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Title:
CYCLODEXTRIN INCLUSION COMPLEXES OF CANNABIS EXTRACTS
Document Type and Number:
WIPO Patent Application WO/2020/168421
Kind Code:
A1
Abstract:
The invention provides cyclodextrin inclusion complexes of cannabis extracts, cannabinoids and cannabis terpenes, and methods of making such complexes. The cyclodextrin inclusion complexes include a host and guest compounds. The host may include cyclodextrin and the guests may include compounds of cannabis extracts. Also provided are mixtures of cyclodextrin inclusion complexes. The host may include cyclodextrin and the guests may include compounds of a cannabinoid extract or compounds of a cannabis terpene extract.

Inventors:
WIMALARATNE PRIYANTHA D C (CA)
Application Number:
PCT/CA2020/050208
Publication Date:
August 27, 2020
Filing Date:
February 18, 2020
Export Citation:
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Assignee:
AGRIMA SCIENT CORP (CA)
International Classes:
A61K47/40; A23L33/105; A61K31/05; A61K31/192; A61K31/352; C07C39/19; C07C39/23; C07C65/19; C07D311/60; C07D311/74; C07D311/80; C07H3/06
Domestic Patent References:
WO2020028897A12020-02-06
WO2019036243A12019-02-21
WO2017136775A12017-08-10
WO2018222346A12018-12-06
WO2003070775A12003-08-28
Foreign References:
CA2424356A12003-04-01
Attorney, Agent or Firm:
THORNE, Lisa et al. (CA)
Download PDF:
Claims:
CLAIMS

1 . A cyclodextrin inclusion complex comprising:

a host comprising a cyclodextrin; and

guests comprising compounds of a cannabis extract.

2. The cyclodextrin inclusion complex of claim 1 , wherein the cannabis extract comprises a cannabinoid extract from cannabis biomass and a terpene extract from cannabis biomass, the cannabis biomass comprising cannabis flowers.

3. The cyclodextrin inclusion complex of claim 2, wherein the cannabinoid extract comprises non-volatile compounds extracted from cannabis flowers and the terpene extract comprises volatile compounds extracted from cannabis flowers.

4. The cyclodextrin inclusion complex of claim 3, wherein the non-volatile

compounds comprise one or more than one cannabinoid and the volatile compounds comprise one or more than one terpene.

5. The cyclodextrin inclusion complex of claim 4, wherein the one or more than one cannabinoid comprise delta-9-tetrahydrocannabinol (A9-THC), delta-9- tetrahydrocannabinoic acid (A9-THCA), delta-9-tetrahydrocannabinol-C4 (A9-THC-C4), delta-9-tetrahydrocannabinoic acid-C4 (A9-THCA-C4), delta-9-tetrahydrocannabiorcol-Ci (A9-THC-Ci), delta-9-tetrahydrocannabiorcolic acid-C4 (A9-THCA-Ci),delta-8- tetrahydrocannabinol (Dd-THC), delta-8-tetrahydrocannabinoic acid (Dd-THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD-C4), cannabidiorcol (CBD-C1), cannabinol (CBN), cannabinolic acid (CBNA), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabinol-C2 (CBN-C2), cannabiorcol-Ci (CBN-C1 ), cannabinodiol (CBND), cannabinodivarin

(CBVD), cannabichromene (CBC), cannabichromenic acid (CBCA), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol monomethylether (CBGM), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic acid (THCVA), cannabicyclol (CBL), cannabicyclovarin

(CBLV), cannabivarin (CBV), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabichromevarin (CBCV), cannabichromevarinic acid (CBCVA), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabielsoin (CBE), cannabielsoic acid-A (CBEA-A), cannabielsoic acid-B (CBEA-B), cannabitriol (CBT), cannabitriolvarin

(CBTV), ethoxy-cannabitriolvarin (CBTVE), cannabifuran (CBF), dehydrocannabifuran (DCBF), cannabichromanon (CBCN), cannabicitran (CBT), 10-oxo-A-6a- tetrahydrocannabinol (OTFIC), A9-cis-tetrahydrocannabinol (cis-TFIC), 3, 4,5,6- tetrahydro-7-hydroxy-a-a-2-trimethyl-9-n-propyl-2,6-methano-2H-1 -benzoxocin-5- methanol (OFI-iso-HHCV), cannabiropsol (CBR), tetrahydroxy-A-9-tetrahydrocannabinol or any combination thereof.

6. The cyclodextrin inclusion complex of claim 4, wherein the one or more than one cannabinoids comprise tetrahydrocannabinol (THC), tetrahydrocannabinoic acid

(THCA), cannabidiolic acid (CBDA), cannabidiol (CBD), cannabinol (CBN),

cannabigerolic acid (CBGA), cannabigerol (CBG), cannabichromene (CBC),

tetrahydrocannabivarin (THCV), cannabidivarin (CBDV) or any combination thereof.

7. The cyclodextrin inclusion complex of claim 4, 5 or 6, wherein the one or more than one terpene comprise myrcene, limonene, linalool, frans-ocimene, b-pinene, a- pinene, b-caryophyllene, D-3-carene, trans- g-bisabolene, trans- a-farnesene, b-fenchol, b-phellandrene, a-humulene, guajol, a-guaiene, a-eudesmol, terpinolene, a-selinene, a- terpineol, fenchone, camphene, c/s-sabinene hydrate, c/s- ocimene, b-eudesmol, b- selinene, a-frans-bergamotene, y-eudesmol, borneol, c/s-b- farnesene, y-curcumene, cis- g-bisabolene, a-thujene, epi-a-bisabolol, ipsdienol, a-ylangene, b-elmene, a-c/s- bergamotene, g-muurolene, a-cadinene, a-longipinene, caryophyllene oxide, a- terpinene, eucalyptol, b-ocimene, g-terpinene, frans-nerolidol, sabinene, p-mentha-1 ,5- diene, camphor, isopulegol, isoborneol, hexahydrothymol, g-terpineol, geranyl acetate, pulegone, geraniol, nerol, a-cedrene, valencene, c/s-nerolidol, cedrol, guaiol or any combination thereof.

8. The cyclodextrin inclusion complex of claim 4, 5 or 6, wherein the one or more than one terpene comprise a-pinene, camphene, b-pinene, b-myrcene, a-terpinene, limonene, eucalyptol, trans^-ocimene, b-ocimene, g-terpinene, sabinene hydrate, terpinolene, fenchone isomers, linalool, fenchyl alcohol, borneol isomers, a-terpineol, trans- caryophyllene, a-humulene, frans-nerolidol, guaiol, a-bisabolol or any combination thereof.

