US 201700.

08870A1
(19) United States
(12) Patent Application Publication (10) Pub. No.: US 2017/0008870 A1
Dibble et al. (43) Pub. Date: Jan. 12, 2017
(54) METHODS FOR OBTAINING PURIFED (52) U.S. Cl.
CANNABS EXTRACTS AND THCA CPC ......... C07D 3II/80 (2013.01); B0ID 1 1/0288
CRYSTALS (2013.01); B0ID II/0292 (2013.01); B0ID
21/009 (2013.01); B0ID 21/0012 (2013.01)
(71) Applicants: Clare J. Dibble, Arvada, CO (US);
Isaac B. Cole, Berkeley, CA (US) (57) ABSTRACT
(72) Inventors: Clare J. Dibble, Arvada, CO (US); The present invention includes a method for obtaining a
Isaac B. Cole, Berkeley, CA (US) higher purity cannabinoid solvent extract from a plant which
(21) Appl. No.: 15/202,385 comprises cannabinoids and/or terpenes. A solvent extrac
tion is performed on the optionally dried plant material,
(22) Filed: Jul. 5, 2016 followed by a step of removing high molecular weight
impurities by a cooling step. Following the cooling step, the
Related U.S. Application Data precipitate is removed and a higher quality filtrate is
obtained which contains higher levels of purity of cannabi
(60) Provisional application No. 62/188.965, filed on Jul. noids and/or terpenes than the starting solvent extract. The
6, 2015. methods of the invention also include a method for obtaining
crystallized THCa, which comprises obtaining a filtrate by
Publication Classification the methods disclosed herein, or obtaining a solvent extract,
(51) Int. C. and allowing crystallization of the THCa to occur. The
CO7D 3II/80 (2006.01) filtrate, crystallized THCa, and residual filtrate remaining
BOID 2L/00 (2006.01) after crystallization of THCa can be used as starting mate
BOLD II/02 (2006.01) rials for products that include cannabinoids and/or terpenes.
US 2017/OOO887.0 A1 Jan. 12, 2017

METHODS FOR OBTAINING PURIFED certain cannabinoids. Fractional distillation, immiscible liq
CANNABS EXTRACTS AND THCA uid-liquid separation, or preparative and flash chromatogra
CRYSTALS phy have been employed individually or in combination to
separate desirable components of plant extracts from less
CROSS-REFERENCE TO RELATED desirable counterparts in other pharmaceutical plant prepa
APPLICATIONS rations and natural products like essential oils. However,
these techniques either tend to be difficult to scale and make
0001. This application claims priority to pending U.S. continuous, or tend to degrade the molecules of interest.
Provisional Application Ser. No. 62/188,965 entitled “Meth 0007. Therefore, improved methods for removing plant
ods for Obtaining Purified Cannabis Extracts and THCA material Such as lignin, lignans, gums and lecithins from
Crystals', filed Jul. 6, 2015, and the disclosure is hereby cannabis oil, and improved methods for obtaining purified
incorporated by reference herein in its entirety. THC or THCa, are desired in the art.
0008. The present invention is directed toward overcom
BACKGROUND ing one or more of the problems discussed above.
SUMMARY OF THE EMBODIMENTS
0002 Cannabinoids are a diverse class of chemical com
pounds that act as a ligand to the brain's cannabinoid 0009. In one embodiment, the present invention discloses
receptors. The clinical usefulness of the cannabinoids, a method for obtaining a higher purity cannabinoid solvent
including A-tetrahydrocannabinol (A-THC), to provide extract from a plant which comprises at least one cannabi
analgesia, help alleviate nausea and emesis, as well as noid. This method includes the steps of performing a solvent
stimulate appetite has been well-recognized. Cannabinoids extraction of the plant to yield a solvent extract; a step of
offer a variety of pharmacological benefits, including, but cooling the solvent extract; and a step of removing the
not limited to, anti-spasmodic, anti-inflammatory, anti-con precipitate from the cooled solvent extract to yield a solvent
Vulsant, anti-psychotic, anti-oxidant, neuroprotective, anti extract filtrate, wherein the solvent extract filtrate has a
inflammatory, anti-cancer, and immunomodulatory effects. higher purity of the at least one cannabinoid. The initial
0003. The cannabis plant is the primary source of can precipitate includes Substances that are capable of carbon
nabinoids Like all terrestrial plants, lignocellulose gives the izing rather than completely evaporating when heated. Such
plant its structure. Lignocellulosic material is composed of as lignocellulosic material, lignin, lignans, and/or lecithin.
carbohydrate polymers such as cellulose and hemicellulose, The solvent may include a short chain hydrocarbon, such as,
and an aromatic polymer called lignin. Lignin is a constitu for example, butane; carbon dioxide, an alcohol, or a ter
ent of the cell walls of almost all dry land plant cell walls. pene. The step of cooling the solvent extract involves
It is the second most abundant natural polymer in the world, cooling until the Solute forms a solid but the temperature and
Surpassed only by cellulose. The non-structural chemical pressure are in a range where the solvent remains fluid. For
components of plant cells are much more highly variable the example ofbutane solvents, this may include cooling the
from plant to plant and within different parts of a plant. solvent extract to a temperature of between about -50° C.
These are referred to as extractives, referencing the relative and about -85° C. for a time period of between about 30
ease with which they can be separated from the lignocellu minutes to about 6 hours. The plant may be cannabis or
lose that composes the structure of the plant. Cannabinoids hemp, and the cannabinoid may be tetrahydrocannabinolic
are the class of chemicals that make the cannabis plant acid (THCa). This method may further optionally include
unique, but terpenoids, Sugars, fatty acids, flavonoids, other the step of crystallizing the THCa from the solvent extract
hydrocarbons, nitrogenous compounds, and amino acids filtrate. Alternatively, the method includes crystallizing the
have also been identified in cannabis plants. THCa directly from the solvent extract, particularly where
0004. The principle cannabinoids present in herbal can the plant (or plant parts) comprise a high percentage of
nabis are cannabinoid acids A-tetrahydrocannabinolic acid cannabinoids and/or THCa. For example, to obtain crystals
(A-THCa) and cannabidiolic acid (CBDa) with small of THCa, the solvent extract filtrate may be cooled to a
amounts of the respective neutral (decarboxylated) cannabi temperature of about -75° C. for a time period of between
noids. In addition, cannabis may contain lower levels of about 12 hours and three days to obtain crystals of THCa of
other minor cannabinoids. greater than about 95% purity. Optionally, THCa may be
precipitated directly from the extract making the filtrate
0005. In general, a crude extract of cannabis can be made lower in (THC+THCa) but replete with cannabinoids and
via Solvent extraction. The resultant oil, or cannabis resin, is terpenes from the plant.
a dark brown, Viscous and sticky oil and generally contains 0010 Various modifications and additions can be made to
up to about 75% of THC (or THCa), depending on the the embodiments discussed without departing from the
extraction conditions. The balance of the cannabis resin
generally contains other cannabinoids, terpenoids and a scope of the invention. For example, while the embodiments
significant amount of other materials that originated in the described above refer to particular features, the scope of this
plant that are not known to have therapeutic value. In invention also included embodiments having different com
bination of features and embodiments that do not include all
particular, the extract may contain lignin, lignans, gums, of the above described features.
pigments, and lecithin. Lignin, as a structural polymer,
would not typically be extracted with polar solvents such as DETAILED DESCRIPTION
water, but may be extracted with non-polar solvents used to 0011 Disclosed herein are methods for improving the
extract resins. purification of plant extracts via removal of undesirable
0006 Crude extracts from cannabis plants are often used impurities and, in the case of cannabis extracts, Subsequent
by patients suffering from diseases and disorders, such crude selective isolation of tetrahydrocannabinolic acid (THCa)
products are less Suitable for use in pharmaceutical formu from other cannabinoids and terpenes. The improved pro
lations. It would be preferable to have purified forms of cess for purifying plant extracts can be conducted in open or
US 2017/OOO887.0 A1 Jan. 12, 2017

