U.S. patent application number 11/669119 was filed with the patent office on 2008-02-07 for compressible intravascular embolization particles and related methods and delivery systems.
This patent application is currently assigned to SURGICA CORPORATION. Invention is credited to Donald K. Brandom, Louis R. Matson, Gerald R. McNamara.
Application Number | 20080033366 11/669119 |
Document ID | / |
Family ID | 38229838 |
Filed Date | 2008-02-07 |
United States Patent
Application |
20080033366 |
Kind Code |
A1 |
Matson; Louis R. ; et
al. |
February 7, 2008 |
COMPRESSIBLE INTRAVASCULAR EMBOLIZATION PARTICLES AND RELATED
METHODS AND DELIVERY SYSTEMS
Abstract
The present invention relates to substantially compressible,
spherical porous embolization particles, including methods of
making and using the particles. Further, the invention relates to
embolization delivery systems for the introduction of the particle
into the vascular luer.
Inventors: |
Matson; Louis R.; (Pollock
Pines, CA) ; McNamara; Gerald R.; (Reno, NV) ;
Brandom; Donald K.; (Davis, CA) |
Correspondence
Address: |
MORGAN, LEWIS & BOCKIUS, LLP
ONE MARKET SPEAR STREET TOWER
SAN FRANCISCO
CA
94105
US
|
Assignee: |
SURGICA CORPORATION
El Dorado Hills
CA
95762
|
Family ID: |
38229838 |
Appl. No.: |
11/669119 |
Filed: |
January 30, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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60764825 |
Jan 30, 2006 |
|
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11669119 |
Jan 30, 2007 |
|
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Current U.S.
Class: |
604/181 ;
424/489; 604/510; 604/533 |
Current CPC
Class: |
A61B 17/1219 20130101;
A61L 24/06 20130101; A61L 2430/36 20130101; A61L 24/0036 20130101;
A61L 24/06 20130101; C08L 29/04 20130101 |
Class at
Publication: |
604/181 ;
424/489; 604/510; 604/533 |
International
Class: |
A61M 5/00 20060101
A61M005/00; A61K 9/14 20060101 A61K009/14 |
Claims
1. A compressible embolization particle comprising a substantially
spherical porous particle having pores that extend to the surface
of said particle wherein said particle has a diameter ranging from
about 1,000 microns to about 10,000 microns when hydrated and fully
expanded.
2. The particle of claim 1, wherein the particle has a diameter
ranging from about 2,000 microns to about 4,500 microns when
hydrated and fully expanded.
3. The particle of claim 1, wherein the particle has a diameter
ranging from about 3,000 microns to about 4,000 microns when
hydrated and fully expanded.
4. The particle of claim 1, wherein the particle comprises a PVA
polymer.
5. The particle of claim 1, wherein said particle is hydrated.
6. The particle of claim 5, wherein said particle can be compressed
in one dimension to about 80% of the diameter of the hydrated
particle.
7. The particle of claim 5, wherein said particle can be compressed
in one dimension to about 25% of the diameter of the hydrated
particle.
8. The particle of claim 1, wherein the surface or interior pores
of a dehydrated particle can have a diameter of 50 microns or
more.
9. The particle of claim 1, wherein the surface or interior pores
of a dehydrated particle can have a diameter of 100-microns or
more.
10. The particle of claim 1, further comprising a porous annular
ring around said particle.
11. An embolization device comprising the embolization particle of
claim 1 and a catheter having a lumen to receive said particle.
12. The device of claim 11, wherein the embolization particle is
disposed in the lumen of said catheter.
13. The device of claim 12, further comprising a 3-way connection
component operably coupled to the catheter, and two syringes
operably coupled to the 3-way connection component.
14. A method of embolization comprising: positioning a distal
portion of the embolization device of claim 12 in proximity to a
target area of a blood vessel, and ejecting the particle from the
lumen of said embolization device such that the particle is
positioned in the target area.
15. The method of claim 14, wherein the particle expands from its
compressed state to an expanded state upon ejection from said
lumen.
16. The method of claim 15, wherein the non-compressed particle has
a diameter that is greater than an inner diameter of the target
area of the blood vessel.
17. The method of claim 16, wherein the particle in the expanded
state is substantially fixed in position in the vessel.
18. A method of loading an embolization particle into a catheter
comprising: positioning an embolization particle of claim 1 in a
luer hub of a catheter; coupling a syringe containing hydration
fluid to the luer hub; operating the syringe to urge the
embolization particle out of the luer hub and into the catheter;
removing the syringe from the luer hub; and urging the embolization
particle through the catheter and into a target area of a patient
with a guidewire.
19. A method of loading an embolization particle into a catheter
comprising: positioning an embolization particle of claim 1 in a
luer hub of a catheter; coupling a three-way stopcock to the luer
hub, wherein the stopcock is coupled to a first and a second
syringe, wherein one or both of the syringes initially contain
hydration fluid; operating the first syringe to urge the
embolization particle out of the luer hub and into the catheter;
and operating the second syringe to urge the embolization particle
through the catheter and into a target area of a vessel.
20. A method of embolization comprising providing at least one
embolization particle of claim 1; urging the embolization particle
through a catheter wherein the particle is in a compressed state;
and positioning the embolization particle in a target vascular
area, wherein the particle expands to an expanded state upon
exiting the catheter.
21. The method of claim 20, wherein the urging of the particle
through the catheter is a guidewire.
22. The method of claim 20, wherein the urging of the particle
through the catheter comprises applying fluid pressure to the
particle.
23. A method of embolization comprising: positioning a first
embolization device in a target vascular area; and positioning a
second embolization device in proximity to the first embolization
device, wherein at least one of said embolization devices comprise
the embolization particle of claim 1.
