U.S. patent application number 10/039816 was filed with the patent office on 2002-07-25 for irradiated stent coating.
Invention is credited to Furst, Joseph G..
Application Number | 20020099438 10/039816 |
Document ID | / |
Family ID | 26716477 |
Filed Date | 2002-07-25 |
United States Patent
Application |
20020099438 |
Kind Code |
A1 |
Furst, Joseph G. |
July 25, 2002 |
Irradiated stent coating
Abstract
An expandable stent for use within a body passageway having a
body member with two ends and a wall surface disposed between the
ends. The body member has a first diameter to permit delivery of
the body member into a body passageway and a second expanded
diameter. The surface of the stent is coated with a biological
agent and a polymer which controls the release of the biological
agent.
Inventors: |
Furst, Joseph G.;
(Middlefield, OH) |
Correspondence
Address: |
Vickers, Daniels & Young
Suite 2000
50 Public Square
Cleveland
OH
44113-2235
US
|
Family ID: |
26716477 |
Appl. No.: |
10/039816 |
Filed: |
October 26, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10039816 |
Oct 26, 2001 |
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09771073 |
Jan 29, 2001 |
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09771073 |
Jan 29, 2001 |
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09273736 |
Mar 22, 1999 |
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10039816 |
Oct 26, 2001 |
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09363052 |
Jul 29, 1999 |
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6206916 |
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60081824 |
Apr 15, 1998 |
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60094250 |
Jul 27, 1998 |
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Current U.S.
Class: |
623/1.16 |
Current CPC
Class: |
A61F 2250/0098 20130101;
A61L 31/10 20130101; A61F 2002/91575 20130101; A61L 31/16 20130101;
A61F 2230/0054 20130101; A61F 2310/0097 20130101; A61F 2002/91566
20130101; A61F 2250/0068 20130101; A61F 2/91 20130101; A61L
2300/602 20130101; A61K 9/0024 20130101; A61F 2/915 20130101; A61F
2002/91533 20130101; A61L 2300/606 20130101 |
Class at
Publication: |
623/1.16 |
International
Class: |
A61F 002/06 |
Claims
What is claimed is:
1. An expandable stent for use within in a body passageway
including a body member, a coating compound, and a biological
agent, said body member having first and second ends and a wall
surface disposed between said first and second ends, said body
member having a first cross-sectional area which permits delivery
of said body member into said body passageway, and a second
expanded cross-sectional area, said biological agent at least
partially coated on the surface of said body member, said coating
compound at least partially securing said biological agent to said
body member, said coating compound including at least one radiation
induced cross-linking.
2. The stent of claim 1, wherein said wall surface is formed by a
plurality of intersecting elongated members, at least some of said
elongated members intersecting with one another intermediate said
first and second ends of said body member, said plurality of
elongated members including a plurality of wires, said wires being
fixedly secured to one another where said wires intersect with one
another.
3. The stent as defined in claim 1, wherein said wall surface is
formed by a plurality of intersecting elongated members, at least
some of said elongated members intersecting with one another
intermediate said first and second ends of said body member, said
plurality of elongated members including a plurality of thin bars,
said bars being fixedly secured to one another where said bars
intersect with one another.
4. The stent as defined in claim 1, wherein said wall surface
includes a plurality of elongated slots.
5. The stent as defined in claim 1, including two body members and
at least one connector member connected between said two body
members, said connector member allowing transverse bending
flexibility of said stent.
6. The stent as defined in claim 2, including two body members and
at least one connector member connected between said two body
members, said connector member allowing transverse bending
flexibility of said stent.
7. The stent as defined in claim 3, including two body members and
at least one connector member connected between said two body
members, said connector member allowing transverse bending
flexibility of said stent.
8. The stent as defined in claim 4, including two body members and
at least one connector member connected between said two body
members, said connector member allowing transverse bending
flexibility of said stent.
9. The stent as defined in claim 1, wherein said body member
includes material to make the body member visible under
fluoroscopy.
10. The stent as defined in claim 1, wherein said body member is at
least partially coated with a material that is visible under
fluoroscopy.
11. The stent as defined in claim 1, wherein said biological agent
is releasably coated on said stent.
12. The stent as defined in claim 2, wherein said biological agent
is releasably coated on said stent.
13. The stent as defined in claim 3, wherein said biological agent
is releasably coated on said stent.
14. The stent as defined in claim 4, wherein said biological agent
is releasably coated on said stent.
15. The stent as defined in claim 6, wherein said biological agent
is releasably coated on said stent.
16. The stent as defined in claim 7, wherein said biological agent
is releasably coated on said stent.
17. The stent as defined in claim 8, wherein said biological agent
is releasably coated on said stent.
18. The stent as defined in claim 1, wherein said coating compound
at least partially delays delivery of said biological agent into
said body passageway.
19. The stent as defined in claim 2, wherein said coating compound
at least partially delays delivery of said biological agent into
said body passageway.
20. The stent as defined in claim 3, wherein said coating compound
at least partially delays delivery of said biological agent into
said body passageway.
21. The stent as defined in claim 4, wherein said coating compound
at least partially delays delivery of said biological agent into
said body passageway.
22. The stent as defined in claim 15, wherein said coating compound
at least partially delays delivery of said biological agent into
said body passageway.
23. The stent as defined in claim 16, wherein said coating compound
at least partially delays delivery of said biological agent into
said body passageway.
24. The stent as defined in claim 17, wherein said coating compound
at least partially delays delivery of said biological agent into
said body passageway.
25. The stent as defined in claim 1, wherein said coating compound
includes a polymer, a copolymer or mixtures thereof.
26. The stent as defined in claim 22, wherein said coating compound
includes a polymer, a copolymer or mixtures thereof.
27. The stent as defined in claim 23, wherein said coating compound
includes a polymer, a copolymer or mixtures thereof.
28. The stent as defined in claim 24, wherein said coating compound
includes a polymer, a copolymer or mixtures thereof.
29. The stent as defined in claim 1, wherein said biological agent
forms a polymer salt complex with said coating compound.
30. The stent as defined in claim 26, wherein said biological agent
forms a polymer salt complex with said coating compound.
31. The stent as defined in claim 27, wherein said biological agent
forms a polymer salt complex with said coating compound.
32. The stent as defined in claim 28, wherein said biological agent
forms a polymer salt complex with said coating compound.
33. The stent as defined in claim 1, wherein said geometrically
shaped member is treated with radiation to reduce the vascular
narrowing of at least a portion of said body passageway.
34. The stent as defined in claim 1, including an angioplasty
balloon, said angioplasty balloon including at least one opening to
allow delivery of said biological agent from an interior of said
balloon to said body passageway.
35. The stent as defined in claim 1, wherein said body member
having substantially the same longitudinal length when said body
member is in its first cross-sectional area and in its said second
expanded cross-sectional area.
36. The stent as defined in claim 30, wherein said body member
having substantially the same longitudinal length when said body
member is in its first cross-sectional area and in its said second
expanded cross-sectional area.
37. The stent as defined in claim 3 1, wherein said body member
having substantially the same longitudinal length when said body
member is in its first cross-sectional area and in its said second
expanded cross-sectional area.
38. The stent as defined in claim 32, wherein said body member
having substantially the same longitudinal length when said body
member is in its first cross-sectional area and in its said second
expanded cross-sectional area.
39. The stent as defined in claim 1, wherein said first and second
ends of said body member having a plurality of end regions, at
least one of said end regions having a substantially smooth
surface.
40. The stent as defined in claim 1, wherein said body member is
substantially tubular shaped.
41. A biological matrix comprising a base compound and biological
agent, said base compound including a polymer, copolymer or
mixtures thereof, said base compound at least partially
encapsulating at least a portion of said biological agent, said
base compound including at least one radiation induced
cross-linking, said at least one radiation induced cross-linking at
least partially entrapping said biological agent in said base
compound and/or forming a bond between said base compound and said
biological agent.
42. The biological matrix as defined in claim 41, including a
plurality of biological agents.
43. The biological matrix as defined in claim 41, wherein said base
compound includes a plurality of a polymer, a copolymer, or
mixtures thereof.
44. The biological matrix as defined in claim 41, wherein said base
compound and biological agent at least partially coated on a stent
or other implant.
45. The biological matrix as defined in claim 41, wherein said base
compound and biological agent at least partially impregnated in a
stent or other implant.
46. The biological matrix as defined in claim 41, wherein said base
compound and biological agent at least partially forming a part of
a stent or other implant.
47. The biological matrix as defined in claim 41, wherein said base
compound at least partially encapsulating said biological
agent.
48. The biological matrix as defined in claim 41, wherein said base
compound at least partially delays delivery of said biological
agent into said body passageway.
49. The biological matrix as defined in claim 41, wherein base
compound forms a polymer salt complex with at least a portion of
said biological agent.
50. A method for producing an expandable stent coated with a
biological agent comprising: a) selecting a stent having a body
member, said body member having a first cross-sectional area which
permits delivery of said body member into a body passageway, and a
second expanded cross-sectional area; b) coating at least a portion
of said body member with a mixture of a coating compound and a
biological agent, said coating compound including polymer,
copolymer and combinations thereof; and, c) applying radiation to
said coating to cause at least one cross-link to form in said
coating compound.
Description
[0001] The present application is a continuation-in-part of
co-pending U.S. patent application Ser. No. 09/771,073 filed Jan.
29, 2001 entitled "Improved Expandable Graft" which in turn is a
continuation-in-part of co-pending U.S. patent application Ser. No.
09/273,736 filed Mar. 22, 1999 entitled "Improved Expandable Graft"
based on U.S. Provisional Patent Application Serial No. 60/081,824
filed Apr. 15, 1998. The present application is also a
continuation-in-part of co-pending U.S. patent application Ser. No.
09/771,073 filed Jan. 29, 2001 entitled "Improved Expandable Graft"
which in turn is a continuation-in-part of U.S. Letters Pat. No.
6,206,916 entitled "Coated Intraluminal Graft" based on U.S.
Provisional Patent Application Serial No. 60/094,250 filed Jul. 27,
1998.
[0002] This invention relates to an implant for use within a body
and, more particularly, an expandable stent which is particularly
useful for repairing various types of body cavities, and even more
particularly to an expandable stent that includes and/or is at
least partially coated and/or impregnated with one or more
biological agents which stent and one or more biological agents are
useful in repairing blood vessels narrowed or occluded by disease.
Although the present invention is particularly applicable to
stents, the biological agent delivery system of the present
invention can be used in conjunction with various types of implants
such as, but not limited to, prosthetic devices. As such, the
biological agent delivery system can form one or more components of
other types of implants and/or be coated and/or impregnated onto at
least a portion of other types of implants to deliver one or more
biological agent to a particular site. Furthermore, the biological
agent delivery system can be used in conjunction with, or used
separate from, a stent and/or other types of implants to deliver a
biological agent into a body cavity, organ or other part of the
body. In addition, the present invention is particularly directed
for use in humans; however, the present invention can be used in
animals and some types of plants.
INCORPORATION BY REFERENCE
[0003] U.S. Pat. Nos. 4,733,665; 4,739,762; 5,195,984; 5,725,572;
5,735,871; 5,755,781; 5,853,419; 5,861,027; 6,007,573; 6,059,810;
6,099,561; 6,200,337; and 6,206,916; U.S. patent application Ser.
Nos. 09/273,736 filed Mar. 22, 1999; and 09/771,073 filed Jan. 29,
2001; and PCT Patent Application No. WO 99/56663 are incorporated
herein by reference to illustrate various types and configurations
of stents, the process or method of manufacturing stents, and the
method by which such stents are used. U.S. Pat. Nos. 5,102,417;
5,464,650; 5,578,075; 5,616,608; 5,679,400; 5,716,981; 5,733,925;
5,981,568; and 6,206,916 and PCT Patent Application Nos. WO
90/13332; WO 91/12779; WO 99/56663; and WO 01/17577 are
incorporated herein by reference to illustrate various biological
agents that can be coated onto stents. These disclosed biological
agents are merely a few examples of the biological agents that can
be used in the present invention.
BACKGROUND OF THE INVENTION
[0004] Heart disease is still one of the most prevalent medical
ailments in the world. Intraluminal endovascular grafting, a type
of angioplasty procedure, has been demonstrated by experimentation
to present a possible alternative to conventional vascular surgery
and is used to treat heart disease. Intraluminal endovascular
grafting involves a tubular prosthetic graft or stent and delivery
within the vascular system. As defined herein, the terms "graft"
and "stent" are used interchangeably. Advantages of this method
over conventional vascular surgery include obviating the need for
surgically exposing, incising, removing, replacing, or bypassing
the defective blood vessel. Over 20 million angioplasty or related
procedures involving occluded vasculature have been preformed
worldwide. About 30% of these angioplasties fail within 30 days.
These failures typically require the procedure to be repeated.
[0005] Several years ago, a product called a stent, named after
Charles Stent, was introduced for use in angioplasty procedures.
The stent reduced the angioplasty failure rate to about 15 percent.
A stent is an expandable metal tubular device that is mounted over
an angioplasty balloon and deployed at the site of coronary
narrowing. The balloon is inflated to expand the stent to
physically open and return patency to the body passageway. After
the stent is expanded, the balloon is deflated and removed and the
stent is permanently disposed to retain the opened body passageway.
The first generation of expandable stents did not offer a
controllable radial expansion. An improved stent disclosed in U.S.
Letters Pat. No. 4,733,665 overcame the problem associated with
controlled stent expansion. However, prior art stents still do not
provide control over the final, expanded configuration of the
stent. For instance, the expansion of a particular coiled,
spring-type stent is predetermined by the method of manufacturing,
material and delivery system. In the case of self-expanding
intraluminal stents, or prostheses, formed of a heat sensitive
material which expands upon exposure to core body temperature, the
amount of expansion is predetermined by the heat expansion
properties of the particular alloy utilized in the manufacture of
the intraluminal stent. Consequently, once the foregoing types of
intraluminal stents were expanded at the desired location within a
body passageway, the expanded size of the stent could not be
increased. If the proposed expanded diameter of the narrow body
passageway was not determined correctly, the stent might not expand
enough to contact the interior surface of the body passageway so as
to be secured thereto and/or not expand the body passageway to the
desired diameter. The stent disclosed in the '665 patent overcame
the problems associated with these past stent designs.
