Note: Descriptions are shown in the official language in which they were submitted.
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I. TITLE
Pelletizing Yew Biomass For Extraction Of Taxanes And Other Natural Products
II. CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit under 35 U.S.C. ~ 119 from U.S.
Provisional Appl.
Ser. No. 60/437,434, filed December 31, 2003. This prior application is
incorporated herein
by references in its entirety.
This patent application is also co-pending with U.S. Appl. No. 60/437,237,
filed
December 31, 2002, and PCT Appl. No. , filed December 30, 2003. Both
applications
are entitled "Harvesting Yew Biomass for Extraction of Taxanes and Other
Natural
Products". Both of these prior applications are incorporated herein by
reference in their
entirety.
III. BACKGROUND OF INVENTION
In one alternative embodiment, the present invention is directed to making Yew
pellets from Yew tree material. The process comprising the steps of (i) adding
from about
1 % to about 20% w/w water to ground Yew tree material; and (ii) compressing
the Yew tree
material in a die to form a pellet. In one embodiment, the resulting pellet
has a final moisture
content of less than 10% by weight. The Yew pellets produced herein are
suitable for
extracting taxane molecules from the pellets.
Yew trees contain a family of natural diterpenoid compounds called taxanes.
One of
these taxanes in particular, taxol, has been developed as a major anticancer
drug which
successfully treats a number of human cancers. The name taxol was given to the
compound
by the original discoverers of this material. Subsequently the name was
registered as a
trademark, and the compound is now referred to in the scientific literature as
'Paclitaxel.'
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However, a large body of scientific and industry publications still refer to
the natural
compound as taxol.
Large-scale extraction of plant biomass has been practiced, and a number of
patents
have been granted for various extraction and purification processes. These
patents generally
fall into two categories: (1) animal feed; and (2) fuel. For example, U.S.
Patent 6,375,447 is
directed to a feed pellet mill that has one inlet for the feed, one outlet for
the pellet, and one
outlet for water expressed from the forming pellet. This allows for excess
water to be
removed from the biomass as the pellet is being formed. U.S. Patent 4,613,339
is directed to
a process that pelletizes spent sorghum residue, "bagasse," by storing and
then pelletizing the
residue. U.S. Patents 5,682,683 and 5,728,447 describes process for forming
pellets of grains
and cereals with a waved-brick structure, providing the pellet with better
handling properties.
Paclitaxel was initially discovered in the bark of the Pacific Yew tree. A
number of
patents described processes for removing the bark from the trunk-wood of the
tree. For
example, U.S. Patent 3,826,433 describes a process for separating the bark
from the shipped
wood through steam, mechanical compression, milling, and screening. U.S.
Patent
Application US2002/0114853 describes the use of pelletization in the
extraction of a variety
of compounds (including taxanes) using selective extraction of components
using acidic and
basic solvents from Taxus yunfaaheusis bark, or Yew tree needles. Other
patents that are
relevant to extractions from biomass may use powdered, pulverized, or shredded
material
(See U.S. Patents 6,1751,035 Bl, 6,264,998 B1, 6,392,070 B 1).
Yew is a name ascribed to a number of trees which are Taxus species; Taxus
being the
main genus in the family Taxaceae. Originally isolated from the bark of the
Pacific Yew
(Taxus bs°evifolia) collected from Washington State, beginning in 1962,
taxol was
subsequently reported as occurring in two other Taxus species, including Taxus
baccata
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(European Yew) and Taxus cuspidata (Japanese Yew), in 1971. Following