24. A method of making a compressible embolization particle,
comprising: mixing polyvinyl alcohol ("PVA"), a porogen, and a gas
to form a foam; and injecting the foam into a mold.
25. The method of claim 24, wherein the mold is a hollow sphere
formed from two halves of a sphere.
26. The method of claim 24, further comprising trimming the annular
ring formed at the junction of said two halves.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to compressible embolization
particles, including supplemental embolization particles, methods
of making and using the particles, and delivery systems for
delivery of the particles.
BACKGROUND OF THE INVENTION
[0002] Some intravascular interventional procedures produce an
artificial embolism in mammals that is useful in controlling
internal bleeding, blocking the blood supply to tumors, or
relieving pressure in a vessel wall near an aneurysm. Known methods
for producing an artificial embolism include use of (1) inflatable
and detachable balloons, (2) coagulating substances, (3)
later-curing polymeric substances, (4) occlusive wire coils, (5)
embolization particles, and (6) supplemental occlusive embolic
materials. Disadvantages relating to the known methods include
recanalization, perforation of blood vessels, inadvertent
downstream embolization due to fragmentation or release of trapped
particles, poor positioning control, instability, imprecise sizing,
and shrinkage or movement of the embolic material.
[0003] Early embolization particles were made by chopping or
grinding polyvinyl alcohol (PVA) foam or sponge. Such PVA foam or
sponge embolization particles are irregularly shaped and generally
contain a range of pore sizes that are produced during the
manufacturing process by whipping air into the PVA solution prior
to crosslinking. Disadvantages of these particles include their
non-precise size (aspect ratios) and open edges on the particles
that cause them to clump together and subsequently plug up delivery
catheters.
[0004] Spherical particles minimize these disadvantages. In
addition, spherical particles can penetrate deeper into the
vasculature than traditional particles due to the uniform shape of
the particle. Existing spherical embolics include Biocompatibles
International plc's Bead Block.TM., Biosphere Medical, Inc.'s
Embosphere.TM. and Boston Scientific Corporation's Contour SE.TM..
The Bead Block.TM. product is a PVA get and does not have
macropores (that is, the pores are less than 1 micron in diameter).
Embosphere.TM. is a get made of an acrylic co-polymer (trisacryl)
and does not have macropores. Contour SE.TM. is made of PVA has an
onion shape but has no surface macropores.
[0005] However, spherical embolization particles have several
disadvantages. For example, the smooth surface of these particles
may affect the stable integration of such particles within the
occlusive mass comprising the particles, clotted blood and
ultimately fibrous tissue. In addition, the compression of such
particles is only about 20-35% in one dimension thereby limiting
the size of the embolization particle that can be used in a given
catheter.
SUMMARY OF THE INVENTION
[0006] The invention includes compressible substantially spherical,
porous embolization particles. The interior porous extend to the
particle surface to form an exterior layer having exterior pores.
The compressible embolization particle preferably has a diameter
from about 1,000 to 10,000 microns or more in its hydrated, fully
expanded state. The particles can be compressed in one dimension to
at least 50% of the diameter of the fully extended particle and in
some cases can be compressed to 5% of the original diameter.
[0007] The compressible embolization particle is preferably
radiopaque. In a preferred embodiment, the compressible
embolization particle is made of a crosslinked polyvinyl alcohol
("PVA") polymer. In some embodiments, the embolization particle
also has an annular porous ring around the spherical particle which
is a generated during particle formation.
[0008] The invention also includes an artificial embolization kit.
The kit has one or more compressible embolization particle as
described herein and a delivery device. The delivery device has a
connection component and two syringes. The connection component is
adapted to connect with the two syringes and to control the flow of
fluid in the delivery device.
[0009] The invention includes an embolization device comprising a
compressible embolization particle(s) and a delivery system such as
a catheter. In some embodiments, the embolization device contains
the particle in the lumen of the catheter.
[0010] The invention also includes a method of embolization where a
percutaneous delivery system containing a compressible embolization
particle is positioned so that the delivery system is in proximity
to a target region of a blood vessel. The particle is compressed in
the lumen of the delivery system and has a cross-sectional diameter
that corresponds to the diameter of the lumen The compressed
embolization particle is then ejected from the delivery system by
pressure or the use of a blunt ended guidewire so that the particle
is initially positioned in the target region. During or after
ejection, the particle expands. The diameter of the uncompressed
hydrated embolization particle is preferably chosen so that after
expansion, the particle attains an expanded state that creates
pressure against the interior surface of the vascular wall. The
embolization particle therefore conforms to the cross section of
the blood vessel.
[0011] The invention also includes a method of loading an
embolization particle into a catheter. In this method an
embolization particle is positioned in a luer hub of a catheter. A
syringe containing hydration fluid is coupled to the luer hub and
operated to urge the embolization particle out of the luer hub and
into the catheter. The syringe is then removed. The particle is
then urged through the catheter and into a target area of a patient
with a guidewire.
[0012] In another embodiment, the invention includes a method of
loading an embolization particle into a catheter where an
embolization particle is positioned in a luer hub of a catheter. A
stopcock is connected to the luer hub and first and second syringes
are connected to the stopcock, at least one syringe initially
containing hydration fluid. The first syringe is operated to urge
the embolization particle out of the luer hub and into the
catheter. The second syringe is operated to urge the particle
through the catheter.
[0013] In another embodiment, the invention includes a method of
embolization. In this method at least one compressible embolization
particle is urged through a catheter and positioned in a target
region of a blood vessel. The particle is in a compressed state
while being urged through the catheter and expands to an expanded
state upon exiting the catheter.
