Note: Descriptions are shown in the official language in which they were submitted.
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COMPOSITIONS COMPRISING NON-CRYSTALLINE FORMS OF CANNABIDIOL
CROSS-REFERENCE TO RELATED APPLICATIONS
This patent application claims priority to U.S. Provisional Patent Application
No. 62/839,564,
filed April 26, 2019; U.S. Provisional Patent Application No. 62/845,231,
filed May 8, 2019; U.S.
Patent Application No. 16/408,428, filed May 9, 2019; U.S. Provisional Patent
Application No.
62/860,224, filed June 11, 2019; and U.S. Provisional Patent Application No.
62/942,442, filed
December 2, 2019, each of which is incorporated by reference in its entirety.
BACKGROUND
Cannabidiol exists as a crystalline solid at room temperature, which has a
melting point of 151
degrees Fahrenheit (66 degrees Celsius). Crystalline cannabidiol lacks robust
bioavailability, for
example, because the human body is incapable of melting it. The pharmaceutical
EPIDIOLEX
contains cannabidiol dissolved in sesame seed oil to increase bioavailability.
Consumers also vaporize and inhale cannabidiol to increase bioavailability.
Cannabidiol
crystallization confounds vaporization in electronic cigarettes and vaporizers
because
crystallization inhibits the flow of cannabidiol toward a heating element.
Prior art methods to
inhibit the crystallization of cannabidiol for use in electronic cigarettes
and vaporizers include the
dissolution of cannabidiol in organic solvents such as propylene glycol and
triglycerides. Organic
solvents dilute the cannabidiol, however, and present unknown health risks.
Improved cannabidiol
formulations are therefore desirable.
SUMMARY
Various aspects of this patent document relate to compositions comprising
liquid cannabidiol,
-- which have either a freezing point or a glass-liquid transition temperature
of less than the melting
point of pure cannabidiol. In preferred embodiments, the freezing point or the
glass-liquid
transition temperature is less than either 70 degrees Fahrenheit or 21 degrees
Celsius.
DETAILED DESCRIPTION
This patent document discloses that the melting point of cannabidiol can be
lowered¨or
eliminated¨by dissolving small amounts of specific solutes in liquid
cannabidiol. The melting
point of cannabidiol can be reduced to less than 70 degrees Fahrenheit (or
less than 21 degrees
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Celsius), for example, to provide concentrated cannabidiol compositions that
are liquids at room
temperature. This discovery allows novel products including concentrated
cannabidiol vape oil.
Various aspects of this patent document relate to a composition, comprising
(i) cannabidiol at a
concentration of at least 70 percent and no greater than 99.5 percent by mass,
and (ii) one or more
solutes selected from terpenes, terpene alcohols, terpenoids, and terpene
oxidation products at a
combined concentration of at least 0.5 percent and no greater than 30 percent
by mass, in which:
the one or more solutes comprise a terpene and a terpene oxidation product;
the terpene is
humulene; the terpene oxidation product is either bicyclohumuladiol,
tricyclohumuladiol,
tricyclohumuladiol II, humulenol II, humulene epoxide I, humulene epoxide II,
or humulene
epoxide III; the composition comprises the humulene and the terpene oxidation
product at a ratio
of at least 1:10 and no greater than 10,000:1 by mass; the cannabidiol is a
liquid; the one or more
solutes are dissolved in the cannabidiol; and either (i) the composition has a
freezing point of less
than 21 degrees Celsius, and the composition lacks a glass-liquid transition
temperature, or (ii) the
composition has a glass-liquid transition temperature of less than 21 degrees
Celsius, and the
composition lacks a freezing point.
In some preferred embodiments, the terpene oxidation product is
bicyclohumuladiol.
In some preferred embodiments, the terpene oxidation product is
tricyclohumuladiol.
In some preferred embodiments, the terpene oxidation product is
tricyclohumuladiol II.
