U.S. patent application number 17/305894 was filed with the patent office on 2021-11-04 for medical devices for fluid delivery.
The applicant listed for this patent is Eliot T. KIM, Richard S. LILLY, Jean C. ORTH, Robert G. QUINTOS, Zaya TUN. Invention is credited to Eliot T. KIM, Richard S. LILLY, Jean C. ORTH, Robert G. QUINTOS, Zaya TUN.
Application Number | 20210338985 17/305894 |
Document ID | / |
Family ID | 1000005720667 |
Filed Date | 2021-11-04 |
United States Patent
Application |
20210338985 |
Kind Code |
A1 |
ORTH; Jean C. ; et
al. |
November 4, 2021 |
MEDICAL DEVICES FOR FLUID DELIVERY
Abstract
Medical devices and methods for delivering fluid. The medical
devices include one or more needles for delivering fluid. The
methods may include expanding an expandable member such as an
inflatable member to expand an expandable scaffold outward toward a
lumen wall.
Inventors: |
ORTH; Jean C.; (Morgan Hill,
CA) ; LILLY; Richard S.; (San Jose, CA) ; KIM;
Eliot T.; (New York, NY) ; TUN; Zaya;
(Livermore, CA) ; QUINTOS; Robert G.; (Newark,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ORTH; Jean C.
LILLY; Richard S.
KIM; Eliot T.
TUN; Zaya
QUINTOS; Robert G. |
Morgan Hill
San Jose
New York
Livermore
Newark |
CA
CA
NY
CA
CA |
US
US
US
US
US |
|
|
Family ID: |
1000005720667 |
Appl. No.: |
17/305894 |
Filed: |
July 16, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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17222361 |
Apr 5, 2021 |
11071847 |
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17305894 |
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PCT/US2020/066929 |
Dec 23, 2020 |
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17222361 |
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62953348 |
Dec 24, 2019 |
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62953342 |
Dec 24, 2019 |
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62965037 |
Jan 23, 2020 |
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62987779 |
Mar 10, 2020 |
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63017173 |
Apr 29, 2020 |
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63073429 |
Sep 1, 2020 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 25/06 20130101;
A61F 2/958 20130101; A61M 25/005 20130101; A61L 27/54 20130101;
A61M 2025/018 20130101; A61M 2205/0266 20130101; A61F 2250/0067
20130101; A61M 25/0155 20130101 |
International
Class: |
A61M 25/01 20060101
A61M025/01; A61F 2/958 20060101 A61F002/958; A61L 27/54 20060101
A61L027/54; A61M 25/06 20060101 A61M025/06; A61M 25/00 20060101
A61M025/00 |
Claims
1. An intravascular apparatus, comprising: an inflatable balloon
carried by a distal region of an elongate member, the inflatable
balloon comprising a cylindrical portion when inflated; an
expandable infusion scaffold comprising at least first and second
expandable infusion spines, each of the at least first and second
infusion spines defining a lumen therein and each including two or
more spaced apart radial openings therethrough, wherein the
expandable infusion scaffold is adapted and positioned about the
inflatable balloon such that inflation of the balloon causes the
scaffold to expand radially and a circumferential distance between
the at least first and second expandable infusion spines to
increase as the balloon is inflated, the at least first and second
infusion spines extending about the cylindrical portion when the
inflatable balloon is inflated; and a plurality of movable
assemblies, each one of the plurality of movable assemblies
disposed in one of the at least first and second expandable
infusion spines and movable within and relative to the infusion
spine, each of the plurality of movable assemblies comprising a
rail that includes a rail lumen, a plurality of needles, and one or
more fluid delivery lumens within the rail lumen that are in fluid
communication with the plurality of needles, wherein the plurality
of needles are coupled to the rail such that movement of the rail
within the corresponding infusion spine moves the plurality of the
needles as a group relative to the infusion spine between delivery
configurations in which each of the plurality of needles are housed
within the infusion spine and deployed configurations in which each
of the plurality of needles extends generally radially out of one
of the radial openings in the infusion spine for delivery of an
agent into a wall of a target vessel.
2. The apparatus of claim 1, wherein each rail further includes a
plurality of radially outwardly disposed openings, each of the
plurality of needles disposed at a location of one of the plurality
of radially outwardly disposed openings.
3. The apparatus of claim 1, wherein each of the plurality of
needles is in fluid communication with a distinct fluid delivery
lumen.
4. The apparatus of claim 3, wherein two or more of the distinct
fluid delivery lumens are disposed adjacent to each other within
the rail lumen.
5. The apparatus of claim 1, wherein the plurality of needles are
in fluid communication with a common fluid delivery lumen.
6. The apparatus of claim 1, wherein each of the rails has a
stiffness that is not constant along a length of the inflatable
balloon.
1. aratus of claim 1, wherein the at least first and second
infusion spines extend along at least half of a length of the
cylindrical portion of the inflatable balloon.
8. The apparatus of claim 1, wherein the inflatable balloon has a
tapered proximal end and a tapered distal end when inflated, and
wherein the cylindrical portion is in between the tapered proximal
and distal ends.
9. The apparatus of claim 1, wherein the inflatable balloon has
length from 10 mm to 200 mm when inflated.
10. The apparatus of claim 1, wherein the at least first and second
infusion spines, in a region in which they overlap with the
cylindrical portion of the inflatable balloon, have a length from
10 mm to 200 mm.
11. The apparatus of claim 1, wherein the expandable infusion
scaffold is attached to the inflatable balloon at a plurality of
discrete, spaced-apart regions of the at least first and second
spines.
12. The apparatus of claim 1, wherein the at least first and second
infusion spines each have a stiffness that is not constant along
the length of the inflatable balloon.
13. The apparatus of claim 1, wherein the one or more fluid
delivery lumens each has a stiffness that is not constant along the
length of the inflatable balloon.
14. The apparatus of claim 1, wherein the at least first and second
infusion spines each comprise one or more of nitinol, stainless
steel, polymer, polyimide, or a braided member.
15. The apparatus of claim 1, wherein the one or more fluid
delivery lumens comprise one or more of nitinol, stainless steel,
polymer, polyimide, or a braided member.
16. The apparatus of claim 1, wherein each rail comprises one or
more of nitinol, stainless steel, polymer, polyimide, or a braided
member.
17. The apparatus of claim 1, wherein the at least first and second
infusion spines are spaced from one another and the needles are
spaced from one another such that when a fluid is delivered from
the needles of the apparatus, substantially the entire vessel wall
from a proximal most needle to a distal most needle is exposed to
the fluid.
18. The apparatus of claim 1, wherein a distal end of each of the
needles is pre-formed to take a perpendicular or near perpendicular
configuration as it exits the corresponding opening.
19. The apparatus of claim 1, wherein the needles are made of
nitinol.
20. The apparatus of claim 1, wherein the needles range in size
from 20 gauge to 38 gauge.
21. The apparatus of claim 1, wherein each of the at least first
and second infusion spines has therein from two to fifty needles
movable relative to the corresponding infusion spine.
22. The apparatus of claim 1, wherein, when deployed, an axial
distance between a distal-most needle of the apparatus and a
proximal-most needle of the apparatus is from 10 mm to 190 mm.
23. The apparatus of claim 1, wherein the infusion spines are not
directly attached to each other.
24. The apparatus of claim 1, wherein the infusion spines are
attached to each other, either directly or indirectly, in at least
one location along their lengths.
25. The apparatus of claim 1, wherein the at least first and second
infusion spines extend non-longitudinally along at least a portion
of a length of the cylindrical portion of the balloon.
26. The apparatus of claim 25, wherein the at least first and
second infusion spines have a spiral configuration along at least a
portion of the length of the cylindrical portion of the
balloon.
27. The apparatus of claim 1, wherein the at least first and second
infusion spines extend longitudinally along at least a portion of a
length of the cylindrical portion of the balloon.
28. The apparatus of claim 1, wherein the at least first and second
infusion spines are not attached to the cylindrical portion of the
balloon.
29. The apparatus of claim 1, wherein the at least first and second
infusion spines are directly or indirectly attached to the
cylindrical portion of the balloon along at least a portion of the
lengths of the at least first and second infusion spines.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 17/222,361, filed Apr. 5, 2021, which is a continuation of
International Application No. PCT/US2020/066929, filed Dec. 23,
2020, which claims priority to the following U.S. Provisional
Applications, the disclosures of which are incorporated herein by
reference in their entireties for all purposes: U.S. Prov. App. No.
62/953,348, filed Dec. 24, 2019; U.S. Prov. App. No. 62/953,342,
filed Dec. 24, 2019; U.S. Prov. App. No. 62/965,037, filed Jan. 23,
2020; U.S. Prov. App. No. 62/987,779, filed Mar. 10, 2020; U.S.
Prov. App. No. 63/017,173, filed Apr. 29, 2020; and U.S. Prov. App.
No. 63/073,429, filed Sep. 1, 2020.
[0002] All publications and patent applications mentioned in this
specification are herein incorporated by reference to the same
extent as if each individual publication or patent application was
specifically and individually indicated to be incorporated by
reference.
FIELD
[0003] Intravascular (e.g., perivascular or adventitial) delivery
of agents for the treatment of peripheral artery disease.
BACKGROUND
[0004] It is estimated that more than 20million patients have
peripheral artery disease (PAD), which can progress to critical
limb ischemia (CLI), the most serious form of PAD.
