U.S. patent application number 10/683314 was filed with the patent office on 2005-01-13 for implantable medical devices.
Invention is credited to Liu, Changdeng, Mather, Patrick, Sahatjian, Ronald A., Tan, Francisca.
Application Number | 20050010275 10/683314 |
Document ID | / |
Family ID | 32097153 |
Filed Date | 2005-01-13 |
United States Patent
Application |
20050010275 |
Kind Code |
A1 |
Sahatjian, Ronald A. ; et
al. |
January 13, 2005 |
Implantable medical devices
Abstract
A medical device includes a balloon catheter having an
expandable member, e.g., an inflatable balloon, at its distal end
and a stent or other endoprosthesis. The stent is, for example, an
apertured tubular member formed of a polymer and is assembled about
the balloon. The stent has an initial diameter for delivery into
the body and can be expanded to a larger diameter by inflating the
balloon.
Inventors: |
Sahatjian, Ronald A.;
(Lexington, MA) ; Tan, Francisca; (Boston, MA)
; Mather, Patrick; (Storrs, CT) ; Liu,
Changdeng; (Storrs, CT) |
Correspondence
Address: |
FISH & RICHARDSON PC
225 FRANKLIN ST
BOSTON
MA
02110
US
|
Family ID: |
32097153 |
Appl. No.: |
10/683314 |
Filed: |
October 10, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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60418023 |
Oct 11, 2002 |
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60488323 |
Jul 18, 2003 |
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60419506 |
Oct 18, 2002 |
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60466401 |
Apr 29, 2003 |
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60488590 |
Jul 18, 2003 |
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Current U.S.
Class: |
623/1.11 ;
264/496; 623/1.19; 623/23.7 |
Current CPC
Class: |
C08L 2205/05 20130101;
C08G 18/4833 20130101; C08L 71/02 20130101; A61F 2/958 20130101;
A61L 31/14 20130101; C08G 61/08 20130101; A61F 2220/0016 20130101;
C08G 18/3893 20130101; C08G 18/718 20130101; A61F 2/88 20130101;
A61F 2002/8483 20130101; A61M 27/008 20130101; C08G 2230/00
20130101; C08L 71/02 20130101; C08G 18/61 20130101; A61F 2250/0037
20130101; C08G 65/336 20130101; C08L 65/00 20130101; C08J 3/005
20130101; C08L 83/00 20130101 |
Class at
Publication: |
623/001.11 ;
623/001.19; 623/023.7; 264/496 |
International
Class: |
A61F 002/04; A61F
002/06; B29C 035/02 |
Claims
What is claimed is:
1. A product comprising a balloon catheter having an expandable
member and a stent mounted on the expandable member, the stent
comprising an apertured tubular member formed of a polymer, the
stent having an initial diameter for delivery into a body lumen and
which can be expanded to a second diameter in the lumen by
expanding the expandable member, wherein during expansion the
polymer does not substantially flow and substantial stress
relaxation or creep does not occur so that the geometry of the
tubular member is maintained.
2. The product of claim 1, wherein the polymer exhibits a plateau
in its plot of storage modulus as a function of temperature.
3. The product of claim 1, wherein the polymer has a melt
temperature from about 40.degree. C. to about 50.degree. C.
4. The product of claim 1, wherein the polymer has a melt
temperature range of less than about 5.degree. C.
5. The product of claim 1, wherein the polymer has a glass
transition temperature from about 40.degree. C. to about 50.degree.
C.
6. The product of claim 1, wherein the polymer has a glass
transition temperature range of less than about 5.degree. C.
7. The product of claim 1, wherein the polymer is elastomeric at
room temperature.
8. The product of claim 1, wherein the polymer is
bioabsorbable.
9. The product of claim 1, wherein the polymer is crosslinked.
10. The product of claim 9, wherein the polymer is radiation
crosslinked.
11. The product of claim 9, wherein the polymer is chemically
crosslinked.
12. The product of claim 1, wherein the polymer is a shape memory
polymer.
13. The product of claim 1, wherein the polymer is selected from
the group consisting of polynorbornene, polycaprolactone, polyenes,
nylons, polycyclooctene (PCO), blends of PCO and styrene-butadiene
rubber, polyvinyl acetate/polyvinylidinefluoride (PVAc/PVDF),
blends of PVAc/PVDF/polymethylmethacrylate (PMMA), polyurethanes,
styrene-butadiene copolymers, polyethylene, trans-isoprene, blends
of polycaprolactone and n-butylacrylate, POSS polyurethane polymers
and blends thereof.
14. The polymer of claim 1, wherein the wherein the polymer
includes an additive selected from the group consisting of drugs,
radiopaque agents and magnetic heating agents.
15. The product of claim 1, wherein the initial diameter is from
about 1 mm to about 5 mm.
16. The product of claim 1, wherein the expanded diameter is from
about 1 mm to about 20 mm.
17. The product of claim 1, wherein the expanded diameter is from
about 100% to about 400% the initial diameter.
18. The product of claim 1, wherein the apertured tubular member is
formed from a plurality of filaments, the plurality of filaments
forming a tubular structure.
19. The product of claim 1, wherein the ratio of apertured open
area to total area of the tubular member is greater than about
0.5.
20. The product of claim 1, wherein the apertures are diamond-like
openings.
21. A product comprising a tubular endoprosthesis having a body
formed of a polymer, the endoprosthesis being designed for delivery
into a body lumen, wherein when the endoprosthesis is expanded in
the lumen under conditions of expanding pressure and temperature,
the wall thickness of the body is substantially maintained.
22. The product of claim 21, wherein a change in the wall thickness
is less than about 1%.
23. The implantable medical device of claim 21, wherein the wall
thickness is from about 0.005 mm to about 5 mm.
24. The product of claim 21, wherein the polymer is selected from
the group consisting of polynorbornene, polycaprolactone, polyenes,
nylons, polycyclooctene (PCO), blends of PCO and styrene-butadiene
rubber, polyvinyl acetate/polyvinylidinefluoride (PVAc/PVDF),
blends of PVAc/PVDF/polymethylmethacrylate (PMMA), polyurethanes,
styrene-butadiene copolymers, polyethylene, trans-isoprene, blends
of polycaprolactone and n-butylacrylate, POSS polyurethanes and
blends thereof.
25. The product of claim 21, wherein the polymer has a melt
temperature from about 40.degree. C. to about 50.degree. C.
26. The product of claim 21, wherein the polymer has a glass
transition temperature from about 40.degree. C. to about 60.degree.
C.
27. The product of claim 21, wherein the polymer is
bioabsorbable.
28. The product of claim 21, wherein the polymer is
crosslinked.
29. The product of claim 28, wherein the polymer is radiation
crosslinked.
30. The product of claim 28, wherein the polymer is chemically
crosslinked.
31. The product of claim 21, wherein the polymer is a shape memory
polymer.
32. The product of claim 21, wherein the polymer exhibits a plateau
in its plot of storage modulus as a function of temperature.
33. The polymer of claim 21, wherein the wherein the polymer
includes an additive selected from the group consisting of drugs,
radiopaque agents and magnetic heating agents.
34. A method of delivering a stent into a lumen using a catheter,
the method comprising: delivering an apertured stent formed of a
polymer and mounted on an expandable member of a catheter into a
lumen, expanding the expandable member to also expand the stent
within the lumen so that the polymer does not substantially flow
and substantial stress relaxation or creep does not occur so that
the geometry of the tubular member is maintained; and unexpanding
the expandable member.
35. The method of claim 34, wherein the expandable member is a
balloon at the distal tip of a catheter.
36. The method of claim 34, wherein the polymer has a melt
temperature from about 40.degree. C. to about 60.degree. C.
37. The method of claim 34, wherein the polymer has a glass
transition temperature is from about 40.degree. C. to about
60.degree. C.
38. The method of claim 34, wherein the lumen is a vascular
lumen.
39. The method of claim 34, wherein the lumen is a non-vascular
lumen.
40. A method of delivering a tubular prosthesis formed of a polymer
into a body lumen, comprising delivering the tubular prosthesis
into the lumen, and expanding the endoprosthesis under conditions
of expanding pressure and rising temperature, wherein during
expansion the wall thickness of the prosthesis is substantially
maintained.
41. A method of making an implantable medical device comprising:
forming a tube from a polymer, the tube having a first diameter and
including a wall; cutting an aperture pattern into the wall of the
tube while the tube has the first diameter; crosslinking the
polymer while the tube has the first diameter; and deforming the
tube to a second diameter, the second diameter smaller than the
first diameter.
42. A method of delivering an implantable medical device
comprising: providing a catheter having an expandable member at its
distal end; placing a device made by the method of claim 41 onto
the expandable member; delivering the device to a body lumen;
expanding the device under conditions of expanding pressure and
temperature to cause expansion of the device to the larger
diameter; and cooling the stent so that the device remains in the
expanded larger diameter in the body lumen; and removing the
catheter from the body, thereby leaving behind the device within
the body.
43. A method of making an implantable medical device comprising:
forming a tube from a polymer, the tube having a first diameter and
including a wall; cutting an aperture pattern into the wall while
the tube has the first diameter; and crosslinking the polymer while
the tube has the first diameter.
44. A method of delivering an implantable medical device
comprising: providing a catheter having an expandable member at its
distal end; placing a device made by the method of claim 43 onto
the expandable member; delivering the device to a body lumen;
expanding the device under conditions of expanding pressure and
temperature to cause expansion of the device to the larger
diameter; and cooling the stent so that the device remains in the
expanded larger diameter in the body lumen; and removing the
catheter from the body, thereby leaving behind the device within
the body.
45. An implantable medical apparatus, comprising: an element
operable for movement within the body by mechanical force applied
to the element, said element including a polymer having a melt or
glass transition temperature in the range above body temperature to
about 60.degree. C. and exhibiting a plateau in a plot of storage
modulus as a function of temperature at melt or glass
transition.
46. The apparatus of claim 45, wherein the element is a stent.
47. The apparatus of claim 46, wherein the stent is a generally
tubular body including an apertured wall.
48. The apparatus of claim 47, wherein the stent is operable for
expansion from a first, smaller diameter to a second larger
diameter for implantation in a lumen, wherein the thickness of the
stent wall varies by about 1% or less between the first and second
diameter.
49. The apparatus of claim 47, wherein the stent can be bent around
a mandrel of about 0.75 cm radius without kinking.
50. A medical device comprising a polymer having a melt or glass
transition temperature above body temperature and exhibiting an
approximate plateau in a plot of storage modulus as a function of
temperature at melt or glass transition.
51. The medical device of claim 50, wherein the melt or glass
transition temperature is above about 37.degree. C.
52. The medical device of claim 50, wherein the melt or glass
transition temperature is above about 50.degree. C.
53. The medical device of claim 50, wherein the melt or glass
transition temperature is between about 37.degree. C. and about
50.degree. C.
54. The medical device of claim 50, wherein the element undergoes a
triggerable event at about the plateau.
55. The medical device of claim 54, wherein the triggerable event
is a change in the flexibility.
56. The medical device of claim 54, wherein the triggerable event
is a change in the porosity.