In some preferred embodiments, the terpene oxidation product is humulenol II.
In some preferred embodiments, the terpene oxidation product is humulene
epoxide I.
In some preferred embodiments, the terpene oxidation product is humulene
epoxide II.
In some preferred embodiments, the terpene oxidation product is humulene
epoxide III.
Various aspects of this patent document relate to a composition, comprising
(i) cannabidiol at a
concentration of at least 70 percent and no greater than 99.5 percent by mass,
and (ii) one or more
solutes selected from terpenes, terpene alcohols, terpenoids, and terpene
oxidation products at a
combined concentration of at least 0.5 percent and no greater than 30 percent
by mass, wherein:
the one or more solutes comprise a terpene and a terpene oxidation product;
the terpene is beta-
caryophyllene; the terpene oxidation product is caryophyllene oxide; the
composition comprises
the beta-caryophyllene and the caryophyllene oxide at a ratio of at least 1:10
and no greater than
10,000:1 by mass; the cannabidiol is a liquid; the one or more solutes are
dissolved in the
cannabidiol; and either (i) the composition has a freezing point of less than
21 degrees Celsius, and
the composition lacks a glass-liquid transition temperature, or (ii) the
composition has a glass-
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liquid transition temperature of less than 21 degrees Celsius, and the
composition lacks a freezing
point.
Various aspects of this patent document relate to a composition, comprising
(i) cannabidiol at a
concentration of at least 70 percent and no greater than 99.5 percent by mass,
and (ii) one or more
solutes selected from terpenes, terpene alcohols, terpenoids, and terpene
oxidation products at a
combined concentration of at least 0.5 percent and no greater than 30 percent
by mass, wherein:
the one or more solutes comprise a terpene and a terpene oxidation product;
the terpene is alpha-
bisabolol; the terpene oxidation product is either caryophyllene oxide or
humulene epoxide II; the
composition comprises the alpha-bisabolol and the terpene oxidation product at
a ratio of at least
1:10 and no greater than 10,000:1 by mass; the cannabidiol is a liquid; the
one or more solutes are
dissolved in the cannabidiol; and either (i) the composition has a freezing
point of less than 21
degrees Celsius, and the composition lacks a glass-liquid transition
temperature, or (ii) the
composition has a glass-liquid transition temperature of less than 21 degrees
Celsius, and the
composition lacks a freezing point.
Various aspects of this patent document relate to a composition, comprising
(i) cannabidiol at a
concentration of at least 50 percent and no greater than 99.5 percent by mass
and (ii) one or more
solutes selected from terpenes, terpene alcohols, and terpenoids at a combined
concentration of at
least 0.5 percent and no greater than 40 percent by mass, in which: the one or
more solutes are
dissolved in the cannabidiol; the composition has either a freezing point or a
glass-liquid transition
temperature; and the freezing point or the glass-liquid transition temperature
is either (i) at least 50
degrees Fahrenheit less than the freezing point of pure cannabidiol or (ii) at
least 27 degrees
Celsius less than the freezing point of pure cannabidiol. In some preferred
embodiments, the
composition comprises the cannabidiol at a concentration of at least 65
percent and no greater than
99.5 percent by mass, and the composition comprises the one or more solutes at
a combined
concentration of at least 0.5 percent and no greater than 35 percent by mass.
In some specific
preferred embodiments, the composition comprises the cannabidiol at a
concentration of at least 70
percent and no greater than 99.5 percent by mass, and the composition
comprises the one or more
solutes at a combined concentration of at least 0.5 percent and no greater
than 30 percent by mass.
In some very specific preferred embodiments, the composition comprises the
cannabidiol at a
concentration of at least 75 percent and no greater than 99.5 percent by mass,
and the composition
comprises the one or more solutes at a combined concentration of at least 0.5
percent and no
greater than 25 percent by mass.
