U.S. patent application number 11/337494 was filed with the patent office on 2006-06-08 for treated medical implant.
This patent application is currently assigned to Boston Scientific Scimed, Inc.. Invention is credited to Leo Klisch, Steven Spencer.
Application Number | 20060122698 11/337494 |
Document ID | / |
Family ID | 34633791 |
Filed Date | 2006-06-08 |
United States Patent
Application |
20060122698 |
Kind Code |
A1 |
Spencer; Steven ; et
al. |
June 8, 2006 |
Treated medical implant
Abstract
A treated medical device is provided. This medical device may be
a stent and may have been treated by placing it into a treatment
chamber, creating a buffer zone of compressible fluid between the
medical implant and the inside surface of the treatment chamber,
and applying a treatment to the medical implant when the medical
implant is at least partially positioned within the treatment
chamber. When the treatment is applied to the medical implant this
may include forcing therapeutic out of an injection nozzle and
towards the medical device. In some instances the buffer zone of
compressible fluid may cause the medical implant to rotate about a
longitudinal axis in a first direction when the medical implant is
at least partially positioned within the treatment chamber.
Inventors: |
Spencer; Steven;
(Minneapolis, MN) ; Klisch; Leo; (Maple Grove,
MN) |
Correspondence
Address: |
KENYON & KENYON LLP
1500 K STREET N.W.
SUITE 700
WASHINGTON
DC
20005
US
|
Assignee: |
Boston Scientific Scimed,
Inc.
|
Family ID: |
34633791 |
Appl. No.: |
11/337494 |
Filed: |
January 24, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10728751 |
Dec 8, 2003 |
6997989 |
|
|
11337494 |
Jan 24, 2006 |
|
|
|
Current U.S.
Class: |
623/1.46 |
Current CPC
Class: |
A61F 2250/0067 20130101;
A61F 2/0077 20130101; B05C 3/09 20130101; A61F 2310/0097 20130101;
B05D 1/22 20130101; B05C 3/109 20130101; B05D 1/002 20130101 |
Class at
Publication: |
623/001.46 |
International
Class: |
A61F 2/06 20060101
A61F002/06 |
Claims
1. A medical implant that has been treated by a method comprising:
placing the medical implant into a treatment chamber having an
inside surface, the inside surface defining the treatment chamber;
creating a buffer zone of compressible fluid between the medical
implant and the inside surface of the treatment chamber when the
medical implant is at least partially positioned within the
treatment chamber; and applying a treatment to the medical implant
when the medical implant is at least partially positioned within
the treatment chamber.
2. The medical implant of claim 1 wherein applying the treatment to
the medical implant includes forcing therapeutic out of an
injection nozzle and towards the medical device.
3. The medical implant of claim 1 wherein the treatment is a
therapeutic.
4. The medical implant of claim 1 wherein the buffer zone of
compressible fluid causes the medical implant to rotate about a
longitudinal axis in a first direction when the medical implant is
at least partially positioned within the treatment chamber.
5. The medical implant of claim 4 wherein the buffer zone of
compressible fluid causes the medical implant to rotate in a second
direction after rotating in the first direction, the second
direction opposite to the first direction.
6. The medical implant of claim 1 wherein the method of treating
the implant further comprises: heating the medical implant after it
has been treated.
7. The medical implant of claim 1 wherein the treatment chamber
that the medical implant is placed into includes a set of fluid
passages to circulate compressible fluid within the treatment
chamber.
8. The medical implant of claim 1 wherein the medical implant
comprises an expandable lattice.
9. The medical implant of claim 1 wherein the method of treating
the implant further comprises: moving the medical implant from a
first position within the treatment chamber to a second position
within the treatment chamber.
10. The medical implant of claim 1 wherein the buffer zone of
compressible fluid prevents contact between the medical implant and
the treatment chamber when the medical implant is positioned within
the treatment chamber.
11. The medical implant of claim 1 wherein another medical device
is already positioned within the treatment chamber when the medical
implant is positioned within the treatment chamber.