57. The medical device of claim 54, wherein the triggerable event
is a change in the coefficient of friction.
58. The medical device of claim 54, wherein the triggerable event
is a change in the surface roughness.
59. The medical device of claim 54, wherein the medical device is a
stent and has a portion that has a collapsed position that can be
reverted to an expanded position by a trigger subsequent to
insertion into the body.
60. A polymeric stent having a portion that has a collapsed
position that can be reverted to an expanded position by heating
above a first temperature subsequent to insertion of the stent into
a cavity or lumen.
61. The stent of claim 60, wherein the stent is in the form of a
coiled elongated element.
62. The stent of claim 61, wherein when the stent is heated to a
second temperature higher than the first temperature, the modulus
of the element lowers sufficiently that the stent can be removed
from a cavity or lumen as a substantially uncoiled element.
63. The stent of claim 60, wherein the portion is at an end of the
stent.
64. The stent of claim 63, wherein the portion of the stent is
flared.
65. The stent of claim 60, wherein at least two portions of the
stent have a collapsed position that can be reverted to an expanded
position following insertion into a cavity or lumen.
66. The stent of claim 61, wherein the elongated element comprises
a strand.
67. The stent of claim 61, wherein the elongated element comprises
a tape.
68. The stent of claim 61, wherein the elongated element comprises
a flattened tube.
69. The stent of claim 68, wherein the flattened tube has a
generally central opening that includes a medicament that can be
released by the inserted stent.
70. The stent of claim 60, wherein the first temperature is greater
than about 37.degree. C.
71. The stent of claim 62, wherein the second temperature is
greater than about 37.degree. C.
72. The stent of claim 60, wherein the stent comprises a polymer
selected from a group consisting of polynorbornene and copolymers
of polynorbornene, polyethylene, styrenic block copolymer
elastomers, polymethylmethacrylate, polyurethane, polyisoprene,
polycaprolactone and copolymers of polycaprolactone, polylactic
acid (PLA) and copolymers of polylactic acid, polyglycolic acid and
copolymers of polyglycolic acid, copolymers of PLA and PGA,
polyenes, nylons, polycyclooctene, polyvinyl acetate,
polyvinylidene fluoride polyvinylchloride (PVC) and blends
thereof.
73. The stent of claim 60, wherein the stent has a length and the
portion comprises less than 50% of the length of the stent.
74. A polymeric stent in the form of a coiled elongated element,
and having a portion that has a collapsed position that can be
reverted to an expanded position by heating above a first
temperature subsequent to insertion of the stent into a cavity or
lumen, and wherein when the stent is heated to a second temperature
higher than the first temperature, the modulus of the element
lowers sufficiently that the stent can be removed from a cavity or
lumen as a substantially uncoiled element.
75. A method of treating a non-vascular cavity or lumen in a
mammal, the method comprising: inserting, into the non-vascular
lumen or cavity of the mammal, a polymeric stent having a portion
in a collapsed position that can be reverted to an expanded
position by heating following insertion; and heating the inserted
stent sufficiently to revert the portion in the collapsed position
to the expanded position.
76. The method of claim 75, further comprising: heating the stent
having the portion in the expanded position sufficiently to soften
the stent; and removing the softened stent from the cavity or
lumen.
77. The method of claim 75, wherein the portion is at an end of the
stent.
78. The method of claim 77, wherein the portion of the stent is
flared.
79. The method of claim 75, wherein at least two portions of the
stent have a collapsed position that can be reverted to an expanded
position following insertion, and wherein during the heating both
portions revert to expanded positions.
80. The method of claim 75, wherein the stent is in the form of a
coiled elongated element.
81. The method of claim 75, wherein the collapsed position that can
be reverted to an expanded position following insertion is not an
end of the stent.
82. The method of claim 80, further comprising: heating the stent
sufficiently to soften the stent; and removing the softened stent
from the cavity or lumen as a substantially uncoiled strand.
83. The method of claim 75, wherein the heating is performed with a
liquid.
84. The method of claim 75, wherein the heating is performed so
that the temperature is less than about 55.degree. C.
85. The method of claim 75, wherein the heating is performed by a
delivery tube including a warmed liquid.
86. The method of claim 75, wherein the delivery tube is a balloon
catheter.
87. The method of claim 75, wherein the heating is performed using
RF energy.
88. The method of claim 75, wherein the heating is performed using
IR energy.
89. The method of claim 75, wherein the heating is performed using
inductive heating.
90. The method of claim 89, wherein the stent further comprises
metal particles.
91. The method of claim 75, wherein the lumen is a urethra.
92. The method of claim 75, wherein the lumen is a biliary
duct.
93. The method of claim 75, wherein the lumen is a cystic duct.
94. The method of claim 75, wherein the lumen is in the
gastrointestinal system.
95. The method of claim 75, wherein the lumen is in the pulmonary
system.
96. The method of claim 75, wherein the lumen is in the hepatic
system.
97. The method of claim 75, wherein the stent comprises a polymer
selected from the group consisting of polynorbornene and copolymers
of polynorbornene, polyethylene, styrenic block copolymer
elastomers, polymethylmethacrylate, polyurethane, polyisoprene,
polycaprolactone and copolymers of polycaprolactone, polylactic
acid (PLA) and copolymers of polylactic acid, polyglycolic acid and
copolymers of polyglycolic acid, copolymers of PLA and PGA,
polyenes, nylons, polycyclooctene, polyvinyl acetate,
polyvinylidene fluoride polyvinylchloride (PVC) and blends
thereof.
98. A polymeric stent comprising metal particles, wherein a portion
of the stent has a collapsed position that can be reverted to an
expanded position by heating after insertion of the stent.
99. The stent of claim 98, wherein the stent can be heated by
inductive heating to revert the portion in the collapsed position
to the expanded position.
100. A stent having an exterior surface that includes a plurality
of protruding elements that extend outwardly from the surface, the
stent also having a portion that has a collapsed position that can
be reverted to an expanded position by heating above a first
temperature subsequent to insertion of the stent into a cavity or
lumen.
101. The stent of claim 100, wherein the protruding elements are
formed of monofilament.
102. The stent of claim 101, wherein the monofilament includes a
plurality of constrictions along its length.
103. The stent of claim 100, wherein the protruding elements are
integral with and formed from the exterior surface.
104. A method of treating a cavity or lumen in a mammal, the method
comprising: inserting, into the lumen or cavity of the mammal, a
polymeric stent having an exterior surface that includes a
plurality of protruding elements that extend outwardly from the
surface, the stent also having a portion that has a collapsed
position that can be reverted to an expanded position by heating
above a first temperature subsequent to insertion of the stent into
a cavity or lumen; and heating the inserted stent sufficiently to
revert the portion in the collapsed position to the expanded
position.
105. The method of claim 104, further comprising: heating the stent
sufficiently to soften the stent; and removing the softened stent
from the cavity or lumen as a substantially uncoiled strand.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit from provisional
application 60/418,023, filed Oct. 11, 2002; 60/488,323, filed Jul.
18, 2003; 60/419,506, filed Oct. 18, 2002; 60/466,401, filed Apr.
29, 2003; and 60/488,590, filed Jul. 18, 2003, all hereby
incorporated by reference in their entirety.
TECHNICAL FIELD This invention relates to implantable medical
devices and methods of delivering the same.
BACKGROUND
[0002] The body includes various passageways such as arteries,
other blood vessels, and other body lumens. These passageways
sometimes become occluded or weakened. For example, the passageways
can be occluded by a tumor, restricted by plaque, or weakened by an
aneurysm. When this occurs, the passageway can be reopened or
reinforced, or even replaced, with a medical endoprosthesis. An
endoprosthesis is typically a tubular member that is placed in a
lumen in the body. Examples of endoprosthesis include stents and
covered stents, sometimes called "stent-grafts".
[0003] An endoprosthesis can be delivered inside the body by a
catheter that supports the endoprosthesis in a compacted or
reduced-size form as the endoprosthesis is transported to a desired
site. Upon reaching the site, the endoprosthesis is expanded, for
example, so that it can contact the walls of the lumen.
[0004] Prostate enlargement, also known as benign prostate
hyperplasia or benign prostate hypertrophy, is a common affliction
among older men. The condition involves swelling of the prostate.
The prostate surrounds the urethra, or urinary tract, and
enlargement of the prostate may restrict passage of urine from the
bladder towards the urethra. Benign prostate hyperplasia is
uncomfortable because it makes urination difficult or impossible.
The condition is also dangerous because it can lead to infection of
the bladder and kidneys.
[0005] Prostate enlargement can be treated with surgery known as
resection. Resection can be accomplished by cutting away a large
portion of the prostate gland. Prostate enlargement can also be
treated with heat treatment, cold treatment, or ablation.
[0006] Sometimes a restricted urethra can be treated with a
prostatic stent to support the urethra and keep it open despite
pressure from the enlarged prostate. A prostatic stent may be
implanted permanently or as an interim solution.
SUMMARY
[0007] The invention relates to implantable medical devices, for
example, a stent including a polymer.
[0008] In one aspect, the invention features a medical device. The
medical device includes a balloon catheter having an expandable
member, e.g., an inflatable balloon, at its distal end and a stent
or other endoprosthesis. The stent is an apertured tubular member
formed of a polymer and is assembled about the balloon. The stent
has an initial diameter for delivery into the body and can be
expanded to a larger diameter by inflating the balloon. The polymer
does not flow substantially during expansion and substantial stress
relaxation or creep does not occur so that the geometry of the
stent is maintained.
[0009] In another aspect, a tubular endoprosthesis including a
polymer body is provided and delivered into a body lumen. The
endoprosthesis is expanded in the body lumen under conditions of
expanding pressure and temperature so that the wall thickness of
the polymer body is substantially maintained.
[0010] In another aspect, a polymer tube is formed to a first,
large diameter. An aperture pattern is cut into the tube wall. The
polymer is crosslinked or crystallized. The polymer tube is
deformed to a second, small diameter. The polymer tube is expanded
in a body lumen to a diameter larger than the second diameter by
application of pressure and heat.
[0011] In another aspect, a polymer tube is formed to a first,
small diameter. An aperture pattern is provided in the tube wall.
The polymer is crystallized or crosslinked. The tube is expanded in
a body lumen by application of pressure and heat.
[0012] In another aspect, an implantable medical apparatus includes
an element operable for movement within the body by mechanical
force applied to the element. The element includes a polymer having
a melt or glass transition temperature in the range above body
temperature to about 50.degree. C. or 60.degree. C. and exhibiting
a plateau in a plot of storage modulus as a function of temperature
at melt or glass transition. In embodiments, the element is a
stent. The stent may be generally a tubular body that includes an
apertured wall. The stent may be operable for expansion from a
first, smaller diameter to a second larger diameter for
implantation in a lumen. The thickness of the stent wall varies by
about 1% or less between the first and second diameter.
