Use of fumaric acid derivatives for treating cardiac insufficiency, and asthma

Abstract

According to a first aspect the invention relates to the use of fumaric acid derivatives selected from the group consisting of dialkyl fumarates, monoalkyl hydrogen fumarates, fumaric acid monoalkyl ester salts, fumaric acid monoamides, monoamido fumaric acid salts, fumaric acid diamides, monoalkyl monoamido fumarates, carbocyclic and oxacarbocyclic oligomers of these compounds and mixtures thereof for preparing a drug for the treatment or prevention of cardiac insufficiency, in particular left ventricular insufficiency, myocardial infarction and angina pectoris. According to a second aspect the invention relates to the use of fumaric acid derivatives, selected from the group consisting of dialkyl fumarates, monoalkyl hydrogen fumarates, fumaric acid monoalkyl ester salts, fumaric acid monoamides, monoamido fumaric acid salts, fumaric acid diamides, monoalkyl monoamido fumarates, carbocyclic and oxacarbocyclic oligomers of these compounds and mixtures thereof for preparing a drug for the treatment of asthma and chronic obstructive pulmonary diseases, especially asthma caused by allergies, infections, analgesics, job conditions or physical effort, mixed forms of asthma, or asthma cardiale.

1 .- 26 . (canceled) 
     
     
         27 . A method for treating chronic obstructive pulmonary disease, comprising administering to a patient in need of said treating a fumaric acid derivative that is:
 (a) a compound selected from the group consisting of a dialkyl fumarate, a monoalkyl hydrogen fumarate, a fumaric acid monoalkyl ester salt, a fumaric acid monoamide, a monoamido fumaric acid salt, a fumaric acid diamide, and a monoalkyl monoamido fumarate;   (b) a carbocyclic oligomer of said compound;   (c) an oxacarbocyclic oligomer of said compound; or   (d) a mixture of any of the foregoing.   
     
     
         28 . The method according to  claim 27 , wherein the fumaric acid derivative is a fumaric acid dialkyl ester of the formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  which are the same or different, independently represent a linear, branched or cyclic, saturated or unsaturated C 1-24  alkyl radical or a C 5-20  aryl radical, and wherein the C 1-24  alkyl radical or the C 5-20  aryl radical is optionally substituted with halogen, hydroxy, C 1-4  alkoxy, C 1-4  alkyl, nitro or cyano. 
       
     
     
         29 . The method according to  claim 27 , wherein the fumaric acid derivative is a fumaric acid monoalkyl ester of the formula (II): 
       
         
           
           
               
               
           
         
         wherein R 1  represents a linear, branched or cyclic, saturated or unsaturated C 1-24  alkyl radical or a C 5-20  aryl radical; 
         A represents hydrogen, an alkaline or alkaline earth metal cation or a physiologically acceptable transition metal cation; and 
         n equals 1 or 2 and corresponds to the valence of A. 
       
     
     
         30 . The method according to  claim 27 , wherein the fumaric acid derivative is
 (i) a compound of formula (I),   
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  which are the same or different, independently represent a linear, branched or cyclic, saturated or unsaturated C 1-24  alkyl radical or a C 5-20  aryl radical, and wherein the C 1-24  alkyl radical or the C 5-20  aryl radical is optionally substituted with halogen, hydroxy, C 1-4  alkoxy, C 1-4  alkyl, nitro or cyano, 
         (ii) a compound of Formula (II) 
       
       
         
           
           
               
               
           
         
         wherein R 1  represents a linear, branched or cyclic, saturated or unsaturated C 1-24  alkyl radical or a C 5-20  aryl radical; A represents hydrogen, an alkaline or alkaline earth metal cation or a physiologically acceptable transition metal cation; and n equals 1 or 2 and corresponds to the valence of A, or 
         (iii) a mixture of a compound of Formula (I) and a compound of Formula (II). 
       
     
     
         31 . The method according to  claim 30 , wherein the fumaric acid derivative is selected from the group consisting of fumaric acid dimethyl ester, fumaric acid diethyl ester, fumaric acid methyl ethyl ester, methyl hydrogen fumarate, ethyl hydrogen fumarate, calcium methyl fumarate, calcium ethyl fumarate, magnesium methyl fumarate, magnesium ethyl fumarate, zinc methyl fumarate, zinc ethyl fumarate, iron methyl fumarate, iron ethyl fumarate and mixtures thereof. 
     
     
         32 . The method according to  claim 27 , wherein a pharmaceutical preparation is administered to the patient, wherein said pharmaceutical preparation comprises an amount of the fumaric acid derivative that corresponds to 1 to 500 mg of fumaric acid. 
     
     
         33 . The method according to  claim 27 , wherein the fumaric acid derivative is fumaric acid dimethyl ester. 
     
     
         34 . The method according to  claim 27 , wherein a pharmaceutical preparation is administered to the patient, wherein said pharmaceutical preparation comprises 10 to 500 mg of fumaric acid dimethyl ester. 
     
     
         35 . The method according to  claim 27 , wherein the administering is orally. 
     
     
         36 . The method according to  claim 33 , wherein the administering is orally. 
     
     
         37 . The method according to  claim 27 , wherein the fumaric acid derivative is in a pharmaceutical preparation suitable for oral, rectal, transdermal, dermal, ophthalmological, nasal, pulmonary or parenteral application. 
     
     
         38 . The method according to  claim 35 , wherein the fumaric acid derivative is provided in the form of tablets, coated tablets, capsules, granulate, solutions for drinking, liposomes, nano-particles, nano-capsules, micro-capsules, micro-tablets, pellets or powders and in the form of granules filled in capsules or sachets, micro-tablets filled in capsules or sachets, pellets filled in capsules or sachets, nano-particles filled in capsules or sachets or powder filled in capsules or sachets. 
     
     
         39 . The method according to  claim 35 , wherein the fumaric acid derivative is present in the form of nano-particles, pellets or micro-tablets which may optionally be filled in sachets or capsules. 
     
     
         40 . The method according to  claim 35 , wherein the fumaric acid derivative is in a solid oral dosage form that is provided with an enteric coating. 
     
     
         41 . The method according to  claim 40 , wherein the solid oral dosage form is a tablet, micro-tablet or pellet. 
     
     
         42 . The method of  claim 27 , wherein the fumaric acid derivative is administered in combination with a glucocorticoid. 
     
     
         43 . The method of any one of  claims 28 ,  33 ,  35 ,  36  or  40 , wherein the fumaric acid derivative is administered in combination with a glucocorticoid. 
     
     
         44 . The method of  claim 27  or  36 , wherein the fumaric acid derivative is administered in combination with a glucocorticoid, and wherein the glucocorticoid is selected from the group consisting of dexamethasone, cortisone, hydrocortisone, prednisolone, prednisone, methylprednisolone, fluocortolone, triamcinolone, beclomethasone, budenoside, flunisonide, fluticasone, betamethasone, and pharmaceutically acceptable salts and derivatives thereof. 
     
     
         45 . The method of  claim 42 , wherein the glucocorticoid is dexamethasone. 
     
     
         46 . The method of  claim 45 , wherein the administering of the fumaric acid derivative and the administering of the glucocorticoid is sequential. 
     
     
         47 . The method of  claim 45 , wherein the fumaric acid derivative and the glucocorticoid are administered in separate dosage units.