[0014] In another embolization method a first embolization device
is positioned in a target region of a blood vessel. A second
embolization device is then positioned in the blood vessel in close
proximity to the first embolization device. At least one of the
embolization devices is a compressible embolization particle as
described herein.
[0015] The invention also includes a method of making a
compressible embolization particle. The method includes mixing a
polymer, such as PVA, a crosslinking agent, a gas and optionally a
porogen to form the foam. The foam is then placed in a spherical
mold having a diameter that corresponds to the desired diameter of
the compressible embolization particle when hydrated for use. After
curing, the particle is removed from the mold and the porogen is
dissolved and separated from the particle to produce the
embolization particle. In some situations, porogen is hydrolyzed in
which case it is removed by rinsing.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 is a cross-sectional view of a spherical polyvinyl
alcohol foam embolization particle, according to one embodiment of
the present invention.
[0017] FIG. 2 is a cross-sectional view of a spherical polyvinyl
alcohol foam embolization particle, according to another embodiment
of the present invention.
[0018] FIGS. 3A, 3B and 3C are Scanning Electron Micrographs
(SEM's) of a dehydrated PVA particle made according to the
invention. FIG. 3A shows a substantially spherical porous particle
at 80.times. magnification having surface pores. Some interior
pores can also be seen. An annular ring can be seen encircling the
"equator" of the particle. FIG. 3B is a close up (300.times.
magnification) of the surface of the north central hemisphere of
the particles in FIG. 3A. FIG. 3C depicts a cross section of a
dehydrated PVA compressible particle at 80.times.
magnification.
[0019] FIG. 4 is a side view of a delivery system, according to one
embodiment of the present invention.
[0020] FIG. 5 is a perspective view of a kit containing a delivery
system and an embolization particle, according to one embodiment of
the present invention.
[0021] FIG. 6 is a side view of a supplemental embolization
particle positioned in a blood vessel in conjunction with an
embolization coil, according to one embodiment of the present
invention.
[0022] FIG. 7 is a side view of a supplemental embolization
particle positioned in a blood vessel in conjunction with two
embolization coils, according to one embodiment of the present
invention.
[0023] FIG. 8 is a side view of a supplemental embolization
particle positioned in a blood vessel in conjunction with
embolization particles, according to one embodiment of the present
invention.
DETAILED DESCRIPTION
[0024] One problem with the larger embolization particles in the
prior art is that they require larger catheters for delivery to the
patient. However, the compressibility of the particles of the
present invention eliminates the need for larger catheters, making
it possible to deliver relatively large particles through small
catheters. Further, smaller particles of the present invention are
also beneficial because such particles can be used with smaller
catheters for delivery.
[0025] The compressible particles can be used for use in the
creation of an artificial embolism that can be used to treat
aneurysms, tumors, bleeding, vascular malformations, or otherwise
be used to block blood flow to undesired areas by occluding blood
vessels. According to one embodiment, the device is a dry,
dehydrated substantially spherical particle of biocompatible
polyvinyl alcohol ("PVA") foam material that when hydrated is
compressible from its original hydrated volume to a constrained or
smaller volume that can subsequently expand back toward the
original volume. This compressibility allows the particle to be
compressed in a delivery catheter having a diameter that is smaller
than the diameter of the hydrated and expanded particle.
[0026] For purposes of this application, compressibility is defined
as the ratio of the amount of the diameter of the particle that has
been compressed to the total diameter of the particle in its fully
expanded state. For example, a particle that has a diameter of 4 mm
in its fully expanded state that can be compressed to 1 mm has a
structural compressibility of 75% (3 mm (the amount of the particle
diameter that the particle was compressed) divided by 4 mm (the
total diameter of the particle in its expanded state)=75%).
[0027] Depending on the choice of catheter internal lumen diameter
and the diameter of the hydrated particle, the particle can be
compressed to a diameter perpendicular to the catheter lumen that
is about 5% to about 90%, about 25% to about 85%, and about 40% to
about 80% of the diameter of the expanded particle. This does not
include the annular ring, if present.
[0028] The compressed particle is delivered to a target region of a
blood vessel by an embolization device comprising a catheter and
the compressible particle. Prior to the embolization procedure, the
compressible particle is placed in the catheter lumen in a
compressed state. After ejection from the lumen, the particle
expands to provide for mechanical fixation of the particle within
the vascular area, thereby providing occlusion of the vascular
area.
[0029] FIG. 1 depicts an expandable embolization particle 10,
according to one embodiment of the present invention. Particle 10
is preferably made of expandable PVA foam material and has a
compressible, porous, spherical structure. In one aspect, the
expandable material is formalin crosslinked PVA foam.
Alternatively, the particle 10 can be made of polyurethane. In
another aspect of the invention, the particle 10 can have any shape
with a circular profile configured to provide a sealed occlusion
with respect to the blood vessel in which it is positioned. For
example, the particle 10 according to one embodiment can be
cylindrical.
[0030] The particle 10 has an interior or inner portion 12 and a
exterior layer 14 (also referred to as an "exterior portion" or
"skin"). The interior portion 12 is more porous and contains pores
with a larger diameter in comparison to the pores present in the
skin 14. According to one embodiment, the pores in the exterior
layer 14 have a diameter that is generally smaller than the
diameter of the pores found the interior portion 12. In other
words, the exterior layer 14 pores have a diameter that is
generally smaller than the diameter of the pores found in the
interior portion 12 of the particle. According to one embodiment,
the pores in the interior portion of the particle are "macropores"
having diameters of 10, 25, 50, 100, 200, 300, 400 or 500 microns
or more. In some embodiments, the skin 14 has fewer pores, fewer
and smaller pores, or no pores in comparison to the interior
portion.