intensive
investigations, taxol was further reported to occur in a number of other Taxus
species and
cultivars. These include, but are not limited to: Taxus globosa (Mexican Yew),
Taxus
floYidana (Florida Yew), Taxus canadensis (Canadian Yew), Taxus wallichiana
(Himalayan
Yew), Taxus yufaraanensis, Taxus clainensis, and also a number of ornamental
hybrids, such as
Taxus media cultivars, e.g.: T.media 'Densiformis', T media 'Hicksii', T media
'Brownii',
T media 'Dark Green Spreader', T.nzedia 'Runyan', T.naedia 'Wardii', T media
'Tautonii',
T. cuspidata 'Capitata', etc.
In the present invention, Yew biomass material may be derived from any Taxus
species, including but not limited to the species and cultivars described
above. Other Taxus
species for use in the present invention are identified in: Chadwick, L.C. and
Keen, R.A. May
1986, "A study of the Genus Taxus", Res. Bull. 1086, Ohio Agricultural
Research and
Development Center; Appendino, G. 1995, "The Phytochemistry of the Yew Tree":
Playtochenaistsy, Natural Products Reports 12(4): 349-360; Convention On
International
Trade in Endangered Species of Wild Fauna and Flora: Eleventh meeting of the
Plants
Committee, LangKawi (Malaysia), 3-7 September 2001, Document PC11 DOC. 22-p.l,
United States of America; and Greer, C.E., Schutzki, R.E., Fernandez, A. and
Hancock, J.F.
Oct./Dec. 1993. "Electrophoretic Characterization of Taxus Cultivars":
HortTechnology,
3(4): 430-433. Each of these references are incorporated herein by reference
in their entirety.
Therefore, in one alternative embodiment, the starting material for this
invention may
be derived from a plant material selected from the group of plants commonly
referred to as
Yew trees. Suitable plants of this group are species of Taxus. Among Taxus
species, Taxus x
media cultivars are preferred. For example, preferred cultivars include, but
are not limited to,
T.nzedia'Hicksii' or T.naedia 'Dark Green Spreader'. While it is convenient to
use certain
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parts of the Yew tree in this invention, the Yew biomass for pelletization can
be derived from
the whole plant or from separated parts such as wood, stems, roots, leaves
(needles), seeds, or
any combination thereof. The material to be pelletized are derived from the
bark or the
needles are used. In one preferred embodiment, the material to be pelletized
is dry ground
yew tree root biomass (powder).
The large-scale processing of Yew tree biomass typically involves some kind of
size-
reduction processing. This is done to produce a more-or-less homogeneous
ground powder
which can be extracted with organic solvents in suitable, large-volume
containers. Problems
arise with handling the ground biomass material, particularly with
transportation, safety, and
ease and efficiency of solvent extractions. Solvent extraction problems arise
from poor
solvent contact due to channeling, 'clumping', or poor solvent circulation.
In the present invention, pellets can be readily made from ground biomass
materials
using commercially available pelletizing mills. Suitable large-scale
pelletizing machinery is
available from various sources, which include California Pellet Mill Co,
Crawfordsville,
Indiana; Sprout-Bauer, Muney, PA; Bliss Industries, Ponca City, OIL.
Typically, very large
and heavy duty machinery is used for the process of pelletizing biomass
materials such as
hay, alfalfa, etc. The machinery used usually involves engines that can range
in capacity up to
tons/hour throughput which utilize massive engines of several hundred HP. The
associated drying and mass transporting systems involve large facilities and
equipment, often
including large storage sheds, silos, semitrailer and rail wagon
transportation, etc. Suitable
methods of harvesting and processing yew biomass material is provided in PCT
Appl. No.
entitled "Harvesting Yew Biomass for Extraction of Taxanes and Other Natural
Products," filed December 30, 2003.
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The advantages of using pelletized Yew biomass materials over non-pelletized
materials
include but are not limited to the following: (i) ease of bulk handling; (ii)
shipping/
transportation / storage; (iii) freedom from dust (cleaner, safety factor,
environmental factor,
reduced product loss); (iv) greater density of solids leads to less volume
required in shipping
and storage; (v) greater density of solids requires smaller processing vessel
volumes; (vi)
non-packing nature of pellets resists volume-unloading issues after transport
(flour can pack
into a cement); (vii) larger size of pellets allows for greater range of
equipment use in
processing (larger filters); (viii) uniform size-diameter distribution vs.
ground biomass; (ix)
extraction of biomass lends itself to faster / easier operation due to non-
packing nature of the
pellets (higher throughput of solvent through bed of pellets); (x) use of
pellets decreases
channeling and loss of contact between pellets and extraction solvent; (xi)
use of pellets
decreases pockets of biomass with low solvent-turnover rates; (xii) stability
of product,
including reduced oxidation due to smaller surface area exposed to the
atmosphere; reduced
microbial fermentation problems (toxins, heat); and (xiii) use of continuous
extraction
equipment including automated counter-current extraction equipment (e.g. Crown
Extractors).