9. The cyclodextrin inclusion complex of any one of claims 1 to 8, wherein the cyclodextrin is a-cyclodextrin, b-cyclodextrin, y-cyclodextrin, 2-hydroxypropyl-p- cyclodextrin, 2-hydroxypropyl-y-cyclodextrin, randomly methylated b-cyclodextrin, sulfobutylether b-cyclodextrin sodium salt or any combination thereof.

10. The cyclodextrin inclusion complex of any one of claims 1 to 9, wherein the cyclodextrin is y-cyclodextrin.

11. Use of a cyclodextrin inclusion complex as defined in any one of claims 1 to 10 for increasing bioavailability of cannabinoids and/or cannabis terpenes in a subject.

12. Use of a cyclodextrin inclusion complex as defined in any one of claims 1 to 10 for increasing water solubility of cannabinoids and/or cannabis terpenes.

13. A mixture of cyclodextrin inclusion complexes comprising:

a first cyclodextrin inclusion complex comprising:

a first host comprising a first cyclodextrin, and first guests comprising compounds of a cannabinoid extract; and

a second cyclodextrin inclusion complex comprising:

a second host comprising a second cyclodextrin, and second guests comprising compounds of a terpene extract.

14. The mixture of cyclodextrin inclusion complexes of claim 13, wherein the cannabinoid extract comprises non-volatile compounds extracted from cannabis flowers and the terpene extract comprises volatile compounds extracted from cannabis flowers.

15. The mixture of cyclodextrin inclusion complexes of claim 14, wherein the non volatile compounds comprise one or more than one cannabinoid and the volatile compounds comprise one or more than one terpene.

16. The mixture of cyclodextrin inclusion complexes of claim 15, wherein the one or more than one cannabinoid comprise delta-9-tetrahydrocannabinol (A9-THC), delta-9- tetrahydrocannabinoic acid (A9-THCA), delta-9-tetrahydrocannabinol-C4 (A9-THC-C4), delta-9-tetrahydrocannabinoic acid-C4 (A9-THCA-C4), delta-9-tetrahydrocannabiorcol-Ci (A9-THC-Ci), delta-9-tetrahydrocannabiorcolic acid-C4 (A9-THCA-Ci),delta-8- tetrahydrocannabinol (Dd-THC), delta-8-tetrahydrocannabinoic acid (Dd-THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD-C4), cannabidiorcol (CBD-C1), cannabinol (CBN), cannabinolic acid (CBNA), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabinol-C2 (CBN-C2), cannabiorcol-Ci (CBN-C1 ), cannabinodiol (CBND), cannabinodivarin

(CBVD), cannabichromene (CBC), cannabichromenic acid (CBCA), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol monomethylether (CBGM), tetrahydrocannabivarin (THCV),

tetrahydrocannabivarinic acid (THCVA), cannabicyclol (CBL), cannabicyclovarin

(CBLV), cannabivarin (CBV), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabichromevarin (CBCV), cannabichromevarinic acid (CBCVA), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabielsoin (CBE), cannabielsoic acid-A (CBEA-A), cannabielsoic acid-B (CBEA-B), cannabitriol (CBT), cannabitriolvarin

(CBTV), ethoxy-cannabitriolvarin (CBTVE), cannabifuran (CBF), dehydrocannabifuran (DCBF), cannabichromanon (CBCN), cannabicitran (CBT), 10-oxo-A-6a- tetrahydrocannabinol (OTFIC), A9-cis-tetrahydrocannabinol (cis-TFIC), 3, 4, 5, 6- tetrahydro-7-hydroxy-a-a-2-trimethyl-9-n-propyl-2,6-methano-2H-1 -benzoxocin-5- methanol (OH-iso-HHCV), cannabiropsol (CBR), tetrahydroxy-A-9-tetrahydrocannabinol or any combination thereof.

17. The mixture of cyclodextrin inclusion complexes of claim 15, wherein the one or more than one cannabinoid comprise tetrahydrocannabinol (THC),

tetrahydrocannabinoic acid (THCA), cannabidiolic acid (CBDA), cannabidiol (CBD), cannabinol (CBN), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV) or any combination thereof.

18. The mixture of cyclodextrin inclusion complexes of claim 15, 16 or 17, wherein the one or more than one terpene comprise myrcene, limonene, linalool, frans-ocimene, b-pinene, a-pinene, b-caryophyllene, D-3-carene, trans- g-bisabolene, trans- a-farnesene, b-fenchol, b-phellandrene, a-humulene, guajol, a-guaiene, a-eudesmol, terpinolene, a- selinene, a-terpineol, fenchone, camphene, c/s-sabinene hydrate, c/s- ocimene, b- eudesmol, b-selinene, a-frans-bergamotene, g-eudesmol, borneol, c/s-b- farnesene, y- curcumene, c/s- g-bisabolene, a-thujene, epi-a-bisabolol, ipsdienol, a-ylangene, b- elmene, a-c/s-bergamotene, g-muurolene, a-cadinene, a-longipinene, caryophyllene oxide, a-terpinene, eucalyptol, b-ocimene, g-terpinene, frans-nerolidol, sabinene, p- mentha-1 ,5-diene, camphor, isopulegol, isoborneol, hexahydrothymol, g-terpineol, geranyl acetate, pulegone, geraniol, nerol, a-cedrene, valencene, c/s-nerolidol, cedrol, guaiol or any combination thereof.

19. The mixture of cyclodextrin inclusion complexes of claim 15, 16 or 17, wherein the one or more than one terpene comprise a-pinene, camphene, b-pinene, b-myrcene, a-terpinene, limonene, eucalyptol, trans^-ocimene, b-ocimene, g-terpinene, sabinene hydrate, terpinolene, fenchone isomers, linalool, fenchyl alcohol, borneol isomers, a- terpineol, trans- caryophyllene, a-humulene, frans-nerolidol, guaiol, a-bisabolol or any combination thereof.

20. The mixture of cyclodextrin inclusion complexes of any one of claims 13 to 19, wherein the first cyclodextrin and the second cyclodextrin are independently a- cyclodextrin, b-cyclodextrin, g-cyclodextrin, 2-hydroxypropyl-p-cyclodextrin, 2- hydroxypropyl-y-cyclodextrin, randomly methylated b-cyclodextrin, sulfobutylether b- cyclodextrin sodium salt or any combination thereof.

21. The mixture of cyclodextrin inclusion complexes of any one of claims 13 to 19, wherein the first cyclodextrin and the second cyclodextrin are y-cyclodextrin.

22. Use of a mixture of cyclodextrin inclusion complexes as defined in any one of claims 13 to 21 for increasing bioavailability of cannabinoids and/or cannabis terpenes in a subject.

23. Use of a mixture of cyclodextrin inclusion complexes as defined in any one of claims 13 to 21 for increasing water solubility of cannabinoids and cannabis terpenes.