[0031] In a further aspect of the invention at least a portion of
the pores of the interior portion are interconnected.
"Interconnected pores" (also referred to as "open pores") as used
in the present application refers to pores that are in fluid
communication within a solid material. The interconnected pores
define an open, interconnected architecture of volume elements
within the particle that can contain liquid in the hydrated state
or gas in a dehydrated state.
[0032] The particles of the present invention are substantially
spherical. The term "substantially spherical" as used herein refers
to a generally spherical shape having a maximum diameter/minimum
diameter ratio of from about 1.0 to about 2.0, more preferably from
about 1.0 to about 1.5, and most preferably from about 1.0 to about
1.2. This definition is intended to include true spherical shapes
and ellipsoidal shapes, along with any other shapes that are
encompassed within the maximum diameter/minimum diameter ratio.
[0033] FIGS. 3A, 3B and 3C are scanning electron micrographs
(SEM's) of a dehydrated PVA particle made according to the
invention. FIG. 3A shows a substantially spherical porous particle
at 80.times. magnification having surface pores. Some interior
pores can also be seen. An annular ring can be seen encircling the
"equator" of the particle. The annular ring is an artifact formed
during curing in the joint between the two halves of the mold used
to make the particle. The ring can be of any desired diameter by
using a die to trim the ring before particle removal from one of
the half molds. The annular ring is believed to impart additional
stability to embolisms formed from the particles.
[0034] FIG. 3B is a close up (300.times. magnification) of the
surface of the north central hemisphere of the particles in FIG.
3A. Interior pores can be readily seen. Some of the surface pores
have diameters as large as about 50 microns with some having
diameters as large as 100 or more microns. FIG. 3C depicts a cross
section of a dehydrated PVA compressible particle at 80.times.
magnification. The interior has some pores having a diameter from
100 to 500 microns with many of the pores having a diameter less
than about 100 micron. The minimum pore size is about 1 micron.
[0035] The exterior layer 14 in FIG. 1 is an outer skin that
provides increased structural strength, thereby reducing risk of
fragmentation. Further, the exterior layer 14 can provide reduced
friction when the exterior layer 14 contacts objects such as the
interior portions of delivery systems during use. Such a strong
exterior layer 14 with reduced exterior friction can aid in
insertion into a blood vessel and reduce risk of recannalization
and further, unintended embolization caused by debris that may be
trapped in the larger inner pores. In one aspect of the invention,
the relatively fewer, smaller, or lack of pores in the skin 14
enhance the structural strength and friction reducing
characteristics of the skin 14. The structural strength of the skin
results in a particle exhibiting much greater compressive size
reduction by allowing for an interior portion having larger, more
compressible pores and a foam with memory, wherein "memory" refers
to the capacity of the particle to recover toward its original
shape after deformation (elastic recovery). That is, the particle
has memory because it can be compressed to a smaller diameter and
upon release of the compressive force will return toward its
original non-compressed diameter.
[0036] The particles of the present invention can be produced in
the following manner. According to one embodiment, a PVA solution
is mixed with a porogen. The amount of PVA in solution prior to
mixing is preferably about 21%. Alternatively, the amount of PVA in
solution can range from about 5% to about 24%.
[0037] The term "porogen" refers to a pore forming material
dispersed in the polymer solution and subsequently removed to yield
pores, voids, or free volume in the material. According to one
embodiment, the porogen is starch that can be solubilized after
particle formation. Alternatively, the porogen can be, but is not
limited to, carbon dioxide, polyethylene glycol, or any of the
inert gases.
[0038] After the PVA and porogen are mixed, a crosslinking
component and crosslinking catalyst are added. The crosslinking
component can be formaldehyde and the catalyst can be hydrochloric
acid. Alternatively, the catalyst can be an acid such as sulfuric
acid or, in a further alternative, almost any known mineral
acid.
[0039] After the crosslinking component and catalyst are added to
the mixture, air or any other inert gas is then added or "whipped"
into the mixture to create a foam. The air is preferably added to
the mixture using a high speed mixer. A single element egg beater
in a high speed air motor (7,000.+-.400 rpm) can be used to make
the foam before the mixture has cross linked to any significant
degree. The mixing continues until the mixture stops expanding.
According to one embodiment, the foam stops expanding after about
30 seconds of mixing. Alternatively, the mixing period lasts for
from about 5 seconds to about 4 minutes. In a further alternative,
the mixing period lasts for from about 10 seconds to about 1
minute.
[0040] Subsequently, the reaction mixture of PVA, porogen, and air
is placed into a mold and heated for about five hours.
Alternatively, the mixture is heated for a period of time ranging
from about three hours to about ten hours. In a further
alternative, the mixture is heated for a period of time ranging
from about 4 hours to about 7 hours. It is understood that
crosslinking begins to occur after the addition of the crosslinking
component and the crosslinking catalyst such that the resulting
product removed from the mold comprises crosslinked PVA.
[0041] The mold, according to one embodiment, is a polypropylene
mold defining a substantially spherical void, thereby producing a
substantially spherical particle. Of course, this definition is
intended to include true spherical shapes and ellipsoidal shapes,
along with any other shapes that are encompassed within the maximum
diameter/minimum diameter ratio.
[0042] The reaction mixture is injected into the spherical void.