closed systems and in a batch or continuous manner. The 0016. The cannabinols have the following general struc
extract to be purified can be from any vegetation, but this ture:
method is particularly Suited to cannabis.
0012 While all natural product precursors exhibit inher
ent variation, it is desirable to obtain a consistent product
from any part of the plant that contains that product within
a single harvest and from different harvests. While a variety OR
of extraction techniques have become commonplace in
cannabis, a secondary separation step is rarely employed. To R2
create high quality products, manufacturers favor extrac
tions from bud and higher grade trim and with targeted
Solvents like lighter hydrocarbons (propane instead of O R3
butane) to help minimize the removal of these impurities
that contribute to off flavors and processing inconsistencies. R = Hor C3
Surprisingly, it is possible to remove the undesirable extrac R2 = H or COOH
tives by sedimentation and removal of said impurities pro R3 = C1, C3, C4, or Cs side chain
motes the crystallization of THCa, when it is present. The Cannabinol type
present inventor also found methods to crystallize THCa
from, for example, extracted bud and higher-quality trim.
0013. In one embodiment, the present invention includes 0017 Below is A-tetrahydrocannabinol.
a method for obtaining a higher purity cannabinoid solvent
extract from a plant which comprises at least one cannabi
noid. The method includes the steps of performing a solvent
extraction of the plant to yield a solvent extract, cooling the
Solvent extract; and removing the precipitate from the
cooled solvent extract to yield a solvent extract filtrate.
Optionally, the cannabis Supernatant can be cooled another
time to yield a precipitate of high purity THCa crystals and
a residual filtrate enriched in other cannabinoids and ter
penes. The methods of the invention result in obtaining a
solvent extract filtrate which has a higher purity of the at CH
least one cannabinoid. These steps are discussed hereinbe
low.
0014. The solvent extract may comprise tetrahydrocan 10018 Tetrahydrocannabinol, such as A THC, helps
nabinol, cannabidiol, and the carboxylic acids thereof from reduce nausea and vomiting, which is particularly helpful to
cannabis plant material. patients undergoing chemotherapy for cancer. Patients Suf
00.15 Exemplary cannabinoids useful for the present fering from AIDS often experience a lack of appetite, of
invention include cannabinols. In one embodiment, the which tetrahydrocannabinol is also helpful in counteracting.
invention includes tetrahydrocannabinols, including the Tetrahydrocannabinol is also useful for glaucoma relief.
most commonly known cannabinoid, tetrahydrocannabinol (0019 THC may be derived from Cannabis sativa or
(THC). The most potent stereoisomer occurs naturally as Cannabis indica, for example.
A-THC where the two chiral centers at C-6a and C-10a are
in the trans configuration as the (-)-trans-isomer, and this 0020. The cannabinoids include cannabinoids which
Stereoisomer is also known as dronobinol. There are seven have a carboxylic acid Substituent, also known as cannabi
double bond isomers in the partially saturated carbocylic noid acids, such as tetrahydrocannabinolic acid (THCa)
ring including A'7-tetrahydrocannabinol, A-tetrahydro which has a carboxylic acid at R. These carboxylic acids are
cannabinol, A-tetrahydrocannabinol, A'-tetrahydrocan designated as “a”. For example, CBD occurs as CBDa in the
nabinol, A'-tetrahydrocannabinol, A'-tetrahydrocannabi cannabis plant. The 2-carboxylic acids of the cannabinoids
nol, and A'-tetrahydrocannabinol, using the can be decarboxylated by heat, light, or alkaline conditions
dibenzopyran numbering: to their respective decarboxylated compounds, such as to
A-THC. See below for the structure of A-THCa.