[0013] In another aspect, the invention features a medical device
including a polymer having a melt or glass transition temperature
above body temperature and exhibiting an approximate plateau in a
plot of storage modulus as a function of temperature at melt or
glass transition. The melt or glass transition temperature may be,
for example, above about 37.degree. C. The medical device may
undergo a triggerable event at about the plateau. The triggerable
event may be, for example, a change in the flexibility, a change in
the porosity, a change in the coefficient of friction or a change
in the surface roughness. The medical device may be, for example, a
stent that has a portion that has a collapsed position that can be
reverted to an expanded position by a trigger subsequent to
insertion into the body.
[0014] Aspects may include one or more of the following features.
The polymer body includes apertures. The polymer body has a ratio
of aperture open area to wall area of about 0.5 or more or 0.7 or
more. The endoprosthesis is expanded by simultaneously applying an
expanding pressure and heat to the endoprosthesis. The polymer body
is heated above the melt or glass transition temperature of polymer
in the polymer body. The polymer body is elastomeric at the melt or
glass transition temperature. The polymer is elastomeric at body
temperature. The polymer is crystalline. The polymer is
crosslinked. The polymer is radiation crosslinked. The melt or
glass transition temperature is about 40 to 50.degree. C. The melt
or glass transition temperature has a transition range of about
5.degree. C. or less. The polymer exhibits a plateau in the melt or
glass transition range in a plot of storage modulus as a function
of temperature. The polymer body includes a drug, radiopaque agent
or magnetic heating agent. The polymer is a shape memory polymer,
e.g. capable of remembering a smaller diameter configuration after
expansion. The polymer is, for example, polynorbornene,
polycaprolactone, polyenes, nylons, polycyclooctene (PCO), blends
of PCO and styrene-butadiene rubber, polyvinyl
acetate/polyvinylidinefluoride (PVAc/PVDF), blends of
PVAc/PVDF/polymethylmethacrylate (PMMA), polyurethanes,
styrene-butadiene copolymers, polyethylene, trans-isoprene, blends
of polycaprolactone and n-butylacrylate and blends thereof. An
expansion pressure of about 1 atm or more is applied. The
endoprosthesis is delivered on a catheter. The endoprosthesis is
delivered to a site of occlusion and the site is simultaneously
dilated while expanding the endoprosthesis. The endoprosthesis is
delivered to a site of lumen curvature and the endoprosthesis is
expanded at the site. The endoprosthesis is delivered to a vascular
lumen. The endoprosthesis is delivered adjacent (into) the
prostate.
[0015] Aspects may include one or more of the following. A heat
applicator applies heat to the stent during inflation of the
balloon to expand the balloon to the expanded diameter. The polymer
has a melt or glass transition temperature in the range of about 40
to 50.degree. C. and a modulus at the melt or glass transition
temperature sufficient to maintain the stent geometry or under
application of pressure and/or heat. The polymer exhibits a plateau
in the storage modulus in the range of melt or glass transition
temperatures. The stent has a wall thickness of about 0.005 to 5
mm. The stent has an initial unexpanded inner diameter in the range
of about 1 mm to 5 mm. The stent has an expanded inner diameter of
about 1 mm to 20 mm. The stent may be expandable to about 100% or
400% or more of the initial inner diameter. An example of a
coronary stent has an initial inner diameter of about 2 mm, and
expanded inner diameter of about 4 mm and the wall thickness is
about 0.005 mm to 0.1 mm. The stent can be in the form of a tube
including aperture areas provided in the tube. The aperture are in
the shape of elongate slots, e.g., when the stent is in the small
diameter condition. The apertures have a dimension of about 1 mm or
less in the small diameter condition. The apertures are in the
shape of diamond-like openings, e.g. when the stent is in an
expanded condition. The stent can be a wire-form formed of one or
more filaments configured to generally define a tube.
[0016] Embodiments may include one or more of the following
advantages. A balloon expandable stent made of a polymer can be
provided that maintains the integrity of the stent geometry on
expansion and heating. Maintenance of stent geometry is desirable
since geometry affects, for example, the resistance to compression
in the body and a predictable geometry is important to avoid
irregular surfaces, kinking, or extensions of material into the
body lumen which can interfere with the flow of body fluid. The
polymers can be elastomers that have melting or glass transitions
at temperatures safe for use in the body and exhibit elastomeric
properties at both the melted or glass transition stage and the
solid or crystalline phase. The stent body exhibits high resistance
to inward compressive forces when the polymer is in the solid or
crystalline phase. The elastomeric nature of the polymer in the
melted or glass state enhances the ability to maintain geometry as
the stent is expanded. For example, the polymer exhibits minimal
flow during expansion and the thickness of the stent remains
substantially constant. Elastomeric properties in the crystalline
or solid state enhance the ability to conform to torturous
curvature in narrow body lumens. High compression resistance allows
the stent to maintain the body lumen open and resist occluding
forces such as elastic recoil or the growth of thrombus from the
vessel wall.
[0017] In another aspect, the invention features a polymeric stent
having a portion that has a collapsed position that can be reverted
to an expanded position by heating above a first temperature
subsequent to insertion of the stent into a cavity or lumen. The
stent may be in the form, for example, of a coiled elongated
element (for example, a strand, a tape or a flattened tube). The
stent may be further heated to a second temperature that is higher
than the first temperature and removed as a substantially uncoiled
element. When the stent is in the form, for example, of a coiled
elongated flattened tube, the flattened tube may include a central
opening that includes a medicament that can be released by the
inserted stent. In some implementations, the medicament is
compounded into the plastic or is a coating on the plastic. In some
implementations, the portion is at an end of the stent and the
portion is flared or stepped. In other implementations, the portion
includes less than 50% of the length of the stent.
[0018] In another aspect, the invention features a polymeric stent
in the form of a coiled elongated element, and having a portion
that has a collapsed position that can be reverted to an expanded
position by heating above a first temperature subsequent to
insertion of the stent into a cavity or lumen. When the stent is
heated to a second temperature higher than the first temperature,
the modulus of the element lowers sufficiently that the stent can
be removed from the cavity or lumen as a substantially uncoiled
element.
[0019] In yet another aspect, the invention features a method of
treating a non-vascular cavity or lumen. The method includes
inserting a polymeric stent having a portion in a collapsed
position that can be reverted, by heating, to an expanded position.
Following insertion, the stent is heated sufficiently to revert the
portion in the collapsed position to the expanded position. The
method may further include heating the stent having the portion in
the expanded position sufficiently to soften the stent, and
removing the softened stent from the cavity or lumen.
[0020] The stent may be, for example, a coiled elongated element
(for example, a rod, a tape or flattened tube) and the heating of
the stent prior to removal allows the stent to be removed in a
substantially uncoiled state. This method provides ease of removal,
for example, for removing prostatic stents that have been inserted
on an interim basis. The heating may be performed, for example, on
a delivery tube.
[0021] In some embodiments, the portion of the stent is at the end
of the stent and may be flared when in the expanded position. In
other embodiments, for example, the portion of the stent is not at
an end of the stent.
[0022] In still another aspect, the invention features a polymeric
stent including metal particles. A portion of the stent has a
collapsed position that can be reverted to an expanded position by
heating. The heating may be performed using inductive heating to
revert the portion in the collapsed position to the expanded
position.
[0023] In another aspect, the invention features a stent having an
exterior surface that includes a plurality of protruding elements
that extend outwardly from the surface. The protruding elements may
be useful in helping the stent retain its position, for example,
after insertion into the prostatic urethra.
[0024] In some embodiments, the protruding elements are formed of
monofilament. The monofilament may include a plurality of
constrictions along its length.
[0025] In some implementations, the stent is a polymeric stent and
the stent has a portion that has a collapsed position that can be
reverted to an expanded position by heating above a first
temperature subsequent to insertion of the stent into a cavity or
lumen.
[0026] The details of one or more embodiments of the invention are
set forth in the accompanying drawings and the description below.
Other features, and advantages of the invention will be apparent
from the description and drawings and from the claims.
DESCRIPTION OF DRAWINGS
[0027] FIGS. 1A and 1B are side views of a portion of a stent in a
small diameter and expanded condition, respectively.
[0028] FIGS. 1C and 1D are cross-sectional views of a portion of a
stent in a small diameter and expanded condition, respectively.
[0029] FIGS. 2A-2C illustrate delivery of a stent into a body
lumen.
[0030] FIG. 3 is a plot of storage modulus as a function of
temperature.
[0031] FIG. 3A is a plot of storage modulus as a function of
temperature for samples of PCO with varying degrees of
crosslinking.
[0032] FIG. 3B is a WAXS 20 plot for samples of PCO with varying
degrees of crosslinking.
[0033] FIG. 4 illustrates manufacture and use of a stent.
[0034] FIG. 5 illustrates manufacture and use of a stent.
[0035] FIG. 6 is a perspective view of a stent with an end in an
expanded position.
[0036] FIG. 7 is a side view of the stent shown in FIG. 6.
[0037] FIG. 8 is a side view of the stent shown in FIG. 6 with the
end in a collapsed position.
[0038] FIG. 8A is a graph of heat flow as a function of temperature
for several POSS polyurethanes.
[0039] FIG. 8B is a graph of storage modulus as a function of
temperature for several POSS polyurethanes.
[0040] FIG. 9 is a perspective view of a wrapping fixture.
[0041] FIG. 10 is a cross-sectional view of a restricted prostatic
urethra.
[0042] FIG. 11 is a cross-sectional view illustrating delivery of a
stent to the prostatic urethra.
[0043] FIG. 12 is a cross-sectional view of a prostatic stent
deployed in the urethra.
[0044] FIG. 13 is a side view of an alternative delivery
system.
[0045] FIG. 13A-13B are side views of an alternative delivery
system.
[0046] FIG. 14 is a cross-sectional view illustrating removal of a
prostatic stent.
[0047] FIG. 15 is a graph of storage modulus (E') VS temperature
for PCO.
[0048] FIG. 16 is a graph of storage modulus (E') VS temperature
for PVAc/PVDF/PMMA blends.
[0049] FIG. 17 is a side view of an alternative stent with two ends
portions in expanded positions.
[0050] FIG. 18 is the stent shown in FIG. 17 with ends in collapsed
positions.
[0051] FIG. 19 is a side view of an alternative stent with three
portions in expanded positions.
[0052] FIG. 20 is a side view of an alternative stent made with a
flattened tube.
[0053] FIG. 21 is a cross-sectional view of the stent shown in FIG.
20, taken along 21-21.
[0054] FIG. 22 is a side view of an alternative stent made with a
tape.
[0055] FIG. 23 is a perspective view of a stent with a plurality of
protruding elements, the end of the stent is in an expanded
position.
[0056] FIG. 24 is a side view of the stent shown in FIG. 23.
[0057] FIG. 25 is a side view of the stent shown in FIG. 23 with
the end in a collapsed position.
[0058] FIG. 26 is a perspective view of an alternative stent with a
plurality of protruding elements, the end of the stent in an
expanded position.
[0059] FIG. 27 is a side view of the stent shown in FIG. 26.
[0060] FIG. 28 is a side view of the stent shown in FIG. 26 with an
end in a collapsed position.
[0061] FIG. 29 DSC traces of PLA (top) quenched from T=180.degree.
C. or (bottom) annealed at T=110.degree. C. for 1 hr.
[0062] FIG. 30 DSC traces for PLA/PVAc blends following annealing
for 1 hour at T=110.degree. C. A heating rate of 10.degree. C./min
was employed. PLA wt-% is indicated with each trace.
