U.S. patent application number 12/016077 was filed with the patent office on 2008-07-24 for endoprosthesis structures having supporting features.
This patent application is currently assigned to Elixir Medical Corporation. Invention is credited to Vinayak Bhat, Brett Cryer, Howard Huang, Motasim Sirhan, John Yan.
Application Number | 20080177373 12/016077 |
Document ID | / |
Family ID | 39636746 |
Filed Date | 2008-07-24 |
United States Patent
Application |
20080177373 |
Kind Code |
A1 |
Huang; Howard ; et
al. |
July 24, 2008 |
ENDOPROSTHESIS STRUCTURES HAVING SUPPORTING FEATURES
Abstract
An endoprosthesis includes a plurality of serpentine rings
having supporting features which increase hoop strength, inhibit
recoil, and provide an increased surface area. The supporting
features may be formed between adjacent axial struts of the
serpentine rings or may be positioned between axial lengths joining
the serpentine rings together.
Inventors: |
Huang; Howard; (Santa Clara,
CA) ; Yan; John; (Los Gatos, CA) ; Cryer;
Brett; (Sunnyvale, CA) ; Sirhan; Motasim; (Los
Altos, CA) ; Bhat; Vinayak; (Cupertino, CA) |
Correspondence
Address: |
TOWNSEND AND TOWNSEND AND CREW, LLP
TWO EMBARCADERO CENTER, EIGHTH FLOOR
SAN FRANCISCO
CA
94111-3834
US
|
Assignee: |
Elixir Medical Corporation
Sunnyvale
CA
|
Family ID: |
39636746 |
Appl. No.: |
12/016077 |
Filed: |
January 17, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60885700 |
Jan 19, 2007 |
|
|
|
Current U.S.
Class: |
623/1.15 |
Current CPC
Class: |
A61L 31/14 20130101;
A61F 2250/0036 20130101; A61L 31/06 20130101; A61F 2/82 20130101;
A61L 31/06 20130101; Y10T 428/139 20150115; A61L 31/148 20130101;
A61F 2002/825 20130101; A61F 2230/0013 20130101; Y10T 428/13
20150115; A61P 9/10 20180101; A61F 2/915 20130101; C08L 67/04
20130101; C08G 63/08 20130101; Y10T 428/1352 20150115 |
Class at
Publication: |
623/1.15 |
International
Class: |
A61F 2/82 20060101
A61F002/82 |
Claims
1. An endoprosthesis comprising: a plurality of circumferentially
expandable serpentine rings, each serpentine ring including axial
struts joined by crowns, wherein the crowns act as hinges allowing
the struts to spread as the ring opens circumferentially; axial
links joining at least some crowns on adjacent rings; and
supporting features extending between at least some adjacent struts
of at least some of the serpentine rings, wherein the supporting
features elongate and the struts remain substantially undeformed as
the rings circumferentially expand.
2. An endoprosthesis as in claim 1, at least partially comprising a
biodegradable material.
3. An endoprosthesis as in claim 1, at least partially comprising a
metal.
4. An endoprosthesis as in claim 1, wherein the serpentine rings
are sufficiently elastic so that they can be constrained in a small
cross-sectional area and released to assume a circumferentially
expanded configuration.
5. An endoprosthesis as in claim 1, wherein the serpentine rings
are sufficiently malleable so that they can be circumferentially
expanded by applying a radially outward force from within the
ring.
6. An endoprosthesis as in claim 1, wherein the supporting feature
comprises a U-shaped connector.
7. An endoprosthesis as in claim 1, wherein the supporting feature
comprises a V-shaped connector.
8. An endoprosthesis as in claim 1, wherein the supporting feature
comprises an S-shaped connector.
9. An endoprosthesis as in claim 1, wherein the supporting feature
comprises a spiral-shaped connector.
10. An endoprosthesis as in claim 9, wherein the spiral-shaped
connector has a ring core.
11. An endoprosthesis as in claim 9, wherein the spiral-shaped
connector has a disk core.
12. An endoprosthesis as in claim 1, wherein the supporting feature
comprises a W-shaped connector.
13. An endoprosthesis as in claim 1, wherein the supporting feature
comprises an N-shaped connector.
14. An endoprosthesis as in claim 1, further comprising at least
one additional supporting feature extending between at least some
of the adjacent struts.
15. An endoprosthesis as in claim 1, wherein the supporting
features extend between midpoints on the adjacent struts.
16. An endoprosthesis as in claim 1, wherein the supporting
features extend between points near the crowns on the adjacent
struts.
17. An endoprosthesis as in claim 1, wherein said supporting
features extend between two points on adjacent axial struts and one
point on the crown which joins the struts.
18. An endoprosthesis as in claim 1, wherein said supporting
features have a cross-sectional area which is less than the
cross-sectional area of the axial struts.
19. An endoprosthesis as in claim 1, wherein at least some of the
supporting features have deflection points which preferentially
yield when the serpentine rings is circumferentially expanded.
20. An endoprosthesis as in claim 19, wherein the deflection points
comprise notches.
21. An endoprosthesis as in claim 1, wherein the axial links
comprise linear beams.
22. An endoprosthesis as in claim 21, wherein the linear beams are
aligned axially.
23. An endoprosthesis as in claim 21, wherein the linear beams are
aligned at an angle relative to the axis.