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HO
.,_
HO
Formula I. Cannabidiol
HO
0
li
4----
...` 0
Formula II. Tetrahydrocannabinol
HO
=0
0
Formula III. (6aS,10aR) Stereoisomer of Tetrahydrocannabinol
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Formula IV. Beta-Caryophyllene *
=
Formula V. Caryophyllene Oxide *
Formula VI. Humulene *
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Flor,0
H
OH
Formula VII. Bicyclohumuladiol *
HO
4,
H
HO i
"
st.
Formula VIII. Tri cyclohumuladiol *
HO
H
....FA
40
44,*
HO*
Formula IX. Tricyclohumuladiol II *
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0
Formula X. Humulene Epoxide I *
00'81*.
Formula XI. Humulene Epoxide II *
Formula XII. Humulene Epoxide III *
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Formula XIII. Humulenol II *
HO
H 4111 00'
Formula XIV. Alpha-Bisabolol *
HO
,0
- 0
Formula XV. Cannabichromene t
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Table I: Names of the Molecules of Formulas I-XV
Formula Common Name Chemical Name
2-[(1R,6R)-6-i sopropeny1-3 -methylcyclohex-2-en-l-y1]-
I Cannabidiol
5-pentylbenzene-1,3-diol
(6aR,10aR)-6,6,9-trimethy1-3 -penty1-6a,7,8,10a-
II Tetrahydrocannabinol
tetrahydro-6H-benzo[c]chromen-1-ol
(6aS,10aR)
(6aS,10aR)-6,6,9-trimethy1-3 -penty1-6a,7,8,10a-
III Stereoisomer of
tetrahydro-6H-benzo[c]chromen-1-ol
Tetrahydrocannabinol
(1R,4E,9S)-4,11,11-trimethy1-8-
IV Beta-caryophyllene *
methylidenebicyclo[7.2.0]undec-4-ene
(1R,4R,6R,10S)-4,12,12-trimethy1-9-methylene-5-
V Caryophyllene oxide *
oxatricyclo[8.2Ø04'6]dodecane
VI Humulene * (1E,4E,8E)-2,6,6,9-tetramethy1-1,4,8-
cycloundecatriene
(2R,9S)-1,5,8,8-tetramethylbicyclo[8.1.0]undec-5-ene-
VII Bicyclohumuladiol *
2,9-diol
(1R,2R,4R,5R,8S,9S)-4,8,11,11-
VIII Tricyclohumuladiol *
tetramethyltricyclo[7.2Ø021undecane-5,8-diol
(1S,2R,4R,5R,8S,9S)-4,8,11,11-
IX Tricyclohumuladiol II *
tetramethyltricycIo[6.3Ø021undecane-5,9-diol
(1S,4E,7E,11S)-1,5,9,9-tetramethy1-12-
X Humulene epoxide I *
oxabicyclo[9.1.0]dodeca-4,7-diene
(1R,3E,7E,11R)-1,5,5,8-tetramethy1-12-
XI Humulene epoxide II *
oxabicyclo[9.1.0]dodeca-3,7-diene
(1R,3E,7E,11R)-3,7 ,10,10-tetramethy1-12-
XII Humulene epoxide III *
oxabicyclo[9.1.0]dodeca-3,7-diene
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Formula Common Name Chemical Name
(1R,4Z,8Z)-6,6,9-trimethy1-2-methylene-4,8-
XIII Humulenol II *
cycloundecadien-l-ol
(1R,4Z,8Z)-6,6,9-trimethy1-2-methylene-4,8-
XIV Alpha-Bisabolol *
cycloundecadien-l-ol
2-methy1-2-(4-methylpent-3-en-1-y1)-5-hydroxy-7-
XV Cannabichromene
penty1-2H-1-benzopyran
* Formulas IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, and XIV depict
stereochemistry, but each
Common Name as used both in this patent specification and in the patent claims
encompasses both
the depicted stereochemistry of a Chemical Formula and each stereoisomer of a
Chemical Formula
because a probability distribution of each stereoisomer exists in natural
products and because
accredited cannabinoid testing laboratories generally do not distinguish
stereoisomers;
t Formula XV does not depict stereochemistry, and "cannabichromene"
encompasses both
stereoisomers of Formula XV.