[0005] Local luminal drug delivery with drug coated balloons (DCBs)
and drug eluting stents (DES) have demonstrated some improvement in
patency rates following above-the-knee revascularization, yet DCBs
and DES have struggled to demonstrate improved patency following
below-the-knee (BTK) interventions. A variety of causes for
inconsistent results from DCB for the treatment of BTK PAD have
been proposed by leaders in the field, such as: the high prevalence
of intimal and medical calcification in BTK lesions that creates a
physical barrier to effective drug penetration into the adventitia
of the vessel, resulting in the inability to effectively inhibit a
key contributor to the restenosis cascade; limited dosage from
smaller drug-coated balloons; and wash-off of the drug from the
balloon surface during device delivery to the target lesion
site.
[0006] To address these limitations, recent attempts have been made
at treating BTK PAD and CLI with an infusion catheter following
primary angioplasty and/or primary atherectomy intervention. Yet
inherent limitations remain with current infusion catheter systems,
inclusive but not limited to, the use of a single infusion channel,
single needle, and/or a fixed length single needle approach. Due to
the limitations of existing infusion catheter systems, treating
longer lesions can be time consuming, inherently user dependent,
and inconsistent in coverage of the delivered therapy, both
circumferentially and longitudinally along the length of the
lesion.
[0007] Approaches are needed that address one or more of the
deficiencies set forth above.
SUMMARY OF THE DISCLOSURE
[0008] The disclosure is generally related to fluid delivery using
medical devices and systems.
[0009] One aspect of the disclosure is an intravascular apparatus
adapted for delivery of a therapeutic agent into a wall of a target
vessel of a human patient. The apparatus may include an inflatable
balloon and an expandable infusion scaffold. The scaffold may
include at least first and second axially-extending infusion spines
circumferentially spaced about an outer surface of the inflatable
balloon. The at least first and second axially-extending infusion
spines may be parallel with or substantially parallel with a long
axis of the inflatable balloon when expanded, and may be expandable
upon inflation of the inflatable balloon. The expandable infusion
scaffold may be coupled to the outer surface of the inflatable
balloon such that a circumferential distance between the at least
first and second axially-extending infusion spines increases as an
inflation pressure within the inflatable balloon is increased and
as the inflatable balloon is expanded. The at least first and
second axially-extending infusion spines may include a lumen
therein and two or more axially-spaced radial openings therein. The
at least first and second axially-extending infusion spines may
have therein two or more needles axially movable relative to the
corresponding infusion spine between a delivery configuration
housed within the infusion spine and a generally radially extending
deployed configuration in which each of the two or more needles
extends out of one of the radial openings in the infusion spine.
The infusion spines may have disposed therein one or more fluid
delivery lumens that are in fluid communication with the two or
more needles that are in the corresponding infusion spine, the one
or more fluid delivery lumens axially movable relative to the
corresponding infusion spine.
[0010] Any two or more needles in this aspect may be operatively
coupled such that they are adapted to be moved axially as a group
relative to one of the infusion spines.
[0011] Any two or more needles in this aspect may be coupled to an
axially moveable rail that is disposed within the infusion spine,
wherein the coupling to the rail operatively couples the two or
more needles such that they are adapted to be moved axially as a
group. Each of the two or more needles may be in fluid
communication with a distinct fluid delivery lumen. Each of the two
or more needles may be coupled to one of the distinct fluid
delivery lumens, optionally with a coupler.
[0012] Any of the rails in this aspect may include a plurality of
radially outwardly disposed openings, wherein each of the two or
more needles may be disposed at a location of one of the plurality
of radially outwardly disposed openings.
[0013] Any of the two or more needles in this aspect may be in
fluid communication with a distinct fluid delivery lumen.
[0014] Any two or more distinct fluid delivery lumens in this
aspect may be disposed adjacent to each other within and along a
portion of the infusion spine.
[0015] Any inflatable member in this aspect may include at least a
portion that has a cylindrical configuration when inflated, and
wherein the at least first and second infusion spines may extend
along the portion of the inflatable balloon that has the
cylindrical configuration. Infusion spines may extend along at
least half of the length of a portion of the inflatable member that
has a cylindrical configuration.
[0016] Any of the inflatable members in this aspect may have a
tapered proximal end and a tapered distal end, and optionally
wherein the inflatable member has a cylindrical configuration
between the tapered proximal and distal ends.
[0017] Any of the inflatable members in this aspect may have a
length from 20 mm to 200 mm.
[0018] Any of the infusion spines in this aspect may have a region
in which they axially overlap with an inflatable member that has a
length from 20 mm to 200 mm.
[0019] Any of the two or more needles in this aspect may be in
fluid communication with a common fluid delivery lumen. A common
fluid delivery lumen may be adapted to be moved axially to axially
translate the two or more needles relative to the infusion
lumen.
[0020] Any of the two or more infusion needles in this aspect may
be advanced out of the infusion spine with a longitudinal and
radial component relative to the long axis of the infusion device.
An axial component of advancement may be one of away from a
proximal end of the infusion device or toward the proximal end of
the infusion device. A radial component of advancement may be one
of away from the long axis of the infusion lumen or toward the long
axis of the infusion lumen.
[0021] Any of the expandable infusion scaffolds in this aspect may
be sized and configured to be delivered within and deployed from a
delivery sheath or a guide catheter.
[0022] Any of the expandable infusion scaffolds in this aspect may
be attached to the inflatable balloon along at least a portion of a
length of the scaffold, and optionally in a plurality of discrete,
axially-spaced regions of the at least first and second spines.
[0023] Any of the expandable infusion scaffolds in this aspect,
including any of the spines, may be attached to the inflatable
member by bonding, optionally with an adhesive.
[0024] Any of the expandable infusion scaffolds in this aspect may
not be attached to the inflatable balloon, wherein the expandable
infusion scaffold may be adapted to be collapsed to a low-profile
delivery configuration and delivered on the inflatable balloon.
[0025] Any of the inflatable members in this aspect may comprise a
non-compliant material.
[0026] Any of the inflatable members in this aspect may comprise
one or more of a compliant or a semi-compliant material.
[0027] Any of the expandable infusion scaffolds in this aspect may
have a stiffness that is not constant along a length of the
inflatable member.
[0028] Any of the infusion spines in this aspect may have a
stiffness that is not constant along a length of the inflatable
member.
[0029] Any of the one or more fluid lumens in this aspect may have
a stiffness that is not constant along the length of the inflatable
member.
[0030] Any number of rail track sub-assemblies (optionally
including any rails) in this aspect may have a stiffness that is
not constant along the length of the inflatable member.
[0031] Any of the infusion spines in this aspect may comprise one
or more of nitinol, stainless steel, polymer, polyimide, or a
braided member.
[0032] Any of the infusion spines in this aspect may include one or
more non-permeable membranes.
[0033] Any of the one or more fluid lumens in this aspect may
comprise one or more of nitinol, stainless steel, polymer,
polyimide, or a braided member.
[0034] Any of the one or more fluid lumens in this aspect may
include one or more non-permeable membranes.
[0035] Any number of rails in this aspect may comprise one or more
of nitinol, stainless steel, polymer, polyimide, or a braided
member.
[0036] Any number of rails in this aspect may include one or more
non-permeable membranes.
[0037] In any apparatus of this aspect, the infusion spines may be
spaced from one another and the needles may be spaced from one
another such that when an agent is delivered from the needles of
the infusion device, substantially an entire vessel wall from a
proximal most needle to a distal most needle is exposed to the
agent.
[0038] Any of the needles in this aspect may include a distal end
that is pre-formed (optionally heat-set) to take a perpendicular or
near perpendicular configuration (e.g., 60-120 degrees) as it exits
the corresponding spine opening.
[0039] Any of the infusion needles in this aspect may be made of
nitinol.
[0040] Any of the infusion needles in this aspect may range in size
from 20 gauge to 38 gauge.
[0041] In any apparatus of this aspect, at least one infusion
needle may have at least one dimension that is different than a
corresponding dimension of at least one other needle.
[0042] Any infusion spine in this aspect may have therein from two
to fifty needles axially movable relative to the spine.
[0043] Any of the needles in this aspect may have a length from 0.1
mm to 3 mm.
[0044] Any of the needles in this aspect may have a distal opening
in fluid communication with one or more fluid delivery lumens.
[0045] Any of the needles in this aspect may have a side opening in
fluid communication with one or more fluid delivery lumens.
[0046] Any apparatus in this aspect may have an axial distance
between a distal-most needle and a proximal-most needle that is
from 10 mm to 190 mm.
[0047] Any apparatus in this aspect may have one or both of distal
most needles and proximal most needles that are axially
aligned.
[0048] Any of the infusion spines in this aspect may not be
directly attached to each other.
[0049] Any of the infusion spines in this aspect may be directly
attached to each other in at least one location along their
lengths.
[0050] Any of the infusion spines in this aspect may have sections
that are parallel to each other when the expandable scaffold is in
a collapsed delivery state and when the scaffold is in an expanded
state.
[0051] This aspect may include any other suitable feature described
or claimed herein.
[0052] Any of the intravascular apparatuses herein may also be
referred to as an infusion device, and vice versa.