[0006] The stent based upon the '665 patent is currently being used
in angioplasty procedures. Stents, including the stent of the '665
patent, are presently used in approximately 30-60 percent of all
angioplasty procedures. However, these stents have several
shortcomings which contribute to procedural failure rates. The
currently used stents are not readily visible under fluoroscopic
guidance procedures. Stent placement is hindered as a result of
poor visibility. As a result, precise positioning of the stent
during the insertion procedure was difficult to achieve.
Consequently, the stent could be inadvertently positioned in the
wrong or non-optimal location in the body passageway. These stents
also shorten longitudinally after radial expansion, which is not
desirable for their intended use. The shortening of the stent
resulted in longitudinal movement of the stent during expansion,
which sometimes resulted in the stent being filly expanded in the
wrong or non-optional position. One stent design was proposed in
U.S. Pat. No. 5,853,419. The stent included a hexagon in the side
wall of the stent which theoretically resulted in the stent
retaining its longitudinal length during expansion. The stent also
included ends that flared outwardly. However, in practice, the
stent does not expand as described in the '419 patent. Due to the
hexagonal configuration of the openings in the stent, the struts
that form the hexagonal configuration cause the ribs of the
hexagonal configuration to bend, buckle or twist when the struts
are being expanded, thus resulting in a reduction in the
longitudinal length of the stent. The bending, buckling or twisting
of the ribs can only be avoided if the struts are made of a very
flexible or bendable material; however, the use of such material
compromises the strength of the stent. Not only does the stent not
retain its longitudinal length, the complex stent design is both
difficult to manufacture and uniformly expand in a body
passageway.
[0007] The improved stent disclosed in U.S. patent application Ser.
No. 09/273,736 filed Mar. 22, 1999, which is incorporated herein by
reference, overcomes these past problems with stents. The patent
application discloses an improved stent that can be coated with one
or more substances in various regions of the stent to improve the
visibility of the stent by various techniques (e.g. fluoroscopy)
during the insertion procedure, thereby improving the positional
accuracy of the stent in the body passageway. The improved stent
also incorporates a unique design which enables the stent to retain
its original longitudinal length during expansion. The improved
stent also is easier to manufacture and substantially uniformly
expands in the body passageway.
[0008] Although the improved stent overcomes the deficiencies of
prior art stents with respect to accurate stent positioning,
problems can still exist with respect to tissue damage by the stent
during insertion and/or expansion of the stent. The two ends of
prior art stents typically include one or more rough, sharp and/or
pointed surfaces. These surfaces can cause irritation and/or damage
to surrounding tissue as the stent is moved within the body
passageways. Such irritation or damage to the surrounding tissue
can create various types of complications during the surgical
procedure. These surfaces can also cause damage to surrounding
tissue during the expansion of the stent. During stent expansion,
the middle of the stent is first expanded by the angioplasty
balloon. As the middle of the stent expands, the ends of the stent
move toward one another. This movement of the ends can result in
the stent ends digging into and/or penetrating the surrounding
tissue. Furthermore, tissue damage can result when the end portions
of the stent are eventually expanded by the angioplasty balloon.
Stent designs that have flared out ends can also cause damage to
tissue during insertion of the stent and expansion of the stent.
U.S. patent application Ser. No. 09/771,073 filed Jan. 29, 2001,
which is incorporated herein by reference, includes a stent design
that overcomes or minimizes tissue damage by the stent during stent
insertion and stent expansion. The stent includes rounded and/or
smooth edges for the end portions of the stent.
[0009] Several problems can develop after the stent is inserted
into a body passageway. One problem is known as in-stent restenosis
wherein the body passageway, which has been previously treated with
a stent, renarrows or closes within the stented segment. The
renarrowing or closure of the body passageway can be caused by a
structural failure of the stent due to contractive forces by the
body passageway on the stent and/or by the body passageway growing
into the openings in the stent. Other problems can include vascular
narrowing and restenosis. Vascular narrowing is defined as a
vascular segment that has not been previously treated by any
interventional means and eventually closes, thereby preventing
fluid body passageway. Restenosis is the renarrowing of a
previously treated vascular segment not involving a stent. Both of
these problems are the result of a body passageway that was not
treated with an invasive angioplasty, narrowing or closing, and
from the insertion of a stent in one portion of the body passageway
causing vascular narrowing or restenosis in another part of the
body passageway. Vascular narrowing, restenosis and in-stent
restenosis are caused by biological factors causing the premature
closing of the body passageways. One such biological factor is
platelet derived growth factor, referred to as PDGF. PDGF is an
intercellular messenger capable of stimulating proliferation of
smooth muscle cells. Smooth muscle cells are known to migrate
within body passageways such as arteries and cause a restenotic
reaction.
[0010] The problems with vascular narrowing, restenosis and
in-stent restenosis are significantly overcome by the use of one or
more drugs. U.S. Letters Pat. No. 6,206,916 entitled "Coated
Intraluminal Graft," which is incorporated herein by reference,
discloses the use of a drug coated on at least a portion of the
stent to inhibit or prevent the occurrence of in-stent restenosis,
vascular narrowing and/or restenosis. Although the intravenous use
of drugs and/or the coating of the stent with drugs can inhibit or
prevent the occurrence of in-stent restenosis, vascular narrowing
and/or restenosis, the continued need for the drugs after the stent
has been inserted can require the patient to be retained in the
hospital for extended periods of time. Alternatively, in-stent
restenosis, vascular narrowing and/or restenosis may occur days or
weeks after the stent insertion procedure and after intravenous use
of drugs has terminated and/or the drug coating on the stent has
been dissolved off the stent. Several other United States patents
disclose the use of various drugs coated on stents. For example,
U.S. Pat. No. 5,716,981, which is incorporated herein by reference,
discloses the use of paclitaxel or an analog or derivative thereof
for use on a stent. U.S. Pat. Nos. 5,733,925 and 5,981,568, which
are incorporated herein by reference, disclose the use of taxol or
a water soluble taxol derivative; cytochalasin or analog thereof;
or other type of cytoskeletal inhibitor for use on a stent. Several
United States patents also disclose the use of polymers to bind the
various drugs to the surface of the stent. Several of these
polymers are disclosed in U.S. Pat. Nos. 5,578,075 and 5,679,400,
which are incorporated herein by reference. U.S. Pat. No.
5,464,650, which is incorporated herein by reference, discloses the
method of applying several coatings of a polymer that has been
mixed with a drug so as to control the delivery of the drug in a
body over a period of time. The method of coating the stent
involves a serves of steps that significant increases the cost,
complexity and time for the manufacture of the stent.
[0011] In view of the present stent technology, there is a need and
demand for a stent that has improved procedural success rates, has
higher viability under fluoroscopy in vivo, retains its
longitudinal dimensions from its original pre-expanded
configuration to its expanded configuration, minimizes damage to
tissue during insertion and expansion of the stent, inhibits or
prevents the occurrence of in-stent restenosis, vascular narrowing
and/or restenosis long after the stent has been inserted into a
body passageway, and is simple and cost effective to
manufacture.
SUMMARY OF THE INVENTION
[0012] This invention pertains to an improved expandable stent
designed to meet the present day needs and demands relating to
stents. The present invention is directed to a stent having a body
member that includes first and second ends and a wall surface
disposed between the first and second ends The wall surface is
typically formed by a plurality of intersecting elongated members,
and at least some of the elongated members typically intersect with
one another at a point intermediate to the first and second ends of
the body member. Alternatively, or in addition, the wall surface
includes one or more slots. The body member has a first
cross-sectional area which permits delivery of the body member into
a body passageway, and a second, expanded cross-sectional area. As
defined herein, the term "body passageway" means any passageway or
cavity in a living organism, including humans, animals and plants.
A "body passageway" in an animal or human includes, but is not
limited to, the bile duct, bronchiole tubes, blood vessels, the
esophagus, trachea, ureter, urethra, the intestines, lymphatic
vessels, nasal passageways, and/or the like. The invention when
used in association with stents is particularly applicable for use
in blood vessels, and will hereinafter be particularly described
with reference thereto. The expansion of the stent body member can
be accomplished in a variety of manners. Typically, the body member
is expanded to its second cross-sectional area by a radially,
outwardly extending force applied at least partially from the
interior region of the body member. Alternatively or additionally,
the body member can include heat sensitive materials that expand
upon exposure to heat The second cross-sectional area of the stent
can be fixed or variable. When the second cross-sectional area is
variable, the second cross-sectional area is typically dependent
upon the amount of radially outward force applied to the body
member. Generally, the body member is expanded so as to expand at
least a portion of the body passageway while retaining the original
length of the body member. In one particular body member design,
the first cross-sectional shape of the body member is substantially
uniformly circular so as to form a substantially tubular body
member; however, the body member can have other cross-sectional
shapes such as, but not limited to, elliptical, oval, polygonal,
trapezoidal, and the like. As can be appreciated, the
cross-sectional shape of the body member can be uniform or
non-uniform in the first and/or second cross-sectional shape. In
addition, if more than one body member is included in a stent, all
the body members can have substantially the same size and shape, or
one or more of the body members can have a different size and/or
shape from one or more other body members.
[0013] Another and/or alternative feature of the present invention
is that the stent includes a plurality of elongated members wherein
one or more elongated members is a wire. In one embodiment, the
elongated members include a plurality of wires wherein the two or
more of the wires are secured to one another where a plurality of
wires intersect with one another. Two or more of the wires can be
connected together by a variety of techniques such as, but not
limited to, welding, soldering, brazing, adhesives, lock and groove
configurations, snap configurations, melting together the wires,
and the like. In another embodiment, the body member is at least
partially in the form of a wire mesh arrangement. The wire mesh
arrangement may be utilized as the stent. The wire mesh arrangement
is designed to be expanded to a second diameter within the body
passageway; the second expanded diameter being variable and
determined by the desired expanded internal diameter of the body
passageway, whereby the expanded wire mesh arrangement will not
migrate from the desired location within the body passageway, and
the expansion of the stent does not cause a rupture of the body
passageway. In still another embodiment, the plurality of wires
forms a plurality of polygonal shaped regions on the body of the
stent. In one specific design, the polygonal regions are aligned
along the longitudinal axis of the body of the stent. In another
specific design, the body of the stent includes a plurality of
polygonal regions that are aligned along the longitudinal axis and
lateral axis of the stent body. In one aspect of this specific
design, the plurality of polygonal regions aligned along the
longitudinal axis of the stent body are oriented substantially the
same with respect to one another, and the plurality of polygonal
regions aligned along the lateral axis are oriented differently
from one another. In one example of this specific design, the
polygonal regions that are aligned along the same longitudinal axis
have a top that lies in the same longitudinal axis and have a
bottom that lies in the same longitudinal axis. In addition, the
polygonal regions that are aligned along the same latitudinal axis
have sides that does not lie in the same latitudinal axis; however,
alternating polygonal regions have sides that are substantially
parallel to one another. In still another specific design, the side
wall of at least one body member includes an even number of
polygonal regions about the peripheral surface of the body member.
In still another embodiment, the polygonal shape, upon expansion,
retains the original longitudinal length of the body of the stent.
In one aspect of this embodiment, a plurality of polygonal shapes
have a substantially parallelogram shape. In another aspect of this
embodiment, the body member includes about 2-15 polygonal shapes
along the longitudinal length of the body member, typically about
2-10 polygonal shapes, and more typically about 2-8 polygonal
shapes; however, more polygonal shapes can be used depending on the
shape and/or size of the body member.
[0014] Yet another and/or alternative feature of the present
invention is that the stent includes a plurality of elongated
members wherein one or more elongated members is a thin bar. In one
embodiment, the elongated members include a plurality of thin bars
wherein two or more of the thin bars are secured to one another
where a plurality of bars intersect with one another. Two or more
of the thin bars can be connected together by a variety of
techniques such as, but not limited to, welding, soldering,
brazing, adhesives, lock and groove configurations, snap
configurations, melting together the thin bars, and the like. In
still another embodiment, the plurality of thin bars forms a
plurality of polygonal shaped regions on the body of the stent. In
one specific design, the polygonal regions are aligned along the
longitudinal axis of the body of the stent. In another specific
design, the body of the stent includes a plurality of polygonal
regions that are aligned along the longitudinal axis and lateral
axis of the stent body. In one aspect of this specific design, the
plurality of polygonal regions aligned along the longitudinal axis
of the stent body are oriented substantially the same with respect
to one another, and the plurality of polygonal regions aligned
along the lateral axis are oriented differently from one another.
In one example of this specific design, the polygonal regions that
are aligned along the same longitudinal axis have a top that lies
in the same longitudinal axis and have a bottom that lies in the
same longitudinal axis. In addition, the polygonal regions that are
aligned along the same latitudinal axis have sides that does not
lie in the same latitudinal axis; however, alternating polygonal
regions have sides that are substantially parallel to one another.
In still another specific design, the side wall of at least one
body member includes an even number of polygonal regions about the
peripheral surface of the body member. In still another embodiment,
the polygonal shape, upon expansion, retains the original
longitudinal length of the body of the stent. In one aspect of this
embodiment, a plurality of polygonal shapes have a substantially
parallelogram shape. In another aspect of this embodiment, the body
member includes about 2-15 polygonal shapes along the longitudinal
length of the body member, typically about 2-10 polygonal shapes,
and more typically about 2-8 polygonal shapes; however, more
polygonal shapes can be used depending on the shape and/or size of
the body member.
