CA2549399C - Process for purifying (-)-.delta.9-trans-tetrahydrocannabinol - Google Patents
Process for purifying (-)-.delta.9-trans-tetrahydrocannabinol Download PDFInfo
- Publication number
- CA2549399C CA2549399C CA2549399A CA2549399A CA2549399C CA 2549399 C CA2549399 C CA 2549399C CA 2549399 A CA2549399 A CA 2549399A CA 2549399 A CA2549399 A CA 2549399A CA 2549399 C CA2549399 C CA 2549399C
- Authority
- CA
- Canada
- Prior art keywords
- stationary phase
- process according
- trans
- tetrahydrocannabinol
- carbon dioxide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 36
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 title claims abstract description 10
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 52
- 230000005526 G1 to G0 transition Effects 0.000 claims abstract description 40
- 229910002092 carbon dioxide Inorganic materials 0.000 claims abstract description 27
- 239000001569 carbon dioxide Substances 0.000 claims abstract description 25
- 239000000203 mixture Substances 0.000 claims abstract description 18
- 238000011210 chromatographic step Methods 0.000 claims abstract description 16
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 15
- 239000005017 polysaccharide Substances 0.000 claims abstract description 15
- 229930003827 cannabinoid Natural products 0.000 claims abstract description 14
- 239000003557 cannabinoid Substances 0.000 claims abstract description 14
- 229940065144 cannabinoids Drugs 0.000 claims abstract description 8
- 238000000926 separation method Methods 0.000 claims abstract description 8
- 150000004676 glycans Chemical class 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 46
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 22
- -1 2-ethylpyridine siloxane Chemical class 0.000 claims description 17
- 239000003607 modifier Substances 0.000 claims description 14
- 239000000741 silica gel Substances 0.000 claims description 10
- 229910002027 silica gel Inorganic materials 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- 229920000856 Amylose Polymers 0.000 claims description 6
- 239000007983 Tris buffer Substances 0.000 claims description 6
- 229940127557 pharmaceutical product Drugs 0.000 claims description 6
- 239000000377 silicon dioxide Substances 0.000 claims description 6
- SBTVLCPCSXMWIQ-UHFFFAOYSA-N (3,5-dimethylphenyl) carbamate Chemical compound CC1=CC(C)=CC(OC(N)=O)=C1 SBTVLCPCSXMWIQ-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000758 substrate Substances 0.000 claims description 3
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 2
- 239000000919 ceramic Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910052726 zirconium Inorganic materials 0.000 claims description 2
- 229960004242 dronabinol Drugs 0.000 description 31
- 238000004587 chromatography analysis Methods 0.000 description 11
- 238000004808 supercritical fluid chromatography Methods 0.000 description 11
- 150000004804 polysaccharides Chemical class 0.000 description 10
- 239000012535 impurity Substances 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000013375 chromatographic separation Methods 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 244000025254 Cannabis sativa Species 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000004810 polytetrafluoroethylene Substances 0.000 description 3
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 3
- 241000218236 Cannabis Species 0.000 description 2
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 2