24. A cyclodextrin inclusion complex comprising a host comprising a cyclodextrin and a guest comprising cannabigerol.

25. The cyclodextrin inclusion complex of claim 24, wherein the cyclodextrin is a- cyclodextrin, b-cyclodextrin, g-cyclodextrin, 2-hydroxypropyl^-cyclodextrin, 2- hydroxypropyl-y-cyclodextrin, randomly methylated b-cyclodextrin, sulfobutylether b- cyclodextrin sodium salt or a combination thereof.

26. The cyclodextrin inclusion complex of claim 24, wherein the cyclodextrin is y- cyclodextrin.

27. Use of a cyclodextrin inclusion complex as defined in claim 24, 25 or 26 for increasing bioavailability of cannabigerol in a subject.

28. Use of a cyclodextrin inclusion complex as defined in claim 24, 25 or 26 for increasing water solubility of cannabigerol.

29. A method of preparing a cyclodextrin inclusion complex, the method comprising: a) extracting volatile compounds from biomass to produce a terpene extract and residual biomass, wherein the biomass comprises cannabis flowers;

b) extracting the residual biomass with an organic solvent to produce a cannabinoid extract;

c) combining the terpene extract and the cannabinoid extract to form a cannabis extract; and

d) combining the cannabis extract with a cyclodextrin to form the cyclodextrin inclusion complex.

30. The method of claim 29, wherein combining the cannabis extract with the cyclodextrin comprises:

a) kneading the cannabis extract with a paste of the cyclodextrin to form a solid; b) drying and grinding the solid to form a powder; and

c) washing, filtering and drying the powder.

31. The method of claim 29 or 30, wherein the cyclodextrin is a-cyclodextrin, b- cyclodextrin, g-cyclodextrin, 2-hydroxypropyl-p-cyclodextrin, 2-hydroxypropyl-y- cyclodextrin, randomly methylated b-cyclodextrin, sulfobutylether b-cyclodextrin sodium salt or a combination thereof.

32. The method of claim 29 or 30, wherein the cyclodextrin is y-cyclodextrin.

33. A method of preparing a mixture of cyclodextrin inclusion complexes, the method comprising:

a) extracting volatile compounds from biomass to produce a terpene extract and residual biomass, wherein the biomass comprises cannabis flowers; b) extracting the residual biomass with an organic solvent to produce a cannabinoid extract;

c) combining the cannabinoid extract with a first cyclodextrin to form a first cyclodextrin inclusion complex;

d) combining the terpene extract with a second cyclodextrin to form a second cyclodextrin inclusion complex; and

e) combining the first and second cyclodextrin inclusion complexes to form the mixture of cyclodextrin inclusion complexes.

34. The method of claim 33, wherein combining the cannabinoid extract with the first cyclodextrin comprises:

a) kneading the cannabinoid extract with a paste of the first cyclodextrin to form a first solid;

b) drying and grinding the first solid to form a first powder; and

c) washing, filtering and drying the first powder.

35. The method of claim 33 or 34, wherein combining the terpene extract with the second cyclodextrin comprises:

a) kneading the terpene extract with a paste of the second cyclodextrin to form a second solid;

b) drying and grinding the second solid to form a second powder; and

c) washing, filtering and drying the second powder.

36. The method of claim 33, 34 or 35, wherein the first cyclodextrin and the second cyclodextrin are independently a-cyclodextrin, b-cyclodextrin, y-cyclodextrin, 2- hydroxypropyl-p-cyclodextrin, 2-hydroxypropyl-y-cyclodextrin, randomly methylated b- cyclodextrin, sulfobutylether b-cyclodextrin sodium salt or a combination thereof.

37. The method of claim 33, 34 or 35, wherein the first cyclodextrin and the second cyclodextrin are y-cyclodextrin.

38. The method of any one of claims 29 to 37, further comprising concentrating the cannabinoid extract by removing the organic solvent after step b).

39. The method of any one of claims 29 to 38, wherein extracting volatile compounds from biomass comprises steam distillation.

40. The method of any one of claims 29 to 39, further comprising drying the residual biomass before extracting the residual biomass with the organic solvent.

41. The method of any one of claims 29 to 40, wherein the organic solvent is a polar organic solvent, a medium polar organic solvent or a non-polar organic solvent.

Description:
CYCLODEXTRIN INCLUSION COMPLEXES OF CANNABIS EXTRACTS

FIELD

[0001] This invention relates to cyclodextrin inclusion complexes. In particular, the invention relates to cyclodextrin inclusion complexes of cannabis extracts, cannabinoids and/or cannabis terpenes and methods of making such complexes.

BACKGROUND

[0002] The cannabis plant, including the flowers of Cannabis sativa, indica and rudralis, contain more than 500 different chemical compounds. These compounds include cannabinoids, amino acids, proteins, glycoproteins, enzymes, terpenes, flavonoids, non-cannabinoid phenols, nitrogenous compounds, sterols, sugars, fatty acids, hydrocarbons, simple alcohols, simple aldehydes, simple ketones, simple acids, simple esters and lactones, steroids, vitamins, pigments and other elements. Some of these compounds are biologically active while others are benign, for example, several of the cannabinoids are biologically active.

[0003] The biologically active cannabinoids include tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), cannabigerol (CBG), tetrahydrocannabivarin (THCV), cannabicyclol (CBL), cannabivarin (CBV),

cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabielsoin (CBE), cannabicitran (CBT) and acids thereof. The relative amounts of these compounds in cannabis vary for different chemovar. For example, some chemovar are dominant in THC while others are dominant with CBD or both THC and CBD. Therefore, extracts from these different chemovar may show different biological activities.

[0004] When cannabis extracts or isolated cannabinoids are consumed orally, most of the fat-soluble hydrophobic compounds pass through the gastrointestinal tract without being absorbed into the body. Cannabinoids and cannabis terpenes are among these compounds that are hydrophobic and insoluble in water. [0005] Cyclodextrins (CD) are non-reducing cyclic oligosaccharides of glucose. Typically, cyclodextrins are products of cyclomaltodextrin glucotransferase-catalyzed degradation of starch. Cyclodextrins can have a variety of structures. Three common cyclodextrins have 6, 7 or 8 D-glycopyranosyl molecules linked in a ring by a-1 ,4- glycosidic bonds. These cyclodextrin rings form a cavity or lumen, with the cavity having a different diameter depending on the number of glucose units present in the ring. Rings with 6, 7 or 8 D-glycopyranosyl residues are referred to as a-, b- or g- cyclodextrin, respectively. The scales of these cyclodextrins are shown in Table 1. In addition, chemically modified cyclodextrins are also available. These modified cyclodextrins may possess improved inclusion specificity, water solubility and other modified physical and chemical properties as compared to natural cyclodextrins.