[0053] One aspect of this disclosure is an intravascular apparatus
adapted for delivery of a fluid agent into a wall of a target
vessel of a human patient. The apparatus may include an inflatable
member (e.g., a balloon) carried by a distal region of an elongate
member, the inflatable member having a cylindrical configuration
when inflated. The apparatus may also include an expandable
infusion scaffold comprising a plurality of axially-extending
infusion spines circumferentially spaced about an outer cylindrical
surface of the inflatable balloon, the at least first and second
axially-extending infusion spines parallel with or substantially
parallel with a long axis of the inflatable balloon when expanded
upon inflation of the inflatable balloon. The expandable infusion
scaffold may be coupled to the outer surface of the inflatable
balloon such that a circumferential distance between the plurality
of axially-extending infusion spines increases as the inflatable
balloon is expanded. The plurality of infusion spines may each
define a lumen therein and having a plurality of radial openings
therein. Each of the plurality of infusion spines may have therein
a plurality of needles axially movable relative to the
corresponding infusion spine between a delivery configuration
housed within the infusion spine and a generally radially extending
deployed configuration in which the plurality needles extends out
of one of the radial openings in the infusion spine. Each of the
plurality of infusion spines may have disposed therein one or more
fluid delivery lumens that are in fluid communication with the
plurality of needles that are in the corresponding infusion spine,
the one or more fluid delivery lumens axially movable relative to
the corresponding infusion spine. Any of the fluid delivery lumens
herein may also be referred to as a fluid lumen.
[0054] Any inflatable member in this aspect may have a tapered
proximal end and a tapered distal end, wherein the cylindrical
configuration may be in between the tapered proximal and distal
ends.
[0055] Any of the plurality of infusion spines in this aspect may
have sections that are parallel to each other when the expandable
infusion scaffold is in a collapsed delivery state and when the
infusion scaffold is in an expanded state.
[0056] Any of the plurality of needles in this aspect may be
operatively coupled such that they are adapted to be moved axially
as a group relative to one of the infusion spines. Any of the
plurality of needles may be coupled to an axially moveable rail
that is disposed within the infusion spine, wherein the coupling to
a rail operatively couples the plurality of needles such that they
are adapted to be moved axially as a group.
[0057] Any individual or group of needles in this aspect may be in
fluid communication with a distinct fluid delivery lumen.
[0058] Any rail in this aspect may include a plurality of radially
outwardly disposed openings, each of the plurality of needles may
be disposed at a location of one of the plurality of radially
outwardly disposed openings.
[0059] Any individual or group of needles in this aspect may be in
fluid communication with a distinct fluid delivery lumen.
[0060] Any two or more distinct fluid delivery lumens in this
aspect may be disposed adjacent to each other within and along a
portion of an infusion spine.
[0061] Any of the plurality of infusion spines in this aspect may
extend along at least half of a length of a portion of the
inflatable member that has the cylindrical configuration.
[0062] Any of the inflatable members in this aspect may have a
tapered proximal end and a tapered distal end, and wherein the
cylindrical configuration may be in between the tapered proximal
and distal ends.
[0063] Any of the inflatable members in this aspect may have a
length from 20 mm to 200 mm.
[0064] Any of the infusion spines in this aspect may have a region
in which the spine axially overlaps with the inflatable member that
has a length from 20 mm to 200 mm.
[0065] Any of the expandable infusion scaffolds in this aspect may
be attached to the inflatable balloon along at least a portion of a
length of the scaffold, and optionally in a plurality of discrete,
axially-spaced regions of the plurality of spines.
[0066] Any of the expandable infusion scaffolds in this aspect may
have a stiffness that is not constant along the length of the
inflatable member.
[0067] Any rail track sub-assembly in this aspect may have a
stiffness that is not constant along the length of the inflatable
member.
[0068] Any apparatus in this aspect may have an axial distance
between a distal-most needle and a proximal-most needle that may be
from 10 mm to 190 mm.
[0069] Any of the infusion spines in this aspect may have sections
that are parallel or substantially parallel to each other when the
expandable scaffold is in a collapsed delivery state and when the
scaffold is in an expanded state.
[0070] This aspect may include any other suitable feature disclosed
or claimed herein.
[0071] One aspect of this disclosure is a method of delivering a
therapeutic agent into a vessel wall. The method may include
delivering an inflatable member in an unexpanded state and an
expandable infusion scaffold in an unexpanded state to a location
within a vessel, the expandable infusion scaffold comprising a
plurality of infusion spines extending along at least portion of
the inflatable member, the infusion spines each having a plurality
of radial openings therein. The method may further include
expanding the balloon radially outward by delivering an inflation
fluid to a volume within the inflatable member, wherein expanding
the inflatable member expands the plurality of infusion spines
radially outward and causes the plurality of infusion spines to
move towards and into contact with an inner wall of the vessel. The
method may further include deploying a plurality of axially-spaced
needles from the radial openings in each of the plurality of
infusion spines and through the vessel wall. The method may further
include delivering a therapeutic agent through the plurality of
needles and into the vessel wall. The method may include retracting
the needles into the openings in the plurality of infusion spines.
The method may include collapsing the infusion scaffold and
removing the infusion scaffold and inflatable member from the
vessel.
[0072] In this aspect, the delivering step may comprise delivering
the infusion scaffold attached to the inflatable member.
[0073] In this aspect, deploying the plurality of axially-spaced
needles may comprise distally translating a rail track within the
infusion spine, wherein the needles may all be coupled to the rail
track.
[0074] In this aspect, deploying the plurality of axially-spaced
needles may comprise distally translating individual rail tracks
within the infusion spine, wherein the needles may each be coupled
to a distinct rail track.
[0075] In this aspect, delivering one or more therapeutic agents
through the needles and into the vessel wall may comprise
delivering fluid through a distinct fluid lumen to each needle in
the infusion spine.
[0076] In this aspect, delivering one or more therapeutic agents
through needles and into the vessel wall may comprise delivering
fluid through a common fluid delivery lumen to all of the needles
in the infusion spine.
[0077] In this aspect, deploying the plurality of axially-spaced
needles from the radial openings may comprise deploying the needles
at the same time.
[0078] In this aspect, delivering the therapeutic agent through the
needles and into the vessel wall may comprise exposing a section of
at least one of the adventitia and the media within the vessel wall
of at least 5 mm in length to the therapeutic agent without having
to move the scaffold axially within the vessel. Exposing a section
of the vessel wall to the therapeutic agent may expose
substantially all of at least one of the adventitia and media along
at least one of a length of the infusion scaffold or a length of
the inflatable balloon.
BRIEF DESCRIPTION OF THE DRAWINGS
[0079] FIG. 1 is a side view of a distal region of an exemplary
infusion device including an expandable scaffold in an expanded
configuration.
[0080] FIG. 2A is a side view of a distal region of an exemplary
infusion device including an expandable scaffold in an expanded
configuration.
[0081] FIG. 2B is a side view of a distal region of an exemplary
infusion device from FIG. 2A with needles deployed from elongate
spines of the scaffold.
[0082] FIG. 3A is an end view of a distal region of an exemplary
infusion device with an inflatable member inflated.
[0083] FIG. 3B is an end view of a distal region of the exemplary
infusion device in FIG. 3A, shown with needles deployed.
[0084] FIG. 4A is an end view of a distal region of the exemplary
infusion device from FIG. 3A, shown within an exemplary vessel.
[0085] FIG. 4B is an end view of a distal region of the exemplary
infusion device in FIG. 3A shown with needles deployed and within
an exemplary vessel.
[0086] FIG. 5 is a distal region of an exemplary infusion device
illustrating needles deployed from spines of an expandable
scaffold.
[0087] FIGS. 6A, 6B, 6C and 6D illustrate views of portions of an
exemplary needle sub-assembly or rail track sub-assembly.
[0088] FIG. 6E illustrates an exemplary needle secured to a fluid
delivery lumen.
[0089] FIG. 6F illustrates an exemplary rail.
[0090] FIG. 6G illustrates a portion of an exemplary infusion
spine.
[0091] FIG. 7A illustrates a top view of an exemplary needle or
rail track sub-assembly.
[0092] FIG. 7B illustrates a side view of the exemplary needle or
rail track sub-assembly from FIG. 7A.
[0093] FIG. 8 is a side view of a plurality of exemplary needles
deployed outward from an infusion spine.
[0094] FIG. 9 illustrates an exemplary cross section of an
exemplary needle or rail track sub-assembly.
[0095] FIG. 10 illustrates an exemplary cross section of an
exemplary needle or rail track sub-assembly.
[0096] FIGS. 11A and 11B illustrate side and end views,
respectively, of an exemplary infusion device in a collapsed lower
profile delivery configuration.
[0097] FIGS. 11C and 11D illustrate side and end views,
respectively, of the exemplary infusion device from FIGS. 11A and
11B in an expanded configuration with needles deployed.
[0098] FIG. 12 illustrates a distal region of an exemplary infusion
device in an expanded configuration.
[0099] FIG. 13 is a side view illustrating an exemplary infusion
device, including a proximal region positioned to be disposed
outside of a patient.
[0100] FIG. 14 is a side view of an exemplary proximal region of an
exemplary infusion device, including an exemplary actuator.
[0101] FIGS. 15A and 15B are proximal end views of a proximal
external region of an exemplary infusion device.
[0102] FIG. 16 is a side view illustrating an exemplary manner in
which an inflatable member may be secured to an infusion
device.
DETAILED DESCRIPTION
[0103] The disclosure herein is related to methods, devices and
systems for the delivery of one or more therapeutic agents for the
treatment of peripheral artery disease. The methods, devices and
systems herein are adapted to efficiently and reliably deliver the
desired dose of agent to a target region of adventitial tissue,
particularly compared to existing drug coated balloons (DCB), drug
eluting stents (DES), and single-needle delivery devices.
