Devices, formulations, and methods for delivery of multiple beneficial agents
View Patent ↗The present invention relates to osmotic delivery devices, formulations, and methods for delivery of two or more beneficial agents. In one aspect, the present invention provides osmotic delivery devices useful for substantially concurrent administration of two or more beneficial agents. In another aspect, the present invention provides beneficial agent formulations for use in the osmotic delivery devices. The formulations include formulations wherein beneficial agents are soluble in the vehicle, suspension formulations comprising particle formulations of one or more beneficial agent, and combinations thereof. Further, methods for treatment of a variety of diseases or conditions using two or more beneficial agents are disclosed, wherein the methods are preferably practiced using the osmotic delivery devices and/or formulations of the invention.
1. An osmotic delivery device comprising: a beneficial agent formulation comprising (i) a non-aqueous, viscous vehicle comprising a solvent and a polymer, the vehicle having a viscosity of between about 12,000 to about 18,000 poise at 33° C., and
(ii) two or more polypeptides, wherein a first polypeptide is Glucagon-like peptide-1 (GLP-1) or exenatide and a second polypeptide is selected from the group consisting of amylin, an amylin analogue, a ghrelin antagonist, a G protein coupled receptor 119 (GRP 119) agonist, and leptin;
wherein the two or more polypeptides are suspended in the vehicle.
2. The device of claim 1 , wherein the two or more polypeptides are formulated into one particle formulation that is suspended in the vehicle.
3. The device of claim 1 , wherein the first polypeptide is formulated into a first particle formulation and the second polypeptide is formulated into a second particle formulation, and the first and second particle formulations are suspended in the vehicle.
4. The device of claim 1 , wherein the first polypeptide is exenatide and the second polypeptide is amylin.
5. The device of claim 1 , wherein the first polypeptide is exenatide and the second polypeptide is an amylin analogue.
6. The device of claim 5 , wherein the amylin analogue is pramlintide.
7. The device of claim 1 , wherein the first polypeptide is exenatide and the second polypeptide is a ghrelin antagonist.
8. The device of claim 1 , wherein the first polypeptide is exenatide and the second polypeptide is a GRP 119 agonist.
9. The device of claim 1 , wherein the first polypeptide is exenatide and the second polypeptide is leptin.
10. The device of claim 1 , wherein the first polypeptide is GLP-1 and the second polypeptide is amylin.
11. The device of claim 1 , wherein the first polypeptide is GLP-1 and the second polypeptide is an amylin analogue.
12. The device of claim 11 , wherein the amylin analogue is pramlintide.
13. The device of claim 1 , wherein the first polypeptide is GLP-1 and the second polypeptide is a ghrelin antagonist.
14. The device of claim 1 , wherein the first polypeptide is GLP-1 and the second polypeptide is a GRP 119 agonist.
15. The device of claim 1 , wherein the first polypeptide is GLP-1 and the second polypeptide is leptin.
16. The device of claim 1 , wherein the beneficial agent formulation comprises a third polypeptide selected from PYY and oxyntomodulin.
17. The device of claim 1 , wherein the solvent is selected from the group consisting of lauryl lactate, lauryl alcohol, and benzyl benzoate.
18. The device of claim 1 , wherein the polymer is polyvinylpyrrolidone.
19. The device of claim 17 , wherein the polymer is polyvinylpyrrolidone.
20. The device of claim 1 , wherein the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone.
21. The device of claim 1 , wherein the vehicle comprises about 25 wt % to about 80 wt % polymer and about 75 wt % to about 20 wt % solvent.
22. The device of claim 1 , wherein the particle formulation comprises a carbohydrate, an antioxidant, and a buffer.
23. The device of claim 22 , wherein the carbohydrate is a non-reducing sugar, the antioxidant is an amino acid, and the buffer is an organic buffer.
24. The device of claim 23 , wherein the non-reducing sugar is selected from the group consisting of sucrose, trehalose, and raffinose.
25. The device of claim 23 , wherein the amino acid is selected from the group consisting of cysteine, methionine, and tryptophan.
26. The device of claim 23 , wherein the organic buffer is selected from the group consisting of citrate, histidine, succinate, and tris.
27. The device of claim 2 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, and (ii) the first and second polypeptides are, respectively, exenatide and amylin or an amylin analogue, and the particle formulation further comprises sucrose, methionine, and citrate buffer.
28. The device of claim 27 , wherein the second polypeptide is amylin.
29. The device of claim 27 , wherein the second polypeptide is an amylin analogue.
30. The device of claim 29 , wherein amylin analogue is pramlintide.
31. The device of claim 2 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, and (ii) the polypeptides are exenatide and a ghrelin antagonist, and the particle formulation further comprises sucrose, methionine, and citrate buffer.
32. The device of claim 2 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, and (ii) the polypeptides are exenatide and a GRP 119 agonist, and the particle formulation further comprises sucrose, methionine, and citrate buffer.
33. The device of claim 2 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, and (ii) the polypeptides are exenatide and leptin, and the particle formulation further comprises sucrose, methionine, and citrate buffer.
