US2021347925A1PendingUtilityA1

Crosslinked poly(allylamine) polymer pharmaceutical compositions

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Assignee: TRICIDA INCPriority: Sep 25, 2017Filed: Jan 11, 2021Published: Nov 11, 2021
Est. expirySep 25, 2037(~11.2 yrs left)· nominal 20-yr term from priority
Inventors:Gerrit KlaernerEric ConnorRandi K. GburMatthew J. KadePaul H. KiersteadKalpesh BiyaniSon H. NguyenScott M. Tabakman
C08F 226/04C08G 73/0206A61K 31/785C08G 73/024C08F 226/02
71
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Claims

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 a target species from the gastrointestinal tract would provide physiological benefits.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A crosslinked poly(allylamine) polymer in bead form comprising the residues of a monoallylamine or a salt thereof and a multiallylamine or a salt thereof wherein (i) the crosslinked poly(allylamine) polymer has a swelling ratio of less than 2 and (ii) sp 2  allyl carbons comprised by the crosslinked poly(allylamine) polymer constitute less than 1.0% of the total number of carbon atoms comprised by the crosslinked poly(allylamine) polymer. 
     
     
         2 . The crosslinked poly(allylamine) polymer of  claim 1  wherein the residues of the multiallylamine or salt thereof are residues of a multiallylamine corresponding to Formula 3 or a salt thereof: 
       
         
           
           
               
               
           
         
         wherein each R 20  is hydrogen, hydrocarbyl or substituted hydrocarbyl, each X 1  is independently hydrocarbyl or substituted hydrocarbyl, X 2  is hydrocarbyl or substituted hydrocarbyl, m is a non-negative integer and n is at least 1. 
       
     
     
         3 . The crosslinked poly(allylamine) polymer of  claim 1  wherein the residue of the monoallylamine or salt thereof are residues of a monoallylamine corresponding to Formula 1 or a salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein R 4  and R 5  are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl. 
     
     
         4 . The crosslinked poly(allylamine) polymer of  claim 2  wherein each R 20  is independently hydrogen, aliphatic, or heteroaliphatic. 
     
     
         5 . The crosslinked poly(allylamine) polymer of  claim 1  wherein the crosslinked poly(allylamine) polymer comprises the residue of a dihaloalkane. 
     
     
         6 . The crosslinked poly(allylamine) polymer of  claim 1  wherein the crosslinked poly(allylamine) polymer comprises the residue of 1,2-dibromoethane, 1,2-dichloroethane, 1-bromo-2-chloroethane, 1,3-dichloropropane, 1,3-dibromopropane, and 1-bromo-3-chloropropane. 
     
     
         7 . The crosslinked poly(allylamine) polymer of  claim 1  wherein sp 2  allyl carbons comprised by the crosslinked poly(allylamine) polymer constitute less than 1% of the total number of carbon atoms comprised by the crosslinked poly(allylamine) polymer. 
     
     
         8 . The crosslinked poly(allylamine) polymer of  claim 1  wherein sp 2  allyl carbons comprised by the crosslinked poly(allylamine) polymer constitute less than 0.1% of the total number of carbon atoms comprised by the crosslinked poly(allylamine) polymer. 
     
     
         9 . The crosslinked poly(allylamine) polymer of  claim 1  wherein the crosslinked poly(allylamine) polymer contains less than 20 ppm allylamine. 
     
     
         10 . The crosslinked poly(allylamine) polymer of  claim 1  wherein the crosslinked poly(allylamine) polymer contains less than 1 ppm allylamine. 
     
     
         11 . The crosslinked poly(allylamine) polymer of  claim 1  wherein the crosslinked poly(allylamine) polymer has a structure corresponding to Formula 4: 
       
         
           
           
               
               
           
         
       
       wherein each R is independently hydrogen or an ethylene crosslink between two nitrogen atoms of the crosslinked amine polymer 
       
         
           
           
               
               
           
         
       
       and a, b, c, and m are integers. 
     
     
         12 . The crosslinked poly(allylamine) polymer of  claim 11  wherein the crosslinked poly(allylamine) polymer has a structure corresponding to Formula 4 and the sum of a and b to c (i.e., a+b:c) is in the range of about 1:1 to 9:1. 
     
     
         13 . The crosslinked poly(allylamine) polymer of  claim 11  wherein the crosslinked poly(allylamine) polymer has a structure corresponding to Formula 4 and 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. 
     
     
         14 . The crosslinked poly(allylamine) polymer of  claim 11  wherein the crosslinked poly(allylamine) polymer has a structure corresponding to Formula 4 and the sum of a and b is 57 and c is 24. 
     
