	US 11,793,799 B2
	Sustained-release anesthetic compositions and methods of preparation thereof
Keelung Hong, San Francisco, CA (US); Hao-Wen Kao, Taipei (TW); Yi-Yu Lin, Taipei (TW); and Luke S. S. Guo, San Francisco, CA (US)
Assigned to TLC Biopharmaceuticals Inc., South San Francisco, CA (US); and Taiwan Liposome Co., Ltd., Taipei (TW)
Appl. No. 16/642,762
Filed by TLC Biopharmaceuticals, Inc., South San Francisco, CA (US); and Taiwan Liposome Co., Ltd., Taipei (TW)
PCT Filed Aug. 28, 2018, PCT No. PCT/US2018/048329 § 371(c)(1), (2) Date Feb. 27, 2020, PCT Pub. No. WO2019/046293, PCT Pub. Date Mar. 7, 2019.
Claims priority of provisional application 62/621,730, filed on Jan. 25, 2018.
Claims priority of provisional application 62/550,983, filed on Aug. 28, 2017.
Prior Publication US 2020/0188374 A1, Jun. 18, 2020
Int. Cl. A61K 31/445 (2006.01); A61P 23/00 (2006.01); A61K 9/06 (2006.01); A61K 47/22 (2006.01); A61K 47/24 (2006.01); A61K 47/28 (2006.01)

CPC A61K 31/445 (2013.01) [A61K 9/06 (2013.01); A61K 47/22 (2013.01); A61K 47/24 (2013.01); A61K 47/28 (2013.01); A61P 23/00 (2018.01)]

16 Claims

1. A method of preparing a sustained-release anesthetic composition, comprising:

creating a highly entrapped lipid structure (HELS) comprising:

at least one amide-type local anesthetic in a free base form, and

a lipid mixture including at least one phospholipid, and

hydrating the HELS with an aqueous buffer solution at a pH of 5.5 to 8.0 to obtain the sustained-release anesthetic composition for locally administering the amide-type local anesthetic to a subject in need thereof; wherein hydrating the HELS forms multilamellar vesicles (MLVs) that entrap the amide-type local anesthetic; the median diameter of the MLVs with the entrapped amide-type local anesthetic is at least 1 μm; and the molar ratio of the entrapped amide-type local anesthetic to phospholipid in the MLVs is at least 0.5:1.