# US 2019/0167574 A1 · Injectable long-acting local anesthetic semi-solid gel formulations > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0167574 A1 - Document ID: US20190167574A1 - Status: Published application - Kind: A1 - Application number: 16/212,206 - Filed: 2018-12-06 - Published: 2019-06-06 - Earliest claimed: 2017-12-06 - Assignees: Mira Pharma Corporation - Applicants: Mira Pharma Corporation - Inventors: Hui Rong Shen; Na Gan - Web page: https://patentgrep.com/patent/US20190167574A1 ## CPC - A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 31/445: Non condensed piperidines, e.g. piperocaine - A61K 31/5575: having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha - A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids - A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters - 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 25/04: Centrally acting analgesics, e.g. opioids - 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 What is disclosed is a controlled release pharmaceutical composition comprising a biocompatible and bioerodible semi-solid gel comprising a triglyceride of ricinoleic acid, a gelling agent, bupivacaine and, optionally, a corticosteroid, an analgesic, or an anti-inflammatory agent. ## Claims ### Claim 1 A pharmaceutical formulation, comprising (A) a glyceride mixture comprising (i) triglyceride of ricinoleic acid; and (ii) glycerides selected from the group consisting of (a) a mixture of C12 to C18 triglycerides (SUP DM) (b) a mixture of C8 to C18 triglycerides (G43/01); (c) a mixtures of hydrogenated coco-glycerides (WIT E85 and WIT E76); and (d) a mixture of C10 to C18 triglycerides (SUP D); or other solid glycerides with a melting point between 37° C. and 75° C.; wherein the ratio (i):(ii), is 10:1 to 6:3 (w:w); and (B) active agents comprising (i) a therapeutically effective amount of bupivacaine to provide analgesia for at least two days; and, optionally, (ii) a corticosteroid, an analgesic or an anti-inflammatory agent; wherein the active agents are solubilized in the glyceride mixture at a concentration of 0.01-60 wt %; and wherein the pharmaceutical composition is a semi-solid gel which is biocompatible, bioerodible, homogeneous, and a single phase; and wherein the pharmaceutical composition consists of a semi-solid gel with a viscosity of 50-2000 cPs at 30° C. ### Claim 2 (depends on 1) The pharmaceutical formulation of claim 1, wherein the active agents comprise a corticosteroid, an analgesic or an anti-inflammatory agent. ### Claim 3 (depends on 2) The pharmaceutical formulation of claim 2, wherein the corticosteroid is a glucocorticosteroid. ### Claim 4 (depends on 2) The pharmaceutical formulation of claim 2, wherein the anti-inflammatory agent is a non-steroidal anti-inflammatory agent (NSAID) selected from the group consisting of ketoprofen, naproxen, meloxicam, COX-1 inhibitors, and COX-2 inhibitors. ### Claim 5 (depends on 1) The pharmaceutical formulation of claim 1, wherein the glyceride mixture comprises SUP DM. ### Claim 6 (depends on 1) The pharmaceutical formulation of claim 1, wherein the glyceride mixture comprises castor oil:SUP DM having a relative concentration of 8:1.0, 8:1.1, 8:1.2, 8:1.3, 8:1.4, 8:1.5, 8:1.6, 8:1.7, 8:1.8, 8:1.9, 8:2.0, 8:2.1, 8:2.2, 8:2.3, 8:2.4, or 8:2.5 (w:w). ### Claim 7 (depends on 1) The pharmaceutical formulation of claim 1, wherein less than 80% of the bupivacaine is released from a depot of the semi-solid gel in five days when measured in vitro at 37° C. ### Claim 8 (depends on 1) The pharmaceutical formulation of claim 1, wherein less than 60% of the bupivacaine is released from a depot of the semi-solid gel in five days when measured in vitro at 37° C. ### Claim 9 (depends on 1) The pharmaceutical formulation of claim 1, wherein less than 66% of the bupivacaine is released from the depot in five days when measured in vitro at 37° C. ### Claim 10 (depends on 1) The pharmaceutical formulation of claim 1, wherein the viscosity is less than 701 cPs at 30° C. ### Claim 11 (depends on 1) The pharmaceutical formulation of claim 1, wherein the pharmaceutical composition releases bupivacaine for at least one week when measured in vitro at 37° C. ### Claim 12 (depends on 1) The pharmaceutical formulation of claim 1, wherein the pharmaceutical composition releases bupivacaine for at least two weeks when measured in vitro at 37° C. ### Claim 13 (depends on 1) The pharmaceutical formulation of claim 1, wherein glyceride mixture has an aqueous solubility of less than 1 mg/ml or less than 0.1 mg/ml in a buffer of physiological pH at 37° C. ### Claim 14 (depends on 1) The pharmaceutical formulation of claim 1, wherein the glyceride mixture comprises castor oil. ### Claim 15 (depends on 1) The pharmaceutical formulation of claim 1, wherein the glyceride mixture comprises ricinoleic acid triester:SUP DM, having a relative concentration of 8:1.8 (w:w). ### Claim 16 (depends on 1) The pharmaceutical formulation of claim 1, wherein less than 80% of the bupivacaine is released from a depot of the semi-solid gel in five days when measured in vitro at 37° C. ### Claim 17 (depends on 1) The pharmaceutical formulation of claim 1, wherein the viscosity is less than 701 cPs at 30° C. ### Claim 18 (depends on 1) The pharmaceutical formulation of claim 1, wherein the pharmaceutical composition releases bupivacaine for at least one week when measured in vitro at 37° C. ### Claim 19 (depends on 1) The pharmaceutical formulation of claim 1, wherein the pharmaceutical composition releases bupivacaine for at least two weeks when measured in vitro at 37° C. ### Claim 20 (depends on 1) The pharmaceutical formulation of claim 1, for use in treating pain following surgery. ### Claim 21 (depends on 1) The pharmaceutical formulation of claim 1, wherein a single injection of the pharmaceutical formulation comprises an amount of bupivacaine effective to provide sensory blockade for 72 hours. ### Claim 22 (depends on 1) The pharmaceutical formulation of claim 1, wherein a single injection of the pharmaceutical formulation causes substantially limited motor blockade.