# US 12,214,080 B2 · Micronized lipids > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,214,080 B2 - Document ID: US12214080B2 - Status: Granted - Kind: B2 - Application number: 17/306,261 - Filed: 2021-05-03 - Published: 2022-11-17 - Granted: 2025-02-04 - Earliest claimed: 2021-05-03 - Assignees: MCAL Therapeutics Inc. - Applicants: MCAL Therapeutics Inc. - Inventors: Thomas Gadek - Web page: https://patentgrep.com/patent/US12214080B2 ## CPC - A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) - A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - A61K 9/0048: {Eye, e.g. artificial tears} - A61K 9/10: Dispersions; Emulsions - A61K 47/02: Inorganic compounds - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin - 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) - 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) ## Abstract The present invention relates to drug delivery vehicles comprising micronized particles that include an active lipid agent, and in particular to micronized lipid particles that comprise an ether lipid such as sn-1-O-eicosanyl-sn-2-palmitoyl-glycerol and its isomers. ## Claims ### Claim 1 A drug delivery vehicle comprising crystalline solid non-polar lipid particles having an average particle size of less than 50 microns, the particles comprising an active agent other than the lipids forming the crystalline solid non-polar lipid particles, wherein the lipids forming the crystalline solid non-polar lipid particles comprise lipids selected from the group consisting of: wherein R1 is an unsubstituted C6 to C30 alkyl or alkenyl; R2 is an unsubstituted C5 to C29 alkyl or alkenyl; and R3 is a hydrogen; wherein R1 is a hydrogen; R2 is an unsubstituted C5 to C29 alkyl or alkenyl; and R3 is an unsubstituted C6 to C30 alkyl or alkenyl; wherein R1 is an unsubstituted C6 to C30 alkyl or alkenyl; R2 is an unsubstituted C5 to C29 alkyl or alkenyl; and R3 is a hydrogen, wherein R1 is an unsubstituted C6 to C30 alkyl or alkenyl; R2 is a hydrogen; and R3 is an unsubstituted C5 to C29 alkyl or alkenyl; wherein R1 is an unsubstituted C5 to C29 alkyl or alkenyl; R2 is a hydrogen; and R3 is an unsubstituted C6 to C30 alkyl or alkenyl; and wherein R1 is an unsubstituted C6 to C30 alkyl or alkenyl; R2 is a hydrogen; and R3 is an unsubstituted C5 to C29 alkyl or alkenyl. ### Claim 2 (depends on 1) The drug delivery vehicle of claim 1, wherein the crystalline solid non-polar lipid particles have a melting point of less than 80 degrees C. ### Claim 3 (depends on 1) The drug delivery vehicle of claim 1, wherein the crystalline solid non-polar lipid particles have a melting point of from 20 to 80 degrees C. ### Claim 4 (depends on 1) The drug delivery vehicle of claim 1, wherein the crystalline solid non-polar lipid particles have a melting point of from 30 to 60 degrees C. ### Claim 5 (depends on 1) The drug delivery vehicle of claim 1, wherein the crystalline solid non-polar lipid particles have an average particle size of less than 20 microns. ### Claim 6 (depends on 1) The drug delivery vehicle of claim 1, wherein the crystalline solid non-polar lipid particles have an average particle size of less than 10 microns. ### Claim 7 (depends on 1) The drug delivery vehicle of claim 1 wherein the crystalline solid non-polar lipid particles comprise an ether lipid selected from the group consisting of 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG), sn-1-O-eicosanyl-2-palmitoyl-glycerol, sn-2-palmitoyl-3-O-eicosanyl-glycerol, 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG), sn-1-O-eicosanyl-3-palmitoyl-glycerol, sn-1-palmitoyl-3-O-eicosanyl-glycerol and mixtures thereof. ### Claim 8 (depends on 7) The drug delivery vehicle of claim 7, wherein the crystalline solid non-polar lipid particles comprise an ether lipid selected from the group consisting of 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) or 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) and mixtures thereof. ### Claim 9 (depends on 8) The drug delivery vehicle of claim 8, wherein the mixture of ether lipid isomers 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) and 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) and mixtures thereof is characterized in comprising greater than 95% (mole percent) of the 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) isomer or greater than 95% (mole percent) of the 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) isomer. ### Claim 10 (depends on 8) The drug delivery vehicle of claim 8, wherein the mixture of ether lipid isomers 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) and 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) is characterized in comprising greater than 98% (mole percent) of the 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) isomer or greater than 98% (mole percent) of the 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) isomer. ### Claim 11 (depends on 8) The drug delivery vehicle of claim 8, wherein the mixture of ether lipid isomers 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) and 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) is characterized in comprising greater than 99% (mole percent) of the 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) isomer or greater than 99% (mole percent) of the 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) isomer. ### Claim 12 (depends on 8) The drug delivery vehicle of claim 8, wherein the mixture of ether lipid isomers 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) and 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) is