Note: Descriptions are shown in the official language in which they were submitted.
PSU003-CANP
Standardized Psychoactive Alkaloid Extract Composition
TECHNICAL FIELD
[0001] This application relates to a composition. Particularly, this
application relates to
psychoactive alkaloid compositions comprising a natural extract.
BACKGROUND
[0002] This background information is provided to reveal information
believed by the
applicant to be of possible relevance to the present invention. No admission
is necessarily
intended, nor should be construed, that any of the following information
constitutes prior
art against the present invention.
[0003] A psychoactive substance is a chemical substance that changes brain
function
and results in alterations in perception, mood, consciousness, cognition, or
behavior.
Psychoactivity of these substances may include sedative, stimulant, euphoric,
deliriant,
and hallucinogenic effects. These substances have been used recreationally, to
purposefully improve performance or alter one's consciousness, or as
entheogens for
ritual, spiritual, or shamanic purposes. Some categories of psychoactive
compounds have
also shown therapeutic value and are prescribed by physicians and other
healthcare
practitioners.
[0004] The active constituents of the majority of psychoactive plants,
fungi, animals, or
yeasts fall within a class of basic, naturally occurring, nitrogen-containing,
organic
compounds called alkaloids (e.g. nicotine, morphine, cocaine, mescaline,
caffeine,
ephedrine, psilocin). Alkaloids have a wide range of pharmacological
activities including
antimalarial, antiasthma, anticancer, cholinomimetic, vasodilatory,
antiarrhythmic,
analgesic, antibacterial, and antihyperglycemic activities. Many alkaloids
have found use
in traditional or modern medicine, or as starting points for drug discovery.
Recently,
psychotropic and stimulant activities of psychoactive alkaloids have been
gaining
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immense interest from researchers as therapeutic agents for treating various
conditions
like alcoholism, opioid addiction, pain to name a few.
[0005] However, naturally occurring psychoactive alkaloid comprising
species have
inconsistent and often low contents of active psychoactive alkaloid (e.g. 0.1-
1% dry wt).
Considering fresh weight, this would mean a further 20X reduction in content
due to the
large moisture content of, for example, fresh mushrooms. The content of
psychoactive
alkaloid in natural sources depends on various factors such as the type of
source,
harvesting season, and type of extraction process, to name a few. Thus, the
lack of
compositions having a specific desired psychoactive alkaloid content with no
or minimal
variability between different batches is a major issue.
[0006] Maintaining physical and chemical stability is another challenge
with
psychoactive alkaloid compositions. Usually a psychoactive alkaloid extract is
in the form
of a sticky tar, which would difficult to handle and formulate into
standardized
compositions with specified amounts of ingredients. Extracts are not usually
amenable to
processing due to poor flowability. Extracts themselves are often not amenable
to drying
because many of the components that are pulled out of a plant or fungus with a
lower
alcohol solvent are not "dry" at room temperature (reduced sugars, oils and
waxes for
example). These same compounds even in low concentration can cause the product
to be
hygroscopic and become clumpy, which makes encapsulation impossible, and makes
tabulation difficult because the powder will not "flow" in the equipment.
[0007] Thus, exposure to moisture causes psychoactive alkaloid extracts to
absorb
moisture to form clumps and become susceptible to microbial growth. Further,
the
alkaloids in these extracts can degrade, usually because of oxidation.
SUMMARY OF INVENTION
[0008] The primary aim of the invention is to standardize the amount of
psychoactive
alkaloid present in the composition. Depending on the embodiment, and the
specific types
of excipient added, a secondary, optional aspect of the invention is the
provision of a
psychoactive alkaloid extract in the form of a dry, flowable and shelf-stable
powder. The
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powder may be used as a dietary supplement or medicine and can be added to
various
edible products, tablets, or capsules, or it may be used for medical research,
including the
study of the treatment of mental illnesses.
[0009] By increasing the active alkaloid concentration through extraction
and then
titrating back to a lower, standardized alkaloid concentration, the product
achieves
consistency in bioactive content from lot to lot. By the addition of specific
types of
excipient, flowability and stability may also be improved in the composition,
as compared
to the extract.
[0010] A useful formulation needs to contain a minimum amount of the active
ingredient and also be of an acceptable total size. For example, a psilocybin
dose might
be 25 mg. If this is required in a single capsule and the powder has a
concentration of the
active ingredient of only 1%, then 2500 mg of powder would be needed. This
would be too
much for a single capsule. However, if the extract can be concentrated to
approx. 15%,
then there is room to add an excipient to get it down to say, a repeatable
10%, which now
means that only 250 mg of powder is needed in the capsule, which is an
acceptable size.
[0011] While the concentration of psychoactive alkaloid in the composition
may, in
some embodiments, be lower than that found in some of the source raw material
(mushrooms or seeds for example), it is a known concentration, which can be
stable from
batch to batch, eliminating the variability found in the natural sources. This
allows for
control and standardization of the dose, even if it is lower than some of the
raw materials
themselves.
[0012] Disclosed herein is a psychoactive alkaloid composition consisting
essentially
of, by weight: 0.1-99.9% of a psychoactive alkaloid extract; a preservative up
to 10%, a
flow agent up to 2%, or both the preservative up to 10% and the flow agent up
to 2%; and
0-94% of a carrier.
[0013] This summary does not necessarily describe all features of the
invention.
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BRIEF DESCRIPTION OF DRAWINGS
[0014] The following drawings illustrate embodiments of the invention,
which should
not be construed as restricting the scope of the invention in any way.
[0015] FIG. 1 illustrates steps of a process for obtaining a standardized
psychoactive
alkaloid composition, according to an embodiment of the present invention.
[0016] FIG. 2 illustrates a process for extracting psychoactive alkaloid
from Psilocybe
cubensis, according to an embodiment of the present invention.
[0017] FIG. 3 illustrates detailed steps of a process for purifying
psychoactive alkaloid
from Psilocybe cubensis, according to an embodiment of the present invention.
[0018] FIG. 4 is a schematic diagram of the apparatus used for obtaining a
psychoactive alkaloid composition, according to an embodiment of the present
invention.
DESCRIPTION
A. Glossary
[0019] To facilitate the understanding of this invention, a number of terms
are defined
below. Terms defined herein have meanings as commonly understood by a person
of
ordinary skill in the areas relevant to the present invention. Terms such as
"a", "an" and
"the" are not intended to refer to only a singular entity but include the
general class of
which a specific example may be used for illustration. The terminology herein
is used to
describe specific embodiments of the invention, but their usage does not
delimit the
invention, except as outlined in the claims.
[0020] As will be understood by one skilled in the art, for any and all
purposes, such as
in terms of providing a written description, all ranges disclosed herein also
encompass
any and all possible subranges and combinations of subranges thereof. Any
listed range
can be easily recognized as sufficiently describing and enabling the same
range being
broken down into at least equal halves, thirds, quarters, fifths, tenths, etc.
