Pulmonary administration of granulocyte colony stimulating factor

• US 5,284,656 A
• Filed: 09/29/1992
• Issued: 02/08/1994
• Est. Priority Date: 03/15/1991
• Status: Expired due to Term

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Platz, Robert M., Winters, Mark A., Pitt, Colin G.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): AZPURU, CARLOS A
• Application Number:
  US07/953,208
• Time in Patent Office: 497 Days
• Field of Search: 424/43, 424/46, 424/85.1, 424/434, 424/435, 514/2, 514/8, 514/21, 514/885, 530/951, 530/350, 530/395, 530/397, 530/838
• US Class Current: 424/435
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• 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
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: Y10S 530/838 Marrow; spleen

Abstract

Granulocyte-colony stimulating factor (G-CSF) can be delivered systemically in therapeutically or prophylactically effective amounts by pulmonary administration using a variety of pulmonary delivery devices, including nebulizers, metered dose inhalers and powder inhalers. Aerosol administration in accordance with this invention results in significant elevation of the neutrophil levels that compares favorably with delivery by subcutaneous injection. G-CSF can be administered in this manner to medically treat neutropenia, as well as to combat or prevent infections.

Claims

1. A method for the pulmonary administration of G-CSF to a mammal, comprising directing a neutrophil stimulating amount of G-CSF into the oral cavity of the mammal while the mammal is inhaling for those is need thereof.

2. A method according to claim 1, wherein G-CSF is administered in the form of a pharmaceutical composition comprising G-CSF in a pharmaceutically acceptable carrier.

3. A method according to claim 2, wherein the composition is in the form of a solution in an aqueous medium or a suspension in a non-aqueous medium.

4. A method according to claim 2, wherein the composition is in the form of a dry powder.

5. A method according to claim 4, wherein G-CSF has a particle size of less than 10 microns.

6. A method according to claim 4, wherein the G-CSF has a particle size between 1 and 5 microns.

7. A method according to claim 2, wherein the G-CSF is human G-CSF.

8. A method according to claim 7, wherein the human G-CSF is recombinant human G-CSF.

9. A method according to claim 8, wherein the recombinant human G-CSF is the product of expression in a transformed eucaryotic or procaryotic host cell.

10. A method according to claim 9, wherein the host cell is procaryotic.

11. A method according to claim 10, wherein the host cell is E. coli.

12. A method according to claim 1, wherein G-CSF is delivered from a mechanical device suitable for pulmonary administration and capable of depositing G-CSF in the lungs of the mammal.

13. A method according to claim 12, wherein the device is a nebulizer, metered dose inhaler or powder inhaler.

14. A method according to claim 13, wherein the device is a jet nebulizer.

15. A method according to claim 13, wherein the device is an ultrasonic nebulizer.

16. A method according to claim 1 wherein the mammal is a human.

17. A method according to claim 16, wherein the administration results in blood neutrophil levels in excess of 1000 neutrophils per μ

L of blood.

18. A method according to claim 16, wherein the administration results in blood neutrophil levels of about 5000 to 6000 neutrophils per μ

L of blood.

19. The method of claim 1 which is used to treat neutropenia.

20. The method of claim 1 which is used to treat infection.

21. The method of claim 1 which is used to prevent infection.