Compositions for and methods of treating acid-base disorders

A method of treating an individual afflicted with metabolic acidosis, the method comprising oral administration of a daily dose of a pharmaceutical composition having the capacity to bind at least 5 mEq of a target species as it transits the digestive system to achieve a clinically significant increase in the serum bicarbonate value of at least 1 mEq/1 from baseline within a treatment period of 15 days, the target species being selected from the group consisting of protons, strong acids, and conjugate bases of strong acids wherein the pharmaceutical composition is a nonabsorbable composition comprising a proton-binding, crosslinked amine polymer comprising the residue of an amine corresponding to Formula 1:

• wherein R1, R2 and R3 are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl provided, however, at least one of R1, R2 and R3 is other than hydrogen, and
• the crosslinked amine polymer is prepared in a two-step process, wherein
• the first polymerization crosslinking step yields preformed amine polymer beads having a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid (“SGF”) and a Swelling Ratio in the range of 1 to 6,
• the resulting preformed amine polymer is then at least partially deprotonated with a base and combined with a non-protonating swelling agent to swell the free amine polymer without protonating the amine functions, and
• in the second crosslinking step, the swollen, deprotonated preformed amine polymer is crosslinked with 1,2-dichloroethane to form a post-polymerization crosslinked polymer.