As a non-
limiting example, each range discussed herein can be readily broken down into
a lower
third, middle third and upper third, etc. As will also be understood by one
skilled in the art,
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all language such as "up to," and the like include the number recited, and any
tolerance
explicitly or implicitly associated with it, and refer to ranges which can be
subsequently
broken down into subranges as discussed above. Finally, as will be understood
by one
skilled in the art, a range includes each individual member.
[0021] The term "psychoactive alkaloid" as used herein refers to alkaloids
that upon
ingestion are capable of changing brain function, resulting in alterations in
perception,
mood, consciousness, cognition or behavior, for example. Psychoactive
alkaloids are
abundant in nature and can be obtained from sources such as a fungus, an
animal, a
mycelium, a spore, a plant, a bacterium, or a yeast. Examples of psychoactive
alkaloids
include, but are not limited to, psilocybin, psilocin, baeocystin,
norbaeocystin, norpsilocin,
aeruginascin, bufotenin, bufotenidine, 5-Me0-DMT (5-methoxy-N,N-
dimethyltryptamine),
N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol,
ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine,
ergometrinine, and/or
chanoclavine. The source of the psychoactive alkaloid can also be another
extract or a
solution comprising a psychoactive alkaloid.
[0022] The term "psychoactive alkaloid extract" or "extract" refers to a
psychoactive
alkaloid extract that is obtained after a psychoactive alkaloid source has
been extracted
according to a process described herein. The extract may be a fluid, as either
a liquid or a
slurry, or is made into a fluid by the addition of a solvent. The term
"extract" may also be
used for the dried form of the fluid extract.
[0023] The term "purified psychoactive alkaloid extract" refers to a
purified extract that
is obtained after a psychoactive alkaloid extract is treated with one or more
resins for
purification as described herein, or by other means of purifying the
concentration of the
psychoactive alkaloid concentration. This purified psychoactive alkaloid
extract is
substantially free of impurities, or contains fewer impurities compared to a
similar
psychoactive alkaloid extract that has not undergone any purification. The
purified
psychoactive alkaloid extract is a fluid, either a liquid or a slurry, or is
made into a fluid by
the addition of a solvent.
[0024] The "impurities" herein are commonly undesired, but not necessarily
harmful,
substances encountered while extracting psychoactive alkaloids from a natural
source.
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Impurities may include sugars, carbohydrates, chitin, chitosan, fats,
minerals, waxes,
and/or proteins. The impurities being removed from a psychoactive alkaloid
extract will
vary depending on the source of the psychoactive alkaloid. Their removal
increases the
concentration of the desired psychoactive alkaloids remaining in the extract.
[0025] The term "substantially" as used herein refers to a majority of, or
mostly, as in
at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%,
99.99%, or at least about 99.999% or more.
[0026] The term "specific pH psychoactive alkaloid solution" used herein
refers to a
solution that is obtained after addition of a suitable acid or a base to a
psychoactive
alkaloid extract to achieve a solution with a desired pH level.
[0027] The term "adsorbed psychoactive alkaloid" refers to one or more
alkaloids that
are adsorbed onto an adsorbent material such as a resin.
[0028] The term "psychoactive alkaloid composition" or "composition" or
"standardized
composition" or "standardized purified composition" is used herein to describe
a
composition including a psychoactive alkaloid extract or a purified
psychoactive alkaloid
extract, which has been standardized by the addition of excipients according
to a
presently described process. The standardized psychoactive alkaloid
composition
includes the psychoactive alkaloid in a specific amount.
[0029] The term "standardization" when used herein refers to a process for
obtaining a
standardized psychoactive alkaloid composition, i.e. a composition with a
defined
concentration by weight of psychoactive alkaloid.
[0030] As used herein, the term "specific amount" when referring to a
psychoactive
alkaloid content means a desired percentage, accurate to one or two decimal
places or
one or two significant figures, of the psychoactive alkaloid content in a
psychoactive
alkaloid composition. The specific amount is defined as a percentage by weight
and can
be selected by a person of skill in the art according to preference.
[0031] The term "% wt" is used to describe the weight percentage of one
component
in a mixture of components.
[0032] The term "resin" used herein is intended to refer to a solid or
highly viscous
substance of plant or synthetic origin that is typically convertible into
polymers. Resins are
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usually mixtures of organic compounds. Resins are typically used in
chromatographic
techniques as a stationary phase to purify and separate compounds depending on
their
polarity. Resins can be physically or chemically modified to provide
specificity to bind or
repel particular molecules within sometimes very complex mixtures.
[0033] As used herein, the term "ion exchange resin" refers to an insoluble
organic
polymer containing charged groups that attract and hold oppositely charged
ions present
in a surrounding solution in exchange for counterions previously held.
Suitable ion
exchange resins to be used herein contain cationic groups that attract and
hold anions
present in a surrounding solution and are sometimes referred to as "anionic
ion-exchange
resins". Similarly, ion exchange resins to be used herein contain anionic
groups that
attract and hold cations present in a surrounding solution and are sometimes
referred to
as "cationic ion-exchange resins".
[0034] The term "macroporous resin" used herein refers to a member of a
class of
very small, highly cross-linked polymer particles. Macroporous resins are
generally used
for the absorption of organic constituents due to their hydrophobic properties
and thus
separate and purify compounds. The adsorption capacity of macroporous resins
not only
correlates with the physical and chemical properties of the adsorbent, but
also with the
size and chemical features of the adsorbed substance.
[0035] The term "therapeutic effects" is intended to qualify the amount of
active
ingredients required in the treatment of a disease or disorder or on the
effecting of a
clinical endpoint. Reference to "treatment" of a patient is intended to
include prophylaxis.
Treatment may also be preemptive in nature, i.e., it may include prevention of
disease.
Prevention of a disease may involve complete protection from disease, for
example as in
the case of prevention of infection with a pathogen or may involve prevention
of disease
progression. For example, prevention of a disease may not mean complete
foreclosure of
any effect related to the diseases at any level, but instead may mean
prevention of the
symptoms of a disease to a clinically significant or detectable level.
Prevention of
diseases may also mean prevention of progression of a disease to a later stage
of the
disease.
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[0036] The term "excipient" means any component added to an active
ingredient to
make a composition. An excipient is inert in relation to the active
ingredient, in that it
essentially does not act in the same way as the active ingredient. An
excipient may be
completely inert, or it may have some other property that protects the
integrity of the
active ingredient or assists its uptake into the human body. There are
multiple types of
excipient, each having a different purpose, and a given excipient may fulfill
more than one
purpose. Examples of types of excipient include flowability agents,
flavorants, colorants,
palatants, antioxidants, bioavailability-increasing agents, viscosity
modifying agents,
tonicity agents, drug carriers, sustained-release agents, comfort-enhancing
agents,
emulsifiers, solubilizing aids, lubricants, binding agents and stabilizing
agents. Specific
excipients include pectin, rice husks, rice, xanthum gum, gum arabic, beta
cyclodextrin,
alpha cyclodextrin, microcrystalline cellulose, sorbitol, dextrose, guar gum,
acacia gum,
cellulose gum, talc, magnesium stearate.
