U.S. patent application number 10/430113 was filed with the patent office on 2003-12-04 for method of making a medical device having a thin wall tubular membrane over a structural frame.
Invention is credited to Grewe, David, Majercak, David Christopher.
Application Number | 20030225447 10/430113 |
Document ID | / |
Family ID | 29420545 |
Filed Date | 2003-12-04 |
United States Patent
Application |
20030225447 |
Kind Code |
A1 |
Majercak, David Christopher ;
et al. |
December 4, 2003 |
Method of making a medical device having a thin wall tubular
membrane over a structural frame
Abstract
The present invention relates to a medical device and method for
making the medical device. In particular, the present invention
relates to membrane covered structural frame, and to a method of
forming a tubular membrane on a structural frame. In one aspect, a
polymeric tube is provided having a first diameter and a first tube
wall thickness. A radially expandable and contractible structural
frame is radially contracted, and inserted into at least a portion
of the structural frame. The radially contracted structural frame
then expands to expand the polymeric tube to a second diameter,
wherein the second diameter is greater than the first diameter. As
the polymeric tube radially expands, the tube wall thickness
becomes thinner, so that the polymeric tube becomes a thin walled
tubular membrane. The polymeric tube and structural frame are then
mechanically attached to each other.
Inventors: |
Majercak, David Christopher;
(Stewartsville, NJ) ; Grewe, David; (Glen Gardner,
NJ) |
Correspondence
Address: |
PHILIP S. JOHNSON
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
29420545 |
Appl. No.: |
10/430113 |
Filed: |
May 6, 2003 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
60379604 |
May 10, 2002 |
|
|
|
Current U.S.
Class: |
623/1.13 ;
264/229; 623/901 |
Current CPC
Class: |
A61F 2/2475 20130101;
A61F 2220/0058 20130101; A61F 2002/91558 20130101; A61F 2002/91583
20130101; A61F 2230/0078 20130101; A61F 2220/005 20130101; A61F
2/2412 20130101; A61F 2002/825 20130101; A61F 2002/91533 20130101;
A61F 2230/0054 20130101; A61F 2/2418 20130101; A61F 2/2415
20130101; A61F 2/915 20130101; A61F 2002/91575 20130101 |
Class at
Publication: |
623/1.13 ;
623/901; 264/229 |
International
Class: |
A61F 002/06 |
Claims
What is claimed is:
1. A method of making a medical device having a thin wall tubular
structure over a radially contractible and expandable structural
frame, the method comprising the steps of: providing a polymeric
tube having a first diameter and a first wall thickness; radially
contracting the structural frame; placing the radially contracted
structural frame at least partially into the polymeric tube;
expanding the structural frame to expand at least a portion of the
polymeric tube to a second diameter having a second wall thickness,
the second diameter of the polymeric tube being greater than the
first diameter, the second wall thickness being smaller than the
first wall thickness; and mechanically attaching the expanded
polymeric tube to the expanded structural frame.
2. The method of claim 1 wherein the step of radially contracting
the structural frame comprises inserting the structural frame into
a sheath, the sheath being sized to have an inside diameter that is
smaller than the outside diameter of the structural frame.
3. The method of claim 1 wherein the step of radially contracting
the structural frame comprises: radially crimping the structural
frame with a crimping device to a reduced diameter; and cooling the
radially crimped structural frame to temporarily maintain the
radially contracted configuration.
4. The method of claim 1 wherein the step of radially expanding the
structural frame comprises: inserting a radial expansion device
into the structural frame along the structural frame's longitudinal
axis; radially expanding the radial expansion device to expand the
structural frame.
5. The method of claim 4 wherein the radial expansion device is an
inflation balloon.
6. The method of claim 4 wherein the radial expansion device is a
radially expanding cage assembly.
7. The method of claim 4 wherein the radial expansion device is a
radially expanding mandrel.
8. The method of claim 4 wherein the radial expansion device is a
tapered mandrel.
9. The method of claim 1 wherein the step of radially expanding the
structural frame comprises removing a sheath constraining the
radially contracted structural frame, thereby allowing the
structural frame to radially expand.
10. The method of claim 1 wherein the step of radially expanding
the structural frame comprises heating the radially contracted
structural frame.
11. The medical device of claim 1 wherein the step of mechanically
attaching the expanded polymeric tube to the expanded structural
frame comprises suturing the polymeric tube to the structural
frame.
