Granted Patent B2

US 12,746,286 · App. 17/792,474 · Granted Sep 29, 2026

Inventors: Yong Gan (Shanghai, CN); Shiyan Guo (Shanghai, CN); Yinyin Sun (Shanghai, CN); Quanlei Zhu (Shanghai, CN)

Assignee: SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

A61K47/24A61K9/08A61K31/445A61K47/12A61K47/44A61P23/02

Abstract

Claims (50)

1 . A long-acting ropivacaine pharmaceutical composition comprising, based on the total weight of the composition, in weight percentage,

0.5% to 10% of ropivacaine;

2% to 25% of a pharmaceutical solvent;

8% to 55% of a pharmaceutical phospholipid;

15% to 89% of a pharmaceutical oil;

2% to 10% of an efficacy enhancer;

0% to 1% of an antioxidant; and

0% to 8% of an acid-base regulator,

wherein the efficacy enhancer is one or more selected from substances having an eicosapentaenoic acid content of no less than 15% and a docosahexaenoic acid content of no less than 10%, or the efficacy enhancer is selected from linseed oil, perilla seed oil, walnut oil, argan oil, fish oil, layer oil and algal oil, and combinations thereof,

wherein the pharmaceutical phospholipid is one or more selected from the group consisting of natural phospholipids, semi-synthetic phospholipids and synthetic phospholipids,

wherein the natural phospholipid is selected from the group consisting of egg yolk lecithin, soybean phospholipid and combinations thereof,

wherein the semi-synthetic phospholipid is selected from hydrogenated egg yolk lecithin, hydrogenated soybean phospholipid and combinations thereof, and

wherein the synthetic phospholipid is one or more selected from the group consisting of dipalmitoyl phosphatidylethanolamine, dipalmitoyl phosphatidic acid, dipalmitoylphosphatidylglycerol, dioleoylphosphatidylethanolamine, dipalmitoylphosphatidylcholine, distearoylphosphatidyl-choline, and dimyristoylphosphatidylcholine.

2 . The long-acting ropivacaine pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition reduces peak plasma concentration of a drug by 30% or more compared with ropivacaine hydrochloride injection at the same dose; and the pharmaceutical composition has a duration of action of 12 h or more.

3 . The long-acting ropivacaine pharmaceutical composition according to claim 1 ,

wherein the ropivacaine includes ropivacaine free base and salts thereof,

wherein the pharmaceutical solvent is one or more selected from the group consisting of benzyl alcohol, ethanol, propylene glycol, glycerin, isopropanol, N-methylpyrrolidone, dimethyl sulfoxide, liquid polyethylene glycol, dimethylacetamide, glycerol monoacetate, polyethylene glycol monomethyl ether, diethylene glycol monoethyl ether, ethyl lactate, ethyl acetate, propylene glycol diethyl ester, diethyl malonate, tetrahydrofuran polyethylene glycol ether, and benzyl benzoate,

wherein the antioxidant is one or more selected from the group consisting of cysteine, α-tocopherol, α-tocopherol acetate, N-acetyl-L-cysteine, butylated hydroxyanisole, dibutylated hydroxytoluene, propyl gallate, tert-butyl hydroquinone, lipoic acid, tea polyphenol, L-ascorbyl palmitate, and glutathione,

wherein the acid-base regulator is one or more selected from the group consisting of arginine, lysine, histidine, glycine, tromethamine, diethanolamine, ethylenediamine, meglumine, hydrochloric acid, acetic acid, anhydrous citric acid, ascorbic acid, lactic acid, tartaric acid, methanesulfonic acid, methionine, sodium hydroxide, and triethanolamine, and

wherein the pharmaceutical oil is one or more selected from the group consisting of natural vegetable oils, semi-natural oils artificially modified from natural vegetable oils, purified oils, and artificially synthesized oils.

4 . The long-acting ropivacaine pharmaceutical composition according to claim 1 ,

wherein the pharmaceutical solvent is one or more selected from the group consisting of benzyl alcohol, propylene glycol, and ethanol,

wherein the antioxidant is one or more selected from the group consisting of α-tocopherol, L-ascorbyl palmitate, and cysteine,

wherein the natural vegetable oils include castor oil, sesame oil, soybean oil, sunflower oil, peanut oil, corn oil, rapeseed oil, olive oil, and cottonseed oil,

wherein the semi-natural oils artificially modified from natural vegetable oils include hydrogenated castor oil,

wherein the artificially synthesized oils include medium chain triglycerides, long chain triglycerides, triacetin, and ethyl oleate.

5 . A method of pain treatment comprising administering a pain relief medicament including the long-acting ropivacaine pharmaceutical composition according to claim 1 .

6 . The method according to claim 5 , wherein the pain relief medicament is administered by local injection.

7 . The method according to claim 5 , wherein the expected total daily dose of the long-acting ropivacaine pharmaceutical composition is 5-1000 mg of the active drug.

8 . The long-acting ropivacaine pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition has a duration of action of 24 h or more.

9 . The long-acting ropivacaine pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition has a duration of action of 48 h or more.

10 . The long-acting ropivacaine pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises, based on the total weight of the composition, in weight percentage,

1% to 8% of ropivacaine;

3% to 23% of the pharmaceutical solvent;

10% to 50% of the pharmaceutical phospholipid;

20% to 76% of the pharmaceutical oil;

2% to 9% of the efficacy enhancer;

0% to 0.5% of the antioxidant; and

0% to 5% of the acid-base regulator.

11 . The long-acting ropivacaine pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises, based on the total weight of the composition, in weight percentage,

1% to 5% of ropivacaine;

5% to 20% of the pharmaceutical solvent;

15% to 45% of the pharmaceutical phospholipid;

22% to 60% of the pharmaceutical oil;

2% to 8% of the efficacy enhancer;

0% to 0.3% of the antioxidant; and

0% to 3% of the acid-base regulator.

12 . The long-acting ropivacaine pharmaceutical composition according to claim 1 , wherein the efficacy enhancer is substances having an eicosapentaenoic acid content of no less than 20% and a docosahexaenoic acid content of no less than 10%.

13 . The method according to claim 5 , wherein a pain treated is postoperative pain.

14 . The method according to claim 6 , wherein the local injection includes subcutaneous or intramuscular injection, direct instillation at the incision, incision infiltration, administration at the nerve plexus, and intra-articular injection.

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (25)