[0037] The term "carrier" means an excipient that aids in delivery of the
active
ingredient or provides bulk to the composition. The amount of carrier included
in a
composition can vary widely in order to control the concentration of the
active ingredient in
the composition. An example of a carrier is starch, maltodextrin, tapioca
maltodextrin or
rice maltodextrin, alpha and beta cyclodextrin, microcrystalline cellulose
(MCC), gum
arabic, xanthum gum, guar gum, or cellulose gum.
[0038] The term "flow agent", "flowability agent" or "anti-caking agent" or
"anti-
adherent" means an excipient that prevents or reduces the formation of lumps
in a
powdered composition. An example of a flow agent is silicon dioxide, stearic
acid,
magnesium stearate, or talc.
[0039] The term "preservative" means an excipient that is added to the
composition to
prevent microbial growth or microbial degradation of the composition. Examples
of
preservative are ascorbic acid, citric acid, lactose, vitamin A, vitamin E,
retinyl palmitate,
selenium, sodium citrate, sodium ascorbate, calcium ascorbate, sodium
benzoate, and
potassium benzoate.
[0040] Throughout the description, specific details have been set forth in
order to provide
a more thorough understanding of the invention. However, the invention may be
practiced
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without these particulars. In other instances, well known elements have not
been shown
or described in detail and repetitions of steps and features have been omitted
to avoid
unnecessarily obscuring the invention. Accordingly, the specification and
drawings are to
be regarded in an illustrative, rather than a restrictive, sense.
[0041]
It will be clear to one having skill in the art that further variations to the
specific
details disclosed herein can be made, resulting in other embodiments that are
within the
scope of the invention disclosed. Steps in the flowchart may be performed in a
different
order, other steps may be added, or one or more may be removed without
altering the
main outcome of the process.
B. Composition
[0042] In some embodiments, the present invention relates to a composition
having, by
weight, 2-99.7% of a psychoactive alkaloid extract, and 0.3-98%, i.e. the
remainder, being
one or more excipients.
[0043] While a broad range of psychoactive extract is possible, if it is above
90% (e.g. as
much as 99.9%) it is likely not to be dryable and/or flowable. Nevertheless,
such a
composition, when standardized, may still have its uses, due to the
reliability and
repeatability of the psychoactive alkaloid content. Below about 2%, the
composition may
be considered to provide too low a dose of psychoactive alkaloid. However,
compositions
with less than 2% (e.g. down to 0.1%) may be possible if micro-dosing is
desired.
[0044] In some embodiments, the psychoactive alkaloid extract has a
psychoactive
alkaloid concentration ranging from 0.1% to 99% by weight of the extract.
Typically it may
be in the range of 1-10% dry wt/wt% for the non-purified extract
concentration. However,
as the composition may be made with purified extract, the psychoactive
concentration
could be as high as 99%. In some embodiments, the psychoactive alkaloid
extract has a
psychoactive alkaloid concentration ranging from 1.03% to 75.22% by weight of
the dry
extract. In some embodiments, the psychoactive alkaloid extract has a
psychoactive
alkaloid concentration ranging from 1.03% to 3.02% by weight of the extract.
In other
embodiments, the psychoactive alkaloid extract is a purified psychoactive
alkaloid extract.
In some embodiments, the purified psychoactive alkaloid extract has a
psychoactive
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alkaloid concentration ranging from 10% to 99% by weight of the extract. In
other
embodiments, the purified psychoactive alkaloid extract has a psychoactive
alkaloid
concentration ranging from 16.12 % to 75.22% by weight of the extract.
[0045] In other embodiments, the psychoactive alkaloid extract includes
naturally
occurring substances selected from fats, sugars, carbohydrates, and proteins,
or any
combination selected therefrom. The aforesaid naturally occurring substances
do not lead
to any side effects or adverse effects when ingested as a part of the
composition.
[0046] The naturally occurring substances are present in the psychoactive
alkaloid
extract in a concentration ranging from 1 - 99.9% by dry weight. The
concentration range
of the naturally occurring substances in the psychoactive alkaloid extract
will vary due to
various factors for example, but not limited to, the source of the
psychoactive alkaloid
extract, the extraction technique used, the efficiency of the extraction
process, and the
amount of the psychoactive alkaloid in the extract.
[0047] In some embodiments, the psychoactive alkaloid extract includes the
psychoactive alkaloid and the naturally occurring substances.
[0048] The psychoactive alkaloid extract of the composition low in (e.g. <20%)
or almost
free of undesired impurities allows a smaller amount of the composition to
achieve a
desired therapeutic effect than if the extract were less concentrated, with
more impurities.
[0049]
The excipients described herein refer to excipients to aid in the
manufacturing
and/or administration of the compositions described herein. Non-limiting
examples of such
excipients are known in the art and include flowability agents, flavorants,
colorants,
palatants, antioxidants, bioavailability-increasing agents, viscosity
modifying agents,
tonicity agents, drug carriers, sustained-release agents, comfort-enhancing
agents,
emulsifiers, solubilizing aids, lubricants, binding agents, stabilizing agents
and other
agents to aid in the manufacturing and/or administration of the compositions.
The
excipients used in the present invention are acceptable for use in
pharmaceutical or
nutraceutical applications or as food ingredients.
[0050] In some embodiments, the excipient is a carrier, a flowability agent, a
preservative or any combination selected therefrom. The amount of excipient in
the
composition will vary depending on the desired amount of the psychoactive
alkaloid
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extract in the composition, and on the concentration of psychoactive alkaloids
in the
extract. It will also depend on the degree of flowability required and the
stability required.
[0051] In some embodiments, the excipients include a flowability agent, in
an amount
up to 2% by weight of the composition. Above 2%, little extra benefit is
gained. In other
embodiments, the excipients include a flowability agent in a concentration
equal to or less
than 2% by weight of the composition. In some embodiments, the flowability
agent is
silicon dioxide. In other embodiments, the flowability agent is magnesium
stearate, stearic
acid or talc, or is selected from any other known, suitable flowability agent.
A combination
of any of these flowability agents may be used. It is also envisaged that
other flowability
agents can be used. The impurities present in the extract tend to have a
negative effect
on the flowability, and flow agents are added to counter these effects. While
there are
known methods of measuring flowability, this is not always necessary as the
product's
lack of adequate flowability is often very evident when one handles the
product.
[0052] In some embodiments, the excipients include a carrier, in an amount up
to 94%
by weight of the composition. In some embodiments, the excipients include a
carrier
ranging from 10-94% by weight of the composition.
[0053] In some embodiments, the carrier is maltodextrin, or in other
embodiments it is
microcrystalline cellulose, coconut flour or corn starch, or any other known,
suitable
carrier. A combination of any of these carriers may be used. It is also
envisaged that other
carriers can be used.
