PZA and cytochrome bc1 inhibitor combination treatment
The present invention relates to novel combinations, which are useful in the treatment of tuberculosis.
1. A combination consisting of the following active ingredients:
(i) PZA, or a pharmaceutically acceptable salt thereof; and
(ii) a cytochrome bc 1 inhibitor, or a pharmaceutically acceptable salt thereof.
2. The combination as claimed in claim 1 , wherein the cytochrome bc 1 inhibitor is Q203, or a pharmaceutically acceptable salt thereof.
3. The combination as claimed in claim 1 wherein the daily dose of PZA (or a pharmaceutically acceptable salt thereof) is 15 to 30 mg/kg (up to 2 g).
4. The combination as claimed in claim 1 wherein the daily dose of the cytochrome bc 1 inhibitor (or a pharmaceutically acceptable salt thereof) is 1.5 to 15 mg/kg (up to 1 g).
5. A pharmaceutical formulation comprising the combination as claimed in claim 1 , and a pharmaceutically acceptable excipient or diluent.
6. A method of treating a patient having a mycobacterial infection comprising administering an effective amount of the combination as claimed in claim 1 .
7. The method as claimed in claim 6 , wherein the mycobacterial infection is latent tuberculosis.
8. A process for preparing the pharmaceutical formulation as defined in claim 5 comprising bringing into association the active ingredients of the combination with one (or more) pharmaceutically acceptable excipient or carrier.
9. A combination comprising the following active ingredients:
(i) PZA, or a pharmaceutically acceptable salt thereof; and
(ii) a cytochrome bc 1 inhibitor, or a pharmaceutically acceptable salt thereof.
10. The method as claimed in claim 7 , wherein the cytochrome bc 1 inhibitor is Q203, or a pharmaceutically acceptable salt thereof.
11. The method as claimed in claim 7 , wherein the daily dose of PZA (or a pharmaceutically acceptable salt thereof) is 15 to 30 mg/kg (up to 2 g).
12. The method as claimed in claim 7 , wherein the daily dose of the cytochrome bc 1 inhibitor (or a pharmaceutically acceptable salt thereof) is 1.5 to 15 mg/kg (up to 1 g).
13. The method as claimed in claim 10 , wherein the daily dose of PZA (or a pharmaceutically acceptable salt thereof) is 15 to 30 mg/kg (up to 2 g).
14. The method as claimed in claim 10 , wherein the daily dose of the cytochrome bc 1 inhibitor (or a pharmaceutically acceptable salt thereof) is 1.5 to 15 mg/kg (up to 1 g).
15. The pharmaceutical formulation as claimed in claim 5 , wherein the cytochrome bc 1 inhibitor is Q203, or a pharmaceutically acceptable salt thereof.
16. The combination as claimed in claim 9 , further comprising additional antibacterial drugs.
17. The combination as claimed in claim 16 , wherein the additional antibacterial drugs are anti-tuberculosis drugs selected from:
agents known to interfere with the respiratory chain of Mycobacterium tuberculosis;
other antibacterial agents that may target the electron transport chain; and
other mycobacterial agents.
18. The combination as claimed in claim 16 wherein the additional antibacterial drugs is:
bedaquiline; and/or
clofazimine.
19. The combination as claimed in claim 16 , wherein the additional antibacterial drugs are selected from: direct inhibitors of the ATP synthase; inhibitors of ndh2; antibacterial agents that target the cytochrome bd oxidase; rifampicin (=rifampin); isoniazid; pyrazinamide; amikacin; ethionamide; ethambutol; streptomycin; para-aminosalicylic acid; cycloserine; capreomycin; kanamycin; thioacetazone; PA-824; delamanid; quinolones/fluoroquinolones; macrolides; rifamycins; rifabutin; rifapentin; delanamid and/or pretonamid.