U.S. patent application number 10/431967 was filed with the patent office on 2003-12-25 for multi-lobed frame based unidirectional flow prosthetic implant.
Invention is credited to Hojeibane, Hikmat, Majercak, David Christopher.
Application Number | 20030236568 10/431967 |
Document ID | / |
Family ID | 29420545 |
Filed Date | 2003-12-25 |
United States Patent
Application |
20030236568 |
Kind Code |
A1 |
Hojeibane, Hikmat ; et
al. |
December 25, 2003 |
Multi-lobed frame based unidirectional flow prosthetic implant
Abstract
The present invention relates to a medical device, and in
particular, to a stent-based valve. The valve has a radially
expandable structural frame having a substantially cylindrical
configuration with first and second open ends and a longitudinal
axis extending there between. The structural frame is formed from a
lattice of interconnected elements and has a plurality of distal
crowns. A biocompatible membrane assembly maintaining a
substantially cylindrical shape about the longitudinal axis is
attached to the structural frame such that the structural frame
supports the biocompatible membrane assembly in a slack condition
between the distal crowns.
Inventors: |
Hojeibane, Hikmat;
(Princeton, NJ) ; Majercak, David Christopher;
(Stewartsville, NJ) |
Correspondence
Address: |
PHILIP S. JOHNSON
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
29420545 |
Appl. No.: |
10/431967 |
Filed: |
May 8, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60379604 |
May 10, 2002 |
|
|
|
Current U.S.
Class: |
623/1.24 ;
623/2.18 |
Current CPC
Class: |
A61F 2002/91583
20130101; A61F 2002/91575 20130101; A61F 2220/005 20130101; A61F
2/2415 20130101; A61F 2/2412 20130101; A61F 2230/0078 20130101;
A61F 2230/0054 20130101; A61F 2002/91558 20130101; A61F 2/2475
20130101; A61F 2/915 20130101; A61F 2002/825 20130101; A61F 2/2418
20130101; A61F 2002/91533 20130101; A61F 2220/0058 20130101 |
Class at
Publication: |
623/1.24 ;
623/2.18 |
International
Class: |
A61F 002/06; A61F
002/24 |
Claims
What is claimed is:
1. A prosthetic valve comprising: a radially expandable structural
frame having a plurality of distal crowns, the structural frame
being formed from a lattice of interconnected elements, and having
a substantially cylindrical configuration with first and second
open ends and a longitudinal axis extending there between; a
tubular biocompatible membrane coaxially disposed over at least a
portion of the structural frame such that the structural frame
supports the biocompatible membrane assembly in a slack condition
between the distal crowns.
2. The prosthetic valve of claim 1 wherein the structural frame
further comprises a valve strut attached to at least one of the
distal crowns and extending in a distal direction substantially
parallel to the longitudinal axis.
3. The prosthetic valve of claim 1 wherein the distal crowns are
articulating.
4. The prosthetic valve of claim 1 wherein the biocompatible
membrane assembly extends in a distal direction past the distal
crowns.
5. A prosthetic valve comprising: a radially expandable structural
frame having a plurality of distal crowns, the structural frame
being formed from a lattice of interconnected elements, and having
a substantially cylindrical configuration with first and second
open ends and a longitudinal axis extending there between; a
tubular biocompatible membrane coaxially disposed over at least a
portion of the structural frame such that the structural frame
supports the biocompatible membrane assembly in a flexible
condition between the distal crowns.
6. A prosthetic valve comprising: a substantially cylindrical
structural frame having a hoop structure, the hoop structure having
a plurality of distal crowns; a substantially cylindrical
biocompatible membrane assembly coaxially disposed over the
structural frame such that the structural frame supports the
biocompatible membrane assembly in a slack condition between the
distal crowns.
7. A prosthetic valve having a radially expandable structural frame
comprising: a cylindrical hoop structure having a plurality of
distal and proximal crowns; a proximal anchor formed from a lattice
of interconnected elements and having a substantially cylindrical
configurations; one or more connecting members, the one or more
connecting members having a first and a second end, the first end
of each connecting member being attached to the proximal anchor and
the second end of each connecting member being attached to the hoop
structure; and a substantially cylindrical biocompatible membrane
assembly attached to the proximal anchor and extending distally
along the one or more connecting members to the distal crowns, such
that the distal crowns.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit under 35 U.S.C. 119(e)
of U.S. Provisional Application Serial No. 60/379,604, filed May
10, 2002.
FIELD OF THE INVENTION
[0002] The present invention relates to a medical device, and more
particularly to a multi-lobed frame based unidirectional flow
prosthetic valve, and the method for fabricating such valve.
BACKGROUND OF RELATED ART
[0003] The human body has numerous biological valves that control
fluid flow through body lumens and vessels. For example the
circulatory system has various heart valves that allow the heart to
act as a pump by controlling the flow of blood through the heart
chambers, veins, and aorta. In addition, the venous system has
numerous venous valves that help control the flow of blood back to
the heart, particularly from the lower extremities.
[0004] These valves can become incompetent or damaged by disease,
for example, phlebitis, injury, or the result of an inherited
malformation. Heart valves are subject to disorders, such as mitral
stenosis, mitral regurgitation, aortic stenosis, aortic
regurgitation, mitral valve prolapse and tricuspid stenosis. These
disorder are potentially life threatening. Similarly, incompetent
or damaged venous valves usually leak, allowing the blood to
improperly flow back down through veins away from the heart
(regurgitation reflux or retrograde blood flow). Blood can then
stagnate in sections of certain veins, and in particular, the veins
in the lower extremities. This stagnation of blood raises blood
pressure and dilates the veins and venous valves. The dilation of
one vein may in turn disrupt the proper function of other venous
valves in a cascading manner, leading to chronic venous
insufficiency.
[0005] Numerous therapies have been advanced to treat symptoms and
to correct incompetent valves. Less invasive procedures include
compression, elevation and wound care. However, these treatments
tend to be somewhat expensive and are not curative. Other
procedures involve surgical intervention to repair, reconstruct or
replace the incompetent or damaged valves, particularly heart
valves.
[0006] Surgical procedures for incompetent or damaged venous valves
include valvuloplasty, transplantation, and transposition of veins.
However, these surgical procedures provide somewhat limited
results. The leaflets of some venous valves are generally thin, and
once the valve becomes incompetent or destroyed, any repair
provides only marginal relief.
[0007] As an alternative to surgical intervention, drug therapy to
correct valvular incompetence has been utilized. Currently,
however, there are no effective drug therapies available.
[0008] Other means and methods for treating and/or correcting
damaged or incompetent valves include utilizing xenograft valve
transplantation (monocusp bovine pericardium),
prosthetic/bioprosthetic heart valves and vascular grafts, and
artificial venous valves. These means have all had somewhat limited
results.
[0009] What is needed is an artificial endovascular valve for the
replacement of incompetent biological human valves, particularly
heart and venous valves. These valves may also find use in
artificial hearts and artificial heart assist pumps used in
conjunction with heart transplants.
SUMMARY OF THE INVENTION
[0010] The present invention relates to a medical device, and in
particular, to a frame-based valve. One embodiment of the invention
comprises a radially expandable structural frame having a plurality
of distal crowns or lobes. The structural frame is formed from a
lattice of interconnected elements, and has a substantially
cylindrical configuration with first and second open ends and a
longitudinal axis extending there between. A tubular biocompatible
membrane is coaxially disposed over at least a portion of the
structural frame such that the structural frame supports the
biocompatible membrane assembly in a slack condition between the
distal crowns. The prosthetic valve may further have a valve strut
attached to at least one of the distal crowns that extends in a
distal direction substantially parallel to the longitudinal axis.
The biocompatible membrane assembly may also extend in a distal
direction past the distal crowns.
[0011] In another embodiment of the invention, the prosthetic valve
comprises a radially expandable structural frame having a plurality
of articulating distal crowns. The structural frame is formed from
a lattice of interconnected elements, and has a substantially
cylindrical configuration with first and second open ends and a
longitudinal axis extending there between. A tubular biocompatible
membrane is coaxially disposed over at least a portion of the
structural frame such that the structural frame supports the
biocompatible membrane assembly in a slack condition between the
distal crowns.
[0012] In still another embodiment of the invention the prosthetic
valve comprises a substantially cylindrical structural frame that
has a hoop structure with a plurality of distal crowns. A
substantially cylindrical biocompatible membrane assembly is
attached to the structural frame such that the structural frame
supports the biocompatible membrane assembly in a slack condition
between the distal crowns.
