U.S. patent application number 11/335317 was filed with the patent office on 2006-08-24 for material delivery system.
This patent application is currently assigned to By-Pass, Inc.. Invention is credited to Mordechay Beyar, Oren Globerman, Rami Keller.
Application Number | 20060190022 11/335317 |
Document ID | / |
Family ID | 35784260 |
Filed Date | 2006-08-24 |
United States Patent
Application |
20060190022 |
Kind Code |
A1 |
Beyar; Mordechay ; et
al. |
August 24, 2006 |
Material delivery system
Abstract
A method for injecting a therapeutic agent into a target tissue,
the method comprising: (a) providing an expandable member; (b)
positioning said expandable member in proximity to the target
tissue; (c) Introducing the therapeutic agent into the expandable
member until a desired pressure is achieved; and (d) creating a
plurality of small apertures in the expandable member.
Inventors: |
Beyar; Mordechay; (Caesarea,
IL) ; Globerman; Oren; (Kfar-Shmaryahu, IL) ;
Keller; Rami; (Tel-Aviv, IL) |
Correspondence
Address: |
WOLF, BLOCK, SCHORR & SOLIS-COHEN LLP
250 PARK AVENUE
NEW YORK
NY
10177
US
|
Assignee: |
By-Pass, Inc.
Orangeburg
NY
|
Family ID: |
35784260 |
Appl. No.: |
11/335317 |
Filed: |
January 19, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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PCT/IL05/00749 |
Jul 14, 2005 |
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11335317 |
Jan 19, 2006 |
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60587335 |
Jul 14, 2004 |
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60599884 |
Aug 10, 2004 |
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60603262 |
Aug 23, 2004 |
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60675477 |
Apr 28, 2005 |
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Current U.S.
Class: |
606/192 |
Current CPC
Class: |
A61B 2018/00708
20130101; A61M 2025/105 20130101; A61M 25/1027 20130101; A61B
2018/00238 20130101; A61M 2025/1088 20130101; A61B 2018/2211
20130101; A61B 2018/00678 20130101; A61B 2018/0066 20130101; A61B
2018/00642 20130101; A61B 2018/00863 20130101; A61B 2018/00744
20130101; A61B 2018/00345 20130101; A61B 2018/00672 20130101; A61M
25/10 20130101; A61B 2018/00029 20130101; A61B 2018/00023 20130101;
A61B 2018/266 20130101; A61F 2/958 20130101 |
Class at
Publication: |
606/192 |
International
Class: |
A61M 29/00 20060101
A61M029/00 |
Claims
1. A method for injecting a therapeutic agent into a target tissue,
the method comprising: (a) providing an expandable member; (b)
positioning said expandable member in proximity to the target
tissue; (c) introducing the therapeutic agent into the expandable
member until a desired pressure is achieved; and (d) creating a
plurality of small apertures in the expandable member.
2. A method according to claim 1, wherein said expandable member
includes at least one balloon.
3. A method according to claim 1, wherein (d) is performed after
(c).
4. A method according to claim 1, wherein (c) is performed after
(d).
5. A method according to claim 1, wherein the desired pressure is
at least 15 atmospheres.
6. A method according to claim 1, wherein the desired pressure is
sufficient to cause said therapeutic agent to exit through said
apertures at a speed of at least 20 meters/second.
7. A method according to claim 1, wherein the therapeutic agent
enters the target tissue intracellularly.
8. A method according to claim 1, wherein the target tissue is
located in a body lumen.
9. A method according to claim 1, wherein at least a portion of
said apertures are aimed transaxially with respect to said
expandable member.
10. A method according to claim 1, wherein at least a portion of
said apertures are aimed radially with respect to said expandable
member.
11. A method according to claim 1, wherein at least a portion of
said apertures are aimed axially with respect to said expandable
member.
12. A method according to claim 8, wherein said body lumen is a
blood vessel.
13. A method according to claim 1, wherein the therapeutic agent
includes a cytotoxic agent.
