US 12,245,995 B2
Epinephrine spray formulations
Steven Hartman, Beverly Hills, CA (US); Michelle Lobel, Beverly Hills, CA (US); Matthew P. Robben, Pittsford, NY (US); Kenneth L. Dretchen, Gaithersburg, MD (US); and Michael Mesa, Boyds, MD (US)
Assigned to Bryn Pharma, LLC, Raleigh, NC (US)
Appl. No. 16/981,859
Filed by Bryn Pharma, LLC, Raleigh, NC (US)
PCT Filed Mar. 15, 2019, PCT No. PCT/US2019/022557
§ 371(c)(1), (2) Date Sep. 17, 2020,
PCT Pub. No. WO2019/182908, PCT Pub. Date Sep. 26, 2019.
Claims priority of provisional application 62/810,261, filed on Feb. 25, 2019.
Claims priority of provisional application 62/747,048, filed on Oct. 17, 2018.
Claims priority of provisional application 62/712,678, filed on Jul. 31, 2018.
Claims priority of provisional application 62/663,100, filed on Apr. 26, 2018.
Claims priority of provisional application 62/644,834, filed on Mar. 19, 2018.
Prior Publication US 2021/0093558 A1, Apr. 1, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/137 (2006.01); A61K 9/00 (2006.01); A61K 9/08 (2006.01); A61K 9/12 (2006.01); A61K 47/02 (2006.01); A61K 47/10 (2017.01); A61K 47/12 (2006.01); A61K 47/20 (2006.01); A61K 47/38 (2006.01); A61M 11/00 (2006.01); A61M 15/08 (2006.01); A61P 37/08 (2006.01)
CPC A61K 31/137 (2013.01) [A61K 9/0043 (2013.01); A61K 9/0078 (2013.01); A61K 9/08 (2013.01); A61K 9/12 (2013.01); A61K 47/02 (2013.01); A61K 47/10 (2013.01); A61K 47/12 (2013.01); A61K 47/20 (2013.01); A61K 47/38 (2013.01); A61M 11/007 (2014.02); A61P 37/08 (2018.01); A61M 15/08 (2013.01); A61M 2205/3553 (2013.01)] 20 Claims
 
1. A pharmaceutical spray formulation, comprising:
(a) from about 1% to about 25% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water, ethanol, propylene glycol, or a combination thereof; and
(b) an antimicrobial preservative including chlorobutanol or chlorobutanol hemihydrate and one or more of an antioxidant, an isotonicity agent, an absorption enhancer, a viscosity modifier, or a buffering agent;
wherein the formulation is configured to be administered into a nostril of a subject as a nasal spray that yields a plasma concentration of at least 0.4 ng/ml within 1 minute of administration; and
wherein the pharmaceutical spray formation has a weight ratio of the epinephrine or pharmaceutically acceptable salt thereof to the chlorobutanol or chlorobutanol hemihydrate of about 12:1 to about 30:1.