[0015] Still yet another and/or alternative feature of the present
invention is that the side wall of at least one body member of the
stent includes a plurality of elongated members that are arranged
to form at least one polygonal shape. In one embodiment, the
polygonal shape, upon expansion, retains the original longitudinal
length of the body of the stent. In one aspect of this embodiment,
a plurality of polygonal shapes have a substantially parallelogram
shape. In another aspect of this embodiment, the body member of the
stent is formed from a flat piece of material. On the surface of
the flat material there are formed a plurality of polygonal shaped
regions. The flat material is rolled or otherwise formed and the
side edges of the flat material are connected together to form the
stent. The side edges of the flat material can be connected
together by a variety of techniques such as, but not limited to,
welding, soldering, brazing, adhesives, lock and groove
configurations, snap configurations, melting together the edges,
and the like. The polygonal regions in the flat material can also
be formed by a variety of techniques such as, but not limited to,
mechanical cutting, laser cutting, etching, molding, stamping,
and/or the like. In one specific design, the polygonal regions are
aligned along the longitudinal axis of the flat material. In
another specific design, the flat material includes a plurality of
polygonal regions are aligned along the longitudinal axis and
lateral axis of the flat material. In one aspect of this specific
design, the plurality of polygonal regions aligned along the
longitudinal axis of the flat material are oriented substantially
the same with respect to one another, and the plurality of
polygonal regions aligned along the lateral axis are oriented
differently from one another. In one example of this specific
design, the polygonal regions that are aligned along the same
longitudinal axis have a top that lies in the same longitudinal
axis and have a bottom that lies in the same longitudinal axis. In
addition, the polygonal regions that are aligned along the same
latitudinal axis have sides that does not lie in the same
latitudinal axis; however, alternating polygonal regions have sides
that are substantially parallel to one another. In still another
specific design, the side wall of at least one body member includes
an even number of polygonal regions about the peripheral surface of
the body member. In still yet another specific design, the body
member includes about 2-15 polygonal shapes along the longitudinal
length of the body member, typically about 2-10 polygonal shapes,
and more typically about 2-8 polygonal shapes; however, more
polygonal shapes can be used depending on the shape and/or size of
the body member.
[0016] Another and/or alternative feature of the present invention
is that the side wall of at least one body member of the stent
includes at least one set of slots. In one embodiment, the one or
more sets of slots are arranged to maintain the original
longitudinal length of the body member when the body member is
expanded. In one aspect of this embodiment, the body member of the
stent is formed from a substantially flat single piece of material.
On the surface of the flat material there are formed a plurality of
slots. The flat material is rolled or otherwise formed and the side
edges of the flat material are connected together to form the
stent. The side edges of the flat material can be connected
together by a variety of techniques such as, but not limited to,
welding, soldering, brazing, adhesives, lock and groove
configurations, snap configurations, melting together the edges,
and the like. The slots in the flat material can also be formed by
a variety of techniques such as, but not limited to, mechanical
cutting, laser cutting, etching, molding, stamping, and/or the
like. In another embodiment, at least one set of slots forms
substantially a V-shape when the body member is unexpanded. In one
aspect of this embodiment, body portion includes a plurality of
V-shapes. In one specific design of this aspect, a plurality of
V-shapes are aligned along the longitudinal axis of the side wall
of the body member and are positioned in a partial stacked position
with respect to one another. Generally the body member includes
about 2-20 V-shapes in each set of V-shapes, typically about 2-10
V-shapes, and more typically about 2-5 V-shapes; however, more
V-shapes per set can be used depending on the shape and/or size of
the body member. In another specific design of this aspect, a
plurality of V-shapes are aligned along the latitudinal axis of the
side wall of the body member. In still another specific design of
this aspect, at least a plurality of the V-shapes are substantially
equally spaced from one another. In another specific design, an
even number of V-shapes are aligned along the latitudinal axis of
the side wall of the body member. In yet another specific design of
this aspect at least a plurality of V-shapes have substantially the
same angle when the body member is unexpanded. In still yet another
specific design of this aspect, the angle formed by the V-shapes is
between 0-90.degree. when the body member is unexpanded, typically
about 10-75.degree., and more typically about 15-60.degree., and
even more typically about 15-45.degree.. In a further specific
design of this aspect, a plurality of slots have a length dimension
that is at least about twice as great as the width dimension of the
slot when the body member is unexpanded, and typically at least
about 3 times as great, and more typically at least about 5 times
as great, and even more typically at least about 10 times as great,
and still even more typically at least about 15 times as great. In
still a further specific design, a plurality V-shapes in a set of
V-shapes are oriented in the same direction with respect to one
another and oriented such that the base of one V-shape is
positioned from the base of an adjacent V-shapes a distance that is
at least about 15% of the length of the legs of the V-shaped slot,
typically about 15-80% of the length of the slots forming a leg of
the V-shape, typically about 20-60% of the length of the leg of the
V-shape, and even more typically about 30-50% of the length of the
leg of the V-shape. In still yet a further specific design, a
plurality of slots have a substantially oval shape. In another
specific design, at least a plurality of slots that form the
V-shape do not intersect with one another. In one design, none of
the slots that form the V-shape intersect with one another.
[0017] Still another and/or alternative feature of the present
invention is that the body member has a biocompatible coating that
is coated and/or impregnated on at least a portion of its wall
surface. The biocompatible coating can be used to reduce
inflammation, infection, irritation and/or rejection of the stent.
In one embodiment, the biocompatible coating includes, but is not
limited to, a metal coating. In one aspect of this embodiment, the
metal coating is plated on at least a portion of the stent. In
another aspect of this embodiment, the metal coating includes, but
is not limited to, gold, platinum, titanium, nickel, tin, or
combinations thereof. In another embodiment, the biocompatible
coating includes, but is not limited to, a polymer and/or a
copolymer coating. In one aspect of this embodiment, the polymer
and/or a copolymer coating includes, but is not limited to,
polytetrafluoroethylene, polyethylene, poly(hydroxyethly
methacrylate) and derivatives thereof, poly(vinyl alcohol),
polycaprolactone, poly(D, L-lactic acid), poly(L-lactic acid),
poly(lactide-co-glycolide), poly(hydroxybutyrate),
poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoester,
polyanhydride, poly(glycolic acid), poly(glycolic
acid-cotrimethylene cabonate), polyphosphoester, polyphosphoester
urethane, poly(amino acids), cyanoacrylates, poly(trimethylene
carbonate), poly(iminocarbonate), copoly(ether-esters),
polyalkylene oxalates, polyphosphazenes, polyiminocarbonates,
aliphatic polycarbonates, polyethylene oxide, polyethylene gylcol,
poly(propylene oxide), polyacrylamides, polyacrylic acid,
polymethacrylic acid, poly(N-vinyl-2-pyrollidone), polyurethanes,
poly(aminoacid), cellulosic polymers (e.g. sodium carboxymethyl
cellulose, hydroxyethyl celluslose), collagens, carrageenan,
alginate, starch, dextrin, gelatins, poly(lactide),
poly(glycolide), polydioxanone, polycaprolactone,
polyhydroxybutyrate, poly(phospazazene), poly(phosphate ester),
poly(lactide-co-glycolide), poly(glycolide-co-trimethylene
carbonate), poly(glycolide-co-caprolactone), polyanhydrides,
polyamides, polyesters, polyethers, polyketones, polyether
elastomers, polyether amide elastomers, polyacrylate-based
elastomers, polyethylene, and/or polypropylene. In still another
embodiment, the biocompatible coating includes, but is not limited
to, living cells.
[0018] Still yet another and/or alternative feature of the present
invention is that the stent, upon expansion, substantially
maintains its original longitudinal length. In one embodiment, the
stent, upon expansion, substantially maintains its original
longitudinal length throughout the expansion of the stent.
[0019] Another and/or alternative feature of the present invention
is that the stent includes at least two body members that are
connected together by at least one connector member that allows
transverse bending and flexibility invariant to the plane of
bending. In ore embodiment, the connector member is a substantially
V-shaped or U-shaped member. In another embodiment, the two body
members are connected together by a plurality of connectors. In one
aspect of this embodiment, two or more of the connectors are spaced
at substantially equal distances from one another. In another
aspect of this embodiment, two or more of the connectors are
substantially symmetrically oriented from one another. In still
another aspect of this embodiment, at least three connectors
connect together two body members, and typically about 3-20
connectors connect together two body members, and even more
typically about 3-10 connectors connect together two body members.
In still another embodiment, the size of the connector is limited
so as not to interfere with the proper expansion of the stent. In
one aspect of this embodiment, the substantially V-shaped or
U-shaped member has a height that is less than about five times the
maximum height of a polygonal shape in the unexpanded stent, and
typically less than about three times the maximum height of a
polygonal shape in the unexpanded stent, and more typically less
than about two times the maximum height of a polygonal shape in the
unexpanded stent, and even more typically less than about 1.75
times the maximum height of a polygonal shape in the unexpanded
stent, and yet even more typically less than about 1.5 times the
maximum height of a polygonal shape in the unexpanded stent, and
still yet even more typically less than about 1.3 times the maximum
height of a polygonal shape in the unexpanded stent. In another
aspect of this embodiment, the substantially V-shaped or U-shaped
member has a height that is less than about 1.5 times the maximum
width of the V-shape in the unexpanded stent, and typically less
than about 1.0 times a maximum width of the V-shape in the
unexpanded stent, and more typically less than about 0.75 times the
maximum width of the V-shape in the unexpanded stent , and even
more typically less than about 0.65 times the maximum width of the
V-shape in the unexpanded stent, and yet typically less than about
0.5 times the maximum width of the V-shape in the unexpanded stent,
and still yet more typically less than about 0.4 times the maximum
width of the V-shape in the unexpanded stent.
[0020] Yet another and/or alternative feature of the present
invention is that the body member is made of and/or includes a
material that is visible under fluoroscopy in vivo. The material to
increase visibility includes, but is not limited to, metals,
polymers and/or copolymers. In one embodiment, the material to
increase visibility is adhered to the surface of at least a portion
of the stent by coating, plating, mounting, welding and/or
braising. In another embodiment, the material to increase
visibility is secured to the stent so as to principally come in
contact with the inner luminal surface of the body passageway. For
instance, when the stent is inserted into a vessel, the material to
increase visibility primarily contacts the inner luminal surface of
the vessel and not any blood-borne components that could accelerate
stent failure rates. In one aspect of this embodiment, the material
to increase visibility is at least partially located at at least
one end, and typically both ends, of the body member. This
positioning of the material on the body member helps to identify
the location of the ends of the body member and the stent as a
whole, thus enhancing the critical placement of the stent so as to
reduce the failure rate. In another aspect of this embodiment, the
material to increase visibility is at least partially located on
the outer surface of the body member at the connector member of the
stent. This location of the material also enhances the critical
placement of the stent around areas of high tortuosity so as to
reduce the failure rate. In still another embodiment, the material
to increase visibility includes gold. In one aspect of this
embodiment, the gold is plated on at least a portion of the
stent.
[0021] Still another and/or alternative feature of the present
invention is that the stent material is treated with gamma, beta
and/or e-beam radiation to reduce the vascular narrowing of the
stented section. The radiation treatment can inactivate the cell
migration and properties thereof within a 3 mm depth of the
arterial wall. The radiation treatment further sterilizes the stent
to reduce infection when the stent is inserted into a body
passageway.
[0022] Another and/or alternative feature of the present invention
is that the stent can be inserted and expanded by standard
procedures. Therefore, the stent can be inserted into a body
passageway until it is disposed at the desired location within the
body passageway. The stent can then be radially expanded outwardly
into contact with the body passageway until the body passageway, at
the desired location, has been expanded, whereby the stent inhibits
or prevents the body passageway from collapsing. In one embodiment,
the stent is at least partially expanded by an angioplasty
balloon.
[0023] Still another and/or alternative feature of the present
invention is a stent that includes rounded, smooth and/or blunt
surfaces that minimize and/or prevent damage to body cavities as
the stent is inserted into a body passageway and/or expanded in a
body passageway. The modified end surfaces are designed to reduce
the cutting and/or piercing of tissue as the stent is positioned in
and/or expanded in a body passageway. Typically, the path from the
point of entry into a body passageway, and the final position of
the stent in the body passageway, are not straight. As a result,
the stent is caused to be weaved through the body passageway to
reach the final position in the body passageway. This weaving of
the stent can result in the front ends, back ends, and/or side
walls of the stent to cut, scrape or otherwise damage tissue in the
body passageway as the stent is moved in the body passageway. The
rounding, smoothing and/or blunting of the surfaces significantly
reduces possible damage to the tissue. Damage to the tissue in the
body passageway can also occur during the expansion of the stent.
The rounding, smoothing and/or blunting of the surfaces likewise
significantly reduces possible damage to the tissue during the
expansion of the stent. In one embodiment, the rounding, smoothing
and/or blunting of the surfaces can be accomplished by a number of
different procedures. Some of these procedures include, but are not
limited to, buffing, grinding, and/or sanding the surfaces. In
another embodiment, the surfaces of the stent are smoothed by
coating and/or impregnating the stent with one or more metals or
compounds. In one aspect of this embodiment, at least a portion of
the stent is coated and/or impregnated with a polymer and/or
copolymer so as to reduce or eliminate the sharp, rough, and/or
pointed surfaces on the stent.
[0024] A further and/or alternative feature of the present
invention is that the stent is at least partially coated and/or
impregnated with one or more vascular active agents that inhibit
and/or reduce restenosis, vascular narrowing and/or in-stent
restenosis. In one embodiment, at least one of the vascular active
agents affects or alters tissue contraction and/or expansion to
inhibit and/or reduce restenosis, vascular narrowing and/or
in-stent restenosis. Prior substances have been coated onto stents
to address one or more problems associated with the use of stents.
These substances include aspirin, heparin, colchicine and
dexamethazone, among others. These substances are used to
inactivate platelets, stop cell division and prevent cell adhesion
The problems associated with the use of these substances have
varied effects. Heparin is not potent enough to extend a clinical
effect. Colchicine has been shown to kill the cells in the
surrounding area and actually propagate the problem. Dexamethazone
has not provided the desired restenosis prevention. As defined
herein, the term "vascular active agent" is defined as a substance
other than aspirin, colchicine, dexamethazone, or heparin. The
vascular active agent is formulated to inhibit, reduce, and/or
prevent restenosis, vascular narrowing and/or in-stent restenosis
in a body passageway. As can be appreciated, the vascular active
agent can be used independently of or in combination with a
"secondary vascular active agent." In one embodiment, the secondary
vascular active agent includes, but is not limited to, an agent
that inhibits, reduces, and/or prevents thrombosis. Such agent can
include, but is not limited to, antithrombotic compounds,
anti-platelet compounds, and/or anticoagulant compounds. In
addition, the "secondary vascular active agent" can include
compounds that include, but are not limited to, metabolic
inhibitors, antineoplastics, proliferation inhibitors, cytotoxic
compounds, antiplatelets, anti-coagulants, fribrinolytics, thrombin
inhibitors, antimitotics, anti-inflammatory compounds, radioactive
isotopes, and/or anti-tumor compounds. Furthermore, the "secondary
vascular active agent" can include, but is not limited to, DNA,
plasmid DNA, RNA, plasmid RNA, ACE inhibitors, growth factors,
cholesterol-lowering agents, vasodilating agents, oligonucleotides,
and/or anti-sense oligonucleotides. Specific secondary vascular
active agents that can be used include, but are not limited to,
aspirin, colchicine, heparin, glucocorticoids (e.g. dexamethazone,
betamethazone), hirudin, tocopherol, angiopeptin, D-Phe-ProArg
chloromethyl ketone, and/or derivatives of these compounds.