Table 1. Cyclodextrin Structures

[0006] Cyclodextrins are generally amphipathic, with the wider rim of the lumen displaying the 2- and 3-OH groups and the narrower ring displaying the 6-OH of the glucose units. These hydrophilic hydroxyl groups are accordingly on the outside of the lumen. The inner surface of the lumen is generally hydrophobic and lined with the anomeric oxygen atoms and the C3- and C5-hydrogen atoms of the glucose units. In aqueous solution, this hydrophobic lumen may contain water molecules that are poorly held by low entropy and can easily be displaced by hydrophobic molecules. Therefore, hydrophilic cyclodextrin can accommodate one or more suitably sized molecules within, or partially within, the lumen of the cyclodextrin, forming a cyclodextrin inclusion complex. For example, non-polar aliphatic and aromatic lipophilic compounds can be formed as cyclodextrin inclusion complexes in order to produce a water soluble compound. In addition, undesirable properties, such as odor or taste, of some organic drugs and food additives can be minimized or eliminated after formation of cyclodextrin inclusion complexes of those molecules. Thus, cyclodextrin inclusion complexes are widely used in the pharmaceutical, food and cosmetic industries for these reasons.

[0007] Cyclodextrin inclusion complexes of individual cannabinoids (specifically for THC, CBD or CBN) have been prepared using refined cannabinoids. However, refinement of cannabinoids is highly time consuming and labour intensive. Thus, there remains a need for inclusion complexes for cannabis extracts.

SUMMARY

[0008] In one aspect, the present invention provides cyclodextrin inclusion complexes of cannabis extracts and methods of making cyclodextrin inclusion complexes.

[0009] Various aspects of the present invention provide cyclodextrin inclusion complexes comprising: a host comprising a cyclodextrin, and guests comprising compounds of a cannabis extract. The cannabis extract may comprise a cannabinoid extract from cannabis biomass and a terpene extract from cannabis biomass, the cannabis biomass comprising cannabis flowers.

[0010] Various aspects of the present invention also provide a mixture of

cyclodextrin inclusion complexes comprising: a first cyclodextrin inclusion complex comprising a first host comprising a first cyclodextrin, and first guests comprising compounds of a cannabinoid extract; and a second cyclodextrin inclusion complex comprising a second host comprising a second cyclodextrin, and second guests comprising compounds of a terpene extract.

[0011] In various aspects, the cannabinoid extract comprises non-volatile

compounds extracted from cannabis flowers and the terpene extract comprises volatile compounds extracted from cannabis flowers. The non-volatile compounds may comprise one or more than one cannabinoid and the volatile compounds may comprise one or more than one terpene. [0012] Various aspects of the present disclosure provide a cyclodextrin inclusion complex comprising a host comprising cyclodextrin and a guest comprising

cannabigerol (CBG).

[0013] Various aspects of the present invention provide use of the cyclodextrin inclusion complexes disclosed herein for increasing bioavailability of cannabinoids and cannabis terpenes in a subject.

[0014] Various aspects of the present invention provide use of the cyclodextrin inclusion complexes disclosed herein for increasing water solubility of cannabinoids and cannabis terpenes.

[0015] Various aspects of the present invention provide methods of preparing cyclodextrin inclusion complexes, the methods comprising: a) extracting volatile compounds from biomass to produce a terpene extract and residual biomass, wherein the biomass comprises cannabis flowers; b) extracting the residual biomass with an organic solvent to produce a cannabinoid extract; c) combining the terpene extract and the cannabinoid extract to form a cannabis extract; and d) combining the cannabis extract with a cyclodextrin to form the cyclodextrin inclusion complexes.

[0016] Various aspects of the present invention provide methods of preparing a mixture of cyclodextrin inclusion complexes comprising: a) extracting volatile

compounds from biomass to produce a terpene extract and residual biomass, wherein the biomass comprises cannabis flowers; b) extracting the residual biomass with an organic solvent to produce a cannabinoid extract; c) combining the cannabinoid extract with a first cyclodextrin to form a first cyclodextrin inclusion complex; d) combining the terpene extract with a second cyclodextrin to form a second cyclodextrin inclusion complex; and e) combining the first and second cyclodextrin inclusion complexes to form the mixture of cyclodextrin inclusion complexes.

[0017] Other aspects and features of the present invention will become apparent to those of ordinary skill in the art upon review of the following description of specific embodiments of the invention in conjunction with the accompanying claims. DETAILED DESCRIPTION

[0018] In the context of the present application, various terms are used in

accordance with what is understood to be the ordinary meaning of those terms.

[0019] In various embodiments, the disclosure provides cyclodextrin inclusion complexes of cannabis extracts, cannabinoids or cannabis terpenes. The term “inclusion complex” refers to a complex in which one component, the host, contains a cavity in which molecular entities of a second component, the guest or guests, are located. The interaction between the host and guest in the cavity may be referred to as a“host-guest interaction”. The term“cannabis extract” refers to an extract from cannabis flowers in which all compounds from the extract, including both biologically active and inactive compounds, are present. These compounds may include, for example, cannabinoids and terpenes.

[0020] In various embodiments, the disclosure provides water soluble cyclodextrin inclusion complexes of compounds of cannabis extracts, cannabinoids and/or cannabis terpenes. The cyclodextrin acts as the host and the compounds of the cannabis extracts, cannabinoids and/or cannabis terpenes are the guest or guests.

[0021] The disclosure also provides cyclodextrin inclusion complexes of a mixture of several cannabinoids from a cannabis extract, a mixture of cannabis terpenes from a cannabis extract, a mixture of refined cannabinoid isolates or individual cannabinoids or cannabis terpenes.

[0022] The cyclodextrin inclusion complexes or mixtures of cyclodextrin inclusion complexes disclosed herein may possess water soluble properties. Typically, cannabinoids and cannabis terpenes are water insoluble and hydrophobic. Inclusion complexes incorporating these compounds are more hydrophilic than the cannabinoids and cannabis terpenes on their own. Thus, the cyclodextrin inclusion complexes may be used to deliver hydrophobic compounds of the cannabis extract, cannabinoids or cannabis terpenes to a subject via buccal, sublingual or gastrointestinal pathways. In various embodiments, delivery of cannabis extracts, cannabinoid extracts, terpene extracts, cannabinoids and cannabis terpenes in the cyclodextrin inclusion complexes disclosed herein may have improved aqueous or water solubility, dissolution, absorption and/or bioavailability properties compared to delivery of cannabis compounds without the cyclodextrin host. In addition, the inclusion complexes disclosed herein may be highly stable, and may result in consumer products having an improved shelf-life compared to cannabis extracts, cannabinoid extracts, terpene extracts, cannabinoids and cannabis terpenes on their own.