The mold, in accordance with one embodiment, has a bleed hole in
communication with the spherical void to allow for excess mixture
to drain from the void as necessary. According to one embodiment,
the mixture is injected using a syringe. In one embodiment, a
volume of the mixture greater than the volume of the void is
injected such that the portions of the mixture in contact with the
mold are compressed or placed under pressure, thereby forcing some
portion of the mixture to escape through the bleed hole. The
compression or pressure placed upon the exterior portions of the
mixture ensures that the entire void is filled with mixture and
that the mixture contacts all or substantially all of the surface
of the mold defining the void, thereby ensuring a smooth, skin or
surface to the resulting particle that can contain pores or a
relatively nonporous skin. According to one embodiment, the
polypropylene in the mold further enhances the smooth--even, in
some cases, glossed--finish of the resulting particle. The
resulting particle consists of an interior portion having larger
pores as a result of the relatively unconstrained, non-compressed
formation in away from the surface of the mold and an exterior
layer or skin that is compacted, relatively smooth, and finished as
a result of the compression on those areas of the mixture caused by
contact with the mold, though one or more macropores may be present
in the skin.
[0043] In one aspect of the invention, the mold has two components,
both of which define a hemispherical void. In this embodiment, the
reaction mixture is injected into both voids in excess such that
when the two molds are coupled to define a spherical void, the
mixture is compressed or pressured in the void and the excess
mixture is forced out of the bleed hole in communication with the
void. Again, the result of the compression or pressure is a
particle with a relatively nonporous or microporous skin or surface
with a substantially smooth finish.
[0044] In use, a particle or particles of the present invention can
be positioned in a target region of a blood vessel to occlude the
vessel. According to one embodiment, the method includes delivery
of the particle to the target region with a delivery system.
[0045] Prior to delivery of the particle, according to one
embodiment of the present invention, the user or physician can
perform angiography to determine the vascular supply to the target
area. Further, the resulting angiogram can be used to determine the
appropriate route for delivery system insertion.
[0046] In accordance with another embodiment, another pre-delivery
step is hydration of the embolization particle. The particle is
hydrated by adding hydration fluid to the particle in a
container--or placing the particle in an amount of hydration fluid
in a container. Optionally, the particle may be compressed while it
is in the fluid. As the particle expands from its compressed state
to its expanded state, hydration fluid is drawn into the voids or
pores in the interior portions of the particle, thereby
accelerating hydration of the particle. According to one
embodiment, this hydration process can be performed in a period of
about 5 seconds. Alternatively, the process can be performed in a
period ranging from about 2 seconds to about 10 seconds. The
hydration fluid is any known fluid for hydrating embolization
particles including contrast agent, saline, or any combination
thereof, where it is understood that the term "saline" encompasses
any salt solution acceptable for physiological use. It is
understood that hydration fluid, may contain contrast agent or may
be a contrast agent. For example, the hydration fluid can be a
contrast agent such as Oxilan 300.RTM..
[0047] Delivery of the particle, according to one embodiment,
includes positioning the delivery system such that the system is in
fluid communication with the target area of the blood vessel. In
one aspect of the invention, the delivery system comprises a
catheter.
[0048] The delivery process further includes placing a compressible
embolization particle into a lumen of the delivery system. In one
aspect of the invention, the diameter of the particle in its
expanded state is greater than the inner diameter of the lumen of
the delivery system such that the particle is in a compressed state
in the lumen.
[0049] The particle is then delivered to the target region by
ejecting or expelling the particle from the lumen of the delivery
system. Upon exit from the lumen into the target area, the particle
expands from its compressed state toward its expanded state. As
depicted in FIG. 2, the particle 20 is configured such that the
diameter of the target region of the blood vessel 22 is greater
than the diameter of the lumen but less than the diameter of the
particle 20 in its fully expanded state such that the particle 20
upon exiting the delivery system expands until the exterior 24 of
the particle 20 contacts the inner wall 26 of the vessel 22. In one
aspect of the invention, the diameter of the vessel 22 as described
above results in the particle 20 being in a compressed state
(though not as compressed as in the lumen of the delivery system),
thus resulting in the particle 20 exerting a continuous outward
pressure on the inner wall 26 of the blood vessel. This pressured
contact between the particle 20 and the blood vessel 22 can help to
stabilize the particle 20 in a single position within the target
area of the blood vessel 22, thereby resulting in occlusion of the
vessel 22. According to one embodiment, the pressured contact works
to retain the particle 20 in the single position in the vessel 22
such that a substantial force is required to move the particle 20.
Alternatively, the pressured contact results in the substantial
mechanical fixation of the particle 20 in a single position in the
blood vessel 22. In one embodiment, additional mechanical fixation
occurs as a result of the blood clotting caused by the presence of
the particle and by the PVA material, and further occurs as a
result of the subsequent healing process. The blood clotting forms
on both sides of the particle or at least downstream of the
particle, thereby providing further mechanical fixation. Further,
during the healing process, the immune system of the human body
recognizes that the particle is a foreign object and attempts to
form tissue around the particle, thereby providing further
mechanical fixation.
[0050] According to one embodiment, the first step in delivering
the particle of the present invention to the target region is
positioning a catheter in a patient such that the distal end of the
catheter is located at or near the target region in the patient's
blood vessel. In one alternative embodiment, the catheter has a
stopcock at the proximal end of the catheter configured to close
off the catheter to prevent loss of blood through the catheter
prior to delivery of a particle of the present invention through
the catheter. In another alternative, a stopcock is placed on the
proximal end of the catheter after the catheter is positioned in
the patient to prevent blood loss through the catheter.
[0051] Once the catheter is positioned appropriately, the
embolization particle of the present invention is positioned in the
connection portion of the catheter (not shown), which is located at
the proximal end of the catheter. According to one embodiment, the
connection portion of the catheter is a luer connector hub such
that the particle is positioned in the connector hub.