12. The medical implant of claim 1 wherein the method of treating
the implant further comprises: discarding the treatment chamber
after the medical device is removed from the treatment chamber.
13. The medical implant of claim 1 wherein the treatment chamber
that the medical device is positioned within defines a cylinder.
Description
RELATED APPLICATIONS
[0001] The present application claims the benefit of priority of
U.S. patent application Ser. No. 10/728,751, filed Dec. 8,
2003.
FIELD OF THE INVENTION
[0002] The present invention is directed to a medical implant that
has been treated in a treatment chamber. More specifically, the
present invention is directed to a medical implant that has been
treated by using a cushion of compressible fluid to levitate the
medical implant in a treatment chamber as the implant is treated in
the chamber.
BACKGROUND
[0003] The positioning and deployment of therapeutic laden implants
at a target site inside the body of a patient is an often repeated
medical procedure. The benefits and purposes of delivering and
placing implants and therapeutics at a target site in the body of a
patient are innumerable and can include enlarging constricted
lumens, reinforcing recently re-enlarged lumens, replacing ruptured
vessels, and treating designated regions, systems, and areas with
therapeutic.
[0004] The vessels, lumens, and other target sites, which can be
treated by implants alone or implants combined with therapeutics,
may be located throughout the body and can include the coronary
vasculature, the esophagus, the trachea, the colon, the biliary
tract, the urinary tract, the prostate, the brain, and the various
other organs. Examples of implants that have been used in these or
other applications include vena cava filters, stents, stent-grafts,
vascular grafts, and intraluminal paving systems.
[0005] Implants used in these and other procedures may have the
therapeutic positioned on their outside surface, their inside
surface, and imbedded or otherwise carried by or within the
material that comprises the implants. Moreover, these implants may
also have been coated with a polymer or other material. The present
invention is directed to new and inventive methods, systems, and
apparatus for coating or otherwise interfacing medical implants,
such as expandable stents, with therapeutics, coatings or both.
BRIEF DESCRIPTION
[0006] A medical implant processing chamber and systems and methods
of processing a medical implant as well as medical implants
processed in accord with these methods are provided in the various
embodiments of the present invention. These embodiments include a
vessel having a treatment chamber with an inside surface, an
outside surface, an entrance, a plurality of fluid passages passing
from the outside surface to the inside surface, and a compressible
fluid supply line coupled to at least one of the fluid passages. In
this embodiment, the passages may be positioned and sized to create
a buffer zone of compressible fluids between the inside surface of
the treatment chamber and a medical implant placed therein.
Embodiments of the present invention also include placing a medical
implant into a treatment chamber, obstructing the medical implant
from contacting the inside surfaces of the treatment chamber by
injecting compressible fluid into the treatment chamber, injecting
a therapeutic into the treatment chamber, and removing the medical
implant after it has been processed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] FIG. 1 is a side view of a treatment chamber in accord with
an embodiment of the present invention.
[0008] FIG. 2 is a sectional view taken along line 2-2 of FIG.
1.
[0009] FIG. 3 is a side view of a treatment chamber in accord with
another embodiment of the present invention.
[0010] FIG. 4 is side view of a treatment chamber in accord with
another embodiment of the present invention.
[0011] FIG. 5 is a sectional view taken along line 5-5 of FIG.
4.
[0012] FIG. 6 is a sectional view taken along line 6-6 of FIG.
4.
[0013] FIG. 7 is a side view of a treatment chamber in accord with
another embodiment of the present invention.
[0014] FIG. 8 is a side view of a treatment chamber in accord with
another embodiment of the present invention.
