U.S. patent application number 14/018166 was filed with the patent office on 2014-01-09 for device and method for management of aneurism, perforation and other vascular abnormalities.
This patent application is currently assigned to Q3 MEDICAL DEVICES LIMITED. The applicant listed for this patent is Q3 MEDICAL DEVICES LIMITED. Invention is credited to Eric K. MANGIARDI.
Application Number | 20140010950 14/018166 |
Document ID | / |
Family ID | 45065065 |
Filed Date | 2014-01-09 |
United States Patent
Application |
20140010950 |
Kind Code |
A1 |
MANGIARDI; Eric K. |
January 9, 2014 |
DEVICE AND METHOD FOR MANAGEMENT OF ANEURISM, PERFORATION AND OTHER
VASCULAR ABNORMALITIES
Abstract
This application is directed to a device comprising a covering
attached to the device. A process of making a device with a
specific covering attached is also disclosed. The application
further discloses a method for the treatment of perforations,
fistulas, ruptures, dehiscence and aneurisms in luminal vessels and
organs of a subject.
Inventors: |
MANGIARDI; Eric K.;
(Charlotte, NC) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Q3 MEDICAL DEVICES LIMITED |
Dublin |
|
IE |
|
|
Assignee: |
Q3 MEDICAL DEVICES LIMITED
Dublin
IE
|
Family ID: |
45065065 |
Appl. No.: |
14/018166 |
Filed: |
September 4, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13149327 |
May 31, 2011 |
|
|
|
14018166 |
|
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|
|
61344183 |
Jun 7, 2010 |
|
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Current U.S.
Class: |
427/2.25 |
Current CPC
Class: |
A61F 2002/075 20130101;
A61L 31/10 20130101; D01D 5/0084 20130101; A61F 2/07 20130101; A61L
31/18 20130101; A61F 2220/0008 20130101; A61F 2/82 20130101; A61F
2250/0031 20130101; A61F 2250/0067 20130101; B05D 1/16 20130101;
A61F 2/915 20130101; A61F 2230/0054 20130101; A61F 2002/072
20130101; B05D 1/18 20130101; A61F 2002/91558 20130101; A61F 2/90
20130101; A61B 17/12109 20130101; B05D 1/36 20130101; A61F
2210/0004 20130101 |
Class at
Publication: |
427/2.25 |
International
Class: |
A61F 2/82 20060101
A61F002/82; B05D 1/36 20060101 B05D001/36 |
Claims
1-13. (canceled)
14. A method of making a device for aneurism and perforation
management, comprising: dipping a rigid, stent like body in a
biodegradable coating material to form a coated stent like body;
and electrospinning fibers of a covering material onto said coated
stent like body.
15. The method of claim 14, wherein the coated stent like body is
covered by electrospinning in a way that the fibers cross one
another interlocking and forming angles.
16-26. (canceled)
27. The method of claim 14, wherein said stent like body comprises
a biodegradable or bioabsorbable material.
28. The method of claim 27, wherein said biodegradable or
bioabsorbable material comprises magnesium, iron or a polymer or
co-polymer material.
29. The method of claim 14, wherein said stent like body comprises
a non-biodegradable or non-bioabsorbable material.
30. The method of claim 29, wherein the non-biodegradable or
non-bioabsorbable material comprises stainless steel, cobalt
chromium, or a non-degradable polymer.
31. The method of claim 14, wherein the covering material comprises
a biodegradable or bioabsorbable material.
32. The method of claim 31, wherein the biodegradable or
bioabsorbable material comprises a poly-(.alpha.-hydroxy acid) or
poly-(L-lactic acid).
33. The method of claim 14, wherein said covering material is mixed
with barium sulphate or other illuminating material.
34. The method of claim 14, wherein the fibers of a covering
material are electrospinned onto said coated stent like body in a
way that the fibers cross one another interlocking and forming
angles.
35. The method of claim 34, wherein the fibers intersect one
another at angles from about 10 degrees to about 90 degrees.
36. The method of claim 14, wherein the fibers of a covering
material are electrospinned onto said coated stent like body in a
way that the fibers are overlapped a minimum of 1 time and a
maximum of 1000 times.
37. The method of claim 36, wherein the fibers of a covering
material are electrospinned onto said coated stent like body in a
way that the fibers are overlapped a minimum of 2 times and a
maximum of about 200 times.
38. The method of claim 14, wherein the fibers of a covering
material are electrospinned onto said coated stent like body in a
way that forms a porous structure.
39. The method of claim 38, wherein the a porous structure has a
honeycomb pattern or circle chain links pattern.
40. The method of claim 38, wherein the a porous structure
comprises large interlocking circles, a deep honey honeycomb
structure, and small circular structures.
Description
[0001] This application is a continuation application of U.S.
patent application Ser. No. 13/149,327, filed May 31, 2011, which
claims priority of U.S. Provisional Patent Application No.
61/344,183, filed Jun. 7, 2010. The entirety of the provisional
application is incorporated herein by reference.
FIELD
[0002] This application generally relates to devices and methods
for the treatment of wounds in luminal vessels and organs, and
other vascular abnormalities. In particular, the invention relates
to a device and methods for the treatment of perforations,
fistulas, ruptures, dehiscence, punctures, incisions, and aneurisms
in luminal vessels and organs of a subject.
BACKGROUND
[0003] Current means of treating perforations in luminal vessels
and organs is through operative procedures, endoscopic suturing,
vascular closure devices, or with an implant used for perforation
management. However, current implants are big and have bulky
coverings, are difficult to use, are not widely accepted, and are,
in many cases, only used as a means of last resort.