In one alternative embodiment of the present invention, it was discovered that
pelletizing ground powdered Yew biomass offers substantial advantages in the
handling,
processing and, most importantly, extraction of taxanes and other material
products from the
biomass. In particular, efficiency and ease of solvent extraction is a major
advantage in
processing the pelletized Yew biomass. Thus, the present invention provides a
process for
manufacturing pelletized Yew material without significant reduction of the
available taxane
content in the biomass. Also, such process does not adversely impact the
extraction process,
such that additional purification and/or extraction steps are required.
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Further, in another alternative embodiment, the present invention provides
stable
pellets from ground, dried Yew roots, at both the laboratory scale and at the
industrial scale.
No significant loss/degradation of extractable paclitaxel resulting from the
present
pelletization process was observed.
IV. SUMMARY OF THE INVENTION
It is an object of the present invention to provide a process for producing
pelletized
Yew biomass for extracting taxanes and other natural products.
Another object of the present invention is to provide an efficient and
economical
process for producing Yew pellets from Yew tree material, including ground
material
(powder).
Another object of the present invention is to provide a process for making
pellets from
Yew tree material (including powdered material) which are easily handled,
stored, and used.
A further object of the present invention is to provide a process for making
Yew
pellets from Yew tree material (including powdered material) wherein the
resulting pellets
have appropriate amounts of water for the extraction process.
A further object of the present invention is to provide a process for making
Yew
pellets with appropriate amounts of water to minimize undesirable microbal
growth of the
pelletized material.
These and other objects and advantages of the present invention will become
more
readily apparent from the following detailed description.
In one alternative embodiment, the foregoing objects and advantages of the
invention
are achieved in accordance with the present invention in which a pelletized
product is
produced from, for example, a finely ground pelletizable Yew tree material, or
a mixture of
finely ground Yew tree materials and water, by pressing the material through
appropriate die
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openings in a commercial or laboratory scale pelletizer such as, for example,
a California
pellet mill, or a Bliss pellet mill. While the invention may be utilized in
the processing of
various raw materials, it has been found especially useful in producing a
pelletized Yew from
a finely ground material.
V: DETAILED DESCRIPTION OF THE INVENTION
In many commercial pelletizing operations, the resulting pellet is a product
of a
controlled manufacturing process. For example, it is well known that
variations in the
amount of water or liquid in the raw material will have a marked effect both
on the ability to
form the material into pellets and on the strength and integrity of the
pellets formed. The
present invention provides a process that forms a stable Yew pellet for
transportation and
extraction of taxanes and other natural products contained therein.
The present invention is suitable for pelletizing Yew biomass at different
scales,
including but not limited to: (i) Laboratory/Pilot Scale Pelletizing Runs; and
(ii) Industrial-
Scale/Large-Scale Pelletizing Runs. A description of each type of run is
described below.
The Yew pellets produced herein are suitable for extracting taxane molecules
from the
pellets.
Laboratory l Pilot-Scale Pelletizing Runs
Pelletizing may be carried out on Taxus media x "Densiformis" ground root
material.
Here, pellets can be made with a California Pellet Mill ("CPM"),
Crawfordsville, IN. This
pelletizing mill comprises dies having 1/8" and 3/16"extrusion holes. During
the
pelletization process, the mill speed may be adjusted to prevent the
temperature from
exceeding 200°F, preferably less than 180°F, more preferably
140°F to 160°F. Water can be
added to the powdered biomass material before pelletization. Other adjustments
to the pellet
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mill can be made to facilitate the pelletization process, such adjustments are
known to those
skilled in the art.