DETAILED DESCRIPTION
[0015] FIG. 1 is a side view of a treatment chamber 10 in accord
with an embodiment of the present invention. In this embodiment,
the treatment chamber 10 includes an outer wall 12 and end plates
11. The outer wall 12 may include a plurality of fluid passages 13
that may be designed and sized to allow compressible fluids, such
as air, nitrogen, carbon dioxide, and other compressible gases, to
pass from outside the outer wall 12 to inside the outer wall 12
and, consequently, into the chamber 10. The end plates 11 in this
embodiment may include exhausts 18, which may be sized and designed
to allow compressible fluid entering the treatment chamber 10 to be
exhausted from the chamber 10. The end plates 11 may be rotatably
coupled to the chamber wall 12 such that they may swing away from
the chamber 10 to allow an implant 14 to be placed within the
chamber 10 for treatment. Arrow 17 indicates the rotational
movement of the end plates 11.
[0016] As indicated above, when end plate 11 is in an open position
an implant 14 may be placed in the treatment chamber 10 in the
direction of arrow 16. Once the implant 14 has been placed within
the chamber, it may then be treated, coated or otherwise interfaced
with a therapeutic or other material. Once the implant 14 has been
interfaced with the therapeutic or other material, it may exit the
treatment chamber 10, in the direction of arrow 15, after the end
plate 11 has been swung away and opened. Once the implant has been
treated and removed, another implant may be placed in the chamber
for its own treatment. This treatment cycle may be repeated as
necessary. Alternatively, the treatment chamber 10 may be designed
or constructed to be used only a single time and then
discarded.
[0017] Before, during, and after the implant is positioned within
the treatment chamber 10, compressible fluid may be injected into
the treatment chamber 10 to retard or preclude the implant 14 from
contacting the inner walls of the treatment chamber 10. The
levitation that results from this injection of compressible fluid
may be helpful to prevent therapeutic or other material, which
coats or has otherwise been deposited in or on the implant, from
being unwantedly damaged, removed or compromised while the implant
14 is in the treatment chamber 10. As described in greater detail
below, the implant 14 may be suspended by the injection of air or
some other suitable compressible fluid into the treatment chamber
10. The injection of the compressible fluid into the chamber 10
creates a buffer zone or fluid bearing between the implant 14 and
the walls 11 of the treatment chamber 10.
[0018] While the implant 14 is within the treatment chamber 10,
therapeutic may be injected into the treatment chamber 10 to coat
or otherwise treat the implant. This therapeutic may be preferably
injected while the implant is being suspended, levitated or rotated
by the compressible fluid. The buffer zone 22 created by the
compressible fluids injected into the treatment chamber serves to
retard or prevent unwanted contact between the implant and the
treatment chamber 10. This unwanted contact could remove, damage or
otherwise compromise therapeutic that coats or is carried by the
implant 14. Thus, by suspending or levitating the implant away from
the treatment chamber 10 walls, an implant may be treated or coated
with a therapeutic within the chamber 10 and then removed from the
chamber without the treated implant coming in contact with or being
significantly compromised by errant contact with the inner walls of
the treatment chamber 10. In addition, to further prevent the
therapeutic from being compromised, it may be allowed to dry on the
implant 14 while the implant 14 remains within the treatment
chamber 10.
[0019] Therapeutic may be injected through the same fluid passages
13 that are injecting the compressible fluid into the treatment
chamber. Therapeutic may also be injected into fluid passages that
do not contain or are not carrying compressible fluid used to
levitate the implant within the treatment chamber 10. Thus, in this
and other embodiments, the fluid passages may be carrying
therapeutic, compressible fluids coatings or a combination. Where
both therapeutic, coatings or both and compressible fluids are
being carried through the same fluid passage the therapeutic or
coatings may be mixed with the compressible fluid upstream of the
fluid passage 13 or may be atomized at or near the entrance or exit
of the fluid passage 13.
[0020] The fluid passages 13 in this and other embodiments may be
angled to circulate the compressible fluid in a vortex or other
defined fluid pattern within the treatment chamber 10. FIG. 2,
which is a sectional view taken along line 2-2 of FIG. 1, shows how
the fluid passages 13 may be angled to create a counterclockwise
rotation of compressible fluids within the treatment chamber 10.
