U.S. patent application number 11/176817 was filed with the patent office on 2005-11-03 for multi-lumen vascular grafts having improved self-sealing properties.
This patent application is currently assigned to SCIMED Life Systems, Inc.. Invention is credited to Henderson, Jamie S..
Application Number | 20050246012 11/176817 |
Document ID | / |
Family ID | 32594374 |
Filed Date | 2005-11-03 |
United States Patent
Application |
20050246012 |
Kind Code |
A1 |
Henderson, Jamie S. |
November 3, 2005 |
Multi-lumen vascular grafts having improved self-sealing
properties
Abstract
The present invention provides an implantable graft, including a
primary tubular body having a first outer wall surface and a first
inner wall surface defining a primary blood contacting lumen, and a
secondary tubular body having a second outer wall surface and a
second inner wall surface. The secondary tubular body is located
about the primary tubular body to form a space therebetween. The
primary and secondary tubular bodies are joined by at least one
rib.
Inventors: |
Henderson, Jamie S.;
(Oakland, NJ) |
Correspondence
Address: |
HOFFMANN & BARON, LLP
6900 JERICHO TURNPIKE
SYOSSET
NY
11791
US
|
Assignee: |
SCIMED Life Systems, Inc.
|
Family ID: |
32594374 |
Appl. No.: |
11/176817 |
Filed: |
July 7, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11176817 |
Jul 7, 2005 |
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10328081 |
Dec 23, 2002 |
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6926735 |
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Current U.S.
Class: |
623/1.27 |
Current CPC
Class: |
A61L 27/507 20130101;
A61F 2/06 20130101; A61L 27/16 20130101; A61L 27/34 20130101; A61L
27/16 20130101; C08L 27/18 20130101 |
Class at
Publication: |
623/001.27 |
International
Class: |
A61F 002/06 |
Claims
What is claimed is:
1. An implantable graft, comprising: a primary tubular body formed
of ePTFE having a first inner wall surface and a first outer wall
surface defining a primary blood contacting lumen; a secondary
tubular body formed of ePTFE having a second inner wall surface and
a second outer wall surface, said secondary tubular body being
located about said primary tubular body to form a space
therebetween, wherein said primary and secondary tubular bodies are
joined by at least one rib, said rib defining a plurality of
secondary lumens; and a self-sealing polymeric material located in
at least one of said secondary lumens.
2. A method of forming an implantable graft comprising a primary
tubular body having a first inner wall surface and a first outer
wall surface defining a primary blood contacting lumen; and a
secondary tubular body having a second inner wall surface and a
second outer wall surface, said secondary tubular body being
located about said primary tubular body to form a space
therebetween, wherein said primary and secondary tubular bodies are
joined by at least one rib and define at least one secondary lumen,
the method comprising the steps of: pre-forming a PTFE structure
from PTFE paste into a tubular shape including said primary lumen
and said secondary lumen; and extruding said pre-formed PTFE
structure through a tubular mold having a die with spacing devices
for holding open said secondary lumens to form a multi-lumen
tube.
3. The method according to claim 2, wherein said pre-forming step
includes compressing said paste in said mold prior to said
extruding step.
4. The method according to claim 3, further comprising the step of
expanding said multi-lumen tube along a longitudinal axis of said
multi-lumen tube.
5. The method according to claim 4, further comprising the step of
sintering said multi-lumen tube so as to form said graft.
6. The method according to claim 2, further comprising the step of
adding a self-sealing polymeric material to at least one of said
non-blood contacting lumen.
7. The method according to claim 6, further comprising the step of
treating at least a portion of said primary tubular body so as to
create a drug delivery system to deliver a drug to an interior of
said graft.
8. The method according to claim 7, comprising the step of adding a
therapeutic agent to at least said portion of said primary tubular
body containing said drug delivery system.
9. The method according to claim 8, wherein said therapeutic agent
is selected from the group consisting of: an antibiotic agent, an
anti-thrombogenic agent, an anti-inflammatory agent, an anesthetic
agent, an anti-coagulant, a vascular cell growth promoter, a
vascular cell growth inhibitor, and a cholesterol lowering
agent.
10. The method according to claim 6, further comprising the step of
perforating a portion of said primary tubular body so as to create
a plurality of first pores connecting an exterior of said graft
with an interior of one or more of said secondary lumen, wherein
said first pores are not present in said secondary lumen containing
said self-sealing material.
11. The method according to claim 7, further comprising the step of
adding a therapeutic agent to one or more of said secondary lumen
containing said first pores.
12. The method according to claim 11, wherein said therapeutic
agent is selected from the group consisting of: an antibiotic
agent, an anti-thrombogenic agent, an anti-inflammatory agent, an
anesthetic agent, an anti-coagulant, a vascular cell growth
promoter, a vascular cell growth inhibitor, and a cholesterol
lowering agent.
13. The method according to claim 6, further comprising the step of
treating at least a portion of said secondary tubular body so as to
create a drug delivery system to deliver a drug to an exterior of
said graft.
14. The method according to claim 7, comprising the step of adding
a therapeutic agent to at least said portion of said secondary
tubular body containing said drug delivery system.
15. The method according to claim 14, wherein said therapeutic
agent is selected from the group consisting of: an antibiotic
agent, an anti-thrombogenic agent, an anti-inflammatory agent, an
anesthetic agent, an anti-coagulant, a vascular cell growth
promoter, a vascular cell growth inhibitor, and a cholesterol
lowering agent.
16. The method according to claim 2, further comprising the step of
perforating a portion of said secondary tubular body so as to
create a plurality of second pores connecting said primary lumen of
said graft with one or more of said secondary lumen, wherein said
second pores are not present in said secondary lumen containing
said self-sealing material.
