U.S. patent application number 09/880615 was filed with the patent office on 2001-10-18 for stent drug delivery system.
Invention is credited to Johnson, Michael W..
Application Number | 20010029660 09/880615 |
Document ID | / |
Family ID | 25475270 |
Filed Date | 2001-10-18 |
United States Patent
Application |
20010029660 |
Kind Code |
A1 |
Johnson, Michael W. |
October 18, 2001 |
Stent drug delivery system
Abstract
Expandable intraluminal stents are provided as well their method
of manufacture. These stents are made of metal, the metal
characterized by a desired porosity, with a drug compressed into
the pores of the stent. The stents are formed by subjecting one or
more powdered metals in a die cavity to a pressure treatment
followed by a heat treatment. The metal may be cast directly in a
stent-like form or cast into sheets or tubes from which the
inventive stents are produced. The so-formed porous metal stent is
then loaded with one or more drugs.
Inventors: |
Johnson, Michael W.;
(Rogers, MN) |
Correspondence
Address: |
VIDAS, ARRETT & STEINKRAUS, P.A.
6109 BLUE CIRCLE DRIVE
SUITE 2000
MINNETONKA
MN
55343-9185
US
|
Family ID: |
25475270 |
Appl. No.: |
09/880615 |
Filed: |
June 13, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09880615 |
Jun 13, 2001 |
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09420094 |
Oct 18, 1999 |
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6253443 |
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09420094 |
Oct 18, 1999 |
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08940696 |
Sep 30, 1997 |
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5972027 |
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Current U.S.
Class: |
29/557 ;
606/1 |
Current CPC
Class: |
Y10T 29/49995 20150115;
A61L 31/146 20130101; B23K 2103/26 20180801; A61L 2300/00 20130101;
B23K 2103/14 20180801; A61F 2/92 20130101; A61L 31/022 20130101;
A61L 2300/608 20130101; B23K 2103/08 20180801; A61F 2250/0067
20130101; A61F 2/91 20130101; B23K 26/40 20130101; C08L 27/18
20130101; B23K 2103/42 20180801; A61F 2/88 20130101; B23K 2103/05
20180801; B23K 2103/50 20180801; A61L 31/16 20130101; A61L 31/048
20130101; B23K 2103/04 20180801; A61F 2/82 20130101 |
Class at
Publication: |
29/557 ;
606/1 |
International
Class: |
B23P 013/04; A61B
017/00 |
Claims
What is claimed is as follows:
1. A method of forming a stent comprising the steps of: providing a
first powdered metal; providing a second powdered metal, the first
powdered metal and second powdered metal having a different
composition or different physical properties or both; treating the
first and second powdered metals to form a stent-preform; forming a
stent from the stent preform.
2. The method of claim 1 wherein the stent preform is a sheet.
3. The method of claim 2 wherein the sheet is rolled into tubular
form during the forming step.
4. The method of claim 3, the sheet having opposing edges, wherein
an edge is secured to an opposing edge during the forming step.
5. The method of claim 1 where the preform is laser cut during the
forming step.
6. The method of claim 1 wherein the stent preform is a tube.
7. The method of claim 1 wherein the treating step includes
subjecting the first and second powdered metals to high pressure to
form the preform.
8. The method of claim 1 wherein the treating step includes
subjecting the first and second powdered metals to high pressure to
form a compact and sintering the compact to form the preform.
9. The method of claim 1 wherein the treating step includes
sintering the first and second powdered metals to form the
preform.
10. The method of claim 1 wherein: the treating step includes
subjecting the first and second powdered metals to high pressure to
form a compact and sintering the compact to form a preform selected
from the group consisting of sheets and tubes and either rolling
the preform in the case where the preform is a sheet to form the
stent or laser cutting the preform in the case where the preform is
a tube to form the stent.
11. The method of claim 1 wherein the first and second metals are
characterized by different average particle size.
12. The method of claim 1 wherein the first and second metals are
elementally different metals.
13. A method of forming a stent comprising the steps of: providing
a tube formed from a powdered metal; cutting the tube to a desired
shape using a laser.
14. The method of claim 13 wherein the powdered metal has been
sintered.
15. The method of claim 13 wherein the powdered metal has been
subjected to high pressure to form a compact and the compact
sintered.
16. The method of claim 15 wherein the tube is formed from at least
two powdered metals, a first powdered metal and a second powdered
metal, the first and second powdered metals having a different
composition or different physical properties or both.
17. The method of claim 13 wherein the tube is formed from at least
two powdered metals, a first powdered metal and a second powdered
metal, the first and second powdered metals having a different
composition or different physical properties or both.
18. A method of forming a stent comprising the steps of: providing
a sheet formed from at least one powdered metal; rolling the sheet
to form a tubular stent.
