U.S. patent application number 10/206620 was filed with the patent office on 2004-01-29 for sectional crimped graft.
This patent application is currently assigned to SCIMED Life Systems, Inc.. Invention is credited to Casey, Thomas V. II, Nelson, Kristoff, Quigley, Fergus.
Application Number | 20040019375 10/206620 |
Document ID | / |
Family ID | 31186631 |
Filed Date | 2004-01-29 |
United States Patent
Application |
20040019375 |
Kind Code |
A1 |
Casey, Thomas V. II ; et
al. |
January 29, 2004 |
Sectional crimped graft
Abstract
The present invention provides a sectional crimped graft that
allows graft flexibility where required and limits the overall
longitudinal extension. The present invention overcomes the
disadvantage of fully crimped grafts by controlling the number of
crimps per unit length, crimp height, crimp geometry and their
location along the graft wall, dependent on the particular end-use
application. In so doing, flexibility and elongation can be
controllably tailored only in areas where significant anatomical
angulation is present. It may also be useful in applications other
than stent grafts such as surgical grafts for aortic and peripheral
areas. Limiting the overall graft longitudinal extension also
facilitates the deployment of the stent-graft into the blood
vessel.
Inventors: |
Casey, Thomas V. II;
(Grafton, MA) ; Nelson, Kristoff; (Boston, MA)
; Quigley, Fergus; (Watertown, MA) |
Correspondence
Address: |
HOFFMANN & BARON, LLP
6900 JERICHO TURNPIKE
SYOSSET
NY
11791
US
|
Assignee: |
SCIMED Life Systems, Inc.
|
Family ID: |
31186631 |
Appl. No.: |
10/206620 |
Filed: |
July 26, 2002 |
Current U.S.
Class: |
623/1.28 ;
264/299; 623/903 |
Current CPC
Class: |
A61F 2/07 20130101; A61F
2/06 20130101; A61F 2/89 20130101 |
Class at
Publication: |
623/1.28 ;
264/299; 623/903 |
International
Class: |
A61F 002/06 |
Claims
What is claimed is:
1. An implantable tubular graft useful to repair or replace a body
passageway comprising: a generally tubular graft having inner and
outer walls and having first and second open ends; a central
portion longitudinally extending between said ends; and the walls
having crimps located only along a portion of their length.
2. The tubular graft of claim 1, wherein the crimps are located
along one or more portions of their length.
3. The tubular graft of claim 1, wherein the crimps are generally
in wave-like pattern.
4. The tubular graft of claim 1, wherein section of the crimps are
of uniform length.
5. The tubular graft of claim 1, wherein section of the crimps are
of variable length.
6. The tubular graft of claim 1, wherein the crimps are of uniform
height.
7. The tubular graft of claim 1, wherein the crimps are of variable
height.
8. The tubular graft of claim 1, wherein at least a portion of said
crimps does not share a common trough formed by adjacent peaks.
9. The tubular graft of claim 1, wherein the crimps are located
between the first and second open ends.
10. The tubular graft of claim 1, wherein the crimps are located
proximal to the first and second open ends.
11. The tubular graft of claim 1, wherein at least one said open
end is mounted over an expandable stent.
12. The tubular graft of claim 1, wherein said graft is mounted
over an expandable stent.
13. The tubular graft of claim 11, wherein said graft and
expandable stent are loaded in a catheter.
14. An implantable tubular graft useful to repair or replace a body
passageway comprising: a generally tubular graft having inner and
outer walls and having first and second open ends; a central
portion longitudinally extending between said ends; and the walls
having one or more individual crimps located along its length,
wherein said individual crimps do not share a common trough formed
by adjacent peaks.
15. A method of producing a partially crimped implantable graft
comprising: providing an elongate tubular textile graft having a
first end and a second open end defining a fluid passageway
therethrough; placing at least a portion of the graft over a
mandrel having a grooved or corrugated surface which serves as a
template for forming crimps; and conforming a portion of the graft
to said mandrel shape to effectuate crimps in said portion of the
graft.
16. The method of claim 15, wherein the grooved or corrugated
surface comprise individually annular ribs or rings.
17. The method of claim 16, wherein the individual annular ribs or
rings comprise sections of uniform length, to thereby effectuate
section of the crimps to be of uniform length in said portion of
the graft.
18. The method of claim 16, wherein the individual annular ribs or
rings comprise sections of variable length to thereby effectuate
section of the crimps to be a variable length in said portion of
the graft.