[0104] The infusion devices herein may include a plurality of
deployable needles, which are spaced axially (also referred to
herein as longitudinally) and circumferentially apart around the
infusion device, allowing more uniform circumferential coverage and
a greater span of tissue along the lesion length to be targeted
with the agent without having to move the infusion device within
the vessel. It is of course understood that any of the treatments
herein may include delivering an agent, after which the infusion
device may be moved to a different location within the vessel
before again delivering the same or a different agent.
[0105] Additionally, the infusion devices herein may be positioned
against a vessel wall upon application of a radially outward force,
which is generally described herein as a force applied by an
inflatable member or balloon, although it is conceivable that
non-inflatable members may alternatively be used. After the
infusion device is apposed against the vessel wall, the needles can
be deployed outward such that they pierce through the vessel wall
and optionally into the adventitia layer of the vessel wall. Once
the needles have been advanced into the wall and optionally into
the adventitia, the desired therapeutic agent is delivered though
the needles, out of the needles, and into the target tissue within
the vessel wall. In some methods, the volume and rate of infusion
may be controlled based on one or more of a desired lesion length
and/or desired volume of agent infusion.
[0106] One or more of any of the following therapeutic agents or
types of agents, including but not limited to any combination
thereof, may be delivered from the infusion devices herein during
any of the methods of use herein: antiplatelet agents;
anti-inflammatory agents; antiproliferative drugs as referred to as
cell-proliferation inhibitors; immunosuppressants such as mTOR and
IMDH inhibitors; anticoagulation drugs; antithrombotic agents;
lipid-lowering drugs; angiotensin-converting enzyme (ACE)
inhibitors; and stem cells. While the disclosure herein focuses on
PAD, the device and systems herein may be used to treat alternative
conditions, such as, for example only, chronic obstructive
pulmonary disease ("COPD"), which is described in U.S. Prov. App.
No. 62/953,342, which is incorporated by reference herein in this
regard. Agents that may be delivered to treat COPD, for example,
include but are not limited to anti-inflammatory agents, receptor
antagonists, and neurotoxins.
[0107] The disclosure that follows describes non-limiting exemplary
infusion devices that are adapted and configured to deliver one or
more therapeutic agents and provide one or more of the advantages
set forth herein, such as efficiently delivering a desired volume
or dose to a target region of tissue in the vessel wall.
[0108] FIG. 1 illustrates a distal region of an example of an
infusion device. Infusion device 100 includes an expandable
infusion scaffold 110 that includes at least first and second
infusion spines 112a , 112b , and 112c (three shown in this
example), which are shown in FIG. 1 in expanded configuration with
the infusion needles deployed. Unless indicated herein to the
contrary, the infusion spines herein may also be referred to as a
plurality of infusion spines. Infusion spines are sized,
positioned, and configured to be expandable by a generally radially
outward force, which in this example is applied by an inflatable
member 150. Any of the inflatable members herein may include one or
more of a compliant material (e.g., polyurethane or silicone), a
non-compliant material (e.g., polyester or nylon), or a
semi-compliant material. As shown, the infusion spines 112a , 112b
and 112c are circumferentially spaced about an outer surface of the
inflatable member 150 with a long axis (LA) of the infusion device
when the spines are expanded. The long axis in this embodiment is
also a long axis of the inflatable member 150. In this example, the
spines are parallel (or substantially parallel) with the long axis
of the infusion device 100 and the inflatable member 150 when
expanded, as shown. As used herein, the phrase substantially
parallel in this context includes slight deviations from being
parallel and includes spines that have configurations that still
facilitate the efficient and effective delivery of therapeutic
agent to the desired tissue. One of skill in the art will
appreciate that substantially parallel as used in this context
allows for some deviation from strictly parallel, such as at an
angle of five or ten degrees relative to a long axis, for
example.
[0109] In this example the inflatable member has a cylindrical
configuration when expanded, as shown. The term cylindrical as used
in this context includes configurations that approximate a cylinder
even if not perfectly cylindrical, which may be the case if a
plurality of infusion spines are attached or engaging an outer
surface of the inflatable member and the balloon does not have a
perfectly cylindrical configuration when expanded. Additionally, an
inflatable member may still be considered to have a cylindrical
configuration even if the inflatable member has at least one end
region that is tapered or has any other configuration that is not
orthogonal with the long axis, such as the tapered distal and
proximal ends of the inflatable member that are shown in FIG. 1.
Additionally, for example, an inflatable member with a general
dumbbell configuration may be considered to have a cylindrical
configuration. Additionally still, when the description herein
describes inflatable members having cylindrical configurations when
expanded, it refers to the configuration the inflatable member
would take after being expanded outside of a patient. This is meant
to clarify that when expanded or inflated within a vessel of the
patient, there may be one or more anatomical restrictions that
prevent the inflatable member from transitioning to the cylindrical
configuration it would assume if expanded outside of a patient,
such as the configuration of the vessel wall in which the infusion
device is placed. In both scenarios, the inflatable member in these
examples is considered to have a cylindrical configuration when
expanded.
[0110] The infusion spines herein may be connected (directly or
indirectly) to the inflatable member, such as by bonding, adhesion,
or using any other suitable technique for securing the spines to an
inflatable member. In any of the examples herein, the spines may
alternatively not be connected to the inflatable member, but they
are still adapted to be expanded by inflation of the inflation
member due to their proximity to the inflatable member. For
example, the expandable infusion scaffold may be delivered on or
over a balloon-based catheter in a compressed low-profile delivery
state, and then expanded by dilating the balloon-based catheter at
the intended location within the vessel.
[0111] FIG. 1 shows an exemplary inflatable member 150 and an
expandable infusion scaffold 110, both in an expanded state or
configuration. For delivery, the expandable infusion scaffold is in
a collapsed delivery configuration in which the infusion spines are
closer to adjacent spines than in the expanded state, such as shown
in FIG. 11A. It is understood that FIGS. 11A-11D are an alternative
embodiment, and the reference to FIG. 11A is meant to illustrate an
infusion scaffold in a collapsed delivery configuration (or at
least a configuration in which it is not fully expanded). During
delivery, the inflatable member is also in a lower profile
unexpanded (and uninflated) collapsed delivery configuration. The
internal volume of the inflatable member is also less in the
delivery state than in the deployed state. Once the infusion device
is delivered to the target location with a vessel, the inflatable
member is inflated, which pressurizes the inflatable member. This
expansion of the inflatable member causes the inflatable member to
increase in a radial dimension and apply a force to the plurality
of infusion spines that are disposed around the inflatable member.
This causes the spines to expand radially and which also causes the
relative circumferential distance between the spines to increase,
an example of which is shown in FIG. 11C. The expandable infusion
scaffold is thus expanded towards the vessel wall by inflating and
expanding the inflatable member.
[0112] The inflatable member may have a variety of collapsed states
or configurations. For example, the inflatable member may be folded
in one or more locations to facilitate its collapse, while in other
embodiments the inflatable member may not have a particular or
well-defined collapsed state.
[0113] The inflatable members herein are sized and configured such
that when expanded, the plurality of infusion spines will be moved
radially outward and in contact or substantial contact with the
vessel wall. It is understood that due to some variability in
vessel wall size, some portion of any of the infusion spines may
not make direct contact with vessel wall. The inflatable member may
be sized such that it may have a deployed diameter that is larger
than an intended vessel size to help ensure that the infusion
spines are in contact or substantial contact with the vessel wall.
Maintaining sufficient pressure in the inflatable member such that
the infusion spines are in substantial contact with the vessel wall
can help support the needles as they are deployed and pierce
through the vessel wall, which is described in more detail
below.
[0114] Any of the expandable scaffolds herein may have infusion
spines that are optionally equidistantly spaced apart along their
lengths, an example of which is shown in FIG. 1. For example, two
infusion spines may be spaced apart 180 degrees around the
inflatable member when the scaffold and infusion spines are
expanded. Alternatively, three infusion spines may be spaced apart
120 degrees around the inflatable member when the scaffold and
infusion spines are expanded. Alternatively, four infusion spines
may be spaced apart 90 degrees around the inflatable member when
the infusion spines are expanded, and so forth. In the collapsed
delivery state, the infusion spines of the scaffold can also have
the same general relative relationship even though they are closer
together and not spaced as far apart.
[0115] While equal spacing between spines may in some applications
provide more complete delivery of the agent to the target tissue
around the vessel wall, in alternative examples the infusion spines
may not all be equidistantly spaced apart around the inflatable
member.
[0116] FIG. 16 illustrates a distal portion of an exemplary
infusion device, wherein the expandable scaffold is not shown for
clarity. In this example, the infusion device includes an
inflatable member 1650, which is shown inflated. A distal end of
inflatable member 1650 is coupled to inner shaft or member 1670,
and a proximal end of inflatable member 1650 is coupled to outer
shaft 1672. The inner and outer shafts 1670 and 1672 define
therebetween inflation fluid pathway 1674, which is in fluid
communication with an interior volume of inflatable member 1650.
The inner volume of inflatable member 1650 and fluid pathway 1674
are in fluid communication with a fluid inflation port, such as
inflation port 1333 or inflation port 1433 shown in FIGS. 13 and
14, and which are described in more detail below. Alternatively,
the inflatable members herein may be secured to the infusion device
in a manner that may be the same or similar to known balloon
angioplasty catheters, examples of which are described in U.S. Pat.
Nos. 4,782,834 and 10,086,175, and which are incorporated by
reference herein for all purposes.