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- NRGGMCIBEHEAIL-UHFFFAOYSA-N 2-ethylpyridine Chemical group CCC1=CC=CC=N1 NRGGMCIBEHEAIL-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 229920002558 Curdlan Polymers 0.000 description 1
- 239000001879 Curdlan Substances 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940078035 curdlan Drugs 0.000 description 1
- 235000019316 curdlan Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000002086 displacement chromatography Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002124 flame ionisation detection Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 230000007943 positive regulation of appetite Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 230000017260 vegetative to reproductive phase transition of meristem Effects 0.000 description 1
- 229920001221 xylan Polymers 0.000 description 1
- 150000004823 xylans Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0329635.7 | 2003-12-23 | ||
| GBGB0329635.7A GB0329635D0 (en) | 2003-12-23 | 2003-12-23 | Process for purifying trans-tetrahydrocannabinol |
| PCT/GB2004/005394 WO2005061480A1 (en) | 2003-12-23 | 2004-12-17 | Process for purifying (-)-δ9-trans-tetrahydrocannabinol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2549399A1 CA2549399A1 (en) | 2005-07-07 |
| CA2549399C true CA2549399C (en) | 2012-12-04 |
Family
ID=30776243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2549399A Expired - Lifetime CA2549399C (en) | 2003-12-23 | 2004-12-17 | Process for purifying (-)-.delta.9-trans-tetrahydrocannabinol |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US7449589B2 (https=) |
| EP (1) | EP1697340B1 (https=) |
| JP (1) | JP5566565B2 (https=) |
| CN (1) | CN100482657C (https=) |
| AT (1) | ATE412644T1 (https=) |
| AU (1) | AU2004303593B2 (https=) |
| CA (1) | CA2549399C (https=) |
| DE (1) | DE602004017506D1 (https=) |
| DK (1) | DK1697340T3 (https=) |
| ES (1) | ES2313118T3 (https=) |
| GB (1) | GB0329635D0 (https=) |
| IL (1) | IL176197A (https=) |
| WO (1) | WO2005061480A1 (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI436991B (zh) * | 2004-11-22 | 2014-05-11 | 歐 賽提克股份有限公司 | 用於純化反-（-）-△９-四氫大麻酚與反-（＋）-△９-四氫大麻酚之方法 |
| TWI366460B (en) * | 2005-06-16 | 2012-06-21 | Euro Celtique Sa | Cannabinoid active pharmaceutical ingredient for improved dosage forms |
| US8980940B2 (en) | 2006-11-10 | 2015-03-17 | Johnson Matthey Public Limited Company | Stable cannabinoid compositions and methods for making and storing them |
| US8039509B2 (en) | 2006-11-10 | 2011-10-18 | Johnson Matthey Public Limited Company | Composition comprising (−)-Δ9-trans-tetrahydrocannabinol |
| JP6087147B2 (ja) * | 2009-06-22 | 2017-03-01 | ジョンソン、マッセイ、パブリック、リミテッド、カンパニーＪｏｈｎｓｏｎ Ｍａｔｔｈｅｙ Ｐｕｂｌｉｃ Ｌｉｍｉｔｅｄ Ｃｏｍｐａｎｙ | プロスタグランジンの精製方法 |
| WO2012071389A2 (en) | 2010-11-22 | 2012-05-31 | Johnson Matthey Public Limited Company | Stable cannabinoid compositions and methods for making and storing them |
| EP3261629A4 (en) * | 2015-02-27 | 2018-12-05 | Ebbu, LLC | Compositions comprising combinations of purified cannabinoids, with at least one flavonoid, terpene, or mineral |
| BR112017018316A2 (pt) | 2015-02-27 | 2018-04-17 | Ebbu Llc | composições compreendendo combinações de canabinoides purificados, com pelo menos um flavonoide, terpeno ou mineral |
| DK3455213T3 (da) | 2016-05-13 | 2022-03-07 | Symrise Ag | Fremgangsmåde til at oprense cannabinoid-forbindelser via simulated moving bed-kromatografi |
| US12485129B2 (en) | 2016-08-29 | 2025-12-02 | Canopy Growth Corporation | Water soluble compositions comprising purified cannabinoids |