Dibenzopyran 0021 Decarboxylation of the cannabinoid acids to the

Numbering corresponding phenols occurs over time, upon heating, or
under alkaline conditions. Heating for 5 minutes at a tem
perature of 200-210°C. will accomplish decarboxylation.
US 2017/OOO887.0 A1 Jan. 12, 2017

THCa is the non-activated, non-psychotropic acid form of

THC. THCa is a known anti-inflammatory and provides
many of the same benefits of THC but without psychotropic
side effects. THCa not only has anti-proliferative abilities
that are crucial in helping inhibit the growth of cancerous
cells, but also, it has anti-spasmodic abilities that helps
Subdue muscle spasms and therefore has potential use
among epileptic patients.
0022 Cannabinoids may also occur as their pharmaceu
tically acceptable salts. As used herein, the expression
“tetrahydrocannabinol’ or “THC' where not otherwise R = Hor COOH
specified—is to encompass any isomers thereof, in particu R2 = C1, C3, C4, or Cs side chain
lar double bond isomers. R = H or CH
0023. A cannabinol useful for the present invention also
includes tetrahydrocannabivarin (THCV) having a propyl 0028. A cannabinoid useful for the present invention also
side chain. includes the naturally occurring cannabidiol type also called
(-)-trans-cannabidiol (CBD).

0024 Tetrahydrocannabivarin THCV is structurally 0029) CBD can occur in up to 40% of the cannabinoid
similar to THC, but acts an antagonist to the CB1 & CB2 extracts from cannabis. CBD generally occurs in the can
receptors in the body. Given this, recent studies have shown nabis plant prior to processing as CBDa which has a
carboxylic acid at R". The 2-carboxylic acids of the can
that THCV is an excellent appetite suppressant as it blocks nabinoids can be decarboxylated by heat, light, or alkaline
the rewarding sensations experienced when eating. THCV conditions to their respective decarboxylated compounds.
also holds anti-convulsive properties useful for treating 0030 CBD and CBDa have been shown effective in
epilepsy. While psychoactive, THCV lends itself to a treating inflammation, diabetes, cancer, mood disorders
shorter, psychedelic, clear-headed effect which is shorter (PTSD to ADD) and neurodegenerative diseases such as
Alzheimer's. It has been shown to have anti-convulsive,
lasting that THC. anti-anxiety, anti-psychotic, anti-nausea and anti-rheuma
0025. A cannabinoid useful for the present invention also toid arthritic and sedative properties, and a clinical trial
showed that it eliminates anxiety and other unpleasant
includes cannabinol (CBN). psychological side effects. CBD does not display the psy
choactive effects of A-THC. CBD was found in one study
to be more effective than aspirin for pain relief and reducing
inflammation. CBD has been shown to be a potent antioxi
dant as well as having neuroprotective and anti-inflamma
OH tory uses.
0031. A cannabinoid useful for the present invention also
includes cannabichromene type, or

OH

R
21, 21
0026 CBN’s primary effects are as an anti-epileptic,
anti-spasmodic and reliever of intra-ocular pressure. Recent O R
studies Suggest that CBN can be administered as an antide
pressant, can be used to prevent convulsions and to sedate R = H or COOH
patients experiencing pain. It is ideal for those Suffering R = C3 or Cs side chain
from glaucoma, inflammation, and insomnia. Cannabichromene type
0027. A cannabinoid useful for the present invention also
includes a cannabidiol type.
US 2017/OOO887.0 A1 Jan. 12, 2017

