US 12,465,568 B2
Cryoprotective agents for particulate formulations
Christian Dohmen, Munich (DE); and Philipp Beck, Munich (DE)
Assigned to ethris GmbH, Planegg (DE)
Appl. No. 17/050,440
Filed by ethris GmbH, Planegg (DE)
PCT Filed Apr. 25, 2019, PCT No. PCT/EP2019/060646
§ 371(c)(1), (2) Date Oct. 24, 2020,
PCT Pub. No. WO2019/207061, PCT Pub. Date Oct. 31, 2019.
Claims priority of application No. 18169325 (EP), filed on Apr. 25, 2018; and application No. 18189010 (EP), filed on Aug. 14, 2018.
Prior Publication US 2021/0137846 A1, May 13, 2021
Int. Cl. A61K 9/1272 (2025.01); A61K 9/00 (2006.01); A61K 9/16 (2006.01); A61K 9/51 (2006.01); A61K 31/7105 (2006.01); A61K 47/10 (2017.01); A61K 47/54 (2017.01); A61K 47/59 (2017.01); A61K 48/00 (2006.01)
CPC A61K 9/1272 (2013.01) [A61K 9/0043 (2013.01); A61K 9/0073 (2013.01); A61K 9/1617 (2013.01); A61K 9/1688 (2013.01); A61K 9/5123 (2013.01); A61K 9/5192 (2013.01); A61K 31/7105 (2013.01); A61K 47/10 (2013.01); A61K 47/549 (2017.08); A61K 47/59 (2017.08); A61K 48/0033 (2013.01); A61K 48/0041 (2013.01)] 19 Claims
 
1. A device for forming an aerosol from a particulate composition suspended in a liquid or for nebulizing such a composition, which device comprises a suspension composition comprising:
(i) a nano- or microparticle formulation comprising particles comprising a therapeutically active agent complexed to a cationic excipient suspended in a liquid phase, and
(ii) at least one cryoprotective additive selected from C3-C5 alkanes substituted by one or two hydroxy groups, wherein the cryoprotective additive is contained in the suspension composition at a concentration of 0.5 to 50% w/v, based on the volume of the liquid phase,
wherein the therapeutically active agent is a mRNA, wherein the suspension composition has been subjected to a freeze-thaw cycle, wherein the suspension composition was retained in a solid, frozen state for 16 hours to two years prior to thawing, and wherein the suspension composition retains its functionality during application to or via the respiratory tract after the freeze-thaw cycle.