12. The medical device of claim 1 wherein the step of mechanically
attaching the expanded polymeric tube to the expanded structural
frame comprises welding the polymeric tube to the structural
frame.
13. The medical device of claim 1 wherein the step of mechanically
attaching the expanded polymeric tube to the expanded structural
frame comprises adhering the polymeric tube to the structural frame
with an adhesive.
14. The medical device of claim 1 wherein the step of mechanically
attaching the expanded polymeric tube to the expanded structural
frame comprises coating at least a porting of the expanded
polymeric tube and the structural frame with a polymer.
15. The method of claim 14 wherein the step of coating comprises
spraying a polymer solution over at least a portion of the expanded
polymeric tube and structural frame.
16. The method of claim 14 wherein the step of coating comprises
dipping at least a portion of the expanded polymeric tube and
structural frame in a polymer solution.
17. The method of claim 14 wherein the step of coating comprises:
dipping at least a portion of the expanded polymeric tube and
structural frame in a polymer solution; and spinning the dip coated
expanded polymeric tube and structural frame to evenly distribute
the coating.
18. A method of placing a tubular structure about a radially
contractible and expandable structural frame, the method comprising
the steps of: providing a porous polymeric tube having a first
diameter and a first wall thickness; radially contracting the
structural frame; placing the radially contracted structural frame
at least partially into the porous polymeric tube; expanding the
structural frame to expand at least a part of the porous polymeric
tube to a second diameter, the second diameter of the porous
polymeric tube being greater than the first diameter; and coating
at least a portion of the expanded porous polymeric tube and the
expanded structural frame, thereby mechanically attaching the
expanded porous polymeric tube to the expanded structural
frame.
19. The method of claim 18 wherein the step of mechanically
attaching the expanded porous polymeric tube to the expanded
structural frame comprises: filling the at least a portion of the
pores in the coated porous polymeric tube with a polymer solution;
and curing the polymer solution, thereby mechanically bonding the
porous polymeric tube to the coated structural frame.
20. The method of claim 1 further comprising performing post
processing of the expanded polymeric tube.
21. The method of claim 20 wherein the step of post processing
includes reshaping the expanded polymeric tube.
22. The method of claim 20 wherein the step of post processing
includes thinning at least a portion of the expanded polymeric
tube.
23. The method of claim 20 wherein the step of post processing
includes thickening at least a portion of the expanded polymeric
tube.
24. The method of claim 20 wherein the step of post processing
includes forming cusps in the expanded polymeric tube.
25. A medical device having a tubular membrane structure
comprising: a radially expandable and collapsible structural frame;
a thin wall membrane positioned over the radially expandable and
collapsible structural frame, the membrane formed at least in part
by radially expanding a polymeric tube with the structural frame;
and a coating over the thin wall membrane, the coating and thin
wall membrane forming the tubular membrane structure, and wherein
the coating mechanically attaches the thin wall membrane to the
structural frame.
26. The medical device of claim 25 wherein the structural frame
comprises a lattice of interconnected elements, and having a
substantially cylindrical configurations with first and second open
ends and a longitudinal axis extending there between.
27. The medical device of claim 25 wherein the thin wall membrane
comprises ePTFE.
28. The medical device of claim 25 wherein the polymeric tube has a
wall thickness before radial expansion in the range from about 25
.mu.m to about 50 .mu.m.
29. The medical device of claim 25 wherein the thin wall membrane
has a wall thickness after radial expansion in the range from about
12 .mu.m to about 25 .mu.m.
30. The medical device of claim 25 wherein the coating comprises a
polymer.
31. The medical device of claim 30 wherein the polymer coating
comprises an elastomeric polymer.
32. The medical device of claim 31 wherein the elastomeric polymer
comprises an elastomeric fluoropolymer.
33. The medical device of claim 32 wherein the elastomeric
fluoropolymer comprises a vinylidene
fluoride/hexafluoropropylene/tetrafluoroethylene.
34. The medical device of claim 31 wherein the elastomeric polymer
comprises siliconized polyurethane.
35. The medical device of claim 34 wherein the siliconized
polyurethane comprises segmented polyetherurethane.
36. The medical device of claim 25 wherein the coating has a wall
thickness from about 12 .mu.m to about 25 .mu.m.
37. The medical device of claim 25 wherein the thin wall membrane
comprises a therapeutic agent.