14. A method according to claim 1, wherein the therapeutic agent
includes a fibrotic agent.
15. A method according to claim 13, wherein said cytotoxic agent
includes an alcohol.
16. A method according to claim 15, wherein said alcohol includes
ethanol.
17. A method according to claim 13, wherein entry of said cytotoxic
agent into said target tissue blocks transmission of an electric
signal through said target tissue.
18. A method according to claim 17, applied to ameliorate Atrial
Fibrillation.
19. A method according to claim 1, wherein the therapeutic agent
includes a chemotherapeutic agent.
20. A method according to claim 1, wherein the target tissue is a
tumor.
21. A method according to claim 20, wherein the tumor is located on
an inner surface of a urinary bladder.
22. A method for reducing a toxic effect of a therapeutic agent on
a non-target tissue, the method comprising: (a) providing an
expandable member; (b) positioning said expandable member in
proximity to a target tissue; (c) introducing an amount of
therapeutic agent into the expandable member until a desired
pressure is achieved; and (d) creating a plurality of small
apertures, in the expandable member; wherein said amount is
sufficient to exert a physiologic effect on cells of said target
tissue but insufficient to exert an effect on cells lying at a
distance greater than a selected distance from said target
tissue.
23. A method according to claim 22, wherein said expandable member
includes at least one balloon.
24. A method according to claim 22, wherein (d) is performed after
(c).
25. A method according to claim 22, wherein (c) is performed after
(d).
26. A method according to claim 22, wherein the therapeutic agent
enters the target tissue intracellularly.
27. A method according to claim 22, wherein said positioning
employs an image guidance system.
28. A method according to claim 27, wherein said positioning
employs an intrabody camera.
29. A method according to claim 22, wherein said target tissue
includes a tumor.
30. A method according to claim 29, wherein said target tissue
includes a tumor in a urinary bladder.
31. A method according to claim 22, wherein said target tissue
includes a portion of a pulmonary vein conducting an electric
signal which contributes to Atrial Fibrillation.
32. A method according to claim 22, wherein said therapeutic agent
enters said target tissue at a concentration of at least 1 nanogram
per milligram of tissue.
33. A method according to claim 22, wherein said therapeutic agent
includes particles with a size in the range of 1 nanometer to 100
micrometers.
34. A method according to claim 33, wherein said particles include
at least one metal.
35. A method according to claim 33, wherein said particles include
at least one nucleic acid sequence.
36. A method for transmucosal delivery of a therapeutic agent to
cells lining a body cavity, the method comprising: (a) providing an
expandable member; (b) positioning said expandable member within
the body cavity; (c) introducing the therapeutic agent into the
expandable member until a desired pressure is achieved; and (d)
creating a plurality of small apertures, in the expandable member;
wherein said pressure is sufficient to propel said therapeutic
agent through a mucosal layer to cells beneath said mucosal
layer.
37. A method according to claim 1, wherein said expandable member
includes at least one balloon.
38. A method according to claim 1, wherein (d) is performed after
(c).
39. A method according to claim 1, wherein (c) is performed after
(d).
40. A method according to claim 36, wherein said body cavity
includes a nostril.
41. A method according to claim 36, wherein said body cavity
includes a nasal sinus.
42. A method according to claim 36, wherein said body cavity
includes a portion of a genitourinary tract.
43. A method according to claim 36, wherein said body cavity
includes a portion of a digestive tract.
44. A method according to claim 36, wherein said body cavity is a
nostril and/or adjoining nasal sinuses and the method provides
relief from rhinitis.
45. A method of treating a tissue, the method comprising: (a)
bringing at least one elongate tube including a plurality of ports
on its side in proximity to a tissue on an inner surface of a
lumen; said tube characterized in that it cannot expand to fill the
entire lumen; and (b) employing a pressure pulse to inject an agent
into said tissue through the ports.
46. A method according to claim 45, wherein said agent includes a
cytotoxic compound.