34. The device of claim 2 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, and (ii) the first and second polypeptides are, respectively, GLP-1 and amylin or an amylin analogue, and the particle formulation further comprises sucrose, methionine, and citrate buffer.
35. The device of claim 34 , wherein the second polypeptide is amylin.
36. The device of claim 34 , wherein the second polypeptide is an amylin analogue.
37. The device of claim 36 , wherein the amylin analogue is pramlintide.
38. The device of claim 2 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, and (ii) the polypeptides are GLP-1 and a ghrelin antagonist, and the particle formulation further comprises sucrose, methionine, and citrate buffer.
39. The device of claim 2 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, and (ii) the polypeptides are GLP-1 and a GRP 119 agonist, and the particle formulation further comprises sucrose, methionine, and citrate buffer.
40. The device of claim 2 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, and (ii) the polypeptides are GLP-1 and leptin, and the particle formulation further comprises sucrose, methionine, and citrate buffer.
41. The device of claim 3 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, (ii) the first polypeptide is exenatide and the first particle formulation further comprises sucrose, methionine, and citrate buffer, and (iii) the second polypeptide is amylin or an amylin analogue and the second particle formulation further comprises sucrose, methionine, and citrate buffer.
42. The device of claim 41 , wherein the second polypeptide is amylin.
43. The device of claim 41 , wherein the second polypeptide is an amylin analogue.
44. The device of claim 43 , wherein the amylin analogue is pramlintide.
45. The device of claim 3 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, (ii) the first polypeptide is exenatide and the first particle formulation further comprises sucrose, methionine, and citrate buffer, and (iii) the second polypeptide is a ghrelin antagonist and the second particle formulation further comprises sucrose, methionine, and citrate buffer.
46. The device of claim 3 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, (ii) the first polypeptide is exenatide and the first particle formulation further comprises sucrose, methionine, and citrate buffer, and (iii) the second polypeptide is a GRP 119 agonist and the second particle formulation further comprises sucrose, methionine, and citrate buffer.
47. The device of claim 3 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, (ii) the first polypeptide is exenatide and the first particle formulation further comprises sucrose, methionine, and citrate buffer, and (iii) the second polypeptide is leptin and the second particle formulation further comprises sucrose, methionine, and citrate buffer.
48. The device of claim 3 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, (ii) the first polypeptide is GLP-1 and the first particle formulation further comprises sucrose, methionine, and citrate buffer, and (iii) the second polypeptide is amylin or an amylin analogue and the second particle formulation further comprises sucrose, methionine, and citrate buffer.
49. The device of claim 48 , wherein the second polypeptide is amylin.
50. The device of claim 48 , wherein the second polypeptide is an amylin analogue.
51. The device of claim 50 , wherein the amylin analogue is pramlintide.
52. The device of claim 3 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, (ii) the first polypeptide is GLP-1 and the first particle formulation further comprises sucrose, methionine, and citrate buffer, and (iii) the second polypeptide is a ghrelin antagonist and the second particle formulation further comprises sucrose, methionine, and citrate buffer.
53. The device of claim 3 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, (ii) the first polypeptide is GLP-1 and the first particle formulation further comprises sucrose, methionine, and citrate buffer, and (iii) the second polypeptide is a GRP 119 agonist and the second particle formulation further comprises sucrose, methionine, and citrate buffer.
54. The device of claim 3 , wherein (i) the solvent is benzyl benzoate and the polymer is polyvinylpyrrolidone, and the vehicle comprises about 25 wt % to about 80 wt % polyvinylpyrrolidone and about 75 wt % to about 20 wt % benzyl benzoate, (ii) the first polypeptide is GLP-1 and the first particle formulation further comprises sucrose, methionine, and citrate buffer, and (iii) the second polypeptide is leptin and the second particle formulation further comprises sucrose, methionine, and citrate buffer.
55. A method of treating a disease or condition in a subject in need of treatment, comprising:
providing the osmotic delivery device of claim 1 to the subject, wherein (i) the osmotic delivery device delivers a therapeutically effective amount of the two or more polypeptides to treat the disease or condition, and (ii) the disease or condition is selected from the group consisting of type II diabetes, being overweight, and obesity.
56. The method of claim 55 , wherein (i) a first polypeptide is exenatide, and (ii) the two polypeptides are formulated into one particle formulation that is suspended in the vehicle or the first polypeptide is formulated into a first particle formulation and the second polypeptide is formulated into a second particle formulation and the first and second particle formulations are suspended in the vehicle.
57. The method of claim 56 , wherein the second polypeptide is amylin.
58. The method of claim 56 , wherein the second polypeptide is an amylin analogue.
59. The method of claim 58 , wherein the amylin analogue is pramlintide.
60. The method of claim 51 , wherein (i) a first polypeptide is GLP-1, and (ii) the two polypeptides are formulated into one particle formulation that is suspended in the vehicle or the first polypeptide is formulated into a first particle formulation and the second polypeptide is formulated into a second particle formulation and the first and second particle formulations are suspended in the vehicle.
61. The method of claim 60 , wherein the second polypeptide is amylin.
62. The method of claim 60 , wherein the second polypeptide is an amylin analogue.
63. The method of claim 62 , wherein the amylin analogue is pramlintide.