Pharmaceutical composition and method of manufacturing

• US 10,238,705 B2
• Filed: 11/06/2015
• Issued: 03/26/2019
• Est. Priority Date: 04/17/2014
• Status: Active Grant

• Current Assignee: Avenir Wellness Solutions Incorporated
• Original Assignee: CURE Pharmaceutical Holding Corp.
• Inventors: Speier, Gary J.
• Primary Examiner(s): Meller, Michael V
• Application Number:
  US14/934,940
• Publication Number:
  US 20160074451A1
• Time in Patent Office: 1,236 Days
• Field of Search: 424725
• CPC Class Codes: A61K 2236/00 Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 36/00 Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines antigens from pollen A61K39/36
• CPC Class Codes: A61K 36/185 Magnoliopsida (dicotyledons)
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: B01D 11/0407 the supercritical fluid acting as solvent for the solute

Abstract

The present invention provides for methods of obtaining an extract of Cannabis plant material as well as subsequent processing of the extract to provide a concentrate of Cannabis. The present invention also provides for pharmaceutical dosage forms (e.g., oral thin films and transdermal patches) that include the concentrate (or extract) of Cannabis, as well as methods of medical treatment that include administering the pharmaceutical dosage forms.

Claims

1. A process for obtaining a first concentrate of Cannabis sativa, Cannabis indica, or a combination thereof, enriched with tetrahydrocannabinols and a second concentrate of Cannabis sativa, Cannabis indica, or a combination thereof enriched with cannabidiols, the process comprising:

(a) contacting plant material comprising Cannabis sativa, Cannabis indica, or a combination thereof, with a supercritical fluid solvent system, at a pressure of about 750-3,000 psi, and at a temperature of about −

20°

C.-70°

C., to provide an extract of Cannabis sativa, Cannabis indica, or a combination thereof; and

(b) removing the supercritical fluid solvent system from the extract;

wherein the (a) contacting of the plant material comprising Cannabis sativa, Cannabis indica, or a combination thereof, with the supercritical fluid solvent system and the (b) removing the supercritical fluid solvent system, is carried out two or more times, such that the process is a fractional supercritical fluid extraction;

wherein a first fractional supercritical fluid extraction is carried out such that (a) contacting of the plant material comprising Cannabis sativa, Cannabis indica, or a combination thereof, with the supercritical fluid solvent system is carried out at a pressure of about 750-1,500 psi and a temperature of about −

20°

C. to about 70°

C. for a period of time of about 1-8 hours, to provide a first concentrate enriched with tetrahydrocannabinols;

wherein a second fractional supercritical fluid extraction is carried out such that (a) contacting of the plant material comprising Cannabis sativa, Cannabis indica, or a combination thereof, with the supercritical fluid solvent system is carried out at a pressure of about 1,500-3,000 psi and a temperature of about −

20°

C. to about 70°

C., for a period of time of about 1-8 hours, to provide a second concentrate enriched with cannabidiols,

wherein each of the fractional supercritical fluid extractions are carried out at different pressures, at different temperatures, or both,

wherein one of the fractional supercritical fluid extractions is carried out at about 55°

C.−

65°

C.

2. The method of claim 1, wherein the first fractional supercritical fluid extraction is carried out in a solvent system that comprises carbon dioxide (CO₂) and at least one of hydrogen (H₂), neon (Ne), nitrogen (N₂), argon (Ar), methane (CH₄), ethane (CH₃CH₃), propane (CH₃CH₂CH₃), ammonia (NH₃), water (H₂O), xenon (Xe), methanol, ethanol, 1-propanol, 2-propanol, 1-hexanol, 2-methoxy ethanol, tetrahydrofuran (THF), 1,4-dioxane, acetonitrile, methylene chloride, dichloroethane, chloroform, ethyl acetate, propylene carbonate, N,N-dimethylaceamide, dimethyl sulfoxide (DMSO), formic acid, carbon disulfide, acetone, toluene, hexanes, pentanes, trifluoromethane (Freon®

23), nitrous oxide (N₂O), sulfur hexafluroide (SF₆), butane (n-C₄H₁₀), isobutane (i-C₄H₁₀), ethyl ether ((C₂H₅)₂O), benzotrifluoride (C₆H₅CF₃), (p-chlorophenyl)trifluoromethane (ClC₆H₄CF₃), chlorofluorocarbon (CFC), hydrofluorocarbon (HFA), and HFA-134a (1,1,1,2-tetrafluoroethane).

3. The method of claim 1, wherein relative to the cannabis plant material, the first concentrate is enriched with tetrahydrocannabinols (THC), such that the first concentrate contains at least about a 10% higher concentration of tetrahydrocannabinols (THC).

