Processing

Please wait...

Settings

Settings

Goto Application

1. WO2004016277 - EXTRACTION OF PHARMACEUTICALLY ACTIVE CANNABINOIDS FROM PLANT MATERIALS

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

Claims :

1. A method of extracting cannabinoids from plant material comprising a decarboxylation step, an extraction with liquid carbon dioxide (CO2), and a step to reduce the proportion of non-target materials in the extract, characterised in that the extraction with liquid CO2 is conducted under sub-critical conditions at a temperature in the range of from 5 to 15°C and a pressure in the range of from 50 to 70 bar.

2. A method as claimed in claim 1 wherein the
decarboxylation step is carried out after extraction with liquid CO2.

3. A method as claimed in claim 1 wherein the
decarboxylation step is carried out prior to extraction with liquid CO2.

4. A method as claimed in any one of claims 1 to 3 wherein the temperature is in the range of from 8 to 12 °C.

5. A method as claimed in claim 4 wherein the
temperature is substantially 100C.

6. A method as claimed in any of the preceding claims wherein the pressure is in the range of from 55 to 65 bar.

7. A method as claimed in claim 6 wherein the pressure is substantially 60 bar.

8. A method as claimed in any of the preceding claims wherein the CO2 has a mass flow in the range of 1000-1500 Kg/h.

9. A method as claimed in claim 8 wherein the CO2 has a mass flow of substantially 1250 Kg/h.

10. A method as claimed in any of the preceding claims wherein the extraction is run for up to 10 hours.

11. A method as claimed in claim 10 wherein the extraction is run for about 8 hours.

12. A method as claimed in any of the preceding claims wherein the CO2 is removed by depressurisation and the recovered extract held at a temperature in the range from -15°C to -200C.

13. A method as claimed in any of the preceding claims wherein the step to reduce the proportion of non-target materials in the extract is a precipitation with a C1-C5 alcohol, wherein the material to be treated is warmed to above room temperature before the C1-C5 alcohol is added.

14. A method as claimed in claim 13 wherein the C1-C5 alcohol is ethanol .

15. A method as claimed in claim 13 or claim 14 wherein the extract is warmed to a temperature in the range from 36°C to 44°C.

16. A method as claimed in claim 15 wherein the extract is warmed to about 40 °C.

17. A method as claimed in any of claims 14 to 16 wherein the C1-C5 alcohol is added in an amount of from 3:1 to 1:1 C1-C5 alcohol vol to weight of the material to be treated.

18. A method as claimed in claim 17 wherein the C1-C5 alcohol is added in an amount of about 2:1 C1-C5 alcohol vol to weight of the material to be treated.

19. A method as claimed in any of claims 13-18 wherein the solution resulting from addition of C1-C5 alcohol to the material to be treated is chilled and insoluble materials allowed to precipitate out.

20. A method as claimed in any of claim 19 wherein the solution resulting from addition of C1-C5 alcohol to the material to be treated is chilled to a temperature in the range from -15°C to -250C.

21. A method as claimed in claim 19 or claim 20 wherein the solution resulting from addition of C1-C5 alcohol to the material to be treated is chilled for up to 52 hours.

22. A method as claimed in any of claims 19 to 21 wherein the precipitate of insoluble materials is removed by filtration.

23. A method as claimed in claim 22 wherein filtration is through a 20μm membrane.

24. A method as claimed in any of claims 13-23 further comprising a multi-step evaporation under reduced pressure.

25. A method as claimed in claim 24 wherein first C1-C5 alcohol is removed and then water is removed.

26. A method as claimed in claimed in claim 25 wherein C1-C5 alcohol is removed by heating to a temperature in the range of 58-62 °C to give a vapour temperature in the range of 38-42°C under a vacuum in the range of 168-172 mbar until there is little or no visible condensate.

27. A method as claimed in claimed in claim 25 or claim 26 wherein water is additionally removed by a stepwise reduction of the vacuum in stages to about 50 mbar

28. A method as claimed in any of claims 3 to 27 wherein the decarboxylation step is carried out prior to extraction with liquid CO2 and is conducted by heating the plant material to temperatures and for times which ensure at least 95% conversion of the acid cannabinoids to their neutral form whilst ensuring thermal degradation of THC to CBN is less than 10%.

29. A method as claimed in claim 28 in which a multi step heating process is conducted in which the plant material is :
i) heated to a first temperature for a first time period to evaporate off retained water and allow for uniform heating of the plant material; and

ii) the temperature is increased to a second temperature for a second time period until at least 95% conversion of the acid cannabinoids to their neutral form has occurred.

30. A method as claimed in claim 29 where the first step is conducted at a temperature in the range of 1000C to 110°C for 10-20 min.

31. A method as claimed in claim 30 wherein the first temperature is about 1050C and the first time period is about 15 minutes .