0032 An exemplary cannabichromene (CBC) is shown rosemary and hops. It is usually found as a mixture with
below: isocaryophyllene (the cis double bond isomer) and C-humu
lene, a ring-opened isomer. Caryophylene is notable for
having a rare cyclobutane ring. Its IUPAC name is 4,11,11
trimethyl-8-methylene-bicyclo7.2.0 undec-4-ene.
0041 Caryophylene is known to be one of the com
pounds that contribute to the spiciness of black pepper. In
another embodiment, the terpene/terpenoid includes citral.
Citral, or 3,7-dimethyl-2,6-octadienal or lemonal, is either a
pair, or a mixture of terpenoids with the molecular formula
CHO. The two compounds are double bond isomers. The
E-isomer is known as geranial or citral A. The Z-isomer is
0033 CBC, like THC and CBD, results from CBCa. CBC known as neral or citral B. Its IUPAC name is 3,7-dimeth
has been shown to inhibit the growth of cancerous tumors ylocta-2,6-dienal. It is also known as citral, geranial, neral,
due to its interaction with anadamide, a human endocan geranialdehyde.
nabinoid. It is also an inflammation and pain inhibitor and 0042. In another embodiment, the terpene/terpenoid
has been Successful for treating migraines and stimulating includes humulene. Humulene, also known as C-humulene
bone growth. Due to its Small quantity in the cannabis plant, or C-caryophyllene, is a naturally occurring monocyclic
CBC works best in conjunction with CBD and THC. sesquiterpene (CH), which is an 11-membered ring
0034. The plant which comprises at least one cannabinoid consisting of 3 isoprene units containing three nonconju
optionally further comprises at least one terpene and/or gated C=C double bonds, two of them being triply substi
terpenoid. The methods of the present invention are also tuted and one being doubly substituted. It was first found in
optionally useful to obtain a higher purity of terpene(s). the essential oils of Humulus lupulus (hops). Humulene is an
Terpenes are a diverse group of organic hydrocarbons isomer of B-caryophyllene, and the two are often found
derived from 5-carbon isoprene units and are produced by a together as a mixture in many aromatic plants.
wide variety of plants. Terpenes are naturally present in 0043. Other exemplary terpenes/terpenoids include men
cannabis; however, they can be removed during the extrac thol, eucalyptol, borneol, pulegone, Sabinene, terpineol and
tion process. thymol.
0035. In one embodiment, the terpene/terpenoid includes 0044. The methods of the present invention may be used
limonene. Limonene is a colorless liquid hydrocarbon clas with a plant which comprises at least one cannabinoid. A
sified as a cyclic terpene. The more common D-isomer plant that comprises at least one cannabinoid includes Can
possesses a strong Smell of oranges and a bitter taste. nabis (hemp). For the botanical and chemotaxonomical
Limonene is a chiral molecule. Biological sources produce differentiation of the genus Cannabis there are two different
one enantiomer—the principal industrial source—citrus concepts. One differentiates between three species, Canna
fruit, contains D-limonene ((+)-limonene), which is the bis sativa Linnaeus, Cannabis indica LAM., and Cannabis
(R)-enantiomer (CAS number 5989-27-5, EINECS number ruderalis, while a different theory only sees the existence of
227-813-5). Racemic limonene is known as dipentene. Its the one collective species Cannabis sativa L. made up of the
IUPAC name is 1-methyl-4-(1-methylethenyl)-cyclohexene. Subspecies Cannabis sativa ssp. sativa and ssp. indica.
It is also known as 4-isopropenyl-1-methylcyclohexenep Moreover the cannabis plant is differentiated into a drug type
Menth-1,8-dieneRacemic: DL-limonene; dipentene. and a fiber type, with differentiation being performed on the
0036. In another embodiment, the terpene/terpenoid basis of the quantity ratio of the main cannabinoids, canna
includes linalool. It is also known as B-linalool, linallyl bidiol (CBD) and A-tetrahydrocannabinol (A-THC). Fiber
alcohol, linaloyl oxide, p-linalool, allo-ocimenol, and 3.7- hemp, whose cultivation is permitted for fiber production,
dimethyl-1,6-octadien-3-ol. Its IUPAC name is 3,7-dimeth must not exceed a A-THC content of 0.3% relative to the
ylocta-1,6-dien-3-ol. dry plant mass, while the drug type may exhibit a A-THC
0037. In another embodiment, the terpene/terpenoid content of approx. 5%-15% relative to the dry plant mass.
includes myrcene. Myrcene, or B-myrcene. C-Myrcene is 0045. The ratio of A-THC to CBD in fiber hemp is
the name for the structural isomer 2-methyl-6-methylene-1, mostly less than 1.5. The varieties rich in A-THC may reach
7-octadiene, which is not found in nature and is little used. a ratio of 2:1 to 7:1. Cannabis sativa L. occurs worldwide in
Its IUPAC name is 7-methyl-3-methylene-1,6-octadiene. all warm and moderate Zones with the exception of the
0038. In another embodiment, the terpene/terpenoid humid tropical rain forests. It is an annual to biennial,
includes C.-Pinene. Pinene is found in conifer, pine and anemogamous herb which may attain a height of up to 8 m.
orange. C.-Pinene is a major constituent in turpentine. Its The dioecous, rarely monecious inflorescences contain the
IUPAC name is (1S,5S)-2,6,6-Trimethylbicyclo[3.1.1 hept active cannabinoids in the resin which is mainly secreted by
2-ene ((-)-C.-Pinene). the numerous glandular bracts in the leaf axils. As a general
0039. In another embodiment, the terpene/terpenoid rule, all the plant parts of Cannabis sativa L. with the
includes B-Pinene. Its IUPAC name is 6,6-dimethyl-2-meth exception of the seeds may contain cannabinoids. The
ylenebicyclo[3.1.1 heptane and is also known as 2(10)- highest cannabinoid concentrations are found in the floral
Pinene; Nopinene; Pseudopinene. It is found in cumin, bracts and fruit stalks. The leaves have a low content of
lemon, pine and other plants. cannabinoids as a function of leaf age, while the stalk and
0040. In another embodiment, the terpene/terpenoid particularly the root exhibit clearly lower cannabinoid con
includes caryophyllene, also known as B-caryophyllene. tentS.
Caryophylene is a natural bicyclic sesquiterpene that is a 0046. In one embodiment, the present invention includes
constituent of many essential oils, including clove, cannabis, a step of a solvent extraction of the plant which comprises
US 2017/OOO887.0 A1 Jan. 12, 2017