[0054] The preservative is selected from ascorbic acid, citric acid,
lactose, vitamin A,
vitamin E, retinyl palmitate, selenium, sodium citrate, sodium ascorbate,
calcium
ascorbate, sodium benzoate, and potassium benzoate. A combination of any of
these
preservatives may be used. It is also envisaged that other preservatives can
be used.
[0055] In some embodiments, the excipients include a preservative, up to 10%
by weight
of the composition. In some embodiments, preservatives are not added to the
composition. There may be cases where a preservative is not required, or not
wanted in
the final product, and so the concentration of preservative will be 0%. At a
certain point
(>10% in this example), the preservative will not give any further benefit,
and so the upper
limit of preservative is 10%.
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[0056]
The composition of the present invention is in a powder form. The components
of the composition are also in powder form. The composition of the present
invention may
be in the form of a free-flowing powder depending on the embodiment. Such
compositions
are thus easy to handle during manufacturing and packaging processes. Further,
the dry,
free-flowing powder form allows the composition to be free from clumps and not
be as
susceptible to microbial growth as a composition with clumping due to moisture
absorption.
[0057] The composition of the present invention has the psychoactive alkaloid
present in
a specific amount. In some embodiments, the specific amount of psychoactive
alkaloid is
accurate to one significant figure. In another embodiment, the specific amount
psychoactive alkaloid is accurate to two, three or four significant figures.
The presence of
the psychoactive alkaloid in a specific amount in the composition allows for
the same
desired specific amount of the psychoactive alkaloid to be present in various
batches of
the psychoactive alkaloid composition.
[0058] The main consideration is that, depending on the source material's
concentration
and the efficiency of the extraction, the concentration of the extract needs
to be blended
down to the required value of standardization. This dictates the amount of
excipient for
each batch, which may be different. Therefore, the amount of excipient that
can be added
can be anywhere between say 0.100% to 99.9%, depending on the source
concentration
before blending. The other excipient components may be held relatively
constant between
batches, or within a much narrower range (i.e. 0-2% flowability agent, 0-10%
preservative,
0-0.5% antioxidant, 0-0.5% bioavailability agent).
C. Basic Standardization Process
[0059] In one embodiment, referring to FIG. 1, a basic process for obtaining
the
composition is shown. The process includes the step 10 of extracting a
psychoactive
alkaloid from a psychoactive alkaloid source to obtain a psychoactive alkaloid
extract. The
extract from the psychoactive alkaloid source may be a fluid, as either a
liquid or a slurry,
or is made into a fluid by the addition of a solvent. In one embodiment, the
extraction step
is followed by completely or partially concentrating the obtained psychoactive
alkaloid
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extract (or solution) by evaporation of the solvent from the extract. In other
embodiments,
partially or completely evaporating the solvent may be considered to be part
of the
extraction step 10. If the solvent from the extract has been completely
evaporated, then
water, more solvent or another solvent is added back.
[0060] In step 12, the extract obtained is filtered, followed by concentration
to obtain a
concentrated psychoactive alkaloid extract. Filtration is performed by any
suitable known
technique.
[0061] In step 14, the concentrated psychoactive alkaloid extract is then
standardized by
adding one or more excipients to the extract, followed by drying to obtain the
standardized
psychoactive alkaloid composition. The concentration of alkaloids in the
extract is
measured and the proportion of dry weight in the extract is calculated. Based
on this
concentration and dry weight content, the amount of excipient to be added is
chosen to
result in a powered composition with a specific amount of psychoactive
alkaloid when the
concentrated extract is dried.
[0062] The drying can be achieved by any technique known in the art for drying
moist
compositions including, for example, spray drying or freeze drying.
D. Extraction
[0063] In some embodiments, referring to FIG. 2, a process for extracting the
psychoactive alkaloid is shown. The psychoactive alkaloid source is dried in
step 16 by
techniques known in the art, such as using a forced air oven.
[0064] In step 18, the dried psychoactive alkaloid source or dried biomass is
mixed with
a solvent and/or left to soak. The solvent in which the extract is carried or
dissolved may
be a primary aliphatic alcohol, a ketone, water, and any combination selected
therefrom.
In some embodiments, the primary aliphatic alcohol is a C1-4 alcohol. In some
embodiments, the primary aliphatic alcohol is 5% ethanol. In some embodiments,
the
primary aliphatic alcohol is ethanol. In some embodiments, the ketone is a C3-
4 ketone. In
yet other embodiments, the water is selected from deionized, distilled,
reverse osmosis, or
otherwise purified water, which is substantially without free ions. In other
embodiments,
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the water is not purified. In an exemplary embodiment, the solvent is a hydro-
ethanol
mixture with 3 parts of ethanol to 1 part of water, by weight.
[0065] In step 20, the mixture of the solvent and the dried psychoactive
alkaloid source
is filtered to obtain a filtrate and a filtrate residue. Some or all of the
solvent is evaporated
from the filtrate residue to obtain the psychoactive alkaloid extract.
Standardization of the
obtained psychoactive alkaloid extract is carried out according to the
standardization step
14 described above.
[0066] Optionally, the filtrate residue obtained in step 20 is extracted with
the solvent
again. The filtrate residue is extracted by repeating the steps 18 and 20.
This results in
another filtrate. The first filtrate and the second filtrate are mixed
together after their
respective filtration steps to result in a bulk filtrate. The solvent from
this bulk filtrate is
partially evaporated to obtain the psychoactive alkaloid extract in a slurry
form for the
standardization step 14.
[0067] In one embodiment, the extraction is carried out at a temperature
ranging from 5-
95 C. The useful temperature range spans most of the liquid state of the
solvent used,
and upper and lower limits are determined by physical practicalities and
limits of the
available apparatus. Still, the temperature of the solvent may be outside of
this range in
other embodiments.
[0068] In other embodiments, the extraction is carried out at a temperature of
70 C.
Temperature, and pressure if applied, are generally selected so that the
solvent does not
boil if elevated temperatures are used. In one embodiment, the extraction is
carried out for
a time duration ranging from 10 minutes to 12 hours. In yet another
embodiment, the
extraction is carried out for a time duration of 4 hours.
E. Purification Process
[0069] In some embodiments, referring to FIG. 3, a process for purifying the
psychoactive alkaloid extract obtained in step 12 (FIG. 1) or step 20 (FIG. 2)
is shown.
[0070] The process includes adding, in step 22, an acid or a base to the
psychoactive
alkaloid extract previously obtained, to result in a specific pH psychoactive
alkaloid
solution.