38. The medical device of claim 25 wherein the thin wall membrane
comprises a pharmaceutic agent.
39. The medical device of claim 25 wherein the coating comprises a
therapeutic agent.
40. The medical device of claim 25 wherein the coating comprises a
pharmaceutic agent.
41. The medical device of claim 25 wherein at least a porting of
the structural frame is coated with a therapeutic agent.
42. The medical device of claim 25 wherein at least a portion of
the structural frame is coated with a pharmaceutic agent.
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 method
of making the medical device. In particular, the present invention
relates to a medical device having a radially expandable structural
frame and a thin wall tubular membrane structure, and a method of
making the medical device having a thin wall tubular membrane on a
radially expandable structural frame.
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. For example, 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. In addition, the vessels and body lumens may
become damaged and require repair.
[0005] Numerous therapies have been advanced to treat symptoms,
including the correction of incompetent valves. Similarly, the
vessels and body lumens may become damaged and require repair. 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, and vessels.
[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 venous valves are generally thin, and once
the valve becomes incompetent or destroyed, any repair provides
only marginal relief. Surgical procedures to repair damage vessels
or body lumens include delivering and implanting expandable grafts
and/or replacing damaged vessels.
[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 and lumens 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. What is also needed is an
artificial endovascular conduit for the repair of incompetent or
damaged vessels or body lumens.
SUMMARY OF THE INVENTION
[0010] The present invention relates to a medical device, and in
particular, a method of placing a tubular membrane on a radially
expandable structural frame. One example of a medical device having
a radially expandable structural frame and a tubular membrane is a
stent-based valve. Another example might include medical devices,
such as grafts and stent grafts, to repair and/or treat vascular
aneurysms, such as abdominal aortic aneurysms.
[0011] One embodiment of the radially expandable structural frame
comprises a proximal anchor and a distal anchor. The proximal and
distal anchors are formed from a lattice of interconnected
elements, and have a substantially cylindrical configuration with
first and second open ends and a longitudinal axis extending there
between.
[0012] The radially expandable structural frame also comprises one
or more struts, each having a first and a second end. The first end
of each strut is attached to the proximal anchor and the second end
of each strut is attached to the distal anchor. The tubular
membrane assembly is placed on the radially expandable structural
frame.
[0013] The present invention provides a method of placing the
tubular membrane about a radially contractible and expandable
structural frame. In accordance with one aspect, the method of the
present invention comprises the steps of providing a polymeric tube
having a first diameter and a first wall thickness. A structural
frame is then radially contracted. The radially contracted
structural frame is then placed, at least in part, into the
polymeric tube. Once the radially contracted structural frame is
placed at the desired location, the structural frame expands into
the polymeric tube, expanding at least a part of the polymeric tube
to a second diameter, and forming a covered frame assembly. The
second diameter of the polymeric tube is greater than the first
diameter. The expanded polymeric tube and structural frame are then
mechanically attached. One method of mechanical attachment includes
coating the covered frame assembly with a polymer.
[0014] A medical device having a tubular membrane structure and a
radially expandable structural frame is also contemplated by the
present invention. The medical device comprises an outer membrane
formed at least in part from a polymeric material, preferably a
polymeric tube positioned and radially expanded over a radially
expandable structural frame, such that the radially expanded
polymeric tube form a thin membrane cover over the structural
frame. An outer coating formed at least in part from a polymer
solution is coated over the radially expanded polymeric tube and
structural frame, such that the outer coating mechanically attaches
the outer membrane to the radially expandable structural frame.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1A shows a perspective view of a prosthetic venous
valve in the deployed state according to one embodiment of the
present invention.
[0016] FIG. 1B shows a perspective view of the prosthetic venous
valve structural frame in the deployed state according to one
embodiment of the present invention.
[0017] FIG. 1C shows a perspective view of the prosthetic venous
valve structural frame having helical connecting members according
to one embodiment of the present invention.
[0018] FIG. 1D shows a perspective view of the prosthetic venous
valve structural frame having an hourglass shape according to one
embodiment of the present invention.
[0019] FIG. 2A shows a perspective view of the proximal stent-based
anchor in the expanded deployed state according to one embodiment
of the present invention.
[0020] FIG. 2B shows a close-up perspective view of a loop having
inner and outer radii according to one embodiment of the present
invention.
