Controlled release pharmaceutical compositions comprising a fumaric acid ester

Abstract

The present invention relates to controlled release pharmaceutical compositions comprising fumaric acid ester(s) as active substance(s). The compositions are suitable for use in the treatment of e.g. psoriasis or other hyperproliferative, inflammatory or autoimmune disorders and are designated to release the fumaric acid ester in a controlled manner so that local high concentrations of the active substance within the gastrointestinal tract upon oral administration can be avoided and, thereby, enabling a reduction in gastro-intestinal related side-effects.

1 - 54 . (canceled) 
     
     
         55 . A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject in need thereof a pharmaceutical composition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate, monomethylfumarate, or a combination of dimethylfumarate and monomethylfumarate in a weight ratio between about 1:10 and 10:1, and (b) one or more pharmaceutically acceptable excipients, wherein the therapeutically effective amount of dimethylfumarate, monomethylfumarate, or a combination of dimethylfumarate and monomethylfumarate is 480 mg per day. 
     
     
         56 . The method of  claim 55 , wherein the pharmaceutical composition is administered in the form of a tablet or a capsule. 
     
     
         57 . The method of  claim 55 , wherein the therapeutically effective amount is administered in separate administrations of 1 to 3 doses. 
     
     
         58 . The method of  claim 57 , wherein the therapeutically effective amount is administered in separate administrations of 240 mg twice daily 
     
     
         59 . The method of  claim 57 , wherein the therapeutically effective amount is administered in separate administrations of 3 doses. 
     
     
         60 . The method of  claim 55 , wherein the pharmaceutical composition consists essentially of dimethylfumarate and one or more pharmaceutically acceptable excipients. 
     
     
         61 . The method of  claim 55 , wherein the pharmaceutical composition consists essentially of monomethylfumarate and one or more pharmaceutically acceptable excipients. 
     
     
         62 . The method of  claim 55 , wherein the pharmaceutical composition is administered to the subject for at least 1 week. 
     
     
         63 . The method of  claim 60 , wherein the therapeutically effective amount is administered to the subject as 240 mg twice daily. 
     
     
         64 . The method of  claim 63 , wherein the therapeutically effective amount is administered to the subject for at least 1 week. 
     
     
         65 . A method of treating a subject in need of treatment for multiple sclerosis consisting essentially of orally administering to the subject 480 mg per day of dimethylfumarate, monomethylfumarate, or a combination of dimethylfumarate and monomethylfumarate in a weight ratio between about 1:10 and 10:1. 
     
     
         66 . The method of  claim 65 , wherein 480 mg of dimethylfumarate per day is administered to the subject. 
     
     
         67 . The method of  claim 66 , wherein the dimethylfumarate is administered in separate administrations of 240 mg twice daily. 
     
     
         68 . The method of  claim 66 , wherein the dimethylfumarate is administered in separate administrations of 3 doses. 
     
     
         69 . A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject a pharmaceutical composition consisting essentially of (a) a therapeutically effective amount of dimethylfumarate and (b) one or more pharmaceutically acceptable excipients, wherein the therapeutically effective amount of dimethylfumarate is 480 mg per day. 
     
     
         70 . The method of  claim 69 , wherein the dimethyl fumarate is administered in separate administrations of 240 mg twice daily. 
     
     
         71 . A method of treating a subject in need of treatment for multiple sclerosis comprising treating the subject in need thereof with a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination of dimethyl fumarate and monomethyl fumarate in a weight ratio between about 1:10 and 10:1, wherein the therapeutically effective amount of dimethylfumarate, monomethylfumarate, or a combination of dimethylfumarate and monomethylfumarate is 480 mg per day.