19. The method of claim 16, wherein the individual annular ribs or
rings are of uniform height to thereby effectuate section of the
crimps to be of uniform height in said portion of the graft.
20. The method of claim 16, wherein the individual annular ribs or
rings are variable height to thereby effectuate section of the
crimps to be of variable height in said portion of the graft.
21. The method of claim 16, wherein the individual annular ribs or
rings are spaced apart to thereby effectuate crimps to be spaced
apart from each other in said portion of the graft.
22. A method of implanting a graft device within a body lumen,
comprising: providing a longitudinal extending tubular graft of
original length, having opposing ends defining a fluid passageway
therethrough and having variable crimps located along only a
predetermined portion of its length; positioning the graft device
about a catheter and deploying said graft within a body vessel; and
allowing said graft to radially expand to contact a body lumen
wall.
23. The method of claim 22, further comprising positioning a stent
about at least a portion of the graft to form a graft device; said
stent and graft being in a longitudinally stretched low profile
state for insertion into the body, thereby increasing the original
length of the graft.
24. The method of claim 23, further comprising deploying said graft
to permit radial expansion and to bring the graft to its
approximate original length.
Description
FIELD OF THE INVENTION
[0001] The present invention relates generally to a vascular
prosthesis for repair or replacement of a blood vessel. More
particularly, the present invention provides a sectionally crimped
vascular graft for repair of damaged or diseased sections of blood
vessels, which can be used alone or in combination with a stent to
form a stent-graft device.
BACKGROUND OF THE INVENTION
[0002] Vascular grafts are well known to repair or replace the
damaged or diseased portions of body vessels such as blood vessels.
It has been a common practice to install crimps in a graft by fully
crimping the graft. Crimping provides several advantages. For
example, textile grafts are much easier for the surgeon to handle
once crimped, because crimping provides a self-supporting feature
and keeps the lumen of the graft open during implementation.
Additional crimping can provide for increased flexibility and
longitudinal extension and contraction, where needed. See U.S. Pat.
No. 4,047,252 to Liebeg et al. In certain applications, however,
flexibility is desired but significant longitudinal extension is
not. Additionally, due to the use of stents in combination with
grafts as composite devices, the need for full-length crimping to
keep the lumen open during implantation is lessened.
[0003] In certain applications, such as endoluminal stent-graft
devices used in thoracic, abdominal or peripheral applications, it
is disadvantageous to have excessive extension subsequent to
implantation. Additionally, use of a "fully crimped" graft on a
thoracic stent-graft has identified issues with graft elongation
within the deployment sheath causing the graft to not fully recover
to its original unloaded length. This is particularly apparent when
fully crimped grafts are used in devices which allow the flow of
arterial blood pressure to be the force which opens the graft
lumen. See U.S. Pat. No. 5,697,970 to Schmitt et al. and U.S. Pat.
No. 5,476,506 to Lunn. Fully crimped grafts have a significant
degree of unwanted elongation extension therefore creating
difficulty during deployment. The graft is delivered in the
compressed state in an elongated fashion with a stent. The stent
can easily return to its original length due to shape memory
properties, but the graft cannot. When full graft length recovery
is required, herein lies the problem. The graft expands with the
stent at each end of the graft, but due to crimping along its
entire length, the graft does not recover to its original length
during deployment. Thus, prior devices have not provided a solution
which balances the need to accommodate vessel angulation
flexibility and to facilitate deployment with the need to minimize
longitudinal extension.
[0004] It is, therefore, desireable to provide a crimped graft
which allows flexibility only where needed, i.e., only use crimping
where needed, thereby minimizing undesirable longitudinal extension
and requiring less recovery during deployment.
SUMMARY OF THE INVENTION
[0005] The present invention provides a sectional crimped graft
that allows graft flexibility only where required and thus limits
the overall longitudinal extension. The present invention overcomes
the disadvantage of fully crimped grafts by controlling the number
of crimps per unit length, crimp height, crimp geometry and their
location along the graft wall. In so doing, flexibility and
elongation can be controllably tailored only in areas where
significant anatomical angulation is present. It may also be useful
in applications other than stent grafts such as surgical grafts for
abdominal and peripheral areas. Limiting the overall graft
longitudinal extension also enhances the deployment of the
stent-graft into the blood vessel.