[0004] Aneurisms occur when an artery balloons out due to increased
blood pressure or a weakening in a blood vessel. Aneurisms can
occur throughout the body. Brain aneurisms, also known as
intracranial or cerebral aneurisms, are life-threatening,
particularly if they rupture. Once an aneurysm forms, it will not
disappear on its own. Medication may help slow its growth, but is
not a cure. Most aneurisms eventually need repair.
[0005] For the treatment of berry or saccular aneurisms, one
current therapy is endovascular coiling, wherein a catheter is
inserted into the femoral artery in the groin, through the aorta,
into the brain arteries, and finally into the aneurysm itself. Once
the catheter is in the aneurysm, platinum coils are pushed into the
aneurysm sac and released to allow the aneurysm to clot or to
change the turbulent flow and stop growing through a release or
diversion of pressure. In another current therapy, the aneurysm is
surgically treated by performing a craniotomy, exposing the
aneurysm, and closing the base of the aneurysm with a clip.
[0006] For fusiform aneurisms, a current treatment strategy is to
place grafts that do not degrade. These grafts have a history of
collecting thrombi that can break off and get pushed further
downstream. Another current treatment strategy is the surgical
option of performing a bypass which is technically challenging and
has many complications on its own.
SUMMARY
[0007] One aspect of the present invention relates to a device for
aneurism and perforation management. The device comprises a rigid,
stent like body and an electrospun fibrous covering that covers the
stent like body for increased stability during placement.
[0008] In one embodiment, the stent like body comprises a
biodegradable or bioabsorbable material.
[0009] In another embodiment, the biodegradable or bioabsorbable
material comprises magnesium, iron, a polymer or co-polymer
material.
[0010] In another embodiment, the stent like body comprises a
non-biodegradable or non-bioabsorbable material.
[0011] In a related embodiment, the non-biodegradable or
non-bioabsorbable material comprises stainless steel, cobalt
chromium, or other alloy or a non-degradable polymer.
[0012] In another embodiment, the fibrous covering comprises a
biodegradable or bioabsorbable material.
[0013] In a related embodiment, the biodegradable or bioabsorbable
material comprises a poly-(.alpha.-hydroxy acid) or poly-(L-lactic
acid).
[0014] In another embodiment, the fibrous covering comprises a
non-biodegradable or non-bioabsorbable material.
[0015] In another embodiment, the covering material is mixed with
barium sulphate or other illuminating material.
[0016] In another embodiment, the stent like body is coated with a
layer of biodegradable material and wherein the fibrous covering
covers the layer of biodegradable material.
[0017] In a related embodiment, the stent like body is coated with
the layer of biodegradable material by dip-coating.
[0018] In another embodiment, the stent like body is treated or
etched with chemical agents, laser or abrasives to allow more
effective attachment of the electrospun fibrous covering to the
stent like body.
[0019] In another embodiment, the stent like body is
expandable.
[0020] Another aspect of the present invention relates to a method
of making device for aneurism and perforation management. The
method comprises dipping a rigid, stent like body in a
biodegradable coating material to form a coated stent like body;
and electrospinning fibers of a covering material onto the coated
stent like body.
[0021] In one embodiment, the coated stent like body is covered by
electrospinning in a way that the fibers cross one another
interlocking and forming angles.
[0022] Another aspect of the present invention relates to a method
for occluding an opening in a luminal vessel. The method comprises
placing at the opening a device comprising an expandable stent like
body coated with a biodegradable material and an electrospun
fibrous covering that covers the stent like body; and expanding the
stent like body to immobilize the device at the opening.
[0023] In one embodiment, the luminal vessel is an artery or a
vein.
[0024] In another embodiment, the opening is an aneurysm,
perforation, rupture or fistula.
[0025] In a related embodiment, the aneurysm is a berry aneurysm or
a fusiform aneurysm.
[0026] In another related embodiment, the aneurysm is a cerebral,
cardiac, pulmonary or aortic aneurysm.
[0027] Another aspect of the present invention relates to a method
for treating condition in a luminal vessel in a subject. The method
comprises introducing into the subject a device comprising an
expandable stent like body that is coated with a biodegradable
material and covered with an electrospun covering; positioning the
device at a treatment site; and expanding the expandable stent like
body to immobilize the device at the treatment site.
[0028] In one embodiment, the expandable stent like body comprises
magnesium, iron or a polymer material.
[0029] In another embodiment, the condition is plaque in a blood
vessel.
[0030] In another embodiment, the condition is an acute myocardial
infarction.
[0031] In another embodiment, the condition is a hole or an opening
in said luminal vessel.
[0032] In another embodiment, the condition is a grafted vessel.
The device is emplaced under the graft to support the graft during
the healing process and prevent leakage at sutures.
[0033] In another embodiment, the device covering can be further
coated with a drug coating that can be eluted to minimize
hyperplastic response or to induce closure of the aneuryism
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] FIGS. 1A-D show exemplary stent devices composed of
bioabsorbable materials such as: (A) magnesium, (B) iron, (C)
composite material, and (D) a bioabsorbable covering.
[0035] FIG. 2 shows an exemplary stent device composed of a
non-biodegradable material.
[0036] FIG. 3 shows an exemplary stent device crimped onto a
catheter after dip-coating or electrospinning.
[0037] FIG. 4 shows an exemplary stent device in dipped form.
[0038] FIG. 5 shows a magnified view of the stent device of FIG.
4.
[0039] FIG. 6 shows a crimped stent device comprising a covering of
fibers applied with electrospinning.
