US 12,138,345 B2
Delivery of agents using metastable liposomes
Jonathan H. Kaufman, Pittsburgh, PA (US); and Michael B. Chancellor, Pittsburgh, PA (US)
Assigned to Lipella Pharmaceuticals Inc., Pittsburgh, PA (US)
Filed by Lipella Pharmaceuticals Inc., Pittsburgh, PA (US)
Filed on Jun. 1, 2022, as Appl. No. 17/829,960.
Application 17/829,960 is a continuation of application No. 16/866,140, filed on May 4, 2020, granted, now 11,357,725.
Application 16/866,140 is a continuation of application No. 15/030,140, granted, now 10,639,278, issued on May 5, 2020, previously published as PCT/US2014/061769, filed on Oct. 22, 2014.
Claims priority of provisional application 61/894,334, filed on Oct. 22, 2013.
Prior Publication US 2023/0098795 A1, Mar. 30, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/127 (2006.01); A61K 9/00 (2006.01); A61K 31/436 (2006.01); A61K 49/00 (2006.01)
CPC A61K 9/1272 (2013.01) [A61K 9/0034 (2013.01); A61K 31/436 (2013.01); A61K 49/0084 (2013.01)] 19 Claims
OG exemplary drawing
 
1. A dosage formulation of metastable liposomes comprising:
multilamellar metastable liposomes having a mean diameter of between one and 100 microns, inclusive, which comprise tacrolimus,
wherein the ratio of the volume enclosed by the liposomes at 25° C. relative to the volume enclosed by the liposomes following heating to a temperature that surpasses the gel-fluid phase transition of one or more lipids forming the liposomes is greater than 1.0;
wherein the tacrolimus is entrapped within the lipid forming the liposomes,
wherein the tacrolimus is present in the dosage formulation in an amount ranging from between 20 to 50 mg; and
wherein the metastable liposomes are prepared by a method comprising:
(a) dispersing the lipid forming the liposomes in a co-solvent system to create an isotropic monophasic solution;
(b) mixing the isotropic monophasic solution with the tacrolimus to form a pre-liposomal solution;
(c) lyophilizing the pre-liposomal solution to produce a pre-liposomal lyophilized formulation; and
(d) rehydrating the pre-liposomal lyophilized formulation of step (c) to produce the liposomes.