     
         15 . The crosslinked poly(allylamine) polymer of  claim 1  wherein the crosslinked poly(allylamine) polymer comprises 15-30 mol % of the residue of a crosslinker selected from the group consisting of 1,2-dibromoethane, 1,2-dichloroethane, 1-bromo-2-chloroethane, 1,3-dichloropropane, 1,3-dibromopropane, 1-bromo-3-chloropropane and combinations thereof. 
     
     
         16 . The crosslinked poly(allylamine) polymer of  claim 1  wherein the crosslinked poly(allylamine) polymer comprises the residue of N,N′-diallyl-1,3-diaminopropane or a salt thereof, the residue of 2-Propen-1-ylamine or a salt thereof, and the residue of 1,2-dichloroethane. 
     
     
         17 . The crosslinked poly(allylamine) polymer of  claim 16  wherein sp 2  allyl carbons comprised by the crosslinked poly(allylamine) polymer constitute less than 0.1% of the total number of carbon atoms comprised by the crosslinked poly(allylamine) polymer. 
     
     
         18 . The crosslinked poly(allylamine) polymer of  claim 16  wherein the crosslinked poly(allylamine) polymer is characterized by a chloride ion binding capacity of at least 1.5 mEq/g in a SIB assay. 
     
     
         19 . The crosslinked poly(allylamine) polymer of  claim 16  wherein the crosslinked poly(allylamine) polymer is characterized by a chloride ion to phosphate ion binding ratio in a SIB assay of at least 1:1, respectively. 
     
     
         20 . The crosslinked poly(allylamine) polymer of  claim 1  wherein (a) the multiallylamine or salt thereof is N,N′-diallyl-1,3-diaminopropane or a salt thereof, (b) the monoallylamine or salt thereof is 2-Propen-1-ylamine or a salt thereof, and (c) the crosslinked poly(allylamine) polymer comprises (i) 10-35 mol % residue of N,N′-diallyl-1,3-diaminopropane or a salt thereof, (ii) 30-80 mol % residue of 2-Propen-1-ylamine or a salt thereof, and (iii) 10-35 mol % residue of 1,2-dichloroethane. 
     
     
         21 . The crosslinked poly(allylamine) polymer of  claim 20  wherein the crosslinked poly(allylamine) polymer is characterized by a chloride ion binding capacity of at least of at least 1.5 mEq/g in a SIB assay. 
     
     
         22 . The crosslinked poly(allylamine) polymer of  claim 20  wherein the crosslinked poly(allylamine) polymer is characterized by a chloride ion to phosphate ion binding ratio in a SIB assay of at least 1:1, respectively. 
     
     
         23 . The crosslinked poly(allylamine) polymer of  claim 20  wherein sp 2  allyl carbons comprised by the crosslinked poly(allylamine) polymer constitute less than 0.1% of the total number of carbon atoms comprised by the crosslinked poly(allylamine) polymer 
     
     
         24 . The crosslinked poly(allylamine) polymer of  claim 1  wherein (a) the multiallylamine or salt thereof is N,N′-diallyl-1,3-diaminopropane or a salt thereof, (b) the monoallylamine or salt thereof is 2-Propen-1-ylamine or a salt thereof, and (c) the crosslinked poly(allylamine) polymer comprises (i) 20-25 mol % residue of N,N′-diallyl-1,3-diaminopropane or a salt thereof, (ii) 50-60 mol % residue of 2-Propen-1-ylamine or a salt thereof, and (iii) 20-25 mol % residue of 1,2-dichloroethane. 
     
     
         25 . The crosslinked poly(allylamine) polymer of  claim 24  wherein the crosslinked poly(allylamine) polymer is characterized by a chloride ion binding capacity of at least of at least 1.5 mEq/g in a SIB assay. 
     
     
         26 . The crosslinked poly(allylamine) polymer of  claim 24  wherein the crosslinked poly(allylamine) polymer is characterized by a chloride ion to phosphate ion binding ratio in a SIB assay of at least 1:1, respectively. 
     
     
         27 . The crosslinked poly(allylamine) polymer of  claim 24  wherein the crosslinked poly(allylamine) polymer is characterized by a proton-binding capacity and a chloride binding capacity in Simulated Gastric Fluid of at least 5 mEq/g in a SGF assay. 
     
     
         28 . The crosslinked poly(allylamine) polymer of  claim 24  wherein the crosslinked poly(allylamine) polymer has a swelling ratio of less than 1.5. 
     
     
         29 . The crosslinked poly(allylamine) polymer of  claim 24  wherein sp 2  allyl carbons comprised by the crosslinked poly(allylamine) polymer constitute less than 0.8% of the total number of carbon atoms comprised by the crosslinked poly(allylamine) polymer. 
     
     
         30 . The crosslinked poly(allylamine) polymer of  claim 25  wherein sp 2  allyl carbons comprised by the crosslinked poly(allylamine) polymer constitute less than 0.1% of the total number of carbon atoms comprised by the crosslinked poly(allylamine) polymer.

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