cannabinoids. The term “plant includes a plant or plant part (precipitate after the first precipitation step) includes the
Such as bark, wood, leaves, stems, roots, flowers, fruits, molecules that contribute to the dark color of certain extracts
seeds, berries or parts thereof). and those that carbonize and leave residual Solids during
0047. Where the starting plant material is freshly har vaporization of a sample. While some cannabinoids are
vested or wet, the plant material may be subjected to a removed with this sediment, their concentration is lower
drying step to remove excess moisture or a freezing step to than the concentration in the original extract, leaving a
immobilize moisture in the plant. Therefore, in one embodi filtrate enriched in at least one cannabinoid. In the case
ment, the cannabis is dried. In another embodiment, the where no THCa is present in the initial extract, such as hemp
cannabis is frozen. Optionally, the plant material comprises or a plant other than a species of cannabis, the resulting
dried bud, trim, or fan leaves, which are optionally milled. filtrate is not subjected to a secondary separation step. If
0048. The plant material is optionally has not been sub THCa is present in the initial filtrate, chilling the initial
ject to a decarboxylation step and the cannabinoids are filtrate a second time after removing the initial sediment
primarily present as their carboxylic acid forms. In other results in precipitated THCa and a residual filtrate relatively
embodiments, the plant material has been Subject to a lower in THC and replete with any other cannabinoids or
decarboxylation step and the cannabinoids are present as terpenes present in the original plant extract.
their neutral forms. If the extract has been subject to a
decarboxylation step or is extracted from hemp or other TABLE 1.
plant material that does not contain THCa, only the first Yields according to prior art processes
sedimentation step is employed, as THCa will not crystalize
if it is not present in the filtrate. In the case that relatively Material Total Solids (g) 96 (THC + THCa)(THC + THCa)(g)
pure THCa is desired, the material may be retained in its acid Starting trim 1OO 10% 10
form by processing fresh or recently dried materials, not Typical butane 12 75% 9
exposing the material or extracts to heat or UV light, and/or extract
maintaining any inert atmosphere that reducing the prob
ability of oxidation reactions, as is known in the art.
0049. In one embodiment, the method includes a step of TABLE 2
performing a solvent extraction of the plant to obtain a
solvent extract. Generally, the solvent extraction step can be Yields according to the instant invention
carried out by methods that are known in the art. Extraction
solvents for use in the methods of the present invention Material Total Solids (g) 96 (THC + THCa)(THC + THCa)(g)
include non-polar solvents such as short chain hydrocarbons Starting trim 1OO 10% 10
(including, for example, propane, butane, hexane, and the Typical butane 12 75% 9
like), alcohols such as ethanol or methanol, and liquid and/or extract
Initial sediment 1.5 60% O.9
Supercritical carbon dioxide, steam, and terpenes. Initial filtrate 1O.S 770, 8.1
0050 Generally, to perform the solvent extraction step, THCa precipitate 6.5 95% 6.2
the solvent is passed over hand harvested or milled plant Residual filtrate 4 48% 1.9
materials in order to extract concentrated fractions. Bulk
Total 12 75% 9
Solids can be retained by a mesh screen, or any other known
methods for filtration or separation between liquids and
Solids may be used. 0053 Typically in cannabis extracts, such a carrier sol
0051. As one example of the process, dried cannabis vent is typically removed immediately following an extrac
material (bud, trim, or fan leaves), which is optionally milled tion process. In the present process, the cannabis solvent
(bowl trim, and/ or blended in a blender), is packed into an extract can be used as collected in the solvent extraction step
extraction column, for example, about 50 g plant matter is without removing the solvent. The ratio of solvent to dry
packed into a 1.5 inch diameter aluminum column 12 inches weight of plant matter extract can be adjusted by adding
in length. Alternatively, 80 to 200 g biomass containing more of the same solvent, a different solvent, or removing
cannabis is placed into a 2 inch diameter stainless steel Some proportion of Solvent. Alternatively, the solvent may
column between 12 and 30 inches in length. The extraction be removed from the extract and the extract re-solubilized in
column packed with the biomass can be, for example, a different solvent.
Supported by a stand with a screen secured on the bottom 0054 The solvent extract, either used as collected, or
and rubber stopper with a center hole containing a nozzle on adjusted in Volume or type of solvent as discussed above, is
the top. 600 mL of cooled 99-96 pure n-butane or (or 95% then used in the additional step(s) of the method.
n-butane with 4.1+% iso-butane) (for example, 10° C. or 0055. In this step of the method, the solvent extract is
colder) is allowed to pass over the column. The liquid that treated to remove higher molecular weight impurities that
flows from the packed bed can be collected in a beaker create carbonized residuals when the rest of the sample is
below the screen end of the tube. The process can be vaporized. Without being bound by theory, the present
repeated several times and the total liquid from the multiple inventor believes that the high molecular weight impurities
runs can be combined. In one embodiment, 200 g or more of to be lignin, lecithin, and/or other undesirable, high molecu
extracted plant matter is processed and 25g or more product lar weight materials that were extracted by the solvent.
(THCa) is obtained. These higher weight impurities can comprise, for example,
0052 Table 1 below shows the fate of initial and Such materials common to plants such as lignin, lignans,
extracted solids and THC as a function of dry weight in a pigments, gums, lignocellulosic material, and lecithin.
typical butane extraction contrasted with the products of the Lignin is commonly understood as a complex polymer of
methods disclosed herein (Table 2). The initial sediment aromatic alcohols and is a component of the cell walls of
US 2017/OOO887.0 A1 Jan. 12, 2017