32. A method as claimed in any of claims 28-31 wherein the plant material has a high CBD content, the second
temperature is in the range from 115°C to 125°C , preferably 1200C and the second time period is in the range from 45 minutes to 75 minutes, preferably about 60 minutes.

33. A method as claimed in any of claims 28-31 wherein the plant material has a high CBD content the second temperature is in the range from 135°C to 145°C , preferably 1400C and the second time period is in the range from 15 to 45 minutes, preferably about 30 minutes.

34. A method as claimed in any of claims 28-31 wherein the plant material has a high CBD content, the second
temperature is in the range from 140°C to 150°C , preferably about 1450C and the second time period is in the range from 55-90 minutes.

35. A method as claimed in any of claims 28-31 wherein the plant material has a high THC content, the second
temperature is in the range from 115°C to 125°C , preferably about 120°C, and the second time period is in the range from 45 minutes to 75 minutes, preferably about 60 minutes.

36. A method as claimed in any of claims 28 to 31 wherein the plant material has a high THC content, the second temperature is from 100°C to 1100C , preferably about 105°C, and the second time period is in the range of 60 to 120 minutes.

37. A method as claimed in any of claims 28 to 31 wherein the plant material has a high THC content, the second temperature is in the range from 140°C to 150°C , preferably about 145CC, and the second time period is in the range of 45 to 55 minutes.

38. A method as claimed in any of claims 28-37 wherein the decarboxylation step is conducted at temperatures and for times which ensure at least 97% conversion of the acid
cannabinoids to their neutral form whilst ensuring thermal degradation of THC to CBN is less than 5%.

39. A method as claimed in any of the preceding claims wherein the plant material is ground, milled or otherwise processed to less than 2mm.

40. A method as claimed in claim 39 wherein the particle size is greater than 1 mm.

41. A method as claimed in any of claims 1-40 further comprising the step of treating an extract derived from the plant material with activated charcoal.

42. A method as claimed in claim 41 wherein the extract derived from the plant material is dissolved in an alcoholic solution.

43. A method as claimed in claim 42 wherein the alcoholic solution is an ethanolic solution.

44. A method as claimed in claim 43 wherein treatment with activated charcoal follows an ethanolic precipitation step.

45. A method of extracting cannabinoids from plant material comprising an extraction with liquid CO2, characterised in that an organic modifier or polar solvent is added to the carbon dioxide.

46. A method as claimed in claim 45 in which the modifier or polar solvent is added in an amount of up to 10% by weight .

47. A method as claimed in claim 45 or 46 wherein the modifier or polar solvent is ethanol .

48. A method as claimed in any of claims 3 to 27 wherein the plant material is agitated.

49. A method as claimed in any of claims 3 to 27 wherein the plant material has a water content of from 8-12%.

50. A botanical drug substance obtainable from botanical raw material from a high THC containing cannabis plant having a THC content, wherein said botanical drug substance is an extract derived from the high THC cannabis plant comprising at least 50% THC w/w of extract, no more than 5% CBD as %w/w of the THC content, and no more than 5% cannabinoids other than THC and CBD as %w/w of the THC content.

51. A botanical drug substance obtainable from botanical raw material from a high CBD containing cannabis plant having a CBD content, wherein said botanical drug substance is an extract derived from the high CBD cannabis plant comprising 50% CBD w/w of extract, no more than 7.5% THC as % w/w of the CBD content, and no more than 5% cannabinoids other than CBD and THC as %w/w of the CBD content.

52. A botanical drug substance as claimed in claim 50 or claim 51 comprising no more than 4ppb aflatoxin.

53. A botanical drug substance as claimed in claim 50 or claim 51 comprising no more than 20ppm total heavy metals.

54. A botanical drug substance as claimed in claim 50 or claim 51 comprising no more than 15% w/w residual solvents.

55. A botanical drug substance as claimed in claim 54 wherein the residual solvent is ethanol.

56. A botanical drug substance as claimed in claim 50 or claim 51 comprising no more than 105 cfu/g TVC, no more than 104 cfu/g fungi, no more than 103 cfu/g enterobacteria and other non gram negative organisms, and no detectable E. coli, Salmonella or S. aureus.

57. A botanical drug substance obtained from cannabis comprising at least 60% cannabinoids, of which at least 90% is THC, about 1.5% is CBD and the remainder comprises other minor cannabinoids .

58. A botanical drug substance obtained from cannabis comprising at least 60% cannabinoids of which at least 85% is CBD, about 3% is THC and the remainder comprises other minor cannabinoids .

59. A botanical drug substance resulting from the mixing of a botanical drug substance as claimed in claim 57 and 58.

60. A method of making a pharmaceutical composition comprising, as an active agent, a botanical drug substance which an extract from at least one cannabis plant, which method comprises preparing a botanical drug substance containing cannabinoids from at least one cannabis plant using an
extraction method according to any one of claims 1 to 48, and formulating the botanical drug substance with one or more pharmaceutically acceptable diluents, carriers or excipients to produce a pharmaceutical composition.