Compositions and methods for treating hyperkalemia
Inventors
Charmot, Dominique • Davidson, James P. • Lin, Fangling • Jacobs, Jeffrey W. • Blinova, Natalia • Labonte, Eric • Langsetmo, Ingrid • Blanks, Robert C.
Assignees
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Publication Number
US-9655921-B2
Publication Date
2017-05-23
Expiration Date
Abstract
The present invention is directed to compositions and methods of removing potassium or treating hyperkalemia by administering pharmaceutical compositions of cation exchange polymers with low crosslinking for improved potassium excretion and for beneficial physical properties to increase patient compliance.
Core Innovation
The invention relates to compositions and methods for removing potassium from the gastrointestinal tract of a patient showing clinical signs of hyperkalemia or suspected of having hyperkalemia by administering a calcium salt of a potassium binding polymer. The potassium binding polymer is crosslinked and has a defined structural relationship in which the ratio of m and n provides a polymer having 1.6% to 1.9% cross-linking. The described polymer is a calcium salt form of a potassium binding polymer.
The disclosed calcium polystyrene sulfonate (Ca-PSS) potassium-binding crosslinked polymers are produced as PS-DVB crosslinked beads formed using suspension/seeded polymerization and inverse-suspension polymerization. The synthesis includes sulfonation to polystyrene sulfonate and conversion to a calcium salt using a calcium salt-forming process described in the partial content. Free-radical initiators and suspension stabilizers/surfactants are described as part of the polymer preparation.
The polymers are characterized by controlled divinylbenzene crosslinking level and polymer particle size distribution and are evaluated by swelling ratio and potassium exchange capacity, with residual styrene reported. The partial content further indicates downstream pharmaceutical formulation concepts for patient administration, including oral and rectal routes and sodium-free oral suspensions, jellies, and chewables.
Claims Coverage
The provided material includes one independent claim for a gastrointestinal potassium removal method, with dependent claims refining the polymer structure and physical parameters using quantitative constraints. The independent claim includes one inventive feature focused on the method and polymer crosslinking definition.
Gastrointestinal potassium removal using a calcium salt of a crosslinked potassium binding polymer with defined m:n cross-linking
A method for removing potassium from the gastrointestinal tract of a patient showing clinical signs of hyperkalemia or suspected of having hyperkalemia, comprising administering a calcium salt of a potassium binding polymer, wherein the crosslinked potassium binding polymer has a structure in which the ratio of m and n provides a polymer having 1.6% to 1.9% cross-linking.
Potassium exchange capacity range
The method is characterized by administering the calcium salt of a potassium binding polymer whose potassium exchange capacity is from about 1 mEq to about 4 mEq per gram of potassium binding polymer.
Water swelling ratio range
The method further requires that the potassium binding polymer has a water swelling ratio of between about 3 grams of water per gram of polymer to about 8 grams of water per gram of polymer.
Substantially spherical particles with controlled median diameter
The method is further limited such that the potassium binding polymer includes substantially spherical particles with a median diameter of about 5 μm to about 130 μm.
Controlled particle-size distribution ratios
The method is characterized by specific limits on the ratios of Dv(0.9) to Dv(0.5) and of Dv(0.5) to Dv(0.1).
The claim coverage centers on administering a calcium salt of a crosslinked potassium binding polymer to remove potassium from the gastrointestinal tract in hyperkalemia or suspected hyperkalemia, with m:n-defined cross-linking of 1.6% to 1.9%. Dependent refinements further constrain potassium exchange capacity, swelling ratio, and particle size distribution metrics.
Stated Advantages
Removes potassium from the gastrointestinal tract of a patient showing clinical signs of hyperkalemia or suspected of having hyperkalemia.
Provides potassium binding and GI removal performance supported by fecal and urinary potassium and phosphate excretion and microscopy and particle-size analyses.
Higher fecal potassium excretion relative to higher-crosslinking resins such as Resonium.
Improved physical properties for patient tolerance and compliance.
Improved patient experience is supported by human consumer acceptability and tactile testing results for Example formulations.
Documented Applications
Removing potassium from the gastrointestinal tract of a patient showing clinical signs of hyperkalemia or suspected of having hyperkalemia.
Supporting performance assessment described via rodent fecal and urinary potassium and phosphate excretion experiments and microscopy and particle-size analyses.
Removing potassium from the gastrointestinal tract in patients with hyperkalemia or suspected hyperkalemia by gastrointestinal administration of a calcium salt of a potassium binding polymer.
Pharmaceutical compositions for oral and rectal administration, including sodium-free oral suspensions, jellies, and chewables.
Rodent in vivo gastrointestinal efficacy evaluation, including fecal potassium and urinary ion outcomes.
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