[0040] FIG. 7 shows a stent device comprising a covering of fibers
applied with electrospinning in a crimped state.
[0041] FIG. 8 shows a magnified view of the stent device of FIG.
7.
[0042] FIG. 9 shows the small circular structure within a covering
of fibers applied with electrospinning.
[0043] FIG. 10 shows electrospun fiber attached to stent device
struts that have been previously covered with electrospun
material.
[0044] FIG. 11 shows a magnified view of the stent device of FIG.
10.
[0045] FIG. 12 shows the electrospun fibers on a stent device that
has been expanded.
[0046] FIG. 13A-B shows a magnified view of the expanded stent
device of FIG. 12.
[0047] FIG. 14 shows the fibers on an electrospun stent device.
[0048] FIG. 15 shows a magnified view of the fibers of FIG. 14.
[0049] FIG. 16 shows a coated strut segment of a stent device.
[0050] FIG. 17 shows an unexpanded stent device.
[0051] FIG. 18 shows an unexpanded stent device that has been
coated.
[0052] FIG. 19 shows an unexpanded stent device that has been
coated.
[0053] FIG. 20 shows a magnified view of the coated stent device of
FIG. 19.
[0054] FIG. 21 shows an electrospun stent device.
[0055] FIG. 22 shows a magnified view of the mesh structure on an
electrospun stent device.
[0056] FIG. 23 shows a magnified view of the mesh structure on an
electrospun stent device.
[0057] FIG. 24 shows a magnified view of the mesh structure on an
electrospun stent device.
[0058] FIG. 25 FIG. 23 shows a magnified view of the mesh structure
on an electrospun stent device.
[0059] FIG. 26 shows a linear coating in a unidirectional form on a
crimped stent device.
[0060] FIG. 27 shows partial expansion of a stent device having a
linear coating in a unidirectional form.
[0061] FIG. 28 shows further expansion of a stent device having a
linear coating in a unidirectional form.
DETAILED DESCRIPTION
[0062] The following detailed description is presented to enable
any person skilled in the art to make and use the invention. For
purposes of explanation, specific nomenclature is set forth to
provide a thorough understanding of the present invention. However,
it will be apparent to one skilled in the art that these specific
details are not required to practice the invention.
[0063] One aspect of the present invention relates to a device for
aneurism and perforation management. The device comprises a stent
like body and a covering that covers the stent like body for
increased stability during placement. In other embodiments, the
device may further comprise other supporting structure used for the
implant. The device can be used to treat abnormal openings, such as
perforations, fistulas, dehiscents, and aneurisms, in luminal
vessels and organs. The device can be implanted into the
neurovascular, peripheral vascular, coronary, cardiac, and renal
systems, among others. The device allows the occlusion of a leak or
weakening in a vessel wall, whereby the device reestablishes a
normal passage long enough for the lumen to heal.
[0064] The shape and the size of the stent like body may vary
depending on the application of the device. The stent like body can
be a stent or an expandable stent. It is well known in the art that
a stent is a device used to support a bodily orifice, cavity,
vessel, and the like to reinforce collapsing, dissected, partially
occluded, weakened, diseased or abnormally dilated or small
segments of a vessel wall. The stent like body may be in any
suitable form, including, but not limited to, scaffolding, a tube,
a slotted tube or a wire form. The stent like body may be rigid,
resilient, flexible, and collapsible with memory. In one
embodiment, the stent like body comprises a biodegradable or
bioabsorbable material.
[0065] The material covering the stent like body will biodegrade
and the stent like body will remain if it is made from a
non-biodegradable, non-bioabsorbable material. In certain
embodiments, the stent like body is also made from a biodegradable
or bioabsorbable material, and will degrade after the degradation
of the biodegradable covering. In other embodiments, the stent like
body is made from a biodegradable or bioabsorbable material, and is
partially covered with the biodegradable covering so that it will
degrade with the biodegradable covering at the same time but at a
slower rate.
[0066] In one embodiment, the covering is an electrospun fibrous
covering comprising a biodegradable material. In another
embodiment, the covering is attached to the stent like body by
dip-coating process. In another embodiment, the stent like body is
first coated with a biodegradable layer by dip-coating process and
then covered with an electrospun fibrous biodegradable
covering.
[0067] In one embodiment, the covering covers the entire stent like
body. In another embodiment, the covering covers a portion of the
stent like body. In another embodiment, the covering covers a
majority of the stent like body but leaves open an end portion of
the stent like body. In another embodiment, the covering covers a
majority of the stent like body but leaves open a middle section of
the stent like body.
[0068] The device is designed to occlude the abnormal opening long
enough for it to heal or, in the case of an aneurysm, for it to
occlude the aneurysm, be it a berry or fusiform aneurysm. Without
wishing to be bound by theory, it is believed that the coating
and/or the covering allows the device to support the vessel wall or
luminal wall over a greater surface area, thereby reducing the risk
of a hyperplastic response. The covering may contain, or is further
coated with, an agent that reduces hyperplastic response.
[0069] As used herein, the term "biodegradable material" or
"bioresorbable material" refers to a material that can be broken
down by either chemical or physical process, upon interaction with
the physiological environment at the implantation site, and erodes
or dissolves within a period of time, typically within days, weeks
or months. A biodegradable or bioresorbable material serves a
temporary function in the body, such as supporting a lumen or drug
delivery, and is then degraded or broken into components that are
metabolizable or excretable.
[0070] In some embodiments, the stent like body of the device is
first coated with a biodegradable material through a dip-coating
process and then covered with the covering by electrospinning. The
coating allows the covering to adhere more effectively to the stent
like body of the device. The coating may contain the same material
as the biodegradable material of the covering, or another
biodegradable material around the stent struts to promote adherence
of the electrospun covering.
