Use of lipid conjugates in the treatment of inflammatory disorders

Abstract

This invention provides for the use of compounds represented by the structure of the general formula (A): wherein L is a lipid or a phospholipid, Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol, Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, X is a physiologically acceptable monomer, dimer, oligomer, or polymer, wherein X is a glycosaminoglycan; and n is a number from 2 to 1000, wherein any bond between L, Z, Y and X is either an amide or an esteric bond in treating a subject suffering from a disease associated with harmful angiogenic processes such as cancer.

What we claim is: 
     
         1 . A method of treating osteoarthritis in a subject in need thereof, comprising the step of administering to said subject a composition comprising a compound of the general formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms; 
         R 2  is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms; 
         Y is either nothing or a spacer group ranging in length from 2 to 30 atoms; 
         X is a glycosaminoglycan; and 
         n is a number from 1 to 1,000; 
         wherein if Y is nothing the phosphatidylethanolamine is directly linked to X via an amide bond and if Y is a spacer, said spacer is a straight or branched chain alkylene selected from the group consisting of —CO-alkylene-CO, —NH-alkylene-NH—, —CO-alkylene-NH—, and said spacer is directly linked to X via an amide or an esteric bond and to said phosphatidylethanolamine via an amide bond, thereby treating osteoarthritis in said subject. 
       
     
     
         2 . The method of  claim 1 , wherein said glycosaminoglycan is hyaluronic acid, heparin, heparan sulfate, chondroitin, chondroitin sulfate, keratan, keratan sulfate, dermatan sulfate or a derivative thereof. 
     
     
         3 . The method of  claim 1 , wherein said compound comprises sugar rings of said glycosaminoglycan, which are intact. 
     
     
         4 . The method of  claim 1 , wherein each of R1 and R2 is dipalmitoyl or dimyristoyl. 
     
     
         5 . The method of  claim 1 , wherein said glycosaminoglycan has a molecular weight of 500,000 to 1,000,000 Daltons. 
     
     
         6 . The method of  claim 1 , wherein said glycosaminoglycan has a molecular weight of 1,000,000 to 2,000,000 Daltons. 
     
     
         7 . The method of  claim 1 , wherein n is a number from 2 to 100. 
     
     
         8 . The method of  claim 1 , wherein joint pain is alleviated in said subject in need thereof. 
     
     
         9 . The method of  claim 1 , wherein knee pain is alleviated in said subject in need thereof. 
     
     
         10 . The method of  claim 1 , wherein progressive stiffness of a joint is alleviated in said subject in need thereof. 
     
     
         11 . The method of  claim 1 , wherein progressive stiffness of a knee is alleviated in said subject in need thereof. 
     
     
         12 . The method of  claim 1 , wherein inflammation of a joint lining is alleviated in said subject in need thereof. 
     
     
         13 . The method of  claim 1 , wherein said composition is administered via the intravenous route. 
     
     
         14 . The method of  claim 1 , wherein said composition is administered via the subcutaneous route. 
     
     
         15 . The method of  claim 1 , said method further comprises administering a second drug for treating osteoarthritis. 
     
     
         16 . The method of  claim 15 , wherein said second drug is selected from the group consisting of: steroid, glucosamine, chondroitin, and methylsulfonylmethane (MSM).