Compositions and methods for the treatment of musculoskeletal related diseases and disorders using metal ion-citrate analog complexes

Abstract

The invention is directed to a composition and associated method for the treatment of musculoskeletal related disorders and diseases. In particular, the present invention provides a class of citrate compounds that can be used to for the treatment of diseases/disorders characterized by the degeneration of musculoskeletal tissues including menisci, bone, articular cartilage, and soft tissues. Examples of suitable citrate and citrate analog compounds include citrates having the following base formula (I): where X may be one of the following: wherein Y, Y′, and Y″ are independently a citrate moiety, O, O—Y, OH, NH, NH—Y, R and R—Y, with R being an alkyl, alkyene, ester, aryl, or phenyl group having from 1 to 6 carbon atoms.

1 - 25 . (canceled) 
     
     
         26 . A method for treating a musculoskeletal disease or disorder, the method comprising the step of administering to a subject in need thereof an effective amount of a composition comprising a citrate compound or a pharmaceutically acceptable salt thereof that is complexed with a metal ion, wherein the musculoskeletal disease or disorder is pain or discomfort in bones or joints; back pain; limitation of motion; arthritis;
 osteoporosis; ligament injury; intervertebral disc degeneration; meniscal injury associated with meniscal degeneration, meniscal tears, and/or meniscus transplantation; or degeneration of menisci, bone, cartilage, or soft tissue; and wherein the citrate compound has the following formula:   
       
         
           
           
               
               
           
         
       
       where X is one of the following: 
       
         
           
           
               
               
           
         
       
       wherein Y is a citrate moiety, O, OH, NH, or R; Y′ and Y″ are independently a citrate moiety, O, O—Y, OH, NH, NH—Y, R or R—Y, with R being an alkyl, alkene, ester, or aryl group having from 1 to 6 carbon atoms; and Z is a carboxyl group, H, or R. 
     
     
         27 . The method of  claim 26 , wherein the metal ion is selected from the group consisting of magnesium, manganese, calcium, strontium, iron, zinc, aluminum, and combinations thereof. 
     
     
         28 . The method of  claim 26 , wherein the ratio of metal ion to citrate compound is from 1:6 to 3:1. 
     
     
         29 . The method of  claim 26 , wherein the composition is administered at a dosage from 2 mg to 200 mg/kg body weight. 
     
     
         30 . The method of  claim 26 , further comprising administering chondroitin sulfate, pentosan polysulfate, or a combination thereof. 
     
     
         31 . The method of  claim 26 , further comprising combining the composition with a steroid prior to administering to a subject. 
     
     
         32 . The method of  claim 26 , wherein the composition is administered orally. 
     
     
         33 . The method of  claim 26 , wherein the composition is administered topically. 
     
     
         34 . The method of  claim 26 , wherein the composition is provided as a caplet, tablet, particle, granule, or powder. 
     
     
         35 . The method of  claim 26 , wherein the composition is provided as a liquid, patch, lotion, ointment, or cream. 
     
     
         36 . The method of  claim 26 , wherein X is 
       
         
           
           
               
               
           
         
       
       Y″ is O; and Y′ and Y are OH.