24. An endoprosthesis comprising: a plurality of circumferentially
expandable serpentine rings, each serpentine ring including axial
struts joined by crowns, wherein the crowns act as hinges allowing
the struts to spread as the ring opens circumferentially; axial
links joining at least some crowns on adjacent rings; and
supporting features extending between at least some adjacent axial
links between adjacent serpentine rings, wherein the supporting
features elongate as the rings circumferentially expand.
25. An endoprosthesis as in claim 24, wherein the supporting
feature comprises a serpentine connector.
26. An endoprosthesis as in claim 24, wherein the supporting
feature comprises a box connector.
Description
CROSS REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the benefit of provisional
application 60/885,700 (Attorney Docket No. 022265-000500US), filed
on Jan. 19, 2007, the full disclosure of which is incorporated
herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to endoprosthesis designs, in
particular biodegradable and non-biodegradable stents and grafts,
which are adapted to be implanted into a patient's body lumen, such
as coronary artery or other blood vessel or body lumen. Stents are
particularly useful in the treatment of atherosclerotic stenosis in
arteries and veins.
[0004] Stents are generally tubular-shaped devices which function
to hold open or reinforce a segment of a blood vessel or other body
lumen such as a coronary artery, carotid artery, saphenous vein
graft, or femoral artery. They also are suitable to support and
hold back a dissected arterial lining that can occlude the fluid
passageway, to stabilize plaque, or to support bioprosthetic
valves. Stents can be formed from various materials, particularly
polymeric and/or metallic materials, and may be non-degradable,
biodegradable, or be formed from both degradable and non-degradable
components. Stents are typically delivered to the target area
within the body lumen using a catheter. With balloon-expandable
stents, the stent is mounted to a balloon catheter, navigated to
the appropriate area, and the stent expanded by inflating the
balloon. A self-expanding stent is delivered to the target area and
released, expanding to the required diameter to treat the disease.
Stents may also elute various drugs and pharmacological agents.
[0005] Referring to FIG. 1, a common pattern employed in present
cardiovascular stents comprises a plurality of serpentine rings 12
joined by short axial links 14. The serpentine rings comprise axial
struts 16, where circumferentially adjacent struts are connected by
crowns 18 which act as hinges in permitting circumferential
expansion of the individual rings 12. These patterns can be used
for both degradable and non-degradable stents and other
endoprostheses.
[0006] In the design of stents and other endoprostheses, a number
of competing objectives must be addressed. For coronary artery
stents, it is usually desirable to be able to collapse the stent to
minimize the cross-sectional area for delivery while maximizing the
surface area of the stent after expansion. A maximized surface area
provides both enhanced wall support to reduce vessel recoil and a
greater capacity to deliver drugs when employing drug-coated
stents. A further design objective is to allow the stent to be
compressed with a minimum force while still maintaining a good hoop
strength after expansion to further resist vessel recoil.
[0007] Thus, what is needed is a stent design or stent material
which enhances radial or hoop strength, reduces vessel recoil after
implantation, provides an increased surface area while maintaining
or reducing the size and mass of the stent. The present invention
meets at least some of these requirements.
[0008] 2. Description of the Background Art
[0009] U.S. Pat. No. 6,773,455 describes a stent having serpentine
rings axially connected via internal expansion elements. US
2003/0093143 describes a stent comprising box structures joined
circumferentially by U-shaped connectors. US2003/0144729 describes
a stent comprising axially spaced serpentine bands connected by
wishbone connectors. See also U.S. Pat. No. 7,291,166 and U.S. Pat.
No. 6,896,695.
SUMMARY OF THE INVENTION
[0010] The present invention provides an endoprosthesis, such as a
stent, graft or other scaffold-like luminal prosthesis, that is
used for treating vascular and other luminal conditions. The
endoprosthesis includes supporting features or elements added to a
base structure. The base structure of the stent is formed from a
series of circumferential serpentine rings connected directly to
each other or with at least one link or strut, generally as shown
in FIG. 1 discussed above, where each ring comprises multiple
expansion segments constructed from crowns and struts. In
accordance with the present invention, the base structure is
reinforced with supporting features which can increase radial
strength and/or reduce recoil upon expansion of the stent compared
to the structure without the supporting features. The supporting
features can contain varying types of shapes such as an I-shape,
C-shape, V-shape, U-shape, S-shape, Y-shape, M-shape, W-shape,
Z-shape, spiral-shape or other types. In a first embodiment, the
supporting features connect at least some of the adjacent struts.
In another embodiment at least one supporting feature connects to
at least one axially connecting link.
[0011] Thus, according to the present invention, an endoprosthesis
comprises a plurality of circumferentially expandable serpentine
rings, axial links joining the adjacent rings, and supporting
features. The circumferentially expandable serpentine rings each
include axial struts joined by crowns, where the crowns act as
hinges allowing the struts to spread as the ring opens
circumferentially. The axial links join the adjacent serpentine
rings by connecting at least some of the crowns on the rings. The
supporting features extend between at least some of the adjacent
struts of at least some of the serpentine rings, where the
supporting features elongate and the struts remain substantially
undeformed as the ring circumferentially expands.