characterized in comprising greater than 95% (mole percent) of the 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) isomer and no greater than 5% (mole percent) of the 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) isomer. ### Claim 13 (depends on 8) The drug delivery vehicle of claim 8, wherein the mixture of ether lipid isomers 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) and 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) is characterized in comprising greater than 98% (mole percent) of the 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) isomer and no greater than 2% (mole percent) of the 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) isomer. ### Claim 14 (depends on 8) The drug delivery vehicle of claim 8, wherein the mixture of ether lipid isomers 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) and 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) is characterized in comprising greater than 99% (mole percent) of the 1-O-eicosanyl-2-palmitoyl-rac-glycerol (1,2-EPRG) isomer and no greater than 1% (mole percent) of the 1-O-eicosanyl-3-palmitoyl-rac-glycerol (1,3-EPRG) isomer. ### Claim 15 (depends on 1) The drug delivery vehicle of any one of claim 1, wherein the crystalline solid non-polar lipid particles further comprise one or more additional lipids selected from the group consisting of a nonpolar mono-, di- or tri-glyceride, a wax ester including cholesterol esters, a sterol, a free fatty acid and combinations thereof. ### Claim 16 (depends on 1) The drug delivery vehicle of claim 1, wherein the active agent is selected from the group consisting of over the counter (OTC) or prescription topical ophthalmics, OTC or prescription topical ophthalmics for the treatment of dry eye, NMDA antagonists, anti-bacterials, antihistamines, decongestants, anti-inflammatoireantiparasitics, miotics, sympathomimetics, anticholinergics, adrenergics, antivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, adrenergic anesthetics, beta blockers, alpha-2-agonists, cycloplegics, prostaglandins and combinations thereof. ### Claim 17 (depends on 1) The drug delivery vehicle of claim 1, wherein the crystalline solid non-polar lipid particles are formulated as an aqueous suspension in a physiologically acceptable carrier. ### Claim 18 (depends on 17) The drug delivery vehicle of claim 17, wherein the liquid composition is a suspension of the crystalline solid micronized lipid particles in water containing phosphate buffered saline (PBS), 3% or less (w/w of the vehicle) polysorbate 80 and 0.3% or less (w/w of the vehicle) xanthan gum and has a pH of from 6.5-8.0 and an osmolality of from 260 to 320 mOsm/L. ### Claim 19 (depends on 17) The drug delivery vehicle of claim 17, wherein the suspension is stable to phase separation of the crystalline solid non-polar lipid particles in the suspension for 6 months at room temperature. ### Claim 20 (depends on 19) The drug delivery vehicle of claim 19, wherein the suspension is chemically stable to <5% isomerization of 1,2-EPRG to the isomeric 1,3-EPRG during storage at room temperature for 6 months. ### Claim 21 (depends on 17) The drug delivery vehicle of claim 17, wherein the suspension is stable to phase separation of the crystalline solid non-polar lipid particles in the suspension for 24 months at room temperature. ### Claim 22 (depends on 21) The drug delivery vehicle of claim 21, wherein the suspension is chemically stable to <5% isomerization of 1,2-EPRG to the isomeric 1,3-EPRG during storage at room temperature for 24 months. ### Claim 23 (depends on 17) The drug delivery vehicle of claim 17, wherein the suspension is sterile. ### Claim 24 (depends on 17) The drug delivery vehicle of claim 17, wherein the suspension comprises a preservative. ### Claim 25 (depends on 17) The drug delivery vehicle of claim 17, wherein the suspension is preservative-free. ### Claim 26 (depends on 17) The drug delivery vehicle of claim 17, wherein the physiologically acceptable carrier is an ophthalmologically acceptable carrier. ### Claim 27 (depends on 17) The drug delivery vehicle of claim 17, wherein the ophthalmologically acceptable carrier comprises an agent selected from the group consisting of a buffering agent, a tonicity agent, a wetting agent, a thickening and viscosity agent, a density adjusting agent and combinations thereof. ### Claim 28 (depends on 17) The drug delivery vehicle of claim 17, wherein the active agent is released from the crystalline solid non-polar lipid particles as individual molecules of the active agent for a period of time after administration as an ophthalmic drop. ### Claim 29 (depends on 28) The drug delivery vehicle of claim 28, wherein the individual molecules are released for a period of from 1 up to 24 hours. ### Claim 30 (depends on 17) The drug delivery vehicle of claim 17, wherein the suspension is provided in a drop dispenser. ### Claim 31 (depends on 1) A method of treating a disease or disorder of the eye selected from the group consisting of dry eye, inflammatory dry eye, evaporative dry eye, meibomian gland dysfunction and symptoms, clinical signs or conditions associated therewith, an unstable tear film resulting in rapid aqueous tear evaporation and keratoconjunctivitis sicca and symptoms or clinical signs associated therewith, in an animal or human subject in need of such treatment, comprising topically administering a drug delivery vehicle according claim 1 comprising an effective amount of the active lipid agent to the eye of the subject.