[0021] FIG. 2C shows a perspective view of the prosthetic venous
valve structural frame having connecting members connected between
the proximal and distal anchors in a peak-to-peak configuration
according to one embodiment of the present invention.
[0022] FIG. 2D shows a perspective view of the prosthetic venous
valve structural frame having connecting members connected between
the distal and proximal anchors in a peak-to-valley configuration
according to one embodiment of the present invention.
[0023] FIG. 2E shows a perspective view of the prosthetic venous
valve structural frame having connecting members connected between
the distal and proximal anchors in a valley-to-valley configuration
according to one embodiment of the present invention.
[0024] FIG. 2F shows a perspective view of the prosthetic venous
valve structural frame having connecting members connected between
the distal and proximal anchors along the strut members according
to one embodiment of the present invention.
[0025] FIG. 3 shows a perspective view of the distal stent anchor
having a plurality of hoop structures according to one embodiment
of the present invention.
[0026] FIG. 4A is a perspective view illustrating one embodiment of
the expanded (deployed) prosthetic venous valve assembly in the
open position.
[0027] FIG. 4B is a section view illustrating one embodiment of the
expanded (deployed) prosthetic venous valve assembly in the open
position.
[0028] FIG. 5A is a perspective view illustrating one embodiment of
the expanded (deployed) prosthetic venous valve assembly in the
closed position.
[0029] FIG. 5B is a section view illustrating one embodiment of the
expanded (deployed) prosthetic venous valve assembly in the closed
position.
[0030] FIG. 6A is a perspective view illustrating a membrane
limiting means according to one embodiment of the present
invention.
[0031] FIG. 6B is a perspective view illustrating a membrane
limiting means according to one embodiment of the present
invention.
[0032] FIG. 6C is a perspective view illustrating a membrane
limiting means according to one 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.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0034] The stent-based valves disclosed with 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. In addition, the method of
placing a membrane assembly over a structural frame can be equally
applied to various medical devices having a radially
expandable/compressible structural frame, including for example,
grafts, stent grafts, and other aneurysm and vessel repair
devices.
[0035] 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).
[0036] A perspective view of an exemplary prosthetic venous valve
in the expanded (deployed) state according to one embodiment of the
present invention is shown in FIG. 1A. The prosthetic venous valve
100 comprises a structural frame 101 and a biocompatible membrane
assembly 102. 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.
[0037] For clarity, a perspective view of the prosthetic venous
valve 100 structural frame 101 is shown in FIG. 1B. The structural
frame 101 consists of proximal and distal anchor structures 103,
104 connected by at least one connecting member 105. In a preferred
embodiment, at least three connecting members 105 are utilized.
[0038] 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 anchor in the
present application describes the upstream anchor of structural
frame 101 regardless of its orientation relative to the body.
Conversely, the use of the term distal is used to describe the down
stream anchor 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.
[0039] The connecting members 105 are attached between the proximal
and distal anchors 103, 104 to further support the biocompatible
membrane assembly 102 (not shown in FIG. 1B). In one embodiment,
the connecting members 105 are substantially straight members,
connecting the stent based proximal and distal anchors 103, 104 in
a direction substantially parallel to the longitudinal axis 106.
Although three connecting members 105 are shown in the illustrated
embodiment, this configuration should not be construed to limit the
scope of the invention.
[0040] Alternatively, the connecting members 105 may be twisted in
a helical fashion as they extend from the proximal to distal
anchors 103, 104. This alternate embodiment is illustrated in FIG.
1C. Specifically, the connection points between the connecting
members 105 and the distal anchor 104, and the connecting members
105 and the proximal anchor 103, are rotationally phased 180
degrees from each other to provide the helical design.
[0041] Each connecting member 105 may also be biased inward
slightly toward the longitudinal centerline 106 of the stent-based
anchors 103, 104, creating a structural frame 101 having an
hour-glass shape with the minimum radius located substantially at
the longitudinal midpoint along the connecting member 105 length.
An hourglass shaped structural frame 101 is illustrated in FIG.
1D.
[0042] 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.
[0043] 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.
[0044] 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.
[0045] 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.
[0046] 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.
[0047] 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.
[0048] 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, such as proximal
and distal anchors 103, 104, may be cut to length from a long wire
mesh tube. The connecting member 105 may then be attached to the
proximal and distal anchors 103, 104 by welding or other suitable
connecting means.
[0049] 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.
[0050] 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.