Arrows 21 indicate the direction of rotation of the fluid and the
implant 14 within the treatment chamber 10. Numeral 22 shows the
buffer zone created between the implant 14 and the inner walls of
the treatment chamber 10.
[0021] Treatment chamber as used herein may be any vessel having
defined walls with inside surfaces. A treatment chamber may be made
from various materials including clear, translucent, and opaque
polymers, metals, and ceramics. Clear polymers, which provide for
the internal viewing of implants being coated or impregnated with
therapeutics in the treatment chamber, may be used in a preferred
embodiment. The treatment chamber may be preferably cylindrical but
it may be other shapes as well. These shapes may include octagons,
other multi-sided polygons, ovals, and non-symmetrical shapes.
Furthermore, the treatment chamber may be sized to hold one or more
implants.
[0022] In a preferred embodiment, a treatment chamber may be sized
to allow implants to be positioned end to end next to one another
but not side by side. In other words, in a preferred embodiment
where both the implants and the treatment chamber are cylindrical,
the inside diameter of the treatment chamber may be slightly larger
than the outside diameter of the implant to be coated. For instance
if the outside diameter of a stent to be coated was 0.5 mm, the
inside diameter of the treatment chamber may be 0.7 mm.
[0023] While cylindrical implants have been shown, any implant that
may be levitated within the treatment chamber and subsequently
treated may be used. It is preferred that any implant to be coated
should be easily rotatable about at least one of its axes. In other
words, it is preferred that an implant to be treated be able to be
readily and consistently spun about one of its axes. Consistent
rotation about at least one axis can reduce the likelihood that a
rotating, suspended implant will contact an inside surface of a
treatment chamber before, during, and after it is interfaced with
coating or other treatment. Thus, by reducing the likelihood of
unwanted contact, the risk of chipping the coating or removing
therapeutic from the implant is reduced.
[0024] The flow rate and pressure of the compressible fluid
injected into the treatment chamber 10 and the size and placement
of the fluid passages 13 may be adjusted to accommodate the size,
shape, and weight of the implant to be coated. It may also be
adjusted depending upon the compressible fluid being used and the
pressure developed within the coating chamber. The size and
placement of the exhaust ports 18 may also affect the flow rate and
pressure of the compressible fluid being used. Still further, to
adjust the amount of compressible fluid that may be needed to
levitate an implant, the implants may be loaded into the chamber in
various orientations, i.e., forward, backward, open, and closed (in
the case of an expandable implant).
[0025] FIG. 3 is a side view of an alternative treatment chamber 30
in accord with another embodiment of the present invention. In FIG.
3, an outer case 35 has been placed around the treatment chamber
32. This outer case 35 has a supply line 39 that may be used to
supply compressible fluids, therapeutics and coatings to the outer
case 35. As the outer case 35 surrounds and tightly engages the
treatment chamber 32, compressible fluids, therapeutics and
coatings entering the outer case 35 through the supply line 39 may
be ultimately forced through the fluid passages 33 and 34 to the
inside of the treatment chamber 32. The compressible fluids
entering the treatment chamber 32 may form a buffer zone with any
implant placed therein while the therapeutic may coat or otherwise
interface with an implant in the treatment chamber 32.
[0026] In this embodiment, the fluid passages in the treatment
chamber are shown having two different diameters, a larger diameter
34 and a smaller diameter 33. By changing the diameters, shapes and
sizes of the fluid passages different fluid circulation patterns
may be created within the treatment chamber. It may be beneficial
to create varying circulation patterns within the treatment chamber
in order to accommodate a specific shape or design of an implant to
be coated. In other words, depending upon the design of the
implant, it may be necessary to provide more levitational force at
certain points of the implant than at others. This may be required
due to uneven weighting of the implant or varying surface designs
of the implant. By varying the sizes and spacing of the fluid
passages, the requisite varying lifting forces can be provided.
