# US 11,299,470 B2 · Systems and methods for separating cannabis-derived compounds using chromatography with liquid or supercritical carbon dioxide > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,299,470 B2 - Document ID: US11299470B2 - Status: Granted - Kind: B2 - Application number: 16/637,256 - Filed: 2018-08-07 - Published: 2020-08-06 - Granted: 2022-04-12 - Earliest claimed: 2017-08-07 - Assignees: Massachusetts Institute of Technology - Applicants: Massachusetts Institute of Technology - Inventors: Clark K. Colton; John M. Moses; Veronica M. Wilson; William H. Dalzell; Mariya Layurova; Tony J. Elian; Truong H. Cai; John MacKay - Web page: https://patentgrep.com/patent/US11299470B2 ## CPC - B01D 15/40: using supercritical fluid as mobile phase or eluent - C07D 311/80: Dibenzopyrans; Hydrogenated dibenzopyrans - A61K 31/658: {o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol} - C07C 37/004: {by obtaining phenols from plant material or from animal material} - C07D 311/78: Ring systems having three or more relevant rings - C07D 401/12: linked by a chain containing hetero atoms as chain links - B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28) - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - 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) - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS ## Abstract Chromatography systems and methods for using carbon dioxide to separate one or more cannabis-derived compounds from other components of a mixture are generally described. Some of the methods described herein comprise transporting a mixture comprising a first cannabis-derived compound and one or more other components through a chromatography column containing a stationary phase comprising a packing material. In some embodiments, the mixture is transported through the column within a mobile phase that comprises carbon dioxide (e.g., supercritical CO2, liquid CO2). The mobile phase may be substantially free of a co-solvent that is in liquid phase at standard room temperature and pressure. In some embodiments, the mobile phase is free of any co-solvent and comprises 100 vol % carbon dioxide. The first cannabis-derived compound may interact with the stationary phase and/or the mobile phase to a different degree than the one or more other components of the mixture, causing at least partial separation of the first cannabis-derived compound from the one or more other components within the column. Due to this separation, at least one fraction of the mobile phase that comprises the first cannabis-derived compound and is substantially free of the one or more other components of the mixture may be collected. ## Claims ### Claim 1 A chromatography method for purifying a cannabis-derived compound from a mixture, comprising: transporting the mixture, which comprises a first component and a second component, through a chromatography column containing a stationary phase comprising a packing material, wherein the first component comprises a first cannabis-derived compound, wherein the mixture is transported within a mobile phase that comprises carbon dioxide and is substantially free of a co-solvent that is in liquid phase at standard room temperature and pressure through the column and in contact with the stationary phase, and wherein the first component and the second component of the mixture are each transported within the mobile phase substantially continuously from a first end of the column to a second end of the column; collecting from the second end of the column a first fraction of the mobile phase comprising the first component over a first time interval, wherein the first fraction is substantially free of the second component; and collecting from the second end of the column a second fraction of the mobile phase comprising the second component over a second time interval different from the first time interval, wherein the second fraction is substantially free of the first component. ### Claim 2 (depends on 1) The chromatography method according to claim 1, wherein the mobile phase is substantially free of any co-solvent. ### Claim 3 (depends on 1) The chromatography method according to claim 1, wherein the carbon dioxide comprises supercritical carbon dioxide. ### Claim 4 (depends on 3) The chromatography method according to claim 3, wherein the transporting step is performed at a temperature in a range between about 31° C. and 70° C. and a pressure in a range between about 1,085.7 psi and about 30,000 psi. ### Claim 5 (depends on 1) The chromatography method according to claim 1, wherein the carbon dioxide comprises liquid carbon dioxide. ### Claim 6 (depends on 5) The chromatography method according to claim 5, wherein the transporting step is performed at a temperature in a range between about 0° C. and about 30° C. and/or a pressure in a range between about 500 psi and about 10,000 psi. ### Claim 7 (depends on 1) The chromatography method according to claim 1, wherein the concentration of carbon dioxide in the mobile phase is at least about 80 vol %. ### Claim 8 (depends on 1) The chromatography method according to claim 1, wherein the concentration of carbon dioxide in the mobile phase is about 100 vol %. ### Claim 9 (depends on 1) The chromatography method according to claim 1, wherein the mobile phase comprises a co-solvent or diluent that is in gaseous phase at standard room temperature and pressure. ### Claim 10 (depends on 9) The chromatography method according to claim 9, wherein the concentration in the mobile phase of the co-solvent that is in gaseous phase at standard room temperature and pressure is about 20 vol % or less. ### Claim 11 (depends on 9) The chromatography method according to claim 9, wherein the co-solvent that is in gaseous phase at standard room temperature and pressure is nitrous oxide, dimethyl ether, ethane, propane, butane, sulfur hexafluoride, and/or a halocarbon. ### Claim 12 (depends on 1) The chromatography method according to claim 1, wherein the first cannabis-derived compound comprises cannabidiol (CBD), cannabinol (CBN), and/or tetrahydrocannabinol (THC). ### Claim 13 (depends on 1) The chromatography method according to claim 1, wherein the second component comprises a second cannabis-derived compound. ### Claim 14 (depends on 1) The chromatography method according to claim 1, wherein the mixture further comprises a third component comprising a third cannabis-derived compound. ### Claim 15 (depends on 14) The chromatography method according to claim 14, further comprising collecting a third fraction of the mobile phase comprising the third component over a third time interval different from the first time interval and the second time interval, and wherein the third fraction is substantially free of the first component and the second component. ### Claim 16 (depends on 1) The chromatography method according to claim 1, wherein the packing material comprises silica, BEH 2-EP, and/or C18. ### Claim 17 (depends on 1) The chromatography method according to claim 1, wherein the first component comprises at least about 50 wt % of components of the mixture transported within the mobile phase collected in the first fraction. ### Claim 18 (depends on 1) The chromatography method according to claim 1, wherein the second component comprises at least about 50 wt % of components of the mixture transported within the mobile phase collected in the second fraction. ### Claim 19 A chromatography system for purifying a first cannabis-derived compound from a mixture, comprising: a chromatography column containing a stationary phase comprising a packing material; a mobile phase comprising carbon dioxide, wherein the mobile phase is substantially free of a co-solvent that is in liquid phase at standard room temperature and pressure; and the mixture, wherein the mixture comprises a first component and a second component, wherein the first component comprises the first cannabis-derived compound. ### Claim 20 (depends on 19) The chromatography system according to claim 19, wherein the mobile phase is substantially free of any co-solvent. ### Claim 21 (depends on 1) The chromatography method according to claim 1, wherein each fraction collected from the second end of the column is substantially free of any co-solvent. ### Claim 22 (depends on 1) The chromatography method according to claim 1, wherein the first component comprises at least about 95 wt % of components of the mixture transported within the mobile phase collected in the first fraction. ### Claim 23 (depends on 19) The chromatography system according to claim 19, wherein the first component comprises at least about 95 wt % of components of the mixture within the mobile phase at an exit of the chromatography column.