Industrial-Scale / Large-Scale Pelletizing Runs
Pellets can be made using a CPM pellet mill. A large CPM pellet mill can
pelletize
approximately 55 metric tons of 'Densiformis' roots biomass during a one-day
run. The
resulting pellets can be i/4 inch in diameter. Preferably the resulting
moisture content in the
pellets can be approximately 5 to 6 wt% water.
Industrial-Scale/Large-Scale Pelletizing Runs
Pellets can also be made using a Bliss Hammer Mill. The Yew ground material
biomass can be dried in a rotating drum and ground further by using this mill.
The pelletizing
can be done in two Sprout pelletizers with smaller dies. The dies can have
1/4" holes with
tapered relief. The throat length for compression can be 1 ll4" long. Water
can be added to
the Yew ground material before pelletization. Each pelletizer mill can process
3,500 lb
ground biomass/hr. Each mill may consume 200 A at 460V 3 phase.
Pelletizing Process
The biomass, after reaching the appropriate conditions of size and content,
are first
harvested. After harvesting, the Yew tree material may be ground by
conventional means.
Suitable equipment for harvesting the tops of yew plants include those
developed by Dr.
Peter Felker (Texas A&M University - I~ingsville) using a flail harvester
(htt~://www.newuses.orR/LGILG-19/l9harvester.html), or http://www.wood~ps.or~/
mechconf/mclauahl.
html).
In one alternative embodiment, the harvesting is directed to the roots of the
Taxus
plant. After the roots have been removed from the soil, they may be piled on a
concrete slab,
and washed using a high pressure hose and a shovel or other suitable device to
turn the mass
over. The roots may be dried through an alfalfa drier and then ground by
conventional means.
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In one embodiment, approximately 5% to 6% w/w water is added to the Yew
biomass. The water content should be carefully monitored. Too much water in
the pellets
could encourage microbial growth, which is undesirable. Also, excess water may
adversely
affect the taxane extraction process, causing a reduction in the extraction
efficiency. In one
embodiment, the water content may be controlled by a water or steam bleed
steam. This is
more desirable.
In another embodiment, the following ranges of water (w/w) may be added to the
Yew tree material: from about 0.25% to about 0.5%; about 0.5% to about 1.0%;
about 1.0%
to 1.5%; 1.5% to about 2.0%; 2.0% to about 3.0%; 3.0% to about 4.0%; 4.0% to
about 5.0%;
5.0% to about 6.0%; 6.0% to about 7.0%; about 7.0% to about 8.0%; 8.0% to
about 9.0%;
about 10.0% to about 11.0%; about 11.0% to about 12.0%; about 12.0% to about
13.0%;
about 13.0% to about 14.0%; about 14.0% to about 15.0%; about 15.0% about to
20.0%.
Other ranges of water include: about 1 % to about 5%; about 5% to about 10%;
about 10% to
about 15%; about 15% to about 20%.
In one preferred embodiment, the pellets are made using a CPM pellet mill. The
speed/capacity of the CPM Pelletizing Mill is affected by the moisture content
of the wetted
biomass. The normal capacity rating of the CPM laboratory pelletizing mill is
about 125
lbs/hr. However, if the moisture content of the wetted biomass is about 30% to
about 36% by
weight, an additional 30-60 lbs/hr additional capacity may be achieved. If the
moisture
content of the wetted biomass is too low, it will plug the dies. Conversely,
if the materials
are too wet, unpelletized material will flush out the die.
The ground solids may be wetted using either water or steam, and then
pelletized to a
diameter of about 4 to 6 mm (3/16 to 1/4 inch). This diameter is preferred for
further
processing the biomass. Smaller diameters may clog the dies, increase the
processing
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temperature, and also increase the wear on the dies. After the pellets are
formed, they may be
allowed to cool, and then transported. The pellets formed from the process of
the present
invention show no loss of taxanes over the course of this treatment.