Heretofore, Applicant is unaware of stents being coated and/or
impregnated with a combination of at least one vascular active
agent and at least one secondary vascular active agent. In
addition, Applicant is unaware of stents being coated and/or
impregnated with a combination of two or more secondary vascular
active agents. Although the prior use of a single secondary
vascular active agent has not resolved problems associated with
instent restenosis, vascular narrowing and/or restenosis, the
combination of two or more of these compounds coated and/or
impregnated on the stent can provide better results. The scope of
this invention encompasses the concept of at least partially
coating and/or impregnating the stent with two or more secondary
vascular active agents by themselves or in combination with one or
more vascular active agents. In one aspect of this embodiment, the
vascular active agent includes a compound that at least partially
inhibits PDGF activity in the body passageway. After a stent is
inserted into a body passageway, the stent may induce some
irritation in the body passageway. The biological factor, PDGF, is
turned on due to such irritation and activates the components of
clotting. These components can cause clotting in the stent area or
in adjacent areas. This clotting can cause the body passageway to
narrow or ultimately close. At least one or more substances coated
and/or impregnated onto the stent are formulated to deactivate
and/or inhibit the activity of the PDGF, thereby reducing the
occurrence of in-stent restenosis, vascular narrowing and/or
restenosis. In another aspect of this embodiment, at least one of
the vascular active agents that is at least partially coated and/or
impregnated onto the stent to inhibit PDGF activity in the body
passageway includes triazolopyrimidime (Trapidil). When the stent
is inserted into a body passageway, some damage to the tissue of
the body passageway can occur. For instance, a damaged endothelium
exposes the connective tissue to platelet aggregation and to local
release of PDGF. Numerous animal models have shown that platelet
adhesion to the vascular wall of this damaged endothelium soon
triggers the proliferation and migration of smooth muscle cells. If
platelets are a source of PDGF, it has now been demonstrated that
endothelial cells, macrophages and smooth muscle cells are also a
source of PDGF following vascular trauma. The influence of Trapidil
on platelet aggregation is linked to inhibition of the synthesis of
thromboxane A2 and the partial blocking of thromboxane A2
receptors. Trapidil is able to normalize an incorrect balance
between thromboxane M and prostacycline. Thromboxane A2 is a
powerful inducer of platelet aggregation. Thromboxane A2 is also
responsible for the contraction of smooth muscles or vessels and
stimulates the proliferation of the arterial intimal cells.
Prostacyclin inhibits platelet aggregation and has vasodilator
properties. Trapidil also has antithrombotic properties and can
significantly reduce thrombosis induced by creation of an
arteriovenous conduit, as compared to aspirin and dipyridamoles,
which only had a modest effect. Trapidil has other desirable
properties such as vasodilation, a decrease in angina and an
increase in HDL levels in patients with ischemic heart disease.
Trapidil effectively inhibits of restenosis. Trapidil has an
affinity to exert clinical effects starting in the second hour of
treatment. The platelet inhibition in the first day of treatment
with Trapidil continues through the thirtieth day. The philosophy
of a multifactorial approach, including but not limited to the
increasing success of angioplasty and stent associated with a
considerable reduction in complications, promotes the use of this
technique in a large scale in the treatment of patients with
coronary heart disease. Restenosis is one of the most important
limitations to the long term benefits of angioplasty and a stent
combination. A pharmacological approach aiming to intervene in the
mechanism of restenosis is needed to supplement the mechanical
approach of the revascularization procedure. Various approaches
have been proposed for the prevention of restenosis. The use of
drugs such as, but not limited to, Trapidil, delivered by a stent
locally to the affected area satisfies this need. As can be
appreciated, Trapidil can be used in combination with one or more
other vascular active agents and/or in combination with one or more
secondary vascular active agents. The amount of Trapidil coated
and/or impregnated into the stent can be varied depending on the
intended use of the stent and/or size of the stent. In one
embodiment, the stent includes up to about 200 mg of Trapidil. In
one aspect of this embodiment, the stent includes at least about 1
.mu.g of Trapidil. In another aspect of this embodiment, the stent
includes about 10 ng to about 50 mg of Trapidil. In still another
aspect of this embodiment, the stent includes about 20 .mu.g to
about 10 mg of Trapidil.
[0025] Still a further and/or alternative feature of the present
invention is that the stent is at least partially coated and/or
impregnated with one or more vascular active agents that promote
blood vessel growth. The ally or partially blocked blood vessel and
tissue about the filly or partially blocked blood vessel become
oxygen starved due to the impaired flow of blood through the fully
or partially blocked blood vessels. When a stent in inserted into
the blood vessel to reestablish a more normal blood flow rate
through the blood vessel, the region around the formerly fully or
partially blocked blood vessel once again begins to receive a
proper oxygen supply. However, prolonged oxygen starvation can
damage the blood vessels and surrounding tissue to an extent that a
substantial time period is required to naturally repair such
damaged tissue. Furthermore, the formerly blocked or partially
blocked blood vessel may be weaker resulting in further damage to
the blood vessel once normal blood flow rates are reestablished.
Many of these problems can be addressed by at least partially
coating and/or impregnating the stent with one or more vascular
active agents that promote blood vessel growth. One non-limiting
blood vessel growth promoter that can be coated and/or impregnated
on the stent is granulo-cyte-macrophage colony-stimulating-factor
(GM-CSF). GM-CSF has been found to simulate blood vessel growth
even in oxygen starved environments. As can be appreciated, GM-CSF
can be used in combination with one or more other vascular active
agents and/or in combination with one or more secondary vascular
active agents. The amount of GM-CSF coated and/or impregnated into
the stent can be varied depending on the intended use of the stent
and/or size of the stent. In one embodiment, the stent includes up
to about 200 mg of GM-CSF. In one aspect of this embodiment, the
stent includes at least about 1 .mu.g of GM-CSF. In another aspect
of this embodiment, the stent includes about 1 .mu.g to about 50 mg
of GM-CSF. In still another aspect of this embodiment, the stent
includes about 20 .mu.g to about 10 .mu.g of GM-CSF.
[0026] Yet another and/or alternative feature of this invention
corresponds to the local delivery of the vascular active agent to
inhibit and/or prevent restenosis, vascular narrowing and/or
in-stent restenosis including, but not limited to, Trapidil,
through an angioplasty balloon with the physical capability to
transfer solute of the vascular active agent through the
angioplasty balloon membrane to the affected sight. As can be
appreciated, a secondary vascular active agent such as, but not
limited to, GM-CSF, can be delivered in combination with the
vascular active agent or in alternative to the vascular active
agent. This delivery can be in the form of a stream, a slow oozing
delivery or a bolus injection. The delivery can be made through
magnetic, electrical or physical arrangements. In one embodiment,
the delivery of a vascular active agent and/or secondary vascular
active agent is accomplished through a separate passageway capable
of channeling the solute of the vascular active agent to the
affected area. This delivery through an angioplasty balloon also
delivers the vascular active agent and/or secondary vascular active
agent to the sight of restenosis, vascular narrowing, in-stent
restenosis, thrombosis and the like, and/or the site to promote
growth of blood vessels. In one aspect of this embodiment, the
angioplasty balloon includes one or more slits or openings wherein
the vascular active agent and/or secondary vascular active agent
can stream, ooze or otherwise flow out of the angioplasty balloon
and into the body passageway. The one or more slits and/or openings
can be designed so as to allow the vascular active agent and/or
secondary vascular active agent to exit the angioplasty balloon
when the angioplasty balloon is in an expanded and unexpanded
state. In one specific design, the one or more slits and/or
openings in the angioplasty balloon inhibit or prevent the vascular
active agent and/or secondary vascular active agent from entering
the body passageway when the angioplasty balloon is in the
unexpanded state.
[0027] Another and/or alternative feature of the present invention
is that the vascular active agent can inhibit and/or reduce
restenosis, vascular narrowing and/or in-stent restenosis, and/or
can promote blood vessel growth, and/or secondary vascular active
agent is at least partially coated and/or impregnated on specific
regions of the stent or totally coats the stent. The thickness of
the coating on the stent can be uniform or varied. Generally, the
thickness of the coating is not as important as the concentration
of the vascular active agent and/or secondary vascular active agent
needed to acquire the desired affect. High concentrations of
vascular active agents and/or secondary vascular active agents can
be coated with thinner coatings, and lower concentrations of
vascular active agents and/or secondary vascular active agents can
be coated with thicker coatings.
[0028] Still another and/or alternative feature of the present
invention is that the vascular active agent can inhibit and/or
reduce restenosis, vascular narrowing and/or in-stent restenosis,
and/or can promote blood vessel growth, and/or secondary vascular
active agent is at least partially coated and/or impregnated onto
the stent by the use of an intermediate compound. Typically, the
compound is a synthetic biocompatible material that does not
adversely affect the vascular active agent and/or secondary
vascular active agent or cause problems or adverse reactions in the
body passageway.
[0029] Still yet another and/or alternative feature of the present
invention is that the stent and/or implant such as, but not limited
to, a prosthetic device, is at least partially coated and/or
impregnated with, and/or at least partially includes one or more
biological agents. As defined herein, the term "biological agent"
is defined as any substance, drug or otherwise, that is formulated
or designed to prevent, inhibit and/or treat one or more biological
problems, such as, but not limited to, viral, fungus and/or
bacteria infection; vascular disorders; digestive disorders;
reproductive disorders; lymphatic disorders; cancer; implant
rejection; pain; nausea; swelling; arthritis; bone disease; organ
failure; immunity diseases; cholesterol problems; blood diseases;
lung diseases and/or disorders; heart diseases and/or disorders;
brain diseases and/or disorders; neuroglial diseases and/or
disorders; kidney diseases and/or disorders; ulcers; liver diseases
and/or disorders; intestinal diseases and/or disorders; gallbladder
diseases and/or disorders; pancreatic diseases and/or disorders;
psychological disorders; respiratory disorders; gland disorders;
skin diseases; hearing disorders; oral disorders; nasal disorders;
eye disorders; fatigue; genetic disorders; burns; scars; trauma;
weight disorders; addiction disorders; hair loss; cramps; muscle
spasms; tissue repair; and/or the like. As such, the term
"biological agent" includes vascular active agents and secondary
vascular active agents. In one embodiment, the "biological agent"
includes the "vascular active agents" and "secondary vascular
active agents" discussed above.
[0030] A further another and/or alternative feature of the present
invention is that the biological agent is at least partially
encapsulated by a material. In one embodiment, the biological agent
includes one or more vascular active agents and/or one or more
secondary vascular active agents to inhibit and/or reduce
restenosis, vascular narrowing and/or in-stent restenosis. In
another embodiment, the biological agent is at least partially
encapsulated in biodegradable polymer and/or copolymer. In one
aspect of this embodiment, the polymer and/or copolymer is at least
partially formulated from aliphatic polyester compounds such as,
but not limited to, PLA (i.e. poly(D, L-lactic acid), poly(L-lactic
acid)) and/or PLGA (i.e. poly(lactide-co-glycoside)). In still
another embodiment, the rate of degradation of the polymer and/or
copolymer is principally a function of 1) the water permeability
and solubility of the polymer and/or copolymer, 2) chemical
composition of the polymer and/or copolymer, 3) mechanism of
hydrolysis of the polymer and/or copolymer, 4) the biological agent
encapsulated in the polymer and/or copolymer, 5) the size, shape
and surface volume of the polymer and/or copolymer, 6) porosity of
the polymer and/or copolymer, and/or 7) the molecular weight of the
polymer and/or copolymer. As can be appreciated, other factors may
also affect the rate of degradation of the polymer and/or
copolymer. The rate of degradation of the polymer and/or copolymer
controls the amount of biological agent released during a specific
time period into the body passageway or other parts of the body. As
can be appreciated, the biological agent can be formed into a pill,
capsule or the like for oral ingestion by a human or animal. The
rate of degradation of the polymer and/or copolymer that is at
least partially encapsulating the biological agent controls the
amount of biological agent that is released into a body passageway
or other part of the body over time. The biological agent can be at
least partially encapsulated with different polymer and/or
copolymer coating thickness, different numbers of coating layers,
and/or with different polymers or copolymers to alter the time
period one at least partially encapsulated biological agent is
released in a body passageway or other part of the body over time
as compared to another at least partially encapsulated biological
agent. Alternatively or in addition, one or more at least partially
encapsulated biological agents can be at least partially
encapsulated in a biodegradable capsule and/or coating, which
biodegradable capsule and/or coating delays the exposure of one or
more of the at least partially encapsulated biological agents to
fluids in a body passageway or other part of the body. As can
further be appreciated, the at least partially encapsulated
biological agent can be introduced into a human or animal by means
other than by oral introduction, such as, but not limited to,
injection, topical applications, intravenously, eye drops, nasal
spray, surgical insertion, suppositories, intrarticularly,
intraocularly, intranasally, intradermally, sublingjally,
intravesically, intrathecally, intraperitoneally, intracranially,
intramuscularly, subcutaneously, directly at a particular site, and
the like. In another aspect of this embodiment, the polymer and/or
copolymer is formed into one or more shapes such as, but not
limited to, spherical, cubical, cylindrical, pyramidal, and the
like.
[0031] Yet a further another and/or alternative feature of the
present invention is that the stent and/or implant is at least
partially coated and/or impregnated with one or more polymers or
copolymers that include one or more biological agents. In one
embodiment, at least one biological agent is combined with a
coating compound and at least partially coated and/or impregnated
on the stent or other implant. In one aspect of this embodiment, at
least one biological agent is mixed with the coating compound prior
to the coating compound being at least partially applied to the
stent or other implant.