plants. Plant lignans are polyphenolic Substances derived funnel using 12.5 cm diameter 101 fast filter paper and
from phenylalanine via dimerization of Substituted cinnamic coffee filter and, if possible, taking care not to disturb the
alcohols, known as monolignols. Plant pigments include cake on the bottom of the beaker. In some embodiments, the
chlorophyl and other carotenoids that absorb light to cata sediment forms bubbles during filtration, indicating solvent
lyze photosynthesis. Gums include complex polysaccha evaporation and possibly a Surfactant nature to the sediment.
rides. Lignocellulosic material is composed of carbohydrate 0060 Optionally, the cooling process can be repeated as
polymers such as cellulose and hemicellulose, crosslinked to many times as necessary for maximum removal of the initial
an aromatic polymer (lignin). The solvent extract will also precipitate. Optionally, sedimentation (precipitation) can be
contain lower molecular weight components such as can repeated until the filtrate is optically clear. In this embodi
nabinoids and Volatile terpenes. ment, the filtrate is returned to a clean beaker and the cooling
0056. In one embodiment, the solvent extract is cooled to step is repeated, followed by the step of removing the
allow for precipitation of the higher molecular weight impu precipitate. For example, the beaker can be cooled another
rities. In the cooling step, the temperature of the solvent 1-3 hours and filtered again in a Buchner funnel with a
extract or co-solvents should be maintained in Such a way coffee filter and slow quantitative filter. The present inventor
that the mixture is chilled but the solvent remains fluid, has found that after two filterings, the solvent and extract are
allowing impurities to condense and settle to the bottom of typically significantly more pure. The more optically clear
the container. the solvent is, the better the separation has gone. If vapor
0057. In one example of the present invention, a con ized, this filtrate leaves no residue or a light waxy white
tainer (Such as a beaker) containing a butane solvent extract residue, but no carbonized black residuals.
is allowed to sit directly on dry ice in a cooler for 1-4 hours. 0061 The solvent extract filtrate typically contains a
The cooler is optionally between about -40°C. and -70° C. higher percentage of cannabinoid(s) and/or terpenes than the
The temperature can be varied during the process, and is initial solvent extract. In the example illustrated in Table 2,
optionally carried out at an average temperature of less than the filtrate THCa concentration has increased from 75% to
about 10° C., less than about 0°C., less than about -10°C., 77%. The solvent extract filtrate, following this step, may be
less than -20°C., less than about -30°C., less than about optionally dried by methods known in the art to remove the
-40°C., less than about -50° C., less than about -60° C., solvent. The dried solvent extract filtrate can then be used as
less than about -70° C., or less than about -80°C. In another desired, as a typical oil, shatter or wax that has not under
embodiment, the temperature at which the cooling takes gone a separation process. For example, the butane can be
place is between about -50° C. and about -85°C. The evaporated from filtrate and the extract gently heated in a
cooling step may take place for between about 1 minute and desiccator or vacuum oven to convert any THCa to THC.
24 hours, between about 10 minutes and about 18 hours, Optionally hemp products or products from other plant
between about 30 minutes and about 12 hours, between extracts would terminate this process here.
about one hour and about 8 hours, between about 2 hours 0062. The methods of the present invention optionally
and about four hours. Alternatively, the cooling step may further comprise crystallization (precipitation) of THCa. In
take place for longer than 10 minutes, longer than 30 this step, the solvent extract filtrate can be treated to allow
minutes, longer than about an hour, longer than about two the THCa to crystallize out of solution. The solvent extract
hours, longer than about three hours, longer than about four filtrate can be collected and used in the crystallization step
hours, longer than about six hours, longer than about eight without any further modification. Alternatively, the solvent
hours, longer than about 12 hours, longer than about 18 extract filtrate can have the ratio of solvent to dry weight of
hours, or about twenty four hours or longer. As an example filtrate adjusted by adding more of the same solvent, a
of a device to facilitate cooling the solvent extract on dry ice, different solvent (co-solvent), or removing some proportion
Pelican ProGear Elite Marine Deluxe Coolers work espe of solvent. Alternatively, the solvent may be removed from
cially well for maintaining low temperatures when filled the filtrate and the filtrate re-solubilized in a different solvent
with dry ice. Alternatively methods for cooling the solvent or solvents for the crystallization step. Crystallization is
extract may also be used, such as storing in a cold environ preferably carried out in highly non-polar solvents, such as
ment Such as in a refrigerator or freezer, or by use of liquid hydrocarbons such as butane, oils such as Vegetable oils and
nitrogen. coconut oil or terpenes.
0058. The present invention also includes removing a 0063 Thus, the solvent extract filtrate, either used as
precipitate from the cooled solvent extract. In some embodi collected, or adjusted in Volume or type of Solvent as
ments, the high molecular weight impurities present in the discussed above, is then optionally used in the crystalliza
Solvent extract turn dark when exposed to air. The precipi tion step.
tate can be removed from the cooled solvent extract by any 0064. The crystallization step is enhanced after the strong
methods known in the art. For example, the precipitate can tasting, dark brown material (without being bound by theory,
be removed by filtration, or by transferring the supernatant understood as high molecular weight lignin, lignans, gums,
to a clean vessel. This process is not intended for removal of lignocellulosic material, and the like) has been removed, as
entrained solids, but can handle Small amounts of material described hereinabove, resulting in higher purity THCa. The
that may inadvertently be included in the mixture. In one crystallization step can be performed by methods as known
embodiment of the present invention, the impurities portion in the art.
constitutes 1-15% of the total extract weight and can be as 0065. In one embodiment, the solvent extract filtrate is
much as 60% THCa. To discard the impurities represents a cooled to allow for crystallization of the THCa. In the
loss of 10% of the total extracted THCa or less. cooling step, the temperature of the solvent extract filtrate
0059. As an example of the removal step, after precipitate should be maintained in Such a way that the mixture is
has formed (on the bottom of the beaker in this example), the chilled but the solvent remains fluid, allowing THCa to
solvent extract is filtered through a vacuum assisted Buchner crystallize and settle to the bottom of the container.
US 2017/OOO887.0 A1 Jan. 12, 2017