14
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[0071] When used, the acid may be acetic acid, adipic acid, ascorbic acid,
phosphoric
acid, ammonium aluminum sulphate, ammonium citrate dibasic, ammonium citrate
monobasic, calcium citrate, calcium fumarate, calcium gluconate, calcium
phosphate
dibasic, calcium phosphate monobasic, hydrochloric acid, sulphuric acid
monobasic,
calcium phosphate tribasic, citric acid, fumaric acid, gluconic acid,
magnesium fumarate,
malic acid, phosphoric acid, potassium acid tartrate, potassium citrate,
potassium
fumarate, sodium citrate, sodium fumarate, sodium gluconate, sodium lactate,
sodium
potassium hexametaphosphate, sodium potassium tartrate, sodium potassium
tripolyphosphate, sodium pyrophosphate tetrabasic, sodium tripolyphosphate,
tartaric
acid, and any combination of one or more of these. In some embodiments, the
acid is
either only hydrochloric acid or only phosphoric acid, for example. It is also
envisaged that
other acids may be used.
[0072] When used, the base may be ammonium bicarbonate, ammonium carbonate,
ammonium hydroxide, calcium acetate, calcium carbonate, calcium chloride,
calcium
hydroxide, calcium lactate, calcium oxide, calcium phosphate dibasic, calcium
phosphate
monobasic, magnesium carbonate, potassium aluminum sulphate, potassium
bicarbonate, potassium carbonate, potassium hydroxide, potassium lactate,
potassium
phosphate dibasic, potassium pyrophosphate tetrabasic, potassium phosphate
tribasic,
potassium tripolyphosphate, sodium acetate, sodium acid pyrophosphate, sodium
aluminum phosphate, sodium aluminum sulphate, sodium bicarbonate, sodium
bisulphate, sodium carbonate, sodium hexametaphosphate, sodium hydroxide,
sodium
lactate, sodium phosphate dibasic, sodium phosphate monobasic, sodium
phosphate
tribasic or any combination selected therefrom. In one embodiment, the base is
solely
sodium hydroxide, for example. Other bases may be used in other embodiments.
[0073] In some embodiments, the specific pH psychoactive alkaloid solution has
a pH
ranging from 2.5-4.5, or from 9-10. In other embodiments, the specific pH
psychoactive
alkaloid solution has a pH of 3, 4, or 9.5. The selection of the pH is chosen
in a manner to
allow for the efficient adsorption of the psychoactive alkaloids onto the
resin(s).
[0074] The process optionally includes partially evaporating the solvent from
the specific
pH psychoactive alkaloid solution.
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[0075] The process optionally includes filtering, centrifuging, or clarifying
the
psychoactive alkaloid solution or specific pH psychoactive alkaloid solution,
as the case
may be, and utilizing the obtained filtrate for the next step 24 of
adsorption. Clarifying may
be performed, for example, by adding an agglomeration agent.
[0076] In step 24, the process involves adsorbing the psychoactive alkaloid(s)
in the
specific pH psychoactive alkaloid solution onto a resin to obtain an adsorbed
psychoactive
alkaloid.
[0077] In step 26, the process involves washing the resin to remove adsorbed
impurities
from the resin. While not all the impurities are adsorbed onto the resin, some
of them may
be. The washing step, substantially, does not remove the adsorbed psychoactive
alkaloids. The washing solvent may be 100% ethanol, 100% reverse osmosis
water, or
any other washing solvent used in ion-exchange resin chromatography, provided
that the
washing removes impurities or by-products that are adsorbed on the resin.
Impurities or
by-products may include, for example, sugars, carbohydrates, chitin, chitosan,
fats,
minerals, waxes, or proteins. There may be one, two or more washing steps
depending
on the embodiment, and the same or different washing solvents may be used for
each
wash.
[0078] In other embodiments, the solvent(s) for washing may include a primary
aliphatic
alcohol, a ketone, water, and any combination selected therefrom. In some
embodiments,
the primary aliphatic alcohol is a C1-4 alcohol. In some embodiments, the
primary
aliphatic alcohol is 5% ethanol. In some embodiments, the primary aliphatic
alcohol is
ethanol. In some embodiments, the ketone is a C3-4 ketone. In yet other
embodiments,
the water is selected from deionized, distilled, reverse osmosis, or otherwise
purified
water that is substantially without free ions.
[0079] After the washing, the process involves eluting, in step 28, the
adsorbed
psychoactive alkaloid from the resin using a solvent to obtain a purified
psychoactive
alkaloid extract. The solvent may be an organic solvent, an acid, a base, or
water, a
combination of an organic solvent and a base, or a combination of an organic
solvent and
an acid, a combination of an organic solvent and water, a combination of water
and a
base, or combination of water and an acid. The solvent from the purified
psychoactive
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alkaloid extract is partially evaporated to obtain the purified psychoactive
alkaloid extract
in a slurry form for the standardization step 14.
[0080] In some embodiments, the solvent used in the elution step 28 may be a
C1-4
alcohol, a C3-4 ketone, water, and any combination selected therefrom. In one
embodiment, the primary aliphatic alcohol is 5% ethanol. In yet another
embodiment, the
water is deionized, distilled, reverse osmosis, or otherwise purified water,
which is
substantially without free ions. In one embodiment, the solvent used in the
elution step 14
is a combination of an organic solvent and an acid. In general, any acidic
environment will
displace some of the ions from the resin, but the rate and optimization of the
desorption
will be affected by the acid concentration. In one embodiment, the solvent
used is a
combination of an organic solvent and a base. In general, any basic
environment will
displace some of the ions from the resin, but the rate and optimization of the
desorption
will be affected by the concentration of the base.
[0081] All the above solvents and combinations thereof are suitable for the
elution step
because all of the psychoactive alkaloids of interest are soluble therein and,
depending on
the choice of resin, they are all capable of pulling the alkaloids of interest
off a resin.
There are many different resins available, and it is a straightforward matter
to select a
suitable resin and elution solvent pair.
[0082] In one embodiment, the elution step is carried out at a temperature in
the range
of 4-75 C. These temperatures are limited by the boiling point of the solvent
used, as well
as the specifications of allowable food-grade resins, as determined by the
manufacturers
of the resins and governmental food and drug administrations. In another
embodiment,
the elution step is carried out at room temperature for convenience, i.e. at
21-25 C.
[0083] In other embodiments, the process for obtaining the purified
psychoactive alkaloid
extract further includes repeating the steps 22 to 28 with the purified
psychoactive alkaloid
extract obtained in step 28 to obtain a further or twice purified psychoactive
alkaloid
extract. For the repeated steps in these embodiments, the resin may be the
same or a
different resin, and the solvent may be the same or a different solvent. While
the purified
psychoactive alkaloid extract may have a low psychoactive alkaloid content,
this may be
increased by evaporation of some or all of the solvent.
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F. Variations
[0084] The psychoactive alkaloid source may be a fungus, a mycelium, an
animal, a
spore, a plant, a bacterium, or a yeast. The psychoactive alkaloid source in
some
embodiments may be a prior extract of one or more psychoactive alkaloids,
where the
prior extract is to undergo a further extraction process. The psychoactive
alkaloid may
include, but is not limited to, psilocybin, psilocin, baeocystin,
norbaeocystin, norpsilocin,
aeruginascin, bufotenin, bufotenidine, 5-Me0-DMT (5-methoxy-N,N-
dimethyltryptamine),
N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol,
ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine,
ergometrinine, and/or
chanoclavine, or any combination selected therefrom. It is possible that other
psychoactive alkaloids, not yet discovered, may also be extracted using the
methods
disclosed herein.