[0006] In accordance with one embodiment of the present invention,
crimps are installed only in pre-determined, intermittent locations
along the length on the graft. One advantage obtained thereby is to
provide needed flexibility to a specific location. Such a graft
structure is particularly useful in thoracic stent-graft devices,
where a .gtoreq.90 degree bend may be present in the treated
thoracic aorta. In addition, by minimizing the number of crimps on
the graft, the excessive longitudinal extension of the graft is
also greatly reduced.
[0007] In accordance with another embodiment of the present
invention, various factors of crimps on the graft can be varied
depending on the desired characteristics for a specific graft
application. Such factors are the height of the crimps, the length
of the crimped section, i.e., the number of crimps, and the
profile, i.e. the cross-sectional geometry of the crimps. The
greater the crimp height and the more crimps, the more the
elongation of the graft. The elongation can be reduced by reducing
the number of crimps per unit length, reducing the height of the
crimps and changing their profile. So, depending on the
characteristics or diameter of the body or blood vessel, the degree
of the crimping can be varied to provide a better fit to the
contour of the vessel wall, provide variable flexibility to better
accommodate tortuous anatomy, and reduce graft extensioning.
[0008] In accordance with further embodiment of the present
invention, there is provided a graft having sections of crimps
along its full length fully-crimped graft, however the degree of
crimping varies upon its length to correspond with expected
vascular angulation. Certain sections are individual crimps which
do not have a common trough formed by their respective adjacent
peaks.
[0009] In accordance with even further embodiment of the present
invention, a method for producing a graft crimped only partially
along its length is provided. The method includes providing an
elongate tubular graft having opposing ends defining a fluid
passageway therethrough; providing a mandrel comprising individual
annular ribs or rings in specific locations; placing a
predetermined portion of the graft over the crimp geometry-forming
mandrel; applying a mechanical or thermal energy, i.e., mechanical
force, fluid pressure, heat, heat and pressure combined, on the
predetermined portion to impose the pattern. Desirably, the shape
of predetermined portion of the graft is heat-set prior to removing
the graft from the mandrel to provide a partially crimped graft
product. In one particularly desirable method, the crimps are
formed using a heat shrink tube disposed about the graft, which
upon subjection to heat shrinks to apply sufficient pressure to the
graft such that the crimp geometry is formed in accordance with the
underlying mandrel pattern. In a further embodiment, a mechanical
roller or similar device is used to impress the graft into the
underlying mandrel pattern, thereby forming the mandrel pattern
imprint on the graft wall.
[0010] In accordance with even further embodiment of the invention,
a method of implanting a graft within a body lumen is provided. The
method includes providing a longitudinal extending tubular graft
having opposing ends with variable crimps located at a
predetermined location along a portion of its length and having at
least one attachment thereabout to form a stent-graft; delivering
the stent-graft to a predetermined position within a body lumen;
permitting the graft to radially expand and contact the inner wall
of the body lumen. Secondly, the stent-graft has associated with it
at least one stent, positioned proximal to the proximal graft
end.
BRIEF DESCRIPTION OF DRAWINGS
[0011] FIG. 1 is an illustration of crimps installed in specific
areas of the graft of the present invention.
[0012] FIG. 2 is an illustration of various sectional crimp grafts
with uniform crimp height of the present invention.
[0013] FIG. 3 is an illustration of various sectional crimp grafts
of variable crimp heights of the present invention.
[0014] FIG. 4 is an illustration of various combinations of
sectional crimp grafts with varying crimp amplitude, frequency and
profile in accordance with the present invention.
[0015] FIG. 5 is an illustration of a graft having sections of
crimps along its full length in accordance with the present
invention. Certain sections are shown where individual crimps do
not have a common trough formed by their respective peaks.
[0016] FIG. 6 is an illustration of stent-graft assembly for
implantation within a body lumen.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0017] Referring now to FIG. 1, one aspect of the present invention
is provided. Stent-graft 10 is an elongate generally tubular body,
desirably a thin walled hollow cylinder 11 having opposed-stent
ends, a first open-stent end 12 and a second open end 13. The graft
is divided into end portions 14 and 15 adjacent open-stent ends 12
and 13, respectively. The graft 10 has central portion 16 extending
longitudinally between the end portions 14 and 15.