[0012] The endoprosthesis may be constructed from a variety of
conventional stent materials and may be either balloon-expandable,
self-expanding, or a combination of both. The serpentine rings of
the self-expanding endoprostheses will be sufficiently elastic so
that they can be constrained in a small cross-sectional area during
delivery and released within the vasculature or other body lumens
to assume a circumferentially expanded configuration. In contrast,
the serpentine rings of the balloon-expandable endoprostheses will
be sufficiently malleable so that they can be circumferentially
expanded by applying a radially outward force from within the
rings, typically using an inflatable balloon or other expandable
structure. Particularly preferred stent materials include metals
and alloys such as iron, zinc, steel, cobalt-chromium,
nickel-titanium, as well as polymers such as poly lactides,
polycaprolactone, polyethylene carbonate, copolymers of
polylactide-glycolide, poly lactide-trimethylenecarbonates, and the
like. Particular materials and fabrication methods are described in
commonly owned application Ser. No. 11/______ (Attorney Docket No.
022265-000520US), filed on the same day as the present
application.
[0013] The supporting features may have a variety of specific
configurations or patterns which are selected to elongate or
otherwise expand as the serpentine rings of the endoprosthesis are
expanded. Exemplary supporting feature configurations include
U-shaped connectors, V-shaped connectors, S-shaped connectors,
spiral-shaped connectors, W-shaped connectors, N-shaped connectors,
Z-shaped connectors, and the like. In order to increase or control
the exposed surface area of the endoprosthesis, the supporting
structures may have variable widths, for example the spiral-shaped
connectors may include ring or disk-shaped cores to enhance or
control the surface area. While the width and cross-sectional area
of the supporting feature will usually be less than the width and
cross-sectional area of the serpentine rings so that expansion of
the supporting features does not deform or deflect the main ring
structure, it will be possible to increase the area of the
supporting feature by providing deflection points which allow the
supporting feature to yield preferentially relative to the
serpentine rings. For example, portions of the supporting feature
may be notched so that they yield first as the endoprosthesis is
expanded.
[0014] In some embodiments, one or more additional supporting
features may be disposed between at least some of the adjacent
struts. When a single supporting feature is employed, it will
usually extend generally between the mid-points on the adjacent
struts, but in other instances could be disposed closer to the ends
of the struts which are not connected together with a crown. In
cases where two or more supporting features are provided between
adjacent pairs of struts, they may be located at any point along
the length of the strut, typically with one being located near the
midpoint and another being located near the free ends (i.e., ends
which are not joined together with the crown).
[0015] The axial links will usually comprise short linear beams,
where the linear beams are axially aligned with the axis of the
endoprosthesis. In other cases, the linear beams may be aligned at
a shallow angle relative to the axis, typically from zero degrees
to 45 degrees.
[0016] Endoprostheses according to the present invention may
comprise a plurality of circumferentially expandable serpentine
rings joined by axial links, where the supporting features extend
between at least some adjacent axial links between adjacent
serpentine rings. These supporting features between the adjacent
axial links elongate as the rings circumferentially expand.
Exemplary supporting features which are connected between the
adjacent axial links include serpentine connectors, usually where
folded portions of the connectors extend into the region between
adjacent axial struts. Alternatively, the connectors could comprise
"box" connectors having symmetric extending lengths which project
into the regions between axial struts.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 illustrates a conventional serpentine ring stent.
[0018] FIGS. 2A and 2B illustrate a first embodiment of the
endoprostheses of the present invention having U-shaped connectors
between adjacent axial struts in a serpentine ring.
[0019] FIG. 3 illustrates the stent structure of FIGS. 2A and 2B
after expansion.
[0020] FIGS. 4 and 5 illustrate an exemplary V-shaped connector as
the supporting feature where the connector can be oriented toward
the crown (FIG. 4) or away from the crown (FIG. 5).
[0021] FIG. 6 illustrates an exemplary S-shaped connector as the
supporting structure.
[0022] FIGS. 7-9 illustrate exemplary spiral-shaped supporting
structures, where FIG. 7 illustrates an everting spiral, FIG. 8
illustrates a spiral having a ring core, and FIG. 9 illustrates a
spiral having a disk core.
[0023] FIG. 10 illustrates an exemplary endoprosthesis structure
having U-shaped connectors located near the open ends of the
serpentine structure.
[0024] FIGS. 11 and 12 illustrate exemplary endoprosthesis
structures having pairs of supporting features between adjacent
axial struts.
[0025] FIG. 13 illustrates a complex supporting feature having both
radially and axially aligned elongating portions.
[0026] FIGS. 14, 15A and 15B illustrate a U-shaped supporting
feature having notch-like yield points which control a two-stage
expansion, as shown in FIGS. 15A and 15B.
[0027] FIGS. 16 and 17 illustrate exemplary endoprosthesis designs
where adjacent serpentine rings are connected by angled axial
links. FIG. 16 further illustrates an M-shaped connector as the
supporting feature while FIG. 17; illustrates a N-shaped connector
as the supporting feature.
[0028] FIGS. 18 and 19 illustrate supporting features connecting
adjacent axial links, where FIG. 18 illustrates a serpentine
pattern, FIG. 19 illustrates a box pattern connector.