[0023] The cyclodextrin inclusion complexes and mixtures of cyclodextrin inclusion complexes disclosed herein may include one or more than one cannabinoid. These cannabinoids may be one or more than one of delta-9-tetrahydrocannabinol (A9-THC), delta-9-tetrahydrocannabinoic acid (A9-THCA), delta-9-tetrahydrocannabinol-C4 (D9- THC-C4), delta-9-tetrahydrocannabinoic acid-C4 (A9-THCA-C4), delta-9- tetrahydrocannabiorcol-C1 (A9-THC-C1 ), delta-9-tetrahydrocannabiorcolic acid-C4 (D9- THCA-C1 ),delta-8-tetrahydrocannabinol (Dd-THC), delta-8-tetrahydrocannabinoic acid (Dd-THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidiol

monomethylether (CBDM), cannabidiol-C4 (CBD-C4), cannabidiorcol (CBD-C1 ), cannabinol (CBN), cannabinolic acid (CBNA), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabinol-C2 (CBN-C2), cannabiorcol-C1 (CBN-C1 ), cannabinodiol (CBND), cannabinodivarin (CBVD), cannabichromene (CBC), cannabichromenic acid (CBCA), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol monomethylether (CBGM), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic acid (THCVA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabivarin (CBV), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabichromevarin (CBCV),

cannabichromevarinic acid (CBCVA), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabielsoin (CBE), cannabielsoic acid-A (CBEA-A), cannabielsoic acid-B (CBEA-B), cannabitriol (CBT), cannabitriolvarin (CBTV), ethoxy-cannabitriolvarin (CBTVE), cannabifuran (CBF), dehydrocannabifuran (DCBF), cannabichromanon (CBCN), cannabicitran (CBT), 10-oxo-A-6a-tetrahydrocannabinol (OTFIC), A9-cis- tetrahydrocannabinol (cis-TFIC), 3,4,5,6-tetrahydro-7-hydroxy-a-a-2-trimethyl-9-n- propyl-2,6-methano-2H-1 -benzoxocin-5-methanol (OFI-iso-HHCV), cannabiropsol (CBR), and/or tetrahydroxy-A-9-tetrahydrocannabinol. [0024] The cyclodextrin inclusion complexes and mixtures of cyclodextrin inclusion complexes disclosed herein may include one or more than one cannabis terpene.

These cannabis terpenes may be one or more than one of myrcene, limonene, linalool, frans-ocimene, b-pinene, a-pinene, b-caryophyllene, D-3-carene, trans- y-bisabolene, trans- a-farnesene, b-fenchol, b-phellandrene, a-humulene, guajol, a-guaiene, a- eudesmol, terpinolene, a -selinene, a -terpineol, fenchone, camphene, c/s-sabinene hydrate, c/s- ocimene, b-eudesmol, b-selinene, a-frans-bergamotene, y-eudesmol, borneol, c/s-b- farnesene, y-curcumene, c/s- g-bisabolene, a -thujene, epi-a-bisabolol, ipsdienol, a-ylangene, b-elmene, a-c/s-bergamotene, y-muurolene, a-cadinene, a- longipinene, caryophyllene oxide, a-terpinene, eucalyptol, b-ocimene, y-terpinene, frans-nerolidol, sabinene, p-mentha-1 ,5-diene, camphor, isopulegol, isoborneol, hexahydrothymol, g-terpineol, geranyl acetate, pulegone, geraniol, nerol, a-cedrene, valencene, c/s-nerolidol, cedrol and/or guaiol.

[0025] In various embodiments, the disclosure provides methods of preparing cyclodextrin inclusion complexes of cannabis extracts, one or more than one

cannabinoid, and/or one or more than one cannabis terpene.

[0026] The methods of preparing the cyclodextrin inclusion complexes and mixtures of cyclodextrin inclusion complexes may comprise extracting volatile compounds from cannabis biomass to produce an extract of volatile compounds and residual biomass. This extract is also referred to as a“terpene extract”. The biomass may be cannabis flowers. The flowers may be from Cannabis sativa, indica, rudralis or a combination thereof. The term“volatile compounds” refers to compounds that have a high vapor pressure at the conditions used for extracting the biomass. The high vapor pressure of volatile compounds results from a low boiling point, which causes the compounds to evaporate or sublimate from the liquid or solid form of the compound. For example, the volatile compounds may have a boiling point between about 80°C and about 300°C.

[0027] The volatile compounds from cannabis flowers comprise terpenes, amongst other compounds. The term“terpene” refers to any organic compound found in the essential oils of plants that is based on isoprene (2-methyl-1 , 3-butadiene), where each terpene comprises at least two isoprene units. The terpenes in the volatile compounds from cannabis flowers comprise hydrocarbons, simple alcohols, simple aldehydes, simple ketones, simple acids, simple esters and lactone-type structures. These cannabis terpenes can include one or more of myrcene, limonene, linalool, trans- ocimene, b-pinene, a-pinene, b-caryophyllene, D-3-carene, trans- g-bisabolene, trans- a- farnesene, b-fenchol, b-phellandrene, a-humulene, guajol, a-guaiene, a-eudesmol, terpinolene, a -selinene, a -terpineol, fenchone, camphene, c/s-sabinene hydrate, cis- ocimene, b-eudesmol, b-selinene, a-frans-bergamotene, g-eudesmol, borneol, c/s-b- farnesene, y-curcumene, c/s- g-bisabolene, a -thujene, epi-a-bisabolol, ipsdienol, a- ylangene, b-elmene, a-c/s-bergamotene, g-muurolene, a-cadinene, a-longipinene, caryophyllene oxide, a-terpinene, eucalyptol, b-ocimene, g-terpinene, frans-nerolidol, sabinene, p-mentha-1 ,5-diene, camphor, isopulegol, isoborneol, hexahydrothymol, g- terpineol, geranyl acetate, pulegone, geraniol, nerol, a-cedrene, valencene, c/s- nerolidol, cedrol and/or guaiol. Cannabis terpenes may play an important role in biological systems following consumption, such as by oral consumption. For example, terpenes may enhance the bioavailability and/or biological activity of cannabinoids. Furthermore, some terpenes may be biologically active in a subject, such as a human.

[0028] In various embodiments, the step of extracting volatile compounds is conducted at a temperature sufficient to decarboxylate the compounds in the biomass to their biologically active forms. Decarboxylation may be necessary in order to obtain the biologically active forms of the compounds. If the extraction process of volatile compounds is steam distillation, the compounds in the biomass may be decarboxylated without the use of thermally induced decarboxylation after a solvent extraction step.

[0029] The concentration of cannabis terpenes in the terpene extract may be standardized and used in a subsequent method step.

