Extended release of neuregulin for treating heart failure
View Patent ↗The present invention provides methods and kits for preventing, treating or delaying various cardiovascular diseases or disorders especially heart failure by extended release of neuregulin to a mammal. Moreover, the extended release of neuregulin is administered by subcutaneous infusion with a pump.
1. A method for treating heart failure in a mammal, the method comprising administering subcutaneous extended release of neuregulin into a mammal in an amount of 0.3 μg/kg/day to 3.0 μg/kg/day, wherein the subcutaneous extended release of neuregulin into a mammal is accomplished through the use of a pump.
2. The method of claim 1 , wherein the mammal is human.
3. The method of claim 1 , wherein the subcutaneous extended release of neuregulin into a mammal is accomplished through the use of a syringe pump.
4. The method of claim 3 , wherein the syringe pump is a mini pump.
5. The method of claim 4 , wherein the mini pump is an insulin pump.
6. The method of claim 1 , wherein neuregulin is in an amount of 1.2 μg/kg/day to 2.0 μg/kg/day.
7. The method of claim 1 , wherein neuregulin is in an amount of 1.2 μg/kg/day.
8. The method of claim 1 , wherein neuregulin is in an amount of 2.0 μg/kg/day.
9. The method of claim 1 , wherein neuregulin is in an amount of 6 EU/kg/day to 60 EU/kg/day.
10. The method of claim 1 , wherein neuregulin is in an amount of 24 EU/kg/day to 40 EU/kg/day.
11. The method of claim 1 , wherein neuregulin is in an amount of 24 EU/kg/day.
12. The method of claim 1 , wherein neuregulin is in an amount of 40 EU/kg/day.
13. The method of claim 1 , wherein the neuregulin is administered to the mammal for an introduction regimen.
14. The method of claim 13 , wherein the introduction regimen includes an administration of neuregulin for at least 3, 5, 7, 10 or 15 consecutive days.
15. The method of claim 14 , wherein the introduction regimen includes an administration of neuregulin for at least 3 consecutive days.
16. The method of claim 14 , wherein the introduction regimen includes an administration of neuregulin for at least 5 consecutive days.
17. The method of claim 14 , wherein the introduction regimen includes an administration of neuregulin for at least 7 consecutive days.
18. The method of claim 14 , wherein the introduction regimen includes an administration of neuregulin for at least 10 consecutive days.
19. The method of claim 14 , wherein the introduction regimen includes an administration of neuregulin for at least 15 consecutive days.
20. The method of claim 13 , wherein the introduction regimen includes an administration of neuregulin for 10 consecutive days.
21. The method of claim 13 , wherein the neuregulin is administered for at least 2, 4, 6, 8, 10, 12, 16, 20 or 24 consecutive hours every day.
22. The method of claim 21 , wherein the neuregulin is administered for at least 2 consecutive hours every day.
23. The method of claim 21 , wherein the neuregulin is administered for at least 4 consecutive hours every day.
24. The method of claim 21 , wherein the neuregulin is administered for at least 6 consecutive hours every day.
25. The method of claim 21 , wherein the neuregulin is administered for at least 10 consecutive hours every day.
26. The method of claim 21 , wherein the neuregulin is administered for at least 12 consecutive hours every day.
27. The method of claim 21 , wherein the neuregulin is administered for at least 16 consecutive hours every day.
28. The method of claim 21 , wherein the neuregulin is administered for at least 20 consecutive hours every day.
29. The method of claim 21 , wherein the neuregulin is administered for at least 24 consecutive hours every day.
30. The method of claim 13 , wherein the neuregulin is administered for 8 consecutive hours every day.
31. The method of claim 13 , wherein the neuregulin is administered to the patients for a maintenance regimen after the introduction regimen.
32. The method of claim 31 , wherein the maintenance regimen includes an administration of neuregulin for at least 3 months, 6 months, 12 months, 1 year, 5 years or even longer after the introduction regimen.
33. The method of claim 32 , wherein the maintenance regimen includes administration of neuregulin for at least 3 months.
34. The method of claim 32 , wherein the maintenance regimen includes administration of neuregulin for at least 6 months.
35. The method of claim 32 , wherein the maintenance regimen includes administration of neuregulin for at least 12 months.
36. The method of claim 32 , wherein the maintenance regimen includes administration of neuregulin for at least 1 year.
37. The method of claim 32 , wherein the maintenance regimen includes administration of neuregulin for at least 5 years.
38. The method of claim 32 , wherein the maintenance regimen includes administration of neuregulin for longer than 5 years.
39. The method of claim 31 , wherein the maintenance regimen includes a repeat of the induction regimen every 3 months, 6 months or 12 months.
40. The method of claim 39 , wherein the maintenance regimen includes a repeat of the induction regimen every 3 months.
41. The method of claim 39 , wherein the maintenance regimen includes a repeat of the induction regimen every 6 months.
42. The method of claim 39 , wherein the maintenance regimen includes a repeat of the induction regimen every 12 months.
43. The method of claim 1 , wherein the extended release of neuregulin into the mammal enhances the ejection fraction (EF) value of the mammal.
44. The method of claim 1 , wherein the extended release of neuregulin into the mammal reduces the Left Ventricular End-Diastolic Volume (LVEDV) of the mammal.
45. The method of claim 1 , wherein the extended release of neuregulin into the mammal reduces the Left Ventricular End-Systolic Volume (LVESV) of the mammal.
46. The method of claim 1 , wherein the extended release of neuregulin into the mammal improves 6 Minute Walk Distance (6 MWD) of the mammal.
47. The method of claim 1 , wherein the extended release of neuregulin into the mammal improves quality of life of the mammal.
48. The method of claim 1 , wherein the neuregulin comprises the EGF-like domain of NRG-1, NRG-2, NRG-3 or NRG-4.
49. The method of claim 48 , wherein the neuregulin comprises the EGF-like domain of NRG-1.
50. The method of claim 48 , wherein the neuregulin comprises the EGF-like domain of NRG-2.
51. The method of claim 48 , wherein the neuregulin comprises the EGF-like domain of NRG-3.
52. The method of claim 48 , wherein the neuregulin comprises the EGF-like domain of NRG-4.
53. The method of claim 1 , wherein the neuregulin comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4.
54. The method of claim 53 , wherein the neuregulin comprises the amino acid sequence SEQ ID NO:1.
55. The method of claim 53 , wherein the neuregulin comprises the amino acid sequence SEQ ID NO:2.
56. The method of claim 53 , wherein the neuregulin comprises the amino acid sequence SEQ ID NO:3.
57. The method of claim 53 , wherein the neuregulin comprises the amino acid sequence SEQ ID NO:4.
58. The method of claim 1 , wherein the neuregulin is selected from the group consisting of NRG-1, NRG-2, NRG-3 and NRG-4.
59. The method of claim 58 , wherein the neuregulin is NRG-1.
60. The method of claim 58 , wherein the neuregulin is NRG-2.
61. The method of claim 58 , wherein the neuregulin is NRG-3.
62. The method of claim 58 , wherein the neuregulin is NRG-4.
63. The method of claim 1 , wherein the neuregulin is NRG-1 β2.