[0013] A prosthetic valve according to another embodiment of the
invention has a radially expandable structural frame comprising a
cylindrical hoop structure having a plurality of distal and
proximal crowns, a proximal anchor, and one or more connecting
members. The proximal anchor has a substantially cylindrical
configuration and is formed from a lattice of interconnected
elements. The one or more connecting members has a first and a
second end, the first end of each connecting member is attached to
the proximal anchor and the second end of each connecting member is
attached to the hoop structure. A biocompatible membrane assembly
is coaxially disposed over the structural frame and attached to the
proximal anchor, such that the biocompatible membrane assembly
extends distally along the one or more connecting members.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 shows a perspective view of a prosthetic venous valve
in the deployed state according to one embodiment of the present
invention.
[0015] FIG. 2A shows a perspective view of the prosthetic venous
valve structural frame in the deployed state
[0016] FIG. 2B shows a close-up perspective view of a loop having
inner and outer radii according to one embodiment of the present
invention.
[0017] FIG. 3A shows a perspective view of a prosthetic valve
having two hoop structures according to another embodiment of the
present invention.
[0018] FIG. 3B shows a perspective view of a structural frame
having two hoop structures according to another embodiment of the
present invention.
[0019] FIG. 3C shows a perspective view of a structural frame
having two hoop structures attached with bridge members.
[0020] FIG. 3D shows a perspective view of a prosthetic venous
valve having connecting members connected between the sinusoidal
structure and proximal anchor according to one embodiment of the
present invention.
[0021] FIG. 3E shows a perspective view of the prosthetic venous
valve structural frame having connecting members connected between
the sinusoidal structure and proximal anchor in a peak-to-peak
configuration according to one embodiment of the present
invention.
[0022] FIG. 4A is a perspective view illustrating one embodiment of
the expanded (deployed) prosthetic venous valve assembly in the
open position.
[0023] FIG. 4B is a section view illustrating one embodiment of the
expanded (deployed) prosthetic venous valve assembly in the open
position.
[0024] FIG. 5A is a perspective view illustrating one embodiment of
the expanded (deployed) prosthetic venous valve assembly in the
closed position.
[0025] FIG. 5B is a section view illustrating one embodiment of the
expanded (deployed) prosthetic venous valve assembly in the closed
position.
[0026] FIG. 6A is a perspective view of a prosthetic valve having
flexible distal crowns capable of deflecting inward during
retrograde blood flow.
[0027] FIG. 6B is a perspective view of a prosthetic valve
according to an embodiment of the present invention.
[0028] FIG. 6C is a perspective view of a prosthetic valve having
valve struts according to an embodiment of the present
invention.
[0029] FIG. 6D is a perspective view illustrating a membrane
limiting means according to one embodiment of the present
invention.
[0030] FIG. 6E is a perspective view illustrating a membrane
limiting means according to one embodiment of the present
invention.
[0031] FIG. 6F is a perspective view illustrating a membrane
limiting means according to one embodiment of the present
invention.
[0032] FIG. 6G is a perspective view of a prosthetic valve having
valve struts according to an embodiment of the present
invention.
[0033] FIG. 7 is a flow diagram illustrating the steps to
electro-statically spin a tubular membrane on a structural frame
according to one embodiment of the present invention.
[0034] FIG. 8A is section view illustrating the expanded (deployed)
prosthetic venous valve assembly in the open position after some
post processing according to one embodiment of the present
invention.
[0035] FIG. 8B shows a close-up section view illustrating a portion
of the valve assembly after some post processing according to one
embodiment of the present invention.
[0036] FIG. 9 is a flow diagram illustrating the steps to
electro-statically spin a tubular membrane on a structural frame
according to one embodiment of the present invention.
[0037] FIG. 10 is a flow diagram illustrating the steps to place a
tubular membrane over a structural frame according to one
embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0038] The stent-based valves of the present invention provide a
method for overcoming the difficulties associated with the
treatment of valve insufficiency. Although stent based venous
valves are disclosed to illustrate one embodiment of the present
invention, one of ordinary skill in the art would understand that
the disclosed invention can be equally applied to other locations
and lumens in the body, such as, for example, coronary, vascular,
non-vascular and peripheral vessels, ducts, and the like, including
but not limited to cardiac valves, venous valves, valves in the
esophagus and at the stomach, valves in the ureter and/or the
vesica, valves in the biliary passages, valves in the lymphatic
system and valves in the intestines.
[0039] In accordance with one aspect of the present invention, the
prosthetic valve is designed to be percutaneously delivered through
a body lumen to a target site by a delivery catheter. The target
site may be, for example, a location in the venous system adjacent
to an insufficient venous valve. Once deployed the prosthetic
venous valve functions to assist or replace the incompetent or
damaged natural valve by allowing normal blood flow (antegrade
blood flow) and preventing or reducing backflow (retrograde blood
flow).
[0040] A perspective view of a prosthetic venous valve in the
expanded (deployed) state according to one embodiment of the
present invention is shown in FIG. 1. The prosthetic venous valve
100 comprises a structural frame 101 and a biocompatible membrane
assembly 102.
[0041] In one embodiment, the membrane assembly 102 is comprised of
a tubular membrane, valve flaps and valve cusps. The flaps and
cusps may be independent components attached to the tubular
membrane to form the membrane assembly 102, but are preferably part
of, and integrated into, the tubular membrane. In a preferred
embodiment, the valve flaps and valve cusps are formed into the
tubular membrane by processing techniques as will be discussed in
greater detail below.
[0042] For clarity, a perspective view of the structural frame 101
according to one embodiment of the present invention is shown in
FIG. 2A. The structural frame 101 consists of a stent based
sinusoidal structure, having a single hoop section 200A with one or
more proximal and distal crowns (lobes) 205, 206 respectively. In a
preferred embodiment, at least three distal crowns 206 are utilized
as illustrated. However, this configuration is not meant to limit
the scope of the invention. Various other configurations having one
or more distal crowns 206 may be used, and would be understood by
one of skill in the art.
[0043] It should be noted that the terms proximal and distal are
typically used to connote a direction or position relative to a
human body. For example, the proximal end of a bone may be used to
reference the end of the bone that is closer to the center of the
body. Conversely, the term distal can be used to refer to the end
of the bone farthest from the body. In the vasculature, proximal
and distal are sometimes used to refer to the flow of blood to the
heart, or away from the heart, respectively. Since the prosthetic
valves described in this invention can be used in many different
body lumens, including both the arterial and venous system, the use
of the terms proximal and distal in this application are used to
describe relative position in relation to the direction of fluid
flow. For example, the use of the term proximal crown in the
present application describes the upstream crown of structural
frame 101 regardless of its orientation relative to the body.
Conversely, the use of the term distal crown is used to describe
the down stream crown on structural frame 101 regardless of its
orientation relative to the body. Similarly, the use of the terms
proximal and distal to connote a direction describe upstream
(retrograde) or downstream (antegrade) respectively.
[0044] As previously disclosed, in one embodiment of the invention,
the structural frame is a stent-based structure. This configuration
facilitates the percutaneous delivery of the prosthetic venous
valve 100 through the vascular system in a compressed state. Once
properly located, the stent-based venous valve 100 may be deployed
to the expanded state.
[0045] The sinusoidal stent based structural frame illustrated in
FIG. 2A is shown having an S shaped pattern. This configuration is
shown for the purpose of example, and is not meant to be construed
as limiting the scope of the invention. One of ordinary skill in
the art would understand that other stent geometries having similar
crowns may be used.
[0046] The sinusoidal stent based structural frame 101 comprises a
tubular configuration of structural elements having proximal and
distal open ends and defining a longitudinal axis 106 extending
there between. The structural frame 101 has a first diameter (not
shown) for insertion into a patient and navigation through the
vessels, and a second diameter D2 for deployment into the target
area of a vessel, with the second diameter being greater than the
first diameter. The structural frame 101, and thus the stent based
venous valve 100, may be either a mechanical (balloon) or
self-expanding stent based structure.
[0047] The structural frame 101 comprises at least one hoop
structure 200A extending between the proximal and distal ends. The
hoop structure 200A includes a plurality of longitudinally arranged
strut members 208 and a plurality of loop members 210 connecting
adjacent struts 208. Together, these strut members 208 and loop
members 210 form the proximal and distal crowns 205, 206
respectively. Adjacent struts 208 are connected at opposite ends in
a substantially S or Z shaped pattern so as to form a plurality of
cells. As previously discussed, one of ordinary skill in the art
would recognize that the pattern shaped by the struts is not a
limiting factor, and other shaped patterns may be used. The
plurality of loops 210 have a substantially semi-circular
configuration, having an inner radii 212 and outer radii 214, and
are substantially symmetric about their centers. The inner and
outer radii 212, 214 respectively, are shown in a close-up
perspective view illustrated in FIG. 2B.
