Combination of HMG-COA Reductase Inhibitors with Phosphodiesterase 4 Inhibitors for the Treatment of Inflammatory Pulmonary Disease

1 . Pharmaceutical composition comprising a pharmaceutical formulation including a first amount of a PDE4 inhibitor or a pharmaceutically acceptable salt thereof, a second amount of a HMG-CoA reductase inhibitor or a pharmaceutically acceptable salt thereof, wherein the first amount and the second amount together comprise an effective amount for the preventive or curative treatment of an inflammatory pulmonary disease, and at least one pharmaceutically acceptable auxiliary.

2 . A combination product comprising the components: (A) a first amount of a PDE4 inhibitor or a pharmaceutically acceptable salt thereof; (B) a second amount of a HMG-CoA reductase inhibitor or a pharmaceutically acceptable salt thereof; wherein the first and the second amount together comprise an effective amount for the preventive or curative treatment of an inflammatory pulmonary disease and wherein each of the components (A) and (B) is formulated in admixture with at least one pharmaceutically acceptable auxiliary.

3 . A kit comprising the components: (A) a pharmaceutical formulation including a first amount of a PDE4 inhibitor or a pharmaceutically acceptable salt thereof, in admixture with at least one pharmaceutically acceptable auxiliary; (B) a pharmaceutical formulation including a second amount of a HMG-CoA reductase inhibitor or a pharmaceutically acceptable salt thereof, in admixture with at least one pharmaceutically acceptable auxiliary; wherein the first and the second amount together comprise an effective amount for the preventive or curative treatment of an inflammatory pulmonary disease.

4 . Pharmaceutical composition according to claim 1 , wherein the PDE4 inhibitor is selected from the group consisting of ROFLUMILAST, ROFLUMILAST N-Oxide, CILOMILAST, AWD-12-281, TOFIMILAST, TETOMILAST, LIRIMILAST, L-869298, OGLEMILAST, 2-{4-[(4aS,8aR)-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydro-1H-phthalazin-2-yl]-piperidin-1-yl}-acetamide and a pharmaceutically acceptable salt of these compounds.

5 . Pharmaceutical composition according to claim 1 , wherein the PDE4 inhibitor is selected from the group consisting of ROFLUMILAST, a pharmaceutically acceptable salt of ROFLUMILAST, ROFLUMILAST-N-oxide and a pharmaceutically acceptable salt of ROFLUMILAST-N-oxide.

6 . Pharmaceutical composition according to claim 1 , wherein the PDE4 inhibitor is ROFLUMILAST.

7 . Pharmaceutical composition according to claim 1 , wherein the PDE4 inhibitor is ROFLUMILAST-N-oxide.

8 . Pharmaceutical composition according to claim 1 , wherein the PDE4 inhibitor is CILOMILAST or a pharmaceutically acceptable salt thereof.

9 . Pharmaceutical composition according to claim 1 , wherein the PDE4 inhibitor is AWD-12-281 or a pharmaceutically acceptable salt thereof.

10 . Pharmaceutical composition according to claim 1 , wherein the PDE4 inhibitor is TOFIMILAST or a pharmaceutically acceptable salt thereof.

11 . Pharmaceutical composition according to claim 1 , wherein the PDE4 inhibitor is TETOMILAST or a pharmaceutically acceptable salt thereof.

12 . Pharmaceutical composition according to claim 1 , wherein the PDE4 inhibitor is OGLEMILAST or a pharmaceutically acceptable salt thereof.

13 . Pharmaceutical composition according to claim 1 , wherein the HMG-CoA reductase inhibitor is selected from the group consisting of LOVASTATIN, PRAVASTATIN, SIMVASTATIN, ATORVASTATIN, FLUVASTATIN, ROSUVASTATIN, PITAVASTATIN, BERVASTATIN, DALVASTATIN, GLENVASTATIN and the pharmaceutically acceptable salts of these compounds.

14 . Pharmaceutical composition according to claim 1 , wherein the HMG-CoA reductase inhibitor is selected from the group consisting of ATORVASTATIN, SIMVASTATIN, PRAVASTATIN, ROSUVASTATIN and the pharmaceutically acceptable salts of these compounds.

15 . Pharmaceutical composition according to claim 1 , wherein the inflammatory pulmonary disease is selected from the group consisting of asthma, COPD, sclerosis, alveolitis, sarcoidosis, idiopathic pulmonary fibrosis and pulmonary hypertension.