Alternatively, in embodiments in which a stopcock is positioned on
the proximal end of the catheter as described above, the connection
portion of the catheter is the stopcock.
[0052] The particle of the present invention, in one aspect of the
invention, has a diameter that is smaller than the inner diameter
of the connection portion of the catheter but larger than the inner
diameter of the catheter lumen such that the particle is easily
positioned in the hub but requires force to be urged into the
catheter lumen. The next step, therefore, is to urge the particle
from the luer connector hub into the catheter lumen. According to
one embodiment, the particle is urged into the catheter lumen using
a syringe containing hydration fluid. That is, with the particle
positioned in the connector hub of the catheter, a syringe is
connected with the hub, thereby locking or enclosing the particle
into the connection between the hub and the syringe. The plunger of
the syringe is then depressed, providing a hydraulic force that
moves the particle into the catheter lumen.
[0053] According to one embodiment, the particle is then urged
along the catheter lumen and urged out of the catheter and into the
target region using a blunt-ended guidewire. The syringe used to
load the particle into the lumen is removed from the catheter. It
is possible to remove the syringe without blood loss through the
catheter because the particle, having in its expanded state a
larger diameter than the lumen of the catheter, has sealed the
lumen of the catheter. Once the syringe is removed, a guidewire is
inserted into the proximal portion of the catheter and contacts the
particle, urging it toward and ultimately out of the distal end of
the catheter and into the target region of the patient's blood
vessel.
[0054] Alternatively, the particle can be delivered using a
delivery system instead of a guidewire. FIG. 4 depicts a delivery
system or device 30, according to one embodiment of the present
invention. The device 30 has a connection component 32 which, in
this embodiment, is a three-way stopcock. The coupling portion 38
of the connection component 32 is coupled to a catheter (not
shown). Syringes 34 and 36 are coupled to the stopcock 32. FIG. 5
depicts an alternative embodiment in which the delivery system is
provided as a kit 40. The kit 40 includes two syringes 42 and 44, a
connection component 46, and a vial 48 containing at least one
embolization particle.
[0055] Using the delivery system 30 of FIG. 4 for exemplary
purposes, the delivery system 30 can be used in the following
manner, according to one embodiment of the present invention.
First, as described above, the embolization particle is positioned
in the connection portion of the catheter. With the particle
positioned in the hub, the coupling portion 38 of the connection
component 32 of the delivery device 30 is coupled to the luer
connection hub of the catheter (not shown), thereby enclosing the
embolization particle within the connection between the coupling
portion 38 and the luer connection hub of the catheter (not
shown).
[0056] According to one embodiment, one of the two syringes 34 or
36 contains hydration fluid and the other of the two syringes 34 or
36 is empty. For purposes of this example, syringe 36 is a 1 ml
syringe that contains hydration fluid, while syringe 34 is empty.
However, according to another embodiment, syringe 36 is empty and
syringe 34 contains hydration fluid. With the particle positioned
within the coupling space of the coupling portion 38 and the
catheter luer connection hub (not shown), the stopcock 32 is
adjusted such that the syringe 36 is in fluid communication with
the syringe 34 and a small amount of hydration fluid is transferred
from the syringe 36 to the empty syringe 34. According to one
embodiment, 0.1 ml of hydration fluid is transferred to the syringe
34. Alternatively, any small amount ranging from about 0.05 ml to
about 1.0 ml can be transferred. Alternatively, an amount of
hydration fluid ranging from about 0.1 to about 0.5 ml can be
transferred. The stopcock 32 is then adjusted such that the syringe
34 is in fluid communication with only the catheter lumen. With the
syringe 34 in fluid communication with the catheter lumen, the user
injects the small amount of hydration fluid from the syringe 34
into the catheter, thereby loading the particle into the catheter
lumen. According to one embodiment, the user pushes the plunger of
syringe 34 quickly and forcefully, thereby urging the particle into
the lumen. In one alternative embodiment, the step of transferring
a small amount of hydration fluid to the syringe 34 and then
forcefully injecting the small amount into the catheter, thereby
loading the particle, can be repeated once or twice to insure
loading of the particle.
[0057] Once the particle is positioned within the catheter lumen,
the particle is urged through the catheter using a syringe
containing hydration fluid. According to one embodiment, syringe 34
is used to urge the particle along the catheter. Alternatively, the
stopcock 32 can be adjusted such that syringe 36 containing
hydration fluid is in fluid communication with the catheter lumen
and syringe 36 can be used to urge the particle along the catheter.
In a further alternative, the delivery device 30 is removed from
the catheter and another, separate syringe containing hydration
fluid is connected to the catheter and used to urge the particle
through the catheter. Alternatively, a guidewire is used to urge
the particle through the catheter.
[0058] According to an alternative embodiment, the present
invention relates to a supplemental occlusion particle configured
to enhance the treatment of aneurysms, tumors, bleeding, and
otherwise completely block blood flow to undesired anatomical areas
by supplementing the occlusion of blood vessels. This embodiment of
the invention relates to the introduction of a secondary,
supplemental compressible embolic device into a target area of a
blood vessel to compliment the action of one or more primary
embolic devices or materials. Such primary embolic devices can be
smaller embolization particles such as Microstat.TM. (Surgical
Corporation); Contour SE.TM. (Boston Scientific Corporation),
Embosphere.TM. (Biosphere Medical Inc.) or Bead Block.TM.
(Biocompatables International Plc), embolization coils, or liquid
polymer embolization systems which cure in vivo.
[0059] FIG. 6 depicts a supplemental occlusion particle 50,
according to an alternative embodiment of the present invention.
The particle 50 is positioned to operate in conjunction with the
embolization coil 52 to provide occlusion of the blood vessel 54.