[0048] The embodiment of the invention illustrated in FIGS. 1 and 2
show a structural frame 101 having a single hoop structure 200A.
However, it should be understood that this configuration is not
meant to be construed as a limiting feature, and other
configurations having a plurality of hoop structures are also
contemplated by the present invention.
[0049] FIGS. 3A through 3C illustrate a structural frame 101 having
two hoop structures 200A and 200B according to another embodiment
of the present invention. FIG. 3A shows a complete prosthetic valve
300 in the expanded (deployed) position, illustrating both the
structural frame 101 and membrane assembly 102. For clarity, FIG.
3B is an illustration of just the structural frame 101 without the
membrane assembly 102. In the illustrated embodiment, the hoop
structures 200A and 200B are rigidly attached at complimentary
points along their respective outer radii of the loops 210.
[0050] In an alternate embodiment shown in FIG. 3C, the hoop
structures 200A, 200B may be attached with one or more bridge
members 305. Each bridge member 305 comprises two ends 316A, 316B.
One end 316A, 316B of each bridge 305 is attached to one loop on
one hoop. Using hoop sections 200A and 200B for example, each
bridge member 305 is connected at end 316A to loop 210 on hoop
section 200A at a point 320. Similarly, the opposite end 316B of
each bridge member 314 is connected to loop 210 on hoop sections
200B at a point 321.
[0051] In any of the above described configurations, the
connections between the hoop structures 200A, 200B etc. may be made
at every loop member 210 around the circumference of the structure;
or alternatively, at a subset of the loop members 210 around the
circumference of the structure. In other words, connected loop
members 210 alternate with unconnected loop members in some defined
pattern.
[0052] Depending on the location of the implanted valve, it may be
desirable to attach the hoop structures to an anchor by means of
one or more connecting members. This configuration may add to the
stability of the implanted valve. The anchor may be in the form of
another sinusoidal stent based structure, such as the structures
depicted in FIGS. 1 through 3C. However, any radially expandable
structural frame that can aid in anchoring prosthetic valve is
contemplated by the present invention. These anchors may be located
downstream (proximal) or upstream (distal) from the lobed
valve.
[0053] FIG. 3D illustrates a prosthetic lobed valve 300
incorporating a proximal anchor and connecting members according to
one embodiment of the invention. For clarity, FIG. 3E shows the
valve 300 structural frame 101 with the membrane structure 102
removed. The illustrated valve 300 comprises a single hoop
structure 200A having proximal and distal crowns 205, 206
respectively. The structural frame also has an anchor 315 proximal
to the hoop structure 200A.
[0054] The anchor 315 illustrated in FIGS. 3D and 3E is
structurally similar to the sinusoidal stent based structure
comprising the hoop structure 200A. The anchor 315 comprises a
tubular configuration of structural elements having proximal and
distal open ends and defining a longitudinal axis 306 extending
there between. The stent anchor 315 has a first diameter (not
shown) for insertion into a patient and navigation through the
vessels, and a second diameter D2 for deployment into the target
area of a vessel, with the second diameter being greater than the
first diameter. The stent anchor 315, and thus the stent based
venous valve 300, may be either a mechanical (balloon) or
self-expanding stent based structure.
[0055] The stent anchor 315 comprises at least one hoop structure
336 extending between the proximal and distal ends. The hoop
structure 336 includes a plurality of longitudinally arranged strut
members 338 and a plurality of loop members 340 connecting adjacent
struts 338. As shown, the stent anchor 315 has three hoop
structures.
[0056] Adjacent struts 338 are connected at opposite ends in a
substantially S or Z shaped pattern so as to form a plurality of
cells. As previously discussed, one of ordinary skill in the art
would recognize that the pattern shaped by the struts is not a
limiting factor, and other shaped patterns may be used. The
plurality of loops 340 have a substantially semi-circular
configuration, having an inner radii and outer radii, and are
substantially symmetric about their centers.
[0057] The connecting member 310 may be connected to the hoop
structure 200A (on the sinusoidal valve structure) and the proximal
anchor 315 at various points along the structures. As illustrated
in FIG. 3E, the connecting members 310 are connected between the
proximal end of the hoop structure 200A and the distal end of the
proximal anchor 315 at the inflection point of the loop members.
This configuration creates a "Peak-to-Peak" connection bridging the
outer radii of the inflection point of loop members 210 on the hoop
structure 200A with the outer radii of the inflection point of the
loop member 340 on the proximal anchor 315.
[0058] Preferably the connecting members 310 are connected to the
inflection point of loop members 210, 340 oriented directly
opposite one another, and are evenly spaced along the circumference
of the tubular structures. This configuration facilitates the
radial expansion of the prosthetic valve from the collapsed
(delivered) state to the expanded (deployed) state, and provides a
substantially symmetrical valve configuration.
[0059] Alternatively, the connecting members 310 may be connected
between the hoop structure 200A and proximal anchor 315 to create a
"Peak-to-Valley" connection between the loop members 210, 340
respectively (not shown). In this configuration the connecting
members 310 are connected to the proximal end of the hoop structure
200A at the outer radii of the inflection point of loop member 210,
and the inner radii of the inflection point of loop member 340 on
the proximal end of the proximal anchor 315.
[0060] In a further embodiment (not shown), the connecting members
310 may be connected between the distal end of the hoop structure
200A and the proximal end of the proximal anchor 315 at the
inflection point of the loop members 210, 340. This configuration
creates a "Valley-to-Valley" connection bridging the inner radii of
the inflection point of loop members 340 on the proximal anchor 315
with the inner radii of the inflection point of the loop member 210
on the hoop structure 200A.
[0061] In still a further embodiment (not shown), the connecting
members 310 may be connected between the strut members 208 of the
hoop structure 200A and the strut members 338 of the proximal
anchor 315.
[0062] In any of the above described configurations, the
connections between the connecting members 310 and the hoops 200
may be made at every inflection point around the circumference of
the structure; or alternatively, at a subset of the inflection
points around the circumference of the structure. In other words,
connected inflection points alternate with unconnected inflection
points in some defined pattern.
[0063] As earlier described, the connecting members 310 are
attached between the sinusoidal stent based structure (having loop
200A in FIGS. 3D and 3E) and the proximal anchor 315 to further
support the biocompatible membrane assembly 102 (not shown in FIG.
3E). In one embodiment, the connecting members 315 are
substantially straight members, connecting the hoop structure 200A
and proximal anchor 315 in a direction substantially parallel to
the longitudinal axis 306. Although three connecting members 315
are shown in the illustrated embodiment, one of skill in the art
would understand that one or more connecting members may be
used.
[0064] Alternatively, the connecting members 315 may be twisted in
a helical fashion as they extend from the hoop structure 200A to
the proximal anchor 315 (not shown). Specifically, the connection
points between the connecting members 315 and the hoop structure
200A, and the connecting members 105 and the proximal anchor 315,
are rotationally phased 180 degrees from each other to provide the
helical design.
[0065] Each connecting member 310 may also be biased inward
slightly toward the longitudinal centerline 306, creating a
structural frame 101 having an hour-glass shape with the minimum
radius located substantially at the longitudinal midpoint along the
connecting member 310 length (not shown). The proximal crowns 205
may similarly be biased inward. This configuration may assist the
prosthetic valve 300 when closing by forming larger valve
cusps.
[0066] The materials for the structural frame 101 should exhibit
excellent corrosion resistance and biocompatibility. In addition,
the material comprising the structural frame 101 should be
sufficiently radiopaque and create minimal artifacts during
MRI.
[0067] The present invention contemplates deployment of the
prosthetic venous valve 100 by both assisted (mechanical)
expansion, i.e. balloon expansion, and self-expansion means. In
embodiments where the prosthetic venous valve 100 is deployed by
mechanical (balloon) expansion, the structural frames 101 is made
from materials that can be plastically deformed through the
expansion of a mechanical assist device, such as by the inflation
of a catheter based balloon. When the balloon is deflated, the
frame 101 remains substantially in the expanded shape. Accordingly,
the ideal material has a low yield stress (to make the frame 101
deformable at manageable balloon pressures), high elastic modulus
(for minimal recoil), and is work hardened through expansion for
high strength. The most widely used material for balloon expandable
structures 101 is stainless steel, particularly 316L stainless
steel. This material is particularly corrosion resistant with a low
carbon content and additions of molybdenum and niobium. Fully
annealed, stainless steel is easily deformable.
[0068] Alternative materials for mechanically expandable structural
frames 101 that maintain similar characteristics to stainless steel
include tantalum, platinum alloys, niobium alloys, and cobalt
alloys. In addition other materials, such as polymers and
bioabsorbable polymers may be used for the structural frames
101.
