US 11,992,501 B2
Compositions for and methods of treating acid-base disorders
Gerrit Klaerner, Hillsborough, CA (US); Eric F. Connor, Los Gatos, CA (US); Randi K. Gbur, Brisbane, CA (US); Matthew J. Kade, Berkeley, CA (US); Paul H. Kierstead, Oakland, CA (US); Jerry M. Buysse, Los Altos, CA (US); Michael J. Cope, Berkeley, CA (US); Kalpesh N. Biyani, Dublin, CA (US); Son H. Nguyen, Milpitas, CA (US); and Scott M. Tabakman, Palo Alto, CA (US)
Assigned to Renosis, Inc., Southlake, TX (US)
Filed by Renosis, Inc., Southlake, TX (US)
Filed on Sep. 24, 2021, as Appl. No. 17/485,177.
Application 17/485,177 is a continuation of application No. 16/099,045, abandoned, previously published as PCT/US2017/031395, filed on May 5, 2017.
Claims priority of provisional application 62/414,966, filed on Oct. 31, 2016.
Claims priority of provisional application 62/408,885, filed on Oct. 17, 2016.
Claims priority of provisional application 62/350,686, filed on Jun. 15, 2016.
Claims priority of provisional application 62/333,059, filed on May 6, 2016.
Prior Publication US 2022/0062328 A1, Mar. 3, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/785 (2006.01); A61K 9/00 (2006.01); A61K 9/14 (2006.01); A61K 33/00 (2006.01); A61P 3/12 (2006.01); A61P 13/12 (2006.01); A61P 43/00 (2006.01); C08F 8/02 (2006.01); C08F 226/02 (2006.01); C08F 226/04 (2006.01)
CPC A61K 31/785 (2013.01) [A61K 9/0053 (2013.01); A61K 9/14 (2013.01); A61K 33/00 (2013.01); A61P 3/12 (2018.01); A61P 13/12 (2018.01); A61P 43/00 (2018.01); C08F 8/02 (2013.01); C08F 226/02 (2013.01); C08F 226/04 (2013.01)] 53 Claims
 
1. A method of treating an individual afflicted with metabolic acidosis, the method comprising oral administration of a daily dose of a pharmaceutical composition having the capacity to bind at least 5 mEq of a target species as it transits the digestive system to achieve a clinically significant increase in the serum bicarbonate value of at least 1 mEq/1 from baseline within a treatment period of 15 days, the target species being selected from the group consisting of protons, strong acids, and conjugate bases of strong acids wherein the pharmaceutical composition is a nonabsorbable composition comprising a proton-binding, crosslinked amine polymer comprising the residue of an amine corresponding to Formula 1:

OG Complex Work Unit Chemistry
wherein R1, R2 and R3 are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl provided, however, at least one of R1, R2 and R3 is other than hydrogen, and
the crosslinked amine polymer is prepared in a two-step process, wherein
the first polymerization crosslinking step yields preformed amine polymer beads having a chloride binding capacity of at least 5 mmol/g in Simulated Gastric Fluid (“SGF”) and a Swelling Ratio in the range of 1 to 6,
the resulting preformed amine polymer is then at least partially deprotonated with a base and combined with a non-protonating swelling agent to swell the free amine polymer without protonating the amine functions, and
in the second crosslinking step, the swollen, deprotonated preformed amine polymer is crosslinked with 1,2-dichloroethane to form a post-polymerization crosslinked polymer.