Pharmaceutical composition and method of manufacturing

• US 10,624,940 B2
• Filed: 03/20/2019
• Issued: 04/21/2020
• 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:
  US16/359,579
• Publication Number:
  US 20190209633A1
• Time in Patent Office: 398 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 and second concentrate of Cannabis sativa, Cannabis indica, or a combination thereof, the process comprising:

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

20°

C. to about 70°

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

(b) removing the supercritical fluid solvent system comprising carbon dioxide from the extract of Cannabis sativa, Cannabis indica, or a combination thereof;

wherein,

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

the first fractional supercritical fluid extraction comprising carbon dioxide is carried out such that contacting of the Cannabis sativa, Cannabis indica, or a combination thereof provides a first concentrate; and

the second fractional supercritical fluid extraction comprising carbon dioxide is carried out such that contacting of the Cannabis sativa, Cannabis indica, or a combination thereof provides a second concentrate;

if the first concentrate is enriched with tetrahydrocannabinol then the second concentrate is enriched with cannabidiol;

if the first concentrate is enriched with cannabidiol then the second concentrate is enriched with tetrahydrocannabinol;

each of the first and the second fractional supercritical fluid extractions comprising carbon dioxide are carried out at a pressure of about 750 to about 3,000 psi, a temperature of about −

20°

C. to about 70°

C., and for a period of time of about 1 to about 8 hours, provided the first and the second fractional supercritical fluid extractions are carried out;

(i) at a different temperature, (ii) at a different pressure, (iii) with a different solvent system comprising carbon dioxide, or (iv) a combination thereof; and

one of the fractional supercritical fluid extractions comprising carbon dioxide is carried out at a temperature of at least 30°

C.

2. The process of claim 1, wherein the first fractional supercritical fluid extraction is carried out in a solvent system that comprises carbon dioxide and a second solvent selected from the group consisting of hydrogen, neon, nitrogen, argon, methane, ethane, propane, ammonia, water, xenon, methanol, ethanol, 1-propanol, 2-propanol, 1-hexanol, 2-methoxy ethanol, tetrahydrofuran, 1,4-dioxane, acetonitrile, methylene chloride, dichloroethane, chloroform, ethyl acetate, propylene carbonate, N,N-dimethylaceamide, dimethyl sulfoxide, formic acid, carbon disulfide, acetone, toluene, hexanes, pentanes, trifluoromethane, nitrous oxide, sulfur hexafluroide, butane, isobutane, ethyl ether, benzotrifluoride, p-(chlorophenyl)trifluoromethane, chlorofluorocarbon, hydrofluorocarbon, and combinations thereof.

3. The process of claim 1, wherein relative to the Cannabis sativa, Cannabis indica, or a combination thereof in step (a), the concentrate enriched with tetrahydrocannabinols contains at least about a 10% higher concentration of tetrahydrocannabinols.

4. The process of claim 1, wherein the second fractional supercritical fluid extraction is carried out in a solvent system that comprises carbon dioxide and a second solvent selected from the group consisting of hydrogen, neon, nitrogen, argon, methane, ethane, propane, ammonia, water, xenon, methanol, ethanol, 1-propanol, 2-propanol, 1-hexanol, 2-methoxy ethanol, tetrahydrofuran, 1,4-dioxane, acetonitrile, methylene chloride, dichloroethane, chloroform, ethyl acetate, propylene carbonate, N,N-dimethylaceamide, dimethyl sulfoxide, formic acid, carbon disulfide, acetone, toluene, hexanes, pentanes, trifluoromethane, nitrous oxide, sulfur hexafluroide, butane, isobutane, ethyl ether, benzotrifluoride, p-(chlorophenyl)trifluoromethane, chlorofluorocarbon, hydrofluorocarbon, and combinations thereof.

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 comprising carbon dioxide, wherein each different solvent system comprising carbon dioxide is selected from the group consisting of polar aprotic, polar protic, nonpolar aprotic, and nonpolar protic.

7. The process of claim 1, wherein relative to the Cannabis sativa, Cannabis indica, or a combination thereof in step (a), the Cannabis concentrate enriched with cannabidiol contains at least about a 10% higher concentration of cannabidiol.

8. The process of claim 1, further comprising purifying the first concentrate of Cannabis sativa, Cannabis indica, or a combination thereof by employing at least one of chromatography, adsorption, crystallization, distillation, liquid-liquid extraction, filtration, fractional distillation, precipitation, recrystallization, and sublimation.

