Process for the preparation of heparanase-inhibiting sulfated hyaluronates and products obtained thereby

摘要

A series of heparanase-inhibiting, sulfated hyaluronates having an average molecular weight of from 6,000 to 38,000 and a degree of sulfation of from 1.8 to 4.0 were prepared from high-molecular weight hyaluronic acid by a method involving partial depolymerization and extensive O-sulfation, comprising a treatment of the starting hyaluronic acid with a sulphuric acid and chlorosulfonic acid mixture and optional size-fractionation, optionally followed by a selective 6-O-desulfation. Extensively sulfated hyaluronates (degree of sulfation of from 2.8 to 4) inhibit heparanase with at least the same potency as heparin. Subsequent O-desulfation affords new 6-O-desulfated, sulfated hyaluronates having a degree of sulfation of from 1.8 to 2.8 and also showing heparanase-inhibiting activity. Said O-sulphated hyaluronates are new glycosaminoglycans useful for the preparation of medicaments with antimetastatic and tumor growth inhibiting activity.