[0051] In one embodiment of the invention, the anchors 103, 104 are
stent-based structures. 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.
[0052] A perspective views of a typical stent-based anchor in the
expanded (deployed) state is shown in FIGS. 2A. Although a Z or S
shaped pattern stent anchor is shown for the purpose of example,
the illustration is not to be construed as limiting the scope of
the invention. One of ordinary skill in the art would understand
that other stent geometries may be used.
[0053] The stent anchors (proximal and distal anchors 103, 104
respectively) each comprise a tubular configuration of structural
elements having proximal and distal open ends and defining a
longitudinal axis 106 extending there between. The stent anchors
103, 104 have 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 anchors
103, 104, and thus the stent based venous valve 100, may be either
a mechanical (balloon) or self-expanding stent based structure.
[0054] Each stent anchor 103, 104 comprises at least one hoop
structure 206 extending between the proximal and distal ends. The
hoop structure 206 includes a plurality of longitudinally arranged
strut members 208 and a plurality of loop members 210 connecting
adjacent struts 208. 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 inter 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.
[0055] The connecting member 105 may be connected to the proximal
and distal anchors 103, 104 at various points along the structure.
As illustrated in FIG. 2C, the connecting members 105 are connected
between the proximal end of the distal anchor 104 and the distal
end of the proximal anchor 103 at the inflection point of the loop
members 210. This configuration creates a "Peak-to-Peak" connection
bridging the outer radii 214 of the inflection point of loop
members 210 on the proximal anchor 103 with the outer radii 214 of
the inflection point of the loop member 210 on the distal anchor
104.
[0056] Preferably the connecting members 105 are connected to the
inflection point of loop members 210 oriented directly opposite one
another, and are evenly spaced along the circumference of the
tubular anchors 103, 104. 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.
[0057] Alternatively, the connecting members 105 may be connected
between the distal and proximal anchors 104, 103 to create a
"Peak-to-Valley" connection between the loop members 210. In this
configuration, illustrated in FIG. 2D, the connecting members 105
are connected to the proximal end of the distal anchor 104 at the
outer radii 214 of the inflection point of loop member 210, and the
inner radii 212 of the inflection point of loop member 210 on the
proximal end of the proximal anchor 103.
[0058] In a further embodiment, the connecting members 105 may be
connected between the distal end of the distal anchor 104 and the
proximal end of the proximal anchor 103 at the inflection point of
the loop members 210 as shown in FIG. 2E. This configuration
creates a "Valley-to-Valley" connection bridging the inner radii
212 of the inflection point of loop members 210 on the proximal
anchor 103 with the inner radii 212 of the inflection point of the
loop member 210 on the distal anchor 104.
[0059] In still a further embodiment, the connecting members 105
may be connected between the strut members 208 of the distal anchor
104 and the strut members 208 of the proximal anchor 103 as shown
in FIG. 2F.
[0060] In any of the above described configurations, the
connections between the connecting members 105 and the anchors 103,
104 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.
[0061] Although stent anchors 103, 104 incorporating a singular
hoop structure are shown in the embodiment illustrated in FIGS. 2A
though 2F, each stent anchor may utilize a plurality of hoop
structures.
[0062] FIGS. 3 shows a distal anchor having a plurality of hoop
structures 306A through 306D according to another embodiment of the
present invention. In the illustrated embodiment, the distal stent
anchor 104 may further comprise a plurality of bridge members 314
that connect adjacent hoops 306A through 306D. Each bridge member
314 comprises two ends 316A, 316B. One end 316A, 316B of each
bridge 314 is attached to one loop on one hoop. Using hoop sections
306C and 306D for example, each bridge member 314 is connected at
end 316A to loop 310 on hoop section 306C at a point 320.
Similarly, the opposite end 316B of each bridge member 314 is
connected to loop 310 on hoop sections 306D at a point 321.
[0063] The proximal and distal anchors 103, 104 secure the
prosthetic valve 100 to the inside wall of a body vessel such as a
vein, and provide anchor points for the connecting members 105.
Once deployed in the desired location, the anchors 103, 104 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. The
connecting members 105 preferably have an inferior radial
stiffness, and will conform much more closely to the native
diameter of the vessel, facilitating the operation of the
biocompatible membrane assembly 102.
[0064] 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.
[0065] 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 a micro-cellular
foam or porous polymeric material, including expanded
Polytetrafluoroethylene (ePTFE), 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.