17. The method according to claim 16, further comprising the step
of adding a therapeutic agent to one or more of said secondary
lumen containing said second pores.
18. The method according to claim 17, wherein said therapeutic
agent is selected from the group consisting of: an antibiotic
agent, an anti-thrombogenic agent, an anti-inflammatory agent, an
anesthetic agent, an anti-coagulant, a vascular cell growth
promoter, a vascular cell growth inhibitor, and a cholesterol
lowering agent.
19. The method according to claim 2, further comprising the step of
forming a textile cover for said graft.
20. The method according to claim 19, further comprising the step
of adhering said textile cover onto said graft after or
simultaneous with said step of forming said textile cover for said
graft.
21. An implantable graft, comprising: a first tubular blood
contacting member having a first inner wall surface and a first
outer wall surface and defining a blood contacting lumen; a second
tubular non-blood contacting member having a second inner wall
surface and a second outer wall surface, said non-blood contacting
member being arranged at least partially non-concentrically about
said blood contacting member so as to define at least one non-blood
contacting lumen therebetween, wherein at least a portion of said
first outer wall and said second inner wall are in contact and
contiguous along a length of said graft, said members being
laminated along said portion.
22. A method of forming a graft according to claim 21, comprising
the steps of: extruding a first tubular member from PTFE paste
having a first inner wall surface and a first outer wall surface
defining a primary blood contacting lumen; extruding a second
tubular member from PTFE paste having a second inner wall surface
and a second outer wall surface; arranging said second tubular
member non-concentrically about said first tubular member along a
length of said graft such that a portion of said first outer wall
contacts a portion of said second inner wall; and laminating said
portions together.
23. The method according to claim 22, wherein said laminating step
includes at least one of heat setting, adhesive welding, and
applying a uniform force to said graft.
24. An implantable graft, comprising: a first tubular body having
an inner wall and outer wall, said inner wall defining a first
blood contacting lumen; and at least two non-blood contacting
lumens positioned between said inner and outer walls of said
tubular body and longitudinally aligned with said blood-contacting
lumen.
25. An implantable graft, comprising: a primary tubular body having
a first outer wall surface and a first inner wall surface defining
a primary blood-contacting lumen; and a secondary tubular body
having an outer wall surface and an inner wall surface, said
secondary tubular body being located about said primary tubular
body, wherein said primary and secondary tubular bodies are joined
by at least one rib; wherein at least a portion of the outer wall
of the primary tubular body, at least a portion of the inner wall
of the secondary tubular body, and the at least one rib define at
least one secondary lumen; and wherein the at least one secondary
lumen is capable of containing (i) a polymeric material that
self-compresses upon puncture and (ii) a physiologically or
pharmaceutically active agent.
26. An implantable graft, comprising: a primary tubular body having
an outer wall surface and an inner wall surface defining a primary
blood-contacting lumen; and a secondary tubular body having an
outer wall surface and an inner wall surface, said secondary
tubular body being located about said primary tubular body, wherein
said primary and secondary tubular bodies are joined by at least
one rib; wherein at least a portion of the outer wall of the
primary tubular body, at least a portion of the inner wall of the
secondary tubular body, and the at least one rib define at least
one secondary lumen; and wherein the at least one secondary lumen
comprises at least one polymer or copolymer selected from the group
consisting of silicone rubbers, synthetic rubbers, polyurethanes,
polyethers, polyesters, and polyamides.
27. An implantable graft, comprising: a primary tubular body having
an outer wall surface and an inner wall surface defining a primary
blood-contacting lumen; and a secondary tubular body having an
outer wall surface and an inner wall surface, said secondary
tubular body being located concentrically about said primary
tubular body to form at least one secondary lumen therebetween,
wherein the at least one secondary lumen contains at least one
gel.
28. The implantable graft of claim 27, wherein the gel is a
hydrogel formed from a natural material.
29. The implantable graft of claim 28, wherein the gel is selected
from the group consisting of gelatin, collagen, albumin, casein,
algin, carboxymethyl cellulose, carageenan, furcellaran, agarose,
guar, locust bean gum, gum arabic, hydroxyethyl cellulose,
hydroxypropyl cellulose, methyl cellulose, hydroxyalkylmethyl
cellulose, pectin, partially deacetylated chitosan, starch and
starch derivatives, and mixtures thereof.
30. An implantable graft, comprising: a primary tubular body having
an outer wall surface and an inner wall surface defining a primary
blood-contacting lumen; and a secondary tubular body having an
outer wall surface and an inner wall surface, said secondary
tubular body being located about said primary tubular body to form
a space therebetween, wherein said primary and secondary tubular
bodies are joined by at least one rib, wherein a self-sealing
polymeric material and a drug are present in said space.
Description
CROSS-REFERENCE TO RELATED APPLICATION:
[0001] The present application is a divisional of U.S. patent
application Ser. No. 10/328,081, filed Dec. 23, 2002, the contents
of which are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates generally to an implantable
prosthesis. More particularly, the present invention relates to an
implantable graft having an integral multi-lumen structure.
BACKGROUND OF THE INVENTION
[0003] Implantable grafts are commonly used in treatment of
diseased blood vessels. One such device is a synthetic vascular
graft designed to replace damaged or dysfunctional tissue. Such
damage or dysfunction can arise, for example, from arterial or
venous pathways that have been damaged by thrombosis, an aneurysm
or occlusion. The graft provides an artificial lumen through which
blood may flow.
[0004] Natural blood vessels are often damaged during treatment of
renal failure. For example, when treating patients with renal
failure using dialysis, it is necessary to have ready access to
blood vessels in order to continuously withdraw blood from the
patient in amounts of over 200 ml/min. For dialysis to be
effective, it must be repeated on a regular schedule of two or more
treatments per week. Each time, a vein is accessed using a
relatively large bore needle. As a result of the repeated
percutaneous access, the vein will often collapse along the
puncture tract or become aneurismal, leaky, or filled with clot.
