PROTON-BINDING POLYMERS FOR ORAL ADMINISTRATION
Pharmaceutical compositions for and methods of treating an animal, including a human, and methods of preparing such compositions. The pharmaceutical compositions contain crosslinked amine polymers and may be used, for example, to treat diseases or other metabolic conditions in which removal of protons and/or chloride ions from the gastrointestinal tract would provide physiological benefits such as normalizing serum bicarbonate concentrations and the blood pH in an animal, including a human.
1 - 115 . (canceled)
116 . A pharmaceutical composition comprising a crosslinked amine polymer, the crosslinked amine polymer comprising residues of a monoallylamine, a multifunctional allylamine, and dichloroethane.
117 . The pharmaceutical composition of claim 116 wherein the monoallylamine residue is a residue of allylamine or a salt thereof.
118 . The pharmaceutical composition of claim 117 wherein the multifunctional amine residue is a multifunctional allylamine residue selected from Table C.
119 . The pharmaceutical composition of claim 117 wherein the multifunctional amine residue is a residue of diallylpropyldiamine (DAPDA) or a salt thereof.
120 . The pharmaceutical composition of claim 116 wherein the multifunctional amine residue is a multifunctional allylamine residue selected from Table C.
121 . The pharmaceutical composition of claim 116 wherein the multifunctional amine residue is a residue of DAPDA or a salt thereof.
122 . The pharmaceutical composition of claim 116 wherein the crosslinked amine polymer comprises the residues of (i) allylamine or a salt thereof, (ii) DAPDA or a salt thereof, and (iii) dichloroethane.
123 . The pharmaceutical composition of claim 116 wherein the crosslinked amine polymer has a chloride binding capacity in SIB of at least 4 mmol/g.
124 . The pharmaceutical composition of claim 116 wherein the crosslinked amine polymer has a ratio of chloride binding capacity to phosphate ion binding capacity in SIB of at least 2.3:1, respectively.
125 . The pharmaceutical composition of claim 116 wherein the crosslinked amine polymer has (i) a proton-binding capacity and a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid; and (ii) a chloride ion binding capacity of at least 4 mmol/g at 1 hour in Simulated Small Intestine Inorganic Buffer (“SIB”).
126 . The pharmaceutical composition of claim 116 wherein the crosslinked amine polymer has (i) a proton-binding capacity and a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid; and (ii) a chloride ion binding capacity of at least 4 mmol/g, and a phosphate ion binding capacity of less than 2 mmol/g in Simulated Small Intestine Inorganic Buffer (“SIB”).
127 . The pharmaceutical composition of claim 116 wherein the crosslinked amine polymer has (i) a proton-binding capacity and a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid; and (ii) a chloride to phosphate ion binding ratio of at least 2.3:1, respectively, in Simulated Small Intestine Inorganic Buffer (“SIB”).
128 . A pharmaceutical composition comprising a crosslinked amine polymer, the crosslinked amine polymer comprising the residues of (i) allylamine or a salt thereof, (ii) DAPDA or a salt thereof, and (iii) dichloroethane.
129 . The pharmaceutical composition of claim 128 wherein the crosslinked amine polymer has a chloride binding capacity in SIB of at least 4 mmol/g.
130 . The pharmaceutical composition of claim 128 wherein the crosslinked amine polymer has a ratio of chloride binding capacity to phosphate ion binding capacity in SIB of at least 2.3:1, respectively.
131 . The pharmaceutical composition of claim 128 wherein the crosslinked amine polymer has (i) a proton-binding capacity and a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid; and (ii) a chloride ion binding capacity of at least 4 mmol/g at 1 hour in Simulated Small Intestine Inorganic Buffer (“SIB”).
132 . The pharmaceutical composition of claim 128 wherein the crosslinked amine polymer has (i) a proton-binding capacity and a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid; and (ii) a chloride ion binding capacity of at least 4 mmol/g, and a phosphate ion binding capacity of less than 2 mmol/g in Simulated Small Intestine Inorganic Buffer (“SIB”).
133 . The pharmaceutical composition of claim 128 wherein the crosslinked amine polymer has (i) a proton-binding capacity and a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid; and (ii) a chloride to phosphate ion binding ratio of at least 2.3:1, respectively, in Simulated Small Intestine Inorganic Buffer (“SIB”).
134 . A pharmaceutical composition comprising a crosslinked amine polymer, which is made by a two-step reaction comprising (i) preparing a preformed amine polymer comprising residues of diallylpropyldiamine (DAPDA) or a salt thereof and residues of allylamine (AAH) or a salt thereof and (ii) crosslinking the preformed polymer with dichloroethane (DCE) to form a cross-linked amine polymer, the cross-linked amine polymer comprising at least one dichloroethane residue.
135 . The pharmaceutical composition of claim 134 wherein the cross-linked amine polymer comprises the residues of allylamine or a salt thereof, DAPDA or a salt thereof, and dichloroethane.
136 . The pharmaceutical composition of claim 134 wherein the cross-linked amine polymer has a chloride binding capacity in SIB of at least 4 mmol/g.
137 . The pharmaceutical composition of claim 134 wherein the cross-linked amine polymer has a ratio of chloride binding capacity to phosphate ion binding capacity in SIB of at least 2.3:1, respectively.
138 . The pharmaceutical composition of claim 134 wherein the cross-linked amine polymer has (i) a proton-binding capacity and a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid; and (ii) a chloride ion binding capacity of at least 4 mmol/g at 1 hour in Simulated Small Intestine Inorganic Buffer (“SIB”).
139 . The pharmaceutical composition of claim 134 wherein the crosslinked amine polymer has (i) a proton-binding capacity and a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid; and (ii) a chloride ion binding capacity of at least 4 mmol/g, and a phosphate ion binding capacity of less than 2 mmol/g in Simulated Small Intestine Inorganic Buffer (“SIB”).
140 . The pharmaceutical composition of claim 134 wherein the crosslinked amine polymer has (i) a proton-binding capacity and a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid; and (ii) a chloride to phosphate ion binding ratio of at least 2.3:1, respectively, in Simulated Small Intestine Inorganic Buffer (“SIB”).