[0071] In particular embodiments, the stent like body is treated or
etched with chemical agents, laser and/or abrasives to allow the
electrospun covering to adhere more effectively to the stent like
body or other supporting structure used for the implant. In such
embodiments, the stent like body itself or the other supporting
structure used for the implant may or may not be coated with a
biodegradable material prior to electrospinning.
[0072] The stent like body can be made of a biodegradable or
bioabsorbable material including, but not limited to, bioabsorbable
metals or alloys and biodegradable polymer materials.
[0073] Examples of bioabsorbable metals and alloys include, but are
not limited to, lithium, sodium, magnesium, aluminum, potassium,
calcium, cerium, scandium, titanium, vanadium, chromium, manganese,
iron, cobalt, nickel, copper, zinc, gallium, silicon, yttrium,
zirconium, niobium, molybdenum, technetium, ruthenium, rhodium,
palladium, silver, indium, tin, lanthanum, cerium, praseodymium,
neodymium, promethium, samarium, europium, gadolinium, terbium,
dysprosium, holmium, erbium, thulium, ytterbium, lutetium,
tantalum, tungsten, rhenium, platinum, gold, lead and alloys
thereof.
[0074] In certain embodiments, the stent like body is made from an
alloy comprising a combination of material that will decompose in
the body comparatively rapidly, typically within a period of
several months, and form harmless constituents. To obtain uniform
corrosion, the alloy may comprise a component, such as magnesium,
titanium, zirconium, niobium, tantalum, zinc or silicon, which
covers itself with a protective oxide coat. A second component,
such as lithium sodium, potassium, calcium, iron or manganese,
which possesses sufficient solubility in blood or interstitial
fluid, is added to the alloy achieve uniform dissolution of the
oxide coat. The corrosion rate can be regulated through the ratio
of the two components.
[0075] Preferably, the alloy is to be composed so that the
corrosion products are soluble salts, such as sodium, potassium,
calcium, iron or zinc salts, or that non-soluble corrosion
products, such as titanium, tantalum or niobium oxide originate as
colloidal particles. The corrosion rate is adjusted by way of the
composition so that gases, such as hydrogen which evolves during
the corrosion of lithium, sodium, potassium, magnesium, calcium or
zinc, dissolve physically, not forming any macroscopic gas
bubbles.
[0076] Alternatively, the stent like body can be made of a
non-biodegradable and non-bioabsorbable material including, but not
limited to, stainless steel, titanium, chromium cobalt or a
non-degradable polymer. The stent like body can also be made of any
suitable pharmaceutically acceptable alloy comprising, but not
limited to, iron, magnesium, manganese, titanium, carbon, chromium,
cobalt, molybdenum, nickel, aluminum, vanadium, zirconium, niobium,
and/or tantalum. In some embodiments, the stent like body can also
be made from a ceramic.
[0077] The covering of the device can be made of a biodegradable or
bioabsorbable material such as, but not limited to, a
poly-(.alpha.-hydroxy acid), preferably poly-(L-lactic acid). In a
further embodiment, the covering material can be mixed with barium
sulphate or other illuminating material to insure proper placement
and visibility during the deployment using fluoroscopy, x-ray, or
other imaging modalities.
[0078] In a particular embodiment, the biodegradable or
bioabsorbable material for the covering of the device is formulated
to begin to degrade in no less than 15 days after the device is
emplaced in the subject. In another embodiment, the biodegradable
or bioabsorbable material for the covering of the device is
formulated to begin to degrade in no less than 30 days after the
device is emplaced in the subject. In a further embodiment, the
biodegradable or bioabsorbable material for the covering of the
device is formulated to begin to degrade in no less than 45 days
after the device is emplaced in the subject. In still another
embodiment, the biodegradable or bioabsorbable material for the
covering of the device is formulated to begin to degrade in no less
than 60 days after the device is emplaced in the subject. In yet
another embodiment, the biodegradable or bioabsorbable material for
the covering of the device is formulated to begin to degrade in no
less than 90 days after the device is emplaced in the subject.
[0079] In a certain embodiment, the biodegradable or bioabsorbable
material for the covering of the device is formulated to fully
degrade within 90 days after the device is emplaced in the subject.
In a further embodiment, the biodegradable or bioabsorbable
material for the covering of the device is formulated to fully
degrade within 120 days after the device is emplaced in the
subject. In another embodiment, the biodegradable or bioabsorbable
material for the covering of the device is formulated to fully
degrade within 150 days after the device is emplaced in the
subject. In still another embodiment, the biodegradable or
bioabsorbable material for the covering of the device is formulated
to fully degrade within 180 days after the device is emplaced in
the subject. In yet another embodiment, the biodegradable or
bioabsorbable material for the covering of the device is formulated
to fully degrade within one year after the device is emplaced in
the subject.
[0080] In one embodiment, the covering of the device comprises a
copolymer made from 34% lactide, 35% caprolactone, 14% trimethylene
carbonate, and 17% glycolide. The copolymer may be deposited on the
stent like body by electrospinning or by film coating. The
copolymer coating would provide strength retention for 30-60 days
and mass absorption in 9-12 months.
[0081] Initial coating of the strut segments of the stent like body
has the benefit and importance of insuring the coating thickness is
much thicker at an area close to the struts, becoming thinner
moving away from struts to the center of a cell, allowing
degradation to occur in the middle of the covering in the cell
structure of the stent as well as allowing for controlled opening
and crimping of the device during manufacturing and deployment in
the target lesions. This particular embodiment allows the covering
of the device to gradually degrade from the center of the cell
towards the struts, and allows the device covering to maintain
increased applied force to keep the covering in place against the
luminal wall during the degradation period.