[0063] FIG. 31 Glass transition temperatures measured following
quenching of the PLA/PVAc blends (solid points). Solid line is best
fit to the Fox equation,
1/T.sub.g=w.sub.a/T.sub.g.sup.a+w.sub.b/T.sub.g.sup.b.
[0064] FIG. 32 Tensile storage modulus versus temperature for a
range of PLA/PVAc blends whose composition is indicated in the
plot.
DETAILED DESCRIPTION
[0065] Referring to FIGS. 1A and 1B, a stent 10 includes a polymer
body 12 generally defining a tube. The stent includes open areas
14. Referring particularly to FIG. 1A, in a small diameter
condition, such as for delivery to a treatment site in the body,
the open areas are relatively small and defined as slots cut
through the wall of the stent. Referring particularly to FIG. 1B,
in the expanded condition, the slots are widened to diamond-like
shapes. The expansion mechanism of the stent utilizes a deformation
(arrows) of the wall material about the open areas. As illustrated,
the expansion results in a generally regular, symmetric, geometric
pattern that resists and distributes inward compression of the
stent by forces imposed by the lumen wall. Referring as well to
FIGS. 1B and 1D, the wall thickness T of the stent does not
substantially change upon expansion from the small diameter
collapsed (T.sub.C) condition to the expanded condition
(T.sub.E)(T.sub.C=T.sub.E). The polymer does not substantially flow
or thin out on expansion, so that a reliable expansion geometry and
wall thickness can be achieved. Other stent constructions are
suitable. For example, filament-form stents in which filaments of
polymer material are arranged to define a generally tubular
structure can be used. Open areas are defined between the
filaments. An example of a stent design including helical filaments
is provided in Wallsten, U.S. Pat. No. 4,655,771. Suitable aperture
wall designs are also described in Palmaz U.S. Pat. No. 4,733,665.
Another suitable arrangement is exemplified by the Express stent,
commercially available from Boston Scientific, Natick, Mass.
[0066] Referring to FIGS. 2A-2C, the delivery of a stent into the
body is illustrated. The stent is delivered utilizing a catheter
24, which includes a catheter body 25 that carries a balloon 26 at
its distal end. At the proximal end, the catheter includes an
inflation apparatus 28 such as a syringe or pump apparatus which
can be used to inject and circulate inflation fluid into the
catheter, where it is directed by a lumen to the interior of the
balloon so that the balloon can be inflated. In addition, the
inflation apparatus can include a heating apparatus 30, to heat the
inflation fluid directed to the balloon. The catheter is delivered
into a vessel 20 to the site of an obstruction 31 typically
utilizing a guidewire 32. The guidewire 32 extends through a lumen
within the body 25 of the catheter.
[0067] Referring particularly to FIGS. 2A and 2B, the stent 10 is
positioned over the inflatable balloon 26. Referring particularly
to FIG. 2A for delivery into the body, the balloon is initially in
a small diameter deflated condition. The stent is in a small
diameter condition over the balloon. Referring particularly to FIG.
2B, when the treatment site is reached, the balloon is inflated by
actuating the inflation apparatus 28. The inflation fluid is heated
to heat the polymer body of the stent 10. By providing outward
radial force while heating the stent, the stent is expanded into
contact with the body lumen. The stent can be expanded
simultaneously with the widening of the obstructed region. After
expansion to the desired diameter, the temperature of the inflation
fluid is typically decreased to reverse the softening of the stent
body 10. Referring particularly to FIG. 2C, after the temperature
of the stent has been reduced in this manner, it remains implanted
in the vessel to resist vessel recoil and reduce restenosis after
the balloon is deflated and the catheter is removed from the
body.
[0068] Suitable polymers include those that maintain stent geometry
under expansion conditions, allowing for intricate stent geometries
such as apertured tubes having high open area to wall ratios. At
temperatures above body temperature and under conditions of radial
expanding pressure, the stent can be expanded without fracture or
substantial irreversible stress relaxation or creep. Typically, the
stent is heated to or above the melt or glass transition
temperature during expansion. In this condition, the polymer is in
a softened state. In this state, the polymer can be predictably
deformed, typically about aperture regions during expansion. In
addition, the soft condition permits proper apposition of the stent
to the lumen wall without kinking and without damage due to
excessive stiffness, which could straighten the lumen from its
native curvature and lead to dissections or other trauma. After the
stent is fully expanded and cooled, the polymer substantially sets
in the proper apposition, e.g. about a native curvature. Excessive
recoil of the stent to a linear configuration is avoided, reducing
trauma about the vessel. At the same time, the polymer can have
some elastomeric properties in the cooled, hardened state so that
the stent can flex with natural vessel motion. After cooling, the
stent exhibits sufficient resistance to inward radial force to
reduce restenosis due to, e.g., lumen wall recoil. The polymer has
sufficient strength so that the stent wall can be kept relatively
thin while resisting restenosis from lumen wall forces.
[0069] Suitable polymers include elastomers that are crosslinked
and/or crystalline. The crosslink and/or crystalline nature is
sufficient to resist excessive creep or stress relaxation when the
polymer is heated and expanded. The polymer can be crosslinked so
that it exhibits the desired elastomeric properties but not
crosslinked to the degree that it becomes excessively brittle. Too
little crosslinking does not establish sufficient resistance to
flow during heating and expansion to maintain stent geometry. In
addition, crosslinking can be adjusted to adjust the melt or glass
transition temperature and transition temperature range. A narrow
melt transition range is desirable, e.g. 5.degree. C. or 10.degree.
C. or less. Crosslinking can be achieved by application of
radiation such as e-beam, UV, gamma, x-ray radiation or by
heat-activated chemical crosslinking techniques. Chemical
crosslinking agents include peroxides, such as benzoyl peroxide or
dicumyl peroxide (DCP), and azo compounds, such as
2,2'-azobis(2,4-dimethyl valeronitrile) or
2,2'-azobis[N-(2-propenyl)-2-methylpropionamide]. Radiation
techniques provide the advantage that the polymer typically does
not have to be substantially heated to achieve crosslinking. An
intricate aperture pattern provided in a stent precursor tube can
be maintained and heat-induced flow of pre-crosslinked polymer can
be avoided. For gamma radiation, an exposure of about 50-300, e.g.
250 kilograys typically provides sufficient crosslinking. Melting
and crystallization temperatures are measured using a differential
scanning calorimetry.
[0070] The polymer can have elastomeric properties in the melted or
softened state. Elastomeric properties at melt or glass transition
can be investigated by measuring the modulus of elasticity or
storage modulus as a function of temperature and determining the
elastomeric nature of the material in the desired expansion
temperature range. Referring to FIG. 3, a plot of storage modulus
as a function of temperature is provided. Storage modulus decreases
as the material is heated. At the melt or glass transition, a
plateau "P" is typically consistent with an elastomeric nature. At
much higher temperatures, the modulus drops off more quickly,
indicating a material which could flow under pressure. To determine
storage modulus, a dynamic mechanical analyzer (Perkin Elmer) can
be used. Dynamic mechanical analysis was carried out in tensile
mode at an operating frequency of 1 Hz, a static force of 10 mN,
and oscillation amplitude of 5 .mu.m (approximately 0.1% strain)
and an automatic tension setting of 125%. Temperature ramps were
conducted at 4.degree. C./minute over the range -100.degree. C. to
100.degree. C.
[0071] Chemically crosslinking PCO also has a direct impact on the
thermomechanical properties, e.g. modulus versus temperature,
through the establishment of a permanent network and indirectly
through morphological transitions. Revealing such effects by the
use of DMA, FIG. 3A shows plots of the tensile storage modulus (E')
versus temperature for cured PCOs prepared with varying amounts of
DCP. All of the PCO samples are characterized by a solid-like
storage modulus (about 1.7 GPa) for temperatures below
T=-70.degree. C. with this modulus value being invariant to the
crosslinking density. For temperatures above T=-70.degree. C., the
apparent onset of T.sub.g in the PCO samples, E' begins to decrease
gradually to a level that is dependent on crosslink density, but
spanning 0.05 to 0.5 GPa. The decrease in the modulus with
crosslinking in this temperature region can be understood from the
results of the DSC and wide angle x-ray scattering (WAXS), FIG. 3B,
that showed crosslinking reduces the degree of crystallinity of
PCO. It is to be expected that the crystalline phase will function
as both the fixing mechanism for shape memory and a means of
controlling room temperature modulus over a full order of
magnitude. For temperatures nearing T=62.degree. C., close to the
melting temperature measured by DSC, the storage modulus of neat
PCO begins to decrease sharply to about 2 MPa at the completion of
melting at 71.degree. C. As found with DSC, this transition
temperature is observed mechanically to decrease with increasing
degree of crosslinking. For temperatures greater than T.sub.m, the
modulus of neat PCO, trace (i), continues to decrease to a point
where the material flows like a viscous liquid, not showing a
persistent rubbery plateau (FIG. 3). This feature hampers the
applicability of neat PCO for use as a shape memory polymer due to
an inability to be deformed as a rubber above T.sub.m without rapid
stress relaxation. On the other hand, cured PCO, which contains
just 1% peroxide, represented by trace (ii), will allow significant
shape memory effects owing to its persistent rubbery plateau above
72.degree. C. As the amount of peroxide increases, the rubbery
plateau modulus increases, allowing for enhanced mechanical energy
storage, but the transition temperature and the steepness of the
transition decrease. In the case of PCO with 10% DCP, shown as
trace (v) in FIG. 3A, the thermomechanical response that is
observed is inconducive to shape memory effects as the fixing
(crystallization) temperature is lower than room temperature so
that shape fixing would require subambient cooling and the
temporary shape would be expected to drift via partial melting. In
addition, the melting transition is too broad for dramatic strain
recovery to be expected.
[0072] Suitable polymers include elastomers that are typically
crosslinked and/or crystalline and exhibit melt or glass
transitions at temperatures that are above body temperature and
safe for use in the body, e.g. at about 40 to 50.degree. C.
Suitable polymers can have an elastic modulus of about 60,000 or
70,000 psi or more at 25.degree. C. (ASTM D638M). Such polymers may
have a variety of room temperature moduli, from rigid glassy
materials having storage moduli of several GPa to compliant rubbers
with moduli as low as tens of MPa. Moreover, the moduli may tuned
over the range 0.5<E<10 MPa, as dictated by the end
application. Suitable polymers include polynorbornene,
polycaprolactone, polyenes, nylons, polycyclooctene (PCO), blends
of PCO and styrene-butadiene rubber, polyvinyl
acetate/polyvinylidinefluoride (PVAc/PVDF), blends of
PVAc/PVDF/polymethylmethacrylate (PMMA), polyurethanes,
styrene-butadiene copolymers, polyethylene (particularly,
crosslinked polyethylene), trans-isoprene, block copolymers of
polyethylene terephthalate (PET) and blends of polycaprolactone and
n-butylacrylate. A suitable PVAc/PVDF tube is formed by compounding
60-80 parts (by weight) PVAc (B-100, mw 500,000, ChemPoint,
Cleveland, Ohio) with 40 to 20 parts PVDF (Grade 1010, Solvay
Fluoropolymers, Houston, Tex.). The PVAc/PVDF is a crystalline
material that can be utilized with or without crosslinking.
