US 11,654,198 B2
Application of combination of polyethylene glycol and local anesthetic in non-narcotic analgesia
Zewang Feng, Beijing (CN); Jinliang Wang, Beijing (CN); Yanli Xiong, Beijing (CN); Juan Shi, Beijing (CN); and Xuan Zhao, Beijing (CN)
Assigned to JENKEM TECHNOLOGY CO., LTD. (TIANJIN), Tianjin (CN)
Appl. No. 16/473,437
Filed by JENKEM TECHNOLOGY CO., LTD. (TIANJIN), Tianjin (CN)
PCT Filed Dec. 22, 2017, PCT No. PCT/CN2017/117956
§ 371(c)(1), (2) Date Jun. 25, 2019,
PCT Pub. No. WO2018/121427, PCT Pub. Date Jul. 5, 2018.
Claims priority of application No. 201611247317.0 (CN), filed on Dec. 29, 2016; and application No. 201710937900.2 (CN), filed on Sep. 30, 2017.
Prior Publication US 2020/0147228 A1, May 14, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/60 (2017.01); A61K 31/167 (2006.01); A61K 31/4458 (2006.01); A61P 23/02 (2006.01); A61K 47/54 (2017.01); A61K 9/00 (2006.01)
CPC A61K 47/60 (2017.08) [A61K 9/0019 (2013.01); A61K 31/167 (2013.01); A61K 31/4458 (2013.01); A61K 47/545 (2017.08); A61P 23/02 (2018.01)] 2 Claims
 
1. A method of using a local anesthetic release system for non-anesthetic analgesia treatment, the method comprising: administering the local anesthetic release system to a subject, the local anesthetic release system is a prodrug of a local anesthetic, wherein the prodrug of the local anesthetic is a conjugate of polyethylene glycol and a local anesthetic, having a structure of a formula (I):
PEG-A-R0—B   (I)
wherein, PEG is a polyethylene glycol residue with a molecular weight of 1-100 KDa;
R0 is a C1-6 alkyl group;
B is a local anesthetic;
a quaternary ammonium salt having a structure of

OG Complex Work Unit Chemistry
 is formed at the junction of B and R0, and Rs0 is selected from a group consisting of F−, Cl−, Br−, I−, mesylate, ethylsulfonate, benzenesulfonate, citrate, lactate, succinate, fumarate, glutamate, citrate, salicylate and maleate;
A is a linking group selected from a structure shown by the following formula A1 or A2:

OG Complex Work Unit Chemistry
wherein, R1 and R6 are independently selected from a C1-6 alkyl group, or R1 and R6 are independently selected from —(CH2)iNHCO(CH2)j—, or —(CH2)iCONH(CH2)j—, and i and j are independently an integer selected from 0 to 6;
R2 is selected from —C═O, —C═S, —O— or —S—;
R3 and R7 are independently selected from —O— or —S—;
R4 and R5 are independently selected from H, C1-6 alkyl or halogen;
R8 and R9 are independently selected from H, C1-6 alkyl or —O(C═O)(CH2)iCH3, and i is an integer selected from 0 to 6;
Rs1 is selected from H or C1-6 alkyl.