[0032] In another aspect of this embodiment, at least one
biological agent is first applied to at least a portion of the
stent or other implant and the coating compound is applied over at
least a portion of the one or more biological agents. In still
another aspect of this embodiment, the coating compound is first
applied to at least a portion of the stent or other implant and at
least one biological agent is at least partially coated onto the
coating compound. As can be appreciated, the stent or other implant
can be at least partially impregnated and/or coated with one or
coating layers of biological agent, coating compound, coating
compound plus biological agent. Furthermore, the coating
compositions and/or thicknesses can be the same or different. In
addition, the concentration and/or type of biological agents in
each coating that is coated onto the stent or implant can be the
same or different. Still further, the coating thickness and/or
coating composition for each coating layer in various regions of
the stent or other implant can be the same or different. Generally,
the coating thickness of each coating on the stent or other implant
is less than about 0.08 inch, and typically less than about 0.01
inch, and even more typically less than about 0.005 inch. The
particular coating sequence on a stent or other implant will
generally depend on 1) the amount of a particular biological agent
to be released over time, 2) the sequence of biological agents to
be released over time, 3) the time period the release of the
biological agent is to begin, 4) the time period the release of the
biological agent is to end, and/or 5) the location in the body the
biological agent is to be released. As can be appreciated, other
factors may dictate the particular coating sequence on a stent or
other implant. The coating compound is formulated to delay and/or
regulate the time and/or amount of one or more biological agents
being released into the body passageway or other part of the body;
and/or to facilitate in the bonding of one or more biological
agents to the stent or other implant. The coating compound can be a
biodegradable compound, a non-biodegradable compound, or a
partially biodegradable compound. The coating compound can be
formulated so as to form one or more bonds with one or more
biological agents or be chemically inert with respect to one or
more biological agents.
[0033] Still a further another and/or alternative feature of the
present invention is that the stent and/or implant is at least
partially formed by a material that includes one or more biological
agents. In one embodiment, one or more biological agents are at
least partially embedded in the stent or other implant so as to
prevent the release, control the release, and/or delay the release
of one or more biological agents into the body passageway or other
part of the body. The material forming at least a portion of the
stent or other implant in which one or more biological agents are
imbedded can be a biodegradable material, a non-biodegradable
material, or a partially biodegradable material. The material can
be formulated so as to form one or more bonds with one or more
biological agents or be chemically inert with respect to one or
more biological agents. Typically, the material is a substantially
non-biodegradable material so that the structural integrity of the
stent or other implant is maintained throughout the life of the
stent or other implant. However, there may be instances wherein the
stent or other implant advantageously becomes fully or partially
degraded over time, thus in such instances, the material can be
biodegradable or partially biodegradable. In one aspect of this
embodiment, the material includes a metal and/or polymer and/or
copolymer. In another embodiment, the material is at least
partially coated and/or impregnated with one or more coating
materials. The coating material can be biodegradable,
non-biodegradable, or partially biodegradable. The coating can
include one or more biological agents. In one aspect of this
embodiment, the coating material at least partially delays and/or
controls the release of one or more biological agents from the
material that at least partially forms the stent or other implant.
In another aspect of this embodiment, the coating material includes
one or more biological agents that are at least partially released
from the coating material together with or exclusive from the one
or more biological agents in the material of the stent or other
implant.
[0034] Still a further another and/or alternative feature of the
present invention is that one or more biological agents at least
partially forms a chemical bond with a material that at least
partially encapsulates one or more of the biological agents; that
at least partially coats and/or impregnates the stent or other
implant; and/or that at least partially forms the stent or other
implant. In one embodiment, one or more of the biological agents
forms a polymer and/or copolymer salt complex with a material that
at least partially encapsulates one or more of the biological
agents; that at least partially coats and/or impregnates the stent
or other implant; and/or that at least partially forms the stent or
other implant. In one aspect of this embodiment, the biological
agent includes, but is not limited to, Trapidal and/or derivatives
thereof; GM-CSF and/or derivatives thereof; taxol and/or
derivatives thereof (e.g. taxotere, baccatin, 10-deacetyltaxol,
7-xylosyl-10-deacetyltaxol, cephalomannine, 10-deacetyl-7-epitaxol,
7 epitaxol, 10-deacetylbaccatin III, 10-deacetylcephaolmannine);
5-Fluorouracil and/or derivatives thereof; Beta-Estradiol and/or
derivatives thereof; Tranilast and/or derivatives thereof; Probucol
and/or derivatives thereof; Angiopeptin and/or derivatives thereof;
paclitaxel and/or derivatives thereof; cytochalasin and/or
derivatives thereof (e.g. cytochalasin A, cytochalasin B,
cytochalasin C, cytochalasin D, cytochalasin E, cytochalasin F,
cytochalasin G, cytochalasin H, cytochalasin J, cytochalasin K,
cytochalasin L, cytochalasin M, cytochalasin N, cytochalasin 0,
cytochalasin P, cytochalasin Q, cytochalasin R, cytochalasin S,
chaetoglobosin A, chaetoglobosin B, chaetoglobosin C,
chaetoglobosin D, chaetoglobosin E, chaetoglobosin F,
chaetoglobosin G, chaetoglobosin J, chaetoglobosin K, deoxaphomin,
proxiphomin, protophomin, zygosporin D, zygosporin E, zygosporin F,
zygosporin G, aspochalasin B, aspochalasin C, aspochalasin D);
aspirin and/or derivatives thereof; dipyridamoles and/or
derivatives thereof; argatroban and/or derivatives thereof;
forskolin and/or derivatives thereof; vapiprost and/or derivatives
thereof; prostacyclin and prostacyclin and/or derivatives thereof;
glycoprotein IIb/IIIa platelet membrane receptor antibody;
colchicine and/or derivatives thereof; dexamethazone and/or
derivatives thereof; dipyridamoles and/or derivatives thereof;
and/or heparin and/or derivatives thereof; glucocorticoids (e.g.
dexamethasone, betamethasone)and/or derivatives thereof; hirudin
and/or derivatives thereof; coumadin and/or derivatives thereof;
prostacyclenes and/or derivatives thereof; antithrombogenic agents;
steroids; seraminr and/or derivatives thereof; thioprotese
inhibitors; nitric oxide; ibuprofen; antimicrobials; antibiotics;
tissue plasma activators; rifamycin and/or derivatives thereof;
monoclonal antibodies; antifibrosis compounds; cyclosporine;
hyaluronate; protamine and/or derivatives thereof; tocopherol
and/or derivatives thereof; angiopeptin and/or derivatives thereof;
tick anticoagulant protein and/or derivatives thereof; methotrexate
and/or derivatives thereof; azathioprine and/or derivatives
thereof; vincristine and/or derivatives thereof; vinblastine and/or
derivatives thereof; fluorouracil and/or derivatives thereof;
adriamycin and/or derivatives thereof; mutamycin and/or derivatives
thereof; Anti-Invasive Factor; Cartilage-Derived Inhibitor;
retinoic acids and/or derivatives thereof, Suramin; Tissue
Inhibitor of Metalloproteinase-1 and/or derivatives thereof; Tissue
Inhibitor of Metalloproteinase-2 and/or derivatives thereof;
Plasminogen Activator Inhibitor-1 and/or derivatives thereof;
Plasminogen Activator Inhibitor-2 and/or derivatives thereof;
estramustine and/or derivatives thereof; methotrexate and/or
derivatives thereof, curacin-A and/or derivatives thereof;
epothilone and/or derivatives thereof; vinblastine and/or
derivatives thereof; tBCEV and/or derivatives thereof; lighter "d
group" transition metals (e.g. ammonium metavanadate, sodium
metavanadate, sodium orthovanadate, vanadyl acetylacetonate,
vanadyl sulfate mono- and trihydrates, ammonium tungstate, calcium
tungstate, sodium tungstate dihydrate, tungstic acid, tungsten (IV)
oxide, tungsten (VI) oxide, ammonium molybdate and its hydrates,
sodium molybdate and its hydrates, potassium molybdate and its
hydrates, molybdenum (VI) oxide, molybdenum (VI) oxide, molybdic
acid, molybdenyl acetylacetonate); Platelet Factor 4; growth
factors (e.g. VEGF; TGF; IGF; PDGF; FGF); Protamine Sulphate
(Clupeine); Sulphated Chitin Derivatives; Sulphated Polysaccharide
Peptidoglycan Complex; Staurosporine; proline analogs
(L-azetidine-2-carboxylic acid (LACA); cishydroxyproine;
d,L-3,4-dehydroproline; Thiaproline; alpha-dipyridyl; beta
aminopropionitrile fumarate;
4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone; Methotrexate
Mitoxantrone; Interferons; alpha 2 Macroglobulin; ChIMP-3;
Chymostatin; beta-Cyclodextrin Tetradecasulfate; Eponemycin;
Camptothecin; Fumagillin; Gold Sodium Thiomalate; D-Penicillamine;
beta-1-anticollagenase; alpha 2-antiplasmin; Bisantrene; Lobenzarit
disodium (N-(2)-carboxyphenyl-4-chloroanthronilic acid disodium;
Thalidomide; Angiostatic steroid; AGM-1470; carboxynaminolmidazole;
penicillins; cephalosporins (e.g. cefadroxil, cefazolin, cefaclor);
aminoglycosides (e.g. gentamycin, tobramycin; sulfonamides (e.g.
sulfamethoxazole); rapamycin, metronidazole; prednisone;
prednisolone; hydrocortisone; adrenocorticotropic hormone;
sulfasalazine; naproxen; fenoprofen; indomethacin; phenylbutazone;
acyclovir; ganciclovir; zidovudine; nystatin; ketoconazole;
griseofulvin; flucytosine; miconazole; clotrimazole; pentamidine
isethionate; quinine; chloroquine; mefloquine; thyroid hormone;
estrogen; progesterone; cortisone; growth hormone; insulin; T.sub.H
1 (e.g., Interleukins-2, -12, and -15, gamma interferon); T.sub.H 2
(e.g. Interleukins-4 and -10) cytokines); estramustine; epothilone;
curacin-A; colchicine; methotrexate; vinblastine;
4-tert-butyl.fwdarw.3-(2-chloroethyl)ureido!benzene ("tBCEU");
alpha-adrenergic blocking agents; angiotensin II receptor
antagonists; receptor antagonists for histamine; serotonin;
serotonin blockers; endothelin; inhibitors of the sodium/hydrogen
antiporter (e.g., amiloride and derivatives therof); agents that
modulate intracellular Ca.sup.2+ transport such as L-type (e.g.,
diltiazem, nifedipine, verapamil) or T-type Ca.sup.2+ channel
blockers (e.g. amiloride); calmodulin antagonists (e.g., H.sub.7);
inhibitors of the sodium/calcium antiporter (e.g. amiloride); ap-1
inhibitors (for tyrosine kinases, protein kinase C, myosin light
chain kinase, Ca.sup.2+/calmodulin kinase II, casein kinase II);
anti-depressants (e.g. amytriptyline, fluoxetine, LUVOX.RTM. and
PAXIL.RTM.); cytokine and/or growth factors as well as their
respective receptors, (e.g., the interleukins, alpha, beta or
gamma-IFN (interferons), GM-CSF, G-CSF, epidermal growth factor,
transforming growth factors alpha and beta, TNF, and antagonists of
vascular epithelial growth factor, endothelial growth factor,
acidic or basic fibroblast growth factors, and platelet derived
growth factor); inhibitors of the IP.sub.3 receptor; protease;
collagenase inhibitors; nitrovasodilators (e.g. isosorbide
dinitrate); anti-mitotic agents (e.g. colchicine, anthracyclines
and other antibiotics, folate antagonists and other
anti-metabolites, vinca alkaloids, nitrosoureas, DNA alkylating
agents, topoisomerase inhibitors, purine antagonists and analogs,
pyrimidine antagonists and analogs, alkyl sulfonates);
immunosuppressive agents (e.g. adrenocorticosteroids,
cyclosporine); sense or antisense oligonucleotides (e.g. DNA, RNA,
plasmid DNA, plasmid RNA, nucleic acid analogues (e.g. peptide
nucleic acids); inhibitors of transcription factor activity (e.g.
lighter d group transition metals); anti-neoplastic compounds;
chemotherapeutic compounds (e.g. 5-fluorouracil, vincristine,
vinblastine, cisplatin, doxyrubicin, adriamycin, or tamocifen),
radioactive agents (e.g. Cu-64, Ca-67, Cs-131, Ga-68, Zr-89, Ku-97,
Tc-99m, Rh-105, Pd-103, Pd-109, In-111, I-123, I-125, I-131,
Re-186, Re-188, Au-198, Au-199, Pb-203, At-211, Pb-212, Bi-212,
H.sub.3P.sup.32O.sub.4); 7E-3B; CAPTOPRIL; CILAZAPRIL; LISINOPRIL;
LOVASTATIN; nitroprusside; phosphodiesterase inhibitors;
prostaglandin inhibitors; thioprotesase inhibitors;
triazolopyrimidine and/or derivatives thereof; calcium channel
blockers; toxins (e.g. ricin, abrin, diphtheria toxin, cholera
toxin, gelonin, pokeweed antiviral protein, tritin, Shigella toxin,
and Pseudomonas exotoxin A); metalloproteinase inhibitors; ACE
inhibitors; growth factors; oligonucleotides; antiplatlet
compounds; antitabolite compourds; anti-inflammatory compounds;
anticoagulent compounds; antimitotic compounds; antioxidants;
antimetabolite compounds (e.g. staurosporin, trichothecenes, and
modified diphtheria and ricin toxins, Pseudomonas exotoxin);
anti-migratory agents (e.g. caffeic acid derivatives, nilvadipine);
anti-matrix compounds (e.g. colchicine, tamoxifen); protein kinase
inhibitors (e.g staurosporin); anti-vital compounds, anti-fungal
compounds and/or anti-protozoal compounds. As can be appreciated,
the biological agent can include other compounds. In one specific
example of this aspect, the Trapidil forms a salt complex with the
coating compound such that the Trapidil forms the cation component
and the coating compound forms the anionic component.
[0035] Still another and/or alternative feature of the present
invention, the material used to at least partially encapsulate one
or more biological agents; at least partially coat and/or
impregnate the stent or other implant; and/or at least partially
form the stent or other implant is a polymer and/or copolymer. In
one embodiment, the polymer and/or copolymer includes one or more
carboxylate groups, phosphate groups, sulfate groups, and/or other
organic anion groups. In one aspect of this embodiment, the polymer
and/or copolymer includes one or more groups which form one or more
anionic bonding sites for cationic salts of the biological agent.