[0117] Once the expandable inflation scaffold is expanded and in
contact with (or at least substantially in contact with) or
directly adjacent the vessel wall, each of a plurality of needles
are deployed outward from a radial opening in the infusion spine,
an example of which is labeled in FIG. 5 as opening 516. FIG. 1
illustrates a plurality of needles deployed from the expandable
infusion scaffold, and in this example shows a plurality of needles
deployed from each of the infusion spines. Needles 114a are shown
deployed from infusion spine 112a . Needles 114b are shown deployed
from infusion spines 112b . Needles 114c are shown deployed from
infusion spines 112c . In this merely illustrative example, there
are three needles shown deployed from each of the infusion spines.
In any of the embodiments herein, each infusion spine may be
associated with from two to fifty needles, all of which can be
deployed from a radial opening in the spine. As used in this
context, the term associated refers to needles that are within any
particular spine in a delivery state, and are deployable from that
particular spine to pierce the vessel wall.
[0118] When this disclosure refers to an infusion spine, it is
generally referring to one of the infusion spines of the expandable
scaffold. Additionally, when a feature is described with respect to
any particular or individual infusion spine, it is understood that
all of the infusion spines of any particular scaffold may also have
any or all of those features. The phrase infusion spine herein may
be used interchangeably with the term spine.
[0119] The needles in any infusion spine herein are generally
axially spaced apart, as shown in the examples of FIGS. 1, 2B and
5, for example. Spacing the needles axially apart can provide
maximum coverage of the therapeutic agent along the length of the
target lesion, which can increase the volume of tissue that may be
targeted by using the infusion devices herein. Additionally, by
having a plurality of infusion spines spaced around or about the
device, with each infusion spine having a plurality of
axially-spaced needles deployable therefrom, the infusion devices
herein can ensure or increase the likelihood of delivering the
agent to as much target tissue around the vessel as possible
without having to rotate or move the infusion device to provide the
desired circumferential coverage of the infused agent. It is of
course understood that the infusion devices herein may also be
moved in between episodes of agent delivery into the vessel wall.
In these instances, the needles may be retracted, and the infusion
device can be moved to a different location within the vessel or to
a different vessel. The inflatable member and the scaffold are
generally collapsed (at least partially) before moving the infusion
device to a new location.
[0120] In any the infusion devices herein, any two axially spaced
needles associated with an infusion spine may be spaced from 1 mm
to 40 mm apart, such as from 5 mm to 35 mm apart, such as from 10
mm to 30 mm apart, such as from 15 mm to 20 mm apart.
[0121] In any of the infusion devices herein, any adjacent pair of
three or more needles that are associated with a single infusion
spine may be equidistantly spaced apart axially. Alternatively, any
adjacent pair of three or more needles associated with a single
infusion spine may not be equidistantly spaced apart axially. It is
of course understood that any spine herein may only be associated
with two needles, and this paragraph is only related to spines that
may be associated with more than two needles.
[0122] In some illustrative embodiments, any of the infusion
devices herein may include from six to 50 needles total. For
example, an infusion device with three spines, each associated with
two needles, would have six needles total.
[0123] FIG. 1 illustrates an example in which the infusion spines
do not have the same lengths and do not have distal ends that
extend as far distally as at least one other distal end. In this
example, the lengths of all of the spines that are shown are
different, and none of their distal ends are axially aligned. In
any of the infusion devices herein, any of the spines may have
lengths that are the same such that their distal ends are axially
aligned with any other spine distal end. In this context, the term
length generally refers to the portion of the spine that overlaps
with the inflatable member rather than a portion of a spine that
may also extend proximally from the inflatable member.
[0124] The needles in different spines may or may not be axially
aligned. For example, the exemplary needle placement in FIG. 1
shows none of the needles being axially aligned with needles in
circumferentially adjacent spines. Any of the needles in the
different infusion spines, however, may be axially aligned.
Likewise, the infusion spines may also be axially aligned. For
example, the infusion device may have rows of needles, with the
rows spaced apart axially along the length of the infusion device,
an example of which is shown in FIG. 5. A row as used in this
context refers to two or more needles in different spines that are
axially aligned. The apertures in the top and bottom spines in FIG.
11C are axially aligned, which will cause the needles associated
with the top and bottom spines in FIG. 11C to be axially aligned
when deployed.
[0125] In any of the infusion devices herein, the number of needles
associated with each of the infusion spines is the same. FIG. 1
shows an example of this, with three needles per infusion spine. In
alternatives, the number of needles in each of the infusion spines
may not be the same. For example, one spine may be associated with
two needles, while a second spine may be associated with three
needles. Any of the infusion devices herein may have an expandable
scaffold with a plurality of spines, optionally wherein none of the
spines has the same number of needles as any other spine.
[0126] FIGS. 2A, 2B, 3A, 3B, 4A and 4B illustrate an exemplary
infusion device 200 with an expandable infusion scaffold 210 that
includes a plurality of infusion spines 212 (one labeled as 212a ).
Any suitable feature from FIG. 1 or described elsewhere herein may
be incorporated into infusion device 200. Infusion device 200 also
includes inflatable member 250 that when inflated and expanded
causes the expandable infusion scaffold 210 to expand, described in
more detail elsewhere herein. Each of the plurality of infusion
spines includes a plurality of radial openings or windows 216
(shown in FIG. 2A), through which the plurality of needles 214
(labeled as 214a , 214b and 214c for the different spines) extend
when deployed. FIGS. 2A (side view), 3A (end view) and 4A (end view
in an exemplary vessel 275) show the infusion device after the
inflatable member 250 has been inflated but with the needles not
yet deployed, while FIGS. 2B, 3B and 4B show exemplary needles 214
deployed through the openings in the infusion spines 212. FIG. 4B
illustrates the needles 214 piercing through the vessel wall 275
and extending into the adventitia "A." FIGS. 4A and 4B illustrate
intimal "I," medial "M," and adventitial "A" layers of the vessel.
Any other disclosure herein from any other example may be
incorporated into the examples in FIGS. 2A-4B.
[0127] Generally, the infusion spines herein include a lumen and a
plurality of openings or windows therein, such as openings 216 in
FIG. 2A. The needles herein are generally disposed within an
infusion spine in a delivery state and are deployed from the
infusion spine out of one of the needle openings to pierce the
vessel wall. The needles herein may be disposed within and deployed
from the infusion spines in a variety of ways. Additionally, the
needles herein may be in fluid communication with a fluid source in
a variety of ways. The examples below are meant to be illustrative.
The needles herein associated with an infusion spine may be
deployable at the same time. The needles herein associated with an
infusion spine may be deployable by moving them together as a unit,
such as if they are coupled to a common axially movable member
within the spine. The needles herein associated with an infusion
spine may be separately deployable from within the spine.
[0128] Each of the plurality of needles associated with an infusion
spine may be coupled to an axially moveable member that is disposed
within the infusion spine, such that axial movement of the axially
moveable member relative to the infusion spine causes the axial
movement of the needle relative to the infusion spine.
[0129] In some embodiments herein, the needles associated with an
infusion spine are all adapted to move together in unison upon the
axial movement of an axially movable member, which may be referred
to in this context as a common axially moveable member. In some
alternatives, the needles associated with an infusion lumen may be
axially moved independently from one another, such as when each
needle is coupled to its own or individual axially moveable member
within the spine.
[0130] In some embodiments the axially moveable member (which may
be referred to as a rail track) is a separate structure that does
not specifically define a fluid lumen, although in these examples
the axially moveable member may house therein one of more fluid
lumens that are in fluid communication with one or more needles.
Additionally, in these embodiments, one or more fluid lumens within
the axially movable member may also be moved axially relative to
the infusion spine in response to axial movement of the axially
moveable member.
[0131] FIG. 5 illustrates an exemplary infusion device 500, which
may incorporate any of the disclosure related to infusion device
100 shown in FIG. 1 or any other feature described herein. Infusion
device 500 includes an expandable infusion scaffold 510, which
includes a plurality of infusion spines 512a , 512b (a third
infusion spine 512c is not visible in the side view of FIG. 5). The
infusion spines 512a and 512b each include a plurality of openings
516 through which the needles are deployed. In this example, each
of the spines is associated with three needles as shown, but more
or fewer may be associated with each infusion spine as is described
elsewhere herein.
[0132] FIGS. 6A-6F illustrates exemplary features of an exemplary
needle subassembly 620 (any of which may be referred to herein as a
rail track subassembly, and vice versa), with the infusion spine
not shown for clarity. Rail track subassembly 620 is configured to
both move the needles to deploy them from the infusion spine
openings, as well as provide housing for one or more fluid lumens
that are in fluid communication with one or more needles, and such
fluid communication to the needles to deliver the agent into the
vessel wall when the needles are deployed from the openings in the
infusion spine. FIG. 6E illustrates an exemplary needle 614a
coupled to fluid lumen 622 with an optional coupler 624. In other
embodiments any of the needles herein may be directly connected to
a fluid lumen. The needle 614a and fluid lumen 622, as shown in
FIG. 6E, are then positioned within rail 623, which is shown alone
in FIG. 6F. Rail 623 is an example of an axially movable member
that is configured to be axially moved to cause the axial movement
of a plurality of needles. Rail 623 is also sized and configured to
house therein one or more fluid lumens, in this case fluid lumen
622'' and fluid lumen 622'', as shown in FIG. 6D. As shown in FIG.