In some embodiments, the composition has a freezing point; the composition
lacks a glass-
liquid transition temperature; and the freezing point is less than either 70
degrees Fahrenheit or 21
degrees Celsius.
In some embodiments, the composition has a glass-liquid transition
temperature; the
composition lacks a freezing point; and the glass-liquid transition
temperature is less than either 70
degrees Fahrenheit or 21 degrees Celsius.
In some embodiments, the composition lacks crystals of cannabidiol.
In some embodiments, the composition comprises cannabidiol at a concentration
of at least 75
percent and no greater than 99 percent by mass.
In some embodiments, the composition lacks tetrahydrocannabinol at a
concentration greater
than 0.3 percent by mass.
In some embodiments, the composition comprises tetrahydrocannabinol at a
concentration
greater than 0.3 percent by mass; the tetrahydrocannabinol is dissolved in the
cannabidiol; and the
composition comprises the cannabidiol and the tetrahydrocannabinol at a ratio
of at least 3:1 and
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no greater than 200:1 by mass.
In some embodiments, the composition comprises (6aS,10aR)-6,6,9-trimethy1-3-
pentyl-
6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol at a concentration of at least
0.05 percent and no
greater than 5 percent by mass, in which the (6aS,10aR)-6,6,9-trimethy1-3-
penty1-6a,7,8,10a-
tetrahydro-6H-benzo[c]chromen-1-ol is dissolved in the cannabidiol.
In some embodiments, the composition comprises molecules having a boiling
point of less than
either 360 degrees Fahrenheit or 182 degrees Celsius at a combined
concentration of at least 95
percent by mass.
In some embodiments, the composition lacks propylene glycol, glycerol,
triglycerides,
phospholipids, fatty acids, and waxes at a combined concentration greater than
5 percent by mass.
In some preferred embodiments, the composition lacks propylene glycol.
In some preferred embodiments, the composition lacks triglycerides.
In some preferred embodiments, the composition lacks phospholipids.
In some preferred embodiments, the composition lacks waxes.
In some embodiments, the composition is a liquid.
In some embodiments, the composition has a viscosity, and the viscosity is
less than 100
pascal-seconds at a temperature of either 70 degrees Fahrenheit or 21 degrees
Celsius. In some
specific embodiments, the viscosity is at least 50 millipascal-seconds and no
greater than 50
pascal-seconds at a temperature of either 70 degrees Fahrenheit or 21 degrees
Celsius.
In some embodiments, the one or more solutes comprise one or more of alpha-
bisabolol, alpha-
phellandrene, alpha-pinene, alpha-terpinene, alpha-terpineol, beta-
caryophyllene, beta-pinene,
borneol, cadinene, camphene, camphor, caryophyllene oxide, citral,
citronellol, delta-3-carene,
eucalyptol, eugenol, gamma-terpinene, geraniol, guaiol, humulene, isopulegol,
limonene, linalool,
myrcene, nerol, nerolidol, ocimene, para-cymene, phytol, pulegone, terpineol,
terpinolene, and
valencene at a combined concentration of at least 0.5 percent and no greater
than 40 percent by
mass. In some specific embodiments, the one or more solutes comprise one or
more of alpha-
bisabolol, beta-caryophyllene, guaiol, humulene, limonene, myrcene, and
terpinolene at a
combined concentration of at least 0.5 percent and no greater than 40 percent
by mass.
In some preferred embodiments, the one or more solutes comprise alpha-
bisabolol.
In some preferred embodiments, the one or more solutes comprise beta-
caryophyllene.
In some preferred embodiments, the one or more solutes comprise caryophyllene
oxide.