9. The process of claim 1, further comprising purifying the second concentrate of Cannabis sativa, Cannabis indica, or a combination thereof by employing at least one of chromatography, adsorption, crystallization, distillation, liquid-liquid extraction, filtration, fractional distillation, precipitation, recrystallization, and sublimation.

10. The process of claim 1, wherein relative to the Cannabis sativa, Cannabis indica, or a combination thereof in step (a), the first concentrate contains a lower concentration of a component selected from the group consisting of:

(i) cannabinol,

(ii) alkaloids,

(iii) terpenes,

(iv) terpenoids,

(v) cannabinoid acids,

(vi) hemp oil, and

(vii) combinations thereof.

11. The process of claim 1, wherein relative to the Cannabis sativa, Cannabis indica, or a combination thereof in step (a), the first concentrate contains at least a 10% lower concentration of a component selected from the group consisting of:

(i) cannabinol,

(ii) alkaloids,

(iii) terpenes,

(iv) terpenoids,

(v) cannabinoid acids,

(vi) hemp oil, and

(vii) combinations thereof.

12. The process of claim 1, wherein relative to the Cannabis sativa, Cannabis indica, or a combination thereof in step (a), the second concentrate contains a lower concentration of a component selected from the group consisting of:

(i) cannabinol,

(ii) alkaloids,

(iii) terpenes,

(iv) terpenoids,

(v) cannabinoid acids,

(vi) hemp oil, and

(vii) combinations thereof.

13. The process of claim 1, wherein relative to the Cannabis sativa, Cannabis indica, or a combination thereof in step (a), the second concentrate contains at least a 10% lower concentration of a component selected from the group consisting of:

(i) cannabinol,

(ii) alkaloids,

(iii) terpenes,

(iv) terpenoids,

(v) cannabinoid acids,

(vi) hemp oil, and

(vii) combinations thereof.

14. The process of claim 1, wherein the first fractional supercritical fluid extraction comprising carbon dioxide is carried out with carbon dioxide as the only solvent.

15. The process of claim 1, wherein the second fractional supercritical fluid extraction comprising carbon dioxide is carried out with carbon dioxide as the only solvent.

16. The process of claim 1, wherein the concentrate enriched with tetrahydrocannabinol comprises at least about 90 wt. % tetrahydrocannabinol.

17. The process of claim 1, wherein the concentrate enriched with cannabidiol comprises at least about 90 wt. % cannabidiol.

18. A process for obtaining a first and second concentrate of Cannabis sativa, Cannabis indica, or a combination thereof, the process comprising:

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

20°

C. to about 70°

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

(b) removing the supercritical fluid solvent system comprising carbon dioxide from the extract of Cannabis sativa, Cannabis indica, or a combination thereof;

wherein,

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

the first fractional supercritical fluid extraction comprising carbon dioxide is carried out such that contacting of the Cannabis sativa, Cannabis indica, or a combination thereof provides a first concentrate; and

the second fractional supercritical fluid extraction comprising carbon dioxide is carried out such that contacting of the Cannabis sativa, Cannabis indica, or a combination thereof provides a second concentrate;

if the first concentrate is enriched with tetrahydrocannabinol then the second concentrate is enriched with cannabidiol;

if the first concentrate is enriched with cannabidiol then the second concentrate is enriched with tetrahydrocannabinol;

each of the first and the second fractional supercritical fluid extractions comprising carbon dioxide are carried out at a pressure of about 750 to about 3,000 psi, a temperature of about −

20°

C. to about 70°

C., and for a period of time of about 1 to about 8 hours, provided the first and the second fractional supercritical fluid extractions are carried out;

(i) at a different temperature, (ii) at a different pressure, (iii) with a different solvent system comprising carbon dioxide, or (iv) a combination thereof;

in step (a), each of the first concentrate and the second concentrate independently contain at least a 10% lower concentration of a component selected from the group consisting of;

(i) cannabinol, (ii) alkaloids, (iii) terpenes, (iv) terpenoids, (v) cannabinoid acids, (vi) hemp oil, and (vii) combinations thereof; and

one of the fractional supercritical fluid extractions comprising carbon dioxide is carried out at a temperature of at least 30°

C.

19. The process of claim 18, wherein the first fractional supercritical fluid extraction comprising carbon dioxide is carried out with carbon dioxide as the only solvent;

and the second fractional supercritical fluid extraction comprising carbon dioxide is carried out with carbon dioxide as the only solvent.

20. The process of claim 18, wherein the concentrate enriched with tetrahydrocannabinol comprises at least about 90 wt. % tetrahydrocannabinol and the concentrate enriched with cannabidiol comprises at least about 90 wt. % cannabidiol.