# US 2018/0021370 A1 · Proton-binding polymers for oral administration > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2018/0021370 A1 - Document ID: US20180021370A1 - Status: Published application - Kind: A1 - Application number: 15/533,705 - Filed: 2015-12-10 - Published: 2018-01-25 - Earliest claimed: 2014-12-10 - Assignees: Tricida, Inc. - Applicants: Tricida, Inc. - Inventors: Gerrit KLAERNER; Eric F. CONNOR; Randi K. GBUR; Matthew J. KADE; Paul H. KIERSTEAD; Jerry M. BUYSSE; Michael J. COPE; Kalpesh N. BIYANI; Son H. NGUYEN; Scott M. TABAKMAN - Web page: https://patentgrep.com/patent/US20180021370A1 ## CPC - A61K 31/785: Polymers containing nitrogen - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 3/12: for electrolyte homeostasis - A61P 7/00: Drugs for disorders of the blood or the extracellular fluid - C08F 8/02: Alkylation - C08F 26/02: by a single or double bond to nitrogen - C08F 226/02: by a single or double bond to nitrogen - C08F 2810/20: leading to a crosslinking, either explicitly or inherently - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS ## Abstract 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. ## Claims ### Claim 1 A process for the preparation of a crosslinked amine polymer, the process comprising (i) swelling a preformed amine polymer with a swelling agent, (ii) dispersing the preformed amine polymer in a reaction mixture comprising a dispersing solvent, a crosslinking agent, and the swelling agent, and (iii) crosslinking the preformed amine polymer in the reaction mixture to form the crosslinked amine polymer, wherein the preformed amine polymer is crosslinked and has an absorption capacity for the swelling agent, and the amount of swelling agent in the reaction mixture is less than the absorption capacity of the preformed amine polymer for the swelling agent. ### Claim 2 (depends on 1) The process of claim 1 wherein the process further comprises deprotonating the preformed amine polymer with a base before it is swollen with the swelling agent. ### Claim 3 (depends on 1, 2) The process of claim 1 or 2 wherein the crosslinks in the preformed amine polymer are primarily carbon-carbon crosslinks and nitrogen-nitrogen crosslinks are primarily formed in the crosslinking step. ### Claim 4 The process of any of the preceding claims wherein the preformed amine polymer has a chloride binding capacity of at least 10 mmol/g in Simulated Gastric Fluid (“SGF”) and a Swelling Ratio in the range of 2 to 10, and the crosslinked amine polymer has a binding capacity for phosphate, citrate and/or taurocholate in SIB or SOB that is less than the binding capacity of the preformed amine polymer for phosphate, citrate and/or taurocholate in that same assay. ### Claim 5 The process of any preceding claim wherein the dispersing solvent comprises a non-polar solvent. ### Claim 6 The process of any preceding claim wherein the dispersing solvent comprises a solvent that is chemically inert to the preformed amine polymer. ### Claim 7 The process of any preceding claim wherein the dispersing solvent comprises a crosslinking solvent. ### Claim 8 (depends on 1, 2, 3, 4) The process of any of claims 1 to 4 wherein the crosslinking agent is the dispersing solvent. ### Claim 9 The process of any preceding claim wherein the swelling agent and the dispersing solvent are immiscible. ### Claim 10 The process of any preceding claim wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 4:1. ### Claim 11 The process of any preceding claim wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 3:1. ### Claim 12 The process of any preceding claim wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 2:1. ### Claim 13 The process of any preceding claim wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 1:1. ### Claim 14 A process for the preparation of a crosslinked amine polymer, the process comprising (i) swelling a preformed amine polymer with a swelling agent, and (ii) crosslinking the preformed amine polymer to form the crosslinked amine polymer in a reaction mixture comprising a crosslinking agent and the swelling agent, wherein the preformed amine polymer is crosslinked and has an absorption capacity for the swelling agent, the amount of swelling agent in the reaction mixture is less than the absorption capacity of the preformed amine polymer for the swelling agent, and the weight ratio of swelling agent to the preformed amine polymer in the reaction mixture is less than 1:1. ### Claim 15 The process of any preceding claim wherein the swelling agent is a polar solvent. ### Claim 16 The process of any preceding claim wherein the swelling agent is water, methanol, ethanol, n-propanol, isopropanol, n-butanol, formic acid, acetic acid, acetonitrile, dimethylformamide, dimethylsulfoxide, nitromethane, propylene