Compounds and compositions for the treatment of muscular disorders and bone disorders

Abstract

The present invention relates to compounds and compositions and their applications as pharmaceuticals for treating, preventing, or reversing injury to skeletal or cardiac muscles, for treating or preventing diseases relating to the structure and function of skeletal or cardiac muscle, and for inducing regeneration or restructuring of skeletal or cardiac muscle as a means of treating diseases relating to abnormalities in skeletal or cardiac muscle structure and function in a human or animal subject. Further aspects relate to the same or similar applications for bone and bone diseases.

What is claimed is: 
     
         1 . A method to induce increased cellular or muscular or bodily production of follistatin and follistatin-like proteins in order to reverse or ameliorate injury to, or weakness of, or loss of, bone, or to prevent fractures, in a subject in need thereof, comprising administering to a subject a therapeutically effective dose of (+)-epicatechin and/or (−)-epicatechin or an epicatechin derivative of either (+)-epicatechin or (−)-epicatechin 
     
     
         2 . The method of  claim 1  wherein the (+)-epicatechin and/or (−)-epicatechin or an epicatechin derivative is administered orally or intravenously or intramuscularly, at 5 mg to 2 grams per day, in a single dose or in divided doses. 
     
     
         3 . The method of  claim 1  wherein the (+)-epicatechin and/or the (−)-epicatechin or an epicatechin derivative is administered at a dose between 0.1 mg/kg of bodyweight per day to 10 mg/kg of bodyweight per day, orally or intravenously or intramuscularly, in a single dose or in divided doses. 
     
     
         4 . The method of  claim 1  wherein the method induces new bone formation or additional bone formation or stronger bone formation or regeneration of bone in order to prevent bone fractures. 
     
     
         5 . A method to induce the increased cellular or muscular or bodily production of follistatin and follistatin-like proteins in order to reverse or ameliorate weakness of bone, thus preventing bone fractures, caused by administration of compounds known to induce weakness of or damage to bone, impairment of bone generation, or impairment of bone growth, including but not limited to corticosteroids such as prednisone, or deflazacort, anticonvulsants such as phenytoin and phenobarbital, chemotherapeutics such as aromatase inhibitors, and progestins. 
     
     
         6 . A method to induce the increased cellular or muscular or bodily production of follistatin or follistatin-like proteins in order to reverse or ameliorate weakness of bone strength, thus preventing bone fractures, associated with genetic predisposition, aging, inactive lifestyle, or low estrogen states such as menopause or post oophorectomy. 
     
     
         7 . A method to induce the increased cellular or muscular or bodily production of follistatin or follistatin-like proteins in order to reverse or ameliorate weakness of bone caused by medical conditions known to be associated with weakness of, or damage to, bone, impairment of bone generation, or impairment of bone growth, such as celiac disease, kidney or liver disease, and inflammatory diseases such as systemic lupus erythematosus and rheumatoid arthritis. 
     
     
         8 . A method to induce the increased cellular or muscular or bodily production of follistatin or follistatin-like proteins in order to reverse or ameliorate weakness of bone in conjunction with the administration of other agents used to treat osteoporosis including calcium, Vitamin D, and calcitonin, in order to prevent bone fractures. 
     
     
         9 . A method to induce increased cellular or muscular or bodily production of follistatin or follistatin-like proteins as a therapeutic to accelerate the healing of bone fractures or to increase the degree of recovery from a bone fracture, such as those experienced in accidents, athletics, or combat. 
     
     
         10 . A method to induce increased cellular or muscular or bodily production of follistatin or follistatin-like proteins in order to prevent systemic loss of bone density, and thus prevent subsequent bone fractures, during the recovery period after orthopedic surgery or after the onset of a disease or condition necessitating long periods of bed rest or physical inactivity, which are known to result in decreased bone density and muscle weakness. 
     
     
         11 . The method of  claim 4  wherein the (+)-epicatechin and/or (−)-epicatechin or an epicatechin derivative is administered orally or intravenously or intramuscularly, at 5 mg to 2 grams per day, in a single dose or in divided doses. 
     
     
         12 . The method of  claim 5  wherein the (+)-epicatechin and/or (−)-epicatechin or an epicatechin derivative is administered orally or intravenously or intramuscularly, at 5 mg to 2 grams per day, in a single dose or in divided doses. 
     
     
         13 . The method of  claim 6  wherein the (+)-epicatechin and/or (−)-epicatechin or an epicatechin derivative is administered orally or intravenously or intramuscularly, at 5 mg to 2 grams per day, in a single dose or in divided doses. 
     
     
         14 . The method of  claim 7  wherein the (+)-epicatechin and/or (−)-epicatechin or an epicatechin derivative is administered orally or intravenously or intramuscularly, at 5 mg to 2 grams per day, in a single dose or in divided doses. 
     
     
         15 . The method of  claim 8  wherein the (+)-epicatechin and/or (−)-epicatechin or an epicatechin derivative is administered orally or intravenously or intramuscularly, at 5 mg to 2 grams per day, in a single dose or in divided doses. 
     
     
         16 . The method of  claim 9  wherein the (+)-epicatechin and/or (−)-epicatechin or an epicatechin derivative is administered orally or intravenously or intramuscularly, at 5 mg to 2 grams per day, in a single dose or in divided doses. 
     
     
         17 . The method of  claim 10  wherein the (+)-epicatechin and/or (−)-epicatechin or an epicatechin derivative is administered orally or intravenously or intramuscularly, at 5 mg to 2 grams per day, in a single dose or in divided doses.