	US 12,285,419 B2
	Bupivacaine multivesicular liposome formulations and uses thereof
Louie D. Garcia, San Diego, CA (US); Soroush M. Ardekani, San Diego, CA (US); Paige N. Davis, San Diego, CA (US); Stephanie M. Kurz, San Diego, CA (US); Damon A. Leon, San Diego, CA (US); Kathleen D. A. Los, San Diego, CA (US); John J. Grigsby, Jr., San Diego, CA (US); Eran Levy, San Diego, CA (US); and Alisha R. Simonian, San Diego, CA (US)
Assigned to Pacira Pharmaceuticals, Inc., San Diego, CA (US)
Filed by Pacira Pharmaceuticals, Inc., San Diego, CA (US)
Filed on Oct. 13, 2022, as Appl. No. 18/046,416.
Claims priority of provisional application 63/255,690, filed on Oct. 14, 2021.
Prior Publication US 2023/0133849 A1, May 4, 2023
Int. Cl. A61K 31/445 (2006.01); A61K 9/127 (2006.01); A61K 47/14 (2017.01); A61K 47/28 (2006.01)

CPC A61K 31/445 (2013.01) [A61K 9/127 (2013.01); A61K 47/14 (2013.01); A61K 47/28 (2013.01)]

38 Claims

1. A composition of bupivacaine encapsulated multivesicular liposomes (MVLs), comprising:

bupivacaine residing inside a plurality of internal aqueous chambers of the MVLs separated by lipid membranes, wherein the lipid membranes comprise DPPG or a salt thereof, DEPC, cholesterol, and a triglyceride selected from the group consisting of triolein, tricaprylin, and combinations thereof; and

an aqueous medium in which the bupivacaine encapsulated MVLs are suspended, wherein the aqueous medium comprises at least one buffering agent in a concentration from about 1 mM to about 50 mM, and wherein the osmolality of the aqueous medium is from about 320 mOsm/kg to about 360 mOsm/kg;

wherein the bupivacaine concentration in the composition is from about 18 mg/mL to about 40 mg/mL, and

wherein the plurality of internal aqueous chambers of the MVLs comprises one or more pH modifying agents, and has a pH from about 3.0 to about 6.6.