19. The method of claim 18 wherein the sheet has been sintered.
20. The method of claim 18 wherein the powdered metal has been
subjected to high pressure to form a compact and the compact
sintered.
21. The method of claim 20 wherein the sheet is formed from at
least two powdered metals, a first powdered metal and a second
powdered metal, the first and second powdered metals having a
different composition or different physical properties or both.
which are characterized
22. The method of claim 18 wherein the sheet is formed from at
least two powdered metals, a first powdered metal and a second
powdered metal, the first and second powdered metals having a
different composition or different physical properties or both.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Continuation of U.S. application Ser.
No. 08/940,696 filed Sep. 30, 1997, the contents of which are
incorporated herein in their entirety by reference.
BACKGROUND OF THE INVENTION
[0002] This invention relates to stents for maintaining the patency
of body passages. Additionally, the stents may serve as drug
delivery vehicles. The invention has particular application to
stenting in blood vessels of the human body and will be described
with reference thereto. However, in a broader sense it relates to
stenting in any body passage, including such passages as the
gastrointestinal tract, urethral and ureteral tracts, bronchial and
esophageal tracts. The invention also has particular reference to
stents comprising compounds useful for the treatment and prevention
of restenosis and also will find application in dilating and
maintaining the patency of various body passages such as ureters
and the like.
SUMMARY OF THE INVENTION
[0003] In accordance with the present invention, a porous stent
made from a powdered metal or polymeric material is disclosed. The
inventive stent is an expandable intraluminal stent comprising a
main body portion having a first end, a second end and a flow
passage defined therethrough, the main body portion being sized for
intraluminal placement within a body passage and subsequent
expansion for implantation. The main body portion of the stent of
the present invention is further characterized in that it is formed
at least in part of at least one porous material, the porous
material having been formed from a powdered metal or polymeric
material.
[0004] In another embodiment of the present invention, a drug is
contained within the pores of the stent for delivery to the
body.
[0005] In another embodiment of the present invention, the stent
may be coated with a drug.
[0006] In another embodiment of the present invention, the stent is
comprised of at least two porous metals.
[0007] The present invention is also directed to a method for
making a porous expandable intraluminal stent comprising the steps
of providing a powdered material, subjecting the powdered material
to high pressure to form a compact, sintering the compact to form a
final porous material and forming a stent from the porous material.
In another embodiment of the above-mentioned inventive method, at
least one drug is loaded into the pores of the stent.
BRIEF DESCRIPTION OF THE FIGURES
[0008] FIG. 1a is a perspective view of one embodiment of a stent
according to the present invention.
[0009] FIG. 1b is an enlargement of a portion of FIG. 1 a showing
pores on the surface of the metal.
[0010] FIG. 2 is a sectional view of another embodiment of a stent
in accordance with this invention.
[0011] FIG. 3 is a perspective view of another embodiment of a
stent according to the present invention.
[0012] FIG. 4a is a plan view development of the inventive stent in
sheet form prior to rolling.
[0013] FIG. 4b is a sectional view of another embodiment of a stent
according to the present invention.
[0014] FIG. 5 is a perspective view of yet another embodiment of a
stent according to this invention.
DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EXEMPLARY
EMBODIMENTS
[0015] The present invention relates to a porous stent made from a
powdered material such as powdered metal or polymer for maintaining
the patency of body passages. Stents to which the present invention
relates may be either balloon expandable or self-expanding as well
as springy in form. For example, self-expanding stents are known
which are braided, woven or mesh-like in structure, although many
other types of self-expanding stents including solid stents are
also known. Such stents have memory characteristics and, if
distorted in length and/or diameter by external forces, they will
return or tend to return to a preformed configuration upon the
release of external forces. This expansion may be due to the
natural springiness of the stent, for instance with a rolled up
sheet stent, or as a result of a phase transition occurring in the
stent material. Balloon expandable stents may be expanded by the
application of a suitable amount of force to the stent.
[0016] The stents of the present invention may be used to deliver
drugs to a desired bodily location. As used in this application,
the term "drug" denotes any compound which has a desired
pharmacologic effect, or which is used for diagnostic purposes.
Useful drugs, in the context of the present invention include, but
are not limited to angiogenic drugs, smooth muscle cell inhibitors,
collagen inhibitors, vasodilators, anti-platelet substances,
anti-thrombotic substances, anti-coagulants, cholesterol reducing
agents and combinations thereof. The drugs may include
radiochemicals to irradiate and/or prohibit tissue growth or to
permit diagnostic imaging of a site.