The finished pellets can be stored or used as desired. In the present
invention, it is
preferred that the pellets be substantially cylindrical or parallelepiped. The
maximum cross
section of each individual pellet should be about 3/16 to about 1/4 inch.
While the
production of cylindrically shaped pellets is preferred, the invention in its
broadest aspects
contemplates producing pellets of any suitable configuration. For example, the
pellets may
be cube-shaped. In one alternative embodiment, the bulk density of pellets
produced in the
present invention can be at least 30 lbs/ft.3, up to 50 lbs/ft.3 In one
alternative embodiment,
the bulk density of the resulting pellet may include the following ranges:
about 30 lbs/ft. 3 to
about 35 lbs/ft.3; about 35 lbs/ft.3 to about 40 lbs/ft.3; about 40 lbs/ft.3
to about 45 lbs/ft.3;
about 45 lbs/ft.3 to about 50 lbs/ft.3
Equipment Used for Pelletizing
The following is a list of pelletizing equipment suitable for pelletizing Yew
biomass.
1. CPM (2975 Arline Circle, Waterloo IA)
A large range of suitable industrious equipment is available from this
company.
2. Andritz Sprout-Bauer (Sherman St, Muncy, PA)
Hammermills with a range of power (22 - 255 kW)
Pellet mills with varying power (30 - 560 kW) and die press area (620 -14313
cmz).
3. Bliss Industries (1415-T W. Summit Ave, Ponca City, OK)
Hammermills with a range of power (6 - 447 kW, 10 - 600 H.P.)
Pellet mills with varying power (50 - 300 kW, 80 - 500 H.P.) and die press
area (1500 - 7800
cmZ).
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Taxanes Extracted from Yew Pellets
An important component of manufacturing pellitized Yew material is to produce
the
pellets without reducing the available taxane content inside the pellet, and
adversely affecting
the taxane extraction process from the pellets. As used herein, "taxane or
taxane molecule"
include but are not limited to a molecule that contains a basic baccatin III
structure with a
(2R,3S)-C6HSCH(Rx)CH(OH)C(O)- group forming an ester with the hydroxyl group
located
at the C-13 position of the basic baccatin III structure. The group
represented by Rx can be an
amino group, a salt of an amino group (e.g., an ammonium salt), an amino group
which is
protected with an amino protecting group, or a substituent which may be
converted into an
amino group. Various isomers, homologues, and analogues of the basic baccatin
III structure,
and of the (2R,3S)-C6HSCH(Rx)CH(OH)C(O)- group also are included in the
definition of a
taxane molecule.
Also, a 10-deacetylbaccatin III structure is contemplated within the scope of
a taxane
molecule. Included within the definition of a taxane or taxane molecule
include, but are not
limited to, primary taxanes, for example taxol A (paclitaxel), taxol B
(cephalomanninc), taxol
C, taxol D, taxol E, taxol F, and taxol G. Further, the definition of a taxane
or taxane
molecule includes docetaxel (TAXOTERE~). (See, e.g., PCT Ser. Appl. No.
PCT/LTS03/105566, which is incorporated herein by reference). As used herein,
a "basic
baccatin III structure" means a compound having the formula as shown in the
aforementioned
application, where each of Rl, R2, R4, R~, Rlo and R13 independently is
hydrogen, an alkyl
group, an acyl group, an aryl group, an arylalkyl group, a vinyl group, an
ether group, an
ester group, a glycoside group, an oxo group, or a hydroxyl protecting group.
Included within
the definition of a basic baccatin III structure is baccatin III, which has
the formula as shown
in the aforementioned application, and 10-deacetylbaccatin III, which has the
formula as
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shown in the aforementioned application, where Ac is an acetyl group (CH3C(O)-
), and Bz is
a benzoyl group (PhC(O)- or C6HSC(O)-).