In one aspect of this embodiment, the polymer and/or copolymer
includes one or more groups that form one or more cationic bonding
sites for anionic salts of the biological agent. In one specific
example of this aspect, the polymer and/or copolymer includes one
or more amine groups and the like. In still another embodiment, the
polymer and/or copolymer includes one or more hydrophobic and/or
hydrophilic groups. As can be appreciated, the polymer and/or
copolymer can include only hydrophobic groups, only hydrophilic
groups, or include a combination hydrophobic groups and hydrophilic
groups. Furthermore, it can be appreciated that the hydrophobic
and/or hydrophilic groups in the polymer and/or copolymer can be
the same or different. Nonlimiting examples of hydrophilic groups
include carboxylate groups (e.g. acrylate groups, methacrylate
groups), alcohol groups, sulfate groups, and the like. Specific
non-limiting examples include acrylic acid groups, methacrylic acid
groups, and/or maleic acid groups. Nonlimiting examples of
hydrophobic groups include ethylene groups, vinyl groups, styrene
groups, propylene groups, urethane groups, ester groups, and/or
alkyl groups. Specific non-limiting examples include ethylene
groups, propylene groups, acrylonitrile groups, and/or methyl
methacrylate groups. In still another embodiment, the general
formula of the polymer and/or copolymer that can be used is set
forth in the following formula:
(Hydrophobic Group).sub.x--(Hydrophilic Group).sub.y.sub.n
[0036] wherein x is the number of hydrophobic monomer units, y is
the number of hydrophilic monomer units, and n is the total number
of all monomer units in the polymer/copolymer chain. The x and y
values can stay constant or vary throughout the polymer/copolymer
chain. In addition, the type of hydrophobic monomer or hydrophilic
monomer can stay constant or vary throughout the polymer/copolymer
chain. Biological agents that form anionic or cationic salts
generally bond with the hydrophilic groups in the polymer and/or
copolymer chain. Consequently, the more hydrophilic groups in the
polymer and/or copolymer chain, the higher the concentration of
biological agents that can bond with the polymer and/or copolymer
chain. As can be appreciated, one or more biological agents may
bond with hydrophobic groups. Therefore, the more hydrophobic
groups in the polymer and/or copolymer chain, the higher the
concentration of biological agent that can bond with the polymer
and/or copolymer chain. Irrespective of whether a biological agent
bonds with a hydrophobic group or hydrophilic group, the ratio of
the hydrophilic groups to the hydrophobic groups in the polymer
and/or copolymer determines the amount of biological agent that
bonds with the polymer and/or copolymer. The number of groups of
hydrophilic groups (y) and hydrophobic groups (x) typically varies
from about 50 to over 10,000. Nonlimiting examples of polymer
and/or copolymers that can be used include poly(ethylene
terephthalate); polyacetal; poly(lactic acid); polyglycolic acid;
polyesters; hydrogels; polytetrafluoroethylene; fluorosilicones
hyaluronates; polymethylmethacrylate; poly(ethylene
oxide)/poly(butylene terephthalate) copolymer; polycaprolactone;
poly(lactide-co-glycolide); poly(hydroxybutyrate);
poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester;
polyarihydride; poly(glycolic acid); copolymers of lactic acid and
glycolic acid; poly (caprolactone); poly (valerolactone); poly
(anhydrides); copolymers of poly (caprolactone) or poly (lactic
acid) with polyethylene glycol; poly(glycolic acid-co-trimethylene
carbonate); polyphosphoester; polyphosphoester urethane; poly(amino
acids); cyanoacrylates; poly(trimethylene carbonate); polyvinyl
alcohol; polyethylene; poly(iminocarbonate); polyorthoesters;
polyacetals; polyorthocarbonates; copoly(ether-esters) (e.g.
PEO/PLA); polyalkylene oxalates; polyphosphazenes; biomolecules
such as fibrin, fibrinogen, cellulose, starch, collagen and
hyaluronic acid; silicones; polyolefins; polyisobutylene and
ethylene-alphaolefin copolymers; acrylic polymers and copolymers;
vinyl halide polymers and copolymers (e.g. polyvinyl chloride);
polyvinyl ethers (e.g. polyvinyl methyl ether); polyvinylidene
halides (e.g. polyvinylidene fluoride, polyvinylidene chloride);
polyacrylonitrile; polyvinyl ketones; polyvinyl aromatics (e.g.
polystyrene); polyvinyl esters (e.g. polyvinyl acetate); copolymers
of vinyl monomers; olefins (e.g. ethylene-methyl methacrylate
copolymers); acrylonitrile-styrene copolymers; ABS resins;
ethylene-vinyl acetate copolymers; polyamides (e.g. Nylon 66,
polycaprolactam); alkyd resins; polycarbonates; polyoxymethylenes;
polyimides; polyethers; epoxy resins; polyurethanes; rayon;
rayon-triacetate; albumin; gelatin; starch; dextrans;
polysaccharides; fibrinogen; poly (hydroxybutyrate); poly
(alkylcarbonate); poly (orthoesters); EVA copolymers; silicone
rubber; poly (methylmethacrylate); cellulose acetate; cellulose
butyrate; cellulose acetate butyrate; cellophane; cellulose
nitrate; cellulose propionate; cellulose ethers; and/or
carboxymethyl cellulose. One particular nonlimiting copolymer chain
that can be used to form a polymer salt complex with a biological
agent such as, but not limited to, Trapidil, is an ethylene-acrylic
acid copolymer. In this copolymer, ethylene is the hydrophobic
group and acrylic acid is the hydrophilic group. The mole ratio of
the ethylene to the acrylic acid in the copolymer determines the
hydrophobicity of the copolymer. Generally a mole ratio for
hydrophobic groups/hydrophilic groups ranges from about 90:10-2:98;
however, other mole ratios can be used. As can be appreciated, a
mole ratio of 2:98 forms a hydrophilic copolymer and a mole ratio
of 90:10 forms a hydrophobic copolymer.
[0037] In still a further another and/or alternative feature of the
present invention, the amount of biological agent that can be
loaded on the polymer/copolymer is dependant on the structure of
the polymer/copolymer. For biological agents that are cationic, the
concentration of biological agent that can be loaded on the
polymer/copolymer is a function of the concentration of anionic
groups in the polymer/copolymer. Alternatively, for biological
agents that are anionic, the concentration of biological agent that
can be loaded on the polymer/copolymer is a function of the
concentration of cationic groups (e.g. amine groups and the like)
in the polymer/copolymer. For instance, when the biological agent
is such as, but not limited to, Tripidil, the maximum concentration
of Tripidil that can be loaded on to the polymer/copolymer is
dependent on the concentration of anionic groups (i.e. carboxylate
groups, phosphate groups, sulfate groups, and/or other organic
anion groups) in the polymer/copolymer, and the fraction of these
anionic groups that can ionically bind the cationic form of
Tripidil. As a result, the concentration of biological agent bound
to the polymer/copolymer can be varied by controlling the amount of
hydrophobic and hydrophilic monomer in the polymer/copolymer, by
controlling the efficiency of salt formation between the biological
agent, and/or the anionic/cationic groups in the polymer/copolymer.
Loading levels of the biological agent in the polymer/copolymer can
be from zero to about 90 percent on a weight by weight basis.
[0038] Therefore, the chemical properties of the biological agent
typically dictates the type of polymer/copolymer to be used so as
to deliver the desired levels of biological agent into a body
cavity to achieve a desired biological response.
[0039] Yet a further another and/or alternative feature of the
present invention is that the stent is at least partially coated
and/or impregnated with one or more coating compounds that includes
one or more biological agents, wherein the one or more coating
compounds are cross-linked to alter the rate of release of the one
or more biological agents into the body passageway or other body
parts. It has been discovered that by causing the one or more
coating compounds to cross-link after being at least partially
coated and/or impregnated onto the stent, the rate at which the one
or more biological agents disassociates from the stent and migrates
into the body passageway can be controlled. As can be appreciated,
the cross-linking of the encapsulated biological agents can be used
to alter the rate of release of the one or more biological agents
into the body passageway or other body parts. The cross-linking can
be instituted by a number to techniques including, but not limited
to, using catalysts, using radiation, using heat, and/or the like.
In one embodiment, the coating compound is exposed to radiation to
cause one or more cross-links to be formed. The radiation can
include, but is not limited to, gamma radiation, beta radiation
and/or e-beam radiation. When the polymer is exposed to radiation,
one or more hydrogen radicals are removed from the polymer and/or
copolymer chain. The removal of the hydrogen radical causes the
polymer and/or copolymer chain to cross-link with another portion
of the polymer and/or copolymer chain or cross-link with a
different polymer and/or copolymer. The cross-linking effect
results in the salt of the biological agents to become partially or
fully entrapped within the cross-linked coating. The entrapped
biological agent takes longer to release itself from the
cross-linked coating compound and to pass into the body passageway.
As a result, the amount of biological agent, and/or the rate at
which the biological agent is released from the stent over time can
be controlled by the amount of cross-linking in the coating
compound. The amount of cross-linking in the coating compound is
controlled by the type and amount of radiation applied to the
coating compound. Gamma radiation is a higher intensity radiation
and e-beam radiation is a lower intensity radiation. Increased
radiation intensities and increased radiation exposure periods
typically result in increased cross-linking of the coating
compound. Each polymer composition has its unique threshold and
capacity for cross-linking. The amount of cross-linking that is
induced by radiation will be dependent on the chemical structure
and composition of the polymer/copolymer. The extent or degree of
cross-linking for each polymer/copolymer in combination with the
biological agent will vary, depending on the type, strength and
duration of radiation, the chemical structure of the biological
agent, the type of polymer/copolymer, and the amount of loading
(weight percent) of the biological agent in the polymer/copolymer.
Reduced solubility of the copolymer/polymer in a body passageway
can reduce the need for induced cross-linking of the
polymer/copolymer. For instance, while the polymer/copolymer may be
hydrophilic, salt formation with a hydrophobic biological agent can
result in a reduction of solubility of the bound polymer/copolymer
in physiological environments. The reduction in solubility of the
bound polymer/copolymer may reduce the need or totally obviate the
need for induced cross-linking by radiation or otherwise. The
hydrophobic nature of the bound polymer/copolymer will control the
rate of release of the biological agent from the polymer/copolymer.
The amount of radiation exposure to the coating compound and the
biological agent is limited so as to prevent degradation of the
biological agent, and/or the coating compound during the
irradiation procedure. Generally, less than about 2000 rads
(irradiation absorbed doses) are applied to the coating compound,
the biological agent, and typically less than about 1000 rads, and
more typically less than about 500 rads, and even more typically
less than about 400 rads.
[0040] Generally, at least about 0.1 rad is applied to the coating
compound, the biological agent, and typically at least about 1 rad,
and more typically at least about 10 rads.
[0041] Still yet a further another and/or alternative feature of
the present invention is that the stent is at least partially
sterilized by subjecting the stent to radiation. Prior to the stent
being inserted into a body passageway, the stent should be free or
substantially free of foreign organisms so as to avoid infection in
the body cavity. In the past, the stent was sterilized by ethylene
oxide. Although this compound effectively sterilized the stent, the
FDA has imposed various restrictions on this compound making it
less desirable to use. Stent sterilization by radiation overcomes
the problems and limitations associated with the use of ethylene
oxide. The radiation destroys most, if not all, of the foreign
organisms on the stent. As a result, sterilization by radiation
reduces the occurrence of infection by foreign organisms as
compared to past sterilization techniques. Generally, less than
about 5000 rads (irradiation absorbed doses) are applied to the
stent to at least partially sterilize the stent, and typically less
than about 1000 rads, and more typically less than about 500 rads.
Generally, at least about 0.1 rad is applied to the stent, and
typically at least about 1 rad, and more typically at least about 5
rads.
[0042] These and other advantages will become apparent to those
skilled in the art upon the reading and following of this
description taken together with the accompanied drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0043] Reference may now be made to the drawings, which illustrate
various embodiments that the invention may take in physical form
and in certain parts and arrangements of parts wherein:
[0044] FIG. 1 is a perspective view of a section of an unexpanded
stent which permits delivery of the stent into a body
passageway;
[0045] FIG. 1A is an enlarged perspective view of one end of the
stent of FIG. 1;
[0046] FIG. 2 is a perspective view of a section of the unexpanded
stent of FIG. 1 in a nontubular state;
[0047] FIG. 3 is a sectional view of the unexpanded stent of FIG. 2
showing a connector used to connect the ends of two tubular body
members of the stent;
[0048] FIG. 3B is a perspective view of the stent of FIG. 1 in a
non-tubular state wherein the stent has rounded edges;
[0049] FIG. 4 is a sectional view of the stent of FIG. 2 showing
the polygonal structure of the stent before and after
expansion;
[0050] FIG. 5 is a perspective view of an additional embodiment of
the present invention showing an unexpanded section of the stent
having a series of slots of FIG. 4;
[0051] FIG. 6 is a sectional view of the stent of FIG. 5 showing a
connector used to connect the ends of two body members of the stent
together;
[0052] FIG. 7 is a sectional view of the stent of FIG. 5 showing a
part of the structure of the stent before and after expansion;
[0053] FIG. 8 is a perspective view of a stent of FIG. 1 showing a
coating that includes a biological agent on the stent;
[0054] FIG. 9 is a perspective view of an angioplasty balloon
delivering fluid materials to a local site;
[0055] FIG. 10 is a graphical representation of the steps for
coating the stent with a biological agent and coating compound;
[0056] FIG. 10A is a graphical representation of the biological
agent entrapped in a cross-linked polymer and/or copolymer;
and,
[0057] FIG. 11 is a graphical representation of the steps to form
cross-linking of a polymer and/or copolymer that includes a
biological agent.