[0027] As can be seen in FIG. 3, the treatment chamber 32 and outer
case 35 are sized to accommodate two implants, a first implant 36
and a second implant 37. These implants have been placed end to end
in this figure. As can also be seen, the treatment chamber, like
the one on FIG. 1, has two end plates 31, one at each end. Like
FIG. 1, these end plates swing up and away to allow access to the
treatment chamber and seal tight against the treatment chamber when
they are closed during the coating and levitation processes. While
circular end plates that swing on an end are shown, various other
configuration may also be plausible. Also, while the exhaust
passages 38 are shown on the end plate 31, they may be placed at
other locations of the treatment chamber 32 as well.
[0028] FIG. 4 is a side view of another embodiment of the present
invention. In FIG. 4, the treatment chamber 40 contains clockwise
fluid passages 42 and counter clockwise fluid passages 43 as well
as a first implant 45 and a second implant 44. Arrows 46 indicate
the direction of travel of the implants 45 and 44 through the
treatment chamber 40. In this embodiment, the implants may be fed
through the treatment chamber in multiple batches or in a
continuous feed process. As can be seen, the treatment chamber 40
is sized to contain two implants at the same time.
[0029] Still further, the fluid passages in this embodiment may be
fed by independent sources of compressed fluid. Thus, depending
upon which fluid passages are being fed compressed fluid, the
implants may be rotated clockwise or counter-clockwise within the
treatment chamber. This may be done to facilitate uniform
application or drying of therapeutic or coatings onto the implants.
The therapeutic in this embodiment as well as in the others may be
added to the treatment chamber via the fluid passages or may be
introduced into the treatment chamber with other means. For
instance, as described in greater detail below, a nozzle may be
placed inside the treatment chamber and the implant and therapeutic
may be injected or sprayed into the treatment chamber via this
nozzle. In so doing, the force of the rotating implant may be used
to draw the therapeutic from the inside of the implant to the
outside of the implant. This may be useful when both the inside and
outside surfaces of the therapeutic needs to be covered. It may
also be useful when the therapeutic is carried within the implant
and needs to be migrated towards the outer surface of the spinning
implant. In other words, when therapeutic or some coating material
is injected on the inside of the implant, the outward forces
associated with the rotation of the implant may cause the
therapeutic to migrate through the implant or along its surfaces
from the inside to the outside if the implant as it is levitated
and spun.
[0030] Still further, different therapeutics may be fed into the
chamber at different locations along the chamber in this and other
embodiments. In so doing, the individual implants may be coated
with different therapeutics at different locations on the implant.
Likewise, the implants may also be coated in layers of different
therapeutics, with the upstream therapeutic creating the underlayer
of a first therapeutic and the downstream therapeutic creating the
upper layer of a second therapeutic.
[0031] FIG. 5 is a sectional view taken along line 5-5 of FIG. 4.
The sectional view of the implant 45, the treatment chamber 40, and
the clockwise fluid passages 42 can be seen in this view. Arrows 51
indicate the direct of the fluid flow within the treatment chamber
as well as the rotations direction of the implant 45. While the
clockwise fluid passages 42 are shown with uniform cross-sections,
they may also have non-uniform cross-sections such as conical or
ridged cross sections, which would accelerate fluid flowing through
these passages.
[0032] FIG. 6 is a sectional view taken along line 6-6 of FIG. 4.
The sectional view of the implant 45, the treatment chamber 40, and
the counterclockwise fluid passages 43 can be seen in this view.
Arrows 61 indicate the direct of the fluid flow within the
treatment chamber as well as the rotational direction of the
implant 45. As above, while the counterclockwise fluid passages 43
are shown with uniform cross-sections, they may also have
non-uniform cross-sections such as conical or ridged
cross-sections, which would accelerate fluid flowing through these
passages.
