Stabilized insulin formulations

• US 4,839,341 A
• Filed: 11/13/1987
• Issued: 06/13/1989
• Est. Priority Date: 05/29/1984
• Status: Expired due to Term

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Massey, Eddie H., Sheliga, Theodore A.
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Moezie, F. T.
• Application Number:
  US07/120,443
• Time in Patent Office: 578 Days
• Field of Search: 514/3, 514/4, 514/494
• US Class Current: 514/6.4
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00

Abstract

This invention provides an insulin formulation stabilized against aggregation containing a hydroxybenzene and a polyethylene glycol-polypropylene glycol polymer of the formula ##STR1## having an average molecular weight of about 8350 and in which the average number of ethyleneoxy units per molecule, designated by the sum of a and c, is about 150, and the average number of propyleneoxy units per molecule, designated as b, is about 30.

Claims

1. An insulin formulation comprising, in a pharmaceutically acceptable aqueous diluent and per each milliliter of formulation, from about 40 U to about 500 U of insulin, from about 1 to about 6 milligrams of a hydroxybenzene, and from about 0.05 to about 10 milligrams of a polyethylene glycol-polypropylene glycol polymer of the formula ##STR3## having an average molecular weight of about 8350 and in which the average number of ethyleneoxy units per molecule, designated by the sum of a and c, is about 150, and the average number of propyleneoxy units per molecule, designated as b, is about 30.

2. Formulation of claim 1, in which the insulin is human insulin.

3. Formulation of claim 2, in which the human insulin is present in a concentration of from about 80 U/ml. to about 100 U/ml.

4. Formulation of claim 1, in which the hydroxybenzene is m-cresol.

5. Formulation of claim 4, in which the m-cresol is present in an amount of from about 2.5 mg. to about 3 mg. per milliliter.

6. Formulation of claim 5, in which phenol is present in addition to m-cresol.

7. Formulation of claim 1, in which the hydroxybenzene is phenol.

8. Formulation of claim 7, in which phenol is present in an amount of from about 2.5 mg. to about 3 mg. per milliliter.

9. Formulation of claim 1, in which a cation selected from zinc or sodium is present.

10. Formulation of claim 9, in which the cation is zinc.

11. Formulation of claim 1, in which the polyethylene glycol-polypropylene glycol polymer is Poloxamer 188.

12. Formulation of claim 11, in which the poloxamer 188 is present in an amount of at least at about 0.2 mg. per milliliter of the final composition.