In some preferred embodiments, the one or more solutes comprise humulene.
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In some very specific embodiments, the composition comprises cannabidiol at a
concentration
of at least 65 percent and no greater than 99 percent by mass; the composition
lacks crystals of
cannabidiol; the composition lacks tetrahydrocannabinol at a concentration
greater than 0.3 percent
by mass; the one or more solutes comprise one or more of alpha-bisabolol, beta-
caryophyllene,
guaiol, humulene, limonene, myrcene, and terpinolene at a combined
concentration of at least 0.5
percent and no greater than 35 percent by mass; the composition comprises
molecules having a
boiling point lower than either 360 degrees Fahrenheit or 182 degrees Celsius
at a combined
concentration of at least 95 percent by mass; the composition lacks propylene
glycol, glycerol,
triglycerides, phospholipids, fatty acids, and waxes at a combined
concentration of greater than 5
percent by mass; the composition has a glass-liquid transition temperature;
the glass-liquid
transition temperature is less than either 70 degrees Fahrenheit or 21 degrees
Celsius; the
composition lacks a freezing point; the composition is a liquid; the
composition has a viscosity;
and the viscosity is at least 50 millipascal-seconds and no greater than 50
pascal-seconds at a
temperature of either 70 degrees Fahrenheit or 21 degrees Celsius.
In some very specific embodiments, the composition comprises cannabidiol at a
concentration
of at least 65 percent and no greater than 99 percent by mass; the composition
lacks crystals of
cannabidiol; the composition comprises tetrahydrocannabinol at a concentration
of greater than 0.3
percent by mass; the tetrahydrocannabinol is dissolved in the cannabidiol; the
composition
comprises cannabidiol and tetrahydrocannabinol at a ratio of at least 3:1 and
no greater than 200:1
by mass; the one or more solutes comprise one or more of alpha-bisabolol, beta-
caryophyllene,
guaiol, humulene, limonene, myrcene, and terpinolene at a combined
concentration of at least 0.5
percent and no greater than 35 percent by mass; the composition comprises
molecules having a
boiling point lower than either 360 degrees Fahrenheit or 182 degrees Celsius
at a combined
concentration of at least 95 percent by mass; the composition lacks propylene
glycol, glycerol,
triglycerides, phospholipids, fatty acids, and waxes at a combined
concentration greater than 5
percent by mass; the composition has a glass-liquid transition temperature;
the glass-liquid
transition temperature is less than either 70 degrees Fahrenheit or 21 degrees
Celsius; the
composition lacks a freezing point; the composition is a liquid; the
composition has a viscosity;
and the viscosity is at least 50 millipascal-seconds and no greater than 50
pascal-seconds at a
temperature of either 70 degrees Fahrenheit or 21 degrees Celsius.
In some embodiments, the composition comprises cannabichromene at a
concentration of at
least 0.1 percent and no greater than 10 percent by mass. In some specific
embodiments, the
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composition comprises cannabichromene at a concentration of at least 0.81
percent and no greater
than 8.1 percent by mass. In some very specific embodiments, the composition
comprises
cannabichromene at a concentration of at least 1.94 percent and no greater
than 6.92 percent by
mass. The combination of cannabichromene and one or more solutes selected from
terpenes,
terpene alcohols, terpenoids, and terpene oxidation products is more effective
at reducing the
freezing point of liquid cannabidiol than the one or more solutes alone.
In some embodiments, the composition comprises cannabigerol at a concentration
of at least
0.1 percent and no greater than 10 percent by mass. In some specific
embodiments, the
composition comprises cannabigerol at a concentration of at least 0.81 percent
and no greater than
8.1 percent by mass. In some very specific embodiments, the composition
comprises cannabigerol
at a concentration of at least 1.94 percent and no greater than 6.92 percent
by mass.
