Pharmaceutical composition and method of manufacturing

• US 10,092,611 B1
• Filed: 05/24/2018
• Issued: 10/09/2018
• 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:
  US15/988,484
• Publication Number:
  US 20180264059A1
• Time in Patent Office: 138 Days
• Field of Search: 424725
• CPC Class Codes: A61K 2236/37 Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
• 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 11/0203 with a supercritical fluid

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. An oral dry laminated thin film consisting essentially of:

a) a hydrophilic polymer; and

b) a cannabis concentrate;

wherein the cannabis concentrate is obtained from a fractional supercritical fluid extraction of cannabis;

wherein relative to the cannabis, the cannabis concentrate is enriched with cannabidiol, such that the cannabis concentrate has at least about a 10% higher concentration of cannabidiol than in the cannabis;

wherein relative to the cannabis, the cannabis concentrate has at least about a 10% lower concentration of tetrahydrocannabinol than in the cannabis;

wherein the oral dry laminated thin film is capable of disintegrating within about 60 seconds when placed in the mouth of a human.

2. The thin film of claim 1, wherein relative to the cannabis, the cannabis concentrate has 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.

3. The thin film of claim 1, wherein relative to the cannabis, the cannabis concentrate is enriched with cannabidiol (CBD), such that the cannabis concentrate has at least about a 10% higher concentration of cannabidiol (CBD).

4. The thin film of claim 1, wherein the cannabis concentrate is obtained from a fractional supercritical fluid extraction (FSFE) of cannabis that consists essentially of:

(a) contacting cannabis with a first supercritical fluid solvent system at a pressure between about 750 psi and 25,000 psi, and at a temperature between about −

15°

C. and 200°

C., to provide a first extract of cannabis and a first extracted cannabis;

(b) removing the first supercritical fluid solvent system from the first extract of cannabis to provide a first concentrate of cannabis;

(c) contacting the first extracted cannabis with a second supercritical fluid solvent system at a pressure between about 750 psi and 25,000 psi, and at a temperature between about −

15°

C. and 200°

C., to provide a second extract of cannabis and a second extracted cannabis; and

(d) removing the second supercritical fluid solvent system from the second extract of cannabis to provide a second concentrate of cannabis.

5. The thin film of claim 3, wherein the first fractional supercritical fluid extraction is carried out in a solvent system that is 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).

6. The thin film of claim 3, wherein the second fractional supercritical fluid extraction is carried out in a solvent system that is 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).

7. The thin film of claim 3, wherein the contacting the cannabis with the first supercritical fluid solvent system and the contacting the first extracted cannabis with the second supercritical fluid solvent system are carried out:

(a) at the same temperature and different pressures;

(b) at different temperatures and the same pressure;

or

(c) at different temperatures and different pressures.

8. The thin film of claim 3, wherein the pressure employed in contacting cannabis with a first supercritical fluid solvent system is greater than the pressure employed in contacting the first extracted cannabis with a second supercritical fluid solvent system.

9. The thin film of claim 1, wherein the pressure employed in contacting cannabis with a first supercritical fluid solvent system is less than the pressure employed in contacting the first extracted cannabis with a second supercritical fluid solvent system.

10. The thin film of claim 3, wherein the temperature employed in contacting cannabis with a first supercritical fluid solvent system is greater than the temperature employed in contacting the first extracted cannabis with a second supercritical fluid solvent system.

11. The thin film of claim 3, wherein the temperature employed in contacting cannabis with a first supercritical fluid solvent system is less than the temperature employed in contacting the first extracted cannabis with a second supercritical fluid solvent system.

12. The thin film of claim 3, further consisting essentially of 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.

13. The thin film of claim 3, further consisting essentially of 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.

14. The thin film of claim 1, wherein the hydrophilic polymer is mucoadhesive.

15. The thin film of claim 1, wherein the hydrophilic polymer is a cellulose derivative, a natural gum, alginate, pectin, or combination thereof.

16. The thin film of claim 1, wherein the hydrophilic polymer is at least one of carboxymethyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone (povidone), sodium alginate, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyethylene glycols, carbopols, polycarbophils, carboxyvinyl copolymers, propylene glycol alginate, alginic acid, methyl methacrylate copolymers, tragacanth gum, guar gum, karaya gum, ethylene vinyl acetate, dimenthylpolysiloxanes, polyoxyalkylene block copolymers, pectin, chitosan, carrageenan, xanthan gum, gellan gum, locust bean gum, and hydroxyethylmethacrylate copolymers.

17. The thin film of claim 3, wherein the cannabis concentrate is obtained from the fractional supercritical fluid extraction (FSFE) of cannabis that further consists essentially of:

(e) contacting the second extracted cannabis with a third supercritical fluid solvent system at a pressure between about 750 psi and 25,000 psi, and at a temperature between about −

15°

C. and 200°

C., to provide a third extract of cannabis and a third extracted cannabis; and

(f) removing the third supercritical fluid solvent system from the third extract of cannabis to provide a third concentrate of cannabis.

18. The thin film of claim 1, wherein the cannabis concentrate is obtained from a fractional supercritical fluid extraction (FSFE) of cannabis that consists essentially of:

(a) contacting cannabis with a first supercritical fluid solvent system at a pressure between about 750 psi and 25,000 psi, and at a temperature between about −

15°

C. and 200°

C., to provide a first extract of cannabis and a first extracted cannabis;

(b) removing the first supercritical fluid solvent system from the first extract of cannabis to provide a first concentrate of cannabis;

(c) contacting the first extracted cannabis with a second supercritical fluid solvent system at a pressure between about 750 psi and 25,000 psi, and at a temperature between about −

15°

C. and 200°

C., to provide a second extract of cannabis and a second extracted cannabis; and

(d) removing the second supercritical fluid solvent system from the second extract of cannabis to provide a second concentrate of cannabis;

wherein the contacting the cannabis with the first supercritical fluid solvent system and the contacting the first extracted cannabis with the second supercritical fluid solvent system are carried out;

(i) at the same temperature and different pressures;

(ii) at different temperatures and the same pressure;

(iii) at different temperatures and different pressures;

or

(iv) with different supercritical fluid solvent systems.

19. The thin film of claim 1, having a moisture content of less than about 10 wt. % water.

20. The thin film of claim 1, which is an edible and pharmaceutically acceptable orally dissolvable thin film capable of adhering to mucosal tissue and capable of administering the cannabis concentrate via absorption in the mouth (buccally or sublingually), the stomach (gastrically), and/or via the small intestines (enterically).

21. The thin film of claim 1, having a thickness of about 0.1 mm to about 10 mm.

22. The thin film of claim 1, having a moisture content of less than about 15 wt. % water.