Method and composition for treatment of insulin requiring mammals

• US 5,814,600 A
• Filed: 06/13/1994
• Issued: 09/29/1998
• Est. Priority Date: 05/24/1991
• Status: Expired due to Term

• Current Assignee: Astrazeneca Pharmaceuticals LP (Astrazeneca PLC)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Young, Andrew A., Rink, Timothy J.
• Primary Examiner(s): Sayala, Chhaya D.
• Application Number:
  US08/259,762
• Time in Patent Office: 1,569 Days
• Field of Search: 514/3, 514/4, 514/12, 514/21
• US Class Current: 514/6.5
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/28 Insulins

Abstract

Method and compositions for treating a mammal by administering to that mammal an insulin (having the in vitro activity of stimulating glucose incorporation into glycogen in rat soleus muscle) and an amylin (having the in vitro activity of suppressing glucose incorporation into glycogen in rat soleus muscle) using specific molar ratios of an insulin to an amylin.

Claims

1. A method of treating a mammal having a need for, or a reduced ability to produce, insulin, comprising administering to said mammal an insulin having an in vitro activity of stimulating glucose incorporation into glycogen in rat soleus muscle, and an amylin having the in vitro activity of suppressing glucose incorporation into glycogen in rat soleus muscle, wherein said insulin and said amylin are administered in a molar ratio of between about 1:

1 and about 67;

1.

2. A method according to claim 1 wherein said method further comprises identifying a mammal having a reduced ability to produce serum insulin compared to the normal ability of said mammal to produce serum insulin.

3. A method according to claim 1 wherein said insulin and said amylin are administered in a molar ratio of between about 7:

1 and about 67;

1.

4. A method according to claim 1 wherein said insulin and said amylin are administered in a molar ratio of between about 1:

1 to about 40;

1.

5. A method according to claim 4 wherein said insulin and said amylin are administered in a molar ratio of between about 2.5:

1 and about 35;

1.

6. A method according to claim 4 wherein said insulin and said amylin are administered in a molar ratio of between about 5:

1 and about 25;

1.

7. A method according to claim 4 wherein said insulin and said amylin are administered in a molar ratio of between about 5:

1 and about 10;

1.

8. A method according to claim 4 wherein said insulin and said amylin are administered in a molar ratio of between about 4:

1 and about 10;

1.

9. A method according any of claims 1-8 wherein said amylin comprises ²⁵,28,29 Pro-human amylin.

10. A method according to any of claims 1-5 or 6-8 wherein said amylin comprises ²⁵,28,29 Pro-human amylin and said mammal is a human.

11. A method according to any of claims 1-5 or 6-8 wherein said amylin comprises ²⁵,28,29 Pro-human amylin and said mammal is a human suffering from diabetes mellitus.

12. A method according to claim 1 wherein said amylin is administered in an amount of at least about 0.2 micrograms per kilogram of said mammal per day.

13. A method according to claim 1 wherein said amylin is administered in an amount of at least about 0.4 micrograms per kilogram of said mammal per day.

14. A method according to claim 1 wherein said amylin is administered in an amount of at least about 0.5 micrograms per kilogram of said mammal per day.

15. A method according to claim 1 wherein said amylin is administered in an amount of between about 0.2 micrograms per kilogram of said mammal per day and about 5 micrograms per kilogram of said mammal per day.

16. A method according to claim 15 wherein said amylin is administered in an amount of between about 0.4 micrograms per kilogram of said mammals per day and about 2 micrograms per kilogram of said mammal per day.

17. A method according to any of claims 12-16 wherein said amylin comprises ²⁵,28,29 Pro-human amylin.

18. A method according to any of claims 12-16 wherein said amylin comprises 25,28,29Pro-human amylin and said mammal is a human.

19. A method according to any of claims 12-16 wherein said amylin comprises ²⁵,28,29 Pro-human amylin and said mammal is a human suffering from diabetes.

20. A method according to claim 1 wherein said mammal is a human suffering from diabetes and said amylin is administered in an amount of at least about 90 micrograms per day.

21. A method according to claim 20 wherein said amylin comprises ²⁵,28,29 Pro-human amylin.

22. A method of treating a mammal having a need for, or a reduced ability to produce, insulin, comprising administering to said mammal a composition comprising an insulin having an in vitro activity of stimulating glucose incorporation into glycogen in rat soleus muscle, and an amylin having the in vitro activity of suppressing glucose incorporation into glycogen in rat soleus muscle, wherein said insulin and said amylin are administered in a suitable molar ratio such that, upon administration of such composition to said mammal, the amount of said amylin said composition will result in plasma levels of amylin of about 3% to about 6% the plasma levels of insulin.

24. A method according to either of claims 22 or 23 wherein said amylin comprises ²⁵,28,29 Pro-human amylin and said mammal is a human.

23. A method of treating a mammal having a need for, or a reduced ability to produce, insulin, comprising administering to said mammal a composition comprising an insulin having an in vitro activity of stimulating glucose incorporation into glycogen in rat soleus muscle, and an amylin having the in vitro activity of suppressing glucose incorporation into glycogen in rat soleus muscle, wherein said insulin and said amylin are administered in a suitable molar ratio such that, upon administration of such composition to said mammal, the amount of said amylin in said composition will result in plasma levels of amylin of about 4% to about 7% the plasma levels of insulin.

25. A composition comprising an insulin having an in vitro activity of stimulating glucose incorporation into glycogen in rat soleus muscle, and an amylin having the in vitro activity of suppressing glucose incorporation into glycogen in rat soleus muscle, wherein said insulin and said amylin are provided in a molar ratio of between about 1:

1 and about 67;

1.

26. A composition according to claim 25 wherein said insulin and said amylin are provided at a molar ratio of between about 7:

1 and about 67;

1.

27. A composition according to claim 25 wherein said insulin and said amylin are provided at a molar ratio of between about 1:

1 to about 40;

1.

28. A composition according to claim 27 wherein said insulin and said amylin are provided at a molar ratio of between about 2.5:

1 and about 35;

1.

29. A composition according to claim 27 wherein said insulin and said amylin are provided at a molar ratio of between about 5:

1 and about 25;

1.

30. A composition according to claim 27 wherein said insulin and said amylin are provided at a molar ratio of between about 5:

1 and about 10;

1.

31. A composition according to claim 27 wherein said insulin and said amylin are provided at a molar ratio of between about 4:

1 and about 10;

1.

32. A composition according to any of claims 25-31 wherein said amylin comprises ²⁵,28,29 Pro-human amylin.