6D, in this example each needle is in fluid communication with a
distinct or individual fluid lumen, but they are coupled to rail
623 such that they move axially together in unison when rail 623 is
moved. With respect to FIG. 6E, each needle is coupled to an
individual fluid lumen as shown, then advanced through rail 623 and
coupled thereto, as is shown in FIGS. 6A-6D. FIG. 6D illustrates
one example of a plurality of individual fluid lumens 622'' and
622''' housed or disposed within a lumen of rail 623. Rail 623, at
least in this exemplary embodiment, can be moved axially to axially
move all of the needles, as well as serve to house the individual
fluid lumens therein.
[0133] The needle subassembly 623 shown in FIG. 6A can then be
positioned in one of the infusion spines, such as by front loading
or back loading. When the needle subassembly 620 is loaded into an
infusion spine, the needles will deflect radially inward towards
the openings 621 that are labeled in FIG. 6F, and the needle
subassembly may be positioned in the infusion spine such that the
needles are just proximal to the infusion spine openings 616,
labeled in the exemplary spine 612 shown in FIG. 6G.
[0134] Any of the needles herein may be formed with a natural bias
towards a deployed configuration in which the needles extend at
least partially radially outward, such as is shown in FIGS. 6A, 6B,
6C, 6D and 6E. When the needles are collapsed radially down or
inward for delivery, they may or may not have a perfectly linear
configuration due to their naturally biased and curved deployed
configuration. When collapsed for delivery, any of the needles may
retain a slight curvature in their configuration.
[0135] The use of the term rail herein does not necessarily impart
any structural limitations. The rails herein may be elongate
members that are sized and adapted to be moveable within an
infusion lumen to facilitate the movement of one or more needles.
Any of the rails herein may be a tubular member or partial tubular
member, such as rail 623 shown in FIGS. 6A-6F, or any other
elongate member (with or without a lumen) that is sized and
configured for axial movement within a spine.
[0136] As part of an exemplary manufacturing of a rail track
assembly, the needle and corresponding fluid lumen may be
front-loaded through the rail. A coupler (e.g., 624'' or 624'''),
if used, may be secured (e.g., bonded, welded, or otherwise secured
thereto) to the needle and fluid lumen as shown in FIG. 6E. The
rail openings 621 may be formed by removing sections of the
material of rail 623, which may itself be an elongate tubular
member, such as a stainless steel or nitinol tubular member.
[0137] Each infusion spine in the exemplary infusion device shown
in FIGS. 6A-6F is associated with at least three subcomponents or
subassemblies--the infusion needle(s), the infusion lumen(s), and
the rail track subassembly housing the respective infusion
needle(s) and infusion lumen(s).
[0138] In any of the examples herein, any of the fluid delivery
lumens may have an outer diameter from 0.001 inches to 0.01 inches,
for example. Fluid delivery lumens herein may also be referred to
herein as fluid lumens.
[0139] In any of the examples herein, any of the axially moveable
members (such as any of the rails) may have an outer diameter from
0.005 inches to 0.05 inches.
[0140] In any of the examples herein, any of the axially moveable
members may have openings (e.g., openings 621) that are axially
spaced from 5 mm to 80 mm apart, such as from 10 mm to 50 mm
[0141] In any of the examples herein, any of the axially moveable
members may have openings (e.g., openings 621) that have a length
from 2 mm to 20 mm.
[0142] In any of the examples herein, any of the spines may have an
outer diameter from 0.01 inches to 0.08 inches.
[0143] In any of the examples herein, any of the spines may have
openings (e.g., openings 216, 516) that are axially spaced apart
from 5 mm to 80 mm.
[0144] In any of the examples herein, any of the spines may have
openings (e.g., openings 216, 516) may have openings with a
diameter or length dimension from 0.05 mm to 10 mm.
[0145] FIGS. 7A and 7B, in top and side views, respectively,
illustrate an exemplary rail track subassembly 720 (spine not shown
for clarity), with three exemplary needles in deployed
configurations. Any of the features from assembly 620 of FIG. 6A
may be incorporated into assembly 720. Rail track subassembly 720
includes rail 723, which has openings 721 therethrough (only one of
which is labeled in FIG. 7A), and in this example there are three
openings 721 in rail 723. Needles 714a are coupled to individual
and distinct fluid lumens 722, optionally via couplers 724 but
alternatively directed connected thereto, which may be secured to
rail 723 to secure the needle to the rail 723 and provide unitary
axial movement of the needles 714 (which are individually labeled
as 714a', 714a'', and 714a''').
[0146] FIGS. 7A and 7B also illustrate how fluid lumens may extend
through the rail 723 lumen. For example, fluid delivery lumen 722'
is in fluid communication with needle 714a' and extends through
rail 723. Fluid delivery lumen 722' extends adjacent to central
needle 714a'' and fluid delivery lumen 722'', as shown in the
central regions of FIGS. 7A and 7B. In the proximal region shown in
FIG. 7A and 7B, all three fluid delivery lumens 722', 722'' and
722''' are adjacent one another within the rail 723. Any of the
fluid delivery lumens herein may include a bend or deviation in its
path such that it can pass next to a different needle and its
associated fluid delivery lumen, which is shown in FIGS. 7A and 7B.
In this manner, the needles can extend in the same direction from
the spine, which can be seen in the top view of FIG. 7A. In the top
view of FIG. 7A, the needles are all extending upward, or out of
the page.
[0147] In some embodiments, the axially movable member may also
define a fluid lumen that is in fluid communication with one or
more needles, such as in the example shown in FIG. 8. FIG. 8
illustrates an exemplary needle assembly 820 shown within an
exemplary spine 812a , which includes top or radially outward
openings 816. Needle assembly 820 is an axially movable member that
in this embodiment also defines a fluid delivery lumen as shown
that is in fluid communication with all of the needles 814a .
Needles 814a are shown in their deployed configuration (tissue not
shown for clarity) extending out of the spine openings 816. Any
other feature from any other example herein may be incorporated
into the features shown in FIG. 8, including use with any other
inflatable member herein.
[0148] In some alternative embodiments, the needles may be
extending from an infusion spine when the infusion device is in a
collapsed delivery configuration. FIGS. 11A-11D illustrate such as
example, with infusion device 1100 shown in a collapsed
configuration in FIGS. 11A and 11B, and expanded in FIGS. 11C and
11D (the needles are shown only in FIGS. 11B and 11D for clarity).
FIGS. 11A and 11C are side views, and FIGS. 11B and 11D are end
views. As shown in FIG. 11B, needles 1114a are tucked within folded
sections of inflatable member 1150 in the collapsed delivery state.
Inflatable member 1150 may include sections of the material that
are easier to fold to facilitate the predictable folding of the
balloon around the infusion spines and needles, as shown in FIG.
11B. An exemplary guidewire 1154 disposed within guidewire lumen
1155 is also shown, which may be used to deliver any of the
infusion devices herein using known guidewire delivery techniques
and methods. FIGS. 11A and 11B also illustrate generally collapsed
delivery configurations of spines and an inflatable member, which
may be incorporated with any of the other examples herein wherein
the needles are not deployed until the inflatable member is
expanded. The inflatable members herein need not, however, collapse
in a predictable manner as is shown in FIG. 11B.
[0149] Any of the lumens herein (e.g., infusion spine lumen, rail
lumen, and/or fluid lumen) may have or benefit from having one or
more regions with sufficient flexibility to allow for the infusion
device to be delivered to the target location in the vasculature.
For example, any of the lumens herein may incorporate a tubular
member with one or more regions with one or more cuts therein
(e.g., a laser cut or other technique) that imparts some degree of
flexibility along at least a portion of its length. Cuts made in
any tubular member herein may be in the form of, for example
without limitation, including combinations thereof, an at least
partial spiral pattern, an at least partial brick pattern, or any
other pattern that increases the flexibility of the infusion lumen.
More than one pattern may be implemented in any lumen (spine lumen,
rail lumen, fluid delivery lumen, etc.), and the shape or
configuration of a cut pattern may change along the length of the
lumen.
[0150] Any of the fluid lumens herein may optionally include a
non-permeable membrane on one or both of an inside or the outside,
such as an elastomeric membrane (e.g., urethane, silicone, or
hydrogel), which can prevent fluid from leaking therethrough. For
example, any lumens that may include or more cuts therein (e.g.,
laser cut tubes) may include one or more membranes secured thereto
to maintain integrity.
[0151] Any of the lumens herein may comprise, for example, any
combination of nitinol, stainless steel, polymer tubing, polyimide,
braided tubing, or other structural material. Any of the lumens
herein may be constructed to provide the desired fluid integrity
and/or flexibility when being delivered to the target delivery
site.
[0152] In some examples, sections of the infusion spine(s) in
between needle regions may be more flexible to provide more
flexibility at those locations, while the spine regions where the
needles are deployed may have relatively higher stiffness to aid
the needle piercing through tissue or calcifications. FIG. 12
illustrates an exemplary infusion device 1200, with inflatable
member 1250 and scaffold 1210 in expanded configurations or states.
Scaffold 1210 includes a plurality of spines 1212a and 1212b .
Spine region 1207 may be configured to be more flexible than distal
region 1209 and proximal region 1211 that are axially adjacent to
region 1207. Needles may be present in regions 1209 and 1211, for
example. Each spine may have a plurality of regions 1207 that are
more flexible that other sections of the spine, any of which may be
axially spaced apart with less flexible spine regions in between,
which is described in more details with respect to FIG. 13.
[0153] FIG. 13 illustrates an exemplary infusion device 1300 shown
with expandable member 1350 in an expanded configuration and a
plurality of needles 1314 (only one of which is labeled) deployed
from openings in spines 1312 (only one spine is labeled, and there
may be additional spines and associated needles). In this example,
the spines include first regions 1312' at and around the locations
where needles extend through openings therefrom, and regions 1312''
axially adjacent and optionally in between first regions 1312'.
