Continuous isolation of cannabidiol and conversion of cannabidiol to delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol
In alternative embodiments, provided are processes comprising the continuous isolation and purification of cannabinoids and further isomerization of the purified cannabidiol to Δ 8 tetrahydrocannabinol (Δ 8 THC) and Δ 9 tetrahydrocannabinol (Δ 9 THC). In alternative embodiments, provided are processes for converting Δ8-THC into Δ 9 -THC. In alternative embodiments, provided are processes for the industrial scale continuous isolation and purification of cannabinoids and further isomerization of the purified cannabidiol to Δ 9 -THC.
1. A method for isolating and separating a cannabinoid from a natural or a synthetic source comprising:
(a) providing or having provided a first extract, aliquot or sample of a natural or synthetic source comprising at least one of cannabidiol (CBD), Δ9 THC, and Δ8 THC, and further comprising other cannabinoids;
(b) providing a continuous chromatography apparatus or device comprising a plurality of stations and a plurality of chromatography columns;
(c) introducing or loading the first extract, aliquot or sample into a first column at a first station, wherein the CBD, Δ9 THC, and Δ8 THC and other cannabinoids reversibly bind to the first column;
(d) moving the first column to a second station, wherein after the first column is moved to the second station a next or second column is introduced into the first station;
(e) eluting the extract from the first column with a first elution solution at the second station;
(f) collecting the first elution fractions from the first column at the second station;
(g) removing all or substantially most of the first elution solution from the first elution fractions to produce a first purified extract substantially free of CBD, Δ9 THC, and Δ8 THC;
(h) when the first column is moved to the next or second station, introducing a next or second column into the first station, and the extract, aliquot or sample is introduced or loaded into the next or second column at the first station;
(i) moving the second column to the next or second station after the first column is moved to a next or third station;
(j) eluting the extract from the first column with a second elution solution at the next or second station;
(k) collecting the second elution fractions from the first column at the second station; and
(l) removing all or substantially most of the second elution solution from the second elution fractions to produce a second purified extract comprising between about 50% and 95% of CBD, Δ9 THC, and Δ8 THC from the first extract, which is separated and isolated from the source.
2. The method of claim 1 , wherein the plurality of stations and the plurality of chromatography columns comprise at least 2, 3, 4, 5, 6, 7, or 8 or more, or between about 3 and 30, stations and/or chromatography columns.
3. The method of claim 2 wherein: (a) the first and second elution solutions are different, or the at least 2, 3, 4, 5, 6, 7, or 8 or more elution solvents are different; or, (b) the method comprises use of at least 2, 3, 4, 5, 6, 7, or 8 or more columns, with at least 2, 3, 4, 5, 6, 7, or 8 or more corresponding elution solutions, and at least 2, 3, 4, 5, 6, 7, or 8 or more corresponding purified extracts.
4. The method of claim 1 , wherein the natural source comprises a plant or microbial material, or a material derived from a plant or a microbial source.
5. The method of claim 1 , wherein the elutions of both steps (e) and (j) are gradient elutions.
6. The method of claim 1 , wherein the elution is by a gradient elution process and the CBD, Δ9 THC, Δ8 THC, and other cannabinoids are separately collected in different or separate gradient elution fractions.
7. The method of claim 1 , wherein the plurality of stations comprises at least six stations, the elution of the first column is by a gradient elution process at each of the at least six stations, and in a first gradient solvent non-polar compounds and terpenes are eluted off the first column at the second station; in a second gradient solvent cannabidiol (CBD) is eluted off the first column at the third station; in a third gradient solvent a CBD/tetrahydrocannabinol (THC) mix is first eluted and then remaining THC is eluted off the first column at the fourth station; in a fourth gradient solvent remaining cannabinoids are eluted off the first column at the fifth station, wherein the remaining cannabinoids comprise CBC, CBG, CBN; and, in a fifth gradient solvent all remaining polar compounds are eluted off the first column at the sixth station, wherein the remaining polar compounds comprise cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA).
8. The method of claim 7 wherein the gradient elution progresses initially with about a 70:30 methanol to water elution solution or equivalent at the second station, which elutes off the first column some of the cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC); then moves to about an 80:20 methanol to water elution solution or equivalent at the third station, which elutes off the column some of the CBD; then moves to about a 90:10 methanol to water elution solution or equivalent at the fourth station, which initially elutes off the column a mix of the remaining CBD and THC, and then only THC; and finally moves to a 100% methanol elution solution at the fifth station, which removes a mix of remaining cannabinoids comprising CBC, CBG, and CBN.
9. The method of claim 1 , wherein some of the first extract material not reversibly bound to the first column at the first station is removed with a first wash solution before the column is moved to the next or second station.
10. The method of claim 1 wherein steps (i) to (l) are repeated on the first column with at least one second additional elution solution.
11. The method of claim 1 wherein steps (h) to (l) are repeated with at least one additional column.
12. The method of claim 1 wherein steps (d) to (g) are repeated on the first column with at least one additional elution solution, wherein the at least one additional elution solution produces a second purified extract substantially free of CBD, Δ9 THC, and Δ8 THC, and other cannabinoids; and when all or substantially most of the second elution solution from the second elution fractions is removed it produces a third purified extract comprising between about 50% and 95% of CBD, Δ9 THC, and Δ8 THC from the first extract separated and isolated from the source.
13. The method of claim 12 , wherein the third purified extract comprises between about 60% and 90% of CBD, Δ9 THC, and Δ8 THC from the first extract separated and isolated from the source.
14. The method of claim 12 , wherein the third purified extract comprises at least about 75% of the CBD, Δ9 THC, and Δ8 THC from the first extract separated and isolated from the source.
15. The method of claim 1 , wherein the extract comprises between about 1% to 50% CBD by weight.
16. The method of claim 15 , wherein the extract comprises between about 10% to 40% CBD by weight.
17. The method of claim 15 , wherein the extract comprises at least 25% CBD by weight.
18. The method of claim 1 , wherein the method further comprises measuring the amount of the cannabinoid in the first or second purified extract.
19. The method of claim 1 , wherein step (l) comprises removing all or substantially most of the second elution solution from the second elution fractions to produce a second purified extract comprising between about 60% and 90% of CBD, Δ9 THC, and Δ8 THC from the first extract, which is separated and isolated from the source.
20. The method of claim 1 , wherein step (l) comprises removing all or substantially most of the second elution solution from the second elution fractions to produce a second purified extract comprising at least about 75% of the CBD, Δ9 THC, and Δ8 THC from the first extract, which is separated and isolated from the source.