The latter can cause significant risk of pulmonary embolism. As a
result, in dialysis treatments, artificial grafts have been used as
an alternative to using a patient's own veins, in an attempt to
avoid these complications.
[0005] Thus, one increasingly useful application of a vascular
prosthesis is as a bypass shunt between an artery and a vein. A
graft surgically placed between an artery and a vein (AV fistula)
is commonly used in dialysis patients. This bypass or fistula is
particularly useful for allowing multiple needle access, as is
required for hemodialysis treatments.
[0006] Grafts can be made from a variety of materials such as
textiles and formed polymers. Vascular grafts are often made from
polytetrafluoroethylene (PTFE) tubes, and in particular, from
expanded polytetrafluoroethylene (ePTFE) tubes. When PTFE is
expanded or stretched to form tubes, the material consists of a
unique microstructure of nodes interconnected by small fibrils. The
space between the nodes that is spanned by the fibrils is defined
as the intemodal distance (IND). By varying the conditions of
manufacture of the ePTFE tubes, such as temperature and rate of
stretching and expansion, it is possible to vary the space between
the nodes and the number and diameter of fibrils. Expanded PTFE is
particularly suitable as an implantable prosthesis as it exhibits
the desirable characteristics of superior biocompatibility and low
thrombogenicity.
[0007] Expanded PTFE products that are stretched and expanded at
high temperatures and rates are more homogeneous in structure. The
IND is smaller and there are a greater number of fibrils in the
ePTFE tubes. As a result, the product is stronger than if it had
been made at lower temperatures and/or slower rates. In addition,
the porosity is reduced. By varying the conditions of manufacture,
it is possible to often obtain a final product having desired
porosity, strength, and flex qualities.
[0008] It is a goal in graft technology to mimic, as closely as
possible, the natural function of the blood vessel being replaced.
This involves finding a graft material and design that will be
sufficiently strong to resist tear and other mechanical damage, to
be sufficiently flexible and compliant to accommodate the natural
variability of flow and pressure of blood, and to be sufficiently
porous to allow for enhanced healing and appropriate tissue
ingrowth to anchor the prosthesis within the blood vessel and
integrate it within the body.
[0009] The internal structure of ePTFE is desirable in a number of
respects. The diameter of the fibrils formed in ePTFE is much
smaller than the diameter of fibers of knitted or woven fabrics
that have been used previously in vascular prostheses. Expanded
PTFE tubes having a relatively large IND also possesses a higher
degree of porosity than PTFE. These characteristics create a better
substrate for cellular ingrowth, improved flexibility, and greater
compliance in a graft. As a result, a prosthesis formed of ePTFE
can more closely approximate the natural function of the blood
vessel being replaced. Consequently, reduced thrombogenicity,
reduced incidence of intima hyperplasia, and improved cellular
ingrowth can be expected from ePTFE grafts as compared to a
prosthesis formed of other presently available materials or
unexpanded PTFE.
[0010] Current graft materials and designs have not fully achieved
the desired result of mimicking natural vessels, and disadvantages
of using the presently available ePTFE grafts remain. For example,
when the IND is large so as to increase porosity and improved
ingrowth, then the radial tensile strength of the tube is reduced
as is the ability of the tube to retain sutures used during
implantation. Such microporous tubes tend to exhibit low axial tear
strength, so that a small tear or nick will tend to propagate along
the length of the tube. Thus, there is a trade-off between optimal
porosity and flexibility, and optimal strength.
[0011] In addition to the usual structural limitations of using
ePTFE for grafts, there is an additional disadvantage of using
implantable ePTFE vascular grafts as access shunts for
hemodialysis. Specifically, it is difficult to elicit natural
occlusion of suture holes created during implantation. As a result,
the PTFE grafts are generally not used to withdraw blood until they
have been in place for a minimum of 14 days after surgery. This
time is required to allow time for protective ingrowth tissue to
form and keep blood from leaking from the suture holes. Use of the
graft before this period may result in complications such as a
hematoma surrounding the graft, false aneurysm, and possibly graft
occlusion. Thus, in order to maintain the integrity of the graft,
blood cannot be withdrawn from a PTFE vascular graft until the
suture holes have healed. However, waiting this amount of time to
treat a dialysis patient causes undesirable build-up of toxins in
the blood with its attendant problems.
[0012] A further problem associated with grafts used for
hemodialysis is that repeatedly piercing the graft can compromise
its integrity, causing large-scale tears in some instances, or more
often result in hematomas where small amounts of blood leak from
the needle entry point. A number of designs for ePTFE vascular
grafts have been developed to address these problems.
[0013] For example, U.S. Pat. No. 4,619,641 discloses a two-piece
coaxial double lumen arteriovenous graft. This graft consists of an
outer tube positioned over an inner tube, the space between being
filled with a self-sealing adhesive. The self-sealing adhesive
helps prevent hematomas caused by piercing the graft. A
disadvantage of this design is that completely filling the space
between tubes with adhesive limits its flexibility and
compliance.
[0014] In an attempt to increase radial tensile and axial tear
strength of ePTFE tubes, U.S. Pat. No. 4,743,480 discloses a method
of altering the extrusion process so as to reorient the fibrils in
the node and fibril matrix.
[0015] U.S. Pat. No. 6,053,939 discloses a single layer ePTFE graft
which releases heparin after grafting. Spaces between the nodes and
fibrils are chemically treated to make the inner surface of the
tube hydrophilic. Tissue-inducing substances and anti-thrombotic
substances (such as heparin) are then covalently bonded to the
hydrophilic inner surface of the tube and pores. The result is a
high patency ratio and reduced risk of thrombosis. Although
increased patency is achieved using this technology, there is still
a period of delay before the graft can safely be used for dialysis.
