Methods and compositions for selectively removing potassium ion from the gastrointestinal tract of a mammal

A pharmaceutical composition for removing potassium ion from a gastrointestinal tract of a mammal, the pharmaceutical composition comprising a pharmaceutical excipient and a core-shell particle, the core-shell particle comprising a core polymer and a shell polymer, the core polymer having a capacity for binding potassium ion, the shell polymer having a persistent selectivity for potassium ion over magnesium ion,

• the pharmaceutical composition having a specific binding for potassium ion of at least 1.5 mmol/gm achieved within a potassium-binding period of less than 18 hours, and the pharmaceutical composition having a specific binding for magnesium ion of not more than 1.0 mmol/gm maintained over a magnesium-binding period of more than 18 hours,
• as determined in vitro in an assay selected from the group consisting of
• (i) a first assay consisting essentially of incubating the pharmaceutical composition at a concentration of 4 mg/ml in a solution consisting essentially of 55 mM KCl, 55 mM MgCl2 and 50 mM 2-morpholinoethanesulfonic acid, monohydrate, at a pH of 6.5 and a temperature of 37° C. for 48 hours with agitation, and directly or indirectly measuring cations bound to the pharmaceutical composition over time,
• (ii) a second assay consisting essentially of incubating the pharmaceutical composition at a concentration of 4 mg/ml in a solution consisting essentially of 50 mM KCl, 50 mM MgCl2, 50 mM 2-morpholinoethanesulfonic acid, monohydrate, 5 mM sodium taurocholate, 30 mM oleate and 1.5 mM citrate, at a pH of 6.5 and a temperature of 37° C. for 48 hours with agitation, and directly or indirectly measuring cations bound to the pharmaceutical composition over time, and
• (iii) a third assay consisting essentially of incubating the pharmaceutical composition at a concentration of 4 mg/ml in fecal water solution, the fecal water solution being a filtered centrifugal supernatant derived by centrifuging human feces for 16 hours at 50,000 g at 4° C. and then filtering the supernatant through a 0.2 um filter, the pharmaceutical composition being incubated in the fecal water solution at a temperature of 37° C. for 48 hours with agitation, and directly or indirectly measuring cations bound to the pharmaceutical composition over time, and
• combinations of one or more of the first assay, the second assay and the third assay;
• the core polymer being a crosslinked cation exchange polymer and the shell polymer being a crosslinked polyvinylamine polymer represented by Formula I:
• wherein n is at least 4, and
• R1 and R2 are independently hydrogen, alkyl, or aryl.