[0085] In some embodiments, the psychoactive alkaloid is a combination of
psilocybin
and psilocin. In another embodiment, the psychoactive alkaloid is psilocybin.
In yet
another embodiment, the psychoactive alkaloid is psilocin.
[0086] In some embodiments, the resin is an adsorbent resin of the macroporous
type,
such as a cation or anion ion-exchange resin, a non-ionic resin, or any
combination
selected therefrom. Representative pharmaceutical, nutraceutical or food-grade
grade
resins for use in accordance with the present invention are known to those
skilled in the
art. For example, pharmaceutical grade non-ionic macroporous resins are
commercially
available, e.g. Amberlite XAD4. In one embodiment, the resin is a cationic
ion-exchange
resin or an anionic-exchange resin. The cationic ion-exchange resin may be
selected from
commercially available cationic ion-exchange resins known in the art,
including but not
limited to Amberlite MAC-3 H. The cationic ion-exchange resin may be in an H+
form or
an Na+ form. The anionic ion-exchange resin may be selected from commercially
available anion exchange resins known in the art, including but not limited to
Amberchrom 50WX8. The anionic ion-exchange resin may be in an OH- form or a
Cl-
form. The resins used may be of any particle size. In some embodiments, the
resins may
be gel type resins, with any size of gel bead.
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[0087] The concentration of psychoactive alkaloid in the purified psychoactive
alkaloid
extract may be different in other embodiments, depending on the amount of
solvent used
for the elution and the potency of the raw materials. In one embodiment, the
purified
psychoactive alkaloid extract is concentrated by evaporating the solvent to
form a purified
psychoactive slurry that has at least of 5% by weight or more of a
psychoactive alkaloid.
In another embodiment, the purified psychoactive alkaloid slurry has 5-68% by
weight of a
psychoactive alkaloid. In yet other embodiments, the purified psychoactive
alkaloid slurry
has a concentration of psychoactive alkaloid outside these ranges, and, when
dried, can
be as low as 0.1% or as high as 99.9% dry wt/wt%.
[0088] In some embodiments, a bioavailability enhancing agent such as citric
acid, beta
cyclodextrin, or alpha cyclodextrin can be added (up to 0.5% by weight) as an
excipient.
In other embodiments, an antioxidant agent such as ascorbic acid may be added
(up to
0.5% by weight) as an excipient.
G. Examples
[0089] In order to further illustrate the present invention, the following
specific
examples are given with the understanding that these examples are intended
only to be
illustrations without serving as a limitation on the scope of the present
invention. All
parameters, dimensions, materials, quantities and configurations described
herein are
examples only and may be changed depending on the specific embodiment.
Accordingly,
the scope of the invention is to be construed in accordance with the substance
defined by
the claims. The process may be scaled up using larger quantities and modified
apparatus.
[0090] Although the examples of the present invention have been formulated
specifically using psilocybe cubensis as a source to obtain a psychoactive
alkaloid extract,
the extract including psilocybin and psilocin, other sources are possible. A
person skilled
in the art would appreciate that the psilocybe cubensis can be readily
substituted by other
sources of psychoactive alkaloids to obtain a variety of other psychoactive
alkaloids
having similar properties, such as baeocystin, norbaeocystin, norpsilocin,
aeruginascin,
bufotenin, bufotenidine, 5-Me0-DMT (5-methoxy-N,N-dimethyltryptamine), N,N-
dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol,
ibotenic
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acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine,
and/or
chanoclavine, to result in compositions with similar efficacy and efficiency
as well. For
example, psilocybe cyanescens and amanita muscaria fungi may be used. For
example,
the venom of the toad Incilius alvarius, the Anadenanthera colubrina tree or
the
Anadenanthera peregrina tree may be used as other sources of psychoactive
alkaloids.
Note that the lists of sources and psychoactive alkaloids are included to
provide
examples, and are non-exhaustive lists.
Example 1: Preparation of a non-purified psychoactive alkaloid extract
[0091] Fresh Psilocybe cubensis, 2.5 kilograms, was dried in a forced air
oven at 25 C
for 5-10 hours, to result in 140 grams of dried biomass. The dried biomass was
pulverized
to a size of 200 mesh with a hammer mill. The dried powdered biomass was then
placed
into an agitated, heat-controlled vessel with 5 kilograms of solvent. The
solvent was a
hydro-ethanol mixture of 3 parts ethanol to 1 part water by weight. The
extraction was
controlled to a constant 70 C, and the time of extraction was 4 hours.
[0092] The extraction slurry was filtered while hot, and the filter residue
was placed
back into the extraction vessel, and extracted with an additional 5 kilograms
of 3:1
ethanol:water mixture by weight. The temperature of extraction was again 70 C
and the
time was 4 hours. The extraction slurry was filtered while hot and the
filtrate from the first
and second extraction were mixed together to obtain a bulk filtrate.
[0093] The bulk filtrate was immediately placed into a rotary evaporator
and the
solvent was concentrated in the rotary evaporator to obtain 186.6 g of the
psychoactive
alkaloid extract in form of a concentrated aqueous slurry at 30% solids,
containing 700 mg
of total alkaloids, which would be a concentration of 1.25% dry wt/wt%, if the
slurry were
to be dried.
Example 2: Preparation of a purified psychoactive alkaloid extract
[0094] Fresh Psilocybe cubensis, 2.5 kilograms, was dried in a forced air
oven at 25 C
for 5-10 hours, resulting in 140 grams of dried biomass. The dried biomass was
then
pulverized to a size of 200 mesh with a hammer mill. The dried powdered
biomass was
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placed into an agitated, heat-controlled vessel with 5 kilograms of solvent.
The solvent
used was a hydro-ethanol mixture of 3 parts ethanol to 1 part water by weight.
The
extraction was controlled to a constant 70 C, and the time of extraction was 4
hours.
[0095] The extraction slurry was filtered while hot, and the filter residue
was placed
back into the extraction vessel, and extracted with an additional 5 kilograms
of 3:1
ethanol:water mixture by weight. The temperature of extraction was again 70 C
and the
time was 4 hours. The extraction slurry was filtered while hot and the
filtrate from the first
and second extraction were mixed together to obtain a bulk filtrate. The bulk
filtrate was
left to cool, in case any precipitate had formed, the insoluble material was
filtered out and
discarded.
