Pharmaceutical formulation for the treatment of diabetes mellitus

• US 5,177,058 A
• Filed: 08/11/1989
• Issued: 01/05/1993
• Est. Priority Date: 08/13/1988
• Status: Expired due to Term

• Current Assignee: Hoechst Aktiengesellschaft (Sanofi )
• Original Assignee: Hoechst Aktiengesellschaft (Sanofi )
• Inventors: Dorschug, Michael
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): Ekstrom, Richard C.
• Application Number:
  US07/392,559
• Time in Patent Office: 1,243 Days
• Field of Search: 514/3, 514/4, 530/304
• US Class Current: 514/5.9
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

Pharmaceutical formulations for the treatment of diabetes mellitus are disclosed, wherein the pharmaceutical formulations contain at least one insulin derivative modified with a base in position B31 of the insulin B chain and having an isoelectric point between 5.8 and 8.5 and/or at least one of its physiologically tolerated salts in a pharmaceutically acceptable excipient and a relatively high zinc ion content in the range from above 1 μg to about 200 μg of zinc/IU. The preferred insulin derivative modified with a base for this pharmaceutical formulation is human insulin-B31-Arg-OH and human insulin-B31-Arg-B32-Arg-OH. The formulation is used for the treatment of diabetes mellitus; it has a particularly favorable action profile.

Claims

1. A pharmaceutical formulation containing at least one insulin derivative modified with a base and having an isoelectric point between 5.8 and 8.5, of the formula I ##STR3## in which R¹ denotes H or H-Phe, R³⁰ represents the radical of a neutral, genetically encodable L-amino acid and

R³¹ represents a physiologically acceptable organic group of basic character having up to 50 carbon atoms, in the build-up of which 0 to 3 α

-amino acids participate and in which any terminal carboxyl function present can be free, or reduced to CH₂ OH,

and containing at least one of its physiologically tolerated salts in a pharmaceutically acceptable excipient with a content of zinc ions,

in which the zinc ion content is in a range from 4.0 μ

g to about 200 μ

g of zinc/IU.

2. A pharmaceutical formulation as claimed in claim 1, wherein R¹ in formula I denotes H-Phe.

3. A pharmaceutical formulation as claimed in claim 1, wherein R³⁰ in formula I denotes Ala, Ser or Thr.

4. A pharmaceutical formulation as claimed in claim 3, wherein R³⁰ in formula I denotes Thr.

5. A harmaceutical formulation as claimed in claim 1, wherein R³¹ in formula I is composed of one, two or three basic naturally occurring amino acids of the series comprising Arg, Lys, Hyl, Orn, Cit and/or His.

6. A pharmaceutical formulation as claimed in claim 5, wherein R³¹ in formula I is Arg-OH or Arg-Arg-OH.

7. A pharmaceutical formulation as claimed in claim 1, wherein the (A1 to A21) and the (B2 to B29) sequences in the insulin derivatives of formula I are the sequences of human, porcine or bovine insulin.

8. A pharmaceutical formulation as claimed in claim 7, wherein the (A1 to A21) and the (B2 to B29) sequences in the insulin derivatives of formula I are the sequences of human insulin.

9. A pharmaceutical formulation as claimed in claim 1, which additionally also contains at least 1 non-modified insulin.

10. A pharmaceutical formulation as claimed in claim 9, wherein the non-modified insulin is human insulin.

11. A method for treating a patient suffering from diabetes mellitus, which comprises administering to said patient a pharmaceutical composition as claimed in claim 1, 9, or 10.