[0030] The residual biomass or an alternative biomass is then extracted with an organic solvent to produce a liquid phase comprising non-volatile compounds. The term “non-volatile compounds” refers to compounds that do not readily evaporate under the conditions used for extracting the volatile compounds. Examples of non-volatile compounds include cannabinoids, nitrogenous compounds, amino acids, proteins, glycoproteins, enzymes, sugars and related compounds, hydrocarbons, fatty acids, steroids, noncannabinoid phenols, flavonoids, vitamins, and pigments. The solvent extraction of the residual biomass may be performed at low temperature, for example, between about -25°C and about -80°C, and may be conducted within a short period of time, such as, for example, less than about 30 minutes, less than about 20 minutes, less than about 10 minutes, less than about 9 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, less than about 3 minutes, less than about 2 minutes, less than about 1 minute, less than about 30 seconds or any amount of time therebetween. In various embodiments, the temperature for solvent extraction is about -25°C. In various embodiments, conducting the solvent extraction at low temperature and for a short period of time may avoid extraction of chlorophyll and/or other undesirable pigments into the liquid phase. However, avoiding the extraction of chlorophyll and/or other pigments into the liquid phase may not be necessary in all embodiments as these compounds may be too large to fit into the cavity of the cyclodextrin and as a result, will not form part of the inclusion complexes.

[0031] The organic solvent may be a polar organic solvent, a medium polar organic solvent or a non-polar organic solvent. For example, the solvent may be ethanol, methanol, propanol, isopropyl alcohol, butanol, tetrahydrofuran, ethyl acetate, acetone, chloroform, diethyl ether, dichloromethane, acetonitrile, dimethylformamide, acetic acid, toluene, 1 ,4-dioxane, dimethyl sulfoxide, pentane, hexane or cyclohexane. Preferably, the solvent is a polar organic solvent such as, for example, ethanol, methanol, ethyl acetate, acetone, chloroform, diethyl ether or combinations thereof.

[0032] Following extraction, the liquid phase may be concentrated by removing the organic solvent to form a concentrated oil. This extract is also referred to as a “cannabinoid extract”. The concentration of cannabinoids in the concentrated oil or cannabinoid extract may be standardized and used in a subsequent method step.

[0033] If the extraction step to isolate the volatile compounds is not performed before the solvent extraction step, then the volatile compounds are lost during removal of the organic solvent. Thus, in order to obtain a combined extract consisting of both volatile and non-volatile compounds (including both the cannabis terpenes and cannabinoids, respectively), the volatile compounds must be isolated prior to solvent extraction. If the biomass is subject to solvent extraction without the prior extraction of the volatile compounds, the obtained cannabinoid extract comprising non-volatile compounds may require decarboxylation in order for some cannabinoids to be in their biologically active form, as described above. Without decarboxylation, the cannabinoid extract comprises cannabinoid acids.

[0034] In various embodiments, the residual biomass is dried prior to solvent extraction. For example, steam distilled residual biomass may be dried before solvent extraction. If the residual biomass has a high moisture content, the final extract may compromise water which may affect the homogeneity of the extract.

[0035] In various embodiments, a new batch of biomass containing volatile

compounds may be used for extraction with the organic solvent. This step may protect the cannabinoid acids (for example, THCA, CBDA, THCVA, CBNA, CBLA and CBGA) from thermal conversion caused during the extraction of volatile compounds from the biomass. Most volatile compounds in the biomass are evacuated from the extract during the solvent evaporation. In various embodiments, the biomass is from the same strain of cannabis plant used for steam distillation to extract the volatile compounds.

[0036] The cannabinoid extract comprising non-volatile compounds may also be produced by supercritical CO2 extraction.

[0037] In various embodiments, the terpene extract and the cannabinoid extract are combined to form a cannabis extract. The amount or ratio of each of the terpene extract and the cannabinoid extract may be adjusted to achieve a suitable ratio of terpenes to cannabinoids in the cannabis extract. In various embodiments, this ratio may be similar to that which is present in the cannabis flowers.

[0038] In various embodiments, the disclosed extracts include a full blend of compounds, including both volatile and non-volatile compounds, found in cannabis flowers, and not only the known biologically active cannabinoids. In various

embodiments, the cannabis extract may have enhanced bioavailability and/or activity following oral consumption as compared to bioavailability and/or activity following oral consumption of the cannabinoids alone. The presence of the volatile compounds, including terpenes, in the cyclodextrin inclusion complexes disclosed herein may enhance the activity of the cannabinoids. In various embodiments, the composition of the combined extract in the cyclodextrin inclusion complexes is about the same as what is present in the cannabis flowers in terms of proportion of cannabinoids to other compounds. Thus, the biological activity of products prepared using the cyclodextrin inclusion complexes of the cannabis extracts disclosed herein may be enhanced compared to the biological activity of cannabinoids on their own or cyclodextrin inclusion complexes of a single, refined cannabinoid, due to the presence of other compounds which enhance the activity of cannabinoids that are found in cannabis flowers.

[0039] Following preparation of the extracts, the concentration of the volatile and non-volatile compounds in the extract may be standardized and used for preparation of cyclodextrin inclusion compounds for oral consumption. Furthermore, the cannabis extract may be combined with a synthetic or isolated form of one or more cannabinoids to produce an extract with certain ratios of compounds.

[0040] Cyclodextrin inclusion complexes of compounds of cannabis extracts may be prepared from the terpene extract and the cannabinoid extract, alone or in combination. Thus, a fully blended cannabis extract, prepared by combining the cannabinoid extract and the terpene extract, can be treated with cyclodextrin to form inclusion complexes, where the host comprises a cyclodextrin and guests comprise the compounds of the cannabinoid extract and the terpene extract. Alternatively, the cannabinoid extract may be prepared as an inclusion complex, wherein the host comprises a cyclodextrin and the guests comprise the compounds of the cannabinoid extract, and the compounds of the terpene extract may be prepared as an inclusion complex separately, wherein the host comprises a cyclodextrin and the guests comprise the compounds of the terpene extract. These two inclusion complexes are then combined in an appropriate ratio to form a mixture which represents the full blend of compounds in the cannabis flower.