First regions 1312' may be considered to include the spine openings
from which the needles extend. First regions 1312' may be less
flexible than regions 1312''. This arrangement may provide
sufficient stiffness to the spine region where the needle extends
therefrom, helping the needle pierce through tissue (or
calcifications), while regions 1312'' can provide more flexibility
for tracking and delivery. Any of the spines herein may include
first and second regions with different stiffness as in the example
of FIG. 13.
[0154] As is set forth herein, the scaffold may or may not be
attached to the inflatable member. In examples in which the
scaffold (including the spines) is attached to the inflatable
member, the spines may be secured to the inflatable member along
their entire length, or less than their entire length. In some
devices, the individual spines may be attached to the inflatable
balloon at a plurality of axially spaced sections or regions along
its length, and not directly attached to the inflatable member at
one or more axially-spaced sections or regions along its length.
For example only, with respect to FIG. 13, the plurality of spines
may be attached to the inflatable member 1350 in regions 1312', but
not attached directly to the inflatable member 1350 in regions
1312''. Not directly attaching the spines to the inflatable member
in regions 1312'' may allow for more movement and flexibility in
the more flexible regions 1312'', which may provide more
flexibility overall in the region of the scaffold, which can help
when delivering the device.
[0155] FIG. 13 also illustrates exemplary rail track or needle
subassemblies 1320' and 1320'' within corresponding spines, which
may include a plurality of needles and one or more fluid lumens,
which are described in more detail herein (there may be as many
subassemblies as there are spines).
[0156] FIG. 13 also illustrates an exemplary proximal region of
infusion device 1300. The proximal region includes an adaptor 1339,
which in this example is a three-port adaptor. Adaptor 1339
includes an inflation port 1333 configured to couple to a fluid
delivery device (e.g., Inflation Device commonly used with
dilatation catheters) to deliver an inflation fluid to inflate
expandable member 1350. Adaptor 1339 also houses a guidewire lumen
1341 therein, which is sized and configured to receive guidewire
1337 therein, which may facilitate delivery of any of the infusion
devices herein over a guidewire. Adaptor 1339 also includes an
actuator coupling region 1335, which may be sized and configured to
couple to an actuation member, an example of which is described in
more detail with respect to FIG. 14.
[0157] Any other feature from any other infusion devices herein may
be incorporated into the example in FIG. 13, and vice versa.
[0158] FIG. 14 illustrates an exemplary proximal region of an
infusion device, any features of which may be incorporated into any
of the infusion devices herein. The proximal region includes
optionally three-port adaptor 1439, which may house a guidewire
lumen 1441 therein that is adapted to receive a guidewire 1437
therein for guidewire delivery. In this example, the proximal
handle region includes an actuator 1482 that is in operational
communication with the rail track subassemblies to facilitate axial
movement thereof, which are generally labeled 1420, but it is
understand there may be two or more (such as the three that are
shown). The rail track sub-assemblies 1420 may have proximal ends
that are attached (directly or indirectly) to an inner surface of
actuator 1482, such as by using any suitable bonding technique,
which thereby causes the rail track subassemblies to move distally
upon distal actuation of the actuator 1482, to thereby deploy the
needles from the spine openings. In this example, actuator 1482 has
a plunger type construction, with a distal member 1484 that is
sized to interface with inner surface 1486 to stop further movement
of the actuator 1482. This stop mechanism is an example of a stop
mechanism that is adapted to control the distal travel of the
actuator 1482. This can be set at any desired distance to control
the amount of needle deployment. The proximal portion also includes
infusion port 1435, which is adapted to be coupled to a source of
therapeutic agent to facilitate delivery thereof through the one or
more delivery lumens and to the needles. A proximal region of an
exemplary spine 1412 is also shown in FIG. 14, but it is understood
that there may be as many spines as there are rail track
sub-assemblies. Any other feature from any other infusion devices
herein may be incorporated into the example in FIG. 14, and vice
versa.
[0159] FIGS. 15A and 15B are proximal end views of the proximal
region illustrated in FIG. 14, including three-port adaptor 1539,
with FIG. 15B highlighting proximal ends of rails 1523 and fluid
delivery lumens 1522 housed therein. FIG. 15A illustrates inflation
port 1533 generally, guidewire lumen 1541 generally, and proximal
ends of rails 1523 and fluid delivery lumens 1522 therein. FIG. 15B
focuses on exemplary rails 1523', 1523'', and 1523'''. In this
example each rail 1523 houses therein three fluid delivery lumens,
1522', 1522'', and 1522''', respectively. The fluid delivery lumens
are in fluid communication with the needles, such that a
therapeutic agent may be delivered into the proximal ends of the
fluid lumens 1522 and to the needles. Any other feature from any
other infusion devices herein may be incorporated into the example
in FIGS. 15A and 15B, and vice versa.
[0160] Any of the needles may be deployable using an external
component (that remains outside the patient) that is operatively
coupled to one or more needles of the infusion device. In some
exemplary embodiments, all of the needles in the infusion device
are deployable in unison, and may be operatively coupled to a
common deployment actuator, an example of which is shown in FIG. 14
and described above. It is understood that other mechanisms may be
used to deploy the needles, either in unison or not in unison. For
example, the external portion (which may be referred to herein as a
proximal region of the infusion device) may have more than one
actuator, each of which may control a subsection of the plurality
of needles.
[0161] Any of the needles herein may be referred to as
microneedles, and may be comprised of nitinol, stainless steel,
and/or a combination of nitinol, stainless steel, and other
materials that adapt the needle to be able penetrate into the
vessel wall. Any of the needles herein may range in length from 0.1
mm-3 mm and in size from 20 gauge to 38 gauge, for example. For
clarity, the lengths and/or size of individual needles may vary
relative to any adjacent needles, either in the same spine or
different spines. Furthermore, the relative inner diameter, outer
diameter, and wall thickness of the individual needles may be
uniform relative to adjacent needles, or they may vary relative to
any adjacent needles, either in the same spine or different spines.
Additionally, any of the needles herein may have at least one of an
inner diameter ("ID") and an outer diameter ("OD") that varies
along the length of the needle.
[0162] Any of the expandable infusion scaffolds herein may be
configured to be an integral part of the balloon system.
Alternatively, any of the expandable scaffolds herein may be
configured as an independent structure that works `in synergy` with
a balloon-based system but is not attached to the balloon system
and is not integral to such. As is described elsewhere herein, and
incorporated into these embodiments, the expandable scaffold may
take the form of various potential configurations designed to
enable infusion lumen structural support and communication with the
microneedles while also facilitating circumferential and
longitudinal infusion of the intended agent to the target
lesion.
[0163] In any of the infusion devices herein, the expandable
infusion scaffold may comprise two or more infusion lumens
extending in a longitudinal (axial direction; proximal-distal) or
non-longitudinal pattern along at least a portion of the length of
the balloon that is either integral to, or to be used in synergy
with the infusion scaffold. Longitudinal in this context refers
generally to at least a portion of an infusion lumen that is
parallel with a longitudinal axis of inflatable balloon. In some
embodiments, the scaffold may comprise two or more infusion lumens
extending in a non-longitudinal pattern along at least a portion of
the length of the balloon that is either integral to, or to be used
in synergy with the infusion scaffold. Any of the infusion lumens
herein may have one or more portions that extend longitudinally and
one or more portions that extend non-longitudinally. Examples of a
non-longitudinal configuration or pattern in this context include a
spiral or helical configuration or other non-longitudinal pattern.
For the sake of illustration, the following describes infusion
lumens that run or extend longitudinally (axially) along at least a
portion of the length of the scaffold. "Longitudinally" (and
derivative thereof) and "axially" (and derivatives thereof) are
generally used synonymously herein. "Linear" may also be used with
longitudinal and axial when made in reference to a linear
longitudinal or linear axial configuration, such as if parallel to
a longitudinal (or long) axis of the infusion device or an
inflatable member.
[0164] In some exemplary embodiments herein (such as in FIG.
6A-6F), the microneedles are secured (e.g., directly attached, or
attached via one or more intermediate components) to a rail or
other elongate member that is loaded into and disposed in the
infusion spine. Exemplary benefits of this design include, but are
not limited to, 1) protection of the balloon, guide catheter,
delivery sheath, vessel wall, or any other structure in proximity
to the microneedles by isolating the sharp needle points during
delivery to the lesion site and/or removal from the lesion site; 2)
the ability to use the scaffold to facilitate controlled dilation
and optionally micro-penetration of the vessel wall ahead of
deploying the infusion needles; and/or 3) added structural support
during deployment of the needles. Needles that are secured to
tracks or other elongate members herein may also enable the depth
of needle deployment to be controlled or adjusted. For example, any
of the rails herein may be in operable communication with an
external portion (e.g., as shown in FIG. 13-15B), wherein one or
more actuators (e.g., rotatable knobs, axially movable sliders) in
the external portion may be adapted to be actuated to control the
relative degree of motion of the rail track subassembly (e.g.,
axial translation), and thereby control the length of the needles
that exit radially or somewhat radially outward from the infusion
spine.
[0165] Any of the microneedles herein may also have one or more
side holes or ports formed therein in addition to or alternatively
to a port at a distal end of the needle. In variations of any of
the embodiments herein, the needles may only have side holes and
may not have a distal hole. Side ports or holes may enable
concurrent infusion at more than one depth within the vessel wall.