In addition, there is still a risk of hematoma caused by repeated
piercing of the graft during dialysis.
[0016] U.S. Pat. No. 5,192,310 discloses a vascular graft having a
primary lumen and at least one secondary lumen which share a common
side wall. The secondary lumen is filled with a self-sealing,
non-biodegradable, biocompatible polymer. However, this graft is
difficult to make using traditional extrusion methods. The graft is
made by using unconventional methods, involving a combination
extrusion and injection molding process. As a result, the
manufacture of this graft is expected to result in a non-uniform
and irregular pattern of nodes and fibrils. This irregular
conformation becomes problematic during the sintering step during
which time melt fractures and other inconsistencies in the
microstructure will occur. Thus, this disclosed method of making
the graft appears unreliable, costly and likely to produce a
defective product.
[0017] Thus, there is a need for a graft which provides desirable
porosity, resists tears at suture holes, and resists blood flow
through puncture holes caused by repeated needle access.
SUMMARY OF THE INVENTION
[0018] One advantage of the present invention is that there is
provided a vascular graft having sufficient porosity, flexibility
and strength to use in procedures requiring repeated needle access
and which includes a self-sealing capability.
[0019] Another advantage of the present invention is that the
inventive vascular grafts can be used within a short period of time
after implantation without adverse impact to the integrity of the
graft.
[0020] A still further advantage of the present invention is that
the inventive grafts are easily and reliably manufactured.
[0021] Another advantage of the present invention is that the
inventive grafts provide superior assimilation capabilities and
resealable properties.
[0022] It is a further advantage of the present invention that a
self-sealing graft is provided which performs a drug delivery
function.
[0023] Briefly stated, the present invention provides an
implantable graft, including a primary tubular body having a first
outer wall surface and a first inner wall surface defining a
primary blood contacting lumen; and a secondary tubular body having
a second outer wall surface and a second inner wall surface. The
secondary tubular body is located about the primary tubular body to
form a space therebetween. The primary and secondary tubular bodies
are joined by at least one rib.
[0024] The present invention further provides an implantable graft,
including a primary tubular body formed of ePTFE having a first
outer wall surface and a first inner wall surface defining a
primary blood contacting lumen, a secondary tubular body formed of
ePTFE having a second outer wall surface and a second inner wall
surface, with the secondary tubular body being located about the
primary tubular body to form a space therebetween. The primary and
secondary tubular bodies are joined by at least one rib, the rib
defining a plurality of secondary lumens. A self-sealing polymeric
material may be located in at least one of the secondary
lumens.
[0025] The present invention also provides a method of forming a
self-sealing ePTFE graft. The method includes the steps of: (1)
pre-forming a PTFE structure from PTFE paste into a tubular shape
having a primary lumen and at least one peripherally located
non-blood contacting lumen, and (2) extruding the pre-formed PTFE
structure through a die having spacing devices for holding open the
non-blood contacting lumen to form a multi-lumen tube.
[0026] Additionally, an implantable graft is provided, including a
first tubular blood contacting member having a first inner wall
surface and a first outer wall surface and defining a blood
contacting lumen, a second tubular non-blood contacting member
having a second inner wall surface and a second outer wall surface.
The non-blood contacting member is arranged at least partially
non-concentrically about the blood contacting member so as to
define at least one non-blood contacting lumen therebetween. At
least a portion of the first outer wall and the second inner wall
are in contact and contiguous along a length of the graft. The
members are laminated along said portion.
[0027] Further, the present invention also provides a method of
forming a graft including: (1) extruding a first tubular member
from PTFE paste having a first outer wall surface and a first inner
wall surface defining a primary blood contacting lumen; (2)
extruding a second tubular member from PTFE paste having a second
outer wall surface and a second inner wall surface; (3) arranging
the second tubular member non-concentrically about the first
tubular member along a length of the graft such that a portion of
the first outer wall contacts a portion of the second inner wall;
and (4) laminating the members to one another where the members are
in contact.
[0028] The invention will be more fully appreciated by reference to
the following detailed description in conjunction with the attached
drawing in which like reference numbers refer to like elements
throughout the several views.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] FIG. 1 is a perspective view of an implantable graft
according to the present invention.
[0030] FIG. 2 is a perspective view of an alternative embodiment of
the present invention.
[0031] FIG. 3 is a perspective view of a further embodiment of the
present invention including a tertiary lumen.
[0032] FIG. 4 is a perspective view of a further embodiment of the
present invention including: a self-sealing elastomeric material, a
plurality of drugs, and drug delivery pores in secondary lumens
according to the present invention.
[0033] FIG. 5 is a perspective view of an embodiment of the present
invention including a textile material around an exterior of the
graft according to the present invention.
[0034] FIG. 6 is a perspective view of a die used to form the graft
as shown in FIG. 1.
[0035] FIG. 7 is a perspective view of an embodiment of the present
invention including a secondary tubular body that is joined to a
tertiary tubular body by at least one secondary rib.
DETAILED DESCRIPTION OF THE INVENTION
[0036] The prosthesis of the present invention includes an
implantable self-sealing tubular structure having a plurality of
secondary lumens between a primary and a secondary tubular
structure. Desirably, the prosthesis is formed from extruded PTFE
or other similar material which exhibits superior
biocompatibility.
[0037] In the present invention, a primary tubular body is formed
which defines a blood contacting lumen. A secondary tubular
structure is formed about and integral with the first tubular
structure at an outer wall of the primary tubular body. A portion
of an inner wall of the secondary tubular body and a portion of an
outer wall of the primary tubular body defines at least one
secondary lumen between the tubular bodies. The secondary lumen may
contain a non-biodegradable self-sealing elastomeric material.
