PREPARATION AND CHARACTERIZATION OF NOVEL POLY(ALKYLAMINE)-BASED HYDROGELS DESIGNED FOR USE AS BILE-ACID SEQUESTRANTS

Preparation of novel poly(alkylamine)-derived hydrogels is described. Polymers are prepared via reaction of various diamines with dihalo com pounds or diepoxides. N-substituted polymers are readily prepared by r eaction of primary amines with dihalo compounds. The resulting covalen tly cross-linked polymers exhibit hydrogel behavior (high swell with w ater) when ionized to polyammonium species at low pH. At high pH, the polymers reside in the free base polyamine form and lose all hydrogel character (they no longer swell in water). Characterization of polymer structure with carbon-13 MMR, thermal analysis, and swell behavior re veals a structure which is highly branched and only loosely cross-link ed. In the ionic polyammonium form thermal stability up to similar to 300 degrees C is observed. The polymers exhibit activity as bile acid sequestrants significantly superior to cholestyramine, as evidenced by their ability to efficiently bind quantities of cholate when tested i n vitro. This behavior indicates that these hydrogels should be very u seful for the treatment of hypercholesterolemia.