[0017] The porous stent may be used as a drug-delivery system to,
for example, prevent restenosis. The drugs may include
radiochemicals to irradiate and prohibit tissue growth. Angioplasty
and stent deployment may cause injury of the endothelial cell layer
of blood vessels, causing smooth muscle cell proliferation, leading
to restenosis. To control smooth muscle cell growth
endothelialization of cells on the inner wall surface of vessels
will prevent or prohibit the smooth muscle growth. To promote
endothelialization human growth factors may be included in the
outer layer and delivered.
[0018] The stent of the present invention may be formed of any
bio-compatible powdered metals such as stainless steel. Powdered
metals typically are available in powder sizes as small as 40
microns or less. While powdered metals of any powder size may be
used in forming the stents of the present invention, preferably
powders 40 microns or less will be used in forming the porous metal
stent of the present invention. More preferably, powdered metals
ranging in size from 6 to 12 microns will be used. Especially
desirable are powders with good flow properties so that the
particles may be dispensed easily into a die cavity for metal
processing. Other suitable metals include, but are not limited to,
spring steel, nitinol and titanium as well as any other
bio-compatible metal which may become available in powdered form in
the future. Suitable metals do not produce toxic reactions or act
as carcinogens. The stent of the present invention may also be
formed of bio-compatible powdered polymeric materials such as
PTFE.
[0019] The stents of the present invention may also be prepared
with different mean pore sizes. Pore size is an important parameter
in that certain macromolecular drugs may be excluded from use where
the pore size is very small. The pore size may also play a role in
determining the extent of cellular infiltration or tissue ingrowth
during implantation of the stent. While cellular ingrowth is
sometimes desirable, it can also lead to complications such as
infection and difficulty in removing the stent. Stents with a mean
pore size of greater than about 10 microns can allow infiltration
of cellular sized biomaterials; stents with mean pore sizes in the
range of 1-10 microns may accommodate infiltration of some of the
above bio-materials. Stents with pore sizes less than about 1
micron will not generally accommodate infiltration of any of the
above biomaterials but can accommodate infiltration of
macromolecular and small biomaterials. Thus, the pore size of the
stent may be varied to foster or inhibit cellular infiltration
and/or tissue ingrowth. Of course, the pore size may also be varied
to facilitate delivery of drugs of different molecular sizes.
[0020] The material processing proceeds with a pressure treatment
step in which the powdered material in a die cavity is subjected to
pressures of up to twenty tons or more. At such high pressures, the
powder begins to interlock, forming a compact with pockets of air
remaining in the metal. The pressure treatment step usually
proceeds at room temperature although warm or hot pressing may be
used. Other techniques to form the compact, as known in the art,
may be substituted for the pressure treatment step. The die cavity
used in this step may be a stent die cavity to allow for direct
casting of the stent or alternatively, may be for some other form
such as a tube or a sheet. Following the pressure treatment step,
the compact has sufficient strength to allow for routine handling
without breakage.
[0021] After ejection from the die, the compact is sintered to form
a coherent metal or polymer mass in the shape of the die.
Alternatively, the pressure treatment step can be eliminated and
the processing limited to a sintering in which the metal or polymer
powder is heated in a die resulting in a low density, highly porous
compound. Although the sintering step may actually partially melt
the metal or polymer as in liquid-phase sintering, in the preferred
embodiment, the sintering step does not melt the metal or polymer
as the temperature is maintained below the melting point of
elemental metal or any alloys that have formed or the polymer
melting point. The sintered metal or polymer will exhibit a
porosity ranging from less than 10 percent to about 80 percent of
the total volume. The percentage porosity is a measure of the void
space within the metal.
[0022] Following sintering, the now porous metal or polymer may be
formed into a stent, if it has not been so-formed already. Any
known process in the art may be used including laser cutting and
braiding of porous metal strands. FIGS. 1a and 1b illustrate one
such stent 10, with pores 14 formed by laser cutting apertures 18
in a sheet of porous metal. FIG. 2 illustrates a stent 20 which is
composed of a number of interconnected members 22, the members and
interconnections 24 made of a metal containing pores 26. A braided
stent may be formed of a series of strands arranged in a crossing
configuration which may be woven, braided or the like. The strands
of porous metal or polymer can be deformed so to provide a reduced
diameter of the stent which facilitates its delivery to the
targeted portion of a vessel or other passageway and once disposed
at the target portion the stent can then be allowed to expand to
its preformed configuration and larger diameter.
[0023] The stents of the present invention may be prepared in a
range of porosities allowing for the production of stents with
differing drug delivery characteristics. The porosity may be
between twenty and eighty percent of the total volume and more
suitably between forty and sixty percent of the volume.