[0069] Where the prosthetic venous valve 100 is self-expanding, the
materials comprising the structural frame 101 should exhibit large
elastic strains. A suitable material possessing this characteristic
is Nitinol, a Nickel-Titanium alloy that can recover elastic
deformations of up to 10 percent. This unusually large elastic
range is commonly known as superelasticity.
[0070] The disclosure of various materials comprising the
structural frame should not be construed as limiting the scope of
the invention. One of ordinary skill in the art would understand
that other material possessing similar characteristics may also be
used in the construction of the prosthetic venous valve 100. For
example, bioabsorbable polymers, such as polydioxanone may also be
used. Bioabsorbable materials absorb into the body after a period
of time, leaving only the biocompatible membrane 102 in place. The
period of time for the structural frame 101 to absorb may vary, but
is typically sufficient to allow adequate tissue growth at the
implant location to adhere to and anchor the biocompatible membrane
102.
[0071] The structural frame 101 may be fabricated using several
different methods. Typically, the structural frame 101 is
constructed from sheet, wire (round or flat) or tubing, but the
method of fabrication generally depends on the raw material form
used.
[0072] The structural frame 101 can be formed from wire using
convention wire forming techniques, such as coiling, braiding, or
knitting. By welding the wire at specific locations a closed-cell
structure may be created. This allows for continuous production,
i.e. the components of the structural frame 101 may be cut to
length from a long wire mesh tube.
[0073] In addition, the complete frame structure may be cut from a
solid tube or sheet of material, and thus the structural frame 101
would be considered a monolithic unit. Laser cutting, water-jet
cutting and photochemical etching are all methods that can be
employed to form the structural frame 101 from sheet and tube
stock.
[0074] As discussed above, the disclosure of various methods for
constructing the structural frame 101 should not be construed as
limiting the scope of the invention. One of ordinary skill in the
art would understand that other construction methods may be
employed to form the structural frame 101 of the prosthetic venous
valve 100.
[0075] The structural frame 101 is radially expandable and assists
in securing the prosthetic valve 100 to the inside wall of a body
vessel such as a vein. Once deployed in the desired location,
radially expandable structural frame (and thus the prosthetic valve
100) will expand to an outside diameter slightly larger that the
inside diameter of the native vessel (not shown) and remain
substantially rigid in place, anchoring the valve assembly to the
vessel.
[0076] The membrane assembly is formed from a flexible
membrane-like biocompatible material that is affixed to the frame
structure 101. The membrane must be strong enough to resist tearing
under normal use, yet thin enough to provide the necessary
flexibility that allows the biocompatible membrane assembly 102 to
open and close satisfactorily.
[0077] FIGS. 4A and 4B are perspective and section views,
respectively, illustrating one embodiment of the expanded
(deployed) prosthetic venous valve assembly 100 in the open
position. The membrane material may be a biological material, such
as a vein or small intestine submucosa (SIS), but is preferably a
synthetic material such as a polymer, for example an elastic or
elastomeric polymer, including a fluoropolymer, fluoroelastomer, or
a bioabsorbable material, such as a bioabsorbable polymer or
bioabsorbable elastomer. Bioabsorbable materials may allow cells to
grow and form a tissue membrane (or valve flaps) over the
bioabsorbable membrane. The bioabsorbable membrane then absorbs
into the body, leaving the tissue membrane and/or flaps in place to
act as a new natural tissue valve.
[0078] To achieve the necessary flexibility and strength of the
membrane assembly 102, the synthetic material may be reinforced
with a fiber, such as an electro-statically spun (ESS) fiber,
porous foam, such as ePTFE, or mesh. The flexible membrane like
biocompatible material is formed into a tube (membrane tubular
structure 400) placed over and around the structural frame 101. The
membrane tubular structure 400 has a first (distal) and second
(proximal) ends 401, 402 respectively, and preferably also has
integrated valve flaps 403 and valve cusps 404. These components
together comprise the membrane assembly 102.
[0079] The first end 401 of the membrane tubular structure 400 is
located at and between the distal crowns 206. The second end 402 of
the membrane tubular structure 400 is preferably located proximal
to at least one half of the most proximal hoop structure, e.g. 200B
in FIG. 3B. In one embodiment of the invention, the membrane
structure 400 completely covers the proximal most hoop structure to
the proximal crowns 205. This configuration allows the structural
frame 101 to expand the membrane tubular structure 400 into the
native vessel wall, anchoring the membrane tubular structure 400 in
place, and providing adequate sealing against retrograde blood
flow.
[0080] The distal end 401 of the membrane tubular structure 400
terminates with the valve flaps 403. The number of valve flaps 403
is directly proportional to the number of distal crowns 206
supporting the membrane tubular assembly 102. Preferably, the
design of the valve flaps 403, and for that matter valve cusps 404,
are such that the tubular membrane structure 400 between the distal
crowns in not tightly drawn or taut. This "slack" facilitates
closing the valve by allowing the valve cusps 404 to act as pockets
that fill during retrograde flow. Conversely, during antegrade
flow, the additional slack in the tubular membrane structure 400 is
pushed to the vessel wall, allowing blood to flow through the valve
leaflets.
[0081] The valve flaps 403 are sufficiently pliable and supple to
easily open and close as the blood flow changes from antegrade to
retrograde. When the valve flaps 403 close (during retrograde flow)
the interior surfaces of the flaps 403 and/or membrane tubular
structure 400 come into contact to prevent or adequately reduce
retrograde blood flow.
[0082] As earlier disclosed, to facilitate closing the valve flaps
403 during retrograde blood flow, valve cusps 404 are formed into
the membrane tubular structure 400. The valve cusps 404 are defined
generally by the intersection of the distal crowns 206 and membrane
tubular structure 400, and are preferably formed at least in part
by the slack tubular membrane 400 between the distal crowns
206.
[0083] The use of the term "cusps" is not meant to limit the scope
of this invention. Although the term "cusps" is often more aptly
used to describe the valve members in semilunar valves, such as the
aortic and pulmonary valves, this discussion refers to both the
cusps of semilunar valves and the "leaflets" of venous and
atrioventricular valves. Accordingly, it should be understood that
the aspects discussed in relation to these valves could be applied
to any type of mammalian valve, including heart valves, venous
valves, peripheral valves, etc.
[0084] During retrograde flow, blood passes the leading edge of
valve flaps 403 and enters the valve cusps 404. Since the membrane
tubular structure 400 (and membrane assembly 102) are substantially
sealed against the inner vessel wall by the structural frame 101,
the valve cusps 404 form a substantially fluid tight chamber. As
the valve cusps 404 fill, the membrane tubular structure 400 is
directed inward until the interior surfaces of the membrane tubular
structure 400 contact each other, particularly along the leading
edges of valve flaps 403, closing the membrane assembly 102. FIGS.
5A and 5B show perspective and section views, respectively,
illustrating one embodiment of the expanded (deployed) prosthetic
venous valve assembly 100 in the closed position.
[0085] In another embodiment of the invention, the distal crowns
206 are flexible and capable of deflecting inward during retrograde
blood flow, further assisting valve 100 when closing and opening. A
perspective view illustrating an example of this embodiment is
shown in FIG. 6A. As illustrated flexible distal crown 606
articulate inward in direction 608 to assist closing the valve 100.
The flexible distal crowns 606 may pivot along a pivot line 610 as
shown, or gradually bend inward along their length.
[0086] In a preferred embodiment of the invention, the membrane
assembly 102 is normally configured in the open position, and only
moves to the closed position upon retrograde blood flow. This
configuration minimizes interference with blood flow (minimized
blocking) and reduces turbulence at and through the valve. The
flexible distal crowns 606 in this embodiment have an inferior
radial stiffness, and provide a natural bias against the movement
of the membrane assembly 102 to the closed position. This bias
assists the valve flaps 403 and valve cusps 404 when returning to
the open position.
[0087] Depending on the application, it may also be desired that
the bias towards opening the membrane assembly 102 (against
closing) be sufficiently high to commence opening the valve before
antegrade blood flow begins, i.e. during a point in time when the
blood flow is stagnant (there is neither antegrade nor retrograde
blood flow), or when minimal retrograde flow is experienced.
[0088] In other applications, it may be desirable to have the valve
assembly normally configured in the closed position, biased closed,
and only open upon antegrade flow.
[0089] In a further embodiment, the valve membrane assembly 102 may
extend past the distal end of the structural frame 101, i.e. past
distal crowns 206, in a distal direction as shown in FIG. 6B.
During retrograde blood flow, the extended section 602 of valve
membrane 102 will collapse upon itself, thus limiting or preventing
fluid flow back through the valve. In such embodiments, the valve
membrane 102 distal the structural frame 101 (i.e. membrane section
602) is of sufficient rigidity to prevent the membrane 102 from
collapsing in through the structural frame 101 and inverting.
