US 11,839,590 B2
Flurbiprofen axetil emulsion for injection and preparation method thereof
Ling Huang, WuHan (CN); Xiaohua Zhang, WuHan (CN); Jinchun Song, WuHan (CN); and Lei Yin, WuHan (CN)
Assigned to Grand life science (wuhan) co., LTD, Wuhan (CN)
Appl. No. 16/652,388
Filed by Grand life science (wuhan) co., LTD, Wuhan (CN)
PCT Filed Jan. 21, 2019, PCT No. PCT/CN2019/072562
§ 371(c)(1), (2) Date Mar. 30, 2020,
PCT Pub. No. WO2020/073559, PCT Pub. Date Apr. 16, 2020.
Claims priority of application No. 201811175197.7 (CN), filed on Oct. 10, 2018.
Prior Publication US 2021/0220303 A1, Jul. 22, 2021
Int. Cl. A61K 31/192 (2006.01); A61K 9/00 (2006.01); A61K 9/107 (2006.01); A61K 47/10 (2017.01); A61K 47/24 (2006.01); A61K 47/26 (2006.01)
CPC A61K 31/192 (2013.01) [A61K 9/0019 (2013.01); A61K 9/107 (2013.01); A61K 47/10 (2013.01); A61K 47/24 (2013.01); A61K 47/26 (2013.01)] 11 Claims
 
1. A method of preparation of a flurbiprofen axetil emulsion for injection, comprising:
adding 40 wt % to 60 wt % of an oil phase based on the total oil phase to a water phase with shear mixing under protection of nitrogen gas for 10 min to 30 min to obtain a crude emulsion A;
adding 20 wt % to 30 wt % of the oil phase based on the total oil phase to the crude emulsion A with shear mixing under the protection of the nitrogen gas for 10 min to 30 min to obtain a crude emulsion B; and
mixing the crude emulsion B with the rest of the total oil phase with shear mixing under the protection of the nitrogen gas for 10 min to 30 min to obtain an initial emulsion;
wherein the oil phase comprises flurbiprofen axetil, an oil phase solvent, an emulsifier, and a stabilizer, and
wherein the water phase comprises water for injection optionally an osmotic pressure regulator,
wherein the oil phase solvent is selected from the group consisting of a refined soybean oil, olive oil, medium-chain triglyceride, and a combination thereof,
wherein the emulsifier is selected from the group consisting of egg yolk lecithin, soybean lecithin, polyethylene glycol glyceryl stearate, and a combination thereof,
wherein the stabilizer is selected from the group consisting of dioleoylphosphatidylserine, dipalmitoylphosphatidic acid, sphingomyelin, and a combination thereof.