[0073] The polymer body can be made of mixtures of polymers or
multiple polymer layers. The polymer forming the stent body can be
compounded to include a drug, which elutes from the polymer, or
radiopaque material. The structural polymer body can be coated with
other polymers to carry drug or control drug delivery from the
structural polymer. The polymer body can also exhibit shape memory
properties. This feature of the polymer can be used in combination
with the expansion properties discussed above. For example, the
polymer can be configured to remember an enlarged or reduced
diameter configuration. For example, the stent can be delivered
into the body, and expanded by a combination of heat and radial
pressure as described above. After a time, the stent can be
retrieved by reheating the stent. In this case, the heating causes
the stent to revert its small diameter condition. The remembered
stent diameter is less than the vessel diameter and the stent can
be more easily removed from the vessel. Such an application might
be useful, for example, for a stent delivered into the prostate
where removal and replacement is desirable.
[0074] Refer to FIGS. 4 and 5, manufacture and use of the stent is
illustrated. Referring particularly to FIG. 4, in a first step, a
polymer tube 40 is constructed by extrusion or molding a suitable
polymer to an initial diameter di which in the same or greater than
the target lumen diameter. (For stents made of polymer strands, the
strands can be formed by extrusion, followed by arranging the
strands into a tube, e.g. by weaving or knitting.) The tube wall is
then cut to provide a pattern of open areas in a desirable
geometric pattern, e.g. by laser cutting. The polymer can be
recrystallized or crosslinked, if necessary. Next, the tube is
heated typically near or above the melt or glass transition and
mechanically deformed to a small diameter, suitable for delivery.
The tube is cooled, e.g. to room temperature. The tube is assembled
onto a catheter, delivered into the body, and expanded by
application of heat, to the melt or glass transition, while
inflating the balloon as discussed above. (If the polymer has shape
memory properties, the polymer tends to expand upon heating to a
larger, remembered diameter.
[0075] Referring particularly to FIG. 5, a polymer tube 50 is
constructed to an initial diameter di, smaller than the vessel
diameter. The tube wall is cut to provide an open area in a
desirable pattern so that when the stent is expanded, a
compression-resistant geometry will result. The polymer is
recrystallized or crosslinked, if necessary. The tube is assembled
in a catheter, delivered into the body, and expanded by heating to
the melt or glass transition temperature while inflating the
balloon to provide an outward radial expansion, as discussed above.
If the polymer has shape memory properties, the stent can be
subsequently re-heated so it reverts back to its remembered small
diameter configuration and removed from the body.
[0076] In particular embodiments, the stent can have an expanded
inner diameter of about 2 to about 20 mm. The initial inner
diameter can be in the range of about 1 to about 3 mm. The wall
thickness is in the range of about 0.005 mm to 20 mm. The wall
thickness variation between delivery and expanded states is within
about 10%, 5% or 1% or less. The ratio of the open area to the wall
area in the expanded state is about 0.5 to 0.7 or more. (The tube
wall area is the area of the tube defined by polymer. The open area
is the open area defined by the apertures.) A particular stent for
coronary use has an initial diameter of about 2 mm, an expanded
diameter of about 4 mm, and a wall thickness of about 0.005 mm to
0.1 mm. The stent can be used for various applications including
coronary, neuro, carotid, peripheral vasculature, ureteral, and
prostate lumens. The stent is particularly useful where the lumen
path is highly curved or irregular.
[0077] The catheter can be, e.g. an angioplasty balloon catheter
with a relatively non-distendable inflating balloon suitable for
expansion of occluded regions of a vascular lumen. The balloon may
include a polymer such as PET, which has a burst pressure of about
1.5 to 5 atm or more. The stent can be heated by heating the
balloon inflation fluid. The balloon inflation fluid can be heated
by e.g., heating the fluid delivery device outside the body using
e.g., resistive heating tape. Alternatively, the catheter can carry
a heating device. For example, a resistive heater or RF heater can
be provided in the interior of the balloon. A heated balloon
catheter is described in Abele et al. U.S. Pat. No. 5,496,311 and
U.S. Pat. No. 4,955,377. Vessel heating as described in the '311
can be used in combination with stent delivery as discussed herein.
Alternatively, the stent can be heated directly. For example, the
polymer can be compounded to include a material, such as magnetic
particles, which are susceptible to heating by magnetic effects,
such as hysteresis effects. A magnetic field can be imposed on the
stent body by a source on a catheter or outside the body. Particles
are available as the Smartbond System from Triton Systems, Inc.,
Chelmsford, Mass. Heating by magnetic effects is discussed in U.S.
Pat. No. 6,056,844. The stent can also be heated during delivery
without applying expansion force to soften the stent, improving its
flexibility and thus improving delivery to a treatment site through
a tortuous vessel path.
EXAMPLE
[0078] A polycyclooctene polymer (Vistenemer 8012 pellets, mw
90,000, Degussa, NJ) is melt processed in an extruder to produce a
tube having dimensions of about 0.118 inch O.D. and 0.070 inch I.D.
(wall thickness about 0.024 inch). The tube is cut to a length of
about 4 cm. The tube is subject to UV excimer laser ablation
cutting to provide an aperture pattern of rectangular slots having
a width of about 0.2 mm and a length of about 8 mm. Beam energy and
pulse rate are selected to avoid substantial heating or melting of
the polymer. The polymer can be compounded with about 10% TiO.sub.2
(T8141, Dupont) to enhance absorption of laser radiation. A
suitable pattern is consistent with the Express stent (commercially
available from Boston Scientific, Natick, Mass.). (Alternatively, a
pattern as described in Palmaz U.S. Pat. No. 4,733,665 can be
used.) The tube is heated to a temperature below its melt point,
e.g., to about 39 to 40.degree. C. in a water bath and expanded by
balloon catheter to a diameter of about 5 mm and positioned on a
mandrel (PTFE tube) to maintain the expanded shape and diameter.
The tube is then cooled to room temperature. The polymer is then
crosslinked by e-beam radiation at 250 K Grays (Steris Isomedics
Services, Northborough, Mass.). Crosslinking fixes the stent in the
condition. (The crosslinked PCO has an elastic (Youngs) modulus of
about 74945 psi at about 25.degree. C. (ASTM D638M)). The stent is
heated to the polymer melt temperature, about 45.degree. C. and
collapsed over a deflated balloon (diameter of about 2 mm) with a 4
mm inflated maximum diameter and 2 cm length. (A suitable balloon
catheter is a 75 cm Meditech UltraThin Catheter, available from
Boston Scientific, Natick, Mass.). The balloon and stent are
immersed in a water bath of about 42 to 45.degree. C. and water the
same temperature is used to inflate the balloon. The stent is
expanded to about 4 mm diameter (ID) at an inflation pressure of
about 1 to 1.5 atm (measured at the delivery syringe). After
expansion, the heating is discontinued and the balloon and
inflation fluid allowed to cool to body temperature (while the
balloon remains inflated). Alternatively, a cooled contrast fluid
can be circulated to the balloon. The stent exhibits no visible
reduction in wall thickness or irregular flow of polymer into the
stent open areas. In addition, in the heated, expanded state, the
stent can be bent around a mandrel of about 0.75 cm radius without
kinking. After the stent is cooled, it maintains the curved
form.
[0079] Referring to FIGS. 6-8, stent 100 includes a coiled rod 120
composed of a polymer. Stent 100 includes an elongated portion 140
having a general diameter d.sub.1 and an end portion 160 having a
maximum diameter d.sub.2. General diameter dl, for example, may be
between about 3 mm and about 25 mm, more preferably between about 6
mm and about 14 mm, and maximum diameter d.sub.2, for example, may
be between about 7 mm and about 30 mm, more preferably between
about 10 mm and about 17 mm. When stent 100 is designed, for
example, for insertion into a urethra, the stent may have an
overall length, for example, of between about 3 mm and about 15 mm,
preferably between about 6 mm and 10 mm, and end portion 160 may
have a length, for example, of from about 3 mm to about 15 mm,
preferably from about 5 mm to about 10 mm. End portion 160 is in a
flared position. Referring to FIG. 8, stent 100 is shown with end
portion 160 in a collapsed position that can be reverted with
heating to the expanded position shown in FIGS. 6 and 7.
[0080] Generally, the portion of the stent in the collapsed
position that can be reverted to the expanded position is, for
example, greater than 5%, 10%, or even 25% of the overall length L
of the stent, and less than 80% or 65% of the overall length L of
the stent. For example, the of the overall length L of the stent
may be between 10% and 65% of the overall length L of the
stent.
[0081] The polymers preferably are cross-linked and/or crystalline
elastomers that have melt or glass transition temperatures that are
above body temperature, for example, greater than 45.degree. C. or
55.degree. C. The degree of cross-linking can be used to adjust,
for example, the melt or glass transition temperature, and range,
of the polymer. The polymer preferably has a relatively narrow, for
example, less that 5.degree. C. or 10.degree. C., melt or glass
transition temperature range.
[0082] The polymer preferably has elastomer properties in its
melted or softened state. Preferred polymers have an elastic
modulus, for example, of about 60,000 psi or 70,000 psi or more at
25.degree. C. (ASTM D638).
[0083] Examples of polymers include polynorbornene and copolymers
of polynorbornene, blends of polynorbornene with KRATON.RTM.
(thermoplastic elastomer) and polyethylene, styrenic block
copolymer elastomers (e.g., styrene-butadiene),
polymethylmethacrylate (PMMA), polyethylene, polyurethane,
polyisoprene, polycaprolactone and copolymers of polycaprolactone,
polylactic acid (PLA) and copolymers of polylactic acid,
polyglycolic acid (PGA) and copolymers of polyglycolic acid,
copolymers of PLA and PGA, polyenes, nylons, polycyclooctene (PCO),
polyvinyl acetate (PVAc), polyvinylidene fluoride (PVDF), blends of
polyvinyl acetate/polyvinylidine fluoride (PVAc/PVDF), blends of
polymethylmethacrylate/polyvinyl acetate/polyvinylidine fluoride
(PVAc/PVDF/PMMA) and polyvinylchloride (PVC).
[0084] In some embodiments, the polymers above are also useful for
the stents of FIGS. 1, 4 and 5.
[0085] Particular polyurethanes are made by reacting (A) a polyol,
(B) a chain extender dihydroxyl-terminated POSS and (C) a
diisocyanate, where POSS stands for a polyhedral oligomeric
silsesquioxane diol. The polyol (A) can be polyethylene glycol
(PEG), polycaprolactone (PCL), polycyclooctene (PCO), trans-1,4
butadiene, transisoprene, polynorbornene diol and polymethacrylate
copolymer, the chain extender(B) can be TMP cyclopentyldiol-POSS,
TMP cyclohexyldiol-POSS, TMP isobutyldiol-POSS,
transcyclohexanediolcyclohexane-POSS, or
transcyclohexanediolisobutyl-POS- S and the diisocyanate (C) can be
selected from a large number of diisocyanates and is preferably
4,4' diphenyl methylene diisocyanate (MDI). Other diisocyanates (C)
that are suitable for use in the synthesis of hybrid polyurethane
SMPs include: toluene-2,4-diisocyanate (TDI),
toluene-2,6diisocyanate, hexamethylene-1,6-diisocyanate (HDI),
4,4'diphenylmethane diisocyanate (MDI), isophorone diisocyanate
(IPDI), and hydrogenate 4,4'-diphenylmethane diisocyanate
(H12MDI).