[0018] Crimps 17 are incorporated in graft 10, extending from the
first end portion 14 towards the central portion 16. Crimps 18 are
incorporated on the other side of the graft extending from the
second end portion 15 towards the central portion 16. Crimping in
the manner shown in FIG. 1 is one example of crimping only on those
areas of the graft where flexibility is required. In FIG. 1, the
flexibility is needed on the portion that is to be bent or used at
a particular angle or curvature. Since this type of flexibility is
not required on other portions of the graft, the rest of the graft
need not be crimped, avoiding excessive longitudinal graft
extension. Alternatively the reduction in crimping height or number
of crimps along the graft length also reduces excessive extension
of the graft. Limiting the overall graft longitudinal extension
facilitates the deployment of catheter into the blood vessel by
reducing the potential for graft catching a stent frame. Moreover,
because the graft may be used with a stent to form a stent-graft
device, crimps along the full length of the graft for the purpose
of facilitating handling by the surgeon is not necessary.
[0019] It is to be understood that while the exemplified embodiment
has been illustrated with specific geometry, a wide variation is
possible within the broad teachings of this invention. A few
examples of variations of crimping are illustrated in FIG. 2. FIG.
2 shows several of many possible sectional crimped graft designs
with uniform crimp heights, simply illustrating that flexibility to
compress and expand has been provided only where needed and
minimizing the longitudinal extension.
[0020] Moreover, the height and linear density of the crimps may be
varied depending on the desired characteristics for a specific
graft application. FIG. 3 shows several non-limiting designs of
variable crimp-heights in accordance with the present invention.
The advantages to varying the height are that it minimizes
excessive longitudinal graft extension and at the same time
provides variable flexibility to better negotiate difficult
anatomical bends. Height also determines degree of elongation.
[0021] The diameter of the grafts of the present invention may
preferably be between the ranges of 3-48 mm. The frequency/length,
i.e., number of crimps per a given length may vary. For example,
about 1 to about 42 crimps per cm may be employed. Desirably about
6 to about 12 crimps per cm may be employed. The height of the
crimps may be in the range of 0.5-1.5 mm, preferably between
0.25-0.5 mm. The length of the crimps along the graft may be in the
range of 5 mm-200 mm preferably between 20 mm-150 mm. The spacing
between the crimps may preferably be in the range of anywhere from
1 mm to 100 mm preferably between 10 mm-30 mm.
[0022] FIG. 4a shows combinations of sectional crimp grafts designs
with several varying factors of the crimps on the graft. Such
designs include crimps having variable and uniform crimp height,
variable number of crimps per unit length, thereby illustrating
that any combination of the graft designs is possible depending on
the flexibility required to negotiate tortuous anatomical bends,
while minimizing elongation.
[0023] FIG. 4b illustrates a sectional crimp graft design with
separate individual crimps with spaces between each other. Certain
sections are individual crimps which do not have a common trough
formed by their respective adjacent peaks. Again, this particular
graft design portrays that the degree or level of flexibility can
be varied based on the physical characteristics of the damaged or
diseased portion of the blood vessel.
[0024] FIG. 5 shows a graft having sections of crimps along its
full length fully crimped graft in accordance with a preferred
embodiment of the present invention. The degree of crimping varies
upon its length to correspond with expected vascular angulation.
For instance, crimps may be of uniform and variable height and
length. The crimps may also preferably be individual crimps spaced
apart from each other which do not have a common trough formed by
their respective adjacent peaks.
[0025] Having described the sectional crimped graft of the present
invention, its construction and manufacture will now be discussed.
As noted, the grafts of the present invention may be constructed of
a variety of materials. Such materials maybe in form of films and
yarns, woven, knitted, braided or extruded material. Textile
materials are specifically useful in vascular graft applications,
in that textile pattern of the material can be constructed to be
very thin and pliable and also capable of permitting sufficient
ingrowth of surrounding tissue, while also being capable of
maintaining a fluid-tight, i.e. low porosity blood-tight wall
structure. The textile graft is desirably a woven material, and can
be flat woven using any known weave pattern. The wall of the graft
may be any conventional useful thickness, for example, 0.10 mm to
about 0.75 mm, but is desirably no greater than about 1.0 mm.
Moreover, any type of textile material suitable for use in the body
can be used as the yarns or fibers of the present invention.
Synthetic materials include a variety of polymers including, but
not limiting to, polyesters, polypropylenes (PP), polyethylenes
(PE), polyurethanes (PU), polytetrafluoroethylenes (PTFE) and
mixtures thereof. Polyethylene terephthalate (PET) is particularly
useful.