16 . (canceled)

17 . (canceled)

18 . A method for the preventive or curative treatment of an inflammatory pulmonary disease comprising administering to a patient in need thereof a pharmaceutical composition comprising a pharmaceutical formulation including a first amount of a PDE4 inhibitor or a pharmaceutically acceptable salt thereof, a second amount of a HMG-CoA reductase inhibitor or a pharmaceutically acceptable salt thereof, wherein the first amount and the second amount together comprise an effective amount for the preventive or curative treatment of an inflammatory pulmonary disease, and at least one pharmaceutically acceptable auxiliary.

19 . A method for the preventive or curative treatment of an inflammatory pulmonary disease comprising administering to a patient in need thereof a combination product comprising the components:

(A) a first amount of a PDE4 inhibitor or a pharmaceutically acceptable salt thereof;

(B) a second amount of a HMG-CoA reductase inhibitor or a pharmaceutically acceptable salt thereof;

wherein the first and the second amount together comprise an effective amount for the preventive or curative treatment of an inflammatory pulmonary disease;

wherein each of the components (A) and (B) is formulated in admixture with at least one pharmaceutically acceptable auxiliary;

and wherein the components (A) and (B) are administered simultaneously, sequentially or separately.

20 . Method according to claim 18 , wherein the PDE4 inhibitor is selected from the group consisting of ROFLUMILAST, ROFLUMILAST N-Oxide, CILOMILAST, AWD-12-281, TOFIMILAST, TETOMILAST, LIRIMILAST, L-869298, OGLEMILAST, 2-{ 4 -[(4aS, 8aR)-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydro-1H-phthalazin-2-yl]-piperidin-1-yl}-acetamide and a pharmaceutically acceptable salt of these compounds.

21 . Method according to claim 18 , wherein the PDE4 inhibitor is selected from the group consisting of ROFLUMILAST, a pharmaceutically acceptable salt of ROFLUMILAST, ROFLUMILAST N-oxide and a pharmaceutically acceptable salt of ROFLUMILAST-N-oxide.

22 . Method according to claim 18 , wherein the PDE4 inhibitor is ROFLUMILAST.

23 . Method according to claim 18 , wherein the PDE4 inhibitor is ROFLUMILAST-N-oxide.

24 . Method according to claim 18 , wherein the PDE4 inhibitor is CILOMILAST or a pharmaceutically acceptable salt thereof.

25 . Method according to claim 18 , wherein the PDE4 inhibitor is AWD-12-281 or a pharmaceutically acceptable salt thereof.

26 . Method according to claim 18 , wherein the PDE4 inhibitor is TOFIMILAST or a pharmaceutically acceptable salt thereof.

27 . Method according to claim 18 , wherein the PDE4 inhibitor is TETOMILAST or a pharmaceutically acceptable salt thereof.

28 . Method according to claim 18 , wherein the PDE4 inhibitor is OGLEMILAST or a pharmaceutically acceptable salt thereof.

29 . Method according to claim 18 , wherein the HMG-CoA reductase inhibitor is selected from the group consisting of LOVASTATIN, PRAVASTATIN, SIMVASTATIN, ATORVASTATIN, FLUVASTATIN, ROSUVASTATIN, PITAVASTATIN, BERVASTATIN, DALVASTATIN, GLENVASTATIN and the pharmaceutically acceptable salts of these compounds.

30 . Method according to claim 18 , wherein the HMG-CoA reductase inhibitor is selected from the group consisting of ATORVASTATIN, SIMVASTATIN, PRAVASTATIN, ROSUVASTATIN and the pharmaceutically acceptable salts of these compounds.

31 . Method according to claim 19 , wherein the inflammatory pulmonary disease is selected from the group consisting of asthma, COPD, sclerosis, alveolitis, sarcoidosis, idiopathic pulmonary fibrosis and pulmonary hypertension.

32 . Method according to claim 19 , wherein the inflammatory pulmonary disease is COPD.

33 . Process for the preparation of a pharmaceutical composition as defined in claim 1 which comprises mixing the PDE4 inhibitor or a pharmaceutically acceptable salt thereof with the HMG-CoA reductase inhibitor or a pharmaceutically acceptable salt thereof.