DETAILED DESCRIPTION OF THE INVENTION
[0029] The present invention provides an endoprosthesis, such as a
stent, that is used for treating vascular or other luminal
conditions with supporting features or elements added to a base
stent structure. The base structure of the stent is formed from one
or more serpentine rings. The rings may be interconnected directly
or with at least one link. Each ring is composed of multiple
expansion segments constructed from crowns and struts. The stent is
then reinforced by supporting features that increase radial
strength (e.g., hoop strength), increase surface area, and/or
reduce recoil compared to the stent without the supporting
features. The at least one supporting feature usually connects
opposite sides of axial struts which expand (spread apart) about
crowns (hinges). Alternatively, the supporting feature may connect
axial links which join the serpentine rings. Upon expansion of the
segment the supporting feature increases radial strength and/or
reduces recoil. The stents may be non-degradable or degradable,
where degradation includes biodegradation, bioerosion,
bioabsorption, corrosion, and disintegration completely or
partially in physiological environment. The supporting feature may
undergo plastic deformation upon expansion to reinforce the base
structure of the stent or alternatively may elastically expand to
provide the reinforcement.
[0030] In one embodiment the at least one supporting feature
undergoes deformation upon expansion and reinforces the base
structure of the stent. Usually the at least one supporting feature
increases the radial strength of the expanded stent by at least
15%, preferably by at least 50%, more preferably by at least 100%
compared to the stent without the at least one supporting feature.
In other embodiments the at least one supporting feature provides a
stent which recoils after expansion by less than 15%, preferably by
less than 7%, more preferably by less than 4%. In one instance, the
at least one supporting feature provides a stent with recoil at
least 28 days after expansion in a mammal of less than 20%,
preferably less than 10%, more preferably less than 6%.
[0031] The supporting features will usually connect from strut to
strut, but may alternatively or additionally from strut to crown,
from strut to link, from link to link, from crown to crown, from
crown to link, or from crown to same crown. Exemplary supporting
features can contain varying types of shapes such as C-shape,
V-shape, U-shape, S-shape, Y-shape, M-shape, W-shape, Z-shape,
spiral-shape or other types. These shapes may be continuous or
discontinuous. At least one type of supporting feature per ring may
be present.
[0032] The supporting feature thickness and/or width may be greater
than, less than or approximately equal to the thickness of the
adjacent expansion segment. In one embodiment the supporting
feature thickness ranges from 0.125 mm (0.0005 in) to 2.5 mm (0.010
in), preferably 0.25 mm (0.001 in) to 1.25 mm (0.005 in), more
preferably 0.5 mm (0.002 in) to 1 mm (0.004 in). In one embodiment
the supporting feature width ranges from 0.125 mm (0.0005 in) to
2.5 mm (0.010 in), preferably 0.25 mm (0.001 in) to 1.25 mm (0.005
in), more preferably 0.5 mm (0.002 in) to 1 mm (0.004 in). In one
embodiment the path length of the supporting feature ranges from
1.25 mm (0.005 in) to 25 mm (1 in), preferably 0.25 mm (0.010 in)
to 0.75 mm (0.250 in), more preferably 0.5 mm (0.020 in) to 2.5 mm
(0.100 in).
[0033] In one embodiment the angle at which the supporting feature
connects to the expansion segment or link is approximately 90
degrees, but the angle may alternatively be less than 90 degrees or
greater than 90 degrees. Usually, the angle at which the supporting
feature connects to the axial strut or link ranges from 30 degrees
to 150 degrees, preferably 45 to 135 degrees, more preferably 60 to
120 degrees.
[0034] The material of the supporting feature may be metallic,
metal alloy, polymeric, composite, ceramic, or combination thereof,
or other type of material, and can be of similar type as the
expansion segment or link, or different type.
[0035] The increase in radial strength and/or reduction of recoil
provided by these designs can be of particular benefit for
biodegradable stents. The endoprosthesis designs and patterns are
applicable to both biodegradable and non-biodegradable materials to
provide an enhanced strength and/or increased elasticity. Exemplary
biodegradable endoprosthesis materials include metallic, metallic
alloy, polymeric, ceramic, composite, as well as other materials in
combinations thereof. The yield strength for the biodegradable
material(s) will usually be at least 50% of ultimate strength,
preferably being at least 75% of ultimate strength, and more
preferably being at least 90% of ultimate strength. For
biodegradable polymeric stent materials, the yield strength can be
measured in water at 37.degree. C. The elastic modulus for
biodegradable metallic stents will usually be at least 50 GPa,
preferably being at least 100 GPa, and more preferably at least 150
GPa. The elastic modulus of biodegradable polymeric stents, in
contrast, will be at least 0.5 GPa, preferably being at least 0.75
GPa, and more preferably being at least 1 GPa, measured in water at
37.degree. C. Higher strain at yield may contribute to greater
recoil of the stent. The yield strain for biodegradable polymeric
stent materials will preferably be no more than 10% when measured
in water at 37.degree. C., preferably being no more than 5%, and
more preferably being no more than 3%. The plastic strain for the
biodegradable polymeric stent materials will preferably be at least
20%, more preferably being at least 30%, and still more preferably
being at least 40%, when measured in water at 37.degree. C., while
the elastic recovery of the strained biodegradable polymeric stent
material is at most 15%, preferably at most 10%, and more
preferably at most 5%, when measured in water at 37.degree. C.
