US 11,964,050 B2
Liposome compositions comprising weak acid drugs and uses thereof
Pei Kan, Taipei (TW); Yi Fong Lin, New Taipei (TW); and Ko Chieh Chen, Taipei (TW)
Assigned to PHARMOSA BIOPHARM INC., Taipei (TW)
Filed by Pharmosa Biopharm Inc., Taipei (TW)
Filed on Jul. 23, 2018, as Appl. No. 16/043,126.
Claims priority of provisional application 62/595,207, filed on Dec. 6, 2017.
Claims priority of provisional application 62/536,034, filed on Jul. 24, 2017.
Prior Publication US 2019/0022004 A1, Jan. 24, 2019
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/127 (2006.01); A61K 31/5585 (2006.01); A61K 47/02 (2006.01); A61P 11/06 (2006.01)
CPC A61K 9/127 (2013.01) [A61K 9/1271 (2013.01); A61K 9/1278 (2013.01); A61K 31/5585 (2013.01); A61K 47/02 (2013.01); A61P 11/06 (2018.01)] 13 Claims
 
1. A pharmaceutical composition, comprising liposomes, said liposomes comprising:
(a) a lipid bilayer formed of a first phospholipid, a second phospholipid, and cholesterol, wherein the first phospholipid is hydrogenated soy phosphatidylcholine (HSPC), dipalmitoyl phosphatidylcholine (DPPC), distearyloyl phosphatidylcholine (DSPC), diarachidoyl phosphatidylcholine, dimyristoyl phosphatidylcholine (DMPC) or any combination thereof and the second phospholipid is distearyloylphosphatidylglycerol (DSPG), or PEG-DSPE; and
(b) an internal aqueous medium inside the lipid bilayer, the internal aqueous medium comprising a bicarbonate salt with a concentration about 50 mM to about 800 mM and a weak acid drug, said weak acid drug is Iloprost, treprostinil, Piroxicam, Meloxicam, and Warfarin sodium,
wherein the liposomes are suspended in an external medium, the pH of the external medium is above the pKa of the weak acid drug and less than about 7, and
wherein the external medium is substantially free of bicarbonate salt such that there is from less than 2% to 0% bicarbonate salt and the encapsulation efficiency of the weak acid drug is at least 80%.