[0082] In one embodiment, the stent like body itself is made from a
biodegradable material so that it will be degraded after the
degradation of the covering. In another embodiment, the stent like
body itself is made from a biodegradable material and is partially
covered with the covering so that the stent like body will start
degradation at the same time with the covering but at a slower
rate. Electrospinning orientation is further enhanced through the
adherence to the covered strut giving it greater elasticity and the
ability to orient to insure the maximum range of opening and
closing of the device without tearing the covering. This technique
of applying the coverings allows the manufacture of a device with a
very low profile of the covering material to cover the support
device and insure ease of delivery. Further, the elastic coverings
of the present invention allow an expandable stent like body,
whether it is balloon expandable or self expanding, to open to its
nominal diameter. This is not possible based on the existing art.
In one embodiment, the struts of the stent like body are encased in
the covering material in a circular form to provide the
adherence.
[0083] Examples of biodegradable polymers include, but are not
limited to, polydioxanone, polycaprolactone, polygluconate,
poly(lactic acid) polyethylene oxide copolymer, modified cellulose,
polyhydroxybutyrate, polyamino acids, polyphosphate ester,
polyvalerolactone, poly-.epsilon.-decalactone, polylactonic acid,
polyglycolic acid, polylactides, polyglycolides, copolymers of the
polylactides and polyglycolides, poly-.epsilon.-caprolactone,
polyhydroxybutyric acid, polyhydroxybutyrates,
polyhydroxyvalerates, polyhydroxybutyrate-co-valerate,
poly(1,4-dioxane-2,3-one), poly(1,3-dioxane-2-one),
poly-para-dioxanone, polyanhydrides, polymaleic acid anhydrides,
polyhydroxy methacrylates, fibrin, polycyanoacrylate,
polycaprolactone dimethylacrylates, poly-.beta.-maleic acid,
polycaprolactone butyl acrylates, multiblock polymers from
oligocaprolactonediols and oligodioxanonediols, polyether ester
multiblock polymers from PEG and poly(butylene terephthalates),
polypivotolactones, polyglycolic acid trimethyl carbonates,
polycaprolactone glycolides, poly(.gamma.-ethyl glutamate),
poly(DTH-iminocarbonate), poly(DTE-co-DT-carbonate), poly(bisphenol
A-iminocarbonate), polyorthoesters, polyglycolic acid trimethyl
carbonate, polytrimethyl carbonates, polyiminocarbonates,
poly(N-vinyl)-pyrrolidone, polyvinyl alcohols, polyester amides,
glycolized polyesters, polyphosphoesters, polyphosphazenes,
poly[p-carboxyphenoxy)propane], polyhydroxy pentanoic acid,
polyanhydrides, polyethylene oxide propylene oxide, soft
polyurethanes, polyurethanes having amino acid residues in the
backbone, polyetheresters such as polyethylene oxide, polyalkene
oxalates, polyorthoesters as well as copolymers thereof, lipids,
carrageenans, fibrinogen, starch, collagen, protein based polymers,
polyamino acids, synthetic polyamino acids, zein,
polyhydroxyalkanoates, pectic acid, actinic acid, carboxymethyl
sulfate, albumin, hyaluronic acid, chitosan and derivatives
thereof, heparan sulfates and derivates thereof, heparins,
chondroitin sulfate, dextran, .beta.-cyclodextrins, copolymers with
PEG and polypropylene glycol, gum arabic, guar, gelatin, collagen
N-hydroxysuccinimide, lipids, phospholipids, polyacrylic acid,
polyacrylates, polymethyl methacrylate, polybutyl methacrylate,
polyacrylamide, polyacrylonitriles, polyamides, polyetheramides,
polyethylene amine, polyimides, polycarbonates, polycarbourethanes,
polyvinyl ketones, polyvinyl halogenides, polyvinylidene
halogenides, polyvinyl ethers, polyisobutylenes, polyvinyl
aromatics, polyvinyl esters, polyvinyl pyrrolidones,
polyoxymethylenes, polytetramethylene oxide, polyethylene,
polypropylene, polytetrafluoroethylene, polyurethanes, polyether
urethanes, silicone polyether urethanes, silicone polyurethanes,
silicone polycarbonate urethanes, polyolefin elastomers, EPDM gums,
fluorosilicones, carboxymethyl chitosans polyaryletheretherketones,
polyetheretherketones, polyethylene terephthalate, polyvalerates,
carboxymethylcellulose, cellulose, rayon, rayon triacetates,
cellulose nitrates, cellulose acetates, hydroxyethyl cellulose,
cellulose butyrates, cellulose acetate butyrates, ethyl vinyl
acetate copolymers, polysulfones, epoxy resins, ABS resins, EPDM
gums, silicones such as polysiloxanes, polydimethylsiloxanes,
polyvinyl halogens and copolymers, cellulose ethers, cellulose
triacetates, chitosans and copolymers and/or mixtures of the
aforementioned polymers.
[0084] In a particular embodiment, the device comprises visibility
or opacity technology allowing visualization of the device using an
imaging means or imbedding the covering or strut coating with the
same or various drugs or illuminating material. In another
embodiment, the covering allows the stent to freely float or to
move in a controlled manner under the coating and covering, with
the level of restriction depending on the thickness of said
covering or coating. In another embodiment, the covering or coating
has varying degrees of degradation. If the covering was formed by
the electrospinning, the filaments would be intertwined and set
with such angles to allow the stent to be crimped and opened as
required in normal applications and the degradation could be
controlled by the density of the material established by the number
of filament crossings and the angles to absorb the load and
stresses of opening and closing and anatomical compressions.