Various aspects of this patent document relate to a method to manufacture a
cannabidiol
product, comprising (i) providing a starting composition comprising liquid
cannabidiol; and (ii)
dissolving one or more terpenes, terpene alcohols, terpenoids, or terpene
oxidation products in the
liquid cannabidiol to produce a composition described anywhere in this patent
document.
Various aspects of this patent document relate to a container comprising (i) a
heating element
and (ii) a chamber that contains at least 2 milligrams and no greater than 2
grams of a composition
described anywhere in this patent document, wherein the heating element is in
thermal
communication with the composition. In some specific embodiments, the
container is configured
to be connected to a battery such that the battery and the heating element are
in electrical
communication that allows the transfer of electrical energy from the battery
to the heating element;
the heating element is operable to convert the electrical energy into
sufficient heat energy; and the
sufficient heat energy is sufficient to heat the composition to a temperature
greater than the boiling
point of the cannabidiol. In some very specific embodiments, the container is
connected to the
battery such that the battery and the heating element are in electrical
communication.
Various aspects of this patent document relate to a method to manufacture a
cannabidiol
product, comprising (i) providing a composition comprising cannabidiol and one
or more solutes,
wherein the cannabidiol is a liquid, and the one or more solutes are dissolved
in the cannabidiol;
(ii) providing a starting container comprising a heating element; and (iii)
inserting at least 2
milligrams and no greater than 2 grams of the composition into the starting
container to produce a
container described anywhere in this patent document.
Various aspects of this patent document relate to a method to manufacture a
cannabidiol
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product, comprising (i) providing a starting composition comprising liquid
cannabidiol; (ii)
dissolving one or more terpenes, terpene alcohols, terpenoids, or terpene
oxidation products in the
liquid cannabidiol to produce a composition described anywhere in this patent
document; (iii)
providing a starting container comprising a heating element; and (iv)
inserting at least 2 milligrams
and no greater than 2 grams of the composition into the starting container to
produce a container
described anywhere in this patent document.
The following example provides a framework to implement certain aspects of the
disclosure,
and this example does not limit the scope of this patent document or any claim
that matures from
the disclosure of this patent document.
Example 1. Production of compositions comprising cannabidiol that do not
crystallize
Cannabinoids were extracted from organic industrial hemp using the system
described in PCT
Patent Application Publication No. 2016/161420 Al to produce crude industrial
hemp extract
comprising 65-70% cannabidiol; 5-10% terpenes, terpene alcohols, and
terpenoids; 2-3%
tetrahydrocannabinol; and other volatile molecules including waxes and
phospholipids. The crude
industrial hemp extract formed crystals of cannabidiol when stored at room
temperature for 24
hours.
The cannabinoids of the crude industrial hemp extract were separated from
other molecules by
distillation in a VTA Short Path Distillation Plant VKL 70
(Verfahrenstechnische Anlagen GmbH
& Co. KG, Germany) to produce a cannabinoid distillate comprising
approximately 90%
cannabidiol and 5% tetrahydrocannabinol. 10 grams of the cannabinoid
distillate was combined
with 0.1 grams of a terpene, terpene alcohol, and terpenoid blend obtained
from True Terpenes
(Oregon, USA) with heating to produce a liquid composition. The blend
contained beta-
caryophyllene (41%), humulene (18%), linalool (13%), limonene, alpha-
bisabolol, nerolidol, beta-
pinene, citronellol, fenchol, and other molecules at lower concentrations.
The liquid composition was stored at room temperature for 1 year with
intermittent exposure to
light and air, and the composition produced no detectable crystals. Cooling
the liquid below room
temperature vitrified the composition into a glass without any detectable
crystal formation.
This example demonstrates that small amounts of terpenes, terpene alcohols,
and terpenoids
can provide robust stabilization of cannabidiol in a liquid state and inhibit
crystal formation over
commercially-relevant timeframes, even when subjected to chemical stress,
provided that lipids
that comprise fatty acids are removed from the liquid state.
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