[0066] 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) and 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.
[0067] The first end 401 of the membrane tubular structure 400 is
located between the proximal and distal anchors 103, 104, and is
preferably located at the approximate longitudinal midpoint of the
connecting members 105 between the two anchors 103, 104. The second
end 402 of the membrane tubular structure 400 extends proximally
from the longitudinal midpoint, and is preferably located proximal
to at least one half of the proximal anchor 103. In one embodiment
of the invention, the membrane structure 400 completely covers the
proximal anchor 103. This configuration allows the proximal anchor
103 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.
[0068] 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 connecting members 105
supporting the membrane tubular assembly 102. 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.
[0069] 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 connecting members 105 and membrane tubular
structure 400.
[0070] 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.
[0071] 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) is substantially
sealed against the inner vessel wall by proximal anchor 103, 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.
[0072] 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
connecting members 105 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.
[0073] 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.
[0074] 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.
[0075] 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).
[0076] 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 or suturing. 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 connecting
members 105. Allowing the distal end 402 to slide along the
connecting members 105 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.
[0077] In some applications, excessive sliding movement of the
membrane assembly 102 is undesirable. In these embodiments, a
limiting means may be integrated into the prosthetic valve 100 to
limit the sliding movement of the membrane assembly 102. Examples
of limiting means are shown in FIGS. 6A to 6C. In each embodiment a
stop 600 (illustrated as stop 600A, 600B, and 600C in FIGS. 6A to
6C respectively) is integrated into the connecting member 105. The
membrane assembly 102 is wrapped around the connecting member 105
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. 6A, the
connecting member 105 has a thickened or "bulbous" section forming
stop 600A. FIG. 6B illustrates an undulating stop 600B
configuration. Similarly, FIG. 6C shows the stop 600C configured as
a double bulbous section. It should be noted that the various
configurations illustrated in FIGS. 6A through 6C are exemplary.
One of ordinary skill in the art would understand that other
configurations of stops may used.
[0078] In one embodiment of the invention the tubular membrane 400
is manufactured from a polymeric membrane, such as a micro-cellular
foam or porous polymeric material. One method for forming the
membrane material over and around the structural frame 101 is shown
in FIG. 7. 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 porous polymeric
material, particularly an ePTFE membrane, needs to be placed over
and around a radially expandable and collapsible 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 medical device is not
meant to limit the scope of the inventive method.
[0079] In this embodiment, a tubular structure fabricated from a
polymeric material that can be processed such that it exhibits an
expanded cellular structure, preferably expanded
Polytetrafluoroethylene (ePTFE), is provided. 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. An ePTFE tube having an Inter Nodal Distance (IND)
in the range of approximately 20 .mu.m to approximately 200 .mu.m,
and preferably approximately 50 .mu.m to approximately 100 .mu.m
has been found to be acceptable. However, one of ordinary skill in
the art would understand that other materials that possess the
necessary characteristics could also be used.
[0080] The method comprises first providing a polymeric tube,
preferably an ePTFE tube, having a first inside diameter and a
first wall thickness as shown in step 700. This polymeric tube,
when fully radially expanded will have a second inside diameter and
second wall thickness.
[0081] The inside diameter of the polymeric tube, before and after
full radial expansion, is an important factor. To achieve proper
seating and affixation of the membrane 400, the polymeric tube
should be generally sized so that there is an interference fit
between the inside diameter of the tube and outside diameter of the
structural frame when fully expanded. The actual first inside
diameter and first wall thickness of the tube are variable, and are
typically determined by the type and application of the medical
device being made. By way of example using venous valve
applications, it has been found that a polymeric tube having a
first inside diameter of approximately 1 mm to 5 mm and a wall
thickness of approximately 25 .mu.m to 100 .mu.m, are acceptable.
Preferably, the polymeric tube for venous valve applications will
have a first inside diameter of approximately 2 mm to 3 mm and a
wall thickness of approximately 25 .mu.m to 50 .mu.m. This
configuration should lead to a membrane 400 having a wall thickness
of approximately 12 .mu.m to 50 .mu.m, and preferably in the range
approximately 12 .mu.m to 25 .mu.m when the valve is deployed, i.e.
full radial expansion.
