O-sulphated bacterial polysaccharides and their use

Abstract

The present invention refers to the preparation of O-sulphated, N-sulphatated or N-acetylated derivatives, both epimerised or non epimerised, of K5, K4, and optionally defructosilated K4 and K40 polysaccharides and to their use as antiinflammatory agents in chronic and acute inflammations.

1 - 29 . (canceled)  
   
   
       30 . An O-sulfated, N-reacetylated K5 polysaccharide comprising: 
 i) a degree of sulfation of position 3 of the N-acetylglucosamine and of position 2 and 3 of glucuronic acid greater than 80%;    ii) a degree of acetylation between about 50 and about 95% of the relevant naturally acetylated polysaccharides; and    iii) a sulfates/carboxyls ratio from about 3.5 to about 4.    
   
   
       31 . The O-sulfated and N-reacetylated polysaccharide according to  claim 30  having a molecular weight from about 1,000 to about 60,000 Da.  
   
   
       32 . The O-sulfated and N-reacetylated polysaccharide according to  claim 31  having a molecular weight from about 5,000 to about 25,000 Da.  
   
   
       33 . A pharmaceutical composition suitable for inhibiting the production of proinflammatory cytokines selected from the group consisting of TNF, IL-1β, and IL-6, said composition comprising the polysaccharide according to  claim 30 .  
   
   
       34 . The pharmaceutical composition according to  claim 33  comprising the N-reacetylated, O-sulfated K5 polysaccharide characterized by the NMR spectrum shown in  FIG. 1 .  
   
   
       35 . A therapeutic method to inhibit the production of pro-inflammatory cytokines selected from the group consisting of TNF-α, IL-1β, and IL-6 in a subject in need of such a treatment comprising administering to said subject a therapeutically effective amount of a compound selected from the group consisting of: 
 a) reacetylated polysaccharides having an acetylation degree-comprised from about 50 to about 95% selected from the group consisting of    O-sulfated, N-reacetylated K5 polysaccharide according to  claim 30;     O-sulfated, N-reacetylated K4 polysaccharide;    O-sulfated, N-reacetylated and epimerized K5 polysaccharide;    O-sulfated, N-reacetylated, epimerized and partially desulfated K5 polysaccharide;    O-sulfated, N-reacetylated, epimerized, partially desulfated, optionally 6O-sulfated K5 polysaccharide; and    b) O-sulfated, N-sulfated and epimerized K5.    
   
   
       36 . The therapeutic method according to  claim 35  wherein the subject in need thereof is suffering from an acute or a chronic inflammation, autoimmune diseases, sepsis, septic shock, osteoarthritis, rheumatoid arthritis, ulcerative colitis, Chron's disease, cachexia and myocardial ischemia.  
   
   
       37 . A composition suitable for reducing or inhibiting the production of proinflammatory cytokines selected from the group consisting of TNF, IL-1β, and IL-6, said composition comprising a polysaccharide selected from the group consisting of: 
 a) reacetylated polysaccharides having an acetylation degree of from about 50 to about 95% selected from the group consisting of:    O-sulfated, N-reacetylated K5 polysaccharide according to  claim 30;     O-sulfated, N-reacetylated K4 polysaccharide;    O-sulfated, N-reacetylated and epimerized K5 polysaccharide;    O-sulfated N-reacetylated, epimerized and partially desulfated K5 polysaccharide;    O-sulfated N-reacetylated, epimerized, partially desulfated, optionally 6O-sulfated K5 polysaccharide; and    b) O-sulfated, N-sulfated and epimerized K5.