0066. In one example of the crystallization step, a con 0071. The products made by the processes of the instant
tainer (Such as a beaker) containing the solvent extract invention, e.g., crystallized THCa, solvent extract filtrate, or
filtrate is allowed to sit in a cooler containing dry ice for residual filtrate, for example, may be used in the acid form,
between about 12 hours and several days. The cooler is or converted to the neutral forms by methods known in the
optionally between about -40° C. and -70° C. In one art. The products made by the processes of the instant
embodiment, the temperature is about -75°C. The tempera invention may be incorporated into any product or formu
ture can be varied during the process, and is optionally lation, such as, for example, those products or formulations
carried out at an average temperature of less than about 10° that are typically known to incorporate a cannabinoid.
C., less than about 0°C., less than about -10°C., less than Convenient formulations include tablets, capsules, oils, gels,
-20° C., less than about -30° C., less than about -40°C., lozenges, troches, hard candies, nutritional bars, nutritional
less than about -50° C., less than about -60° C., less than drinks, metered sprays, creams, Suppositories, transdermal
about -70° C., or less than about -80° C. In another patches, among others. The compositions may be combined
embodiment, the temperature at which the cooling takes with a pharmaceutically acceptable excipient Such as gela
place is between about -50° C. and about -85° C. The tin, oil(s), and/or other pharmaceutically active agent(s). The
cooling step may take place for between about one hour and crystallized THCa may be used in the acid form, or con
one week, between about 10 hours and about four days, verted to the neutral form by methods known in the art.
between about one day and about three days. Alternatively, 0072 The products may be advantageously combined
the cooling step may take place for longer than one hour and/or used in combination with other therapeutic or pro
longer than about ten hours, longer than about 18 hours, phylactic agents, such as one or more cannabinoids and/or
longer than about 24 hours, longer than about 36 hours, terpenes. In many instances, administration in conjunction
longer than about 48 hours, longer than about 72 hours, with the subject products enhances the efficacy of such
longer than about 96 hours, longer than about 120 hours, or agents.
about 168 hours or longer. Alternatively methods for cooling 0073. The inventor has found that following the steps of
the solvent extract filtrate may also be used, such as storing the invention, 95+% pure THCa is readily crystallized from
in a cold environment such as in a refrigerator or freezer, or solution in quantities greater than 50% of the total extracted
by use of liquid nitrogen. Optionally, the crystallization step THCa. The balance of the THC and THCa remains in the
is performed without vibrating or disturbing the solvent solvent with the rest of the plant extract in the residual
extract filtrate. The preferred crystallization container mate filtrate, which is enriched in cannabinoids and terpenes
rial is glass. Optionally, the crystallization may be per relative to the original plant extract. The residual filtrate,
formed under pressure or vacuum. following crystallization of THCa, is relatively depleted in
0067. In one embodiment, the crystallization step is THCa, but will contain other cannabinoids and terpenes. The
encouraged and/or enhanced by increasing Surface area. residual filtrate may be combined with other materials
Methods to increase surface area for crystallization are and/or formed into products or formulations as described
known in the art, such as glass beads, which are optionally herein.
added prior to the crystallization. 0074 The present invention provides for the purity of the
0068 Crystals of THCa can be harvested by methods crystallized THCa to be at least 80%, at least 81%, at least
known in the art. In one example, crystals may be obtained 82%, at least 83%, at least 84%, at least 85%, at least 86%,
by filtering solvent and extract and capturing the retentate as at least 87%, at least 88%, at least 89%, at least 90%, at least
well as removing crystals by Scraping them from the glass 91%, at least 92%, at least 93%, at least 94%, at least 95%,
beads through a sieve with a metal spatula. Optionally, the at least 96%, at least 97%, at least 98%, or at least 99% pure
crystallization step may be repeated as many times as (w/w)
desired. The mother liquor can be subjected to another 0075 Optionally, any product should have solvent thor
cooling step to test if crystals will continue to form. The oughly removed.
present inventor has found that if yellow oil is present with 0076 Accordingly, the present invention includes a
the crystals, the separation from the other terpenes has method for obtaining crystallized THCa from a plant which
ceased to be effective. Crystallization should optionally be comprises at least one cannabinoid. These steps include
terminated before or when extracted oils begin to condense performing a solvent extraction of the plant to yield a solvent
and foul the pure THCa. extract, cooling the solvent extract, removing the precipitate
0069. The present inventor has found two morphologies from the cooled solvent extract to yield a solvent extract
of crystals, “sheet” and “ball crystals. Which morphology filtrate; allowing THCa to crystallize from the solvent
dominates seems to be influenced by the process conditions extract filtrate; and collecting the crystallized THCa.
and the quality of the starting material. 0077. The present invention also includes a method for
0070. In one embodiment, after the crystals of THCa obtaining crystallized THCa from a plant which comprises
have been collected according to the methods of the present at least one cannabinoid, such as THCa, directly from the
invention, the remaining extract can be collected and used Solvent extract. In this method, a plant or specific plant parts,
by evaporating the solvent. The residual filtrate was found to such as bud and/or trim, that are relatively enriched for one
contain cannabinoids and terpenes extracted from the origi or more cannabinoids, such as THCa, are optionally used.
nal bud or trim, and THC and THCa that did not crystallize This method encompasses directly crystallizing THCa from
during the course of the run. The residual filtrate can also be the solvent extract, by performing a solvent extraction of the
incorporated into finished products of their own, but retain plant or specific plant parts in accordance with the methods
Some of the characteristics of the original material instead of of the invention. The method then comprises cooling the
being quality independent from the source materials, like the solvent extract to allow the THCa to crystallize from the
crystallized THCa. Solvent extract according to the methods disclosed in the
US 2017/OOO887.0 A1 Jan. 12, 2017

present invention, and collecting the crystallized THCa. The Crystallization

invention also encompasses THCa obtained by the methods
of the invention. I0084 THCa, the acid precursor to THC, was crystallized
0078 All percentages and amounts in the present appli out of solution using the filtered solvent extract. Glass beads
cation, if not otherwise defined, are to be defined as weight were added to the beaker before putting it into an undis
percents (w/w). turbed deep freeze (-75° C.). Crystals formed in between 12
0079 While various aspects and features of certain hours and several days. The crystals were harvested by
embodiments have been summarized above, the following filtering solvent and extract and capturing the retentate as
detailed description illustrates a few embodiments in further well as removing crystals by Scraping them from the glass
detail to enable one of skill in the art to practice such beads through a sieve with a metal spatula. After collecting
embodiments. The described examples are provided for the crystals, the butane and extract mixture were returned to
illustrative purposes and are not intended to limit the scope the deep freeze to collect additional crystals. Two morpholo
of the invention. gies of crystals were observed, “sheet” and “ball crystals.
0080. Unless otherwise indicated, all numbers used The THCa crystals were 98+% pure THCa in quantities
herein to express quantities, dimensions, and so forth used greater than 50% of the total extracted THCa. The balance
should be understood as being modified in all instances by of the THC and THCa remained in the solvent with the rest
the term “about.” In this application, the use of the singular of the plant extract residual filtrate which is enriched in
includes the plural unless specifically stated otherwise, and cannabinoids and terpenes relative to the original plant
use of the terms “and” and 'or' means “and/or unless eXtract.
otherwise indicated. Moreover, the use of the term “includ
ing, as well as other forms, such as “includes and Termination
“included,” should be considered non-exclusive. Also, terms
such as "element” or “component' encompass both elements I0085. When the crystallization ceased to provide a clean
and components comprising one unit and elements and separation, the remaining extract was collected by evapo
components that comprise more than one unit, unless spe rating the solvent. This residual filtrate contained cannabi
cifically stated otherwise. noids and terpenes extracted from the original bud or trim,
and THC and THCathat did not crystallize during the course
EXAMPLES of the run.
0081. The following examples are provided for illustra I0086) The below table shows yields from each step of the
tive purposes only and are not intended to limit the scope of process.
the invention.