[0036] The biodegradable stent materials may have a widely varying
persistence. Usually, the material will substantially degrade
within three years after implantation, more usually within one
year, and still more usually within six months. When degrading
under physiological conditions, such as vascular conditions, after
one month the biodegradable stent will preferably retain at least
25% of the hoop strength, preferably maintaining at least 40%, and
more preferably maintaining at least 70%.
[0037] The biodegradable polymeric stent materials may degrade by
any of several known mechanisms, including bulk erosion, surface
erosion, and combinations thereof. The biodegradable polymeric
stent material usually degrades by at least one of hydrolytic
degradation, enzymatic degradation, oxidative degradation, photo
degradation, degradation under physiological environment or
combination thereof.
[0038] Suitable the biodegradable polymeric stent material
includes, but are not limited to, polyesters, polyanhydrides,
polyamides, polyurethanes, poly(ester urethane), polyureas,
polyethers, polyalkylene carbonates, polyacrylic acids, polyamines,
polyester amides, polyester amines, polyvinylacetate, polyethylene
imine, polycyanoacrylates, polyphosphazenes, polyphosphates,
polyphosphonates, polyurethanes, polyureas, polysulfonates,
polysulfonamides, polylactides, polyglycolides, regenerated
cellulose, or biopolymers or blends, block polymers, copolymers or
combinations thereof. Examples of these polymers include but are
not limit to poly(L-lactic acid), poly(L/D-lactic acid),
poly(L/DL-lactic acid), poly(glycolic acid),
poly(lactide-co-glycolide), and copolymers and isomers,
polydioxanone, poly(ethyl glutamate), poly(hydroxybutyrate),
polyhydroxyvalerate and copolymer poly(3-hydroxy
butyrate-co-hydroxy valerate), polycaprolactone, polyanhydride,
poly(ortho esters); poly(ether esters), poly(trimethyl carbonate),
Poly(L-lactic acid-co-trimethylene carbonate), Poly(L/D-lactic
acid-co-trimethylene carbonate), Poly(L/DL-lactic
acid-co-trimethylene carbonate), Poly(caprolactone-co-trimethylene
carbonate), Poly(glycolic acid-co-trimethylene carbonate),
Poly(glycolic acid-co-trimethylene carbonate-co-dioxanone),
polyethylene carbonate, copolymers of polyethylene carbonate and
poly(trimethylene carbonate), polypropylene carbonate, poly
(iminocarbonates), poly(malic acid), modified poly(ethylene
terephthalate), poly(butylene succinate), poly(butylene succinate
adipate), poly(butylene succinate terephthalate), poly(butylene
adipate-co-terephthalate), starch based polymers, hylaronic acid,
oxidized or non-oxidized regenerated cellulose copolymers and other
aliphatic polyesters, or suitable copolymers thereof. The
biodegradable polymeric stent material in this invention can be
homopolymers, copolymers, graft polymer, block polymers, polymers
with special functional groups or end groups such as acidic or
hydrophilic type or a blend of two or more homopolymers or
copolymers.
[0039] The biodegradable polymeric stent material can have varying
molecular architecture such as linear, branched, crosslinked,
hyperbranched or dendritic. The biodegradable polymeric stent
material in this invention can range from 10 KDa to 10,000 KDa in
molecular weight, preferably from 100 KDa to 1000 KDa, more
preferably 300 KDa to 600 KDa.
[0040] In certain embodiments, the biodegradable polymeric stent
material incorporates at least one additive. The additives can
affect strength, recoil, or degradation rate or combination
thereof. Additives can also affect processing of biodegradable
stent material, radiopacity or surface roughness or others.
Additives can be biodegradable or non-biodegradable. The additives
can be incorporated in to the biodegradable stent material by
blending, extrusion, injection moulding, coating, surface
treatment, chemical treatment, mechanical treatment, stamping, or
others or combinations thereof. The additives can be chemically
modified prior to incorporation in to the biodegradable stent
material.
[0041] In one embodiment, the weight percentage of the additives
can range from 0.01% to 25%, preferably 0.1% to 10%, more
preferably 1% to 5%. In one embodiment, the additive includes at
least nanoclay, nanotubes, nanoparticles, exfoliates, fibers,
whiskers, platelets, nanopowders, fullerenes, nanosperes, zeolites,
polymers or others or combination thereof. Examples of nanoclay
includes Montmorillonite, Smectites, Talc, or platelet-shaped
particles or others or combination thereof. Clays can be
intercalated or exfoliated. Example of clays include Cloisite NA,
93A, 30B, 25A, 15A, 10A or others or combination thereof. Examples
of fibers include cellulose fibers such as Linen, cotton, rayon,
acetate; proteins fibers such as wool or silk; plant fiber; glass
fiber; carbon fiber; metallic fibers; ceramic fibers; absorbable
fibers such as polyglycolic acid, polylactic acid, polyglyconate or
others. Examples of whiskers include hydroxyapetite whiskers,
tricalcium phosphate whiskers or others.
[0042] In another embodiment, the additives includes at least
modified starch, soybean, hyaluronic acid, hydroxyapatite,
tricarbonate phosphate, anionic and cationic surfactants such as
sodium docecyl sulphate, triethylene benzylammonium chloride,
pro-degradant such as D2W (from Symphony Plastic Technologies),
photodegradative additives such as UV-H (from Willow Ridge
Plastics), oxidative additives such as PDQ (from Willow Ridge
Plastics), TDPA, family of polylactic acid and its random or block
copolymers or others.