Exemplary benefits of having one or more side holes in the needle
include, but are not limited to, enabling local delivery of the
therapeutic agent or diagnostic agent into the medial layer of the
vessel as well as deep into the adventitial layer of the
vessel.
[0166] Any of the rails herein may also be referred to as a support
shaft, any of which may be solid or have a lumen therein. The rails
herein may be made of any number of potential materials such as
nitinol or stainless steel onto which the needles can be bonded or
attached (directly or indirectly), and which may optionally be
slatted or laser cut along at least a portion thereof to provide
enhanced trackability. Additionally, any of the rails herein may be
comprised of more than one type of material along the length of the
device. Any of the individual needles herein may include a first
end that may be straight or linear and the other free end may be
pre-formed (e.g., heat set) to take a perpendicular or near
perpendicular configuration (e.g. 60-120 degrees) to the surface of
the vessel when the needle is in its deployed state. A straight or
linear section of a needle may be individually secured (e.g.,
directly attached) to an axially moveable member such as a rail,
allowing the free end to be free to deform and assume its deployed
shape (e.g., pre-set shape) as it exits the infusion spine
opening.
[0167] Axial spacing between needles may be optimized based on the
desired anatomical coverage of the agent within the vessel wall,
along with spacing to facilitate optimal delivery and trackability
of the infusion device to the target lesion.
[0168] In any of the embodiments herein, any number of distal ends
of individual infusion spines may be axially staggered (or axially
offset, or spaced axially) relative to any other infusion spine
distal ends, further enhancing trackability of the distal end
region of the device (an example of which is in FIG. 1). In any of
the embodiments herein, at least two lumens may have distal ends
that are axially aligned, but those distal ends may be axially
spaced from one or more other infusion lumen distal ends. In this
fashion, any number of infusion lumen distal ends may be axially
aligned or axially staggered relative to any number of other
infusion lumen distal ends. In the exemplary embodiment shown in
FIG. 1, the infusion lumens are circumferentially staggered or
off-set around or about the scaffold and inflatable member, as well
as having distal ends that are axially offset. In the exemplary
embodiment shown in FIG. 5, the infusion lumens are
circumferentially staggered or off-set around or about the scaffold
and inflatable member, but axially aligned at the distal ends.
[0169] As described elsewhere herein, the individual rail remains
inside the respective infusion spine, serving as a mechanism by
which to advance and retract the microneedles. One or more openings
(or windows) in the infusion spine provide guidance (or a pathway)
for the microneedle(s) to exit the infusion spine and can also be
adapted to function as added structural support as the needle
penetrates into the vessel wall. Any of the infusion spine windows
or openings herein (which may also be described as "space," and as
such may be defined by surrounding structure in the infusion spine,
for example) may be configured with a slight tented structure
around the perimeter thereof to offer additional guidance and
structural support, or they may be configured to be flat or concave
relative to the cross-section of the infusion spine. The infusion
spines herein may also be configured to have a structure located
just distal or just proximal to an opening or window (the structure
may define the surface(s) of the "opening") that is configured to
function as an additional intraluminal guide or ramp as the needle
advances out of the infusion spine opening.
[0170] In any of the examples herein, advancement and retracting of
one or more rails or support shafts, to which one or more
microneedles are secured (directly or indirectly), may be enabled
through a mechanical turn dial (or any other rotatable handle
actuator) or any other mechanical actuation mechanism with
intuitive settings to guide the user during deployment and
retraction of the microneedles.
[0171] In any of the examples herein, after the microneedles are
deployed, infusion may be initiated using, for example only, a
controlled mechanism of volume delivery based on the lesion length
and desired volume of agent infusion.
[0172] In any of the examples herein, the number of needles per
infusion spine may be of any desired number, inclusive but not
limited to the range of two to fifty microneedles per infusion
spine. In some embodiments, the microneedles may be attached or
otherwise secured by techniques such as welding, soldering,
mechanical crimping, adhesive, or other techniques to a rail and/or
fluid delivery lumen. The needles herein may be bonded directly to
a fluid delivery lumen, or they be bonded to one or more
intermediate elements such as a coupler. Further, as is described
in more details elsewhere herein, the depth of needle deployment
may be controlled or adjusted, for example, by utilizing one or
more controls in an external portion of the device that may be
adapted to control the relative degree of motion of the rail track
or support shaft subassembly and thereby control the length of
needle that exits radially or somewhat radially outward from the
device.
[0173] In some examples herein, each needle associated with a spine
is in fluid communication with an individual and separate fluid
delivery lumen. This may offer several advantages including, but
not limited to 1) enabling more tightly controlled dosing through
the individual infusion needs; 2) enabling more tightly controlled
direction of fluid delivery, and 3) enabling simultaneous delivery
of separate complementary therapy agents.
[0174] Any of the fluid delivery lumens herein may have one of a
variety of cross-sectional shapes inclusive of, but not limited to,
round and kidney shaped. This may be done to help reduce the
overall profile of the needle assembly without compromising the
volume of agent that can be infused through the lumen(s). FIG. 10
is a sectional view through one of three needles associated with a
particular spine (spine not shown for clarity). FIG. 10 shows
exemplary rail 1023, exemplary needle 1014 and fluid delivery
lumens 1022 and 1024 that are in fluid communication with a second
and third needle, respectively, which are not shown as they are
axially spaced from needle 1014. For example only, needle 1014 may
be a proximal needle with two additional needles distal to needle
1014. In this example, rail 1023 is mechanically crimped and has a
non-circular outer profile as shown. Fluid delivery lumens 1022 and
1024 have non-circular sectional shapes, which in this example can
be approximated to kidney shaped, and may be crescent shaped in
other embodiments. Alternatively, FIG. 9 illustrates a cross
section of a rail track assembly 920 (920 is also pointing to the
rail element) including needle 914a and fluid delivery lumens 922'
and 922'', wherein the cross section of the rail and the fluid
delivery lumens are circular.
[0175] Any of the lumens herein may be comprised of one or more
materials inclusive of, but not limited to, polyimide, polymer,
nitinol, composite, and/or combination thereof. Any of the fluid
delivery lumens and needles within a rail may be secured using a
variety of potential techniques such as, without limitation,
crimping, welding, soldering, potting, adhesive, or other
techniques inclusive of a combination thereof. In any of these
embodiments, any single needles may thus be in fluid communication
with a unique or distinct fluid delivery lumen that is only in
fluid communication with that particular needle and not any other
needles. In alternatives, a plurality of needles may be in fluid
communication with a first fluid delivery lumen, and a different
needle may be in fluid communication with a second fluid delivery
lumen.
[0176] In any of the embodiments herein wherein the expandable
scaffold is attached to the inflatable member, the scaffold and/or
individual spines may be bonded to the balloon or secured between
the balloon and an additional thin walled layer of material, for
example.
[0177] As disclosed elsewhere herein, in any of the embodiments
herein, the infusion scaffold may be independent from the expansion
balloon (not integrated therewith), yet is adapted to function in
synergy with the expansion balloon. In these embodiments, the
scaffold may be deployed prior to inflation of the balloon. For
example, upon retraction of an outer scaffold sheath, the scaffold
may be adapted to be self-expanding, partially self-expanding, or
non-self-expanding. The expansion balloon may be then advanced
within the scaffold and dilated to continue to or fully expand the
infusion scaffold. The scaffold structure may be deployed passively
by retracting an outer sheath (as would a self-expanding stent) or
by a mechanical means activated in the handle of the device. The
infusion scaffolds herein may be compatible with any off-the-shelf
angioplasty balloon, and the balloon may optionally be drug-coated
or uncoated. In some of these embodiments, the scaffold may be
pre-loaded onto the expansion balloon (yet not attached thereto),
with both delivered to the target lesion in unison, and the
infusion scaffold may then be expanded as the dilatation balloon is
expanded. The scaffolds herein may thus be at least partially
deployed with an expansion balloon, but need not be bonded
thereto.
[0178] In alternative examples, the scaffolds herein may be
independent without the use of an expansion balloon. For example,
the scaffold may be deployed into a target vessel and expanded
radially. Radial expansion may be accomplished passively by
retracting an outer sheath (as would a self-expanding stent that is
commonly used in the field) and/or by a mechanical mechanism
activated in the handle of the device. In an exemplary embodiment,
the infusion scaffold is configured and adapted to be expanded
using a mechanical mechanism or approach that compresses parts of
the infusion scaffold longitudinally. The needles may then be
advanced, as is described in more detail herein.
[0179] In some methods of use, the expandable scaffolds herein may
be delivered about an inflatable member, either attached to the
balloon or not. After the inflatable member and scaffold are
delivered to the target location within a vessel, an inflation can
be delivered to an inner volume within the inflatable balloon to
cause its expansion. This balloon expansion applies a force to the
expandable scaffold, causing the scaffold and spine to radially
expand towards the vessel wall. The balloon can be expanded until
the infusion device makes contact with the vessel wall. The needles
may then be deployed from the spine opening and through the vessel
wall, which is described in more detail elsewhere herein, and
optionally by distally advancing one or more rails within the
spines. The agent may then be delivered from a fluid source,
through the one or more fluid delivery lumens, and out of the one
or more needle ports and into the vessel wall optionally including
the adventitia. The needles may be retracted by retracting one or
more rails, and the scaffold and inflatable member may then be
collapsed. The infusion device may then be recaptured (e.g., within
a sheath or guide catheter) within a delivery sheath and removed
from the patient or delivered to another location for a subsequent
agent delivery process.
* * * * *