[0033] FIG. 7 is a side view of another alternative embodiment of
the present invention. In this embodiment, the treatment chamber 70
is maintained on an angle with its entrance being higher than its
exit. The direction of flow of implants being processed in the
treatment chamber 70 can be seen with arrows 76. The treatment
chamber 70 contains end plates 77 and has several fluid lines 78
coupled to it. These fluid lines 78, which are coupled to fluid
passages in the treatment chamber 70, may be individually
controlled to control the rotation, drying, movement, etc. of the
implants begin treated within the treatment chamber. Thus, in a
batch process application, an implant may be fed in the entrance of
the treatment chamber and suspended by the air leaving fluid lines
781 and 782, while air leaving fluid line 783 prevents the implant
from advancing further down into the treatment chamber. The air
passing through 783 into the treatment chamber may then be reduced,
allowing the implant to pass. In the next portion of the treatment
chamber, a second therapeutic may be added, a second layer may be
added, and the therapeutic may be dried. Upstream of the implant,
after it has moved, a second implant may also be added to be
treated as well. This implant may be retained in the uphill portion
of the treatment chamber by increasing fluid flow though line 783.
Alternatively, the lines may be sequentially activated to both
suspend and urge the implant through the coating chamber. In this
example, the downstream lines may be only activated once the
implant is moved near and, in so doing, the implant may be urged
through the treatment chamber.
[0034] As suggested above, therapeutic may be injected into the
treatment chamber by a therapeutic nozzle. This nozzle 75 may move
inside the rotating implant and eject therapeutic from its tip
while it is being drawn back, out of the chamber, in the direction
of arrow 79.
[0035] The treatment chamber in this embodiment and other
embodiments may also contain drying coils that may be activated to
heat and dry the therapeutic onto the implant prior to the implants
removal from the chamber.
[0036] FIG. 9 is a side view of another embodiment of the present
invention. In this embodiment the treatment chamber 80 has two
therapeutic nozzles 82 and 83, one for each end. Therapeutic nozzle
83 may move from position b to position a as an implant is treated
while therapeutic nozzle 82 may move from position c to position d
as an implant is treated. As can also be seen, the therapeutic
nozzles may have various configurations. These configurations may
depend upon the therapeutic being ejected.
[0037] Medical implants that may be coated or treated in accord
with the present invention include catheters, vascular catheters,
balloon catheters, guide wires, balloons, filters (e.g., vena cava
filters), vascular stents (including covered stents such as PTFE
(polytetrafluoroethylene)-covered stents), stent grafts, cerebral
stents, cerebral aneurysm filler coils (including GDC (Guglielmi
detachable coils) and metal coils), vascular grafts, myocardial
plugs, pacemaker leads, heart valves and intraluminal paving
systems, filterwires, venous valves, bifurcation stents, and aortic
stents.
[0038] Therapeutics that may be used are numerous and include
pharmaceutically active compounds, nucleic acids with and without
carrier vectors such as lipids, compacting agents (such as
histones), viruses (such as adenovirus, adenoassociated virus,
retrovirus, lentivirus and a-virus), polymers, hyaluronic acid,
proteins, cells and the like, with or without targeting
sequences.
[0039] Other examples of therapeutic agents used in conjunction
with the present invention include, for example, pharmaceutically
active compounds, proteins, cells, oligonucleotides, ribozymes,
anti-sense oligonucleotides, DNA compacting agents, gene/vector
systems (i.e., any vehicle that allows for the uptake and
expression of nucleic acids), nucleic acids (including, for
example, recombinant nucleic acids; naked DNA, cDNA, RNA; genomic
DNA, cDNA or RNA in a non-infectious vector or in a viral vector
and which further may have attached peptide targeting sequences;
antisense nucleic acid (RNA or DNA); and DNA chimeras which include
gene sequences and encoding for ferry proteins such as membrane
translocating sequences ("MTS") and herpes simplex virus-1
("VP22")), and viral liposomes and cationic and anionic polymers
and neutral polymers that are selected from a number of types
depending on the desired application.
[0040] Non-limiting examples of virus vectors or vectors derived
from viral sources include adenoviral vectors, herpes simplex
vectors, papilloma vectors, adeno-associated vectors, retroviral
vectors, and the like.