In one alternative embodiment, the present invention is directed to a process
for
making Yew pellets comprising the following steps: (a) adding from about 1 %
to about 20%
w/w water to ground Yew tree material; and (b) compressing the wetted Yew tree
material in
a die to form a pellet whereby by the resulting pellet has a final moisture
content less than
10% by weight. In one alternative embodiment, the Yew tree material is ground
into a
powder. In another embodiment, the Yew material is derived from roots.
In another alternative embodiment, the process of the present invention
provides a
resulting pellet having a bulk density from about 301bs/ft3 to about
SOlbs/ft3. In another
embodiment, the present process provides a resulting pellet having a final
diameter from
about 1/16 inch to about 1 inch, or from about 3/16 inch to about'/4 inch or
the final diameter
is 1/a inch.
In another embodiment, in carrying out the present process the diameter of the
extrusion holes of the die is from about 1/16 inch to about 1 inch, or from
about 3/16 inch to
about'/4 inch. Further, in another embodiment, the temperature of the
resulting pellet as it
emerges from the die is from about 100°F to about 212°F, or from
about less than 180°F or
from about 130°F to about 160°F.
In another alternative embodiment, the present invention is directed to a Yew
pellet
having a final moisture content less than 10% by weight. In another
embodiment, the pellet
has a final moisture content from about 1 % to about 6% by weight, or from
about 4% to
about 6% by weight. In another embodiment, the pellet of the present invention
has a final
bulk density from about 30 lbs/ft3 to about 50 lbs/ft3. In another embodiment,
the diameter of
the pellet is from about 1/16 inch to about 1 inch or 3/16 inch to about 1/4
inch or 1/4 inch.
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Turning the pellet mill to higher throughput can reduce the quality of the
pellets.
Also, as the thickness of the die is increased, the resulting pellets become
harder and the
capacity and ability of the mill to run are adversely affected. In one
alternative embodiment,
the die is made of high carbon steel. Carbon steel is more preferable than
chrome or stainless
steel dies.
The use of additives can be important with powered biomass materials. In the
case of
ground root biomass, the use of additives is less important, and in some
instance is not
required. With Yew tops, for example, it is advantageous to use binder
additives to facilitate
production of pellets suitable for extraction. Such binders may include, but
are not limited to,
guar gum, starches, vegetable oils, alginates, xanthan gums, locust bean gum
and other
suitable binders.
The invention is further demonstrated by the following examples. The examples
are for
purposes of illustration and is not intended to limit the scope of the present
invention.
VI. Examples
Example 1-Pelletizing Process
1. 2000 grams of dry ground Yew tree root biomass (powder).
2. 200 g water added to the Yew biomass.
3. The biomass and water were mixed in a HOBART blender with eccentric
drive/paddle.
4. The die is first purged with oats, forming pelletized oats.
5. The wetted biornass was run through a CPM'CL3' Laboratory pellet mill. This
mill
had a 3 HP motor (220 Volts). The temperature of the resulting pellets were
approximately 160° F. The pellets were dark in color, ranging in length
of about 1/2
inch to 1 inch.
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6. After 20 minutes, the moisture content of the pellets was approximately
10.3%. After
30 minutes, it was approximately 10.4%. The bulk density of the pellets was 39
lb./ft3' The bulk density of the biomass powder was approximately 18 lbs/ ft3'
Capacity tests were run on the pellet mill to determine the mill's capacity
for the
biomass material. For example, to produce 118 inch pellets, the capacity for
the mill was 117
lbs/hr.
Example 2 -Additives
In some instances, additives can be used to facilitate production of pellets
suitable for
taxane extraction. The following examples describe an additive (Guar Gum) that
can be
added to the wetted biomass. Each pelletizing run followed the general
protocol shown in
Example 1. To evaluate the amount of fines, the die was heated beforehand.
1 % Guar Gum
Guar gum run: 3/16" pelletizing; 2000 g of ground Yew root biomass; 200 g H20;
20
g guar gum;
Guar Gum Source - *non-food grade Rawtec UFF-MV (5/21/01 RX 1036)
Temperature higher: more fines in 155°F; 128 lb/hr
Bulk density: 40 lb/ft3; and
Wgt. fines 208 g; wgt pellets 1822 g; 10.2% fines; 90% conversion.