Furthermore, the material of the support, coating and covering of
the device allow normal body fluids to flow unobstructed. In yet
another embodiment, the device is covered in a single layer, double
layer, triple layer or multiple layers depending on the need. The
covering can be on the outside of the stent like body, on the
inside of the stent like body, or encapsulating the of the stent
like body.
[0085] In another embodiment, the device comprises a
therapeutically effective amount of a therapeutic agent or agents.
In particular embodiments, the device comprises at least one
therapeutic agent. In other embodiments, the device comprises one
therapeutic agent or more than one therapeutic agent. In still
other embodiments, the device comprises two, at least two, three,
four, or five therapeutic agents. In a particular embodiment, a
therapeutic agent comprised on the device is an analgesic or
anesthetic agent. In another particular embodiment, a therapeutic
agent comprised on the device is an antibiotic, antimicrobial,
antiviral, or antibacterial agent. In another embodiment, a
therapeutic agent comprised on the device is a thrombotic or
coagulant agent. In another embodiment, a therapeutic agent
comprised on the device is an anti-thrombotic or anticoagulant
agent.
[0086] In certain embodiments, the therapeutic agent is comprised
in a pharmaceutical composition formulated for sustained-release.
Sustained-release, also known as sustained-action,
extended-release, time-release or timed-release,
controlled-release, modified release, or continuous-release,
employs a pharmaceutically acceptable agent that dissolves slowly
and releases the therapeutic agent over time. A sustained-release
formulation allows the topical release of steady levels of the
therapeutic agent directly at the site where it would be
therapeutically effective.
[0087] In one embodiment, the pharmaceutical composition is
formulated for sustained release by embedding the active ingredient
in a matrix of insoluble substance(s) such as acrylics or chitin. A
sustained release form is designed to release the therapeutic agent
at a predetermined rate by maintaining a constant drug level for a
specific period of time. This can be achieved through a variety of
formulations, including, but not limited to liposomes and
drug-polymer conjugates, such as hydrogels.
[0088] In another embodiment, the therapeutic agent is comprised in
a pharmaceutical composition formulated for delayed-release, such
that the therapeutic agent is not immediately released upon
administration. An advantage of a delayed-release formulation is
that the therapeutic agent is not released from the device until
the device has been emplaced in the desired location. In some
embodiments, the therapeutic agent is fist coated onto the device
and is then coated over with a pharmaceutical composition
formulated for delayed-release.
[0089] In a particular embodiment, the therapeutic agent is
delivered in a vehicle that is both delayed release and sustained
release.
[0090] In another embodiment, a therapeutic agent comprised on the
device is applied to the exterior surface of the device. A
therapeutic agent may be applied to the exterior of the cover or
may be mixed or imbedded into the covering material. In some
embodiments, the device may contain an additional coating on its
exterior that delays the release of the therapeutic agent or
modulates the release of the therapeutic agent over time. In one
embodiment, the covering of the device is further coated with a
drug coating that can be eluted to minimize hyperplastic response
or to induce closure of the aneurysm.
[0091] In another embodiment, a therapeutic agent comprised on the
device is applied to the interior surface of the device. In further
embodiments, therapeutic agents are applied to both the interior
and to the exterior surfaces of the device. Therapeutic agents
applied to the interior and exterior surfaces of the device may be
the same or different. As a non-limiting example, a coagulant agent
may be applied to the exterior surface of the device to facilitate
the healing of a perforation, while an anti-coagulant may be
applied to the interior of the device to prevent restriction of the
flow of bodily fluids and cells through the device.
[0092] Various biodegradable or bioabsorbable implants can be used
in the coronary, peripheral vascular, or non-vascular space that
could be covered with the electro spinning process or dip-coated
process to be used to occlude various defects or leaks. Exemplary
materials include, but are not limited to, magnesium (FIG. 1A),
iron (FIG. 1B), or polymer materials (FIG. 1C). Coverings of the
device (FIG. 1D) can also be made of biodegradable or bioabsorbable
materials.
[0093] The device can also be made from a material that is not
biodegradable and that is a more traditional and commonly used
material such as, but not limited to, stainless steel, titanium or
cobalt chromium (FIG. 2). The device can also be made of any
suitable pharmaceutically acceptable alloy comprising, but not
limited to, iron, titanium, carbon, chromium, cobalt, molybdenum,
nickel, aluminum, vanadium, zirconium, niobium, and/or tantalum.
The stent like body of the device can also be made from a ceramic.
This stent like body would be coated or spun in the tube diameter
it was cut from, or some other diameter from about 50% less the
tube diameter to about 100% of its maximum expanded diameter which
is an embodiment of this process to assist with the expansion of
the stent.
[0094] The device can be crimped to its nominal diameter on a
catheter (FIG. 3) after it is covered from an electrospinning or
dip-coated process. Use of the Device
[0095] A further aspect of the present invention is a method of
treating an aneurysm or occluding an opening in a luminal vessel in
a mammal using the device of the present invention.
[0096] In another embodiment, the opening in the luminal vessel has
been sutured, stapled, cauterized or glued and the device is used
to support the luminal wall during the healing process and prevent
leakage.
[0097] The aneurysm may be a cerebral aneurysm, an aortic aneurysm
or a peripheral aneurysm. The form of the aneurysm may be fusiform,
saccular or berry.