carbonate, or a combination thereof. ### Claim 17 The process of any preceding claim wherein the swelling agent is water. ### Claim 18 The process of any preceding claim wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 0.5:1. ### Claim 19 The process of any preceding claim wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 0.4:1. ### Claim 20 The process of any preceding claim wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 0.3:1. ### Claim 21 The process of any preceding claim wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is at least 0.15:1. ### Claim 22 The process of any preceding claim wherein the crosslinking agent comprises at least two amine-reactive functional groups. ### Claim 23 The process of any preceding claim wherein the crosslinking agent is a compound containing at least two amine-reactive groups selected from the group consisting of alkyl halides, epoxides, phosgene, anhydrides, carbamates, carbonates, isocyanates, thioisocyanates, esters, activated esters, carboxylic acids and derivatives thereof, sulfonates and derivatives thereof, acyl halides, aziridines, α,β-unsaturated carbonyls, ketones, aldehydes, and pentafluoroaryl groups. ### Claim 24 The process of any preceding claim wherein the crosslinking agent is a crosslinking agent selected from Table B. ### Claim 25 The process of any preceding claim wherein the crosslinking agent is a dichloroalkane. ### Claim 26 The process of any preceding claim wherein the crosslinking agent is dichloroethane or dichloropropane. ### Claim 27 The process of any preceding claim wherein the swelling agent and the crosslinking agent are immiscible. ### Claim 28 The process of any preceding claim wherein the preformed polymer is combined with the crosslinking agent and the dispersing solvent before the polymer is swollen with the swelling agent. ### Claim 29 The process of any preceding claim wherein the process additionally comprises forming the preformed amine polymer in a solvent system and the crosslinked amine polymer is formed without isolation of the preformed amine polymer from the solvent system. ### Claim 30 The process of any preceding claim wherein the preformed amine polymer comprises the residue of an amine corresponding to Formula 1: ### Claim 31 The process of any preceding claim wherein the preformed amine polymer comprises the residue of an amine corresponding to Formula 1a wherein R4 and R5 are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl. ### Claim 32 (depends on 31) The process of claim 31 wherein R4 and R5 are independently hydrogen, aliphatic or heteroaliphatic. ### Claim 33 (depends on 31) The process of claim 31 wherein R4 and R5 are independently hydrogen, allyl, or aminoalkyl. ### Claim 34 The process of any preceding claim wherein the preformed amine polymer comprises the residue of an amine of Table C. ### Claim 35 The process of any preceding claim wherein the preformed amine polymer comprises the residue of allylamine. ### Claim 36 The process of any preceding claim wherein the preformed amine polymer comprises the residue of diallylpropyldiamine. ### Claim 37 The process of any preceding claim wherein the preformed amine polymer is a copolymer comprising the residues of allylamine and diallylpropyldiamine. ### Claim 38 The process of any preceding claim wherein the preformed amine polymer is characterized by a first selectivity for chloride relative to citrate, phosphate and/or taurocholate in SIB and/or SOB and the crosslinked polymer is characterized by a second selectivity for chloride relative to citrate, phosphate and/or taurocholate in SIB and/or SOB wherein: (i) the crosslinked polymer has an increased binding capacity for chloride and a decreased binding capacity for phosphate in SIB relative to the preformed amine polymer, (ii) the crosslinked polymer has an increased binding capacity for chloride and a decreased binding capacity for phosphate in SOB relative to the preformed amine polymer, (iii) the crosslinked polymer has an increased binding capacity for chloride and a decreased binding capacity for citrate in SOB relative to the preformed amine polymer, or (iv) the crosslinked polymer has an increased binding capacity for chloride and a decreased binding capacity for taurocholate in SOB relative to the preformed amine polymer. ### Claim 39 (depends on 38) The process of claim 38 wherein the crosslinked polymer has a decreased binding capacity for chloride in SGF relative to the preformed amine polymer ### Claim 40 (depends on 38) The process of claim 38 wherein relative to the preformed amine polymer the post-polymerization crosslinked polymer has (i) an increased binding capacity for chloride and a decreased binding capacity for phosphate in SIB and (ii) a decreased binding