1/2 % Guar Gum
Guar gum run: 1/8" pelletizing;
2000 g of ground Yew root biomass; 200 g HZO;
g guar gum ( _ %z%) (added as powder);
Temp 150°F to 163°F;
Rate: 13 6 lb/hr.;
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Wgt. pellets: 1894 g; wgt fines. 139 g; or 7% fines; and
Bulk density: 35 lblft3.
2 % Guar Gum
Guar gum run: 1/8" pelletizing;
2000 g ground Yew root biomass; 200 g H20;
40 g guar gum (=2%) (added as powder);
Temp 162°F to 174°F;
Rate Capacity: 145 lb/hr.
Fines 140 g; pellets 193 ° g; 7% fines;
Bulk density: 37 lb/ft3.
Control Run (No Guar Gum Added)
2000 g ground Yew root biomass; 200 g H20;
1l8" pelletizing;
Temp: 148°F to 170°F;
Rate: capacity 95 lb/hr;
Wgt fines: 95 g; wgt of pellets 2000 g;
4.5% fines; and
Bulk density: 34 lb/ft3.
Example 3 - Extraction of Taxanes From Pellets
A series of experiments were run to confirm that paclitaxel and other taxanes
survive the
pelletizing process of the present invention. Specifically, Yew pellets were
extracted using
hot methanol in a Soxhlet apparatus: 1/8" pellets (no additives), 3/16"
pellets (no additives),
and non-pelletized biomass powder (from which the pellets were made). Table 1
shows the
recovery of taxanes.
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TABLE 1
Soxhlet Thimble
Wgt. Grams
Exp. Run No. Tare Gross Mass of Biomass
1 12.5 47.8 35.3 g starting
material
2 13.2 50.7 37.5 g dry ground
biomass
3 14.3 73.8 59.5 g 1/8"
pellets,
no additives
4 13.0 68.2 55.2 g 1/8"
pellets,
no additives
12.8 74.7 61.9 g 3116"
pellets,
no additives
6 11.1 70.2 59.1 g 3116"
pellets,
no additives
HPLC analysis showed good recovery of total taxanes approximately
(approximately
0.02% w/w) for both pellets and non-pellets. HPLC analysis also showed good
recovery of
paclitaxel (approximately 0.01 % w/w) for both pellets and non-pellets. These
tests showed
no significant loss/degradation of extractable paclitaxel as a result of the
pelletization
process.
The invention, as described above, may be varied in certain aspects. For
example,
pellet production may be accomplished continuously or in separate batches. In
addition,
operating parameters may be varied, depending on many factors. These factors
include
available materials, economic considerations and energy needs of specific
consumers.
However, it is to be understood that these and other factors can be made by
those skilled in
the art without distracting from the sprit and scope of the invention.
Throughout the description, where the present invention is described as
having,
including, or comprising specific components, or where processes are described
as having,
including, or comprising specific process steps, it is contemplated that the
present invention
16
CA 02512170 2005-06-29
WO 2004/060626 PCT/US2003/041824
also consists essentially of, or consists of, the recited components or
processing steps.
Further, it should be understood that the order of steps or order for
performing certain actions
are immaterial so long as the invention remains operable. Moreover, two or
more steps or
actions may be conducted simultaneously so long as the invention remains
operable. Also,
one or more steps or elements may be omitted from the claimed invention, or
the invention
described herein suitably may be practiced in the absence of any component or
step which is
not specifically disclosed herein, so long as the invention remains operable.
Further, the present invention may be embodied in other specific forms without
departing from the spirit or essential characteristics thereof. The foregoing
embodiments are
therefore to be considered illustrative rather than limiting the invention
described herein.
The content of each patent and non-patent document referred to herein is
expressly
incorporated herein by reference in its entirety.
17