47. An apparatus for injecting a therapeutic agent into a target
tissue, the apparatus comprising: (a) an expandable member
including an outer wall characterized by a plurality of nascent
holes therein, said outer wall defining an inner cavity; (b) a fill
mechanism adapted to introduce a therapeutic agent into said inner
cavity at a desired pressure; and (c) a release mechanism adapted
to transform said nascent holes into actual holes.
48. An apparatus according to claim 47, wherein said expandable
member is shaped to conform to an anatomic structure.
49. An apparatus according to claim 48, wherein said shape of said
expandable member positions said nascent holes towards a
target.
50. An apparatus for reducing a toxic effect of a therapeutic agent
on a non-target tissue, the apparatus comprising: (a) an expandable
member including an outer wall characterized by a plurality of
nascent holes therein, said outer wall defining an inner cavity,
said expandable member adapted for positioning in proximity to a
target tissue; (b) a fill mechanism adapted to introduce an amount
of therapeutic agent into said inner cavity at a desired pressure;
and (c) a release mechanism adapted to transform said nascent holes
into actual holes; wherein said amount is sufficient to exert a
physiologic effect on cells of said target tissue but insufficient
to exert an effect on cells lying at a distance greater than a
selected distance from said target tissue.
51. An apparatus according to claim 50, wherein said expandable
member is shaped to conform to an anatomic structure.
52. An apparatus according to claim 51, wherein said shape of said
expandable member positions said nascent holes towards a
target.
53. An apparatus for injecting a therapeutic agent into a target
tissue, the apparatus comprising: (a) an expandable member
characterized by at least one protrusion adapted for engagement by
a lumen and at least a portion not engageable by said lumen and
including an outer wall, said outer wall defining an inner cavity;
(b) a fill mechanism adapted to introduce a therapeutic agent into
said inner cavity at a desired pressure; and (c) a plurality of
injection ports.
54. An apparatus according to claim 53, wherein said outer wall is
characterized by a plurality of nascent holes therein and the
device includes a release mechanism adapted to transform said
nascent holes into injection ports.
55. An apparatus according to claim 53, wherein a shape of said
expandable member positions at least one injection port facing
axially with respect to said device.
56. An apparatus for injecting a therapeutic agent into a target
tissue, the apparatus comprising: (a) an expandable member
including an outer wall, said outer wall defining an inner cavity;
(b) a fill mechanism adapted to introduce a therapeutic agent into
said inner cavity at a desired pressure; and (c) at least one
injection port facing axially with respect to said device.
57. An apparatus according to claim 56, wherein said outer wall is
characterized by a plurality of nascent holes therein and the
device includes a release mechanism adapted to transform said
nascent holes into injection ports.
Description
RELATED APPLICATIONS
[0001] The present application is a continuation in part of PCT
application IL/2005/000749 filed on Jul. 14, 2005 which claims the
benefit under 119(e) of 60/587,335 filed Jul. 14, 2004, 60/599,884
filed Aug. 10, 2004, 60/603,262 filed Aug. 23, 2004 and 60/675,477
filed Apr. 28, 2005, an inventor common to all of these
applications is Mordechay Beyar, the disclosures of which are
incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to the delivery of materials,
for example, high speed intrabody needle-less injection.
BACKGROUND OF THE INVENTION
[0003] A common treatment for a blocked artery, especially a
coronary artery, is PTCA, in which a balloon is inflated inside the
lumen of the artery, causing the lumen to increase, while
compressing the blockage and/or forcefully expanding the artery.
One problem with this method is restenosis, in which the artery
responds to the PTCA procedure by inflammation and inward growth.
Another problem is collapse of the wall of the artery back into its
lumen.
[0004] The use of a stent attempts to help with one or both
problems, by providing continual support against collapse.
Restenosis may still occur and common practices are coating the
stent with a material that prevents vessel growth and/or using
local irradiation for the same effect. Some problems have been
reported with these methods, for example, thrombosis formation.
