Rapid Acting and Prolonged Acting Inhalable Insulin Preparations

• US 20070086952A1
• Filed: 09/29/2006
• Published: 04/19/2007
• Est. Priority Date: 09/29/2005
• Status: Abandoned Application

• Current Assignee: Biodel Inc. (Ipsen Sa)
• Original Assignee: Biodel Inc. (Ipsen Sa)
• Inventors: Pohl, Roderike, Steiner, Solomon
• Application Number:
  US11/537,335
• Publication Number:
  US 20070086952A1
• Time in Patent Office: Days
• US Class Current: 424/45
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• 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
• CPC Class Codes: A61K 9/0031 Rectum, anus
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions

Abstract

It has been discovered that by combining a chelator, such as ethylenediaminetetraacetic acid, with an acidifier, such as citric acid, the insulin is absorbed much more rapidly than in the absence of the chelator and acidifier, with a commercially available rapid, intermediate or long lasting insulin such as glargine, one can increase and/or prolong the bioavailability of the insulin mixture. The formulations are suitable for administration by injection or to a mucosal surface such as the pulmonary or oral regions, although subcutaneous injection is preferred.

Claims

1. A formulation comprising insulin selected from the group consisting of intermediate acting, and long acting insulin with an effective amount of a chelator and an acidifying agent to enhance the rate or amount of uptake by a patient.

2. The formulation of claim 1 further comprising a rapid acting insulin.

3. The formulation of claim 1, wherein the chelator is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), penicillamine, alginic acids, Chlorella, Cilantro, Alpha Lipoic Acid, Dimercaptosuccinic Acid (DMSA), dimercaptopropane sulfonate (DMPS), and oxalic acid.

4. The formulation of claim 3, wherein the chelator is ethylenediaminetetraacetic acid (EDTA).

5. The formulation of claim 1, wherein the agent is a charged compound and wherein the chelator and solubilizing agent are present in effective amounts to mask charges on the agent.

6. The formulation of claim 1 wherein the solubilizing agent is an acid selected from the group consisting of acetic acid, ascorbic acid, citric acid, and hydrochloric acid.

7. The formulation of claim 6, wherein the solubilizing agent is citric acid.

8. The formulation of claim 1, wherein the insulin is natural or recombinant human insulin.

9. The formulation of claim 1 in a solid formulation for administration to a mucosal surface.

10. The formulation of claim 1 in a formulation for administration by injection.

13. A method of administering insulin to a patient in need thereof comprising administering the formulation of claim 1 to the patient.

14. The method of claim 13 wherein the formulation is administered to a mucosal surface selected from the group consisting of oral, sublingual, buccal, nasal, rectal, and vaginal.

15. The method of claim 13 wherein the formulation is administered by injection.

11. A. formulation suitable for pulmonary administration of an insulin in combination with an effective amount of a chelator and an acidifying agent to enhance the rate or amount of uptake by a patient.

12. The formulation of claim 11 wherein the insulin is a natural or recombinant insulin selected from the group consisting of rapid, intermediate and long acting insulins.

16. A method of administering insulin to a patient in need thereof comprising administering the formulation of claim 11 to the pulmonary region of a patient.