US 12,268,781 B2
Sustained-release pharmaceutical compositions comprising a therapeutic agent for treating dementia and uses thereof
Keelung Hong, South San Francisco, CA (US); Hao-Wen Kao, South San Francisco, CA (US); Yi-Yu Lin, South San Francisco, CA (US); and Walter Gwathney, South San Francisco, CA (US)
Assigned to TAIWAN LIPOSOME CO., LTD., Taipei (TW); and TLC BIOPHARMACEUTICALS, INC., South San Francisco, CA (US)
Appl. No. 17/262,300
Filed by TAIWAN LIPOSOME CO., LTD., Taipei (TW); and TLC BIOPHARMACEUTICALS, INC., South San Francisco, CA (US)
PCT Filed Jul. 23, 2019, PCT No. PCT/US2019/042933
§ 371(c)(1), (2) Date Jan. 22, 2021,
PCT Pub. No. WO2020/023445, PCT Pub. Date Jan. 30, 2020.
Claims priority of provisional application 62/702,563, filed on Jul. 24, 2018.
Prior Publication US 2021/0378961 A1, Dec. 9, 2021
Int. Cl. A61K 9/127 (2006.01); A61K 9/1271 (2025.01); A61K 31/13 (2006.01); A61K 31/27 (2006.01); A61K 47/02 (2006.01); A61K 47/26 (2006.01); A61K 47/28 (2006.01)
CPC A61K 9/1271 (2013.01) [A61K 31/13 (2013.01); A61K 31/27 (2013.01); A61K 47/02 (2013.01); A61K 47/26 (2013.01); A61K 47/28 (2013.01)] 15 Claims
 
1. A pharmaceutical composition, comprising:
(a) at least one liposome comprising a bilayer membrane, said bilayer membrane comprises about 40 to about 80 mole % of a first lipid that is selected from the group consisting of phosphatidylcholine (PC), 1,2-distearoyl-sn-glycero-3-phosphocholine (HSPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1-palmitoyl-2-stearoyl-sn-glycero-3-phosphocholine (PSPC) and any combination thereof, about 20 to about 40% mole % of cholesterol and optionally 0.1-30% mole % of a second lipid that is selected from the group consisting of a phosphatidylethanolamine, phosphatidylglycerol, N-(carbonyl-methoxypolyethyleneglycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG-DSPE), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DPPG) and any combination thereof;
(b) a trapping agent that is selected from the group consisting of about 10 to 200 mM triethylammonium sucrose octasulfate, about 100 to 600 mM ammonium sulfate, about 0.1 to 10 mM dextran sulfate and any combination thereof; and
(c) a therapeutic agent that is an acetylcholinesterase inhibitor or memantine,
wherein the molar ratio of the therapeutic agent to the lipid is equal to or higher about than 0.2 and the therapeutic agent is encapsulated in the liposome with an encapsulation efficiency higher than about 50%.