# US 7,608,674 B2 · Pharmaceutical compositions comprising cross-linked small molecule amine polymers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,608,674 B2 - Document ID: US7608674B2 - Status: Granted - Kind: B2 - Application number: 10/980,991 - Filed: 2004-11-03 - Published: 2005-07-07 - Granted: 2009-10-27 - Earliest claimed: 2003-11-03 - Assignees: Ilypsa, Inc. - Inventors: Eric Connor; Dominique Charmot; Han-Ting Chang; Florence Roger; Gerrit Klaerner; Son Hoai Nguyen; Jonathan Mills; Jerry M. Buysse; Angela Lee; Deidre Madsen; Jun Shao; Michael J. Cope; John Fordtran - Web page: https://patentgrep.com/patent/US7608674B2 ## CPC - C08G 73/02: Polyamines - A61K 31/13: Amines {(A61K31/04 takes precedence)} - 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 13/12: of the kidneys - C08G 73/0206: {Polyalkylene(poly)amines} - C08L 39/02: Homopolymers or copolymers of vinylamine - C08L 79/02: Polyamines - C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS - 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 - C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06) ## Abstract Anion-binding polymers are described. The anion-binding polymers in some cases are low swelling anion-binding polymers. In some cases, the anion-binding polymers have a pore volume distribution such that a fraction of the polymer is not available for non-interacting solutes above a certain percentage of the MW of the target ion for the polymer. In some cases, the anion-binding polymers are characterized by low ion-binding interference, where the interference is measured in, for example, a gastrointestinal simulant, relative to non-interfering buffer. Pharmaceutical composition, methods of use, and kits are also described. ## Claims ### Claim 1 A pharmaceutical composition comprising a particulate crosslinked amine polymer as an active ingredient and a pharmaceutically acceptable excipient, the particulate crosslinked amine polymer particles having a chloride content of less than about 20 mol % of the amine group content and a size in the range of 5 to 500 microns, the crosslinked amine polymer comprising repeat units derived from polymerization of a non- polymeric amine and a crosslinking agent such that the polymer has a swelling ratio of less than about 5 as measured in a physiological medium, the non-polymeric amine being selected from the group consisting of (i) a non-polymeric amine of formula (I) wherein each n, independently, is equal to or greater than 3; m is equal to or greater than 1; and each R1, independently, is H or optionally substituted alkyl or aryl or is linked to a neighboring R1 to form an optionally substituted alicyclic, aromatic, or heterocyclic group; provided the non-polymeric amine of formula I is not 1,3-diaminopropane, and (ii) a non-polymeric amine of formula (IV) wherein each n, independently, is equal to or greater than 3; each r, independently, is 0, 1, or 2; and each R1, independently, is H or optionally substituted alkyl or aryl or is linked to a neighboring R1 to form an optionally substituted alicyclic, aromatic, or heterocyclic group. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1 wherein the non-polymeric amine is a non-polymeric amine of formula IV. ### Claim 3 (depends on 2) The pharmaceutical composition of claim 2 wherein the non- polymeric amine is and n is 3, 4 or 5. ### Claim 4 (depends on 3) The pharmaceutical composition of claim 3 wherein n is 3. ### Claim 5 (depends on 3) The pharmaceutical composition of claim 3 wherein n is 5. ### Claim 6 (depends on 3) The pharmaceutical composition of claim 3 wherein the polymer particles have a size in the range of 25 to 250 microns. ### Claim 7 The pharmaceutical composition of 3 wherein the polymer particles are spherical beads having a diameter of 25 to 250 microns. ### Claim 8 (depends on 1) The pharmaceutical composition of claim 1 wherein the polymer particles have a size in the range of 25 to 250 microns. ### Claim 9 The pharmaceutical composition of 1 wherein the polymer particles are spherical beads having a diameter of 25 to 250 microns. ### Claim 10 (depends on 1) The pharmaceutical composition of claim 1 wherein the crosslinking agent is 1,3-dichloropropane or epichlorohydrin. ### Claim 11 (depends on 1) The pharmaceutical composition of claim 1 wherein the crosslinking agent is epichlorohydrin. ### Claim 12 (depends on 2) The pharmaceutical composition of claim 2 wherein the polymer particles have a size in the range of 25 to 250 microns. ### Claim 13 The pharmaceutical composition of 2 wherein the particles are spherical beads having a diameter of 25 to 250 microns. ### Claim 14 (depends on 2) The pharmaceutical composition of claim 2 wherein the crosslinking agent is 1,3-dichloropropane or epichlorohydrin. ### Claim 15 (depends on 2) The pharmaceutical composition of claim 2 wherein the crosslinking agent is epichlorohydrin. ### Claim 16 (depends on 1) The pharmaceutical composition of claim 1 wherein the polymer has a gel pore volume distribution where less than about 20% of the pore volume of the gel is accessible to non-interacting solutes of molecular weight greater than about 200 as measured in a physiological medium. ### Claim 17 (depends on 3) The pharmaceutical composition of claim 3 wherein the polymer has a gel pore volume distribution where less than about 20% of the pore volume of the gel is accessible to non-interacting solutes of molecular weight greater than about 200 as measured in a physiological medium. ### Claim 18 (depends on 1) The pharmaceutical composition of claim 1 wherein the polymer binds phosphate ion in vivo with a binding capacity of greater than 0.5 mmol/g. ### Claim 19 (depends on 3) The pharmaceutical composition of claim 3 wherein the polymer binds phosphate ion in vivo with a binding capacity of greater than 0.5 mmol/g. ### Claim 20 (depends on 1) The pharmaceutical composition of claim 1 wherein the