[0098] The device may also be used in the treatment of a
perforation, fistula, or dehiscent in a vessel.
[0099] A further embodiment for use of the present invention is
carotid stenting, wherein placement of the device prevents a plaque
from breaking off during stent placement and to insure the plaque
is trapped behind the implant until the covering dissolves.
[0100] Another embodiment is in the treatment of an acute
myocardial infarction, wherein placement of the device traps a
thrombus or other such material or plaque against the luminal wall
to prevent the thrombus from being pushed down stream.
[0101] A further embodiment for use of the present invention is in
association with graft placement, wherein the device is emplaced
under a graft to support it during the healing process and prevent
leakage at the sutures.
[0102] In each of these methods, the method comprises the steps of
(a) introducing into the subject a device comprising (i) a stent
like body coated with a biodegradable material, and (ii) an
electrospun fibrous biodegradable covering that covers said stent
like body, (b) positioning the device adjacent to the area in need
of treatment, and (c) expanding the device to allow it stays at the
treatment site.
[0103] After implantation, the material covering the stent like
body will biodegrade and the stent like body will remain if it is
made from a non-biodegradable, non-bioabsorbable material. In
certain embodiments, the stent like body is also made from a
biodegradable or bioabsorbable material, and will degrade after the
degradation of the biodegradable covering. In other embodiments,
the stent like body is made from a biodegradable or bioabsorbable
material, and is partially covered with the biodegradable covering
so that it will degrade with the biodegradable covering at the same
time but at a slower rate.
Dip-Coating
[0104] Stent in dip-coated form (FIG. 4) has an increased covering
thickness around the strut segments to allow for expansion, having
ripples 1 in the material that will allow it to expand beyond the
current state. The device with a higher thickness or density of
coating starting with the individual struts and then dip-coated
again after to insure that the device covering will degrade from
the middle of the cell 2 to the struts. Higher magnification (FIG.
5) shows that the covering is thicker around the arch of the stent
3 and tapers off as you move away from the struts. The covering is
much thinner in the middle of the cell 4 than close to the struts,
allowing the device to biodegrade from the middle of the cell to
the strut segments versus at the attachment points to the
struts.
Electrospinning
[0105] The process of electrospinning can be carried out by any
method known in the art. The method used in the present invention
is not to be limited to a single method of electrospinning.
Exemplary, non-limiting, processes for electrospinning are
described, for example, by Yuan, X et al. (Yuan, X et al.
Characterization of Poly-(L-Lactic Acid) Fibers Produced by Melt
Spinning. J. Appl. Polym, Sci. 2001, 81:251-260.) and in ZEUS
Technical Newsletter, Electrospinning-Fibers at the Nano-scale.
2009 (Zeus Industrial Products, Inc., Orangeburg, S.C.).
[0106] In the coating of the device by electrospinning, the device
is covered in a way that the fibers cross one another interlocking
and forming angles. In one embodiment, the fibers intersect one
another at angles with angles from about 1, 5, 10, 15, 20, 25, 30,
35, 40 or 45 degrees to about 45, 50, 55, 60, 65, 70, 75, 80, 85,
90 or 95 degrees. In another embodiment, the fibers intersect one
another at angles with angles from about 1 degree to about 95
degrees. In a further embodiment, the fibers intersect one another
at angles with angles from about 5 degrees to about 95 degrees. In
another embodiment, the fibers intersect one another at angles with
angles from about 10 degrees to about 90 degrees.
[0107] The fibers are overlapped to allow for the stresses during
crimping, loading, and expansion to be born by all the materials
filaments with the stress loads being on the various filaments and
their respective angles which allows the distribution of the
stresses and the loads in all directions versus a uniform direction
which is required for the opening and closing of a cylindrical tube
of varying lengths. In one embodiment, the fibers are overlapped a
minimum of about 1 time and a maximum of about 1000 times. In a
preferred embodiment, the fibers are overlapped a minimum of about
1 time and a maximum of about 500 times. In another preferred
embodiment, the fibers are overlapped a minimum of about 2 times
and a maximum of about 500 times. Yet in another preferred
embodiment, the fibers are overlapped a minimum of about 2 times
and a maximum of about 400 times. In still another preferred
embodiment, the fibers are overlapped a minimum of about 2 times
and a maximum of about 300 times. In a more preferred embodiment,
the fibers are overlapped a minimum of about 2 times and a maximum
of about 200 times. In a most preferred embodiment, the fibers are
overlapped a minimum of 2 times and a maximum of 200 times.
[0108] FIG. 6 shows a crimped stent that has an electrospun
covering. A magnified view of the same stent (FIG. 7) in its
crimped state shows the electrospun fibers with mesh like cross
section fibers 5. An angle 6 of the electrospun material allows the
device to be opened to its full expansion through the use of the
preformed angle of the electrospun material. Shapes which form in
the mesh, such as a triangle 7, circles, rectangles, or ovals allow
the device to expand to its optimal diameter. This design shows
that through the use of various geometrical shapes the device can
expand without putting fibers under strains that cause them to
break.
[0109] An electrospun stent may have a porous structure (FIG. 8) in
a honeycomb pattern or circle chain links that allow the covering
to expand during the opening process of the device. This porous
structure can comprise large interlocking circles 8, a deep
honeycomb structure 9, and small circular structures 10 that allow
for expansion and ease of drug loading as well as visibility
material.
[0110] In a device having a covering formed by an electrospinning
apparatus having a conical circular opening that release the
polymers (FIG. 9), variation in the strand fibers and the hole
sizes 11 are regulated and oriented by changes in heat, viscosity
of the material and molecular chain lengths. Modifying the opening
of the dispersion tube that releases the material to be electrospun
can modify the covering fiber thickness.