[0026] Woven tubular textile products are particularly useful in
manufacturing vascular grafts in variety of shapes and sizes. After
the graft is woven, a predetermined portion of the graft may then
be subjected to one or more crimping process. In one aspect of the
invention the graft is placed on a mandrel having a grooved or
corrugated surface therein. The grooved surface is a series of
individual annular ribs or rings in specific locations. These ribs
or rings supply the template by which the crimps in the graft wall
are formed. The predetermined portion of the graft is then placed
over the crimp geometry forming mandrel and forced into the groove
by mechanical or fluid force and cause the graft wall to assume the
mandrel's groove shape, thereby forming annular crimps in the graft
wall. The graft may preferably be heated to set the desired crimp
pattern, which maybe varying from about 10 to 30 crimps per inch of
longitudinal graft length. Alternate such grooves or crimps are
shown in U.S. Pat. Nos. 5,697,970 and 5,476,506, the contents of
all of which are incorporated herein by reference.
[0027] The amplitude (height) of the crimping and the number of
crimps is determined based on the body lumen be longitudinally
stretched so as to conform to that portion of the body lumen. The
degree of crimping is varied in the graft to accommodate the
curvature in the aortic arch ranging from about 30.degree. to about
180.degree. angles. The specific portions of the graft to be
crimped are also chosen. For instance, if in using the graft a
.gtoreq.90 degree angulation is anticipated, crimping need only be
incorporated on that portion of the graft where the bending will
take place, providing greater flexibility only where required. In
other words, crimping is formed only as required at portions of the
graft to yield flexibility with conformance to the body. Crimping
is also formed as required to provide longitudinal extension to
permit loading of the graft for delivery as will be described in
detail below.
[0028] Referring to FIG. 6, illustrated therein schematically is a
stent-graft of the present invention at a preloaded stage for
deployment into a vascular vessel. Stent 61 is disposed within and
preferably attached to end portions 14 and/or 15 of graft 10. A
stent 61 can alternatively be constructed as lining within a graft
(not shown) extending from one end of the graft to the other to
provide both fastening of the graft to the stent and additionally
structural stability.
[0029] The partially crimped graft of the present invention, graft
10, preferably with the end portions 14 and 15 affixed to stent 61,
is positioned on a catheter 62 to be delivered endoluminally.
During delivery or deployment, the stent-graft 10 stretches
longitudinally to provide an open lumen and maintains its
flexibility. As opposed to fully crimped grafts, which do return to
their original length, the grafts of the present invention more
readily return to their original length, thereby permitting
longitudinal flexibility where required, while maintaining
structural integrity for long term patency. For example, graft's
original length will be at 100% at a relaxed state, which is the
pre-loaded stage, as shown in FIG. 6. Upon delivery of the
prostheses, i.e. stent-graft assembly, the graft's length may
stretch longitudinally, in the range of 150%-250% and then once the
graft is delivered within the body vessel, it is released,
preferably the graft's length will come back to its original
position, which may vary up to 100% of its original length.
[0030] Various methods of deployment of the graft of the present
invention into a vascular vessel of a patient. One such method is
by mounting the stent-graft device on a balloon catheter. The
balloon is then expanded to expand the stent, and trap and/or
sandwich the end portions of the graft between the expanded stent
and the wall of the healthy portion of the vessel. Then the balloon
is deflated and catheter removed from the patient, thereby
releasing said stent-graft assembly in place.
[0031] Another method is due to the utilization of self-expanding
stents which are generally made of nitinol, which has the ability
to perform well while both in spring-like mode, as well as in a
memory mode based on temperature and processing. A stent is
disposed within the graft, preferably at the open ends of the
graft. The self-expanding stents which have spring-like action will
cause the stent to radially expand or stents which expand upon
increase in temperature due to the memory imparted properties of
the stent material, such as nitinol. When such self-expanding
stent-graft is deployed within the blood vessel, the stent expands
so as to expand the graft into contact with the lumen to be
repaired, and further securely anchor the graft in place to prevent
the movement of the prosthesis once properly implanted.
[0032] Another method is the utilizing of a sheath. The graft/stent
assembly is disposed within a tubular sheath having a longitudinal
bore, which holds the graft and stents in a compressed condition so
that it may be smoothly delivered intraluminally via the delivery
catheter. Once properly located, the sheath is retracted and the
graft is removed from the sheath, which permits the stents to
expand, thereby opening the graft so it substantially conforms to
the interior wall of a lumen.