[0041] Inclusion complexes can also be formed using individually refined

cannabinoids. For example, inclusion complexes with delta-9-tetrahydrocannabinol (D9- TFIC), delta-9-tetrahydrocannabinoic acid (A9-TFICA), delta-9-tetrahydrocannabinol-C4 (A9-TFIC-C4), delta-9-tetrahydrocannabinoic acid-C4 (A9-TFICA-C4), delta-9- tetrahydrocannabiorcol-Ci (A9-THC-Ci), delta-9-tetrahydrocannabiorcolic acid-C4 (D9- THCA-Ci),delta-8-tetrahydrocannabinol (Dd-THC), delta-8-tetrahydrocannabinoic acid (Dd-THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidiol

monomethylether (CBDM), cannabidiol-C4 (CBD-C4), cannabidiorcol (CBD-C1), cannabinol (CBN), cannabinolic acid (CBNA), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabinol-C2 (CBN-C2), cannabiorcol-Ci (CBN-C1), cannabinodiol (CBND), cannabinodivarin (CBVD), cannabichromene (CBC), cannabichromenic acid (CBCA), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol monomethylether (CBGM), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic acid (THCVA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabivarin (CBV), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabichromevarin (CBCV),

cannabichromevarinic acid (CBCVA), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabielsoin (CBE), cannabielsoic acid-A (CBEA-A), cannabielsoic acid-B (CBEA-B), cannabitriol (CBT), cannabitriolvarin (CBTV), ethoxy-cannabitriolvarin (CBTVE), cannabifuran (CBF), dehydrocannabifuran (DCBF), cannabichromanon (CBCN), cannabicitran (CBT), 10-oxo-A-6a-tetrahydrocannabinol (OTFIC), A9-cis- tetrahydrocannabinol (cis-TFIC), 3,4,5,6-tetrahydro-7-hydroxy-a-a-2-trimethyl-9-n- propyl-2,6-methano-2H-1 -benzoxocin-5-methanol (OFI-iso-HHCV), cannabiropsol (CBR), tetrahydroxy-A-9-tetrahydrocannabinol, or any combination thereof can be prepared.

[0042] Inclusion complexes can also be formed using individually refined terpenes. For example, complexes with myrcene, limonene, linalool, frans-ocimene, b-pinene, a- pinene, b-caryophyllene, D-3-carene, trans- g-bisabolene, trans- a-farnesene, b-fenchol, b-phellandrene, a-humulene, guajol, a-guaiene, a-eudesmol, terpinolene, a-selinene, a- terpineol, fenchone, camphene, c/s-sabinene hydrate, c/s- ocimene, b-eudesmol, b- selinene, a-frans-bergamotene, y-eudesmol, borneol, c/s-b- farnesene, y-curcumene, cis- g-bisabolene, a-thujene, epi-a-bisabolol, ipsdienol, a-ylangene, b-elmene, a-c/s- bergamotene, g-muurolene, a-cadinene, a-longipinene, caryophyllene oxide, a- terpinene, eucalyptol, b-ocimene, g-terpinene, frans-nerolidol, sabinene, p-mentha-1 ,5- diene, camphor, isopulegol, isoborneol, hexahydrothymol, g-terpineol, geranyl acetate, pulegone, geraniol, nerol, a-cedrene, valencene, c/s-nerolidol, cedrol, guaiol, or any combination thereof can be prepared.

[0043] In various embodiments, cyclodextrin inclusion complexes can be prepared using any naturally occurring cyclodextrin, including a-, b- and g-cyclodextrins, and combinations thereof. The water solubility of the inclusion complexes may be varied, depending on which cyclodextrin is used. Typically, inclusion complexes prepared with y-cyclodextrin have higher solubility than inclusion complexes prepared with a- or b- cyclodextrins. In addition, synthetically modified cyclodextrins may also be used in preparation of the inclusion complexes disclosed herein. These inclusion complexes may show very high water solubility. For example, inclusion complexes may be prepared with 2-hydroxypropyl^-cyclodextrin, 2-hydroxypropyl-y-cyclodextrin, randomly methylated b-cyclodextrin, sulfobutylether b-cyclodextrin sodium salt or other synthetic cyclodextrins with very high water solubility.

[0044] In various embodiments, a ratio of cannabis extract, cannabinoid extract or terpene extract to cyclodextrin may be different according to the amount of

cannabinoids, terpenes and other compounds present in the starting material (biomass) and depending on the type of cyclodextrin used for inclusion complex formation. In various embodiments, the weight ratio of cannabis extract, cannabinoid extract or terpene extract to cyclodextrin may be about 1 :3, about 1 :6, about 1 :12, about 1 :24, about 1 :48 or any ratio therebetween.

[0045] The cyclodextrin inclusion complexes may be prepared by kneading, co precipitation and solution/solvent evaporation steps, amongst other methods. The choice of method may depend on the nature of the starting materials and on the production scale. In various embodiments, the cyclodextrin inclusion complexes may be prepared without any petroleum-based solvents.

[0046] For example, a cyclodextrin may be mixed with water to form a paste. The paste may be kneaded with the cannabis extract, cannabinoid extract, terpene extract, individually refined cannabinoids and/or cannabis terpenes dissolved in a solvent until this mixture is homogeneous. For example, the solvent may be 98% ethanol or another organic solvent which dissolves the cannabis extract, cannabinoid extract, terpene extract, individually refined cannabinoids and/or cannabis terpenes. The mixture is then dried. Once the cyclodextrin inclusion complexes are formed, the solid may be washed with 98% ethanol, or another organic solvent, to remove any unwanted fats, oils, waxy compounds and other unnecessary impurities. The cleaned solid of the cyclodextrin inclusion complexes may then be dried and ground into very fine particles or a powder. This drying step may be conducted at elevated temperature such as, for example, between about 40°C and about 50°C, or any temperature therebetween, under atmospheric pressure. In various embodiments, no further purification steps are required. Alternatively, the powder may be washed, filtered and dried. The cyclodextrin inclusion complexes may be produced free from any solvent or heavy metals and may be used directly for a product for human consumption.

[0047] In various embodiments, the yield of the cyclodextrin inclusion complexes may be almost quantitative. For example, the cyclodextrin inclusion complexes may be formed in about 80% yield, about 85% yield, about 90% yield, about 91 % yield, about 92% yield, about 93% yield, about 94% yield, about 95% yield, about 96% yield, about 97% yield, about 98% yield, about 99% yield, about 99.5% yield, about 99.6% yield or greater.

[0048] In various embodiments, the cyclodextrin inclusion complexes may be used or formulated as a solid or liquid for consumption by a subject, using carriers known to a person of ordinary skill in the art. For example, the cyclodextrin inclusion complexes may be used or formulated as a capsule, a tablet, a powder, a solution, a suspension, an emulsion, a syrup, a food product, a supplement, etc., as known to a person of ordinary skill in the art. The amount of these products to be given to a subject will vary depending, for example, on the body weight and age of the subject, manner of consumption, any conditions the subject may have, and may be determined by a person of ordinary skill in the art. The subject may be a mammal, such as a human.

[0049] In various embodiments, the cyclodextrin inclusion complexes may provide efficient delivery of cannabinoids, terpenes and/or other cannabis compounds into the body through sublingual, buccal or gastrointestinal routes. The cyclodextrin inclusion complexes may be suitable for delivery to the gastrointestinal tract and avoid hepatic first-pass metabolism via oral consumption. In various embodiments, formulation of the hydrophobic compounds in cannabis extracts as cyclodextrin inclusion complexes may have increased hydrophilicity compared to the hydrophilicity of these compounds without inclusion in a cyclodextrin and therefore, may have increased bioavailability.