Rigidity may be provided by inserting structural elements 620 into
the membrane assembly 102 as shown in FIG. 6B. Alternatively, the
membrane assembly 102 may have ribs or thickened sections processed
into the membrane to provide sufficient rigidity.
[0090] In another embodiment of the present invention, one or more
valve struts may extend distally from the end of the structural
frame 101 providing rigidity sufficient to support the valve
membrane 102, particularly membrane section 602 from inverting.
These valve struts may be an integral part of the structural frame
101, and made from similar material.
[0091] FIG. 6C illustrates a valve 100 having valve struts 630
according to one embodiment of the present invention. In the
embodiment shown, the valve struts 630 extend from the distal end
of the structural frame 101, in particular, from the outside radii
214 of the distal crown 206 comprising the hoop structure 200A. In
an alternate embodiment, the valve strut 630 may extend from the
inside radii 212 of the proximal crown 205 comprising the hoop
structure 200A. This alternate embodiment is shown in FIG. 6G.
Still other embodiments having different connection points would be
understood by one of skill in the art.
[0092] Although three valve struts 630 are shown for illustrative
purposes, this exemplary embodiment is not meant to limit the scope
of the invention. One of skill in the art would understand that one
or more valve struts may be used and still accomplish the general
intent of the invention.
[0093] As earlier described, the membrane assembly 102 is made from
a flexible membrane-like biocompatible material formed into the
membrane tubular structure 400. The membrane 400 can be woven,
non-woven (such as electrostatic spinning), mesh, knitted, film or
porous film (such as foam).
[0094] The membrane assembly 102 may be fixedly attached to the
structural frame by many different methods, including attachment
resulting from radial pressure of the structural frame 101 against
the membrane assembly 102, attachment by means of a binder, heat,
or chemical bond, and/or attachment by mechanical means, such as
welding, suturing or coating. Preferably some of the membrane
assembly 102, such as distal end 402 of tubular membrane 400, is
slideably attached to the structural frame 101, particularly along
valve struts 630. Allowing the distal end 401 to slide along the
valve struts 630 may allow or improve the opening and closing of
the flaps 403. The sliding movement may also assist the cusps 404
when filling and emptying.
[0095] In some applications, excessive sliding movement of the
membrane assembly 102 is undesirable. In these embodiments, a
limiting device may be integrated into the prosthetic valve 100 to
limit the sliding movement of the membrane assembly 102. Examples
of limiting devices are shown in FIGS. 6D to 6F. In each embodiment
a stop 600 (illustrated as stop 600A, 600B, and 600C in FIGS. 6D to
6F respectively) is integrated into the valve struts 630. The
membrane assembly 102 is wrapped around the valve struts 630 and
bonded to itself to form a loop collar 605. The loop collar 605
must be sized to inhibit the distal end 402 of the membrane
assembly 102 from sliding past the stop 600. In FIG. 6D, the valve
struts 630 has a thickened or "bulbous" section forming stop 600A.
FIG. 6E illustrates an undulating stop 600B configuration.
Similarly, FIG. 6F shows the stop 600C configured as a double
bulbous section. It should be noted that the various configurations
illustrated in FIGS. 6D through 6F are exemplary. One of ordinary
skill in the art would understand that other configurations of
stops may used.
[0096] In one embodiment of the invention the tubular membrane 400
is manufactured from a fiber reinforced elastomer, such as an
elastomeric fluoropolymer. The elastomer allows the tubular
membrane 400 to be extremely thin and elastic, while the fiber
provides the necessary strength. One method used to produce this
type of reinforced membrane valve is an Electro-Static Spinning
(ESS) process. Alternatively, a reinforcing fiber may be would
around the structural frame 101, and an ESS membrane formed over
the reinforcing fiber and structural frame 101.
[0097] The ESS process can be used to form a tubular membrane on
many different types of structural frames, including frames
associated with stents, stent grafts, valves, including
percutaneously delivered venous valve, AAA (Abdominal Aortic
Aneurysm) devices, local drug delivery devices, and the like. The
disclosure of the ESS process for forming the tubular membrane 400
on the structural frame of a stent-based venous valve is exemplary,
and thus not meant to limit the scope of this invention.
[0098] FIG. 7 shows the steps for electro-statically spinning a
reinforced tubular membrane onto a structural frame according to
one embodiment of the present invention. The ESS process comprises
first placing a transfer sheath over a spinning mandrel as shown in
step 700. The transfer sheath is a thin material that is used to
prevent the ESS spun fiber from adhering to the mandrel. In
instances where the mandrel itself is not electrically conducting,
the transfer sheet may also provide the necessary electrical
conductivity to attract the ESS spun fiber.
[0099] In one embodiment of the invention, the transfer sheath
comprises a thin polymer tube, preferably fluoropolymer, of such a
thickness that it can be easily deformed, and preferably collapsed,
so that it is capable of being withdrawn conveniently from the
lumen of the structural frame 101 and/or membrane tubular structure
400. The use of a transfer sheath made of other fibrous or sheet
materials, such as other polymer, polymeric or metallic materials
is not excluded. Most preferably, the transfer sheath will be made
of an ePTFE tube.
[0100] To enhance electrical conductivity and reduce the time it
takes to build up the ESS layer, the ePTFE tube may be first coated
with gold on at least a portion of the interior surface before
placing the tube on the mandrel. This process may be completed by
coating the inside of the tube, but is preferably done by coating
the exterior of the ePTFE tube and then inverting the tube so that
the gold coating is on the interior surface. The process may also
be completed by inverting the tube so that the interior surface to
be coated is exposed on exterior of the tube, coating the now
exposed interior surface, and the inverting the tube so that the
interior coated surface is back on the inside of the tube.
[0101] It should be noted that under certain circumstances it may
not be necessary to use the transfer sheath. Such circumstances may
include, for example, where the spinning mandrel is
electro-statically conducting and has a surface or surface
treatment that will prevent the ESS spun fiber from adhering to the
mandrel.
[0102] In a preferred embodiment, the spinning mandrel is
electrically conducting, and more preferably, is a metal coated
with Teflon.RTM.. However, electrical conduction may not be
essential. In such embodiments the spinning mandrel may be of any
suitable material, including plastic material. Non-conductors may
be used so long as the charge is capable of being transferred (i.e.
bleed off) onto the transfer sheet or through the material
itself.
[0103] The spinning mandrel may be hollow or solid, and preferably
has a smooth surface to facilitate sliding between the transfer
sheath and mandrel during removal. However, it may be desirable to
maintain some degree of frictional resistance between the transfer
sheath and mandrel to reduce slippage between the two components
during the ESS process.
[0104] The valve structural frame 101 is then placed on the
transfer sheath, step 710, and the ESS fiber is spun directly onto
the valve structural frame 101 as shown in step 720. Preferably,
the structural frame 101 is configured in the expanded or deployed
state prior to placing the structural frame 101 on the spinning
mandrel. This is generally the case when the structural frame 101
is of the self-expanding design. In other embodiments, such as
balloon-expandable designs, the expansion mechanism may be
integrated within the spinning mandrel to expand the structural
frame during the spinning process.
[0105] The expandable mandrel may also be used for
electro-statically spinning a fiber onto a self-expanding
structural frame 101. In such instances, the self-expanding
structural frame 101 is placed on the spinning mandrel in the
expanded state, and the expansion mechanism on the expandable
mandrel is mandrel activated to further radially expand the
structural frame to a "super-expanded" state. ESS fiber is then
spun directly onto the super-expanded structural frame 101. The
larger diameter of the super-expanded structural frame 101 allows
more material to be deposited on the structural frame, creating
slack between the distal crowns, which may result in less post
processing procedures. Post processing is described in step
760.
[0106] Electro-static spinning of a fiber is generally known in the
art, and typically involves creating an electrical potential
between a source component, i.e. the fiber or preferably a fiber
forming liquid, and a downstream component, i.e. the spinning
mandrel, transfer sheath or structural frame. The electrical
potential causes the source component, typically the fiber forming
liquid, to be attracted to, and thus move towards, the downstream
component.
[0107] The electrical potential is created by providing an
electrical charge to either the source or downstream component, and
grounding the other component. Preferably, the source component
will receive an electrical charge, while the downstream component
is grounded.
[0108] Many different methods are known in the art for producing an
electrical charge on a source component. In one embodiment, a fiber
forming liquid is introduced into an electric field, whereby the
fiber forming liquid is caused to produce a charged fiber. In
another, more preferred embodiment, a device (introducer device)
introducing the fiber forming liquid into the process is
electrically charged, thus causing the fiber forming liquid to
assume a like charge.