capacity in SGF. ### Claim 41 (depends on 38) The process of claim 38 wherein relative to the preformed amine polymer the post-polymerization crosslinked polymer has (i) an increased binding capacity for chloride and a decreased binding capacity for phosphate, citrate and/or taurocholate, in combination, in SOB and (ii) a decreased binding capacity in SGF. ### Claim 42 A process for the preparation of a crosslinked amine polymer, the process comprising crosslinking a preformed amine polymer in a reaction mixture to form the crosslinked amine polymer, the reaction mixture comprising the preformed amine polymer, a swelling agent that swells the preformed amine polymer and dichloroethane. ### Claim 43 (depends on 42) The process of claim 42 wherein the reaction mixture comprises a dispersing solvent. ### Claim 44 (depends on 42, 43) The process of claim 42 or 43 wherein the reaction mixture comprises a dispersing solvent dispersing solvent that is chemically inert to the preformed amine polymer. ### Claim 45 (depends on 42, 43) The process of claim 42 or 43 wherein the reaction mixture comprises a dispersing solvent and the dispersing solvent is dichloroethane. ### Claim 46 (depends on 42, 43, 44, 45) The process of any of claims 42 to 45 wherein the swelling agent and dichloroethane are immiscible. ### Claim 47 (depends on 42, 43, 44, 45, 46) The process of any of claims 42 to 46 wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 4:1. ### Claim 48 (depends on 42, 43, 44, 45, 46) The process of any claims 42 to 46 wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 3:1. ### Claim 49 (depends on 42, 43, 44, 45, 46) The process of any claims 42 to 46 wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 2:1. ### Claim 50 (depends on 42, 43, 44, 45, 46) The process of any claims 42 to 46 wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 1:1. ### Claim 51 (depends on 42, 43, 44, 45, 46) The process of any claims 42 to 46 wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 0.5:1. ### Claim 52 (depends on 42, 43, 44, 45, 46) The process of any claims 42 to 46 wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 0.4:1. ### Claim 53 (depends on 42, 43, 44, 45, 46) The process of any claims 42 to 46 wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is less than 0.3:1. ### Claim 54 (depends on 42, 43, 44, 45, 46) The process of any claims 42 to 46 wherein the weight ratio of the swelling agent to preformed amine polymer in the reaction mixture is at least 0.15:1. ### Claim 55 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54) The process of any of claims 42 to 54 wherein the preformed amine polymer is deprotonated with a base before it is crosslinked in the reaction mixture. ### Claim 56 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55) The process of any of claims 42 to 55 wherein the preformed amine polymer is crosslinked and the crosslinks are primarily carbon-carbon crosslinks. ### Claim 57 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56) The process of any of claims 42 to 56 wherein the swelling agent is a polar solvent. ### Claim 58 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56) The process of any of claims 42 to 56 wherein the swelling agent is water, methanol, ethanol, n-propanol, isopropanol, n-butanol, formic acid, acetic acid, acetonitrile, dimethylformamide, dimethylsulfoxide, nitromethane, propylene carbonate, or a combination thereof. ### Claim 59 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56) The process of any of claims 42 to 56 wherein the swelling agent is water. ### Claim 60 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59) The process of any of claims 42 to 59 wherein the preformed amine polymer comprises the residue of an amine corresponding to Formula 1: ### Claim 61 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59) The process of any of claims 42 to 59 wherein the preformed amine polymer comprises the residue of an amine corresponding to Formula 1a wherein R4 and R5 are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl. ### Claim 62 (depends on 61) The process of claim 61 wherein R4 and R5 are independently hydrogen, aliphatic or heteroaliphatic. ### Claim 63 (depends on 61) The process of claim 61 wherein R4 and R5 are independently hydrogen, allyl, or aminoalkyl. ### Claim 64 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59) The process of any of claims 42 to 59 wherein the preformed amine polymer comprises the residue of an amine of Table C. ### Claim 65 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59) The process of any of claims 42 to 59 wherein the preformed amine polymer comprises the residue of allylamine. ### Claim 66 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59) The process of any of