[0086] The particular polyurethanes described directly above may be
prepared the non-limiting schemes illustrated below. A graph of
heat flow as a function of temperature for several POSS
polyurethanes is shown in FIG. 8A and a graph of storage modulus as
a function of temperature for several POSS polyurethanes is shown
in FIG. 8B. 1
[0087] This scheme shows an example of synthesis of TPU using
polyethylene glycol as polyol, TMP Isobutyldiol-POSS as chain
extender to react with 4,4' diphenyl methylene diisocyanate in
toluene. 2
[0088] This scheme shows an example of synthesis of TPU using
polycaprolactone diol as polyol, TMP Isobutyldiol-POSS as chain
extender to react with 4,4' diphenyl methylene diisocyanate. 3
[0089] This scheme shows an example of synthesis of TPU using
polyocyclooctene as polyol, TMP Isobutyldiol-POSS as chain extender
to react with 4,4' diphenyl methylene diisocyanate.
[0090] Any of the polymers mentioned above may be filled with, for
example, nanoparticles of clay and silica to, for example, increase
the modulus of the plastic. Dispersing agents and/or
compatibilizing agents may be used, for example, to improve the
blending of polymers and the blending of polymers with fillers.
Dispersing agents and/or compatibilizing agents include, for
example, ACRAWAX.RTM. (ethylene bis-stearamide), polyurethanes and
ELVALOY.RTM. (acrylic-functionalized polyethylene). The polymers
can be cross-linked by application of radiation such as e-beam, UV,
gamma, x-ray radiation or by heat-activated chemical crosslinking
techniques. Radiation techniques provide the advantage that the
polymer typically does not have to be substantially heated to
achieve crosslinking. For e-beam radiation, an exposure of about
200-300, e.g. 250 kilograys, typically provides sufficient
crosslinking.
[0091] Referring to FIG. 9, wrapping fixture 200 can be used for
making coiled stent 100. Wrapping fixture 200 includes a base 220
for support, a mandrel 240 with a flared end 260, slits 280 for
fixing the plastic rod 120, an aperture 290 for fixing the plastic
rod 120 on the non-flared end and a fixing screw 299 for releasably
fixing mandrel 240 to wrapping fixture 200.
[0092] Stent 100 is manufactured from plastic rod 120 made by a
variety of methods known in the art (e.g., extrusion, coextrusion,
injection molding, casting, compression molding). If casting is
used, the polymers may have tunable critical temperatures and
rubber modulus have been synthesized using a thermosetting random
copolymer formed from two vinyl monomers that yield controlled
T.sub.g and casting-type processing. Such copolymers were
crosslinked with a difunctional vinyl monomer (crosslinker), the
concentration of crosslinker controlling the rubber modulus and
thus the work potential during recovery. Rod 120 may have a
diameter, for example, of about 0.25 mm to about 2.5 mm or more.
Plastic rod 120 and wrapping fixture 200 are heated to the
softening temperature of the polymer, making the plastic rod 120
malleable. The rod 120 is inserted into aperture 290 that is
machined through mandrel 240 to fix the rod at the starting end.
The rod 120 is tightly wrapped around mandrel 240, including flared
end 260. To fix plastic rod 120 in place, plastic rod 120 is pushed
into slits 280. The overall length of the stent 100 may be, for
example, about 2 mm to about 150 mm or more. The overall length
required depends upon the application. The plastic rod 120, now
fixed in place on the mandrel 240, is heated to above the softening
point of the material and maintained at that temperature long
enough to anneal the rod and fix the shape. Typically, the time
required to fix the shape is from about 0.25 hr to 10 hr or more.
After cooling, stent 100 is removed from mandrel 240. Before
packaging, the flared end of the coil is tapered down and collapsed
so that the diameter along the entire length of the stent is
approximately d.sub.1. Collapsing the flared end 160 of stent 100
allows for ease of insertion, for example, into a restricted
prostatic urethra.
Example 1
[0093] A 56:24:20 mixture of PVAc/PVDF/PMMA is dry bended and
loaded into the hopper of an extruder. The PVAc is grade B-100, the
PVDF is Solvay SOLEF.RTM. 1010 and the PMMA is Atofina
PLEXIGLAS.RTM. V045. The mixture is melt processed to produce 1.27
mm (0.05 inch) monofilament. The rod is made into a coil by winding
it around wrapping fixture 200. The fixture and the rod are
immersed into a 50.degree. C. water bath. At this temperature, the
rod becomes malleable enough to wind easily around the mandrel and
secured in place to prohibit the uncoiling of the helical shape.
The mandrel is removed from the fixture with the stent locked in
place and placed into an oven at 110.degree. C. for one hour to
anneal the stent. This annealing process locks the permanent shape
of the coil. The mandrel and coil are cooled to room temperature,
and the stent is removed from the mandrel. The stent had on overall
length of approximately 73 mm and a flared end portion length of
approximately 7 mm. The diameter d.sub.1 of the body is
approximately 6 mm and the maximum diameter d.sub.2 of the flare on
the open end is approximately 11 mm. Before packaging, the flared
end of the coil is tapered down with brief heating to 50.degree. C.
and manipulation, followed by cooling, so that the diameter is
approximately 6 mm along the entire length of the stent.
Example 2
[0094] A 70:30 mixture of PVAc/PVDF is dry bended and loaded into
the hopper of an extruder. The mixture is melt processed to produce
1.27 mm (0.05 inch) monofilament. The rod is made into a coil by
winding it around wrapping fixture 200. The fixture and the rod are
immersed into a 50.degree. C. water bath. At this temperature, the
rod becomes malleable enough to wind easily around the mandrel and
secured in place to prohibit the uncoiling of the helical shape.
The mandrel is removed from the fixture with the stent locked in
place and placed into an oven at 110.degree. C. for one hour to
anneal the stent. This annealing process locks the permanent shape
of the coil. The mandrel and coil are cooled to room temperature,
and the stent is removed from the mandrel. The stent had on overall
length of approximately 73 mm and a flared end portion length of
approximately 7 mm. The diameter d.sub.1 of the body is
approximately 6 mm and the maximum diameter d.sub.2 of the flare on
the open end is approximately 11 mm. Before packaging, the flared
end of the coil is tapered down with brief heating to 50.degree. C.
and manipulation, followed by cooling, so that the diameter is
approximately 6 mm along the entire length of the stent.
[0095] Referring to FIG. 10-12, stent 100 may be, for example,
inserted into restricted urethra 300 on delivery tube 320. During
insertion, end portion 160 is in a collapsed position. After
insertion, warm water (e.g., 45.degree. C.-55.degree. C.) is
flushed through delivery tube 320 that is in thermal contact with
stent 100. Heating reverts the collapsed end 160 to a flared,
expanded position (FIG. 12). The flared, expanded position allows
stent 100 to remain fixed in position, for example, in the
prostatic urethra.
[0096] Referring to FIG. 13 for a little more detail, delivery tube
320 is a long cylindrical tube into which a ureteral scope 380 is
inserted. Delivery tube 320 has a distal end 330 over which stent
100 is placed. Delivery 320 is fitted with a side port 350
including a stopcock 370 through which saline can be flushed for
irrigation. Delivery tube 320 with stent 100 in place is delivered
into, for example, the prostatic urethra with the aid of a ureteral
scope. Once stent 100 is in place, hot saline is flushed through
port 350 to revert the collapsed end 160 to a flared, expanded
position (FIG. 12). The flared, expanded end allows stent 100 to
remain fixed in position, for example, in or adjacent the prostatic
urethra or external sphincter between the prostate and the bladder
to prevent migration. The direction of the flare can, of course, be
oriented in other directions. The scope and delivery tube 320 are
withdrawn, leaving stent 100 in place.
[0097] Referring to FIGS. 13-13A, an alternative delivery system is
illustrated that includes a tube 320 with a screw on tip 331 onto
which a stent 100 is placed after collapsing the end portion 160.
The assembly is inserted into, for example, the prostatic
urethra.
[0098] Other delivery methods are within the claims. Stent 100 may
be, for example, inserted into restricted urethra 300 on balloon
catheter (not shown). During insertion, end portion 160 is in a
collapsed position. After insertion, warn water is flushed through
the guide wire lumen of the balloon catheter to flood the area and
to heat the stent. Heating of the stent by the water reverts the
collapsed end 160 to a flared, expanded position The flared,
expanded position allows stent 100 to remain fixed in position, for
example, in the prostatic urethra. If there is an obstruction in
the lumen into which the stent is deployed the stricture can be
dilated using the balloon to help the stent open fully and maintain
a uniform diameter inside the vessel.
[0099] Referring to FIG. 14, coiled stent 100 with an end 160 in
the expanded position can be removed with the aid of a catheter
equipped with a grasping device 360 and a ureteral scope 380 for
visualizing stent 100 in, for example, the prostatic urethra. Once
end 400 of stent 100 has been visualized with ureteral scope 380,
the stent is grasped with grasping device 360. Next, ureteral scope
380 is removed from the catheter and is replaced with a heating
device (not shown), e.g. a catheter. Heating stent 100 above the
softening point of the polymer, e.g., from about 45.degree. C. to
about 55.degree. C. for polycyclooctene (PCO), and pulling the end
400 of stent 100 through the orifice 420 allows the stent to be
removed in a substantially uncoiled state.
[0100] Although FIG. 11 shows heating of stent 100 with a warm
liquid on a delivery tube, other heating methods are possible. For
example, heating may be accomplished with the use of IR, RF or
inductive heating.
[0101] Although insertion into a prostatic urethra has been used as
an example, insertion of stent 10 into other body lumens or
cavities is possible. For example, other body lumens or cavities
include the biliary duct, cystic duct, a ureter, a bulbar urethra
or a hepatic duct.
[0102] Referring to FIG. 15, the modulus of polycyclooctene (PCO)
that can, for example, be the polymer of stent 100 is shown as a
function of temperature. Below approximately -65.degree. C.
(T.sub.g, region A), PCO exists a rigid, glassy polymer. Above
T.sub.g, but below T.sub.m, PCO exists as a flexible elastomer
(region B). Above T.sub.m, PCO exists as a relatively low modulus
elastomer. Above T.sub.m, for example, stent 100 composed of PCO
can be removed from a lumen or cavity of the body, the prostatic
urethra, for example, in a substantially uncoiled state.
[0103] Referring to FIG. 16, the modulus of a ternary blend of
PVAc/PVDF/PMMA that can, for example, be the polymer of stent 100
is shown as a function of temperature. Adding PMMA offers the
advantage, for example, of increasing the modulus of the blend.