[0043] In another embodiment, the additive can induce degradation
of non-degradable polymeric stent material. For example
pro-degradant such as D2W (from Symphony Plastic Technologies),
photodegradative additives such as UV-H (from Willow Ridge
Plastics), oxidative additives such as PDQ (from Willow Ridge
Plastics), TDPA or others or combination thereof can initiate
degradation of non degradable stent materials such as polyethylene,
polypropylene, polyethylene terephthalate or others. In still other
embodiments, the additives include electroactive or electrolyte
polymers, hydroscopic polymers, dessicants, or others. The additive
may include an oxidizer such an acids, perchlorates, nitrates,
permanganates, salts or other or combination thereof. The additive
may include a monomer of the biodegradable polymeric stent
material. For example glycolic acid is an additive to polyglycolic
acid or its copolymer stent material. The additive may include
water repellent monomers, oligomers or polymers such as bees wax,
low MW polyethylene or others. In other embodiments, the additive
can be water attractant monomers, oligomers or polymers such as
polyvinyl alcohol, polyethylene oxide, glycerol, caffeine,
lidocaine or other. In other embodiments, the additive can affect
crystallinity of the biodegradable polymeric stent material.
Example of additive of nanoclay to PLLA affects its crystallinity.
In still other embodiments, the biodegradable polymeric stent
material can have increased crystallinity upon exposure to
radiation such as gamma or ebeam. The cumulative radiation dose can
range from 1 Mrad to 100 Mrad, preferably 5 to 50 Mrad, more
preferably 10 to 30 Mrad. The biodegradable stent material has
increased crystallinity by increasing orientation of polymer chains
with in the biodegradable stent material in radial and/or
longitudinal direction by drawing, pressurizing and/or heating the
stent material. In another embodiment, the drawing, pressurizing
and/or heating the stent material occurs simultaneously or
sequentially.
[0044] Specific methods for preparing biodegradable polymeric
stents having the patterns disclosed herein are described in
copending application Ser. No. 11/______ (Attorney Docket No.
022265-000520US), filed on the same day as the present application,
all disclosure of which is incorporated herein by reference.
[0045] In the present invention, the stent material may include
pharmacological agents, such as immunomodulators, anti-cancer,
anti-proliferative, anti-inflammatory, antithrombotic,
antiplatelet, antifungal, antidiabetic, antihyperlipidimia,
antiangiogenic, angiogenic, antihypertensive, healing promoting
drugs, or other therapeutic classes of drugs or combination
thereof. Illustrative immunomodulators agents include but are not
limited to rapamycin, everolimus, ABT 578, AP20840, AP23841,
AP23573, CCl-779, deuterated rapamycin, TAFA93, tacrolimus,
cyclosporine, TKB662, myriocin, their analogues, pro-drug,
metabolites, slats, or others or combination thereof.
[0046] Illustrative anticancer agents include acivicin,
aclarubicin, acodazole, acronycine, adozelesin, alanosine,
aldesleukin, allopurinol sodium, altretamine, aminoglutethimide,
amonafide, ampligen, amsacrine, androgens, anguidine, aphidicolin
glycinate, asaley, asparaginase, 5-azacitidine, azathioprine,
Bacillus calmette-guerin (BCG), Baker's Antifol (soluble),
beta-2'-deoxythioguanosine, bisantrene hcl, bleomycin sulfate,
busulfan, buthionine sulfoximine, BWA 773U82, BW 502U83.HCl, BW
7U85 mesylate, ceracemide, carbetimer, carboplatin, carmustine,
chlorambucil, chloroquinoxaline-sulfonamide, chlorozotocin,
chromomycin A3, cisplatin, cladribine, corticosteroids,
Corynebacterium parvum, CPT-11, crisnatol, cyclocytidine,
cyclophosphamide, cytarabine, cytembena, dabis maleate,
dacarbazine, dactinomycin, daunorubicin HCl, deazauridine,
dexrazoxane, dianhydrogalactitol, diaziquone, dibromodulcitol,
didemnin B, diethyldithiocarbamate, diglycoaldehyde,
dihydro-5-azacytidine, doxorubicin, echinomycin, edatrexate,
edelfosine, eflomithine, Elliott's solution, elsamitrucin,
epirubicin, esorubicin, estramustine phosphate, estrogens,
etanidazole, ethiofos, etoposide, fadrazole, fazarabine,
fenretinide, filgrastim, finasteride, flavone acetic acid,
floxuridine, fludarabine phosphate, 5-fluorouracil, Fluosol.RTM.,
flutamide, gallium nitrate, gemcitabine, goserelin acetate,
hepsulfam, hexamethylene bisacetamide, homoharringtonine, hydrazine
sulfate, 4-hydroxyandrostenedione, hydrozyurea, idarubicin HCl,
ifosfamide, interferon alfa, interferon beta, interferon gamma,
interleukin-1 alpha and beta, interleukin-3, interleukin-4,
interleukin-6,4-ipomeanol, iproplatin, isotretinoin, leucovorin
calcium, leuprolide acetate, levamisole, liposomal daunorubicin,
liposome encapsulated doxorubicin, lomustine, lonidamine,