[0082] A radially expandable and collapsible structural frame is
then radially contracted, as shown in step 710, to a diameter that
is slightly smaller than the first inside diameter of the polymeric
tube. In some embodiments, the radially expandable structural frame
may be fabricated in the radially contracted pre-deployed state. In
such instances, contraction of the radially expandable structural
frame may not be necessary.
[0083] Contraction of the structural frame may be achieved by
several difference methods. One particular method useful in
embodiments where the structural frame is of the self-expanding
type includes crimping the structural frame and then inserting the
crimped structural frame into a sheath that has an inside diameter
that is smaller than the outside diameter of the structural frame.
The sheath is further sized to allow the radially contracted
structural frame and sheath to be inserted into the polymeric tube.
The interior surface of the sheath may inherently possess low
friction characteristics to reduce the effort needed to insert the
structural frame.
[0084] Crimping involves radially contracting the structural frame
with a crimping tool, machine or similar device. Crimping devices
for radially contracting radially contractible structural frame are
well known in the art.
[0085] The radially contracted structural frame is then introduced
into the polymeric tube as shown in step 720. In a preferred
embodiment, the structural frame is introduced into the polymeric
tube in such a fashion that at least a portion of the radially
contracted frame is covered by the tube.
[0086] Some polymeric tubes, such as ePTFE tubes, tend to
longitudinally shrink when radially expanded. When materials having
these characteristics are used, it may be desirable to use tubes
that are longer than necessary to accommodate this shrinkage.
Alternatively, much longer tubes can be used, and any longitudinal
excess trimmed after full radial expansion.
[0087] Once positioned at the desired location, the structural
frame is then radially expanded into the polymeric tube to a second
diameter. The second diameter of the polymeric tube is greater than
the first diameter, and enables a mechanical interference fit
between the tube and structural frame as shown in step 730. The
combination structural frame and polymeric membrane may be referred
to as a covered frame assembly.
[0088] Radial expansion of the structural frame may be executed by
many different means, including through the expansion of a
mechanical assist device, such as by the radial expansion of an
inflation balloon, cage assembly or mandrel placed inside the frame
assembly. In instances where the structural frame is held
compressed using a sheath, such as where the structural frame is of
a self expanding type, radial expansion of the structural frame may
be performed by sliding the sheath back off the structural frame,
thereby allowing the self expanding structural frame to radially
self expand.
[0089] In another, more preferred embodiment, that can be used
where the self expanding structural is fabricated of a shape memory
alloy, such as Nitinol, the radial contraction and expansion of the
structural frame 101 can take advantage of the shape memory
characteristics of the material when cooled and subsequently
heated. 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 radial contraction
allows the structural frame to remain in the contracted
configuration until being heated. Accordingly, the Nitinol
structural frame 101 can be cooled, contracted, and then introduced
into the polymeric tube without the need for a sheath. Once in
place, the structural frame can be heated to activate the Nitinol
memory characteristics, causing the Nitinol structural frame 101 to
self expand to the pre-contraction size and configuration, thus
expanding the polymeric tube.
[0090] In such instances, radial contraction of the structural
frame may be performed by crimping, using a crimping machine as is
well known in the art.
[0091] The polymeric tube is inherently radially plastic, and has
very little recoil properties. As the structural frame is radially
expanded against the polymeric tube, the polymeric tube similarly
radially expands. This radial expansion causes the tube wall to
thin, providing a polymeric tube with a second wall thickness that
is smaller than the first wall thickness.
[0092] It is important to note that the radially expandable
structural frame and polymeric tube must be sized appropriately to
allow the desired second wall thickness to be attained when the
structural frame is at its expanded deployed state. For venous
valve applications, it has been found that a second wall thickness
of approximately 12 .mu.m to 50 .mu.m is acceptable. Preferably,
the polymeric tube for venous valve applications will form a
membrane having a second wall thickness of approximately 12 .mu.m
to 25 .mu.m after expansion to the second diameter.
[0093] In embodiments where self-expanding structural frames 101
are used, the structural frame 101 may not initially achieve the
desired second diameter when allowed to self expand into the
polymeric tube. Instead, the self expanding structural frame and
polymeric tube may expand to an equilibrium point, having an
intermediate inside diameter greater than the first inside
diameter, but smaller than the desired second inside diameter. In
such instances, the self-expanding structural frame/polymeric tube
may have to additionally be mechanically expanded.