[0104] Referring once again to FIG. 15 and to FIGS. 6-8, heating
stent 100 in the expanded position briefly above T.sub.m (region C)
and then cooling rapidly below T.sub.m (e.g., region B) "freezes"
stress into stent 100. Stent 100 reverts from its collapsed
position to its expanded position upon re-heating above T.sub.m
(region C) because the modulus of the material lowers sufficiently
to release the residual stress that was "frozen" into stent 100
during the rapid cooling.
[0105] FIGS. 17-28 show other examples of stents.
[0106] Referring to FIGS. 17 and 18, coiled stent 500 has two end
portions 520 and 540 in expanded positions. End portions 520 and
540 can be collapsed (FIG. 18) for ease of insertion into a body
cavity or lumen, and reverted with heat to expanded positions.
[0107] Referring to FIG. 19, coiled stent 600 has two end portions
620 and 660 and a central portion 640 in expanded positions. All
three portions may be collapsed (not shown), and then reverted to
expanded positions.
[0108] Referring to FIGS. 20 and 21, coiled stent 700 made from a
flattened tube 710 has an end portion 720 in an expanded position.
The flattened tube can, for example, add strength to the stent. The
tube can have a major diameter, for example, of between about 1.0
mm to about 3.0 mm, more preferably between about 1.5 mm to about
2.25 mm, and major inner diameter, for example, of between about
0.5 mm to about 2.5 mm, more preferably between about 1.25 mm and
about 1.75 mm. End portion 720 may be collapsed (not shown) and
then reverted to an expanded position. Referring to FIG. 21,
flattened tube 710 has an interior 740 that may be filled with, for
example, a medicament. The medicament, for example, may be
triclosan or salicylic acid. Release of medicament from flattened
tube 710, for example, may reduce the risk of infection. Interior
740 may also be filled with, for example, paclitaxel or
mitoxantrone. Release of the these medicaments from interior 740
may be, for example, useful for treating prostate cancer and
reducing prostatic hyperplasia.
[0109] Referring to FIG. 22, coiled stent 800 made from tape 810
has an end portion 820 that may be collapsed and then reverted to
an expanded position. Tape 810, for example, may have a thickness
from about 0.5 mm to about 2.0 mm, more preferably from about 0.75
mm to about 1.25 mm, and a width, for example, of from bout 1.0 mm
to about 3.0 mm, more preferably from about 1.75 mm to about 3.00
mm. In this particular embodiment, an aperture 840 is provided so
that a trailing string (not shown) can be included for ease of
removal with the grasping device shown in FIG. 14.
[0110] Referring to FIGS. 23-25, coiled stent 900 is made from
plastic rod and has an end portion 920 that may be collapsed and
then reverted to an expanded position. Stent 900 includes a
plurality of protruding elements 940 that are integral with and
extend outwardly from the plastic rod from which the stent is made.
Referring now to FIGS. 26-28, coiled stent 1000 is made from
plastic rod, for example, oriented monofilament, and has an end
portion 1020 that may be collapsed and then reverted to an expanded
position. Stent 1000 includes a plurality of protruding elements
1060 that extend outwardly from the plastic rod from which the
stent is made. The friction provided by protruding elements
940,1060 can help to hold stent 900,1000 in place within, for
example, the prostatic urethra.
[0111] Protruding elements 940 are made, for example, by cutting
into the plastic rod with, for example, a sharp edged instrument,
for example, a knife, so as penetrate a depth into the plastic rod.
The depth of penetration P is adjusted to provide acceptable
frictional properties, while minimizing the impact on the
mechanical properties of the plastic rod. In some implementations,
the maximum depth of penetration into the plastic rod, measured
inwardly from the outer surface of the plastic rod is, for example,
from about 1 to about 50% of the average thickness of the plastic
rod. If the depth penetration is too large, the mechanical
properties of the plastic rod may be reduced and if the depth of
penetration is too low, the resulting protruding elements may be
too small to provide the appropriate frictional properties when
expanded in a body cavity or lumen, for example, the prostatic
urethra. Other cutting means are possible, for example, water knife
and laser cutting means, to reduce the impact of the cutting on the
mechanical properties of the plastic rod. The shape of the plastic
rod from which the stent is made may be of other forms than that
shown above. For example, it may be in the form of, for example, a
coiled elongated flattened tube and the flattened tube may include
a central opening that includes a medicament that can be released
by the inserted stent.
[0112] In some implementations, stent 900 is manufactured from
plastic rod made by a variety of methods known in the art (e.g.,
extrusion and coextrusion). The plastic rod may have a diameter,
for example, of about 0.25 mm to about 2.5 mm or more. In a
preferred method, the protruding elements are put onto the plastic
rod before wrapping the mandrel shown and discussed above. After
wrapping the mandrel, the plastic rod and wrapping fixture 200 are
heated to the softening temperature of the polymer, making the
plastic rod malleable. The protrusions are annealed in the "up"
position, that is, with the protruding elements extending outwardly
by "prying up" the protruding elements that results from cutting.
Prying up the protruding elements may be achieved by, for example,
running a surface across the protruding elements in a direction
opposite the cut direction. Annealing is continued to fix the
shape. After cooling, the stent is removed from mandrel. Before
packaging, the flared end of the coil is tapered down along with
protruding elements and collapsed so that the diameter along the
entire length of the stent is approximately d.sub.1. Collapsing the
flared end and protruding elements allows for ease of insertion,
for example, into a restricted prostatic urethra. In some
implementations, the flared end and the main body are collapsed to
have a diameter less than d.sub.1. Upon heating, the end portion
reverts to its expanded position and the protruding elements revert
to their up positions. If a medicament is placed in the cavities
960 from which the protruding elements 940 are carved, it may be
released upon expansion of the stent.
[0113] Stent 1000 with protruding elements 1060 is made by, for
example, wrapping a thicker plastic rod with a thinner plastic rod,
for example, a monofilament, that includes a plurality of
constrictions, for example, knots along its length. The elevation E
above an outer surface of the thicker plastic rod is adjusted to
provide acceptable frictional properties. In some implementations,
the maximum elevation above an outer surface of the thicker plastic
rod is, for example, from about 1 to about 50% of the average
thickness of thicker plastic rod. If the elevation E is too large,
insertion of stent 1000 into, for example, a prostatic urethra may
become difficult and if the maximum elevation above the protruding
elements is too small, the protruding elements may not provide the
appropriate frictional properties when expanded in a body cavity or
lumen, for example, the prostatic urethra. The shape of the rods
from which the stent is made may be of other forms than that shown
above. For example, it may be in the form of, for example, a coiled
elongated flattened tube and the flattened tube may include a
central opening that includes a medicament that can be released by
the inserted stent.
[0114] In some implementations, stent 1000 is manufactured from
plastic rod made by a variety of methods known in the art (e.g.,
extrusion and coextrusion). The thicker plastic rod may have a
diameter, for example, of about 0.25 mm to about 2.5 mm or more.
The thinner plastic rod from which the protruding elements are
fashioned may have a diameter of, for example, from about 0.2 mm to
about 20 mm. In a preferred method, the constrictions, for example,
knots, are placed on the thinner plastic rod and the thinner
plastic rod is wrapped around the outer surface of the thicker
plastic rod. The ends of the thinner plastic rod are heat staked to
hold the thinner plastic rod onto the outer surface of the thicker
plastic rod. Now, the assembly of the thinner and thicker plastic
rod is wrapped around the mandrel shown and discussed above. After
wrapping the mandrel, the plastic rods and wrapping fixture 200 are
heated to the softening temperature of the polymer of the thicker
plastic rod, making the plastic rod malleable. Annealing is
continued to fix the shape. After cooling, the stent is removed
from mandrel. Before packaging, the flared end of the coil is
tapered down so that the diameter along the entire length of the
stent is approximately d.sub.1. Collapsing the flared end and
protruding elements allows for ease of insertion, for example, into
a restricted prostatic urethra. In some implementations, the
thinner plastic rod may contain a medicament that is released upon
expansion, for example, in the prostatic urethra. In other
implementations, the thinner plastic rod is made of a degradable
material and the degradable material is filled with a
medicament.
[0115] In some embodiments, the entire stent, for example, the
stents of FIGS. 4, 5, 20, 23 and 26, may have an expanded
position.
Other Embodiments
[0116] In some of the embodiments of any of the above stents, only
a portion or portions of the stent (e.g., the portion(s) having an
expanded position) may be composed of the polymer. The remainder of
the stent may be, for example, composed of a non-polymeric material
(e.g., a metal or metal alloy, e.g., Ni/Ti alloy). Moreover, the
stent may be composed of multiple layers of materials, for example,
by co-extruding the layers when making an elongated element. The
stent may be a multiple segment stent.
[0117] The polymer in any of the above stents may be a blend of
polymers, for example, miscible blends of a semicrystalline
polymers with an amorphous polymer. For those blends that are
miscible at the molecular level, a single glass transition results,
without broadening. Additionally, in such miscible blends the
equilibrium crystallinity (which controls the plateau modulus
between T.sub.g and T.sub.m where shape fixing is performed) also
changes dramatically and systematically with blend composition;
i.e., relative levels of each component.
[0118] Polymers blends with a relatively high modulus in the fixed
state at room temperature, having a tunable and sharp transition,
the permanent shape of which can be remolded repeatedly above
certain melting temperatures are prepared by the blending of
crystalline polymers (C') with amorphous polymers (A'), such that
they are a single miscible phase in the molten state (allowing
processing to stress-free native states) but crystalline to a
limited and tailored extent and which further vitrify on cooling to
room temperature. The recovery of the polymer blend may be fast,
for example, within seconds. Examples for (C') include
poly(vinylidene fluoride) (PVDF) (T.sub.g=-35.degree. C.,
T.sub.m=175.degree. C.), polylactide (PLA) (T.sub.g=56.degree. C.,
T.sub.m=165.degree. C.), poly(hydroxy butyrate), poly(ethylene
glycol) (PEG), polyethylene, polyethylene-co-vinyl acetate,
poly(vinyl chloride) (PVC), and poly(vinylidene chloride) (PVDC)
and copolymers of poly vinylidene chloride (PVDC)/poly vinyl
chloride (PVC). Examples for (A') include poly(vinyl acetate)
(PVAc) (T.sub.g=35.degree. C.), poly methyl acrylate (PMA), poly
ethyl acrylate (PEA), atactic poly methyl methacrylate (aPMMA),
isotactic poly methyl methacrylate (iPMMA), syndiotactic poly
methyl methacrylate (sPMMA), and other poly alkyl
methacrylates.
[0119] In some preferred embodiments formed from two miscible
polymer blends, the blend is prepared by mixing amorphous
poly(vinyl acetate) (PVAc) (T.sub.g=35.degree. C.) with
semicrystalline polylactide (PLA) (T.sub.g=56.degree. C.,
T.sub.m=165.degree. C.) or poly(vinylidene fluoride) (PVDF). The
polymers show complete miscibility at all blending ratios with a
single glass transition temperature, while crystallization
(exclusive of PVAc) is partially maintained. The T.sub.g's of the
blends are employed as the critical temperature for triggering the
shape recovery while the crystalline phases serve as physical
crosslinking sites for elastic deformation above T.sub.g, but below
T.sub.m.
