USE OF A COMPOUND CAPABLE OF REDUCING THE URIC ACID LEVEL FOR THE PREVENTION AND/OR THE TREATMENT OF LUNG INFLAMMATION AND FIBROSIS

• US 20110243911A1
• Filed: 09/18/2009
• Published: 10/06/2011
• Est. Priority Date: 09/18/2008
• Status: Active Grant

• Current Assignee: Centre National De La Recherche Scientifique
• Original Assignee: Centre National De La Recherche Scientifique
• Inventors: Ryffel, Bernhard, Couillin, Isabelle
• Granted Patent: US 8,569,017 B2
• Time in Patent Office: Days
• US Class Current: 424/94.4
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/4152 having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 31/77 of oxiranes
• CPC Class Codes: A61K 38/44 Oxidoreductases (1)
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: C12Q 1/62 involving uric acid
• CPC Class Codes: C12Y 107/03003 Factor-independent urate hydroxylase (1.7.3.3), i.e. uricase
• CPC Class Codes: G01N 2800/122 Chronic or obstructive airway disorders, e.g. asthma COPD
• CPC Class Codes: G01N 33/5308 for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
• CPC Class Codes: Y10T 436/148888 Uric acid

Abstract

The present invention is directed to the use of a compound capable of reducing the uric acid level in a mammal for the prevention and/or the treatment of IL-1β driven lung pathology, particularly to treat lung inflammation such as chronic fibrosis, COPD and interstitial fibrosis and other IL-1β driven lung pathologies including those of autoimmune origin. Preferred compounds capable of reducing the uric acid level are selected from the group consisting of xanthine oxidase inhibitors, such as allopurinol, recombinant enzyme uricase and uricosuric compound capable of enhancing uric acid excretion, such as probenecid. The invention further relates to a method for identifying in vitro whether a patient presents an IL-1β driven lung pathology or is at risk to develop an IL-1β driven lung pathology, or for the screening of a compound for treating an IL-1β driven lung pathology.

Claims

1-11. -11. (canceled)

12. A method for the prevention and/or the treatment of IL-1β

driven lung pathology in a mammal in need thereof, comprising the step of administering an effective amount of a compound capable of reducing the uric acid level in said mammal.

13. A method according to claim 12, wherein said IL-113 driven lung pathology is selected from the group consisting of lung inflammation, lung fibrosis and lung pathologies from autoimmune origin.

14. A method according to claim 12, wherein said driven lung pathology is a lung inflammation leading to fibrosis and respiratory failure.

15. A method according to claim 12, wherein said compound is selected from the group consisting of:

a xanthine oxidase inhibitor, and a pharmaceutically acceptable salt thereof,

an uricase, a recombinant uricase, and a functional fragment thereof,

and

an uricosuric compound, an inhibitor of the tubular organic anion transporter resulting in the augmentation of renal elimination of uric acid, and a pharmaceutically acceptable salt thereof.

16. A method according to claim 15, wherein said xanthine oxidase inhibitor compound is selected from the group consisting of:

allopurinol,

azapropazone (the 3-dimethylamino-7-methyl-1,2-(n-propylmalonyl)-1,2-dihydro -1,2,4-benzotriazine dihydrate),

substituted thiazolopyrimidines,

1,2,4-triazole compound which may be substituted at the 1, 2 or 4 position with a substituted alkyl group and has aromatic rings at the 3 and 5 positions, a hydrate, and a salt thereof,

and

febuxostat.

17. A method according to claim 15, wherein said recombinant uricase is rasburicase.

18. A method according to claim 17, wherein said uricase is pegylated.

19. A method according to claim 15, wherein said uricosuric compound or inhibitor of the tubular organic anion transporter resulting in the augmentation of renal elimination of uric acid is selected from the group consisting of probenecid, benzbromarone, sulfinpyrazone, thromboxane synthetase inhibitors and thromboxane receptor antagonists.

20. A method according to claim 12, wherein said composition is administered by intravenous injection, by intramuscular injection or orally.

23. A method according to claim 13, wherein lung fibrosis is selected from the group consisting of chronic fibrosis, chronic obstructive pulmonary disease (COPD) and interstitial fibrosis.

21. A method for identifying in vitro whether a patient presents an IL-1β

driven lung pathology or is at risk to develop a IL-1β

driven lung pathology, said method comprising the steps of;

a) obtaining from the patient to be tested a biological fluid sample;

b) determining the level of uric acid in said sample; and

c) identifying whether said patient presents or is at risk to develop such a pathology by comparing the level of uric acid obtained for the patient to be tested with the level of uric acid obtained in a blood sample for normal patients and/or for patients exhibiting a IL-1β

driven lung pathology.

22. A method for screening a compound for the treatment of lung pathology associated to IL-1β

pathway (“

IL-1β

driven lung pathology”

), said method comprising the step of identifying whether said compound to be tested is a xanthine oxidase inhibitor, an uricase, an uricosuric compound or an inhibitor of the tubular organic anion transporter resulting in the augmentation of renal elimination of uric acid.