Example 1 Material Total Solids (g) 96 (THC + THCa)(THC + THCa)(g)

Starting trim 1OO 10% 10
Extraction Typical butane 12 75% 9
extract
0082 Dried cannabis material (bud, trim, or fan leaves, Initial sediment
Initial filtrate
1.5
1O.S
60%
770,
O.9
8.1
milled) was obtained. 50 g plant matter was added to a 1.5 THCa precipitate 6.5 95% 6.2
inch diameter aluminum column 12 inches in length, Sup Residual filtrate 4 48% 1.9
ported by a stand with a screen secured on the bottom and
rubber stopper with a center hole containing a nozzle on the Total 12 75% 9
top. In a well ventilated area, two 300 mL cans of 10° C.
99+% pure n-butane were poured into the top of the column,
about 5-10 minutes. The extract was collected in a beaker I0087. The description of the various embodiments has
and placed on dry ice in a cooler. The extraction was been presented for purposes of illustration and description,
repeated two times and the extracts were combined prior to but is not intended to be exhaustive or limiting of the
the separation step. invention to the form disclosed. The scope of the present
invention is limited only by the scope of the following
Separation claims. Many modifications and variations will be apparent
to those of ordinary skill in the art. The embodiments
0083. The beaker containing the extract was allowed to described and shown in the figures were chosen and
sit directly on dry ice in a Pelican ProGear Elite Marine described in order to explain the principles of the invention,
Deluxe Coolers cooler for 4 hours at approximately -70° C. the practical application, and to enable others of ordinary
Precipitate was observed on the bottom of the beaker. The skill in the art to understand the invention for various
extract was filtered through a vacuum assisted Buchner embodiments with various modifications as are suited to the
funnel using 12.5 cm diameter 101 fast filter paper and particular use contemplated. All references cited herein are
coffee filter taking care not to disturb the cake on the bottom incorporated in their entirety by reference.
of the beaker. The filtrate was returned to a clean beaker and
put back in the cooler on top of the dry ice for 3 hours and What is claimed is:
filtered again in a Buchner funnel with a coffee filter and 1. A method for obtaining a higher purity cannabinoid
slow quantitative filter. After two filterings, the solvent
extracts were optically clear. The retentate turned brown Solvent extract from a plant which comprises at least one
upon the solvent evaporation, is believed to be lignin, cannabinoid, comprising:
lecithin, and/ or other undesirable, high molecular weight a) performing a solvent extraction of the plant to yield a
materials that were extracted by the solvent. Solvent extract;
US 2017/OOO887.0 A1 Jan. 12, 2017

b) cooling the solvent extract; and 11. The method of claim 9, wherein the crystallization
c) removing the precipitate from the cooled solvent step comprises cooling the solvent extract filtrate.
extract to yield a solvent extract filtrate, wherein the 12. The method of claim 1, wherein the solvent is butane.
solvent extract filtrate has a higher purity of the at least 13. The method of claim 9, comprising separating the
one cannabinoid. crystals of THCa from the solvent extract filtrate.
2. The method of claim 1, wherein the precipitate com 14. A method for obtaining crystallized THCa from a
prises lignocellulosic material. plant which comprises at least one cannabinoid, comprising:
3. The method of claim 2, wherein the precipitate com a) performing a solvent extraction of the plant to yield a
prises lecithin or lignin. Solvent extract;
b) cooling the solvent extract;
4. The method of claim 1, wherein the solvent is selected c) removing the precipitate from the cooled solvent
from the group consisting of a short chain hydrocarbon, extract to yield a solvent extract filtrate;
carbon dioxide, an alcohol, or a terpene. d) allowing THCa to crystallize from the solvent extract
5. The method of claim 1, wherein the solvent extract is filtrate; and
cooled to a temperature of between about -50° C. and about e) collecting the crystallized THCa.
-85° C. for a time period of between about 30 minutes to 15. The method of claim 14, wherein the solvent is a short
about 6 hours. chain hydrocarbon or a terpene.
6. The method of claim 1, wherein the cannabinoid 16. The method of claim 14, wherein the precipitate
comprises tetrahydrocannabinolic acid (THCa). comprises lignocellulosic material.
7. The method of claim 1, wherein the solvent extract 17. The method of claim 14, wherein the solvent extract
filtrate has a higher purity of at least one cannabinoid filtrate is chilled to a temperature of between about -50° C.
compared to the solvent extract. and about -85° C. for a time period of between about 30
8. The method of claim 1, wherein the solvent extract minutes to about 6 hours.
filtrate has a higher purity of at least one terpene compared 18. The method of claim 14, wherein the solvent extract
to the solvent extract. filtrate is cooled to a temperature of about -75° C. for a time
9. The method of claim 1, wherein the method further period of between about 12 hours and three days.
comprises crystallizing tetrahydrocannabinolic acid (THCa) 19. The method of claim 14, wherein the crystallized
from the solvent extract filtrate. THCa is greater than 95% pure.
10. The method of claim 9, wherein the THCA is selec 20. THCapurified by the method of claim 14.
tively crystallized away from other soluble cannabinoids. k k k k k