claims 42 to 59 wherein the preformed amine polymer comprises the residue of diallylpropyldiamine. ### Claim 67 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59) The process of any of claims 42 to 59 wherein the preformed amine polymer is a copolymer comprising the residues of allylamine and diallylpropyldiamine. ### Claim 68 (depends on 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67) The process of any of claims 42 to 67 wherein the preformed amine polymer is characterized by a first selectivity for chloride relative to citrate, phosphate and/or taurocholate in SIB and/or SOB and the crosslinked polymer is characterized by a second selectivity for chloride relative to citrate, phosphate and/or taurocholate in SIB and/or SOB wherein: (i) the crosslinked polymer has an increased binding capacity for chloride and a decreased binding capacity for phosphate in SIB relative to the preformed amine polymer, (ii) the crosslinked polymer has an increased binding capacity for chloride and a decreased binding capacity for phosphate in SOB relative to the preformed amine polymer, (iii) the crosslinked polymer has an increased binding capacity for chloride and a decreased binding capacity for citrate in SOB relative to the preformed amine polymer, or (iv) the crosslinked polymer has an increased binding capacity for chloride and a decreased binding capacity for taurocholate in SOB relative to the preformed amine polymer. ### Claim 69 (depends on 68) The process of claim 68 wherein the crosslinked polymer has a decreased binding capacity for chloride in SGF relative to the preformed amine polymer ### Claim 70 (depends on 68) The process of claim 68 wherein relative to the preformed amine polymer the post-polymerization crosslinked polymer has (i) an increased binding capacity for chloride and a decreased binding capacity for phosphate in SIB and (ii) a decreased binding capacity in SGF. ### Claim 71 (depends on 68) The process of claim 68 wherein relative to the preformed amine polymer the post-polymerization crosslinked polymer has (i) an increased binding capacity for chloride and a decreased binding capacity for phosphate, citrate and/or taurocholate, in combination, in SOB and (ii) a decreased binding capacity in SGF. ### Claim 72 A pharmaceutical composition comprising a crosslinked amine polymer having a chloride ion binding capacity of at least 4 mmol/g in Simulated Small Intestine Inorganic Buffer (“SIB”). ### Claim 73 A pharmaceutical composition comprising a crosslinked amine polymer having a ratio of chloride ion binding capacity to phosphate ion binding capacity in Simulated Small Intestine Inorganic Buffer (“SIB”) of at least 2.3:1, respectively. ### Claim 74 A pharmaceutical composition comprising a crosslinked amine polymer having a chloride ion binding capacity of at least 1 mmol/g in Simulated Small Intestine Inorganic Buffer (“SIB”), a phosphate ion binding capacity of less than 0.4 mmol/g in SIB, and a chloride ion to phosphate ion binding ratio in SIB of at least 2.3:1, respectively. ### Claim 75 A pharmaceutical composition comprising a crosslinked amine polymer having a ratio of chloride ion binding capacity to phosphate ion binding capacity in Simulated Small Intestine Inorganic Buffer (“SIB”) of at least 2.3:1, respectively, and a Swelling Ratio of less than 5. ### Claim 76 A pharmaceutical composition comprising a crosslinked amine polymer having a retained chloride content of at least 30% of the chloride that was initially bound in a GI Compartment Transit Assay (“GICTA”). ### Claim 77 A pharmaceutical composition comprising a crosslinked amine polymer having a retained chloride content of at least 0.5 mmol chloride/g of polymer in a GI Compartment Transit Assay (“GICTA”). ### Claim 78 A pharmaceutical composition comprising a crosslinked amine polymer having a retained chloride content of at least 0.5 mmol chloride/g of polymer in a GI Compartment Transit Assay (“GICTA”) and a chloride retention at the end of the GICTA of at least 30% of the chloride that was initially bound in the GICTA. ### Claim 79 A pharmaceutical composition comprising a crosslinked amine polymer having a chloride ion binding capacity of at least 2 mmol chloride/g polymer at 4 hours in Simulated Small Intestine Inorganic Buffer (“SIB”). ### Claim 80 A pharmaceutical composition comprising a crosslinked amine polymer having a chloride ion binding capacity of at least 2 mmol chloride/g polymer at 4 hours in Simulated Small Intestine Inorganic Buffer (“SIB”) and a crosslinked amine polymer having a chloride ion binding capacity of at least 2 mmol chloride/g polymer at 24 hours in Simulated Small Intestine Inorganic Buffer (“SIB”). ### Claim 81 A pharmaceutical composition comprising a crosslinked amine polymer having a