[0120] The preferred blends are formed from poly vinyl
acetate(PVAC) and poly(lactic acid) (PLA) or poly(vinylidene
fluoride) (PVDF). However, examples of other suitable blends
include the pair PVDF/PMMA and ternary blends of PVDF/PMMA/PVAc.
The PMMA and the combination of PMMA/PVAc serve the same role as
PVAc in the blends as have been previously described. An advantage
of adding PMMA is that the critical temperature can be increased
arbitrarily to about 80.degree. C. and the room temperature modulus
can also be increased. The PVDF may be substituted by
poly(vinylidene chloride) (PVDC), by copolymers of poly(vinylidene
chloride/ply(vinyl chloride), or by any "C" polymer vide supra.
[0121] It has further been found that blending poly(vinyl chloride)
with poly(butyl acrylate) or poly (butyl methacrylate) (PVC/PBA)
has certain advantages. In the PVDF/PVAc case, PVAc simultaneously
lowers the crystallinity of PVDF while increasing T.sub.g. PVC may
serve the same role as PVDF, but it already has a low degree of
crystallinity, but a relatively high T.sub.g (.about.80.degree.
C.). Thus in this embodiment, the second component (PBA) serves
only the role of decreasing T.sub.g. This can also be achieved with
smal molecule plasticizers, most notably dioctylphthalate (DOP),
but is preferred to use a biocompatible polymeric plasticizer for
intended implantable applications. The range of PBA compositions is
10-40%, with 20% being the most advantageous, yielding a
T.sub.g.about.40.degree. C.
[0122] Melt blending of PLA/PVAc and PVDF/PVAc of varying blend
ratios was performed in a 30 ml Brabender mixer. The mixer was
equilibrated at T=180.degree. C. for 5 minutes after which the
mixer blade rotation was adjusted to 25 RPM and the premixed
polymers pellets added to the chamber over the course of 1 minute.
The polymers were mixed for 10 minute to ensure good dispersion.
Nitrogen was purged through the chamber to mitigate potential
oxidative degradation during mixing. After mixing, the blend was
taken out of the chamber, cooled to room temperature, and then
pressed between heated platens of a Carver press at 180.degree. C.
for 5 minutes under a load of 8 metric tons. A spacer was used to
control the thickness of the film and rapid cooling to room
temperature was carried out. The films thus formed were used for
the subsequent thermal and mechanical characterization.
[0123] The TGA results demonstrated that both PLA and PVAc are
stable for T<300.degree. C. Above this temperature PLA degrades
completely (no char yield), while the PVAc degrades to yield an
intermediate char yield of 25 wt % for 375<T<425.degree. C.
but complete degradation above 450.degree. C. Blend processing and
thermal and dynamic mechanical analyses (DSC and DMA) were
performed below 250.degree. C., to completely avoid
degradation.
[0124] The crystallization behavior of semicrystalline PLA was
investigated via DSC. The PLA samples were first heat pressed at
180.degree. C. for 10 minutes and then quenched to room temperature
with water cooling. One sample was directly analyzed by DSC, while
another was first annealed at 110.degree. C.
(=1/2(T.sub.g+T.sub.m)) for 1 hour to reach an equilibrium level of
crystallinity. FIG. 29 shows a comparison of thermal behavior for
these two samples. It was observed that quenching the PLA melt
results in a low degree of crystallinity and virtually no
recrystallization on heating, both indicating slow crystallization.
Annealing at 110.degree. C. for 1 hour results in significant
crystallization evidenced by a large melting endotherm at
T=155.degree. C. The melting temperature did not shift dramatically
due to annealing, but the endotherm shape did change. Complementary
WAXD experiments yielded the same conclusions.
[0125] The crystallization behavior selected of polymer blends was
also analyzed. All of the samples were heat pressed at 180.degree.
C. for 10 minutes and then annealed at 10.degree. C. for 1 hour
before thermal analysis, providing a standard condition for
extensive crystallization. FIG. 30 summarizes the first DSC heating
trace of the samples measured after annealing. The results indicate
that PVAc itself is amorphous (though with large physical aging
content) but that incorporation of PLA leads to crystallization in
proportion to the PLA wt-%. Also, the peak endotherm positions
(melting transitions) shift slightly to higher temperatures with
increasing PLA content. Quenching these samples to T=20.degree. C.
and reheating to 200.degree. C. again showed clearly that single
T.sub.g's are observed and that crystallization can be largely
suppressed. Importantly for shape memory, the single glass
transition events were not broadened in the blends relative to the
pure components, suggesting that the amorphous phase was quite
homogeneous for all of the blends. The observed T.sub.g values are
plotted in FIG. 31 along with the best fit with the Fox equation,
showing slight positive deviation. This leads to a conclusion that
strong interactions between the two polymers that reduces free
volume of the polymer blends and hence, increased glass transition
temperature relative to the Fox equation prediction has
occurred.
[0126] In order to elucidate the effect of PVAc on the degree of
crystallinity and the crystal structures, the crystalline
diffraction patterns were observed via wide-angle x-ray
diffraction. The results indicate that the PVAc phase has only an
amorphous halo, thus being totally amorphous, while the PLA
exhibits three very strong diffraction peaks at
2.theta.=22.3.degree., 25.0.degree. and 28.6.degree., corresponding
to d-spacings of 5.92, 5.29, and 4.64 A.degree., respectively. Upon
addition of PVAc, all of the peak intensities were depressed, but
the peak positions remained essentially unchanged. Consistent with
the DSC results, the degree of crystallinity increases in
proportion to PLA addition. From the peak width at half height, it
was found that the crystalline lamellae size did not decrease,
although the degree of crystallinity decreased, with increasing
PVAc content. This means that the decrease in crystallinity and
depression of the melting transitions are not due to a change of
crystal size, but rather may be due to a thinning of the lamellae
thickness or to a decrease of the crystal concentration.
[0127] The storage modulus of the polymer blends was also measured
using DMTA, first investigating the effects of annealing on the
storage modulus. Below their glass transition temperatures,
T.sub.g, both samples exhibit similar high storage moduli (3 GPa),
as well as similar softening points. When heated above T.sub.g, the
storage modulus of thermally quenched samples decreases sharply to
about 2 MPa; however, further increasing the temperature induces a
modulus increase attributed to recrystallization of the samples at
higher temperatures. This also proved that the sample is not in an
equilibrium state and that its mechanical properties in the rubbery
region depend on thermal history. To reach equilibrium, the sample
was annealed at 110.degree. C. for 1 hour as previously described
for DSC analyses. The storage modulus above T.sub.g shifts to about
200 MPa until melting, the increase being due to an increase of the
degree of crystallinity on annealing to tune the rubbery modulus at
equilibrium state,. PLA was blended in different proportions to
PVAc and annealed as above. Storage moduli for such blends were
measured and the results are plotted in FIG. 32. It can be seen
that, below T.sub.g, all of the samples show similar large moduli
while above T.sub.g the moduli decrease to a plateau whose
magnitude depends on crystallinity and thus PLA content. This trend
is in accordance with that of DSC and XRD, and can be explained by
the fact that the increase of storage moduli came from the physical
crosslinking formed by crystals and the filler effect of the high
modulus crystalline phase.
[0128] Stress-free shape memory tests were carried out in hot water
at 65.degree. C., with an annealed sample composed of 30% PLA. The
results show that the sample features quick and complete shape
memory behavior: the sample recovers to the original shape
(straight bar) within 10 seconds, with most of the recovery being
accomplished within the first several seconds.
[0129] The same characterizations were carried out on the blends of
PVDF and PVAc as above disclosed. The TGA and DSC results show that
PVDF is also thermally stable up to 300.degree. C., and the
mixtures form only one glass transition, the values fall between
the Tgs of the two homopolymers and changes with changing
composition. At the same time, the melting points and the degrees
of crystallinity were depressed with the incorporation of amorphous
PVAc.
[0130] The storage moduli of the blends, which give the rigidity of
the materials, were also measured. The results are similar to those
of the PLA/PVAc blends, the PVDF/PVAc blends being very rigid below
the critical temperatures (T.sub.g), and featuring a sharp modulus
changes at the Tg to a plateau modulus ranging from several MPa to
tens of MPa, depending on the degree of crystallinity of the
blends. These plateau moduli can be tuned by adjusting the degree
of crystallinity of the blend, that is, adjust the blend
composition.
[0131] The polymer in any of the above stents may be bioabsorbable
or non-bioabsorbable. Bioabsorbable polymers include, for example,
polyurethanes and polyurethane copolymers such as those described
above with the general formula (directly below), where X/Y is, for
example, 1 to 20, n is, for example, 2 to 1000, and the total
degree of polymerization m is, for example, 2 to 100 4
[0132] The bioabsorbability of the polymers is enhanced by
copolymerization of polyurethane and POSS with suitable monomers.
Examples of suitable monomers include caprolactone, ethyleneglycol,
ethylene oxide, lactic acid, and glycolic acid. The copolymers from
these monomers can hydrolyze and cleave the polymer linkage.
[0133] Other embodiments of stents can also be formed to include
materials described above. In some embodiments, an implantable
medical stent may be delivered into the body using a catheter. The
stent can be delivered in a small diameter form and then expanded
at a treatment site by triggering a shape change (for example, by
heat application) caused by the shape memory properties of the
polymer. The stent can also be expanded by a mechanical expander
such as an inflatable balloon of the type used on an angioplasty
catheter.
[0134] In some embodiments, the stent is sized (e.g., an expanded
inner diameter of about 2 mm to about 20 mm) and configured for use
in the vascular system, particularly the coronary arteries, and
implanted after or simultaneously with an angioplasty procedure to
maintain an open lumen and reduce restenosis. Vascular stents are
described in U.S. Provisional Application No. 60/418,023, which is
hereby incorporated in full by reference. For example, a stent for
coronary use can have an initial diameter of about 2 mm, an
expanded diameter of about 4 mm, and a wall thickness of about
0.005 mm to 0.1 mm. Other exemplary applications include neuro,
carotid, peripheral, and vasculature lumens. The vascular stent can
be bioabsorbable or non-bioabsorbable.
[0135] In other embodiments, a stent, e.g., a bioabsorbable or a
non-bioabsorbable stent, is constructed for use in nonvascular
lumens, such as the esophagus, ureteral, biliary, or prostate.
[0136] In other embodiments, the stent is conductive to allow an
electrical current to pass through the stent, for example, to
deliver electricity to an area of the body or to trigger, for
example, a physical change in the stent, for example, a change in
the diameter of the stent.
[0137] In still other embodiments, the stent, for example, of FIGS.
4, 23 and 26, is made porous by, for example, adding a chemical
foaming agent to the polymer from which the stent is made during
the production the plastic strand. In some implementations, the
stent is porous and includes a medicament. The initial porosity of
the stent can be reduced, for example, by the application of heat
and pressure before deployment in the body. Upon deployment of the
stent in the body, the porosity is increased by a triggering event,
for example, the application of heat to the stent at the desired
site of treatment.
* * * * *