[0005] Injection of drugs from outside the body using needle-less
methods is known in the art.
[0006] US application publication 2003/0083612, the disclosure of
which is incorporated herein by reference describes a needle-less
device for injecting drugs from outside the body.
[0007] Injection of materials inside the body is also generally
known.
[0008] T. Hirano, A. Nakagawa, H. Ohyama, H. Jokura, K. Takayama
and R. Shirane "Pulsed liquid jet dissector using holmium: YAG
laser--a novel neurosurgical device for brain incision without
impairing" Acta Neuroehir (2003) 145: 401-406, the disclosure of
which is incorporated herein by reference, describes the use of a
Ho: YAG laser to evaporate water in a tube and thereby creates a
forward (tube axis) plume of material.
[0009] Takayuki Hirano, M D, Makoto Komatsu, Toshiro Seaeki,
Hiroshi Uenohara, Akira Takahashi, Kazuyoshi Takayama and Takashi
Yoshimoto "Enhancement of Fibrinolytics With a Laser-Induced Liquid
Jet" Lasers in Surgery and Medicine 29:360-368 (2001), the
disclosure of which is incorporated herein by reference describes
the forward injection of a thrombosis dissolving material.
[0010] U.S. Pat. No. 5,614,502 Mar. 25, 1997 "High pressure impulse
transient drug delivery for the treatment of proliferative
diseases" and U.S. Pat. No. 6,716,190 Apr. 6, 2004 "Device and
method for the delivery and injection of therapeutic and diagnostic
agents to a target site within a body", the disclosures of which
are incorporated herein by reference, describe methods of material
delivery inside the body, including transvascularly.
[0011] W. J. Walker, I. M. Faireley "A simplified technique for the
per catheter delivery of Isobutyl 2--Cyanoacrylate in the
Embolisation of Bleeding Vessels", Journal of Interventional
Radiology 1987 2, 59-63, the disclosure of which is incorporated
herein by reference, describes the injection of glue into a lumen
and against walls of an artery, in order to block it.
[0012] U.S. Pat. No. 6,280,414, the disclosure of which is
incorporated herein by reference describes a tube system for
delivering a drug to the wall of a blood vessel.
[0013] U.S. Pat. No. 5,713,860 issued to Kaplan, the disclosure of
which is incorporated herein by reference, teaches a lumen based
system including a balloon to deliver medication.
[0014] U.S. Pat. NO. 5,611,775, the disclosure of which is
incorporated herein by reference teaches methods of delivery of
therapeutic or diagnostic liquid into tissue surrounding a body
lumen. The methods include providing a catheter having an
expandable member with a plurality of small apertures and advancing
this catheter into the body. The member is expanded to touch or
approach the lumen wall. This patent teaches use of pressures in
the range of 0.75 to 10 atmospheres to create a velocity of 0.5 to
15 M/s in material ejected through the apertures.
[0015] In other clinical scenarios, it is common to employ
medicines or methods which are not cell type specific in order to
eliminate a certain type of cell. Many chemotherapeutic agents are
generally cytotoxic. Systemic administration of these compounds
causes undesirable side effects such as nausea, hair loss, appetite
suppression, weight loss and lethargy. In certain types of cancer,
such as urinary bladder cancer, an intrabody lumen may be infused
or "washed" with a chemotherapeutic agent in order to limit
systemic toxic effects. In additional clinical scenarios, a mucosal
layer covering cells lining a lumen reduces a potential efficacy of
"washing".
SUMMARY OF THE INVENTION
[0016] An aspect of some embodiments of the present invention
relates to injecting a medicament into a target tissue by retaining
the medicament within an intra-body balloon until a desired
pressure is achieved and then providing a plurality of apertures
through which the medicament may exit. In an exemplary embodiment
of the invention, the medicament exits the balloon through the
apertures at a desired velocity. Optionally, the pressure is
further increased after the apertures are provided. Optionally, the
desired pressure is 15 atmospheres or more. Optionally, the desired
velocity is 10, optionally 20, optionally 60 M/s or more.