polymer has a gel pore volume distribution where less than about 20% of the pore volume of the gel is accessible to non-interacting solutes of molecular weight greater than about 200 as measured in a physiological medium, and the polymer binds phosphate ion in vivo with a binding capacity of greater than 0.5 mmol/g. ### Claim 21 (depends on 3) The pharmaceutical composition of claim 3 wherein the polymer has a gel pore volume distribution where less than about 20% of the pore volume of the gel is accessible to non-interacting solutes of molecular weight greater than about 200 as measured in a physiological medium, and the polymer binds phosphate ion in vivo with a binding capacity of greater than 0.5 mmol/g. ### Claim 22 (depends on 1) The pharmaceutical composition of claim 1 wherein the polymer particles have a chloride content of less than about 5 mol % of the amine group content. ### Claim 23 (depends on 1) The pharmaceutical composition of claim 1 wherein the polymer particles are substantially chloride-free. ### Claim 24 (depends on 1) The pharmaceutical composition of claim 1 wherein the composition is in the form of a powder. ### Claim 25 (depends on 3) The pharmaceutical composition of claim 3 wherein the composition is in the form of a powder. ### Claim 26 (depends on 1) The pharmaceutical composition of claim 1 wherein the composition is contained within a sachet. ### Claim 27 (depends on 3) The pharmaceutical composition of claim 3 wherein the composition is contained within a sachet. ### Claim 28 (depends on 1) The pharmaceutical composition of claim 1 wherein the composition is in the form of a sterile packaged powder. ### Claim 29 (depends on 3) The pharmaceutical composition of claim 3 wherein the composition is in the form of a sterile packaged powder. ### Claim 30 (depends on 1) The pharmaceutical composition of claim 1 wherein the composition is in the form of a soft or hard gelatin capsule. ### Claim 31 (depends on 3) The pharmaceutical composition of claim 3 wherein the composition is in the form of a soft or hard gelatin capsule. ### Claim 32 A pharmaceutical composition comprising a particulate crosslinked amine polymer as an active ingredient and a pharmaceutically acceptable excipient, the particulate crosslinked amine polymer particles being spherical beads having a size in the range of 5 to 500 microns, the crosslinked amine polymer comprising repeat units derived from polymerization of a non-polymeric amine and a crosslinking agent such that the polymer has a swelling ratio of less than about 5 as measured in a physiological medium, the non-polymeric amine being selected from the group consisting of (i) a non-polymeric amine of formula (I) wherein each n, independently, is equal to or greater than 3; m is equal to or greater than 1; and each R1, independently, is H or optionally substituted alkyl or aryl or is linked to a neighboring R1 to form an optionally substituted alicyclic, aromatic, or heterocyclic group; provided the non-polymeric amine of formula I is not 1,3-diaminopropane, and (ii) a non-polymeric amine of formula (IV) wherein each n, independently, is equal to or greater than 3; each r, independently, is 0, 1, or 2; and each R1, independently, is H or optionally substituted alkyl or aryl or is linked to a neighboring R1 to form an optionally substituted alicyclic, aromatic, or heterocyclic group. ### Claim 33 (depends on 32) The pharmaceutical composition of claim 32 wherein the non- polymeric amine is a non-polymeric amine of formula IV. ### Claim 34 (depends on 33) The pharmaceutical composition of claim 33 wherein the non- polymeric amine is and n is 3, 4 or 5. ### Claim 35 (depends on 34) The pharmaceutical composition of claim 34 wherein n is 3. ### Claim 36 (depends on 34) The pharmaceutical composition of claim 34 wherein n is 5. ### Claim 37 (depends on 34) The pharmaceutical composition of claim 34 wherein the polymer particles have a size in the range of 25 to 250 microns. ### Claim 38 (depends on 33) The pharmaceutical composition of claim 33 wherein the crosslinking agent is 1,3-dichloropropane or epichlorohydrin. ### Claim 39 (depends on 33) The pharmaceutical composition of claim 33 wherein the crosslinking agent is epichlorohydrin. ### Claim 40 (depends on 32) The pharmaceutical composition of claim 32 wherein the polymer has a gel pore volume distribution where less than about 20% of the pore volume of the gel is accessible to non-interacting solutes of molecular weight greater than about 200 as measured in a physiological medium. ### Claim 41 (depends on 34) The pharmaceutical composition of claim 34 wherein the polymer has a gel pore volume distribution where less than about 20% of the pore volume of the gel is accessible to non-interacting solutes of molecular weight greater than about 200 as measured in a physiological medium. ### Claim 42 (depends on 32) The pharmaceutical composition of claim 32 wherein the composition is in the form of a powder. ### Claim 43 (depends on 34) The pharmaceutical composition of claim 34 wherein the composition is in the form of a powder. ### Claim 44 (depends on 34) The pharmaceutical composition of claim 34 wherein the composition is contained within a sachet. ### Claim 45 (depends on 34) The pharmaceutical composition of claim 34 wherein the composition is contained within a sachet. ### Claim 46 (depends on 32) The pharmaceutical composition of claim 32 wherein the composition is in the form of a sterile packaged powder. ### Claim 47 (depends on 34) The pharmaceutical composition of claim 34 wherein the composition is in the form of a sterile packaged powder. ### Claim 48 (depends on 32) The pharmaceutical composition of claim 32 wherein the composition is in the form of a soft or hard gelatin capsule. ### Claim 49 (depends on 34) The pharmaceutical composition of claim 34 wherein the composition is in the form of a soft or hard gelatin capsule.