maytansine, mechlorethamine hydrochloride, melphalan, menogaril,
merbarone, 6-mercaptopurine, mesna, methanol extraction residue of
Bacillus calmette-guerin, methotrexate, N-methylformamide,
mifepristone, mitoguazone, mitomycin-C, mitotane, mitoxantrone
hydrochloride, monocyte/macrophage colony-stimulating factor,
nabilone, nafoxidine, neocarzinostatin, octreotide acetate,
ormaplatin, oxaliplatin, paclitaxel, pala, pentostatin,
piperazinedione, pipobroman, pirarubicin, piritrexim, piroxantrone
hydrochloride, PIXY-321, plicamycin, porfimer sodium,
prednimustine, procarbazine, progestins, pyrazofurin, razoxane,
sargramostim, semustine, spirogermanium, spiromustine,
streptonigrin, streptozocin, sulofenur, suramin sodium, tamoxifen,
taxotere, tegafur, teniposide, terephthalamidine, teroxirone,
thioguanine, thiotepa, thymidine injection, tiazofurin, topotecan,
toremifene, tretinoin, trifluoperazine hydrochloride, trifluridine,
trimetrexate, tumor necrosis factor, uracil mustard, vinblastine
sulfate, vincristine sulfate, vindesine, vinorelbine, vinzolidine,
Yoshi 864, zorubicin, QP-2, epothilone D, epothilone C Taxol, such
as, paclitaxel, docetaxel, ABJ879, patupilone, MN-029, BMS247550,
ecteinascidins such as ET-743, tetrahydroisoquinoline alkaloid,
sirolimus, actinomycin, methotrexate, antiopeptin, vincristine,
mitomycin, 2-chlorodeoxyadenosine or others, antifungal agents such
as caspofungin, farnesylated dibenzodiazepinone, ECO-4601,
fluconazole, or others, angiogenesis drugs such as follistatin,
leptin, midkine, angiogenin, angiopoietin-1, becaplermin, Regranex,
anti-angiogenesis drugs such as canstatin, angiostatin, endostatin,
retinoids, tumistatin, vasculostatin, angioarrestin, vasostatin,
bevacizumab, prinomastat, or others, antidiabetic drugs such as
metformin, hypertension drugs such as candesartan, diovan,
diltiazem, atenolol, adalat or others, anti-ischemia drugs such as
ranolazine, isosorbide dinitrate, or others.
[0047] Illustrative antiinflammatory agents include classic
non-steroidal anti-inflammatory drugs (NSAIDS), such as aspirin,
diclofenac, indomethacin, sulindac, ketoprofen, flurbiprofen,
ibuprofen, naproxen, piroxicam, tenoxicam, tolmetin, ketorolac,
oxaprosin, mefenamic acid, fenoprofen, nambumetone (relafen),
acetaminophen (Tylenol.RTM.), and mixtures thereof, COX-2
inhibitors, such as nimesulide, NS-398, flosulid, L-745337,
celecoxib, rofecoxib, SC-57666, DuP-697, parecoxib sodium, JTE-522,
valdecoxib, SC-58125, etoricoxib, RS-57067, L-748780, L-761066,
APHS, etodolac, meloxicam, S-2474, and mixtures thereof,
glucocorticoids, such as hydrocortisone, cortisone, prednisone,
prednisolone, methylprednisolone, meprednisone, triamcinolone,
paramethasone, fluprednisolone, betamethasone, dexamethasone,
fludrocortisone, desoxycorticosterone, fluticasone propionate,
piroxicam, celeoxib, mefenamic acid, tramadol, meloxicam, methyl
prednisone, pseudopterosin, or others, hypercalcemia drugs such as
zoledronic acid, alendronate or others, antithrombosis drugs like
plavix, heparin, Arixtra and Fraxiparine or others or mixtures
thereof.
[0048] Use of analogues, prodrugs, derivatives, precursors,
fragments, salts, or other modifications or variations of
pharmaceutical agents are all included.
[0049] Analogs, derivatives, prodrugs, salts, synthetic or biologic
equivalents of these pharmaceutical agents can be released from the
stents depending on the type of treatment needed, such as
hyperproliferative diseases, stenosis, wound healing, cancer,
aneurysm, diabetic disease, abdominal aortic aneurysm,
angiogenesis, hypercalcemia, ischemia, fibrillation, arrhythmia or
others.
[0050] The agents can be released from the implant using
non-degradable, partially degradable, fully degradable coatings or
a combination as disclosed in prior patent application which is
referenced and incorporated in this application in its entirety.
The agents can be incorporated as a matrix with the coating or
applied on the stent and covered with the coating as a rate
limiting barrier, or the drug agent directly coated onto the stent
surface.
[0051] The solvent used to incorporate the agent and the coating on
a stent can be an organic solvent such as dichloromethane,
tetrahydrofuran, ethanol, or other solvents. In one embodiment, the
solvent used to coat the agent and/or agent-polymer matrix does not
affect the chemical or mechanical properties of the polymeric stent
material.
[0052] In one embodiment, supercritical fluids such as
supercritical carbon dioxide is used as a carrier solvent for the
agent and/or the polymer and coats the stent with agent and/or
agent-polymer matrix. The use of non-reactive gas such as carbon
dioxide removes the need to use other organic solvents which can
alter chemical and physical properties of the pharmacological
agent.