[0096] The bulk filtrate's pH was then adjusted to 9.5 (+/- 0.5) with 1 M
NaOH to form
a specific pH psychoactive alkaloid solution. This solution was then mixed
with 150g of
Amberchrom 50WX8 Strong Anion Exchange resin in its hydrogen form. The
solution
was agitated for 4 hours and then filtered. The filtrate was discarded. The
resin was rinsed
with 2.0 L of 100% Et0H and then 2.0 L of H20. Finally, the psilocybin
fraction was eluted
with 2.0 L of 2% NaCI / 80% Et0H for 4 hours.
[0097] The eluted fraction was brought to a pH of 4.0 with 2 M HCI to
result in another
specific pH psychoactive alkaloid solution. This solution was then centrifuged
at 3000g to
remove any solid precipitates. The solvent from the solution was then
evaporated in a
rotary evaporator to result in a volume of solvent evaporated was 400 mL.
[0098] This solution was again centrifuged for 15 minutes at 3000g to
remove any
solid precipitate. The supernatant was loaded onto a column of Amberlite XAD4
macroporous resin (45.53 g of dry resin) at a flow rate of 2 bed volumes per
hour. All
400 mL of the extract was loaded onto the column and washed with 5 bed volumes
of
reverse osmosis water. The washing step was followed by elution with 5 bed
volumes with
5% ethanol (by weight). A final washing was carried out with 100% ethanol.
Each of these
fractions was collected separately. The 5% ethanol fraction was collected and
concentrated in a rotary evaporator to obtain 1.143 g of 30% liquid slurry
containing
175 mg of total alkaloids, a concentration of 54% dry wt/wt%.
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Example 3.1: Preparation of a psychoactive alkaloid composition with a non-
purified
psychoactive alkaloid extract
[0099] The psychoactive alkaloid extract obtained in example 1 was mixed
with 2.8 g
of silicon dioxide (flow agent), 0.140 g of ascorbic acid (preservative), and
81.06 g of
tapioca maltodextrin (carrier). The final formulated slurry was then subjected
to spray-
drying and 140 g of the standardized powdered composition was produced with
the
desired specific amount of psychoactive alkaloid. The total
psilocybin/psilocin
concentration by dry weight was 0.5% in this composition. The exact weight
percentages
of the components in the composition are depicted TABLE 1.
Example 3.2: Preparation of a psychoactive alkaloid composition with a
purified
psychoactive alkaloid extract
[0100] The purified psychoactive alkaloid extract obtained in example 2 was
mixed
with 5.85 mg of ascorbic acid (preservative) and 822 mg of rice maltodextrin
(carrier). The
final formulated slurry was then subjected to lyophilization and 1.171 g of
the standardized
powdered composition was produced. The total psilocybin/psilocin concentration
by dry
weight was 15.01% in the composition. The exact weight percentages of the
components
in the composition are depicted TABLE 1.
Example 3.3
[0101] A purified psychoactive alkaloid solution resulting from resin
treatment after
extraction from 140 g of dried Psilocybe cubensis was concentrated in a rotary
evaporator
to form 3.90 g of concentrated aqueous slurry at 30% solids, containing 195.1
mg of total
psychoactive alkaloids. The slurry, with a psychoactive alkaloid concentration
of 5.00% by
weight, was mixed with 0.03 g of SiO2, 0.02 g of ascorbic acid and 2.55 g of
maltodextrin.
This standardized slurry was then subjected to spray-drying, and a final
powdered alkaloid
extract with a 5.00% total psilocybin, psilocin, baeocystin and norbaeocystin
concentration
by dry weight was obtained.
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Example 3.4
[0102] An extract from 140 g dried Psilocybe cubensis mushrooms using a 75%
ethanol solvent resulted in a concentrated slurry, for which the alkaloid
content was 2.16 g
and the total solid content was 46.4 g. To the slurry, 4.7 g of ascorbic acid,
1.9 g of SiO2
and 47 g of maltodextrin were added. After spray drying, this resulted in 100
g of
powdered psychedelic mushroom extract with a total alkaloid concentration of
1.00% by
weight.
Example 3.5
[0103] Psychoactive compounds were extracted from 140 g of dried Psilocybe
cubensis using 100% reverse osmosis water as the solvent. Water was evaporated
to
result in a concentrated slurry, for which the alkaloid content was 1.82 g and
the total solid
content was 68.18 g. In this example, 6.3 g of ascorbic acid, 2.5 g of SiO2
and 63 g of
maltodextrin are added to the concentrated slurry, which was then dried. This
resulted in
140 g of powdered psilocybin mushroom extract with a total alkaloid
concentration of
0.50% by weight.
Example 3.6
[0104] An extraction of psychoactive compounds from 140 g dried Psilocybe
cyanescens mushrooms was performed using 100% methanol as the solvent. The
extraction slurry was filtered to remove residue with undissolved Psilocybe
cyanescens
from the filtrate. All the methanol was evaporated from the filtrate, then
1.25 liters of
reverse osmosis water at room temperature was added to the remaining solid to
form a
slurry, for which the alkaloid content was 2.87 g and total solid content was
47.14 g. Next,
1.84 g of SiO2 and 46 g of maltodextrin were added to the slurry, which was
then dried.
This resulted in 95 g of powdered psychedelic mushroom extract with a total
alkaloid
concentration of 1.50% by weight.
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Example 3.7
[0105] An extract obtained according to example 2 was used as the starting
point.
Compared to example 3.2, greater amounts of preservative (351 mg), flow agent
(351 mg)
and carrier (16.515 g) were added to the composition. This resulted in a
standardization of
the amount psychoactive alkaloid in the composition to 1.00% instead of
15.01%.
Example 3.8
[0106] A purified psychoactive alkaloid solution resulting from resin
treatment after
extraction from 140g of dried Psilocybe cubensis was concentrated in a rotary
evaporator
to form 3.90 g of concentrated aqueous slurry at 30% solids, containing 195.1
mg of total
psychoactive alkaloids. Compared to example 3.3, greater amounts of
preservative
(0.49 g), flow agent (0.39 g) and carrier (18.43 g) were added to the
composition. This
resulted in a standardization of the amount psychoactive alkaloid in the
composition to
1.00% instead of 5.00%.
Example 3.9
[0107] A purified psychoactive alkaloid solution was obtained after
multiple cation
exchange resin treatments following extraction from 140g of dried Psilocybe
cubensis.
Silicon dioxide, maltodextrin and ascorbic acid were added to form a
composition
standardized to 60.00%.
Example 3.10
[0108] This is as example 3.9, except that the only excipient that was
added was
preservative (ascorbic acid). This resulted in a standardization of the
psychoactive
alkaloid content of the composition to 75.00%.
[0109] The exemplary compositions obtained are depicted in TABLE 1.
Compositions
of examples 3.1 and 3.4-6 are compositions with a psychoactive alkaloid
extract that has
not been purified. Compositions of examples 3.2, 3.3 and 3.7-10 are
compositions with a
purified psychoactive alkaloid extract.