4. The method of claim 1, wherein the second fractional supercritical fluid extraction is carried out in a solvent system that comprises carbon dioxide (CO₂) and at least one of hydrogen (H₂), neon (Ne), nitrogen (N₂), argon (Ar), methane (CH₄), ethane (CH₃CH₃), propane (CH₃CH₂CH₃), ammonia (NH₃), water (H₂O), xenon (Xe), methanol, ethanol, 1-propanol, 2-propanol, 1-hexanol, 2-methoxy ethanol, tetrahydrofuran (THF), 1,4-dioxane, acetonitrile, methylene chloride, dichloroethane, chloroform, ethyl acetate, propylene carbonate, N,N-dimethylaceamide, dimethyl sulfoxide (DMSO), formic acid, carbon disulfide, acetone, toluene, hexanes, pentanes, trifluoromethane (Freon®

23), nitrous oxide (N₂O), sulfur hexafluroide (SF₆), butane (n-C₄H₁₀), isobutane (i-C₄H₁₀), ethyl ether ((C₂H₅)₂O), benzotrifluoride (C₆H₅CF₃), (p-chlorophenyl)trifluoromethane (ClC₆H₄CF₃), chlorofluorocarbon (CFC), hydrofluorocarbon (HFA), and HFA-134a (1,1,1,2-tetrafluoroethane).

5. The process of claim 1, wherein each fractional supercritical fluid extraction is carried out with a different supercritical fluid solvent system.

6. The process of claim 1, wherein each fractional supercritical fluid extraction is carried out with a different supercritical fluid solvent system, each independently selected from:

(i) polar aprotic, (ii) polar protic, (iii) nonpolar aprotic, and (iv) nonpolar protic.

7. The process of claim 1, wherein each fractional supercritical fluid extraction is carried out with the same supercritical fluid solvent system.

8. The process of claim 1, wherein each fractional supercritical fluid extraction is carried out with the same supercritical fluid solvent system, selected from:

(i) polar aprotic, (ii) polar protic, (iii) nonpolar aprotic, and (iv) nonpolar protic.

9. The method of claim 1, wherein relative to the cannabis plant material, the cannabis concentrate is enriched with cannabidiol (CBD), such that the cannabis concentrate contains at least about a 10% higher concentration of cannabidiol (CBD).

10. The method of claim 1, further comprising purifying the first concentrate of cannabis employing at least one of chromatography, adsorption, crystallization, distillation, liquid-liquid extraction, filtration, fractional distillation, precipitation, recrystallization, and sublimation.

11. The method of claim 1, further comprising purifying the second concentrate of cannabis employing at least one of chromatography, adsorption, crystallization, distillation, liquid-liquid extraction, filtration, fractional distillation, precipitation, recrystallization, and sublimation.

12. The method of claim 1, wherein relative to the cannabis plant material, the first concentrate contains a lower concentration of at least one of (i)-(vi):

(i) cannabinol (CBN),

(ii) alkaloids,

(iii) terpenes,

(iv) terpenoids,

(v) cannabinoid acids, and

(vi) hemp oil.

13. The method of claim 1, wherein relative to the cannabis plant material, the first concentrate contains at least a 10% lower concentration of at least one of (i)-(vi):

(i) cannabinol (CBN),

(ii) alkaloids,

(iii) terpenes,

(iv) terpenoids,

(v) cannabinoid acids, and

(vi) hemp oil.

14. The method of claim 1, wherein relative to the cannabis plant material, the second concentrate contains a lower concentration of at least one of (i)-(vi):

(i) cannabinol (CBN),

(ii) alkaloids,

(iii) terpenes,

(iv) terpenoids,

(v) cannabinoid acids, and

(vi) hemp oil.

15. The method of claim 1, wherein relative to the cannabis plant material, the second concentrate contains at least a 10% lower concentration of at least one of (i)-(vi):

(i) cannabinol (CBN),

(ii) alkaloids,

(iii) terpenes,

(iv) terpenoids,

(v) cannabinoid acids, and

(vi) hemp oil.

16. The process of claim 1, wherein the first fractional supercritical fluid extraction is carried out with carbon dioxide (CO₂) as the sole solvent.

17. The process of claim 1, wherein the second fractional supercritical fluid extraction is carried out with carbon dioxide (CO₂) as the sole solvent.

18. The process of claim 1, wherein the first concentrate is enriched with tetrahydrocannabinols (THCs), such that the first concentrate comprises at least about 90 wt. % tetrahydrocannabinols (THCs).

19. The process of claim 1, wherein the second concentrate is enriched with cannabidiols (CBDs), such that the second concentrate comprises at least about 90 wt. % cannabidiols (CBDs).