[0109] Several methods may be used to introduce the fiber forming
liquid into the process, including spraying the fiber forming
liquid from a nozzle, or injecting the fiber forming liquid from a
needle, orifice or drip tube. In a preferred embodiment, the fiber
forming liquid is sufficiently viscous to be extruded into the
process with an extrusion device.
[0110] Once the fiber forming liquid is introduced into the
process, it is hardened to form the ESS fiber. Hardening of the
liquid into an ESS fiber may be accomplished, for example, by
cooling the liquid until the fiber forming liquid will not lose its
fibrous shape. Other methods for hardening the fiber may also
include hardening by introducing a chemical hardener into the fiber
forming liquid, or directing an air stream over the electrically
drawn fiber forming liquid stream. In a preferred embodiment, a
polymer is put into solution with a solvent to form a viscous fiber
forming liquid. As the fiber forming liquid is drawn from the
introducer device, the solvent comes out of solution forming the
polymer fiber.
[0111] Various drying techniques may be applied to evaporate the
solvent and bring the polymer out of solutions. Drying techniques
may include, for example, applying heat or airflow to or over the
coated fiber spun frame assembly. In addition, the solvent may dry
naturally without applying artificial drying techniques.
[0112] The viscosity of the fiber forming liquid may be adjusted
based on the material used for the source component, and the
percent solids desired as the source component reaches the
downstream component. Typical concentrations range from 2 to 100
percent. The choice of concentration depends on the material, its
molecular weight, the solvent efficiency, and temperature. The
concentration and temperature also control the diameter of the
fiber. These viscosities will typically produce a fiber at the
downstream component having percent solids in the range of about 95
percent to about 100 percent, and preferably over 99 percent. This
is desirable in order to produce structures that contain entangled
or point bonded fibers. Concentrations lower than 95 percent can be
used if it is desired to allow filaments to fuse together into a
sheet-like barrier structure.
[0113] The hardened fiber is then collected onto the structural
frame. Collecting of the fiber involves attracting the ESS fiber to
the downstream component (i.e. spinning mandrel, transfer sheath or
structural frame) of the ESS system, while spinning the downstream
component. In a preferred embodiment, where the source component is
electrically charged, a downstream component is grounded to
complete the electric potential between the source and downstream
component, and thus attract the ESS fiber. In other embodiments, a
downstream component may be electrically charged to attract the ESS
fiber where the source component is grounded. In still other
embodiments, various combinations of downstream components may be
electrically charged to enhance electrical conductivity and reduce
the time it takes to build up the ESS layer.
[0114] Particular ESS fibers suitable for this spinning process
include fluoropolymers, such as a crystalline fluoropolymer with an
85/15% (weight/weight ratio) of vinylidene
fluoride/hexafluoropropylene (VDF/HFP). Solvay Solef.RTM. 21508 and
Kynarflex 2750-01 are two such examples. However, one of skill in
the art would understand that any material possessing the desired
characteristics may be used, including, for example: bioabsorbable
polymers, such as polyglycolic acid, polylactic acid, poly
(paradioxanone), polycaprolactone, poly (trimethylenecarbonate) and
their copolymers; and semicrystalline bioelastomers, such as 60/40%
(weight/weight ratio) of polylactic acid/polycaprolactone
(PLA/PCL), 65/35 (weight/weight ratio) of polyglycolic
acid/polycaprolactone (PGA/PCL), or nonabsorbable siliconized
polyurethane, non-siliconized polyurethanes, siliconized
polyureaurethane, including siliconized polyureaurethane end capped
with silicone or fluorine end groups, or natural polymers in
combination thereof. It should be noted that
poly(trimethylenecarbonate) can not be spun as a homopolymer.
[0115] The spinning process should be continued until an ESS fiber
tube, or fabric, is formed having a wall thickness of between 5
.mu.m and 100 .mu.m or more, preferably, approximately 20 .mu.m.
The ESS fiber spun structural frame 101 is then removed from the
spinning mandrel, step 730, before the transfer sheath is removed
from the fiber spun frame, step 740. Once this step is completed,
the fiber spun structural frame is coated in a solution of polymer,
such as fluoroelastomer, as shown in step 750.
[0116] Several different methods may be utilized to perform the
coating process on the fiber spun structural frame, including spray
coating with an air or airless sprayer, dip coating, chemical vapor
deposition, plasma coating, coextrusion coating, spin coating and
insert molding. In still another preferred embodiment, the fiber
spun structural frame is first dip coated in a polymer solution,
and then spun about its longitudinal axis to more evenly distribute
the coating. In this embodiment, the fiber spun structural frame is
not first removed from the spinning mandrel. Instead, the
frame/mandrel assembly is dip coated and spun before removing the
fiber spun structural frame from the spinning mandrel. Still other
methods for coating the fiber spun structural frame would be
obvious to one of skill in the art.
[0117] The coating process may act to encapsulate and attach at
least a portion of the spun ESS reinforcement fiber to the
structural frame 101. It should be noted that it in some
embodiments of the invention, some movement between the membrane
assembly 102 and the structural frame 101 is desired. Accordingly,
not all of the ESS fiber spun structural frame may be coated.
[0118] The coating process may also remove some porosity of the
membrane material. However, it may be desirable to maintain some
porosity in particular embodiments to promote biological cell grown
on and within the membrane tubular structure.
[0119] The coating solution preferably comprises a polymer put into
solution with a solvent. As the solvent evaporates, the polymer
comes out of solution forming the coating layer. Accordingly, for
the process to work properly, the solvent used in the coating
solution should not dissolve or alter the ESS fibers being coated.
By way of example, a coating solution of 60/40% VDF/HFP in methanol
(methanol being the solvent) has been found to be a suitable
solution for coating an ESS fiber comprised of 85/15% VDF/HFP.
[0120] In one embodiment of the invention, the polymer comprising
the coating is Daikin's Dai-El G701BP, which is a 60/40% VDF/HFP.
In addition, Daikin's Dai-El T630, a thermoplastic elastomer based
on vinylidene fluoride/hexafluoropropylene/tetrafluoroethylene
(VDF/HFP/TFE) can also be used. Again, one of ordinary skill in the
art would understand that other materials having suitable
characteristics may be used for the coating, for example, other
polymers, such as siliconized polyurethane, including Polymer
Technology Group's Pursil, Carbosil, Purspan and Purspan F.
[0121] The coating process may be repeated until the desired
characteristics and thickness are achieved. For venous valves a
thickness of between 12 .mu.m and 100 .mu.m and preferably between
25 .mu.m and 50 .mu.m has been found to be acceptable.
[0122] Once the coating process is complete some post processing of
the membrane tubular structure 400 may take place to achieve
particular desired characteristics or configurations. This may
include creating the final form of the membrane assembly 102. The
post processing step is shown as optional step 760 in FIG. 7.
[0123] The post processing step 760 may be used to form or shape,
for example, a valve cusp, similar to cusp 404, in the membrane
tubular structure 400. In addition, post processing may change the
characteristics of the membrane tubular structure 400 by thickening
or thinning the membrane in particular locations. Thickening the
membrane may add rigidity and reinforcement to a particular area.
Thinning the membrane may make the membrane more pliable, which is
a desirable characteristic for the valve flaps 403. Still other
post processing procedures may change the physical shape of the
membrane tubular structure 400, for example, by forming the loop
collar 605 along the distal edge of membrane tubular structure 400.
The loop collar 605 may assist in controlling the movement
(translational and circumferential) of the membrane assembly 102
along the valve struts 630. The loop collars 605 may also reduce
fatigue and tear stresses in the membrane.
[0124] FIGS. 8A and 8B show an example of the result of a post
processing step that forms a loop collar 605 according to one
embodiment of the present invention. To achieve this result, the
membrane tubular structure 400 is wrapped around at least one
element of structural frame 101 (valve struts 630) and bonded to
itself at bond point 800.
[0125] Another method for electro-statically spinning a tubular
membrane onto a radially expandable structural frame according to
another embodiment of the present invention is shown in FIG. 9.
Although similar to the process described above, this alternative
method provides an ESS spun membrane on the inside, as well as the
outside of the structural frame. The inner and outer ESS spun
membranes may mechanically adhere to each other, and in a sense
encapsulated the structural frame. This configuration provides some
additional features, including having a smoother interior surface
that reduces turbulence, improves flow dynamics and lowers the
chance of thrombosis formation.
[0126] Similar to the embodiment described earlier, the ESS process
comprises first placing a transfer sheath over a spinning mandrel
as shown in step 900. It should be noted that under certain
circumstances it may not be necessary to use the transfer sheath.
Such circumstances may include, for example, where the spinning
mandrel is electro-statically conducting and has a surface or
surface treatment that will prevent the ESS spun fiber from
adhering to the mandrel.