Optionally, at least a portion of the medicament is injected
intracellularly.
[0017] In an exemplary embodiment of the invention, the target
tissue is located in a body lumen. Optionally, the injection is
transaxial or radial with respect to the balloon. Optionally, the
injection is axial with respect to the balloon. Optionally the body
lumen is a blood vessel (e.g. coronary artery, pulmonary vein or
peripheral blood vessel), a prostate gland, a urinary bladder, a
nostril, a nasal sinus, an ear canal, an airway, a portion of the
digestive tract or a portion of the female reproductive tract.
Optionally, the medicament is a cytotoxic agent, for example
Rapamycin or Paclitaxel. Optionally, the medicament is a fibrotic
agent, optionally including collagen and/or elastin.
[0018] In an exemplary embodiment of the invention, a cytotoxic
agent is injected into a target tissue. Optionally the target
tissue is a portion of a blood vessel wall. Optionally the blood
vessel is a pulmonary vein. Optionally, the injection causes
ablation of a portion of the vessel wall. Optionally, the injection
prevents transmission of an electric signal. Optionally, the
velocity of injected material may reach 20 m/s, 30 m/s, 50 m/s, 100
m/s, 150 or 200 m/s or smaller, intermediate or larger speeds. In
an exemplary embodiment of the invention, the cytotoxic agent
contains an alcohol, optionally ethanol.
[0019] In an exemplary embodiment of the invention, ablated tissue
in the pulmonary vein blocks transmission of an electric signal.
Optionally, blocking of the signal relieves symptoms of Atrial
Fibrillation.
[0020] In an exemplary embodiment of the invention, the target
tissue is a tumor located on an inner surface of a urinary
bladder.
[0021] In an exemplary embodiment of the invention, the target
tissue is a tumor located on an inner surface of a digestive organ
such as the stomach, small intestine or large intestine.
[0022] In an exemplary embodiment of the invention, the cytotoxic
agent contains a chemotherapeutic agent and injection of the agent
directly into one or more tumors spares adjacent and/or remote
normal tissue from a toxic effect of the chemotherapeutic
agent.
[0023] In an exemplary embodiment of the invention, the balloon
delivers a medicament to cells covered by mucosa. Optionally, the
cells are located in a nostril or nasal sinus. Optionally, the
cells are located in a genitourinary tract (e.g. vagina, cervix,
uterus, bladder or urethra). In an exemplary embodiment of the
invention, the medicament is delivered to nostrils and/or nasal
sinuses to provide relief from rhinitis.
[0024] An aspect of some embodiments of the invention relates to
use of elongate tube(s) including ports on their side in proximity
to a tissue on an inner surface of a lumen and employing a pressure
pulse to inject an agent into the tissue through the ports. In an
exemplary embodiment of the invention; the tube(s) are
characterized in that they cannot expand to fill the entire lumen.
Optionally, the delivered material is cytotoxic.
[0025] An aspect of some embodiments of the invention relates to a
high speed ejection of material from radial holes formed in an
intra-body balloon. In an exemplary embodiment of the invention,
the balloon includes means for providing a high pressure impulse
inside the balloon. Optionally, the means is within the balloon or
within a short distance from the balloon, for example, 15 mm.
[0026] In an exemplary embodiment of the invention, the ejected
material is used to penetrate the walls of tubular organs, for
example, a blood vessel or a prostate, optionally for preventing
restenosis.