[0033] The stent may be made from a variety of materials including
stainless steel, titanium, platinum, gold and other bio-compatible
metals. Thermoplastic materials which are inert in the body may
also be employed. Alternatively, thermoplastic materials that
exhibit known controlled degradation (biodegradable) are useful
stent materials. Shaped memory alloys having super elastic
properties generally made from specific ratios of nickel and
titanium, commonly known as nitinol, are among the preferred stent
materials.
[0034] Various stent types and stent constructions may be employed
in the invention. Among the various stents useful include, without
limitation, self-expanding stents and balloon expandable extents.
The stents may be capable of radially contracting, as well and in
this sense can best be described as radially distensible or
deformable. Self-expanding stents include those that have a
spring-like action which causes the stent to radially expand, or
stents which expand due to the memory imparted properties of the
stent material for a particular configuration at a certain
temperature. Nitinol is one material which has the ability to
perform well while both in spring-like mode, as well as in a memory
mode, based on temperature and processing. Other materials are of
course contemplated, such as stainless steel, platinum, gold,
titanium algiloy and their combinations (e.g.: gold coat, sterling
silver, or gold/platinum cored nitinol, and other biocompatible
metals, as well as polymeric stents).
[0035] The configuration of the stent may also be chosen from a
host of geometries. For example, wire stents can be fastened into a
continuous helical patterns, with or without a wavelike or zig-zag
in the wire, to form a radially deformable stent. Individual rings
or circular members can be linked together such as by struts,
sutures, welding or interlacing or locking of the rings to form a
tubular stent. Tubular stents useful in the present invention also
include those formed by etching or cutting a pattern from a tube.
Such stents are often referred to as slotted stents. Furthermore,
stents may be formed by etching a pattern into a material or mold
and depositing stent material in the pattern, such as by chemical
vapor deposition or the like.
[0036] Moreover, it is anticipated that graft 10 can be partially
or wholly coated with natural coatings, or synthetic coatings,
hydrophilic or drug delivery-type coatings which facilitate
long-term healing of diseased vessels. Such a coating is preferably
bioabsorbable, and is preferably a therapeutic agent or drug,
including, but not limited to, anti-thrombogenic agents (such as
heparin, heparin derivatives, urokinase, and PPack
(dextrophenylalanine proline arginine chloromethylketone));
anti-proliferative agents (such as enoxaprin, angiopeptin, or
monoclonal antibodies capable of blocking smooth muscle cell
proliferation, hirudin, and acetylsalicylic acid);
anti-inflammatory agents (such as dexamethasone, prednisolone,
corticosterone, budesonide, estrogen, sulfasalazine, and
mesalamine); antineoplastic/antiproliferativ- e/anti-miotic agents
(such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine,
vincristine, epothilones, endostatin, angiostatin and thymidine
kinase inhibitors); anesthetic agents (such as lidocaine,
bupivacaine, and ropivacaine); anti-coagulants (such as
D-Phe-Pro-Arg chloromethyl keton, an RGD peptide-containing
compound, heparin, antithrombin compounds, platelet receptor
antagonists, anti-thrombin antibodies, anti-platelet receptor
antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors
and tick antiplatelet peptides); vascular cell growth promotors
(such as growth factor inhibitors, growth factor receptor
antagonists, transcriptional activators, and translational
promotors); vascular cell growth inhibitors (such as growth factor
inhibitors, growth factor receptor antagonists, transcriptional
repressors, translational repressors, replication inhibitors,
inhibitory antibodies, antibodies directed against growth factors,
bifunctional molecules consisting of a growth factor and a
cytotoxin, bifunctional molecules consisting of an antibody and a
cytotoxin); cholesterol-lowering agents; vasodilating agents; and
agents which interfere with endogenous vascoactive mechanisms.
While the foregoing therapeutic agents have been used to prevent or
treat various conditions, they are provided by way of example and
are not meant to be limiting, as other therapeutic drugs may be
developed which are equally applicable for use with the present
invention.
[0037] While the invention has been described by the foregoing
detailed description and the drawings in relation to the preferred
embodiments, it will be understood by those skilled in the art that
various changes may be made without deviating from the spirit and
scope of the invention.
* * * * *