Pharmaceutical composition and method of manufacturing

• US 9,044,390 B1
• Filed: 04/17/2014
• Issued: 06/02/2015
• Est. Priority Date: 04/17/2014
• Status: Active Grant

• Current Assignee: Avenir Wellness Solutions Incorporated
• Original Assignee: Gary J. Speier
• Inventors: Speier, Gary J.
• Primary Examiner(s): MELLER, MICHAEL V
• Application Number:
  US14/255,296
• Time in Patent Office: 411 Days
• Field of Search: 424/725
• US Class Current: 1/1
• 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. A process for obtaining a concentrate of Cannabis sativa or Cannabis indica, the process comprising:

(a) contacting Cannabis sativa or Cannabis indica plant material with a 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 an extract of Cannabis sativa or Cannabis indica; and

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

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

wherein each contacting of the Cannabis sativa or Cannabis indica with a supercritical fluid solvent system independently occurs at a pressure between about 750 psi and 25,000 psi, and independently occurs at a temperature between about −

15°

C. and 200°

C.;

wherein at least one of the supercritical fluid extractions is carried out at a temperature of at least about 80°

C.; and

wherein each supercritical fluid solvent system independently comprises carbon dioxide (CO₂) and optionally one or more additional solvents and optionally one or more co-solvents, selected from the group consisting 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 hexafluoroide (SF₆), butane (n-C₄H10), isobutane (i-C₄H₁₀), ethyl ether ((C₂H₅)₂O), benzotrifluoride (C₆H₅CF₃), (p-chlorophenyl) trifluoromethane (ClC₆H₄CF₃), chlorofluorocarbon (CFC), hydrofluorocarbon (HFA), HFA-134a (1,1,1,2-tetrafluoroethane), and mixtures thereof.

2. The process of claim 1, wherein each pressure is independently selected from (i) 750-4,000 psi, (ii) 4,000-7,000 psi, and (iii) 7,000-25,000 psi.

3. The process of claim 1, wherein each fractional supercritical fluid extraction is carried out at a different pressure, each selected from (i) 750-4,000 psi, (ii) 4,000-7,000 psi, and (iii) 7,000-25,000 psi.

4. The process of claim 1, wherein each temperature is independently selected from (i) −

15-70°

C., (ii) 70-100°

C., and (iii) 100-200°

C., with the proviso that at least one of the supercritical fluid extractions is carried out at a temperature of at least about 80°

C.

5. The process of claim 1, wherein each fractional supercritical fluid extraction is carried out at a different temperature, each selected from (i) −

15-70°

C., (ii) 70-100°

C., and (iii) 100-200°

C., with the proviso that at least one of the supercritical fluid extractions is carried out at a temperature of at least about 80°

C.

6. The process of claim 1, wherein each fractional supercritical fluid extraction is independently carried out employing a supercritical fluid solvent system which is:

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

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

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

8. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica comprises at least one of:

cannabinol (CBN),

cannabinolic acid (CBNA),

Δ

(9)-tetrahydrocannabinol (Δ

(9)-THC),

Δ

(9)-tetrahydrocannabinolic acid (Δ

(9)-THCA),

Δ

(9)-cannabidiol (Δ

(9)-CBD),

Δ

(9)-tetrahydrocannabidiolic acid (Δ

(9)-CBDA),

Δ

(8)-tetrahydrocannabinol (Δ

(8)-THC),

Δ

(8)-tetrahydrocannabinolic acid (Δ

(8)-THCA),

Δ

(8)-tetrahydrocannabidiol (Δ

(8)-CBD),

Δ

(8)-tetrahydrocannabidiolic acid (Δ

(8)-CBDA),

Δ

(9)-tetrahydrocannabivarin (Δ

(9)-THV),

cannabigerol (CBG),

cannabigerolic acid (CBGA),

cannabichromene (CBC),

cannabichromenic acid (CBCA),

cannabicyclol (CBL),

cannabicyclolic acid (CBLA),

β

-caryophyllene epoxide,

mentha-1,8(9)-dien-5-ol,

pulegone,

limonene,

limonene oxide,

α

-terpinene,

terpinen-4-ol,

carvacrol,

carvone,

1,8-cineole,

p-cymene,

fenchone,

pulegone-1,2epoxide,

β

-myrcene,

cannaflavin A, and

cannaflavin B.

9. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica, relative to the Cannabis sativa or Cannabis indica plant material, is at least partially purified from at least one of terpenes, alkaloids, hemp oil, and cannabinoid acids.

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

11. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica comprises Δ

(9)-tetrahydrocannabinol (Δ

(9)-THC).

12. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica comprises Δ

(9)-tetrahydrocannabinolic acid (Δ

(9)-THCA).

13. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica comprises Δ

(9)-cannabidiol (Δ

(9)-CBD).

14. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica Δ

(9)-tetrahydrocannabidiolic acid (Δ

(9)-CBDA).

15. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica comprises Δ

(8)-tetrahydrocannabinol (Δ

(8)-THC).

16. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica comprises Δ

(8)-tetrahydrocannabinolic acid (Δ

(8)-THCA).

17. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica comprises Δ

(8)-tetrahydrocannabidiol (Δ

(8)-CBD).

18. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica comprises Δ

(8)-tetrahydrocannabidiolic acid (Δ

(8)-CBDA).

19. The process of claim 1, wherein the concentrate of Cannabis sativa or Cannabis indica comprises Δ

(9)-tetrahydrocannabivarin (Δ

(9)-THV).

20. The process of claim 1, wherein any one or more supercritical fluid solvent system independently comprises an additive selected from the group consisting of methanol, ethanol, 1-propanol, 2-propanol, 1-hexanol, 2-methoxy ethanol, tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, ammonia, chloroform, propylene carbonate, N,N-dimethylaceamide, dimethyl sulfoxide, formic acid, water, carbon disulfide, acetone, propane, toluene, hexanes, pentanes, C₆H₅CF₃, p-ClC₆H₄CF₃, and mixtures thereof.