Cannabidiol compositions having modified cannabinoid profiles
Inventors
HALLOW, Daniel M. • He, Jun • Dobish, Mark C. • Petrovic, Denis • Mkrtchyan, Gnel
Assignees
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Publication Number
US-12144795-B2
Publication Date
2024-11-19
Expiration Date
Abstract
The present disclosure relates to the preparation of a highly pure cannabidiol compound by a novel synthesis route. The cannabidiol compound can be prepared by an acid-catalyzed reaction of a di-halo olivetol with menthadienol, followed by two crystallization steps. The highly pure cannabidiol compound is produced in high yield, stereospecificity, or both, and shows exceedingly low levels of Δ-9-tetrahydrocannabinol at the time of preparation and after storage.
Core Innovation
The disclosure relates to cannabidiol compositions and formulations in which delta-9-tetrahydrocannabinol is present in an amount less than 10 ppm. The disclosed compositions include stable cannabidiol and delta-9-tetrahydrocannabinol combinations, including compositions in which delta-9-tetrahydrocannabinol remains below 10 ppm upon storage for 2 years or less. The disclosure also characterizes cannabidiol as crystalline, including crystalline polymorph Form A, for use in compositions and formulations with controlled delta-9-tetrahydrocannabinol content.
A further aspect provides cannabidiol compositions with additional quantitative purity constraints, including a cannabidiol to delta-9-tetrahydrocannabinol ratio less than 1:0.0001 as measured by UPLC. The disclosure includes pharmaceutical formulations comprising cannabidiol, delta-9-tetrahydrocannabinol present at less than 10 ppm, and pharmaceutically acceptable excipient, including formulations provided in particular physical forms.
The disclosure also provides methods to prepare and recrystallize cannabidiol compositions with delta-9-tetrahydrocannabinol content below 10 ppm. Another aspect reports crystallization and isolation of cannabidiol crystalline material, including recrystallization from a mixture of cannabinoids using isooctane and seeding with (−)-cannabidiol, to obtain a crystalline cannabidiol composition with delta-9-tetrahydrocannabinol below 10 ppm.
Claims Coverage
The independent claims cover five inventive feature groupings: compositions with delta-9-tetrahydrocannabinol below 10 ppm, stable compositions maintaining that limit after storage, compositions defined by a cannabidiol-to-delta-9-tetrahydrocannabinol ratio measured by UPLC, pharmaceutical formulations with pharmaceutically acceptable excipient, and methods for preparing and recrystallizing cannabidiol compositions to achieve delta-9-tetrahydrocannabinol below 10 ppm.
Controlled THC in cannabidiol composition
A composition comprising cannabidiol and delta-9-tetrahydrocannabinol wherein delta-9-tetrahydrocannabinol is present in an amount less than 10 ppm.
Stable controlled-THC cannabidiol composition
A stable composition comprising cannabidiol and delta-9-tetrahydrocannabinol, wherein delta-9-tetrahydrocannabinol is present in an amount less than 10 ppm upon storage for 2 years or less.
Ultra-low THC ratio by UPLC
A composition comprising cannabidiol and less than 10 ppm delta-9-tetrahydrocannabinol, wherein the ratio of cannabidiol to delta-9-tetrahydrocannabinol is less than 1:0.0001 as measured by UPLC.
Pharmaceutical formulation with controlled THC
A formulation comprising cannabidiol, delta-9-tetrahydrocannabinol wherein delta-9-tetrahydrocannabinol is present in an amount less than 10 ppm, and a pharmaceutically acceptable excipient.
Crystallization and recrystallization preparation to controlled-THC cannabidiol
A method of preparing a cannabidiol composition comprising contacting di-halo olivetol with menthadienol in the presence of a protic acid catalyst to prepare di-halo cannabidiol, contacting the di-halo cannabidiol with a reducing agent to prepare a first cannabidiol composition, contacting the first cannabidiol composition with a first solvent, crystallizing a second cannabidiol composition from said solvent, and recrystallizing crystalline cannabidiol composition having less than 10 ppm delta-9-tetrahydrocannabinol from a second solvent.
Seeded isooctane recrystallization from cannabinoid mixture
A method of recrystallizing cannabidiol from a mixture of cannabinoids to prepare a composition comprising cannabidiol and less than 10 ppm delta-9-tetrahydrocannabinol, the method comprising contacting said mixture of cannabinoids with isooctane to form a solution, heating said solution, cooling the solution, seeding said solution with (−)-Cannabidiol to prepare a suspension, allowing said suspension to warm with stirring, cooling the suspension, separating a solid material from said suspension, washing solid material with isooctane, and drying the solid material to obtain a crystalline composition.
The claims cover cannabidiol-containing compositions and formulations where delta-9-tetrahydrocannabinol is kept below 10 ppm, including stability over up to 2 years, with an additional analytical constraint requiring a cannabidiol-to-delta-9-tetrahydrocannabinol ratio less than 1:0.0001 measured by UPLC. The claim set also includes method claims directed to preparation and recrystallization steps that produce crystalline cannabidiol meeting the <10 ppm delta-9-tetrahydrocannabinol requirement.
Stated Advantages
Maintenance of low delta-9-tetrahydrocannabinol levels (less than 10 ppm) in a stable composition upon storage for 2 years or less.
High quantitative purity expressed by a cannabidiol-to-delta-9-tetrahydrocannabinol ratio less than 1:0.0001 as measured by UPLC.
Crystalline cannabidiol composition characterized and obtained with delta-9-tetrahydrocannabinol content less than 10 ppm.
Documented Applications
Pharmaceutical formulations comprising cannabidiol and delta-9-tetrahydrocannabinol at less than 10 ppm together with a pharmaceutically acceptable excipient.
Preparation of a cannabidiol composition and recrystallization from a mixture of cannabinoids to obtain a crystalline cannabidiol composition having less than 10 ppm delta-9-tetrahydrocannabinol.
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