Optionally, a pharmacologically or physiologically active agent may
be supplied in the graft for delivery to the patient.
[0038] In an advantageous aspect of the invention, the device is a
vascular graft implanted into the patient's arterial or venous
system so that blood flow is established through the primary
lumen.
[0039] Referring now to FIG. 1, a multi-lumen graft of the present
invention is shown. The graft, generally indicated by the numeral
2, is an elongate tubular structure including a primary tubular
body 4 having an inner wall surface 6 and an outer wall surface 8.
The inner wall surface 6 defines a blood contacting primary lumen
10. The primary tubular body 4 includes a plurality of ribs 12 each
having a radial apex 14. A secondary tubular body 16 having an
inner wall surface 18 and an outer wall surface 20 is arranged
about the primary tubular body 4. The apexes 14 of the ribs 12 are
in contact and integral with that portion of the inner wall surface
18 of the secondary tubular body 16 with which they are in contact.
The outer wall 8 of the primary tubular body 4 and the inner wall
18 of the secondary tubular body 16 between the ribs 12 define a
plurality of secondary lumens 22. These secondary lumens 22 are
non-blood contacting. There is no particular limitation to the
number of secondary lumens 22.
[0040] Although FIG. 1 shows four secondary lumens, there are no
particular limitations to the number of secondary lumens present in
the graft. Similarly, there is no particular limitation as to the
shape of the secondary lumens, although a narrow cross-section is
preferred so as to maintain a cross-sectional size of the graft
which approximates, as closely as possible, the natural vessel
being replaced. The ribs may be thin to separate the lumens or may
be relatively thick to serve a structural support function as well.
Relative thicknesses of the material forming the primary and
secondary tubular bodies may be varied with respect to one another.
In addition, the size and shape of the ribs and the secondary
lumens may be the same or different.
[0041] Referring now to FIG. 2, an alternative embodiment of the
multi-lumen graft according to the invention is shown. As in the
previous embodiment, the graft 2 is comprised of a primary tubular
body 4 having an inner wall surface 6 and an outer wall surface 8.
The inner wall surface 6 defines a blood contacting primary lumen
10. A secondary tubular body 16 having an inner wall surface 18 and
an outer wall surface 20 is arranged about the primary tubular body
4. In this embodiment, the primary tubular body 4 is arranged at
least partially non-concentrically within the secondary tubular
body 16 so that a portion of the outer wall surface 8 of the
primary tubular body 4 and a portion of the inner wall surface 18
of the secondary tubular body 16 are in contact and are made
integral by use of, for example, an adhesive 46. The portion of
these walls that are not in contact define a secondary lumen 22. In
this embodiment, there is a single secondary lumen 22 which is
substantially crescent-shaped.
[0042] In a further aspect of the present invention, multiple
layers of lumens including tertiary lumens are present on the
graft. In this aspect, the graft may be designed so that access to
the primary lumen is through at least one secondary lumen and one
tertiary lumen.
[0043] Referring now to FIG. 3, a further alternative embodiment of
the multi-lumen graft according to the invention is shown. The
structure of the graft is as described in the embodiment shown in
FIG. 1. In this embodiment, there are four secondary lumens 22
arranged concentrically about the primary lumen 10. Additionally, a
tertiary tubular body 24 is provided including an inner wall
surface 26 and an outer wall surface 28. The tertiary tubular body
24 is arranged about the secondary tubular body 16 in a partially
non-concentric manner so that a portion of the inner wall surface
26 of the tertiary tubular body 24 is in contact and made integral
with a portion of the outer wall surface 20 of the secondary
tubular body 16 by an adhesive 46. The portion of these walls that
are not in contact define a tertiary lumen 30. In this embodiment,
the secondary lumens 22 are arranged intermediate the primary lumen
10 and the tertiary lumen 30.
[0044] In this particular aspect of the invention, the tertiary
lumen, which is closest to the skin or access point, includes a
self-sealing material, while a secondary lumen, which is closer to
the primary lumen through which blood flows, may include a
self-sealing material and/or a physiologically or pharmacologically
active agent.
[0045] Referring to FIG. 7. a further alternative embodiment of the
multi-lumen graft according to the invention is shown. The
structure of the graft is as described in the embodiment shown in
FIG. 3. In the embodiment shown in FIG. 7, the secondary tubular
body 16 is attached to the tertiary tubular body 24 by at least one
rib 12.
[0046] It is to be understood that the arrangement of contacting
tubular bodies and tubular bodies connected by ribs may be used in
any appropriate combination. Thus, the tubular bodies may be
connected entirely by a ribbed connection, or entirely by
non-concentric wall surface contact or any combination thereof.
[0047] In one advantageous aspect, the primary lumen is of a
sufficient internal diameter (ID) to allow blood flow therethrough.
This means that the ID of the primary lumen will typically be from
about 3 mm to about 24 mm depending on the application.
[0048] The tubular structures of the present invention can be made
from any suitable biocompatible material that can be arranged to
form a microporous structure. Suitable materials include
polyimides, silicone, polyurethanes, polyurethane ethers,
polyurethane esters, polyurethane ureas, and mixtures and
copolymers thereof. Desirable materials include polyethylene
terephthalate (Dacron.TM. brand polyester), and other synthetic
polyester fibers such as mandrel spun polyurethane and silicone
elastomeric fibers. Particularly desirable polymeric materials
which are useful for this purpose include fluoropolymers, for
example, either expanded or unexpanded polytetrafluoroethylene
(PTFE). At least one of the tubular bodies is desirably made from
PTFE, more desirably at least the primary tubular body is formed
from ePTFE.
