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Use of fumaric acid derivatives for treating cardiac insufficiency, and asthmaRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, 25 Or More Peptide Repeating Units In Known Peptide Chain StructureUse of fumaric acid derivatives for treating cardiac insufficiency, and asthma description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070027076, Use of fumaric acid derivatives for treating cardiac insufficiency, and asthma. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] The present invention relates to the use of fumaric acid derivatives for preparing a drug for treating cardiac insufficiency, and asthma. PRIOR ART [0002] Fumaric acid dialkyl esters and fumaric acid monoalkyl esters and salts thereof have been successfully used for treating psoriasis for a long time. The use has been described in a number of patents, cf. e.g. DE 25 30 372, DE 26 21 214 or EP-B-0 312 697. [0003] Also, the use of fumaric acid mono- and diesters for treating autoimmune diseases such as e.g. polyarthritis or multiple sclerosis (cf. DE 197 21 099.6 and DE 198 53 487.6), but also for use in transplantation medicine (cf. DE 198 53 487.6 and DE 198 39 566.3) has been described. Moreover, the use of fumaric acid mono- and diesters for treating NFkappaB-mediated diseases as well as the treatment of mitochondrial diseases and/or as NFkappaB inhibitor is known from DE 101 01 307.8 and DE 100 00 577.2. All mentioned publications describe fumaric acid mono- and diesters, optionally in the form of certain salts. [0004] Also, the use of fumaric acid mono- and diamides for treating said indications is known from DE 101 33 004.9. These amides are formed with amino acids and preferably with specific peptides. Finally, fumaric acid oligomers and their use for treating said diseases are known from DE 102 17 314.1. [0005] A paroxysmal, marked respiratory distress is understood by asthma (bronchial asthma) from which approx. 4 to 5% of the population of the industrial nations are suffering, there being an upward tendency. This respiratory distress is based on a variable and reversible obstruction of the respiratory tract due to a hyperreactive bronchial system, which is triggered by exogenic and/endogenic stimuli. These include chemical or physical provocative factors, infections, physical effort and/or emotional factors. After a longer duration of the disease, secondary diseases such as a chronic bronchitis, a pulmonary emphysema, bronchiectases, atelectases or a pulmonary heart disease or a respiratory cardiac insufficiency usually occur. [0006] Depending upon the cause, differentiation is made between the following variants of asthma, namely asthma caused by allergies, infections, analgesics, job conditions or physical effort, mixed forms of asthma or asthma cardiale (cardiac asthma), nasal asthma and asthma uremicum. In particular, asthma cardiale may result in respiratory distress due to increased congestion in the lesser circulation in the case of a left ventricular insufficiency. [0007] Nowadays, beta-2 sympathomimetics, corticosteroids, parasympatholytics, theophylline, anti-inflammatory agents and anti-allergic agents are, for instance, administered in the drug treatment of and/or for alleviating asthma, in addition to the still proven means of just avoiding the triggering stimulus. [0008] On a molecular level, asthma seems to be characterized by an increased activity of Th2 lymphocytes in the lung, which, in turn, results in an increased release of some Th2 cytokines which, ultimately, gives rise to the known features of asthma such as IgE isotype switching, mucus production and recruitment and activation of eosinophils. Moreover, Th2 cytokines seem to result in the differentiation of further Th2 cells through the signal transduction pathway known as JAK-STAT, from which a self-enhancing circle results. An increased proliferation of mesenchymal cells, in particular bronchial smooth muscle cells, was also observed. [0009] The so-called JAK-STAT signal transduction pathway (JAnus Kinase Signal Transducer and Activator of Transcription pathway) is a pathway for transmitting information to be transmitted by signal peptides such as e.g. cytokines to the interior of the cell and/or the nucleus. Signal transduction takes place through STAT proteins that are present in the cytoplasm and are at first inactive; 7 different STAT proteins are know in man. As a result of a receptor ligand bonding on the cell surface, these STAT proteins are quickly activated by means of phosphorylation, e.g. by means of the Janus kinase. Phosphorylation results in the homo- or heterodimerization of the STAT proteins, the dimers being rapidly transported into the nucleus, where they bond to a target promoter and drastically enhance the transcription rate of this promoter. [0010] An acute or chronic inability of the heart to deliver the output of blood required for metabolism and/or receive the venous return under stress (stress insufficiency) or already at rest (=rest insufficiency) are understood by cardiac insufficiency. The insufficiency may occur as a pure left ventricular or right ventricular insufficiency, but may as well affect both ventricles. [0011] The clinical picture of cardiac insufficiency can be attributed to various causes in terms of etiology, above all to inflammatory and degenerative changes of the myocardium and endocardium, coronary circulatory disorders, myocardial infarction and injuries. Subsequently, cardiac insufficiency results in changes in the peripheral circulation, breathing disorders, in particular cardiac asthma, renal insufficiency and disorders of the electrolyte metabolism and edemas and a reduced functional capacity of the skeletal muscles. [0012] As regards to the indication, differentiation is made between acute cardiac insufficiency, energetic cardiac insufficiency, energetic-dynamic cardiac insufficiency and hypodynamic cardiac insufficiency, also called HEGGLIN syndrome II, excitomotoric cardiac insufficiency, cardiac insufficiency as a result of cardiac arrythmics, hypoxemic, latent, primary, compensated, relative or stress insufficiency and/or left ventricular insufficiency. [0013] At present, contraction-promoting substances are used for the drug treatment of cardiac insufficiency, glycosides (above all digoxin and digitoxin) being still used today for treating the chronic forms. However, during the last few years, vasodilators (nitro-compounds and dihydralazine, alpha blockers, calcium antagonists and above all ACE inhibitors) have gained in importance. ACE inhibitors are most important for long-term treatment. Moreover, diuretics are used. Acute forms are treated with catecholamines, possibly also with amrinone. [0014] It is an object of the invention to provide a further agent for the treatment of cardiac insufficiency and asthma. In particular, it is an object of the invention to provide a therapeutic agent for both cardiac asthma and left ventricular insufficiency in the area in which they overlap with each other. It is another object of the invention to provide a therapeutic agent for both indications individually or in the area in which they overlap with each other, which, due to its good tolerance, is suited for long-term therapy. [0015] The present object is attained by the use of fumaric acid derivatives for preparing pharmaceuticals or pharmaceutical preparations for treating asthma and/or cardiac insufficiency, in particular in man. SUMMARY OF THE INVENTION [0016] 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 pharmaceutical preparation for the treatment or prevention of cardiac insufficiency, in particular left ventricular insufficiency, myocardial infarction and angina pectoris. [0017] 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 pharmaceutical prepration 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. [0018] The present invention likewise concerns a method for inhibiting .sup.3H-thymidine uptake by bronchial smooth muscle cells, and a method of inhibiting proliferation of these cells as described below and in the appending claims. [0019] The present invention finally concerns the use of the above fumaric acid derivatives for inhibiting the PDGF induced STAT1 activation; DESCRIPTION OF THE DRAWINGS [0020] FIG. 1 is a bar chart which shows the extent of infarctions after administration of DMF, ischemia and for controls. [0021] FIG. 2 shows the percentage inhibition of PDGF-induced .sup.3H-thymidine incorporation in bronchial smooth muscle cells, when DMF is added. Continue reading about Use of fumaric acid derivatives for treating cardiac insufficiency, and asthma... Full patent description for Use of fumaric acid derivatives for treating cardiac insufficiency, and asthma Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Use of fumaric acid derivatives for treating cardiac insufficiency, and asthma patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. 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