US 12,285,524 B2
Sustained-release pharmaceutical compositions comprising an antipsychotic drug and uses thereof
Keelung Hong, South San Francisco, CA (US); Jonathan Fang, 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. 17/266,201
Filed by TAIWAN LIPOSOME CO., LTD., Taipei (TW); and TLC BIOPHARMACEUTICALS, INC., South San Francisco, CA (US)
PCT Filed Jul. 31, 2019, PCT No. PCT/US2019/044318
§ 371(c)(1), (2) Date Feb. 5, 2021,
PCT Pub. No. WO2020/033195, PCT Pub. Date Feb. 13, 2020.
Claims priority of provisional application 62/715,979, filed on Aug. 8, 2018.
Prior Publication US 2021/0308051 A1, Oct. 7, 2021
Int. Cl. A61K 9/1271 (2025.01); A61K 9/00 (2006.01); A61K 31/519 (2006.01); A61K 31/551 (2006.01)
CPC A61K 9/1271 (2013.01) [A61K 9/0019 (2013.01); A61K 31/519 (2013.01); A61K 31/551 (2013.01)] 14 Claims
 
1. A pharmaceutical composition, comprising
(a) at least one liposome comprising a bilayer membrane, said bilayer membrane comprises about 45 to about 79.9 mole % of a first lipid that is a 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) or any combination thereof, about 20 to about 55% mole % of cholesterol and optionally 0.1-20% mole % of a second lipid that is 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) or any combination thereof;
(b) a trapping agent that is triethylammonium sucrose octasulfate, ammonium sulfate, dextran sulfate, or any combination thereof; and
(c) an antipsychotic drug that is aripiprazole, olanzapine, quetiapine, risperidone, clozapine, or any combination thereof,
wherein when the antipsychotic drug is aripiprazole or clozapine, the trapping agent is triethylammonium sucrose octasulfate, when the antipsychotic drug is olanzapine, the trapping agent is ammonium sulfate; when the antipsychotic drug is quetiapine, the trapping agent is dextran sulfate and when the antipsychotic drug is risperidone, the trapping agent is triethylammonium sucrose octasulfate or ammonium sulfate;
wherein the molar ratio of the drug to the lipid is equal to or higher than 0.47 and the antipsychotic drug is encapsulated in the liposome with an encapsulation efficiency higher than 60%.