[0127] An ESS fiber is then spun directly onto the transfer sheath
creating an inner coat membrane as shown in step 910. The ESS
process should continue until an ESS tube is formed having a wall
thickness of between 2 .mu.m and 50 .mu.m or more, and preferably,
approximately 20 .mu.m. As previously stated, the inner coat
membrane covers some or all of the interior surface of structural
frame 101. The structural frame 101 is then radially expanded and
placed over the inner coat membrane on the spinning mandrel as
shown in step 920. Expansion of the structural frame 101 may be
achieved by several different methods. One method includes taking
advantage of the thermal and shape memory characteristics of
particular materials. For example, shape memory materials, such as
Nitinol, possess little or no recoil ability when cooled, but
exhibit a high degree of memory, i.e. the ability to return to a
configured shape, when heated. Cooling the Nitinol structural frame
101 before expansion allows the structural frame to remain in the
expanded configuration until being heated. Accordingly, the Nitinol
structural frame 101 can be cooled, expanded, and then placed over
the inner coat membrane. Once in place, the structural frame can be
heated to activate the Nitinol memory characteristics, causing the
Nitinol structural frame 101 to contract to the pre-expansion size
and configuration.
[0128] The structural frame 101 is sized such that when configured
in the expanded or deployed state, it will fit tightly over the
inner coat membrane on the spinning mandrel. To fit the structural
frame 101 over the inner coat membrane, the structural frame 101
may have to be radially expanded ("super-expanded") to a diameter
slightly larger than the expanded deployed state to allow the
structural frame 101 to fit over the inner coat membrane.
[0129] Once the structural frame 101 is placed over the inner coat
membrane, another ESS fiber is spun directly onto the structural
frame, as shown in step 930, to form a top-coat membrane. The ESS
process should continue until the top-coat membrane tube is formed
having a wall thickness of between 2 .mu.m and 50 .mu.m or more,
and preferably, approximately 20 .mu.m. The top-coat membrane may
cover and adhere to the inner coat membrane through the
interstitial spaces between the elements that comprise the
structural frame 101.
[0130] As stated in an earlier described embodiment of the
invention, the structural frame 101 is configured on the mandrel in
the expanded deployed state prior to spinning the top-coat
membrane. In other embodiments, it may be desirable to expand
(super expand) the structural frame 101 on the spinning mandrel
during or prior to the spinning process. This procedure may alter
the configuration and properties of the spun membrane, resulting in
less post processing of the membrane. Post processing is described
in step 960.
[0131] The structural frame 101, with the inner coat and top coat
membranes, is then removed from the spinning mandrel, as shown in
step 940, and coated with a solution of highly elastic polymer as
shown in step 950. As stated previously, the coating process may be
achieved using several different coating methods, including spin
coating, spray coating, dip coating, chemical vapor deposition,
plasma coating, co-extrusion coating and insert molding.
[0132] As previously described, a representative elastomeric
polymer is a fluoroelastomer. The coating process may be repeated
until the desired characteristics and thickness are achieved. For a
venous valve application, a thickness of between 12 .mu.m and 100
.mu.m, and preferably between 25 .mu.m and 50 .mu.m, has been found
to be acceptable.
[0133] Once the coating process is complete, some post processing
of the tubular membrane may take place, as shown as an optional
step 960 in FIG. 9.
[0134] Although each of the above described ESS methods spin the
fiber directly on to the structural frame, one of ordinary skill in
the art would understand that a tubular membrane may also be spun
separately, and then placed over the structural frame 101 by known
methods.
[0135] Another, more preferred method for forming the membrane
material over and around the structural frame 101 is shown in FIG.
10. As described earlier, this method is presented in the context
of a prosthetic valve application. However, the method may be
applied generally to any application where a micro-cellular foam or
pourous material, particularly an ePTFE membrane, needs to be
placed over and around a radially expandable structural frame.
Exemplary structural frames may include stents, stents grafts,
valves (including percutaneously delivered venous valves), AAA
(Abdominal Aortic Aneurysm) devices, local drug delivery devices,
and the like. Accordingly, the disclosed device is not meant to
limit the scope of the inventive method.
[0136] In this embodiment, a tubular structure is fabricated from a
polymer material that can be processed such that it exhibits an
expanded cellular structure, preferably expanded
Polytetrafluoroethylene (ePTFE). The ePTFE tubing is made by
expanding Polytetrafluoroethylene (PTFE) tubing, under controlled
conditions, as is well known in the art. This process alters the
physical properties that make it satisfactory for use in medical
devices. However, one of ordinary skill in the art would understand
that other materials that possess the necessary characteristics
could also be used.
[0137] The method comprises first placing a transfer sheath over a
mandrel as shown in step 1000. As described earlier, the transfer
sheath is a thin material that is used to prevent the tubing and
coating from adhering to the mandrel. The transfer sheath may be
made of sheet metal, metal foil, or polymer sheet, such as for
example Polytetrafluoroethylene (PTFE) . Preferably, the transfer
sheath will be made of a material that can be easily deformed, and
preferably collapsed so that it can be withdrawn conveniently from
the lumen of the tube once the process is complete.
[0138] The transfer sheath/mandrel combination are then coated in a
solution of highly elastic polymer, such as fluoroelastomer, as
shown in step 1010, to form an inner membrane. As stated
previously, the coating may be applied using various methods,
including, for example, spin coating, spray coating, dip coating,
chemical vapor deposition, plasma coating, co-extrusion coating and
insert molding.
[0139] In one embodiment of the invention, the coating solution
comprises a polymer put into solution with a solvent, such as
methanol. In addition, most solvents can be used with expanded
Polytetrafluoroethylene (ePTFE).
[0140] In a preferred embodiment of the invention, the polymer
comprising the coating includes Daikin's Dai-El T630, a
thermoplastic elastomer based on vinylidene
fluoride/hexafluoropropylene/tetrafluoroethylene (VDF/HFP/TFE) and
blends thereof. Again, one of ordinary skill in the art would
understand that other materials having suitable characteristics may
be used for the coating, for example, other polymers, such as
siliconized polyurethanes and blends thereof, including Polymer
Technology Group's Pursil, Carbosil, Purspan and Purspan F.
[0141] The coating process should continue until the inner membrane
achieves a wall thickness of between 6 .mu.m and 100 .mu.m or more,
preferably between 12 .mu.m to 25 .mu.m.
[0142] In an alternate embodiment, a polymer tube, preferably an
ePTFE tube, may be expanded and placed over the sheath/mandrel
combination (step 1015), before being contracted (step 1020).
Expansion may be by any suitable expansion means known in the art,
including mechanical expansion, such as by means of a balloon
expansion device or expandable cage, expansion by utilizing a
tapered mandrel (i.e. sliding the polymer tube over a tapered
mandrel of increasing diameter) , etc. In addition other means may
be used in conjunction with the expansion means to assist placing
the tube over the sheath mandrel combination. These assist means
may include, for example, thermally expanding the tube with heat,
or chemically expanding the tube with a solvent. These methods are
known in the art.
[0143] Contraction of the tube is typically done by reversing the
method used to expand the tube. For example, where the tube is
naturally elastic and expanded by a mechanical expansion means,
removing the expansion means would allow the tube to contract
towards it pre-expansion configuration. In addition the contraction
of the tube may be enhanced by applying heat or chemicals
(solvents).
[0144] Once the tube is expanded over the sheath/mandrel, the whole
assembly may be coated with a solution of highly elastic polymer,
such as fluoroelastomer as shown in step 1025 to form the inner
membrane. The coating process is similar to that shown in step 1010
above, and may be achieved by any method known in the art capable
of achieving the desired result, including spin coating, spray
coating, dip coating, chemical vapor deposition, plasma coating,
co-extrusion coating and insert molding.
[0145] The coating process described in step 1025 should continue
until the inner membrane described in the alternate embodiment is
coated with a polymer base having a wall thickness of between 6
.mu.m and 100 .mu.m or more, preferably between 12 .mu.m to 25
.mu.m.
[0146] The structural frame 101 is then radially expanded and
positioned over the inner membrane as shown in step 1030. The
structural frame 101 may be radially expanded using any know
expansion means, including a balloon expansion device or frame
expansion device. In one embodiment of the invention, the
structural frame 101 is constructed from a shape memory alloy, such
as Nitinol. As previously described, Nitinol characteristically
holds a deformed shaped when cooled, and returns to its original
shape when heated. Accordingly, it is possible to hold a Nitinol
structural frame 101 in the radially expanded state by cooling the
frame before the expansion means is removed. This will facilitate
placement of the Nitinol structural frame over the inner
membrane.