The particle 50 is configured to expand from a compressed state
having a first volume to an expanded state having a second,
relatively larger volume in comparison with the first. According to
one embodiment, the particle 50 is configured to expand within the
vessel 54 and thereby provide a degree of blood-flow-blocking
mechanical fixation to support or enhance the embolic action of the
primary device 52. According to one embodiment, the use of the
supplemental particle 50 in cooperation with a primary embolization
device such as the coil 52 results in complete or substantially
complete occlusion and reduces or even eliminates the risk of
recanalization.
[0060] In an alternative embodiment as depicted in FIG. 7, the
particle 50 is positioned to operate in conjunction with two
embolization coils 52 and 56 to provide occlusion. As shown in yet
another alternative embodiment in FIG. 8, the particle 50 can also
be used in conjunction with smaller embolization particles 58 or
any other known embolization device.
[0061] The supplemental occlusion particle 50, in accordance with
one aspect of the invention, is an embolic PVA particle as
described above and depicted in FIG. 1, having an inner, porous
portion and an outer layer comprised of fewer and/or closed pores
having an average diameter that is smaller than the average
diameter of the pores in the inner portion of the particle
Alternatively, the supplemental occlusion particle 50 is any
embolic device having materials with a highly compressible porous
structure, such as crosslinked PVA foams. In a further alternative,
the PVA foam can also be configured radiopaque by a variety of well
known methods. In yet another alternative, the supplemental
occlusion particle can be any known embolic particle or device
capable of expanding radially inside the vessel and thereby
providing a degree of mechanical fixation to support the blocking
action of the primary embolization device to provide complete and
permanent occlusion of the vessel.
[0062] In use, the supplemental particle can operate in the
following manner. According to one embodiment, the supplemental
particle is positioned in operable proximity to the primary
occlusion device. That is, the supplemental particle is positioned
in a location such that it operates to enhance the degree of
blood-flow blockage created by the primary device. The supplemental
particle is positioned using a delivery method or system. According
to one embodiment, the particle is positioned using a guidewire as
described herein. Alternatively, the particle is positioned using
one of the systems depicted in FIG. 4 or 5 or a similar system. The
delivery system is positioned with respect to the target area of
the blood vessel to allow for positioning the particle in the
target area. The particle is placed in the lumen of the delivery
system which, according to one embodiment, is a catheter. The lumen
has a smaller inner diameter than the diameter of the particle in
its expanded state. As such, the particle is retained in a
compressed state by the lumen. The particle is then expelled or
ejected from the lumen of the delivery device into the blood vessel
at the target area such that it is positioned in operable proximity
with the primary device. Upon or during exit from the lumen, the
supplemental particle expands in the blood vessel.
[0063] Tables I-VI compare the compressibility and catheter
compatibility of Embosphere.TM. particles (Tables I and II),
Contour SET.TM. particles (Tables III and IV) and Maxistat.TM.
particles (which are within the scope of the invention) (Tables V
and VI).
[0064] Although the present invention has been described with
reference to preferred embodiments, persons skilled in the art will
recognize that changes may be made in form and detail without
departing from the spirit and scope of the invention.
TABLE-US-00001 TABLE I CATHETER COMPATIBILITY OF EMBOSPHERE
MICROSPHERES From Their Catheter Compatibility Chart Embosphere
Microspheres (microns) Catheter ID (inches) Catheters MFG 40-120
100-300 300-500 500-700 700-900 900-1200 0.035-0.038 All 4Fr and 5F
X X X X X X 0.028 EmboCath BioSphere X X X X X 0.024-0.027 Terumo
Progreat Bost Sci FasTracker-325 Bost Sci Renegade Hi-Flo Cordis X
X X X X MassTransit Micro Rebar-027 Ther 0.019-0.023 RapidTransit
Cordis Renegade Bost Sci X X X X TurboTracker-18 Bost Sci
0.014-0.018 Regatta Cordis Prowler-10 Cordis X X X Prowler-14
Cordis Tracker Excel-14 Bost Sci 0.008-0.130 Spinnaker Elite 1.5
Bost Sci Spinnaker Elite 1.8 Bost Sci X X Magic 1.5 Balt
[0065] TABLE-US-00002 TABLE II COMPRESSIBILITY OF EMBOSPHERE
MICROSPHERES EMBOSPHERE High End High End of Particle of Particle
Range in Embosphere Compatible Range in Microns Inches Smallest ID
Size (Inches) Compression.sup.1 300 0.011811 0.008 32.3% 500
0.019685 0.014 28.9% 700 0.027559 0.019 31.1% 900 0.035433 0.024
32.3% 1200 0.047244 0.035 25.9% .sup.1Embosphere Catheter
Compatibility Chart states up to 33% compression
[0066] TABLE-US-00003 TABLE III CATHETER COMPATIBILITY OF CONTOUR
SE MICROSPHERES From Their Catheter Compatibility Chart Contour SE
Microspheres (microns) Catheter ID Including Catheters MFG 100-300
300-500 500-700 700-900 900-1200 0.038 Selective 4Fr and 5F Bost
Sci X X X X X 0.024 FasTracker-325 Bost Sci X X X X Renegade Hi-Flo
0.021 Renegade-18 Bost Sci X X X 0.013 Excelisor SL-10 Bost Sci X X
0.011 Spinnaker Elite 1.5Fr Bost Sci X
[0067] TABLE-US-00004 TABLE IV COMPRESSIBILITY OF CONTOUR SE
PARTICLES CONTOUR SE High End of Particle High End of Particle
