# US 11,992,483 B2 · Emulsions for local anesthetics > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,992,483 B2 - Document ID: US11992483B2 - Status: Granted - Kind: B2 - Application number: 17/369,369 - Filed: 2021-07-07 - Published: 2022-10-06 - Granted: 2024-05-28 - Earliest claimed: 2021-03-31 - Assignees: Cali Biosciences US, LLC - Applicants: Cali Pharmaceuticals, LLC - Inventors: Andrew Xian Chen; Lijia Chen; Damian McLoud - Web page: https://patentgrep.com/patent/US11992483B2 ## CPC - A61K 31/445: Non condensed piperidines, e.g. piperocaine - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} - A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)} - A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol - A61K 31/381: having five-membered rings - A61K 31/47: Quinolines; Isoquinolines - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame} - A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones - A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids - A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14) - A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like - A61P 23/02: Local anaesthetics - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Use of an emulsion for pain relief comprising a local anesthetic, lecithin, oil and an aqueous phase, wherein local anesthetic is non-covalent bound to the emulsion oil droplets and the emulsion is physically and chemically stable and said emulsion provides better safety, extended release pharmacokinetics and a prolonged duration of action of the local anesthetic. ## Claims ### Claim 1 A method for relief of a pain in a subject in need thereof, the method comprising: administering to the subject an effective amount of a water-in-oil emulsion composition, comprising: an amide local anesthetic, which is ropivacaine, a pharmaceutically acceptable salt thereof or a combination thereof, wherein the amide local anesthetic is no more than about 4% by weight of the emulsion; an oil phase, the oil phase comprising lecithin and a vegetable oil at a weight ratio between 2:1 to 5:4; and a water-miscible organic solvent between 6% and 10% of the emulsion weight; an aqueous phase, where the water content is less than 5% of the emulsion weight, wherein small water droplets are dispersed in the oil phase and the emulsion contains particles or water droplets with a diameter between about 30 nm and about 500 nm. ### Claim 2 (depends on 1) The method of claim 1, wherein the vegetable oil is a member selected from the group consisting of sesame oil, soybean oil, olive oil and a combination thereof. ### Claim 3 (depends on 2) The method of claim 2, wherein the vegetable oil which is sesame oil. ### Claim 4 (depends on 1) The method of claim 1, wherein the lecithin is a member selected from the group consisting of LIPOID S75, LIPOID S 100, LIPOID E80, Phospholipond 90G and a combination thereof. ### Claim 5 (depends on 1) The method of claim 1, wherein the lecithin contains no less than 75% by weight phosphatidylcholine. ### Claim 6 (depends on 1) The method of claim 1, wherein the water-miscible organic solvent selected from a group consisting of ethanol, propylene glycol, glycerol and liquid polyethylene glycol. ### Claim 7 (depends on 1) The method of claim 1, wherein the composition has a viscosity between about 2 and about 40,000 centipoises. ### Claim 8 (depends on 1) The method of claim 1, wherein the composition is a translucent or white opaque liquid and is filterable through a 0.2-micron filter. ### Claim 9 (depends on 1) The method of claim 1, wherein more than 90% by weight of the amide local anesthetic is non-covalently bound to the oil droplets. ### Claim 10 (depends on 1) The method of claim 1, wherein the oil droplets or particles in the emulsion are non-liposomal and substantially free of liposomal bilayer membrane structure. ### Claim 11 (depends on 1) The method of claim 1, wherein the composition is diluted with saline to a 2:1 ratio or greater, which represents volume of diluent-to-the volume of emulsion, or with water to a 4:1 ratio or greater before administration. ### Claim 12 (depends on 1) The method of claim 1, wherein the composition is administered to the subject by a member selected from the group consisting of wound infiltration, instillation, and nerve block. ### Claim 13 (depends on 1) The method of claim 1, wherein the composition is administered using a syringe, a syringe with a needle or a syringe with a catheter. ### Claim 14 (depends on 1) The method of claim 1, wherein the composition is provided in a vial or a syringe, ready-to-inject or ready-to-administer. ### Claim 15 (depends on 1) The method of claim 1, wherein administration of the composition provides a prolonged pharmacokinetic profile with a lower Cmax, longer Tmax and greater T1/2 compared to the same local anesthetic in a solution formulation. ### Claim 16 (depends on 1) The method of claim 1, wherein administering the ropivacaine composition by wound infiltration or instillation maintains a ropivacaine plasma level below its cardiotoxic level. ### Claim 17 (depends on 1) The method of claim 1, wherein the administration of the composition does not cause any detectable local anesthetic systemic toxicity (LAST). ### Claim 18 (depends on 1) The method of claim 1, wherein the pain is a member selected from the group consisting of somatogenic, neurogenic, and psychogenic pain. ### Claim 19 (depends on 1) The method of claim 1, wherein the pain is post-operative pain or cancer pain. ### Claim 20 (depends on 1) The method of claim 1, wherein administration of the composition provides pain relief for at least 24 hours in the subject. ### Claim 21 (depends on 1) The method of claim 1, wherein the composition provides pain relief by reducing the pain intensity as measured by a pain intensity scale by no less than 10% for up to 72 hours. ### Claim 22 (depends on 1) The method of claim 1, wherein administration of the composition provides a quick onset of relief within 60 minutes and lasts for about 48-72 hours after administration. ### Claim 23 (depends on 1) The method of claim 1, wherein the composition provides a delay or reduction in opioid use by the subject. ### Claim 24 (depends on 1) The method of claim 1, wherein the emulsion composition comprises about 30% to about 40% vegetable oil by weight of the emulsion. ### Claim 25 (depends on 1) The method of claim 1, wherein the emulsion composition comprises about 50% to about 60% lecithin by weight of the emulsion. ### Claim 26 (depends on 1) The method of claim 1, wherein the emulsion composition comprises: about 2.55% w/w ropivacaine HCl monohydrate; about 52% w/w soy lecithin; about 0.02% w/w EDTA disodium dihydrate; about 8% w/w ethanol; about 36% w/w sesame oil; and about 0.1% w/w L-cysteine.