Pharmaceutical compositions and treatment methods

• US 7,396,827 B2
• Filed: 12/13/2002
• Issued: 07/08/2008
• Est. Priority Date: 03/16/2000
• Status: Expired due to Fees

• Current Assignee: BioVie Inc.
• Original Assignee: Hollis-Eden Pharmaceuticals, Inc.
• Inventors: Heggie, William, Ahlem, Clarence N., Carvalho, Luis D.
• Primary Examiner(s): PRYOR, ALTON NATHANIEL
• Application Number:
  US10/319,356
• Publication Number:
  US 20040043973A1
• Time in Patent Office: 2,034 Days
• Field of Search: 514/178, 514/176, 552/536
• US Class Current: 514/176
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 31/5685 having an oxo group in position 17, e.g. androsterone
• 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 9/127 Liposomes
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07J 1/00 Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
• CPC Class Codes: C07J 1/0011 substituted in position 17 by a keto group
• CPC Class Codes: C07J 3/005 the carbon atom being part of a carboxylic function
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides compositions comprising formula 1 steroids, e.g., 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate and one or more excipients, typically wherein the composition comprises less than about 3% water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16α-bromo-3β-hydroxy-5α-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen (viral) replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using certain steroids and steroid analogs. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

Claims

1. A method to treat inflammation associated with atopic asthma, sarcoidosis, rheumatoid arthritis, osteoarthritis, atopic dermatitis, subepithelial fibrosis in airway hyperresponsiveness, chronic sinusitis, fibrosing alveolitis or an infection in a subject in need thereof, comprising administering to the subject an effective amount of 16α

-bromo-3β

-hydroxy-5α

-androstan-17-one hemihydrate.

2. The method of claim 1 wherein the subject is a human.

3. The method of claim 1 wherein the 16α

-bromo-3β

-hydroxy-5α

-androstan-17-one hemihydrate is administered to the subject in a buccal or sublingual formulation.

4. The method of claim 1 wherein the 16α

-bromo-3β

-hydroxy-5α

-androstan-17-one hemihydrate is administered to the subject as a parenteral suspension, liposome or colloid formulation.

5. The method of claim 3 or 4 wherein 0.05 to about 30 mg/kg/day of 16α

-bromo-3β

-hydroxy-5α

androstan-17-one hemihydrate is administered to the subject once or twice per day.

6. The method of claim 1 wherein the inflammation is associated with atopic asthma.

11. The method of claim 1 wherein the inflammation is associated with an infection.

12. The method of claim 11 wherein the infection is a virus infection or a bacterial infection.

13. The method of claim 1 wherein the inflammation is associated with rheumatoid arthritis or osteoarthritis.

14. The method of claim 1 wherein the inflammation is associated with subepithelial fibrosis in airway hyperresponsiveness or fibrosing alveolitis.

15. The method of claim 12 wherein the virus infection is a retrovirus infection.

16. The method of claim 11 wherein the infection is a parasite infection.

17. The method of claim 16 wherein the parasite infection is a Plasmodium infection.

7. A method to treat an inflammation condition selected from the group consisting of atopic asthma, sarcoidosis, rheumatoid arthritis, osteoarthritis, atopic dermatitis, subepithelial fibrosis in airway hyperresponsiveness, chronic sinusitis and fibrosing alveolitis in a human in need thereof, comprising administering to the human an effective amount of 16α

-bromo-3β

-hydroxy-5α

-androstan-17-one hemihydrate and a glucocorticoid.

8. The method of claim 7 wherein the inflammation condition is atopic asthma, sarcoidosis, atopic dermatitis, subepithelial fibrosis in airway hyperresponsiveness, chronic sinusitis, or fibrosing alveolitis.

9. The method of claim 7 wherein the inflammation condition is atopic asthma.

10. The method of claim 9 wherein the 16α

-bromo-3β

-hydroxy-5α

-androstan-17-one hemihydrate has an average particle size of about 0.1-10 μ

m.