Ibuprofen ester derivative and emulsion preparation thereof
The application related to an ibuprofen ester derivative and an emulsion preparation thereof. A carboxyl group of racemic ibuprofen or S-ibuprofen is derivatized so that Compound N9 and a dextrorotatory enantiomer N9(S) thereof are obtained and further prepared into an emulsion preparation, which overcomes the problems of safety and compliance of patients existing in clinical application of existing ibuprofen/dexibuprofen injections and achieves the purposes of reducing vascular irritation, increasing clinical use approaches, and improving the stability of preparations in clinical applications.
1 . An ibuprofen ester derivative, a racemate, stereoisomer, or pharmaceutically acceptable salt thereof, wherein the ibuprofen ester derivative is a compound represented by Structural Formula (1):
2 . The ibuprofen ester derivative according to claim 1 , wherein the compound represented by Structural Formula (1) is selected from a dextrorotatory enantiomer thereof, which has the following structure:
3 . The ibuprofen ester derivative according to claim 2 , wherein the dextrorotatory enantiomer N9(S) of the compound represented by Structural Formula (1) is a mixture of the following compounds N9(S)A and N9(S)B at any ratio:
4 . An emulsion preparation containing an ibuprofen ester derivative, comprising:
(a) a compound represented by Structural Formula (1), a racemate, stereoisomer, or pharmaceutically acceptable salt thereof:
(b) an emulsifier; and
(c) an oil.
5 . The emulsion preparation containing an ibuprofen ester derivative according to claim 4 , wherein based on a total weight of 100% of the emulsion preparation, a mass percentage of the active ingredient is 0.1-10%.
6 . The emulsion preparation containing an ibuprofen ester derivative according to claim 4 , wherein the compound represented by Structural Formula (1) is selected from a dextrorotatory enantiomer thereof, which has the following structure:
7 . The emulsion preparation containing an ibuprofen ester derivative according to claim 4 , wherein the emulsifier is selected from egg-yolk lecithin and/or soybean lecithin and has a mass percentage of 0.5-15%.
8 . The emulsion preparation containing an ibuprofen ester derivative according to claim 4 , wherein the oil is selected from one or more of sesame oil, median chain triglyceride, soybean oil, sunflower kernel oil or peanut oil and has a mass percentage of 0.1-15%.
9 . The emulsion preparation containing an ibuprofen ester derivative according to claim 4 , further comprising a stabilizer, wherein the stabilizer is selected from oleic acid or/and sodium oleate and has a mass percentage of 0.01-1%.
10 . The emulsion preparation containing an ibuprofen ester derivative according to claim 4 , further comprising an isosmotic adjusting agent, wherein the isosmotic adjusting agent is selected from one or more of sucrose, glucose, sorbitol, xylitol, sodium chloride or glycerin.
11 . The emulsion preparation containing an ibuprofen ester derivative according to claim 4 , further comprising a pH adjusting agent, wherein the pH adjusting agent is selected from one or more of citric acid, hydrochloric acid, citric acid, fumaric acid, lysine, tartaric acid, histidine, sodium citrate, sodium hydroxide, sodium citrate, sodium dihydrogen phosphate or disodium hydrogen phosphate.
12 . The emulsion preparation containing an ibuprofen ester derivative according to claim 4 , wherein the emulsion preparation is in a form of a fat emulsion injection or a nanoemulsion injection and has an average particle size within a range of 10-550 nm.