[0050] In various embodiments, the inclusion complexes disclosed herein may be stored in a closed container at room temperature. However, storage with refrigeration may be preferred for some embodiments.

EXAMPLES

[0051] These examples illustrate various aspects of the invention, evidencing a variety of conditions for preparing cyclodextrin inclusion complexes of compounds of cannabis extracts. Selected examples are illustrative of advantages that may be obtained compared to alternative preparation methods, and these advantages are accordingly illustrative of particular embodiments and not necessarily indicative of the characteristics of all aspects of the invention.

[0052] As used herein, the term“about” refers to an approximately +/-10% variation from a given value. It is to be understood that such a variation is always included in any given value provided herein, whether or not it is specifically referred to.

Example 1 : Preparation of cyclodextrin inclusion complexes of cannabis extracts

[0053] (a) Extraction of volatile compounds from cannabis flowers: 908 grams (2.0 lbs) of dried and cleaned flowers from a hybrid (THC and CBD dominant) strain of Cannabis sativa L. were steam distilled for three hours. The steam distilled oil fraction containing the volatile compounds collected in the receiving unit was transferred into a clean container and dried using anhydrous sodium sulphate. The dried oil fraction was filtered to remove solid particles to obtain a clear oily liquid as a filtrate. This filtrate was the terpene extract. The concentration of terpenes in this extract was determined by GC-MS. Analysis showed that the terpene extract contained a-pinene, camphene, b- pinene, b-myrcene, a-terpinene, limonene, eucalyptol, trans^-ocimene, b-ocimene, g- terpinene, sabinene hydrate, terpinolene, fenchone isomers, linalool, fenchyl alcohol, borneol isomers, a-terpineol, trans- caryophyllene, a-humulene, frans-nerolidol, guaiol and a-bisabolol. The total weight of the filtrate was 3.8 g.

[0054] (b) Formation of cyclodextrin inclusion complexes with the terpene extract:

0.5 grams of prepared oil was dissolved in 3.0 ml_ of 98% ethanol. Separately, 4.2 g of y-cyclodextrin was mixed with a sufficient quantity of water to prepare a paste. These two components were combined and kneaded for 2 hours, until the paste became homogeneous. The paste was then air dried at room temperature for two days. The dried solid was ground into a powder, and the powder was washed with 98% ethanol and filtered. Analysis of the filtrate by GC-MS showed an absence of any previously detected terpenes in solution, indicating that cannabis terpenes formed an inclusion complex with g-cyclodextrin. The filtrate was then dried at 40°C, ground again, and sieved to form fine powdery particles. No smell was detected from the dried particles. The total weight of the cyclodextrin inclusion compounds of volatile compounds was 4.6 9

[0055] (c) Extraction of non-volatile compounds from cannabis flowers: 908 grams (2 lbs) of dried and cleaned flowers from a hybrid (THC and CBD dominant) strain of Cannabis sativa L. was mixed with 10 L of 95% ethanol and extracted at -25°C under atmospheric pressure for 1 minute. The liquid was separated from the solid biomass and the extraction was repeated with 8 L of 95% ethanol at -25°C. The combined ethanol extracts were then filtered under suction. The solvent was removed from the filtrate using a rotary evaporator under reduced pressure at 45°C to obtain the

cannabinoid extract as an oily resin. The concentration of cannabinoids in this extract was determined by HPLC. Analysis showed that the mixtured contained THC (46.02%), THCA (0.04%), CBDA (0.18%), CBD (45.27%), CBN (0.16%), CBGA (0.19%), CBG (2.01 %), CBC (2.42%), THCV (0.24%), CBDV (0.14%) as the major detectable cannabinoids. The total weight of the cannabinoid extract was 188.0 g.

[0056] (d) Formation of cyclodextrin inclusion complexes with the cannabinoid extract: 6.25 grams of the cannabinoid extract was dissolved in 15 mL of 98% ethanol. Separately, 51.5 g of g-cyclodextrin was mixed with a sufficient quantity of water to prepare a paste. Both the cannabinoid extract and the g-cyclodextrin paste were combined and kneaded for 3 hours, until the paste became homogeneous. The paste was then air dried at room temperature for two days. The dried solid was ground into a powder, and the powder was washed with 98% ethanol and filtered. Analysis of the filtrate by HPLC showed the absence of any previously detected cannabinoids in solution, indicating that cannabinoids formed an inclusion complex with y-cyclodextrin. The filtrate was dried in an oven at 45°C, ground again and sieved to form fine powdery particles. No smell was detected from the dried particles. The total weight of the cyclodextrin inclusion complex of non-volatile compounds was 56.1 g.

[0057] (e) A blend of cyclodextrin inclusion complexes was made by mixing 1.2 g of the inclusion compounds made in (b) and 56.1 g of the inclusion compounds made in (d). This ratio (1 :50) represents the actual amount of cannabinoids and terpenes in cannabis flowers. The blend was mixed, ground and sieved.

Example 2: Preparation of cyclodextrin inclusion complexes of cannabigerol (CBG)

[0058] 1.0 g of isolated cannabigerol (99.9%) was dissolved in 5.0 ml_ of 98% ethanol. Separately, 4.2 g of g-cyclodextrin was mixed with a sufficient quantity of water to prepare a paste. The CBG solution and g-cyclodextrin paste were combined and kneaded for 2 hours, until the paste became homogeneous. The paste was then air dried at room temperature for two days. The dried solid was ground, washed with 98% ethanol and filtered. Analysis of the filtrate by HPLC showed an absence of CBG in solution, indicating that CBG formed an inclusion complex with g-cyclodextrin. The solid precipitate was dried in an oven at 45°C, ground and sieved to form fine white powdery particles. The total weight of the CBG inclusion complexes was 4.9 g.

[0059] Although various embodiments of the invention are disclosed herein, many adaptations and modifications may be made within the scope of the invention in accordance with the common general knowledge of those skilled in this art. Such modifications include the substitution of known equivalents for any aspect of the invention in order to achieve the same result in substantially the same way. Numeric ranges are inclusive of the numbers defining the range. The word "comprising" is used herein as an open-ended term, substantially equivalent to the phrase "including, but not limited to", and the word "comprises" has a corresponding meaning. As used herein, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a thing" includes more than one such thing. Citation of references herein is not an admission that such references are prior art to the present invention. Any priority document(s) and all publications, including but not limited to patents and patent applications, cited in this specification are incorporated herein by reference as if each individual publication were specifically and individually indicated to be incorporated by reference herein and as though fully set forth herein. The invention includes all embodiments and variations substantially as hereinbefore described and with reference to the examples and drawings.