[0041] Non-limiting examples of biologically active solutes include
anti-thrombogenic agents such as heparin, heparin derivatives,
urokinase, and PPACK (dextrophenylalanine proline arginine
chloromethylketone); antioxidants such as probucol and retinoic
acid; angiogenic and anti-angiogenic agents and factors;
anti-proliferative agents such as enoxaprin, angiopeptin,
rapamycin, angiopeptin, monoclonal antibodies capable of blocking
smooth muscle cell proliferation, hirudin, and acetylsalicylic
acid; anti-inflammatory agents such as dexamethasone, prednisolone,
corticosterone, budesonide, estrogen, sulfasalazine, acetyl
salicylic acid, and mesalamine; calcium entry blockers such as
verapamil, diltiazem and nifedipine;
antineoplastic/antiproliferative/anti-mitotic agents such as
paclitaxel, 5-fluorouracil, methotrexate, doxorubicin,
daunorubicin, cyclosporine, cisplatin, vinblastine, vincristine,
epothilones, endostatin, angiostatin and thymidine kinase
inhibitors; antimicrobials such as triclosan, cephalosporins,
aminoglycosides, and nitroftirantoin; anesthetic agents such as
lidocaine, bupivacaine, and ropivacaine; nitric oxide (NO) donors
such as linsidomine, molsidomine, L-arginine, NO-protein adducts,
NO-carbohydrate adducts, polymeric or oligomeric NO adducts;
anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD
peptide-containing compound, heparin, antithrombin compounds,
platelet receptor antagonists, anti-thrombin antibodies,
anti-platelet receptor antibodies, enoxaparin, hirudin, Warfarin
sodium, Dicumarol, aspirin, prostaglandin inhibitors, platelet
inhibitors and tick antiplatelet factors; vascular cell growth
promotors such as growth factors, growth factor receptor
antagonists, transcriptional activators, and translational
promoters; 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; agents
which interfere with endogenous vascoactive mechanisms; survival
genes which protect against cell death, such as anti-apoptotic
Bcl-2 family factors and Akt kinase; and combinations thereof.
Cells can be of human origin (autologous or allogenic) or from an
animal source (xenogeneic), genetically engineered if desired to
deliver proteins of interest at the insertion site.
[0042] Polynucleotide sequences useful in practice of the invention
include DNA or RNA sequences having a therapeutic effect after
being taken up by a cell. Examples of therapeutic polynucleotides
include anti-sense DNA and RNA; DNA coding for an anti-sense RNA;
or DNA coding for tRNA or rRNA to replace defective or deficient
endogenous molecules. The polynucleotides can also code for
therapeutic proteins or polypeptides. A polypeptide is understood
to be any translation product of a polynucleotide regardless of
size, and whether glycosylated or not. Therapeutic proteins and
polypeptides include as a primary example, those proteins or
polypeptides that can compensate for defective or deficient species
in an animal, or those that act through toxic effects to limit or
remove harmful cells from the body. In addition, the polypeptides
or proteins that can be injected, or whose DNA can be incorporated,
include without limitation, angiogenic factors and other molecules
competent to induce angiogenesis, including acidic and basic
fibroblast growth factors, vascular endothelial growth factor,
hif-1, epidermal growth factor, transforming growth factor "and $,
platelet-derived endothelial growth factor, platelet-derived growth
factor, tumor necrosis factor ", hepatocyte growth factor and
insulin like growth factor; growth factors; cell cycle inhibitors
including CDK inhibitors; anti-restenosis agents, including p15,
p16, p18, p19, p21, p27, p53, p57, Rb, nFkB and E2F decoys,
thymidine kinase ("TK") and combinations thereof and other agents
useful for interfering with cell proliferation, including agents
for treating malignancies; and combinations thereof. Still other
useful factors, which can be provided as polypeptides or as DNA
encoding these polypeptides, include monocyte chemoattractant
protein ("MCP-1"), and the family of bone morphogenic proteins
("BMP's"). The known proteins include BMP-2, BMP-3, BMP-4, BMP-5,
BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12,
BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMP's are
any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric
proteins can be provided as homodimers, heterodimers, or
combinations thereof, alone or together with other molecules.