[0024] The stent may be impregnated with one or more drugs by any
known process in the art including high pressure loading in which
the stent is placed in a bath of the desired drug or drugs and
subjected to high pressure or, alternatively, subjected to a
vacuum. The drug may be carried in a volatile or non-volatile
solution. In the case of a volatile solution, following loading of
the drug, the volatile carrier solution may be volatilized. In the
case of the vacuum, the air in the pores of the metal stent is
evacuated and replaced by the drug-containing solution.
[0025] In accordance with the present invention, the stent may
further be coated with one or more layers of one or more drugs to
allow for longer term drug elution optionally employing a number of
different drugs over time. As such, the drug in the pores would not
be eluted until the coating of drug has been absorbed, thereby
allowing for longer term drug treatment than would be available
from the coated metal alone.
[0026] FIG. 3 shows a coil stent 30 in which the porous metal stent
30 further comprises such a coating 32 (the pores have been omitted
for clarity).
[0027] The inventive stent may also be formed from a rolled up flat
sheet comprised of a porous metal or polymer as shown in FIG. 4a.
The sheet 35 contains a plurality of apertures 36 and pores 38 as
well as tabs 37. The tabs are inserted into the holes 36a-c when
the stent is rolled, as shown in FIG. 4b. The stent may be rolled
tightly for delivery and implantation and be self-expandable to the
extent that it tends to unroll. The stent may further be laminated
with a layer of drug over the porous surface of the stent.
Otherwise, it may simply be expanded by independent expansion means
such as a balloon catheter positioned inside the stent as is
already known in the art.
[0028] Another embodiment of the invention contemplates the
fabrication of any stent design per se taken from the prior art,
the stent prepared from a porous metal or polymer, the pores of the
metal or polymer including one or more drugs.
[0029] Another embodiment of the invention is an expandable
intraluminal stent comprising a main body portion having a first
end, a second end and a flow passage defined therethrough, the main
body portion being sized for intraluminal placement within a body
passage and subsequent expansion for implantation, the main body
portion being further characterized in that it is formed at least
in part of at least two metals, the two metals comprising a first
porous metal characterized by a first porosity and mean pore size
and a second porous metal characterized by a second porosity and
mean pore size. FIG. 5 depicts one such stent, 40, the first metal
42 containing first pores 44 therein and the second metal 46
containing second pores 48 therein.
[0030] In the above embodiment, one drug may be loaded into the
pores of the first porous metal and a second drug loaded into the
pores of the second porous metal. Alternatively, the same drug can
be loaded into both the first and second porous metals.
[0031] The present invention is also directed to a method for
making a porous metal, expandable intraluminal stent comprising the
steps of providing a powdered metal or polymeric material,
subjecting the powder to high pressure to form a compact, sintering
the compact to form a final porous metal or polymer, forming a
stent from the porous metal and, optionally, loading at least one
drug into the pores. The drug(s) may be loaded into the pores by
placing the stent in a liquid bath comprising the at least one drug
at high pressure, by placing the stent in a liquid bath within a
chamber, the liquid bath comprising the drug(s), and reducing the
pressure within the chamber below ambient pressure or by any other
method known in the art.
[0032] In yet another embodiment, the invention is directed to a
method of making an expandable intraluminal stent of varying
porosity comprising the steps of providing two or more metal and/or
polymeric powders in a die, subjecting the two or more powders to
high pressure to form a compact, sintering the compact to form a
final porous metal or polymer of varying porosity, forming a stent
from the porous metal or polymer and, optionally, loading at least
one drug into the pores. The two or more powdered metals and/or
polymers can comprise at least two different metals and/or polymers
or can comprise one metal or polymer, the one metal or polymer
provided in at least two different average particle sizes or can
comprise several different metals or polymers provided in several
different average particle sizes. In such a way, the porosity of
the stent in different regions of the stent can be tailored by
forming the stent of several different powdered metals or polymers
comprising a combination of different elemental metals or alloys or
polymers in powdered form, or using the same elemental metal, alloy
or polymer but providing it in several powders of different average
particle size or by some combination of different metals and/or
polymers and same metals and/or polymers of different particle
size.
[0033] While the invention has been described in connection with
what is presently considered to be the most practical and preferred
embodiments, it is to be understood that the invention is not to be
limited to the disclosed embodiments but, on the contrary, is
intended to cover various modifications and equivalent arrangements
included within the spirit and scope of the appended claims.
[0034] The above Examples and disclosure are intended to be
illustrative and not exhaustive. These examples and description
will suggest many variations and alternatives to one of ordinary
skill in this art. All these alternatives and variations are
intended to be included within the scope of the attached claims.
Those familiar with the art may recognize other equivalents to the
specific embodiments described herein which equivalents are also
intended to be encompassed by the claims attached hereto.
* * * * *