[0111] One can further modify the flow and alignment of the polymer
fibers by changing the opening shape from a circle to one in the
shape of an oval, cross, diamond, star, octagon, other polygons or
other such shapes. Additionally, the dispersing tube can have a
tapered inner surface of varying shapes that can also modify the
process of alignment or application. Additionally, because the
material and the receiving device have different charges, you can
further control the fiber application by reversing the direction of
the application device versus moving the coated device to modify
the fiber orientation. By moving the applicator cone versus the
device in the opposite or in the direction of the desired laying
down of the fibers one can better control the fiber angles, shapes,
and thickness to achieve the desired or optimal results. The shape
of the holes 12, 13 can also be varied by the application
procedure.
[0112] Electrospun fiber can be attached to struts that have been
previously covered with electrospun material (FIG. 10) to insure
that the struts have a thicker amount of material than the center
of the cell and that the material has increase sticking and elastic
characteristics. In this case, the denser more fibrous adherence is
aligned on the struts 14, while the center of the cells 15 have
less of the covering but still have the porous and cross sectional
aspect of the fibers.
[0113] A magnified view of the optimal fiber alignment (FIG. 11)
shows the strut adherence 16 and the center of the cell structure
17 and optimal orientation of circular and fibrous longitudinal
fibers as well as angulations that form the optimal covering for
the stent.
[0114] The configuration allows the fibers to maintain their
integrity when the stent is expanded (FIG. 12), where the fibers
maintain their optimal orientation in the expanded form, as seen in
the center of the cells 18, 19. Further magnification of the
expanded stent (FIG. 13) shows the optimal configuration of the
fibers adhered to the strut of the stent 20. Yet further
magnification shows that the structural fibers 21 are optimal for
expansion and red blood cells or drug application.
[0115] Magnification of fibers on an expanded stent (FIG. 14) show
how the stretch coming off the struts and the various optimal
shapes formed during the electrospinning process to allow for
expansion. The shapes may include: a "Y" or "V" angulated connector
22 for optimal expansion, multiple circular connect rings of
varying sizes 23, or a large base circle 24 that may be integrated
with smaller base circles 25. The maximum density of the
electrospun covering at center of the struts 26 tapers to a lower
density away from the center of the struts 27 and to a lower
density at the edges of the struts 28. A further magnified view of
the stent covering (FIG. 15) shows the detailed view of the
angulated mesh 29 allowing for optimal expansion.
[0116] FIG. 16 shows a magnified view of a coated strut segment,
while FIG. 17 shows an unexpanded stent. Another view of a covered
stent (FIG. 18) shows increased thickness close to stent strut 30,
the elasticity of the polymer fibers connected to the strut
segments 31 and the elongated connectivity 32.
[0117] Further magnification of an electrospun coated stent (FIG.
19) shows the thickness around strut segments 33, 34.
[0118] Close up of the stent with angles of 5% to 95% and circle
combinations (FIG. 20) shows connectivity to covered stent fiber
and directional covering 35 and the circle and fiber orientation
and combination 36.
[0119] A view of an electrospun stent (FIG. 21) shows angles in the
covering at a macro level 37 and covered filaments 38.
[0120] A microscopic view of the mesh (FIG. 22) and the cross
orientation that allows for expansion of the mesh shows a view of
an expanded micro cell 39. A lower magnification (FIG. 23) of the
same angle 40 is seen in an expanded view of the mesh. FIG. 24
shows an electrospun coating with a different orientation and
filament thickness 41.
[0121] Electrospinning allows the formation of various fibers and
angles with different filament thickness (FIG. 25). Additionally,
variation of crystalinity by spinning the material on the device
when the device is at a variant temperature of up to 38.degree. C.
above or below room temperature will have an impact on the
formation of the patterns, adherence to the device, and filament
roughness or smoothness. Based on a temperature change in the
spinning process and a combination of a change in the device, the
orientation patterns of the spun filaments as well as the
elasticity of the filaments can be modified. For example, if the
device is cold and the spun material is hot, this will
substantially change the outcome versus if the device and the
material are at the same temperature.
[0122] Variations in processing have an impact on changing the
filament surface characteristics 42. Changing the surface quality
of the filaments affects their ability to expand or to have more
friction, depending on the actual surface quality of the filaments,
which has a direct impact on the opening behavior of the device;
smoother surface, easier opening, and less tearing of the
filaments. Greater roughness of the fibers translates to a greater
surface area coefficient of friction and the potential to increase
risk of tearing or when there is a filament disruption for the
others to maintain their integrity 43.
[0123] Electrospinning provides an advantage over linear coating of
a stent in a unidirectional form (FIG. 26), because the linear
coating does not provide a mesh which allows elasticity of the
coating as the device is expanded. Accordingly, as a linear coated
device is expanded, this lack of elasticity results in the
destruction of the fibers (FIG. 27) and failure in the expanded
stent (FIG. 28) to provide a surface capable of occluding an
opening in a luminal vessel.
[0124] The above description is for the purpose of teaching the
person of ordinary skill in the art how to practice the present
invention, and it is not intended to detail all those obvious
modifications and variations of it which will become apparent to
the skilled worker upon reading the description. It is intended,
however, that all such obvious modifications and variations be
included within the scope of the present invention, which is
defined by the following claims. The claims are intended to cover
the components and steps in any sequence which is effective to meet
the objectives there intended, unless the context specifically
indicates the contrary.
* * * * *