[0094] As described previously, mechanical expansion may be by
several different mechanical assist devices, such as by the radial
expansion of an inflation balloon, cage assembly or mandrel placed
inside the frame assembly. Since the polymeric tube offers very
little radial elasticity, i.e. is inherently radially plastic, it
will not tend to recoil back to the intermediate equilibrium point
once fully expanded to the desired second inside diameter. Instead,
the structural frame 101 will be allowed to achieve its natural
self-expanded second diameter. Accordingly, the polymeric tube will
achieve and maintain the desired second inner diameter.
[0095] The expanded polymeric tube may then be attached to the
frame assembly as shown in step 740. Attachment of the polymeric
tube to the structural frame can be accomplished by several
different methods, including attachment resulting from radial
pressure of the structural frame against the polymeric tube,
attachment by means of a binder, heat, or chemical bond, and/or
attachment by mechanical means, such as by welding, adhesives or
suturing. Preferably, the expanded polymer tube is mechanically
attached to the structural frame by a coating process.
[0096] As earlier disclosed, the polymeric tube is preferably a
micro-cellular foam or porous polymeric material. When the cover
frame assembly is coated with a coating solution, the coating
solution at least partially fills the pores in the polymeric tube
and at least partially encapsulates the structural frame. As the
coating solution dries and cures, the solution binds to the
polymeric tube through the pores, mechanically attaching the
membrane to the structural frame. In addition to attaching the
expanded polymeric tube to the structural frame, the coating
becomes an integral part of the polymeric tube, and together they
form the membrane structure e.g. membrane 400.
[0097] The coating solution is preferably a highly elastic polymer,
such as fluoroelastomer. These highly elastic polymers can be
applied to the covered frame assembly by using various methods,
including, for example, spin coating, spray coating, dip coating,
chemical vapor deposition, plasma coating, co-extrusion coating and
insert molding.
[0098] In still another preferred embodiment, the covered frame
assembly is first dip coated in a polymer solution, and then spun
about its longitudinal axis to more evenly distribute the coating.
Still other methods for coating the fiber spun structural frame
would be obvious to one of skill in the art.
[0099] As disclosed earlier, the coating process may act to
partially encapsulate and attach at least a portion of the expanded
polymeric tube (i.e. the membrane assembly 102) to the structural
frame 101. It should be noted that 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
covered frame assembly may be coated.
[0100] The coating process may also remove some porosity from 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.
[0101] The coating solution preferably comprises a polymer put into
solution with a solvent, such as methanol. In addition to methanol,
most solvents can be used with expanded Polytetrafluoroethylene
(ePTE). 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 polymeric tube being coated. By way of
example, a coating solution of vinylidene
fluoride/hexafluoropropylene/tetrafluoroethylene (VDF/HFP/TFE) in
methanol (methanol being the solvent) has been found to be a
suitable solution for coating a polymeric tube.
[0102] 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. Other preferred polymers include siliconized
polyurethanes, including silicone-urethane copolymers, and blends
thereof. Silicone-urethane copolymers can consist of segmented
polyetherurethane with aromatic urea as hard segments and poly
(tetramethyleneoxide) [PTMO] as soft segments. Silicone (20 to 25%)
is added by replacing PTMO with polydimethylsiloxane, and fluorine
(0.5 to 2%) can be added by surface-modifying end groups. 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 and blends thereof. Preferred
siliconized polyurethanes include Polymer Technology Group's
Pursil, Carbosil, Purspan and Purspan F.
[0103] The coating process should continue until the membrane
(coating and radially expanded polymeric tube) achieves a wall
thickness of approximately 12 .mu.m to 100 .mu.m or more,
preferably approximately between 25 .mu.m to 50 .mu.m.
[0104] Once the coating process is complete, some post processing
of the membrane structure may take place to achieve particular
desired characteristics or configurations, and improve the
mechanical bonding to the structural frame 101. This post
processing step is shown as optional step 750 in FIG. 7.
[0105] By way of example, for valve applications, the post
processing step 750 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, for
example, assist in controlling the translational and
circumferential movement of the membrane assembly 102 along the
connecting members 105. The loop collars 605 may also reduce
fatigue and tear stresses in the membrane.
[0106] 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 (connecting member 105) and bonded
to itself at bond point 800.
[0107] 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 disclosed in the present invention.
[0108] 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
polymeric tube or coating solution, membrane assembly or structural
frame 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/antimitot- ic 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.
[0109] 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 sub combinations 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. 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.
* * * * *