[0049] In one advantageous aspect of the invention, the materials
forming the lumens and ribs of the graft possess an intemodal
distance of from about 1 .mu.m to 200 .mu.m. Even more
advantageously, the internodal distance is from about 10 .mu.m to
100 .mu.m.
[0050] In one advantageous aspect, the inventive graft is made
using PTFE which possesses desirable porosity, radial tensile
strength, and resistance to tears at suture points. Advantageously,
at least the primary tubular body is formed of ePTFE having an
intemodal distance (IND) in excess of about 40 microns. Grafts
having IND's in this range generally exhibit long-term patency as
the larger pores promote formation of the intima layer along the
inner blood contacting surface. Tubes having an IND less than about
40 microns exhibit lesser healing characteristics, however offer
superior radial tensile strength and suture retention strength, and
are also within the scope of the invention.
[0051] The inner and outer tubular bodies of the present invention
may be formed by a variety of methods. For example, extrusion
processes such as ram extrusion; polymeric casting techniques such
as solvent casting and film casting; molding techniques such as
blow molding, injection molding and rotational molding; and other
thermoforming techniques useful with polymeric materials may be
employed and chosen to best serve the type of material used and
specific characteristics of the membrane desired.
[0052] One method for manufacturing porous PTFE tubing generally,
is described, for example, in U.S. Pat. No. 3,953,566, U.S. Pat.
No. 3,962,153, and U.S. Pat. No. 4,973,609, the entireties of which
are herein incorporated by reference. Generally, a PTFE tube may be
formed in four steps including preparation of a PTFE paste,
extrusion of a tube, expansion of the tube, and sintering of the
tube. Briefly, a PTFE paste dispersion is made for later extrusion
by admixing a fine, virgin PTFE powder such as F-104, F-103, Virgin
PTFE Fine Powder (Dakin America, Orangeburg, N.Y.) with a liquid
lubricant such as odorless mineral spirits or naphtha, i.e.,
Isopar.RTM. (Exxon Chemical Co., Houston, Tex.), to form a PTFE
paste of the desired consistency. The PTFE paste is either passed
through a tubular extrusion dye or coated onto a mandrel to form a
tubular extrudate. Next, the wet extrudate is dried to evaporate
the lubricant at either room temperature or temperatures near the
lubricant's dry point. After the PTFE resin or paste is formed and
dried, it is stretched and/or expanded. Stretching refers to
elongation of formed resin while expansion refers to enlargement of
the formed resin perpendicularly to its longitudinal axis. The
stretching/expansion step occurs at a temperature less than
327.degree. C., typically in the range of 250-326.degree. C. by an
expansion rate of at least two to one (2:1). Finally, the tubular
extrudate is sintered by heating it to a temperature of about
350-370.degree. C. This results in an amorphous locking of the
polymer.
[0053] The tubular bodies may be made integral at the rib apexes
and wall surface contact points or the contacting wall surfaces in
a variety of ways, depending on the particular materials which form
the tubular bodies. Generally, as best shown in FIGS. 1-4, the
primary and secondary tubular bodies 4 and 16 are laminated
together at their points of contact. Numerous techniques may be
employed to laminate or bond the primary tubular body 4 to the
secondary tubular body 16. Heat setting, adhesive welding,
application of uniform force and other bonding techniques known in
the art may all be employed to bond or secure the tubular bodies 4
and 16 at their points of contact, be they rib 12 apexes 14 or
contacting wall surfaces 8 and 18. In each of these bonding
techniques, it is contemplated that the points of contact be made
integral.
[0054] Alternatively, it is possible to form the tubular bodies
integrally during an extrusion process. In this case, desirably,
the mandrel, dye and mold for the graft are designed so as to
evenly distribute and form the PTFE paste into a desired shape and
to produce a graft having a uniform node and fibril structure
throughout the graft.
[0055] In one aspect of the invention, the tubular structures of
the present invention which includes a rib or ribs may be formed of
expanded PTFE by extrusion of a pre-formed PTFE structure having
the shape of the final graft. Extrusion is performed using dies
having the appropriate number of spacers to form the desired number
of ribs. FIG. 6 is a perspective view of an exemplary die 44,
corresponding to the illustrated graft of FIG. 1. The die 44 may be
manufactured from materials available and well known in the art. A
die mold in the form of a hollow cylinder (not shown) is placed
around the die and the extrudate forms the graft by passing
therethrough.
[0056] In grafts formed from ePTFE, the rate of stretching and the
stretch ratio affect the porosity of the finished product in a
predictable manner allowing a prosthetic device to be produced
having a specified porosity. The rate of stretching refers to the
percentage of elongation per second that the resin is stretched
while the stretch ratio refers to the relationship between the
final length of the stretched resin and the initial length of the
stretched resin. For example, stretching an extruded PTFE tube at a
stretch ratio of two to one and a stretch rate of sixty results in
a porosity of approximately 40. This porosity is a unit-less number
as determined in accord with the American Society For Testing of
Materials' (ASTM's) Special Technical Publication Number 898. For
example, based on stretch ratios ranging from two to one, to six to
one, a stretch rate of sixty percent per second yields a porosity
of between approximately 40 and approximately 90. A stretch rate of
one hundred and forty percent per second at this ratio yields a
porosity of between approximately 60 and approximately 85. Finally,
a stretch rate of nine hundred percent per second at this same
ratio yields a porosity of between approximately 65 and
approximately 85.
[0057] In addition to the intemodal distance and porosity, the
geometry of the node and fibril network of PTFE can be controlled
during stretching and expansion. In the case of uniaxial
stretching, that is, elongation of the formed PTFE resin along the
direction of extrusion, the nodes are elongated causing the longer
axis of each node to be oriented perpendicularly to the direction
of stretch. Accordingly, the fibrils are oriented parallel to the
direction of stretch. Biaxial stretching additionally includes
expanding the PTFE resin in the radial direction and can be
utilized to produce a prosthetic device having a composite
porosity. As in uniaxial stretching, the rate and ratio of radial
expansion affects the resulting porosity of the prosthetic
device.