DETAILED DESCRIPTION OF THE INVENTION
[0058] Referring now to the drawings wherein the showing is for the
purpose of illustrating preferred embodiments of the invention only
and not for the purpose of limiting the same, FIGS. 1-8 disclose a
stent for a body passageway. The apparatus and structures of the
present invention may be utilized not only in connection with an
expandable stent for at least partially expanding occluded segments
of a body passageway, but also for additional uses. For example,
the expandable stent may be used for, but not limited to, such
purposes as 1) a supportive stent placement within a blocked
vasculature opened by transluminal recanalization, which are likely
to collapse in the absence of an internal support; 2) forming a
catheter passage through mediastinal and/or other veins occluded by
inoperable cancers; 3) reinforcement of catheter created
intrahepatic communications between portal and/or hepatic veins in
patients suffering from portal hypertension; 4) supportive stent
placement of narrowing of the esophagus, the intestine, the ureter
and/or the urethra; and/or 5) supportive stent reinforcement of
reopened and previously obstructed bile ducts. Accordingly, use of
the term "stent" encompasses the foregoing usages within various
types of body passageways, and also encompasses use for expanding a
body passageway.
[0059] The expandable stent 20, as shown in FIGS. 1, 1A, 2, 3, 3B,
and 4, generally comprises a two tubular shaped body members 30,
40, each having a first end 32, 42, a second end 34, 44, and a wall
surface 36, 46 disposed between the first and second ends. The wall
surface is formed by a plurality of intersecting elongated members
50, with at least some of the elongated members intersecting with
one another intermediate the first and second ends of each body
member. As can be appreciated, the stent can be formed of only one
body member or be formed by more than two body members. Body
members 30, 40 each have a first diameter which permits delivery of
the body members into a body passageway. As shown in FIG. 1, the
two body members have substantially the same first diameter. In
addition, FIG. 1 discloses that the first diameter of each body
member is substantially constant along the longitudinal length of
the two body members. As can be appreciated, the diameter of the
two body members can differ, and in addition or alternatively, one
or both of the body members can have a varying first diameter along
at least a portion of the longitudinal length of the body member.
Body members 30, 40 each have a second expanded diameter. The
second diameter typically varies in size; however, the second
diameter can be nonvariable in size.
[0060] Elongated members 50, which form wall surface 36, 46 of body
members 30, 40, can be any suitable material which is compatible
with the human body and the bodily; fluids with which the stent may
come into contact. Typically, the elongated members are made of a
material, include a material, and/or are coated with a material
readily visible in vivo under fluoroscopic view. The elongated
members also are made of a material which has the requisite
strength and elasticity characteristics to permit the body members
to be expanded from their original cross-sectional size to their
expanded cross-sectional size and to further permit the body
members to retain their expanded configuration with the enlarged
cross-sectional size. Suitable materials for the fabrication of the
body members of the stent include, but are not limited to,
collagen, gold; platinum; platinum-iridium alloy; alloys of cobalt,
nickel, chromium and molybdenum; stainless steel; tantalum;
titanium; nickel-titanium alloy; and/or any suitable polymer and/or
copolymer material (e.g. poly(L-lactide), poly(D,L-lactide),
poly(glycolide), poly(L-lactide-co-D,L-lactide),
poly(L-lactide-co-glycolide), poly(D,L-lactide-co-glycolide),
poly(glycolide-co-trimethylene carbonate), polydioxanone,
polyethylene oxide, polycaprolactone, polyhydroxybutyrate,
polyphosphazene), poly(D,L-lactide-co-caprolactone),
poly(glycolide-co-caprolactone, poly(phosphate ester),
polyanhydrides, poly(ortho esters), poly(phoshate ester),
poly(amino acid), polyacrylate, polyacrylamid, poly(hydroxyethyl
methacrylate), elastin polypeptide co-polymer, polyurethane,
polysiloxane and their copolymers) having the requisite
characteristics previously described. Typically, the one or more
body members are primarily made of stainless steel.
[0061] Elongated members 50 are generally small diameter wires or
bars that have a maximum cross-sectional length or diameter of up
to about 0.02 inches, and generally about 0.0005 to 0.008 inch, and
typically about 0.002 to 0.004 inch; however, other cross-sectional
lengths or diameters can be used. The cross-sectional length or
diameter of the elongated members is designated by "a" in FIG. 2.
It should, of course, be understood that each elongated member can
have a variety of different cross-sectional configurations along
part, or the complete length of, each elongated member. Such
configurations include circular, oval, elliptical, diamond,
triangular, trapezoidal, polygonal (e.g. square, rectangular,
hexagonal, etc.). In addition, the cross-sectional length or
diameter of the elongated members can be the same or different.
[0062] Referring to FIGS. 1, 2, 3B, and 4, the elongated members on
body members 30, 40 are arranged so as to form a plurality of
polygonal shapes such as, but not limited to parallelogram shapes
80, 90. The parallelogram pattern is such that similarly oriented
parallelograms are aligned on substantially the same longitudinal
axis of the body member. This pattern is best shown in FIGS. 2 and
3B. Referring now to FIG. 2, each parallelogram 80, 90 is formed by
four sides 82a, 82b, 82c, 82d, 92a, 92b, 92c, 92d. As shown in FIG.
2, a set of parallelogram shapes are aligned along a single
longitudinal axis of body member 30 which are defined by sides
82a-d, sides 82a of each parallelogram of body member 30
substantially lie in a single longitudinal axis. Likewise, sides
82c of each parallelogram of body member 30 substantially lie in a
single longitudinal axis. In addition, sides 82a and 82c of each
parallelogram are substantially parallel to each other. Sides 82b
and 82d of each parallelogram are substantially parallel to one
another. Sides 82b and 82d are shown to slope from left to right.
The slope angle between sides 82b and 82c and sides 82a and 82d
ranges between 0-90.degree., and typically about 10-60.degree.. The
parallelogram shape has a height "b." Height b will vary depending
or the size of the unexpanded body member. The maximum of height
"b" is about 1 inch, and generally about 0.005 to 0.5 inch, and
typically about 0.001 to 0.1 inch; however, other heights can be
used. Sides 82a and 82c can have the same or different length from
sides 82b and 82d. The length of the sides can be up to 2 inches,
and generally ranges from 0.005 to 1 inch, and typically 0.01 to
0.5 inch. As shown in FIG. 2, all the sides have substantially the
same length. Each of the parallelograms has substantially the same
dimensions.
[0063] Referring now to a set of parallelogram shapes aligned along
a longitudinal axis of body member 30 which are defined by sides
82a'-d', sides 82a' of each parallelogram of body member 30
substantially lie in a single longitudinal axis. Likewise, sides
82c' of each parallelogram of body member 30 substantially lie in a
single longitudinal axis. In addition, sides 82a' and 82c' of each
parallelogram are substantially parallel to each other. Sides 82b'
and 82d' of each parallelogram are substantially parallel to one
another. Sides 82b' and 82d' are shown to slope from right to left.
The slope angle between sides 82b' and 82c' and sides 82a' and 82d'
ranges between 0-90.degree., and typically about 10-60.degree.. The
parallelogram shape has a height "b'." Height b' will vary
depending or the size of the unexpanded body member. The height
ranges of b' are generally the same as b. The length ranges of
sides 82a-d are also generally the same as 82a-d'. As shown in FIG.
2, all the sides have substantially the same length. Each of the
parallelograms has substantially the same dimensions. In addition,
the shape and size of the parallelograms is substantially the same
as the parallelogram defined by sides 82a-d. As shown in FIG. 2,
the orientation of the parallelograms alternates along the
latitudinal axis from parallelograms having sides 82b and 82d
sloping from left to right and parallelograms having sides 82b' and
82d' sloping from right to left. A similar parallelogram pattern
exists on body member 40. As shown in FIGS. 2 and 3B, the
orientation of the parallelograms that are aligned along the same
longitudinal axis for body members 30 and 40 is substantially the
same. As can be appreciated, this parallelogram pattern allows the
body members to be expanded without the body members having a
reduction in length in the longitudinal direction. Since a
parallelogram is a four sided figure with opposite sides being
parallel, the longitudinal axis of structure of body members 30 ,
40 remains substantially the same during the expansion of the body
members. As can be appreciated, the orientation of the
parallelograms on one or more body members of the stent can be
patterned differently so long as the longitudinal length of the
body member remains substantially the same during the expansion of
the body member. The symmetrical orientation of the parallelogram
pattern on the body members illustrated in FIGS. 1, 2, and 3B
results in more uniform expansion of the stent when in the body
passageway. In one specific design of a stent to be used in a blood
vessel, the cross-sectional length or diameter of the elongated
members are substantially uniform and about 0.0025 to 0.0035 inch,
the size of the parallelograms in the two body members are
substantially the same, the heights b and b' of the parallelograms
are substantially the same and are about 0.015 to 0.025 inch, the
lengths of the sides of each parallelogram are substantially the
same and are about 0.03 to 0.08 inch, and the slope angles of the
sides of the parallelograms are about 15-40.degree..
[0064] To provide flexibility to the stent, body members 30, 40 are
connected together by a several connector members 70. One such
connector member is a connector member having a "U" shaped member
72 as shown in FIGS. 1, 2 and 3. As best shown in FIGS. 1 and 2,
connector member 70 joins end 34 of body member 30 to end 42 of
body member 40. Four connector members are shown to connect the two
body members together. Connector member 70 also includes a bar
member 74. The bar member spans between the second end of "U"
shaped member 72 and end 42 of body member 40. The first end of "U"
shaped member 72 is connected to end 34 of body member 30. As best
shown in FIG. 2, connectors 70 do not connect to all of the ends 34
of body member 30 or all of the ends 42 of body member 40.
Referring to FIG. 3, the connector member has certain dimensions
that enhance the flexibility of the stent. The cross-sectional
length or diameter of the "U" shaped member is generally the same
as the cross-sectional length or diameter "a" of the elongated
members; however, other cross-sectional lengths or diameters of the
"U" shaped member can be used. The height of the legs of the "U"
shaped member is generally equal to 2a+ (b or b') wherein "a" is
the cross-sectional length or diameter of the elongated members and
b or b' is the height of the parallelograms in the unexpanded
state. As can be appreciated, other heights of the legs of the "U"
shaped member can be used. The width "c" of the "U" shaped member
also affects the flexibility of the connector member and the stent.
The width generally is about 1-4 times the cross-sectional length
or diameter "a" of the "U" shaped member, and typically about 1.2-2
times the cross-sectional length or diameter "aa" of the "U" shaped
member; however, other width's can, be used in addition, the
spacing of the "U" shaped member from ends 34 of body member 30 and
end 42 of body member 40 also affects the flexibility of the
connector member and the stent. As shown in FIG. 2, the "U" shaped
portion of the connector member is spaced a distance from the ends
of the body members that is substantially equal to cross-sectional
length or diameter "a" of the elongated members. Bar member 74 has
a sufficient length to form the desired spacing of the "U" shaped
portion of the connector member from ends of body member 40. The
connector member allows the body members to transverse, bend and
improve flexibility invariant to the plane of bending. As can be
appreciated, other shaped connectors which include an arcuate
portion can be used.
[0065] Referring now to FIG. 1A, ends 32, 34, 42, and 44 are
treated so as to have generally smooth surfaces 60. Generally, the
ends are treated by filing, buffing, polishing, grinding, and/or
the like of the end surfaces. As a result, sharp edges, pointed
surfaces and the like are substantially eliminated from the end
section. Typically all the ends of the body members are treated to
have smooth surfaces. The smooth surfaces of the ends reduce damage
to surrounding tissue as the body member is positioned in and/or
expanded in a body passageway. In addition to the ends having
generally smooth surfaces, the elongated members 50 and/or joints
between the elongated members are formed, filed, buffed, ground,
polished, and/or the like to also have generally smooth surfaces.
Furthermore, connector members 70 and/or the connection points
between the connector members and the elongated members are formed,
filed, buffed, ground, polished, and/or the like to have generally
smooth surfaces. The substantial removal of sharp edges, pointed
surfaces and the like from the entire stent reduces damage to
surrounding tissue as the stent is positioned in and/or expanded in
a body passageway. As can be appreciated, the ends of the body
members, the elongated members, the joints between the elongated
members, the connector members, and/or the connection points
between the elongated members and the connector members can
additionally or alternatively be coated with a material that
reduces or eliminates any sharp and/or rough surfaces. The coating,
if used, is generally a polymer and/or copolymer material. The
coating can be nonbiodegradable, biodegradable or
semi-biodegradable. Typically the coating thickness is less than
the cross-sectional thickness of the elongated members. One
non-limiting example of a coating thickness is about 0.00005 to
0.0005 inches.
[0066] Elongated members 50 and/or connector members 70 can be
formed by a variety of processes. Typically, the elongated members
and connector members are formed by etching, laser cutting and/or
punching a single piece of material so that the individual
intersections of the elongated members and/or the connections
between the elongated members and the connector members need not be
welded, soldered, glued or otherwise connected together. For
example, the stent can be formed from a thin-walled metal tube, and
the openings between the elongated members and the connector
members are formed by an etching process, such as electromechanical
or laser etching, whereby the resultant structure is a stent having
a plurality of intersecting elongated members and connector members
as shown in FIG. 1. This technique enhances the structural
integrity of the structure and reduces the number of rough surfaces
at the intersection points. An alternative method or process to
form the stent is to use a flat piece of material and form the
openings between the elongated members and the connector members by
an etching process, such as electromechanical or laser etching,
stamping, laser cutting, drilling, and/or the like. Such a flat
piece of material is illustrated in FIGS. 3 and 3B. Referring
specifically to FIG. 3B, the complete stent with the cut out
regions is shown prior to the stent being formed into a tubular
shape or some other cross-sectional shape. The flat sheet includes
seven (7) formed parallelograms along the latitudinal axis of the
sheet and one partially formed parallelogram. The flat sheet also
includes ten (10) parallelograms along the longitudinal axis of the
sheet. Four "U" shaped connector members are formed along the
latitudinal axis of the sheet. The connector members divide the
parallelograms along the longitudinal axis of the sheet into two
sets of five (5), thus each body member has five (5) parallelograms
along the longitudinal axis and seven (7) fully formed
parallelograms and one partially formed parallelogram along the
latitudinal axis. As shown in FIG. 3B, body members 30, 40 each
have an elongated top bar 38, 48. In addition, body members 30, 40
each have a plurality of ends 39, 49 formed from sides 82b', 82d',
92b', and 92d' that are not connected to sides 82c' and 92c',
respectively. When the flat sheet is formed into a tubular shape or
some other cross-sectional shape, ends 39, 49 are connected to top
bar 38, 48 thereby resulting in a fully formed parallelogram,
thereby resulting in eight (8) fully formed parallelograms about
the outer surface of body members 30, 40. Typically, the flat sheet
is designed so as to form an even number of fully formed
parallelograms about the outer surface of body members 30, 40. This
even number of formed parallelograms facilitates in the desired
expansion of the stent in the body passageway. The connections
between ends 39, 49 and top bar 38, 48 can be formed by welding,
soldering, brazing, adhesives, lock and groove configurations, snap
configurations, melting together the ends and the top bars, and the
like. Typically, after the connection has been made, the surfaces
around the connection are smoothed to remove sharp and/or rough
surfaces. FIG. 3B illustrates ends 32, 34, 42, and 44 as being
smooth surfaces. Ends 39 are also shown as being relatively smooth
surfaces.