[0027] In an exemplary embodiment of the invention, the walls in
the balloon comprise pressure sensitive holes which open only at a
threshold internal pressure level, for example, a level above
regular (e.g., PTCA) balloon inflation pressures. Optionally, the
spatial density and/or diameter of the holes vary along the length
of the balloon, for example, to enhance uniformity of material
provision and/or for other reasons, such as spatially-non-uniform
treatment. In an exemplary embodiment of the invention, the drop of
pressure caused by the opening of the holes is not sufficient to
deflate the balloon in a period of less than, for example, 1
minute, 10 seconds, 5 seconds, 1 second, 0.5 seconds or
intermediate or lesser values. In some designs in accordance with
the invention, the holes are too small to pass enough material
under the applied pressure to significantly deflate and/or
depressurize the balloon. In some designs, additional incoming
pressure is applied to the balloon which can more than compensate
for pressure loss through the holes. In some designs, pressure is
released through the main lumen of the balloon, in addition to or
instead of the holes. Optionally, an ongoing pressure and the shape
of the holes are selected to achieve a desired material injection
velocity envelope shape. In an exemplary embodiment of the
invention, the hole sizes are selected so that leakage at one hole
will not significantly affect the pressure at other holes, at least
not within a short time period, such as 10 ms, 30 ms, 50 ms or
intermediate or greater times. In an exemplary embodiment of the
invention, the pressure loss within such time frames is less than
30%, 20% 10% or less of the balloon base (without the impulse)
pressure.
[0028] In an exemplary embodiment of the invention, a same balloon
is used both for PTCA and/or stenting and for material provision.
Thus, for example, the balloon can be used for PTCA at regular
balloon pressures and then, when the stenosis is compressed, the
pressure can be increased to eject re-stenosis inhibiting
material.
[0029] In an exemplary embodiment of the invention, the balloon, at
or about the holes, is in full contact with the surrounding tissue.
Optionally, a minimum contact pressure is ensured.
[0030] In an exemplary embodiment of the invention, the high
pressure source comprises an explosion, for example, sudden
evaporation of water caused by electricity and/or energy
absorption. In an exemplary embodiment of the invention, a laser
light source provides the energy. Optionally, the balloon includes
a mirror or target for energy distribution control, so that some or
all of the energy is distributed by the target, rather than by
absorption in the balloon filling. In an alternative embodiment, a
mechanical means provides the impulse. For example a thin metallic
or plastic plate that releases kinetic energy (e.g., due to its
expansion) when irradiated by the laser light, may be used.
Optionally, the laser light releases stored energy, for example,
changing the shape of a shape-memory element or freeing a spring
from a constraint.
[0031] Optionally, multiple pressure sources (for example multiple
laser fibers to provide multiple sources of heat for expansion) are
provided in the balloon.
[0032] Optionally, means are provide to direct the advancing of a
resulting high pressure wave and/or shock wave.
[0033] An aspect of some embodiments of the invention relates a
balloon with pressure sensitive holes that open to allow material
passage only above a certain threshold pressure. Optionally, the
holes are arranged radially on the balloon. Optionally,
alternatively or additionally, one or more axial holes are
provided. Optionally, the holes include a layer of material, for
example, part of a layer used on the balloon, which layer is torn
when the pressure rises and/or by a shockwave. Optionally, the
holes are formed using multiple balloon layers, at least one of
which is aperture. Optionally, the holes are formed during
manufacture by drilling in the balloon (e.g., using a water jet, a
laser, a hot needle, micro mechanical drill and/or chemical
means).
[0034] Optionally, one or more apertures (or exit ports) in the
balloon are created by a laser source used for injecting the
material. The apertures may be, for example through or partial
(blind). Optionally, a multi-fiber laser source is used and the
laser light is used both for creating passages through the balloon
and for increasing the pressure inside the balloon. A single pulse
or a series of pulses may be used for this task, optionally pulses
of different energies. Optionally, the balloon wall itself serves
as a target that absorbs laser energy, and parts of which heats
explosively.
[0035] In an exemplary embodiment of the invention, the threshold
pressure is above a regular PTCA inflation pressure, for example,
above 5, 10, 15 or 20 atmospheres.
[0036] Optionally, the balloon is strengthened surrounding the
holes and/or at other locations thereon, to prevent tearing.
