New low molecular weight sulfated polysaccharides, useful as wound-healing agents for connective tissue, are derived from marine bacterial exopolysaccharides by depolymerization and sulfatation

摘要

Low molecular weight, sulfated polysaccharide derivatives (A) from native marine exopolysaccharides (EPS), excreted by marine mesophilic bacteria derived from hydrothermal media, are new. Low molecular weight, sulfated polysaccharide derivatives (A) from native marine exopolysaccharides (EPS), excreted by marine mesophilic bacteria derived from hydrothermal media, are new. (A) are prepared by: (a) radical depolymerization of native EPS to derivatives (B) of molecular weight not over 0.1 MD; (b) sulfatation of (B), optionally freeze-dried, by adding enough of at least one sulfatation agent to form (A) with a degree of substitution by sulfate 10-45wt.% of the final product; and (c) optionally dialysis. ACTIVITY : Vulnerary; Antiinflammatory; Antibacterial; Cytostatic; Immunosuppressive; Dermatological. MECHANISM OF ACTION : (A) stimulate proliferation of fibroblasts, so promote reconstruction and remodeling of injured tissues; inhibit secretion of proinflammatory cytokines (especially interleukin-1Lbeta and tissue necrosis factoralpha ) and matrix metalloproteases (especially gelatinase A and stromelysin 1) by fibroblasts; inhibit the classical complement system; promote fibroblast proliferation at the expense of myofibroblasts; and promote selective proliferation of medullar cells committed to mesenchymal differentiation at the expense of other subpopulations. A two-dimensional culture of dermal fibroblasts was incubated in nutrient medium containing 10 mu g/ml of HE 800 DRNS (produced from the exopolysaccharide of Vibrio diabolicus by depolymerization, de-N-acetylation and sulfatation). After 10 days, the number of cells was 146% of that in a control culture without HE 800 DRNS.