[0067] Referring now to FIG. 4, there is shown a single
parallelogram shape 80. The left parallelogram shape is
representative of the parallelogram shapes in body members 30, 40
when the stent is in an unexpanded configuration. The length of the
sides of the parallelogram are illustrated as being generally the
same, thereby forming a rhombus. The angle between sides 82b and
82c and sides 82a and 82d is about 15-30.degree.. When the stent is
expanded, the parallelogram shape deforms thereby causing the angle
between sides 82b and 82c and sides 82a and 82d to increase. A
fully expanded stent would result in the angle between sides 82b
and 82c and sides 82a and 82d to be about 90.degree. thereby
causing the parallelogram to form into a square or rectangle.
Generally, the stent is not fully expanded, thus an angle of less
than 90.degree. is formed between sides 82b and 82c and sides 82a
and 82d. The right side dashed parallelogram illustrates the
typically expanded configuration of the parallelogram. In the
expanded state, the angle between sides 82bb and 82cc and sides
82aa and 82dd generally remain the same and generally range between
about 60-90.degree., and typically about 65-80.degree..
[0068] Referring now to FIGS. 5, 6, and 7, a second embodiment of
the present invention is illustrated. As shown in FIG. 5, a stent
100 includes two body members 110, 112. As can be appreciated,
stent 100 can include more than two body members. Body members 110,
112 include ends 140, 142 of body member 10 and ends 144, 146 of
body member 112. The two body members are connected together by
several connector members 120. Generally, connector members 120
include an arcuate shaped member 122, and typically is "U" shaped,
similar to shape and size of connector members 70 as shown in FIG.
3B. Connector member 120 also includes a bar member 124. The
connector members provide flexibility to the stent body members
110, 112. The bar member spans between the second end of "U" shaped
member 122 and end. As best shown in FIGS. 5 and 6, the "U" shaped
member alternates between being corrected to end 142 and end 144
and similarly, the bar member alternates between being connected to
end 144 and end 142. The "U" shaped members are typically spaced
apart a sufficient distance so as to avoid contacting one another
in the unexpanded state. In addition, the "U" shaped members are
typically spaced apart a sufficient distance so as to avoid
contacting one another in the expanded state. The connector members
allow the body members to transverse, bend and improve flexibility
invariant to the plane of bending. As can be appreciated, other
shaped connectors which include an arcuate portion can be used.
[0069] Referring to FIG. 5, body members 110, 112 are substantially
symmetrical to one another and typically have substantially
identical dimensions. Each body member includes a plurality of
slots 130, 132. Slots 130, 132 are generally equal in length and
width; however, the width and/or length of the slots can vary. Each
slot 130 includes two ends 130a, 130b and each slot 132 includes
two ends 132a, 132b. Each series of slots 130 along a longitudinal
axis of the stent are arranged substantially parallel to one
another. Similarly, each series of slots 132 along a longitudinal
axis of the stent are arranged substantially parallel to one
another. Slots 130 and 132 that are positioned closest to one
another form a series of "V" shapes along a longitudinal axis of
the stent. Ends 130a and 132a form the base of the "V" shape. As
shown in FIG. 5, four different series of "V" shapes are positioned
along a longitudinal axis of the stent. As shown in FIG. 5, all the
"V" shapes are symmetrically oriented on each body member. The
angle between slots 130 and 132 is between about 0-90.degree., and
generally about 5-60.degree., and typically about 10-30.degree..
The width of each slot is up to about 0.5 inch, and generally about
0.0005 to 0.25 inch, and typically about 0.001 to 0.1 inch. The
length of each slots is up to about 2 inches, and generally about
0.005 to 1 inch, and typically about 0.01 to 0.5 inch. As can be
appreciated, the slot arrangement is such that the stent retains
its longitudinal length from its unexpanded to its expanded state.
The configuration of slots 130, 132 in the pre-expanded and
post-expanded position is shown in FIG. 7. The slot configuration
in the left figure illustrates the slots in the unexpanded state.
The slot configuration in the right figure illustrates the slots in
the expanded state. As illustrated in the expanded state, the slots
130 and 132 begin to align and the angle between the slots
increases. Generally, the angle between the slots in the expanded
state is between about 45-90.degree., and typically about
60-80.degree.. In one specific design of a stent to be used in a
blood vessel, four sets of "V" shaped slots are positioned in each
body member and eight connector members are used to connect the two
body members together. The length of all the slot members are
substantially the same. The angle between slots is about
15-25.degree. in the unexpanded state. The width of each slot is
about 0.002-0.007 inch. The length of each slot is 0.05-0.2
inch.
[0070] The slots in the body members can be formed in a variety of
manners. In one method or process, the stent is formed from a flat
piece of material and the slots and connector members are formed by
an etching process, such as electromechanical or laser etching,
stamping, laser cutting, drilling, and/or the like. After the slots
are formed, the stent is generally treated so as to have generally
smooth surfaces 60. Generally, the ends, slots and connector
members are treated by filing, buffing, polishing, grinding, and/or
the like. As a result, sharp edges, pointed surfaces and the like
are substantially eliminated. The smooth surfaces reduce damage to
surrounding tissue as the body member is positioned in and/or
expanded in a body passageway. As can be appreciated, the ends of
the body members, the slots, and/or the connector members can
additionally or alternatively be coated and/or impregnated with a
material that reduces or eliminates any sharp and/or rough
surfaces. The coating, if used, is generally a polymer and/or
copolymer material. The coating can be non-biodegradable,
biodegradable or semi-biodegradable. Typically the coating
thickness is less than the half the width of the slots. One
non-limiting example of a coating thickness is about 0.00005 to
0.0005 inches. After the flat material has the slots and connector
members inserted therein, the flat material is rolled or otherwise
formed and the side edges of the flat material are connected
together form the stent. The side edges of the flat material can be
connected together by a variety of techniques such as, but not
limited to, welding, soldering, brazing, adhesives, lock and groove
configurations, snap configurations, melting together the edges,
and the like. The cross-sectional shape of the stent is typically
circular; however, other cross-sectional shapes can be formed such
as, but not limited to, oval, elliptical, diamond, triangular,
trapezoidal, polygonal (e.g. square, rectangular, hexagonal, etc.).
The connection between the edges is generally treated to reduce or
eliminate the rough or sharp surfaces.
[0071] Referring now to FIG. 8, a stent 200 is shown to include a
compound 210 on the elongated members 220 and connector 230 of the
body member. Compound 210 is or includes a vascular active agent
that inhibits and/or prevents restenosis, vascular narrowing and/or
in-stent restenosis. One preferable compound that is or is included
in the vascular active agent is a PDGF inhibitor. One type of PDGF
inhibitor that is used is Trapidil; however, other PDGF inhibitors
can be used. As can be appreciated, compound 210 can also or
alternatively include one or more secondary vascular active agents
and/or other biological agents.
[0072] The amount of vascular active agent and/or secondary
vascular active agent and/or other biological agent delivered to a
certain region of a body passageway can be controlled by varying
the coating thickness, drug concentration of the vascular active
agent and/or secondary vascular active agent and/or other
biological agent, the amount of surface area of the body member 200
that is coated and/or impregnated with the vascular active agent
and/or secondary vascular active agent and/or other biological
agent, and/or the size of cavity openings in the stent As can be
appreciated, the vascular active agent and/or secondary vascular
active agent and/or other biological agent can be combined with, or
at least partially coated with, another compound that affects the
rate at which the vascular active agent and/or secondary vascular
active agent and/or other biological agent is released from the
surface of the stent. A bonding compound can be used in conjunction
with compound 210 to assist in binding compound 210 to body member
200. In addition, or alternatively, the bonding compound can be
used to control the release of compound 210 into the body
passageways. In one particular application, the bonding compound is
biodegradable and dissolves over the course of time. The bonding
agent is coated at one or more thicknesses over compound 210 to
delay delivery of compound 210 into a body passageway.
[0073] Referring now to FIGS. 10, 10A and 11, the vascular active
agent and/or secondary vascular active agent and/or other
biological agent is combined with a polymer and/or copolymer prior
to being at least partially coated onto the stent. The polymer
and/or copolymer can be formulated to bond the vascular active
agent and/or secondary vascular active agent and/or other
biological agent to the stent; however, the polymer and/or
copolymer can be used in combination with other compounds to
facilitate in the bonding of the vascular active agent, secondary
vascular active agent and/or other biological agent and/or polymer
and/or copolymer to the stent. Referring now to FIG. 10, there is
illustrated a typical process whereby one or more vascular active
agents, one or more secondary vascular active agent, one or more
other biological agents, and/or other compounds are coated to the
stent. As shown in FIG. 10, the vascular active agent and/or
secondary vascular active agent and/or other biological agent is
mixed with a polymer and/or copolymer prior to coating the stent.
The polymer and/or copolymer is formulated to delay and/or regulate
the time and/or amount of vascular active agent and/or secondary
vascular active agent and/or other biological agent being released
into the body passageway. The polymer and/or copolymer can be a
biodegradable compound, a non-biodegradable compound, or a
partially biodegradable compound. The polymer and/or copolymer can
be formulated so as to form one or more bonds with the vascular
active agent and/or secondary vascular active agent and/or other
biological agent, or be chemically inert with respect to the
vascular active agent and/or secondary vascular active agent and/or
other biological agent. Generally, the polymer and/or copolymer
form at least one bond with one or more vascular active agents
and/or secondary vascular active agents and/or other biological
agents. The bond is generally formed in a polymer and/or copolymer
salt complex. For example, when the vascular active agent is or
includes Trapidil, the Trapidil forms a salt complex with the
polymer and/or copolymer. The Trapidil forms the cation component
of the salt complex and the polymer and/or copolymer forms the
anionic component of the salt complex. Typically, the carboxylate
groups, phosphate groups, and/or sulfate groups in the polymer
and/or copolymer form the bond with this vascular active agent.
[0074] After the vascular active agent and/or secondary vascular
active agent and/or other biological agent has been mixed with the
polymer and/or copolymer, the mixture is coated onto the stent.
After the stent or a portion of the stent has been coated with the
mixture, the coated stent can be subjected to radiation. The
radiation causes the polymer and/or copolymer to form cross-linking
between the polymer and/or copolymer chains. The cross-linking
alters the rate of release of the one or more vascular active
agents and/or secondary vascular active agents and/or other
biological agents into the body passageway. The radiation typically
includes, but is not limited to, gamma radiation, beta radiation,
and/or e-beam radiation; however, other types of radiation (e.g.
inferred, ultraviolet) can be used in conjunction with or as an
alternative to gamma radiation, beta radiation, and/or e-beam
radiation. When the polymer and/or copolymer is exposed to
radiation, one or more hydrogen radicals are typically removed from
the polymer and/or copolymer chain. This process is illustrated in
FIG. 11. As can be appreciated, other elements in the polymer
and/or copolymer can be removed and/or disassociated from the
polymer and/or copolymer when the polymer and/or copolymer is
exposed to radiation. In FIG. 11, a polymer and/or copolymer chain
includes a carboxyl group that has formed a salt complex with
Trapidil. Radiation is applied to the polymer and/or copolymer salt
complex resulting in removal of one or more hydrogen atoms from the
polymer and/or copolymer chain. The removal of the hydrogen radical
causes the polymer and/or copolymer chain to cross-link with
another portion of the polymer and/or copolymer chain or cross-link
with a different polymer and/or copolymer as shown in FIG. 11. FIG.
10A illustrates the vascular active agent and/or secondary vascular
active agent and/or other biological agent being entrapped or
partially entrapped within the cross-linking of the polymer and/or
copolymer. The entrapped vascular active agent and/or secondary
vascular active agent and/or other biological agent takes longer to
release itself from the cross-linked coating compound and to pass
into the body passageway. As a result, the amount of vascular
active agent and/or secondary vascular active agent and/or other
biological agent, and/or rate at which the vascular active agent
and/or secondary vascular active agent and/or other biological
agent released from the stent over time can be controlled by the
amount of cross-linking in the coating compound. The amount of
cross-linking in the coating compound is controlled by the type and
amount of radiation applied to the coating compound. The amount of
radiation exposure to the polymer and/or copolymer salt complex is
controlled so as to prevent degradation of the vascular active
agent, secondary vascular active agent, other biological agent,
and/or polymer and/or copolymer during the irradiation procedure.
In addition to the radiation causing cross-linking, the radiation
sterilizes the stent. The radiation destroys most if not all of the
foreign organisms on the stent and/or on any coating on the stent.
As a result, sterilization by radiation reduces the occurrence of
infection by foreign organisms.
[0075] Referring now to FIG. 9, a vascular active agent and/or
secondary vascular active agent and/or other biological agent 240
is delivered into a body passageway A via angioplasty balloon
250.
[0076] Balloon 250 includes one or more slots 260 to allow delivery
of vascular active agent and/or secondary vascular active agent
and/or other biological agent 240 into body passageway A. Balloon
250 can be used to both deliver compound 210 and expand the stent
200, or be used in conjunction with another balloon or stent
expanding device. When the vascular active agent includes one or
more PDGF inhibitors, local delivery of the inhibitor by a stent
and/or via a balloon is highly advantageous.
[0077] The present invention has been described with reference to a
number of different embodiments. It is to be understood that the
invention is not limited to the exact details of construction,
operation, exact materials or embodiments shown and described, as
obvious modifications and equivalents will be apparent to one
skilled in the art. It is believed that many modifications and
alterations to the embodiments disclosed will readily suggest
themselves to those skilled in the art upon reading and
understanding the detailed description of the invention. It is
intended to include all such modifications and alterations insofar
as they come within the scope of the present invention.
* * * * *