Alternatively or, in addition, molecules capable of inducing an
upstream or downstream effect of a BMP can be provided. Such
molecules include any of the "hedgehog" proteins, or the DNAs
encoding them.
[0043] Coatings used with the present invention may comprise
various polymeric material/drug agent matrices. These may be
formed, for example, by admixing a drug agent with a liquid
polymer, in the absence of a solvent, to form a liquid polymer/drug
agent mixture. Curing of the mixture typically occurs in-situ. To
facilitate curing, a cross-linking or curing agent may be added to
the mixture prior to application thereof. Addition of the
cross-linking or curing agent to the polymer/drug agent liquid
mixture must not occur too far in advance of the application of the
mixture in order to avoid over-curing of the mixture prior to
application thereof. Curing may also occur in-situ by exposing the
polymer/drug agent mixture, after application to the luminal
surface, to radiation such as ultraviolet radiation or laser light,
heat, or by contact with metabolic fluids such as water at the site
where the mixture has been applied to the luminal surface. In
coating systems employed in conjunction with the present invention,
the polymeric material may be either bioabsorbable or biostable.
Any of the polymers described herein that may be formulated as a
liquid may be used to form the polymer/drug agent mixture.
[0044] The carriers and coatings used in the present invention may
be hydrophilic or hydrophobic and may be selected from the group
consisting of polycarboxylic acids, cellulosic polymers, including
cellulose acetate and cellulose nitrate, gelatin,
polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone,
polyanhydrides including maleic anhydride polymers, polyamides,
polyvinyl alcohols, copolymers of vinyl monomers such as EVA,
polyvinyl ethers, polyvinyl aromatics, polyethylene oxides,
glycosaminoglycans, polysaccharides, polyesters including
polyethylene terephthalate, polyacrylamides, polyethers, polyether
sulfone, polycarbonate, polyalkylenes including polypropylene,
polyethylene and high molecular weight polyethylene, halogenated
polyalkylenes including polytetrafluoroethylene, polyurethanes,
polyorthoesters, proteins, polypeptides, silicones, siloxane
polymers, polylactic acid, polyglycolic acid, polycaprolactone,
polyhydroxybutyrate valerate and blends and copolymers thereof as
well as other biodegradable, bioabsorbable and biostable polymers
and copolymers. Coatings from polymer dispersions such as
polyurethane dispersions (BAYHDROL.RTM., etc.) and acrylic latex
dispersions are also within the scope of the present invention. The
polymer may be a protein polymer, fibrin, collagen and derivatives
thereof, polysaccharides such as celluloses, starches, dextrans,
alginates and derivatives of these polysaccharides, an
extracellular matrix component, hyaluronic acid, or another
biologic agent or a suitable mixture of any of these, for example.
In one embodiment of the invention, the preferred polymer is
polyacrylic acid, available as HYDROPLUS.RTM. (Boston Scientific
Corporation, Natick, Mass.), and described in U.S. Pat. No.
5,091,205. U.S. Pat. No. 5,091,205 describes medical devices coated
with one or more polyisocyanates such that the devices become
instantly lubricious when exposed to body fluids. In another
preferred embodiment of the invention, the polymer is a copolymer
of polylactic acid and polycaprolactone.
[0045] While various embodiments of the present invention have been
described, other embodiments are also plausible. For instance the
multiple fluid lines of FIG. 7 may be used on the embodiment of
FIG. 3 in order to allow selective activation of the various small
and large fluid passages. Likewise, while passages are generally
shown as being consistently sized along the same circumference of
the treatment chamber that may not always be the case as the
passages may be different sizes or shapes along the same
circumferential line. Moreover, the passages may not always be
along uniform cross-sectional lines.
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