| WO2018044953A1 (en) | 2016-08-29 | 2018-03-08 | Ebbu, LLC | Water soluble compositions comprising purified cannabinoids |
| US10239808B1 (en) | 2016-12-07 | 2019-03-26 | Canopy Holdings, LLC | Cannabis extracts |
| US11299470B2 (en) | 2017-08-07 | 2022-04-12 | Massachusetts Institute Of Technology | Systems and methods for separating cannabis-derived compounds using chromatography with liquid or supercritical carbon dioxide |
| US10307392B2 (en) | 2017-10-21 | 2019-06-04 | Alexander Kariman | Compound and method for treatment of diseases and disorders |
| EP3745884A1 (en) | 2018-01-31 | 2020-12-09 | Canopy Holdings, Llc | Hemp powder |
| US10751380B2 (en) | 2018-03-08 | 2020-08-25 | Alexander Kariman | Compound and method for treating spasms, inflammation and pain |
| US11324718B2 (en) | 2018-10-09 | 2022-05-10 | Sartorius Chromatography Equipment | Method for purifying cannabinoids |
| CA3119729A1 (en) | 2018-10-10 | 2020-04-16 | Treehouse Biotech, Inc. | Synthesis of cannabigerol |
| CN111848356A (zh) * | 2019-04-30 | 2020-10-30 | 黑龙江阳光工业大麻研究院 | 一种大麻二酚的制备方法 |
| EP4337356A1 (en) * | 2021-05-13 | 2024-03-20 | Grow Group Plc | Method for selective recovery of lipophilic compounds |
| CN114814009B (zh) * | 2022-04-07 | 2024-06-07 | 国家烟草质量监督检验中心 | 一种同时适用于新型烟草产品中酚类化合物及尿液中酚类化合物的代谢物的分析方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6403126B1 (en) | 1999-05-26 | 2002-06-11 | Websar Innovations Inc. | Cannabinoid extraction method |
| US20030050334A1 (en) | 2001-04-30 | 2003-03-13 | Murty Ram B. | Process for extraction of Delta-9-Tetrahydrocannabinol and other related cannabinoids and preparation of specific strength marijuana cigarettes |
| GB0112752D0 (en) | 2001-05-25 | 2001-07-18 | Johnson Matthey Plc | Synthesis of cannabinoids |
-
2003
- 2003-12-23 GB GBGB0329635.7A patent/GB0329635D0/en not_active Ceased
-
2004
- 2004-12-17 AU AU2004303593A patent/AU2004303593B2/en not_active Ceased
- 2004-12-17 EP EP04806191A patent/EP1697340B1/en not_active Expired - Lifetime
- 2004-12-17 ES ES04806191T patent/ES2313118T3/es not_active Expired - Lifetime
- 2004-12-17 WO PCT/GB2004/005394 patent/WO2005061480A1/en not_active Ceased
- 2004-12-17 CN CNB2004800382570A patent/CN100482657C/zh not_active Expired - Fee Related
- 2004-12-17 US US10/584,122 patent/US7449589B2/en not_active Expired - Lifetime
- 2004-12-17 DE DE602004017506T patent/DE602004017506D1/de not_active Expired - Lifetime
- 2004-12-17 CA CA2549399A patent/CA2549399C/en not_active Expired - Lifetime
- 2004-12-17 JP JP2006546314A patent/JP5566565B2/ja not_active Expired - Lifetime
- 2004-12-17 DK DK04806191T patent/DK1697340T3/da active
- 2004-12-17 AT AT04806191T patent/ATE412644T1/de active
-
2006
- 2006-06-08 IL IL176197A patent/IL176197A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005061480A1 (en) | 2005-07-07 |
| JP5566565B2 (ja) | 2014-08-06 |
| CN1898230A (zh) | 2007-01-17 |
| AU2004303593B2 (en) | 2010-12-23 |
| IL176197A0 (en) | 2006-10-05 |
| ATE412644T1 (de) | 2008-11-15 |
| IL176197A (en) | 2011-04-28 |
| EP1697340B1 (en) | 2008-10-29 |
| GB0329635D0 (en) | 2004-01-28 |
| DE602004017506D1 (de) | 2008-12-11 |
| ES2313118T3 (es) | 2009-03-01 |
| EP1697340A1 (en) | 2006-09-06 |
| CN100482657C (zh) | 2009-04-29 |
| DK1697340T3 (da) | 2009-03-02 |
| CA2549399A1 (en) | 2005-07-07 |
| AU2004303593A1 (en) | 2005-07-07 |
| US20070276031A1 (en) | 2007-11-29 |
| US7449589B2 (en) | 2008-11-11 |
| JP2007516271A (ja) | 2007-06-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |