SYSTEMES DE DELIVRANCE AUX VOIES GASTRO-INTESTINALES SOUS FORME ORALE LIQUIDE DE CANNABINOIDES PURIFIES A L`AIDE DE LA VITAMINE E TPGS

LIQUID ORAL GASTROINTESTINAL DELIVERY SYSTEM OF PURIFIED CANNABINOIDS USING VITAMIN E TPGS

Abrégé anglais

This disclosure relates to new methods for delivering an aqueous cannabinoid
solution orally for
absorption through the gastrointestinal tract. The composition includes 1)
active forms of
cannabinoids and/or purified cannabinoids, 2) Vitamin E TPGS and 3) Water. The
self-emulsifying composition decreases Hepatic First Pass Metabolism and
increases
absorption of cannabinoids. The composition increases shelf stability and even
distribution of
Cannabinoids throughout the solution, improving upon previous oral, aqueous
cannabinoid
delivery solutions.

Revendications

Claims
WHAT IS CLAIMED IS:
1. A method of formulating an aqueous cannabis concentrate. The method
comprising: 1) a
purified Cannabinoid, 2) Vitamin E TPGS to produce a concentrate, dispersing
the
concentrate into an aqueous solution, wherein the concentrate becomes water
soluble.
2. A composition, comprising: a first purified cannabinoid; Vitamin E TPGS and
Water.
The composition of claim 1 , comprising a ratio of Vitamin E TPGS to the
purified
cannabinoid of about 1000:1 to about 5:1 by percent mass.
3. The composition of claim 1 , comprising water.
4. The composition of claim 1 , comprising Vitamin E TPGS.
5. The composition of claim 4, comprising a micelle.
6. The composition of claim 1 , comprising a purified Cannabinoid 0-10% mass
7. A method of claim 1, wherein a purified cannabinoid is heated to 40C to
100C
8. A method of claim 1, wherein Vitamin E TPGS is heated to 40C to 100C
9. A method of claim 1, A purified Cannabinoid and Vitamin E TPGS are combined
until
homogeneous for 1 minute to 1 hour.
10. A method of claim 1, heating water to 50C to 100C
11. A method of claim 14, where cliam 14 and 15 are mixed for 15 minutes to 24
hours
12. A method of claim 14, where the particle size is 20nm to 250nm
13. The method of claim 14, wherein the component is a liquid, or the
component is a gel
having a viscosity between 0.3 centipoise and 250,000 centipoise.

Description

Classification
A61K9/107 - Emulsions/ Micelles
A61K31/355 - Tocopherols
A61K9/4858 - Organic compounds
A61K9/08 - Solutions
Synonyms
Vitamin E TPGS
TPGS
d-a tocopheryl polyethylene glycol 1000 succinate
Tocopheryl Polyethylene Glycol Succinate.
Description
Technical Field
This disclosure relates to the cannabis industry. In particular, this
disclosure relates to
water-soluble cannabinoid formulations, including methods for creating said
water-soluble
cannabinoid formulations.
This disclosure relates generally to a delivery system to improve the
administration of
cannabinoids and standardized Cannabis extracts through a self-emulsifying
drug delivery
system, which optimizes cannabinoid dissolution properties, decreases hepatic
first-pass
metabolism and increases absorption, thereby enhancing bioavailability through
the
gastrointestinal tract.
Background
The word "cannabis" refers to a genus of flowering plants. Plants of genus
cannabis include
several species, including Cannabis Sativa, Cannabis Indica, and Cannabis
Ruderalis.
Can nabinoids are of particular interest for research and commercialization.
Most extractions of
cannabis plant matter aim to extract cannabinoids, particularly
tetrahydrocannabinol (THC) and
Cannabidiol(CBD). THC is useful for relieving pain, treating glaucoma and
relieving nausea.
THC is also gaining immense popularity as a recreational drug substance.
Usually,
cannabinoids are extracted from the cannabis plant as part of a crude mixture,
further refined
and combined with other chemical compounds found in the cannabis plant. Other
Cannabinoids
of interest are CBG (Cannabigerol) and CBN (Cannabinol).
Current methods of administration cannabinoids fail to take full advantage of
cannabinoid
properties. For example, burning plant matter and inhaling the vapour does not
allow for
selection of certain cannabinoids for their certain desired benefit. One can
choose a plant with
certain known properties, e.g., THC content, but there is still little to no
control over selecting
individual cannabinoids. Inhaling smoke also leads to many harmful and toxic
compounds
introduced into the body. Current oral liquid delivery technologies have slow
onset to due poor
absorption, long offset times due to hydrophobic nature of cannabinoids and
have a bitter taste.
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There exists a need for new cannabinoid formulations. In particular, there
exists a need for
water-soluble cannabinoid formulations. Additionally, there exists a need for
methods for
producing aqueous cannabinoid formulations. Furthermore, there exists a need
for making
formulations with increased permeability into the bloodstream. There also
exists a need for
cannabis formulations which provide increased bioavailability of cannabinoids.
This offers a
faster onset time for patients and more accurate dosing for recreational
consumers.
The oral liquid delivery technology allows the hydrophobic nature of cannabis
oil and distillate to
be altered into a hydrophilic state which improves flavour profile, absorption
time and in a
precise dosing mechanism.
Detailed Description
Unless specifically indicated otherwise, all technical and scientific terms
used herein have the
same meaning as commonly understood by those of ordinary skill in the art to
which this
invention belongs. In addition, any method or material similar or equivalent
to a method or
material described herein can be used in the practice of the present
invention. For purposes of
the present invention, the following terms are defined. The term "cannabis"
refers to plants of
the genus cannabis, including cannabis sativa, cannabis indica, and cannabis
ruderalis.
The term "cannabinoid" refers to a chemical compound that shows direct or
indirect activity at a
cannabinoid receptor. There are two main cannabinoid receptors, CNR1 (also
known as CBI)
and CNR2 (also known as CB2). Other receptors that research suggests have
cannabinoid
activity include the GPR55, GPR18, and TRPVI receptors. The term
"phytocannabinoid" refers
to cannabinoids that occur in a plant species or are derived from cannabinoids
occurring in a
plant species. Examples of cannabinoids include, but are not limited to,
tetrahydrocannabinol
(THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG),
cannabichromene (CBC),
cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV),
cannabidivarin
(CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), and cannabigerol
monomethyl ether (CBGM).tetrahydrocannabinol, A9-tetrahydrocannabinol(THC), A8-
tetrahydrocannabinol, standardized marijuana extracts, A8-tetrahydrocannabinol-
DM H, tetrahydrocannabinol propyl propyl analogue (THCV), 11 -hydroxy-
tetrahydrocannabinol, 11-nor-9-
carboxy-tetrahydrocannabinol, 5'-azido-A8-tetrahydrocannabinol, AMG-1, AMG-3,
AM411,
AM708, AM836, AM855, AM919, AM926, AM938, cannabidiol(CBD), cannabidiol propyl
analogue(CBDV), cannabinol (CBN), cannabichromene (CBC), cannabichromene
propyl
analogue, cannabigerol (CBG), cannabicyclol (CBL), cannabielsoin (CBE),
cannabinodiol
(CBDL), and cannabitriol (CBTL), CF 47497, CF 55940, CF 55244, CF 50556, CT-3
or IP-751
(ajulemic acid), dimethylheptyl HHC, HU-210, HU-211, HU-308, WIN 55212-2,
desacetyl-L-
nantradol, dexanabinol, JWH-051, JWH-133, levonantradol, L-759633, nabilone, 0-
1184,
cannabicyclohexanol (CP-47,497 C8 homolog), 10-hydroxycannabidiol,
l',2',3',4',5'-
pentanorcannabino1-3-carboxylic acid, l'-hydroxycannabinol, 11-
hydroxycannabinol, 9- carboxy-1
1-norcannabinol, l'-oxocannabino1,11-nor-A8-THC-9-carboxylic acid, 2'-carboxy-
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3',4',5'-trinor-A9-THC, 5'-carboxy-A9-THC, 9-carboxy-11-nor-A9-THC, 9-carboxy-
II-nor-A8- THC,
[(6aR,10aR)-3-[(IS,2R)-1,2-dimethylheptyl]-6a,7,10,10a-tetrahydro-6, 6,9-
trimethy1-6H-
dibenzo[b,d]pyran-l-ol], 9-carboxy-1 1-nor- (2 or 4)-chloro-A8-THC, 8a-II-
dihydroxy-A9-THC, 8[3-1
I-Dihydroxy-A9-THC, 5'-Dimethylamino-A8-THC, 11-hydroxy-A9-THC, l'-hydroxy-A9-
THC
(Isomer B), I 1-hydroxy-A8-THC, 2'-hydroxy-A9-THC, 3'-hydroxy-A9-THC, 4'-
hydroxy-A9- THC,
5'-hydroxy-1i9-THC, 8a-hydroxy-A9-THC, 8I3-hydroxy-A9-THC, 5'-methylamino-A8-
THC,
5'-N-methyl-N-4-(7-nitrobenzofurazano)amino-A8-THC, (-)-trans-A8-THC, 5'-
trimethylammonium-A8-THC phenolate, 5'-Trimethylammonium-11-hydroxy-A8-THC
phenolate,
and mixtures thereof;
The term "distillate" refers to a solution that has been concentrated by any
known means of
evaporation or distillation of the cannabis plant that is in a purified state.
As used herein, the term "purified" means isolated from the plant using
chromatography,
distillation, extractions, or similar technique resulting in a greater than
60% purity. In some
embodiments the "purified" compositions disclosed herein are greater than 70%
purity. In some
embodiments the "purified" compositions disclosed herein are greater than 80%
purity. In some
embodiments the "purified" compositions disclosed herein are greater than 90%
purity.
0029] THC/CBD: 0:1 - 1:0- 1:1, 2:1, 3:1, 4:1, 5:1, 10:1, 20:1 etc.,
[0030] CBD/THC:0:1 - 1:0- 1:1, 2:1, 3:1, 4:1, 5:1, 10:1, 20:1 etc.,
[0031] THC/CBN:0:1 - 1:0- 1:1, 2:1, 3:1, 4:1, 5:1, 10:1, 20:1 etc.,
[0032] CBN/THC: 0:1 - 1:0- 1:1, 2:1, 3:1, 4:1, 5:1, 10:1, 20:1 etc.,
[0033] CBD/CBN:0:1 - 1:0- 1:1, 2:1, 3:1, 4:1, 5:1, 10:1, 20:1 etc.,
[0034] CBN/CBD: 0:1- 1:0- 1:1, 2:1, 3:1, 4:1, 5:1, 10:1, 20:1 etc.,
[0035] THC/CBD/CBN: 1-99% THC: 1-99% CBD : 1-99% CBN.
The term "vitamin E" refers to a group of compounds that include both
tocopherols and
tocotrienols including, but not limited to a-tocopherol, [3-tocopherol, y-
tocopherol, 6- tocopherol,
a-tocotrienol, f3-tocotrienol, y-tocotrienol, 6-tocotrienol, salts thereof,
and combinations thereof.
Vitamin E can be obtained from sources including, but not limited, to
soybeans, sunflowers, and
combinations thereof.
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Disclosed herein are new cannabinoid formulations, including water-soluble
cannabinoid
formulations. In one embodiment, the formulations disclosed herein are used
for creating other
new formulations. In one embodiment, the formulations disclosed herein are
soluble in other
liquids, e.g., aqueous liquids such as juices, soft drinks, coffee, tea, etc.
and can be used as an
active ingredient in dry foods.
In some embodiments, the method further comprises mixing a quantity of vitamin
E with the
extract to produce a cannabis oil composition. Disclosed herein are methods of
making
formulations with increased permeability into the bloodstream. Also disclosed
herein are
cannabis formulations, which provide increased bioavailability of
cannabinoids. Disclosed herein
is a new composition comprising a first purified cannabinoid and Vitamin E
TPGS.
Example 1
The following examples illustrate certain aspects of the above-described
invention. They should
not be read as limiting the full scope of the invention.
The cannabis distillate and vitamin E TPGS is heated to 600 for 15 minutes
separately and then
combine until homogenous at 65C. The vitamin E is 4 parts to one part of
cannabis oil. Water is
then brought to 70C. The mixture of purified cannabis and Vitamin E TPGS is
than slowly added
to the water while stirring, continuing to stir until cloudy dispersion
becomes clear while
maintaining a temperature above 65C. Remove heat and continue to stir at room
temperature
for 2 hours to ensure complete uniformity.
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