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Alkaloid
Alkaloid Amount in
Extract Preservative Flow Agent Carrier Total
Amount in Standardized
Mass Mass Mass Mass Mass Extract Composition
Ex. (dry %) (dry %) (dry %) (dry %) (dry
%) (wt/wt%) (wt/wt%)
3.1 40.0 0.1 2.0 57.9 100.0 1.25 0.50
3.2 29.3 0.5 0.0 70.2 100.0 51.23 15.01
3.3 31.0 0.5 0.8 67.6 100.0 16.12 5.00
3.4 46.4 4.7 1.9 47.0 100.0 2.16 1.00
3.5 48.7 4.5 1.8 45.0 100.0 1.03 0.50
3.6 49.6 0.0 1.9 48.4 100.0 3.02 1.50
3.7 2.0 2.0 2.0 94.0 100.0 51.23 1.00
3.8 6.2 2.5 2.0 89.3 100.0 16.12 1.00
3.9 79.6 5.0 1.0 14.4 100.0 75.22 60.00
3.10 99.7 0.3 0.0 0.0 100.0 75.22 75.00
TABLE 1
In the columns, the extract mass (dry %), preservative mass (dry %), flow
agent mass
(dry %), and carrier mass (dry %) are the dry weight percentages of the
psychoactive
alkaloid extract, preservative, flow agent and carrier in the standardized
composition
respectively. The total mass (dry %) is the total dry weight percentage of the
standardized
composition. The alkaloid amount in the extract (wt/wt%) is the dry weight
percentage of
the psychoactive alkaloid in the extract, as if the extract were in its dried
state. Note that it
is possible for the extract to remain in the slurry state as the excipients
are added. The
alkaloid amount in the standardized composition (wt/wt%) is the dry weight
percentage of
the psychoactive alkaloid in the final composition. It can be seen that a wide
variability in
extract concentration from different batches can be standardized to the same
concentration in the composition, e.g. by looking at examples 3.4, 3.7 and
3.8.
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F. Apparatus
[0110] Referring to FIG. 4, an example of the apparatus is shown
schematically. Raw
Psilocybe cubensis mushrooms were added to a hopper 100 and were released in
batches into container 102. The raw fungal material was then dried in a forced
air oven
104 to result in dried biomass. The dried biomass was placed into a grinder
106 for
grinding.
[0111] The dried powdered biomass was placed into a heat-controlled vessel
110 and
solvent (S) was added to the heat-controlled vessel. The vessel 110 was
surrounded by
an insulating wall 108. Alternately, an insulating jacket can be wrapped
around the vessel.
The insulating wall 108 or jacket helps to maintain the contents 112 under a
constant
temperature (T) between 5 ¨ 95 C. The pressure (P) inside the extraction
vessel 110 may
be regulated up to 100 MPa (15,000 psig).
[0112] After the extraction, the bottom of the extraction vessel 110 was
opened at
outlet 114 and the extraction slurry was collected in a container 120. The
extraction slurry
was then fed into a filter 122 and a first filtrate was collected in container
124. The first
filtrate residue 130 was then fed back (R) into the agitated, heat-controlled
vessel 110 and
more solvent (S) was added for a second extraction. After the second
extraction, the
extraction slurry was collected in the container 120 and was then fed into a
filter 132. After
filtration, the obtained second filtrate was collected in container 136.
[0113] After the two filtration stages, the filtrates were mixed in
container 140 to obtain
a bulk filtrate. In other embodiments, if there is only a single filtration
step, this mixing step
is not required.
[0114] The bulk filtrate was placed in a rotary evaporator 142 and part of
the solvent
was evaporated from the bulk filtrate. The resultant extract was transferred
to a container
144, where the pH of the extract was adjusted, followed by centrifugation 146
to remove
the solid precipitates. The resultant supernatant was loaded onto a column 150
of resin.
An initial wash was given to the column with a solvent to remove impurities
from the resin,
and fraction 154 was collected. A second wash was given to the column with
another
solvent to elute the psychoactive alkaloids from the column and result in
fraction 156. A
final wash was given to the column with another solvent to wash any impurities
from the
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column, to prepare the column for use again, and the fraction 158 was
obtained. The
elution fraction 156 with the psychoactive alkaloids was then concentrated in
a rotary
evaporator 160 to result in the purified psychoactive alkaloid extract.
[0115] In a container 164 the purified psychoactive alkaloid extract and
desired
excipients were added together and thoroughly mixed to result in a final
standardized
slurry having a specific amount of alkaloids. The final standardized slurry
was then
subjected to spray-drying 168 to obtain a final powdered composition 170 with
a total
psilocybin/psilocin concentration defined as a percentage to two decimal
places or two
significant figures by dry weight.
[0116] In other embodiments, parts of the apparatus may be reused or
duplicated. For
example, if desired, the elution fraction 156 may be reloaded into the
container 144 for pH
adjustment and the steps from thereon can be repeated to allow for further
purification of
the obtained purified psychoactive alkaloid extract.
[0117] In one embodiment, the psychoactive alkaloid extract was obtained
after
evaporating the solvent from the bulk filtrate. The psychoactive alkaloid
extract was
transferred to a container 164 and desired excipients were added together, and
thoroughly mixed to result in a final standardized slurry having a specific
amount of
alkaloids. The final standardized slurry was then subjected to spray-drying
168 to obtain a
final powdered composition 170 with a total psilocybin/psilocin concentration
defined as a
percentage to two decimal places or two significant figures by dry weight.
H. Conclusion
[0118] Chemical and physical stability may be determined using rigorous
stability
testing protocols. This would be a necessary study for the product to be
considered made
using a good manufacturing process. The initial specifications and ongoing
specifications
of the extract should be determined during a testing regime over time,
temperature,
relative humidity etc. to determine the physical and chemical stability.
Studies are on-
going, but a 5 year shelf life with a minimum of 2 years is targeted in terms
of physical and
chemical stability.
27
Date Recue/Date Received 2020-12-18
PSU003-CANP
[0119] Throughout the description, specific details have been set forth in
order to
provide a more thorough understanding of the invention. However, the invention
may be
practised without these particulars. In other instances, well known elements
have not
been shown or described in detail and repetitions of steps and features have
been omitted
to avoid unnecessarily obscuring the invention. Accordingly, the specification
and
drawings are to be regarded in an illustrative, rather than a restrictive,
sense.
[0120] All parameters, dimensions, materials, quantities and configurations
described
herein are examples only and may be changed depending on the specific
embodiment.
Numbers and percentages are given to the nearest significant figure. For
example 10%
includes the range between exactly 9.5% and exactly 10.5%. Accordingly, the
scope of
the invention is to be construed in accordance with the substance defined by
the claims.
The process may be scaled up using larger quantities and a modified apparatus.
[0121] It will be clear to one having skill in the art that further
variations to the specific
details disclosed herein can be made, resulting in other embodiments that are
within the
scope of the invention disclosed. Steps in the flowcharts may be performed in
a different
order, other steps may be added, or one or more may be removed without
altering the
main outcome of the process.
28
Date Recue/Date Received 2020-12-18