[0053] In one embodiment the crystallinity of the pharmaceutical
agent on the stent material is greater than 90%, preferably greater
than 93%, more preferably greater than 95%.
[0054] In one embodiment, the pharmacological agent can be
incorporated in the biodegradable polymeric stent material and
extruded into stent tubing prior to laser cutting of the stent from
the tubes. In another embodiment the agent is incorporated in a
protective coating to prevent degradation of the agents during
extrusion or laser cutting.
[0055] In one embodiment, the rate of agent release can be
configured to be release at certain times and for certain durations
corresponding to the degradation rate of the stent material or
biological response events within the stent material environment.
For example, an anti-inflammatory, antiproliferative, or
immunomodulator drug or a combination of these can be made to
release during the entire degradation period. Multiple drugs can be
released to match the degradation rate of the coating and/or
degradation rate of the implant. Antiplatelet or anti-thrombotic
agents can be released in the initial phase and anti-inflammatory
or antiproliferative or immunosuppressants can be released
concurrently or at the later phase.
[0056] Referring now to FIGS. 2A and 2B, a stent 10 according to
the present invention has the same base pattern as the stent
illustrated in FIG. 1, including a plurality of adjacent serpentine
rings 12 joined by axial links 14. As illustrated, the stent 10
includes six adjacent serpentine rings 12, where each ring includes
six serpentine segments comprising a pair of axial struts 16 joined
by a hinge-like crown 18 at one end. The number of rings and
segments may vary widely depending on the size of the desired size
of the stent. According to the present invention, a supporting
feature 20 is disposed between adjacent axial struts 16 and
connected so that it will expand, usually elongate,
circumferentially with the struts, as shown in FIG. 3. The
supporting features 20 are in a generally closed U-shaped
configuration prior to expansion, as shown in FIGS. 2A and 2B, and
open into a shallow V-shape along with the opening of the axial
struts 16 about the crowns 18 during radial expansion of the
serpentine rings 12, as shown in FIG. 3. Supporting features 20
enhance the hoop strength of the stent after radial expansion, help
resist recoil after expansion is completed, and provide additional
area for supporting the vascular or other luminal wall and
optionally for delivering drugs into the luminal wall.
[0057] While U-shaped supporting feature 20 are illustrated in
FIGS. 2A and 2B, a variety of other configurations may be utilized,
as illustrated in FIGS. 4-17. In FIG. 4, V-shaped supporting
features 22 are disposed between the adjacent axial struts 16. The
supporting features 24 of FIG. 5 are generally the same as those in
FIG. 4, except they are pointed in the opposite direction, i.e.,
away from the crowns 18 rather than toward the crowns. S-shaped
connectors 26 are illustrated in FIG. 6, while spiral-shaped
connectors 28 are shown in FIG. 7. FIG. 8 shows an alternative
spiral-shaped connector 30 having an open ring at its center, while
FIG. 9 shows a similar supporting feature 32 having a disk at its
center.
[0058] As shown thus far, the supporting features 20-32 have been
connected to the adjacent axial struts 16 near the midpoints of
said struts. Supporting features 34 may also be connected near the
open ends of the axial struts 16, as shown in FIG. 10, or may be
connected in pairs or in greater number, as shown in FIG. 11. FIG.
12 illustrates a pair of connectors 34 joined near the midpoint,
while FIG. 13 illustrates a complex supporting feature 40 joined
between adjacent axial struts 16 at three points, two near the open
end of the struts and a third on the inner side of the crown
18.
[0059] Referring now to FIGS. 14, 15A and 15B, the supporting
features 42 may have deflection points 44 formed along their
lengths in order to control expansion. For example, by placing
notches 44 in the middle of the U-shaped connector 42, the
supporting features may be programmed to first open at the
deflection points 44, as illustrated in FIG. 15A, and to later open
at the crown of the connector, as shown in FIG. 15B. Such
programmed opening helps assure that the axial struts 16 may expand
without being significantly hindered by the forces needed to expand
the supporting features 42.
[0060] Still further variations in the structure and positioning of
the supporting features and axial links may be provided. As shown
in FIG. 16, the supporting features 50 may comprise N-shaped
connectors while the axial links 52 may be angled relative to the
axial direction of the endoprosthesis. Similarly, as shown in FIG.
17, N-shaped supporting features 60 may be provided to join
serpentine rings held together by angled axial links 62.
[0061] Referring now to FIGS. 18 and 19, the supporting features
may also be connected between axial links 14 in the endoprostheses
of the present invention. The supporting feature 70 has a generally
serpentine configuration with a bent or folded portion extending
into the region between adjacent axial struts 16. The supporting
feature 72 in the endoprosthesis of FIG. 19 is similar to 70,
except that the supporting feature includes a box region having a
pair of projections 74 extending into the regions between adjacent
axial struts 16. In both cases, the supporting features 70 and 72
will both enhance the hoop strength of the serpentine ring after
radial expansion, inhibit recoil, and provide an enhanced surface
area for supporting tissue and delivering active agents.
[0062] While the above is a complete description of the preferred
embodiments of the invention, various alternatives, modifications,
and equivalents may be used. Therefore, the above description
should not be taken as limiting the scope of the invention which is
defined by the appended claims.
* * * * *