Optionally, the strengthening is by providing a braid of material
surrounding the aperture.
[0037] An aspect of some embodiments of the invention relates to a
strengthened apertured balloon, which includes a plurality of holes
therein and which is strengthened near the holes, to prevent
tearing of the balloon at the holes. Optionally, the strengthening
is by elongate elements, such as fibers, having a length comparable
or greater than the balloon diameter and optionally disposed
axially, radially and/or otherwise along the balloon surface.
[0038] An aspect of some embodiments of the invention relates to
injection of a structural material into the walls of tubular
organs. Optionally, the injection is using a balloon that contacts
the walls, optionally using needle-less injection. Optionally,
alternatively or additionally, one or more needles is used to
inject the structural material.
[0039] In an exemplary embodiment of the invention, the structural
material is a hardening material. Alternatively, the injected
material does not harden.
[0040] In an exemplary embodiment of the invention, the structural
material is sufficient to enhance the structure of the wall and
prevent collapse thereof.
[0041] In an exemplary embodiment of the invention, the structural
material is used to strengthen one or more of a stented vessel, a
PTCAed vessel, an aneurysm, a prostate and/or an anastomosis
region.
[0042] Optionally, the injected material is adapted to dissipate
with time, be bio-absorbed and/or migrate out of the walls, for
example, due to dilution in inter-cellular fluids.
[0043] According to an exemplary embodiment of the invention, there
is provided a method for injecting a therapeutic agent into a
target tissue, the method comprising: [0044] (a) providing an
expandable member; [0045] (b) positioning said expandable member in
proximity to the target tissue; [0046] (c) introducing the
therapeutic agent into the expandable member until a desired
pressure is achieved; and [0047] (d) creating a plurality of small
apertures in the expandable member.
[0048] Optionally, the expandable member includes at least one
balloon.
[0049] Optionally, (d) is performed after (c).
[0050] Optionally, (c) is performed after (d).
[0051] Optionally, the desired pressure is at least 15
atmospheres.
[0052] Optionally, the desired pressure is sufficient to cause said
therapeutic agent to exit through said apertures at a speed of at
least 20 meters/second.
[0053] Optionally, the therapeutic agent enters the target tissue
intracellularly.
[0054] Optionally, the target tissue is located in a body
lumen.
[0055] Optionally, at least a portion of said apertures are aimed
transaxially with respect to said expandable member.
[0056] Optionally, at least a portion of said apertures are aimed
radially with respect to said expandable member.
[0057] Optionally, at least a portion of said apertures are aimed
axially with respect to said expandable member.
[0058] Optionally, the body lumen is a blood vessel.
[0059] Optionally, the therapeutic agent includes a cytotoxic
agent.
[0060] Optionally, the therapeutic agent includes a fibrotic
agent.
[0061] Optionally, the cytotoxic agent includes an alcohol.
[0062] Optionally, the alcohol includes ethanol.
[0063] Optionally, entry of said cytotoxic agent into said target
tissue blocks transmission of an electric signal through said
target tissue.
[0064] Optionally, the method is applied to ameliorate Atrial
Fibrillation.
[0065] Optionally, the therapeutic agent includes a
chemotherapeutic agent.
[0066] Optionally, the target tissue is a tumor.
[0067] Optionally, the tumor is located on an inner surface of a
urinary bladder.
[0068] According to an exemplary embodiment of the invention, there
is provided a method for reducing a toxic effect of a therapeutic
agent on a non-target tissue, the method comprising: [0069] (a)
providing an expandable member; [0070] (b) positioning said
expandable member in proximity to a target tissue; [0071] (c)
introducing an amount of therapeutic agent into the expandable
member until a desired pressure is achieved; and [0072] (d)
creating a plurality of small apertures, in the expandable member;
wherein said amount is sufficient to exert a physiologic effect on
cells of said target tissue but insufficient to exert an effect on
cells lying at a distance greater than a selected distance from
said target tissue.
[0073] Optionally, the expandable member includes at least one
balloon.