[0147] The structural frame 101 may then be radially contracted
over the inner membrane, as shown in step 1040. It is desirable to
maintain a slight interference fit between the structural frame 101
and the inner membrane. The method to radially contract the
structural frame 101 may depend on the material and type of
construction of the structural frame 101, and is not meant to limit
the scope of the invention. As described above, a structural frame
101 constructed from a shape memory alloy, such as Nitinol, can be
radially contracted (to the pre-expanded and cooled size) by
heating. Depending on the material used, other methods that may
also be employed to radially contract the structural frame include,
simply removing the expansion means providing the radial expansion
force, or applying a compressive force about the structural frame
101. Still other methods to radially contract the structural frame
101 would be obvious to one of skill in the art.
[0148] Once the structural frame 101 is contracted over the inner
membrane, a second polymer tube, preferably an ePTFE tube, is
expanded and placed over the structural frame, as shown in step
1050, forming an outer membrane. The tube is then contracted into
position as shown in step 1060. As described earlier, the tube may
be expanded by several different means, including mechanical,
thermal, or chemical (solvents) expansion. Similarly, contraction
of the tube may be accomplished by the methods described in step
1020.
[0149] In embodiments where two separate ePTFE tubes are used for
the inner and outer membranes, as described in steps 1015 and 1050
respectively, each tube should have a wall thickness of between 25
.mu.m and 50 .mu.m before expansion; yielding a wall thickness of
between 6 .mu.m and 10 .mu.m after expansion and placement. It
should be noted that these membranes may or may not be bonded
together. If only a single ePTFE tube is used for the outer
membrane only, as described in step 1050 (not following alternate
steps 1015 through 1025), the tube should have a wall thickness
before expansion of between 50 .mu.m and 100 .mu.m; yielding a wall
thickness after expansion of between 12 .mu.m and 20 .mu.m.
[0150] The inner and outer membranes combine to form a membrane
structure. In the valve example described above, the membrane
structure would represent membrane tubular structure 400, while the
structural frame would represent the structural frame 101.
[0151] Once the membrane structure is formed, some or all of the
assembly may be optionally coated with a solution of a highly
elastic polymer, such as a elastomeric polymer, as shown in step
1070. The coating may be applied by any method known in the art,
including spin coating, spray coating, dip coating, chemical vapor
deposition, plasma coating, co-extrusion coating and insert
molding.
[0152] As described earlier (see step 1010) the coating solution
may be a fluoroelastomer. In one embodiment of the invention, the
coating is Daikin G701BP, which is a 60/40% VDF/HFP. Again, one of
ordinary skill in the art would understand that other materials
having suitable characteristics might be used for the coating, for
example, other polymers, such as siliconized polyurethane.
[0153] The coating process should continue until the coating
achieves a wall thickness of between 6 .mu.m and 100 .mu.m or more,
preferably between 12 .mu.m to 25 .mu.m.
[0154] Once the coating process is complete, some post processing
of the membrane structure may take place to achieve particular
desired characteristics or configurations. This post processing
step is shown as optional step 1080 in FIG. 10.
[0155] By way of example, for valve applications, the post
processing step 1080 may be used to form or shape valve cusps,
similar to cusps 404, or valve flaps, such as flaps 403, in the
membrane structure. In addition, post processing may change the
characteristics of the membrane structure by thickening or thinning
the membrane in particular locations. Thickening the membrane may
add rigidity and reinforcement to a particular area. Thinning the
membrane may make the membrane more pliable. Still other post
processing procedures may change the physical shape of the membrane
structure, for example, by forming the loop collar 605 along the
distal edge of membrane assembly 102. The loop collar 605 may
assist in controlling the translational and circumferential
movement of the membrane assembly 102 along the valve struts 630.
The loop collars 605 may also reduce fatigue and tear stresses in
the membrane.
[0156] It is important to note that the local delivery of drug/drug
combinations may be utilized to treat a wide variety of conditions
utilizing any number of medical devices, or to enhance the function
and/or life of the device. Medical devices that may benefit from
this treatment include, for example, the frame based unidirectional
flow prosthetic implant subject of the present invention.
[0157] Accordingly, in addition to the embodiments described above,
therapeutic or pharmaceutic agents may be added to any component of
the device during fabrication, including, for example, the ESS
fiber, polymer or coating solution, membrane tube, structural frame
or inner and outer membrane, to treat any number of conditions. In
addition, therapeutic or pharmaceutic agents may be applied to the
device, such as in the form of a drug or drug eluting layer, or
surface treatment after the device has been formed. In a preferred
embodiment, the therapeutic and pharmaceutic agents may include any
one or more of the following: antiproliferative/antimitotic agents
including natural products such as vinca alkaloids (i.e.
vinblastine, vincristine, and vinorelbine), paclitaxel,
epidipodophyllotoxins (i.e. etoposide, teniposide), antibiotics
(dactinomycin (actinomycin D) daunorubicin, doxorubicin and
idarubicin) anthracyclines, mitoxantrone, bleomycins, plicamycin
(mithramycin) and mitomycin, enzymes (L-asparaginase which
systemically metabolizes L-asparagine and deprives cells which do
not have the capacity to synthesize their own asparagine);
antiplatelet agents such as G(GP) ll.sub.b/lll.sub.a inhibitors and
vitronectin receptor antagonists; antiproliferative/antimitotic
alkylating agents such as nitrogen mustards (mechlorethamine,
cyclophosphamide and analogs, melphalan, chlorambucil),
ethylenimines and methylmelamines (hexamethylmelamine and
thiotepa), alkyl sulfonates-busulfan, nirtosoureas (carmustine
(BCNU) and analogs, streptozocin) , trazenes-dacarbazinine (DTIC);
antiproliferative/antimito- tic antimetabolites such as folic acid
analogs (methotrexate), pyrimidine analogs (fluorouracil,
floxuridine, and cytarabine), purine analogs and related inhibitors
(mercaptopurine, thioguanine, pentostatin and
2-chlorodeoxyadenosine {cladribine}); platinum coordination
complexes (cisplatin, carboplatin), procarbazine, hydroxyurea,
mitotane, aminoglutethimide; hormones (i.e. estrogen);
anticoagulants (heparin, synthetic heparin salts and other
inhibitors of thrombin); fibrinolytic agents (such as tissue
plasminogen activator, streptokinase and urokinase), aspirin,
dipyridamole, ticlopidine, clopidogrel, abciximab; antimigratory;
antisecretory (breveldin); anti-inflammatory: such as
adrenocortical steroids (cortisol, cortisone, fludrocortisone,
prednisone, prednisolone, 6.alpha.-methylprednisolone,
triamcinolone, betamethasone, and dexamethasone), non-steroidal
agents (salicylic acid derivatives i.e. aspirin; para-aminophenol
derivatives i.e. acetominophen; indole and indene acetic acids
(indomethacin, sulindac, and etodalac), heteroaryl acetic acids
(tolmetin, diclofenac, and ketorolac), arylpropionic acids
(ibuprofen and derivatives), anthranilic acids (mefenamic acid, and
meclofenamic acid), enolic acids (piroxicam, tenoxicam,
phenylbutazone, and oxyphenthatrazone) , nabumetone, gold compounds
(auranofin, aurothioglucose, gold sodium thiomalate);
immunosuppressives: (cyclosporine, tacrolimus (FK-506), sirolimus
(rapamycin), azathioprine, mycophenolate mofetil); angiogenic
agents: vascular endothelial growth factor (VEGF), fibroblast
growth factor (FGF); angiotensin receptor blockers; nitric oxide
donors; anti-sense oligionucleotides and combinations thereof; cell
cycle inhibitors, mTOR inhibitors, and growth factor receptor
signal transduction kinase inhibitors; retenoids; cyclin/CDK
inhibitors; HMG co-enzyme reductase inhibitors (statins); and
protease inhibitors.
[0158] While a number of variations of the invention have been
shown and described in detail, other modifications and methods of
use contemplated within the scope of this invention will be readily
apparent to those of skill in the art based upon this disclosure.
It is contemplated that various combinations or subcombinations of
the specific embodiments may be made and still fall within the
scope of the invention. For example, the embodiments variously
shown to be prosthetic "venous valves" may be modified to instead
incorporate prosthetic "heart valves" and are also contemplated.
Moreover, all assemblies described are believed useful when
modified to treat other vessels or lumens in the body, in
particular other regions of the body where fluid flow in a body
vessel or lumen needs to be controlled or regulated. This may
include, for example, the coronary, vascular, non-vascular and
peripheral vessels and ducts. Accordingly, it should be understood
that various applications, modifications and substitutions may be
made of equivalents without departing from the spirit of the
invention or the scope of the following claims.
[0159] The following claims are provided to illustrate examples of
some beneficial aspects of the subject matter disclosed herein
which are within the scope of the present invention.
* * * * *