Magnesium containing insulin solution

• US 5,070,186 A
• Filed: 04/19/1989
• Issued: 12/03/1991
• Est. Priority Date: 10/20/1986
• Status: Expired due to Fees

• Current Assignee: NOVO Industri A/S Bagsvaerd
• Original Assignee: Novo Industri A/S (Novo Nordisk A/S)
• Inventors: Joergensen, Klaus
• Primary Examiner(s): Schain, Howard E.
• Assistant Examiner(s): PERKINS, SUSAN
• Application Number:
  US07/340,331
• Time in Patent Office: 958 Days
• Field of Search: 514/3, 514/4, 530/303, 530/304, 530/305
• US Class Current: 530/304
• CPC Class Codes: C07K 14/62 Insulins

Abstract

Insulin preparations with improved properties for parenteral administration can be prepared at pH values of about 3 to 8.5 by presence of magnesium ions in concentration of about 0.005 to 0.5M, a preferred range is 0.02M to 0.5M.

Claims

1. Insulin preparations for parenteral administration containing at least 20 insulin units per ml, comprising a solution of an insulin and magnesium ions in a magnesium concentration in the range from about 0.02 to 0.5M, the preparation having a pH value in the range from about 3 to 8.5.

2. Preparation, according to claim 1, characterized in that it has a pH value in the range from about 4 to about 6.2.

3. Preparation, according to claim 2, characterized in that the pH value is in the range from about 5 to 6.

4. Preparation, according to claim 1, characterized in that the magnesium concentration is in the range from 0.02M to 0.3M.

5. Preparation, according to claim 4, characterized in that the magnesium concentration is in the range of 0.08M to 0.3M.

6. Preparation, according to claim 1, characterized in that it has an activity in the range from about 30 to 500 insulin units per ml.

7. Preparation, according to claim 6, characterized in that it has an activity in the range from about 40 to 100 insulin units per ml.

8. Preparation, according to claim 1, characterized in that it contains protamine.

9. Solution, according to claim 8, characterized in that it contains about 5% to 50% (weight/weight) of protamine based upon the content of insulin, with the proviso that the pH value is below 6.2.

10. Preparation, according to claim 1, characterized in that it contains less than about 1 zinc ion per hexamer insulin.

11. Process of preparing insulin solutions for parenteral administration which comprises mixing a water soluble magnesium salt, an insulin and water, the magnesium concentration being in the range from about 0.02M to 0.5M, the insulin concentration being in the range from about 20 to 500 insulin units per ml, the pH being adjusted to a level in the range from about 3 to 8.5.

12. Process according to claim 11 further comprising a magnesium concentration range from 0.08M to 0.3M, an insulin concentration range from 40 to 100 insulin units per ml and a pH in the range from about 5 to 6.