chloride ion binding capacity in a 24-hour Simulated Small Intestine Organic and Inorganic Buffer (“SOB”) assay of at least 5.5 mmol chloride/g polymer. ### Claim 82 A pharmaceutical composition comprising a crosslinked amine polymer having (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”). ### Claim 83 A pharmaceutical composition comprising a crosslinked amine polymer having (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”). ### Claim 84 A pharmaceutical composition comprising a crosslinked amine polymer having (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”). ### Claim 85 A pharmaceutical composition comprising a crosslinked amine polymer having a selectivity for chloride over citrate, phosphate and taurocholate in Simulated Small Intestine Organic and Inorganic Buffer (“SOB”), at (i) 1 hour, (ii) 4 hours, (iii) 12 hours, (iv) 18 hours, (v) 24 hours, (vi) 30 hours, (vii) 36 hours, or even (viii) 48 hours. ### Claim 86 (depends on 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96) A method of treating an acid/base disorder in an animal including a human by removing HCl through oral administration of a pharmaceutical composition of any of claims 72 to 96. ### Claim 87 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71) A method of treating an acid/base disorder in an animal including a human by removing HCl through oral administration of a pharmaceutical composition comprising a crosslinked amine polymer prepared by the process of any of claims 1 to 71. ### Claim 88 A polymer comprising a structure corresponding to Formula 4: wherein each R is indendently hydrogen or an ethylene crosslink between two nitrogen atoms of the crosslinked amine polymer and a, b, c, and m are integers. ### Claim 89 (depends on 88) The polymer of claim 88 wherein m is a large integer indicating an extended polymer network. ### Claim 90 (depends on 88, 89) The polymer of claim 88 or 89 wherein a ratio of the sum of a and b to c a+b:c) is in the range of about 1:1 to 5:1. ### Claim 91 (depends on 88, 89) The polymer of claim 88 or 89 wherein a ratio of the sum of a and b to c (i.e., a+b:c) is in the range of about 1.5:1 to 4:1. ### Claim 92 (depends on 88, 89) The polymer of claim 88 or 89 wherein a ratio of the sum of a and b to c (i.e., a+b:c) is in the range of about 1.75:1 to 3:1. ### Claim 93 (depends on 88, 89) The polymer of claim 88 or 89 wherein a ratio of the sum of a and b to c (i.e., a+b:c) is in the range of about 2:1 to 2.5:1. ### Claim 94 (depends on 88, 89) The polymer of claim 88 or 89 wherein the sum of a and b is 57 and c is 24. ### Claim 95 (depends on 88, 89, 90, 91, 92, 93, 94) The polymer of any of claims 88 to 94 wherein 50-95% of the R substituents are hydrogen and 5-50% are an ethylene crosslink between two nitrogens of the crosslinked amine polymer. ### Claim 96 (depends on 88, 89, 90, 91, 92, 93, 94) The polymer of any of claims 88 to 94 wherein 55-90% of the R substituents are hydrogen and 10-45% are an ethylene crosslink between two nitrogens of the crosslinked amine polymer. ### Claim 97 (depends on 88, 89, 90, 91, 92, 93, 94) The polymer of any of claims 88 to 94 wherein 60-90% of the R substituents are hydrogen and 10-40% are an ethylene crosslink between two nitrogens of the crosslinked amine polymer. ### Claim 98 (depends on 88, 89, 90, 91, 92, 93, 94) The polymer of any of claims 88 to 94 wherein 65-90% of the R substituents are hydrogen and 10-35% are an ethylene crosslink between two nitrogens of the crosslinked amine polymer. ### Claim 99 (depends on 88, 89, 90, 91, 92, 93, 94) The polymer of any of claims 88 to 94 wherein 70-90% of the R substituents are hydrogen and 10-30% are an ethylene crosslink between two nitrogens of the crosslinked amine polymer. ### Claim 100 (depends on 88, 89, 90, 91, 92, 93, 94) The polymer of any of claims 88 to 94 wherein 75-85% of the R substituents are hydrogen and 15-25% are an ethylene crosslink between two nitrogens of the crosslinked amine polymer. ### Claim 101 (depends on 88, 89, 90, 91, 92, 93, 94) The polymer of any of claims 88 to 94 wherein 80-85% of the R substituents are hydrogen and 15-20% are an ethylene crosslink between two nitrogens of the crosslinked amine polymer. ### Claim 102 (depends on 88, 89, 90, 91, 92, 93, 94) The polymer of any of claims 88 to 94 wherein about 81% of the R substituents are hydrogen and about 19% are an ethylene crosslink. ### Claim 103 (depends on 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102) A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a crosslinked amine polymer of any of claims 88 to 102. ### Claim 104 A method of treating an acid/base disorder in an animal including a human by removing HCl through oral administration of a pharmaceutical composition of Embodiment 103.