[0058] In a particularly advantageous aspect of the invention, the
geometry of the node and fibril network of ePTFE includes nodes
oriented perpendicular to the direction of stretch. In a
particularly preferred aspect, the nodes are uniformly oriented
perpendicular to the direction of stretch.
[0059] In a further aspect of the present invention, one or more of
the secondary lumens desirably include a non-biodegradable
polymeric material which self-compresses after puncture by a needle
so as to seal the puncture site. This material serves a
self-sealing function in the graft of the present invention.
Desirably, the self-sealing material is biocompatible.
[0060] A number of different materials may serve as the
self-sealing polymeric material contemplated in the present
invention. Some materials which may be used as a self sealing
component in various forms include, but are not limited to,
polymers and copolymers, including thermoplastic elastomers and
certain silicones, silicone rubbers, synthetic rubbers,
polyurethanes, polyethers, polyesters, polyamides and various
fluoropolymers, including, but not limited to, PTFE, ePTFE, FEP
(fluorinated ethylene propylene copolymer), and PFA
(polyfluorinated alkanoate).
[0061] Furthermore, an exterior of the graft or a secondary lumen
may be coated with an elastomeric material such as fluorine rubber,
silicone rubber, urethane rubber, acrylic rubber or natural rubber
to perform the self-sealing function. Among the fluorine rubber
materials are a vinylidene fluoride/hexafluoropropylene copolymer,
a vinylidine fluoride/chlorotrifluoroethylene copolymer, and a
tetrafluoroethylene/pro- pylene copolymer.
[0062] Preferably, the self-sealing polymeric material is
crosslinked. For example, a fluorine rubber may be compounded with
an acid acceptor, a crosslinking agent, and if desired, a filler
before crosslinking. Examples of the acid acceptor are magnesium
oxide and calcium oxide. Examples of the crosslinking agent are
aliphatic polyamine derivatives, organic peroxides, and
isocyanates. A typical compounding composition includes 100 parts
by weight of a vinylidene fluoride/hexafluoropropylene copolymer,
15 parts of magnesium oxide, and 0.5 to 3 parts by weight of an
aliphatic polyamine derivative. Preferably, the material is in a
cross-linked state so as to prevent deterioration in the body.
[0063] The self-sealing material may be introduced into the graft
by adhering in a layer to at least one surface of the primary and
secondary tubular bodies. The adhesion may take place by mechanical
means, chemical means (use of an adhesive), thermobonding or
combinations thereof. Some polymers, particularly thermoplastic
elastomers, become sufficiently tacky through heating to adhere to
ePTFE tubular structures.
[0064] In use, the self-sealing component may function by exerting
a force in the direction of the puncture. If the self-sealing
material is adhered to both the primary and secondary tubular
bodies, then either layer or both will seal the puncture site.
[0065] It is further within the purview of the present invention to
include a flowable polymeric material as the self-sealing material.
The term flowable as used herein refers to an amorphous material
which fills a void created by a deformation or puncture.
[0066] A number of different flowable polymer layers may also be
employed in the secondary and/or tertiary lumens to provide a
self-sealing graft. The flowable polymer layer seals the graft by
possessing an amorphous quality which fills in any space left open
subsequent to puncture of the graft. It may simply fill in the
space left open or it may additionally penetrate into the punctured
secondary lumen to fill any void left from puncture of a tubular
body.
[0067] An example of a flowable polymer which may be used as the
self-sealing polymeric material in the present invention is an
uncured or partially cured polymer. The polymer may be cured by a
number of activating means which would activate curing subsequent
to puncture of the graft, thereby sealing with the curing of the
polymer. Examples of materials for such a flowable layer include,
but are not limited to, uncured elastomers such as natural or
synthetic rubbers, and natural gums such as gum arabic. Materials
that are particularly useful in a flowable layer include
non-crosslinked polyisobutylene which is also known as uncured
butyl rubber.
[0068] Another flowable polymer layer which may be employed in the
present invention is a gel. Gels are generally suspensions or
emulsions of polymers which have properties intermediate between
that of the liquid and solid states. A hydrogel may also be used in
the present invention, and refers to polymeric material which
swells in water without dissolving, and which retains a significant
amount of water in its structure. The gels and hydrogels employed
in the present invention may be biodegradable, or
non-biodegradable. They also further may have polymeric beads
suspended within the gel to effectuate sealing of the graft. Some
examples of gels which may be used in the present invention
include, but are not limited to, silicone gels, gum arabic, and low
molecular weight ethylene/vinyl acetate polymers.
[0069] Suitable gels further include hydrogels formed from natural
materials including, but not limited to, gelatin, collagen,
albumin, casein, algin, carboxy methyl cellulose, carageenan,
furcellaran, agarose, guar, locust bean gum, gum arabic,
hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose,
hydroxyalkylmethyl cellulose, pectin, partially deacetylated
chitosan, starch and starch derivatives, including amylose and
amylopectin, xanthan, polylysine, hyaluronic acid, and its
derivatives, their salts, and mixtures thereof.
[0070] In an advantageous aspect, a physiologically or
pharmacologically active agent may be coated or otherwise
incorporated into the graft according to the invention. Any drug or
bio-therapeutic agent may be coated onto a surface or incorporated
into a lumen of the graft of the present invention. Examples of
suitable drugs or bio-therapeutic agents may include, without
limitation, thrombo-resistant agents, antibiotic agents, anti-tumor
agents, cell cycle regulating agents, their homologs, derivatives,
fragments, pharmaceutical salts, and combinations thereof.
