulin in the treatment of Type I or Type II Diabetes Mellitus in a patient in need thereof comprising subcutaneously administering to the patient an aqueous pharmaceutical formulation comprising 270-330 U/mL insulin glargine [equimolar to 270-330 IU human insulin].
39 . The method of claim 38 , wherein the aqueous pharmaceutical formulation further comprises at least one excipient selected from the group consisting of zinc, m-cresol, glycerol, and polysorbate 20.
40 . The method of any one of claims 32 , 34 , 36 , or 38 , wherein the aqueous pharmaceutical formulation is administered once daily.
41 . The method of any one of claims 33 , 35 , 37 , or 39 , wherein the aqueous pharmaceutical formulation further comprises 90 μg/mL zinc, 2.7 mg/mL m-cresol, and 20 mg/mL glycerol 85%.
42 . The method of any one of claims 33 , 35 , 37 , or 39 , wherein the aqueous pharmaceutical formulation further comprises 90 μg/mL zinc, 2.7 mg/mL m-cresol, 20 μg/mL polysorbate 20, and 20 mg/mL glycerol 85%.
43 . The method of any one of claims 33 , 35 , 37 , or 39 , wherein the zinc in the aqueous pharmaceutical formulation is present in the form of zinc chloride.
44 . The method of any one of claims 32 , 34 , 36 , or 38 , wherein the pH of aqueous pharmaceutical formulation is between 3.4 and 4.6.
45 . The method of claim 44 , wherein the pH of the aqueous pharmaceutical formulation is 4.0.
46 . The method of any one of claims 33 , 35 , 37 , or 39 , wherein the aqueous pharmaceutical formulation further comprises 90 μg/mL zinc chloride, 2.7 mg/mL m-cresol, and 20 mg/mL glycerol 85%, and wherein the pH of the aqueous pharmaceutical formulation is 4.0.
47 . The method of any one of claims 32 , 34 , 36 , or 38 , wherein the pharmacokinetic profile and pharmacodynamic profile of the 270-330 U/mL aqueous pharmaceutical formulation are flatter than the pharmacokinetic profile and pharmacodynamic profile of an aqueous pharmaceutical formulation comprising 100 U/mL of insulin glargine, and wherein the pH of the 270-330 U/mL aqueous pharmaceutical formulation is between 3.4 and 4.6.
48 . A method of treating Type I or Type II Diabetes Mellitus in a patient in need thereof comprising subcutaneously administering to the patient an aqueous pharmaceutical formulation comprising 270-330 U/mL of insulin glargine [equimolar to 270-330 IU human insulin], wherein the pH of the aqueous pharmaceutical formulation is between 3.4 and 4.6.
49 . The method of claim 48 , wherein the pH of the aqueous pharmaceutical formulation is 4.0.
50 . The method of claim 48 , wherein the aqueous pharmaceutical formulation further comprises at least one excipient selected from the group consisting of zinc, m-cresol, glycerol, and polysorbate 20.
51 . The method of claim 50 , wherein the aqueous pharmaceutical formulation further comprises 90 μg/mL zinc, 2.7 mg/mL m-cresol, and 20 mg/mL glycerol 85%.
52 . The method of claim 51 , wherein the zinc is present in the form of zinc chloride.
53 . The method of claim 50 , wherein the aqueous pharmaceutical formulation further comprises 90 μg/mL zinc, 2.7 mg/mL m-cresol, 20 μg/mL polysorbate 20, and 20 mg/mL glycerol 85%.
54 . The method of claim 53 , wherein the zinc is present in the form of zinc chloride.
55 . The method of any one of claims 32 , 34 , 36 , 38 , or 48 , wherein the aqueous pharmaceutical formulation further comprises an analogue of exendin-4.
56 . The method of claim 55 , wherein the analogue of exendin-4 is selected from the group consisting of lixisenatide, exenatide and liraglutide.
57 . The method of claim 56 , wherein the aqueous formulation comprises 0.1 μg to 10 μg lixisenatide per Unit insulin glargine.
58 . The method of claim 57 , wherein the aqueous formulation comprises 0.2 to 1 μg lixisenatide per Unit insulin glargine.
59 . The method of claim 58 , wherein the aqueous formulation comprises 0.25 μg to 0.7 μg lixisenatide per Unit insulin glargine.