Range in Contour SE Compatible Range in Microns Inches Smallest ID
Size (Inches) Compression 300 0.011811 0.011 6.9% 500 0.019685
0.013 34.0% 700 0.027559 0.021 23.8% 900 0.035433 0.024 32.3% 1200
0.047244 0.038 19.6%
[0068] TABLE-US-00005 TABLE V Compressibility of Surgica Maxistat
Particles.sup.(1) MaxiStat Catheter Dehydrated Particle Smallest
Particles Size Calculated % Swelling Hydrated Particle Size in ID
Size Range upon Hydration in Product Size (microns) Inches (Inches)
Compression in microns Mean saline MaxiStat 2500 2500 0.098425
0.027 72.6% 1875 2250 2062.5 21.2% MaxiStat 3000 3000 0.11811 0.035
70.4% 2250 2625 2437.5 23.1% MaxiStat 3500 3500 0.137795 0.035
74.6% 2625 2800 2712.5 29.0% MaxiStat 4000 4000 0.15748 0.035 77.8%
2800 3200 3000 33.3% .sup.(1)The Maxistate particles are
substantially spherical porous embolization particles made by
Surgica Corporation (El Dorado Hills, CA)
[0069] TABLE-US-00006 TABLE VI Maxistat .TM. PVA Foam Embolization
Particles (microns) Catheter 1,875- 2,250- 2,625- 2,800- ID
Catheters MFG 2,250 2,625 2,800 3,200 0.038 Soft-Vu AngioDynamics
Simmons X X X X "Sidewinder" ST 0.035 Mariner AngioDynamics
Hydrophilic Coated X X X X Simmons- "Sidewinder" 0.027 Slip-Cath
Cook Infusion X Catheter
EXAMPLES
Example 1
[0070] A crosslinked PVA embolization particle was prepared in the
following manner. A mixture of 26.2 grams of PVA and 98.9 grams of
deionized water was rapidly heated to 100.degree. C. and held for
12 minutes. Subsequently, 39.9 grams of the resulting PVA solution
was transferred for reaction purposes into a reaction kettle (a
glass beaker) and set aside and allowed to cool. Separately, a
mixture of 15 grams of rice starch and 135 grams of deionized water
was heated to 80.degree. C. and then 9.5 grams of the material was
added to the PVA solution and thoroughly mixed. To this resulting
mixture was added 3.6 grams of concentrated hydrochloric acid and
6.4 grams of about 37% formaldehyde (formalin solution) to form the
reaction solution.
[0071] The reaction solution was then placed in a 2 liter glass
reaction kettle and mixed at about 7000 rpm with a high-speed mixer
having a high-speed air motor and using a mixing blade to whip air
into the mixture until the foam stopped expanding and the resulting
mixture achieved an appearance similar to whipped cream, which
required about 30 seconds of mixing. The mixing blade was similar
in configuration to an egg beater.
[0072] After mixing, the reaction mixture was transferred to
spherical molds of 2.5 mm, 3.0 mm, 3.5 mm and 4.0 mm diameter and
allowed to cure for 5 hours at 55.degree. C. The polypropylene
molds used in this example have two identical 1 inch by 1 inch
square pieces that are 0.2 inches in thickness. Each piece defines
a hemisphere on one side, wherein the hemisphere is sized according
to the desired size of the embolization particle. Further, each
piece also defines a 0.039 inch bleed hole in fluid communication
with the hemisphere, thereby allowing relief of any overfill amount
through the bleed hole.
[0073] The resulting products were partially acetalized crosslinked
PVA sponges, which were then thoroughly washed to remove excess
formaldehyde and hydrochloric acid. Certain portions of the
resulting sponges were then removed, including the center ring and
the poles (flashing), to create substantially spherical particles
of 2.5 mm, 3.0 mm, 3.5 mm and 4.0 mm in diameter in their hydrated,
fully expanded state. The sponges were then dried for 16.5 hours at
50.degree. C. to complete the manufacturing process.
Example 2
[0074] The same procedure performed in Example 1 was repeated, but
the formaldehyde additive was reduced to 5.2 grams. It was believed
that the reduction in formaldehyde would change the pot-life of the
reaction solution, wherein "pot-life" is intended to mean the
useful life of the mixture (after some period of time, the mixture
ages to the point that it cannot be used to create a particle of
the present invention). However, no significant change in pot-life
was observed.
Example 3
[0075] The same procedure performed in Example 1 was repeated, but
the hydrochloric acid additive was reduced to 5.0 grams. The
resulting sponges had both an increased firmness and increased
resilience in comparison to the sponges produced in Example 1,
wherein firmness is a qualitative measure of the compressibility of
the particle. Further, the pot-life of the reaction material was
decreased by about 30 seconds.
Example 4
[0076] The same procedure performed in Example 1 was repeated, but
the hydrochloric acid additive was reduced to 2.1 grams. The
resulting sponges had both a decreased firmness and decreased
resilience in comparison to the sponges produced in Example 1 such
that the resulting sponges in the present example were
significantly less "sponge-like" in comparison to the sponges
produced in Example 1.
Example 5
SEM Images
[0077] The instrument used was a Quanta 600 Environmental Scanning
Electron Microscope manufactured by the FEI Company (Hillsboro,
Oreg.) and available at the Scripps Institute of Oceanography (San
Diego, Calif.).
[0078] All samples were prepared (methods well known in the art) by
Critical Point Drying, exchanging 200 proof ethanol for the saline
hydration fluid, then exchanging the ethanol with liquid CO2
(4.times.), then finally heating to drive the CO.sub.2 off as a
gas. The samples were then transferred to carbon tape and sputter
coated with gold/palladium. The samples were then imaged under high
vacuum SEM. FIG. 3A-3C were made according to this protocol.
* * * * *