[0071] Useful thrombo-resistant agents may include, for example,
heparin, heparin sulfate, hirudin, chondroitin sulfate, dermatan
sulfate, keratin sulfate, lytic agents, including urokinase and
streptokinase, their homologs, analogs, fragments, derivatives and
pharmaceutical salts thereof.
[0072] Useful antibiotics may include, for example, penicillins,
cephalosporins, vancomycins, aminoglycosides, quinolones,
polymyxins, erythromycins, tetracyclines, chloramphenicols,
clindamycins, lincomycins, sulfonamides, their homologs, analogs,
fragments, derivatives, pharmaceutical salts and mixtures
thereof.
[0073] Useful anti-tumor agents may include, for example,
paclitaxel, docetaxel, alkylating agents including mechlorethamine,
chlorambucil, cyclophosphamide, melphalan and ifosfamide;
antimetabolites including methotrexate, 6-mercaptopurine,
5-fluorouracil and cytarabine; plant alkaloids including
vinblastine, vincristine and etoposide; antibiotics including
doxorubicin, daunomycin, bleomycin, and mitomycin; nitrosureas
including carmustine and lomustine; inorganic ions including
cisplatin; biological response modifiers including interferon;
enzymes including asparaginase; and hormones including tamoxifen
and flutamide; their homologs, analogs, fragments, derivatives,
pharmaceutical salts and mixtures thereof.
[0074] Useful anti-viral agents may include, for example,
amantadines, rimantadines, ribavirins, idoxuridines, vidarabines,
trifluridines, acyclovirs, ganciclovirs, zidovudines, foscarnets,
interferons, their homologs, analogs, fragments, derivatives,
pharmaceutical salts and mixtures thereof.
[0075] The agent may be provided in any of a variety of methods.
For example, it is possible to form the graft with monomers
including functional groups to which the agents will bind. The
graft can be dip coated with a mixture of a drug in an appropriate
buffer. After allowing the drug to react with the functional
groups, the graft may be dried. See the method as taught in U.S.
Pat. No. 6,358,557, for example. Alternatively, it is also possible
to use the porous nature of the graft material to hold therapeutic
agents therein. The therapeutic agent may be added to the graft by
addition of a therapeutic drug solution under pressure.
Furthermore, it may be possible to add a therapeutic agent
containing gel to one or more secondary lumens and to perforate
portions of the wall surfaces of the tubular bodies to create pores
for dispensing the gel slowly into the primary lumen or an exterior
of the graft over time.
[0076] Referring now to FIG. 4, a multi-lumen graft 2 according to
the invention includes a self-sealing polymeric material 32 in one
of the secondary lumens 22. Another of the secondary lumens 22
includes a first drug 34 for treating a patient intravenously. The
graft further includes secondary pores 38 arranged between a
secondary lumen 22 and the secondary tubular body 16. A further
drug 40 may be provided to a patient via the secondary pores 38. It
is to be understood that, although the self-sealing polymeric
material and the drugs are in separate lumens, it is also possible
for a single lumen to contain one or more drugs as well as the
self-sealing polymeric material. For example, it is possible to
coat a surface of a secondary lumen adjacent the primary lumen
surface with a material containing dissolvable time-released drug
in a lumen filled with a self-sealing gel. The timed-release drug
may enter the bloodstream while the self-sealing gel performs its
function. The timed release of the drug does not necessarily rely
on structural pores for drug delivery. It is possible for the drug
to penetrate the intact surface of the secondary lumen.
[0077] In a further aspect of the invention, the graft may further
include a support member such as a textile layer or sleeve on one
or more of an exterior or an interior of the graft. A suitable
textile for this purpose is a knit biocompatible material such as
polyester or polyethylene terephthalate (DACRON), for example.
Referring now to FIG. 5, a textile sleeve 42 is shown covering the
multi-lumen graft 2. The textile sleeve 42 serves to provide
additional strength to the implant, and/or to aid in resisting tear
from suture holes.
[0078] The graft according to the present invention may be used
advantageously, for example, in implanting a self-sealing graft
device to replace or augment part of an arteriovenous (AV) pathway
in an individual in need thereof. In the method, a surgeon or other
qualified person surgically exposes the desired region for
introduction of the graft of the invention. The desired site may be
an area of occlusion or weakness in the patient's arteriovascular
system, or the site for an AV bypass in a dialysis patient, for
example. An interruption of the patient's blood flow is performed,
and the device is surgically implanted and sutured or otherwise
secured in place so that blood flow is established through the
primary lumen. Once the graft is in place, the bloodstream can be
accessed by a cannula, intravenous needle or the like through a
secondary lumen. When the cannula or needle is withdrawn, the
self-sealing elastomeric material on the secondary lumen will block
access of blood to the puncture hole created by the needle, thus
preventing blood from escaping from the area of access.
[0079] The grafts of the present invention are particularly suited
for use as AV bypasses for dialysis patients. The graft will be
resistant to leaks at suture holes because many of the suture holes
will be formed through the secondary lumens containing the
self-sealing material. This will allow use of the implant without
having to wait extended periods of time to heal suture hole leaks.
Further, even after repeated access to the device by a large bore
needle, the implant will resist leakage of blood from the primary
lumen. Additionally, if a drug delivery aspect is included in the
graft, appropriate therapeutic drugs will be available at the site
of injury to facilitate fast and reliable healing.
[0080] The invention may be embodied in other specific forms
without departing from the spirit of essential characteristics
thereof. The present embodiments are therefore to be considered in
all respects as illustrative and not restrictive, the scope of the
invention being indicated by the appended claims rather than by the
foregoing description, and all changes which come within the
meaning and range of equivalency of the claims are therefore
intended to be embraced therein.
* * * * *