[0074] Optionally, (d) is performed after (c).
[0075] Optionally, (c) is performed after (d).
[0076] Optionally, the therapeutic agent enters the target tissue
intracellularly.
[0077] Optionally, the positioning employs an image guidance
system.
[0078] Optionally, the positioning employs an intrabody camera.
[0079] Optionally, the target tissue includes a tumor.
[0080] Optionally, the target tissue includes a tumor in a urinary
bladder.
[0081] Optionally, the target tissue includes a portion of a
pulmonary vein conducting an electric signal which contributes to
Atrial Fibrillation.
[0082] Optionally, the therapeutic agent enters said target tissue
at a concentration of at least 1 nanogram per milligram of
tissue.
[0083] Optionally, the therapeutic agent includes particles with a
size in the range of 1 nanometer to 100 micrometers.
[0084] Optionally, the particles include at least one metal.
[0085] Optionally, the particles include at least one nucleic acid
sequence.
[0086] According to an exemplary embodiment of the invention, there
is provided a method for transmucosal delivery of a therapeutic
agent to cells lining a body cavity, the method comprising: [0087]
(a) providing an expandable member; [0088] (b) positioning said
expandable member within the body cavity; [0089] (c) introducing
the therapeutic agent into the expandable member until a desired
pressure is achieved; and [0090] (d) creating a plurality of small
apertures, in the expandable member; wherein said pressure is
sufficient to propel said therapeutic agent through a mucosal layer
to cells beneath said mucosal layer.
[0091] Optionally, the expandable member includes at least one
balloon.
[0092] Optionally, (d) is performed after (c).
[0093] Optionally, (c) is performed after (d).
[0094] Optionally, the body cavity includes a nostril.
[0095] Optionally, the body cavity includes a nasal sinus.
[0096] Optionally, the body cavity includes a portion of a
genitourinary tract.
[0097] Optionally, the body cavity includes a portion of a
digestive tract.
[0098] Optionally, the body cavity is a nostril and/or adjoining
nasal sinuses and the method provides relief from rhinitis.
[0099] According to an exemplary embodiment of the invention, there
is provided a method of treating a tissue, the method
comprising:
[0100] (a) bringing at least one elongate tube including a
plurality of ports on its side in proximity to a tissue on an inner
surface of a lumen; said tube characterized in that it cannot
expand to fill the entire lumen; and
[0101] (b) employing a pressure pulse to inject an agent into said
tissue through the ports.
[0102] Optionally, the agent includes a cytotoxic compound.
[0103] In an exemplary embodiment of the invention, there is
provided an apparatus for injecting a therapeutic agent into a
target tissue. The apparatus comprising: [0104] (a) an expandable
member including an outer wall characterized by a plurality of
nascent holes therein, said outer wall defining an inner cavity;
[0105] (b) a fill mechanism adapted to introduce a therapeutic
agent into said inner cavity at a desired pressure; and [0106] (c)
a release mechanism adapted to transform said nascent holes into
actual holes.
[0107] Optionally, the expandable member is shaped to conform to an
anatomic structure.
[0108] Optionally, the shape of said expandable member positions
said nascent holes towards a target.
[0109] In an exemplary embodiment of the invention, there is
provided an apparatus for reducing a toxic effect of a therapeutic
agent on a non-target tissue The apparatus comprising: [0110] (a)
an expandable member including an outer wall characterized by a
plurality of nascent holes therein, said outer wall defining an
inner cavity, said expandable member adapted for positioning in
proximity to a target tissue; [0111] (b) a fill mechanism adapted
to introduce an amount of therapeutic agent into said inner cavity
at a desired pressure; and [0112] (c) a release mechanism adapted
to transform said nascent holes into actual holes; wherein said
amount is sufficient to exert a physiologic effect on cells of said
target tissue but insufficient to exert an effect on cells lying at
a distance greater than a selected distance from said target
tissue.
[0113] Optionally, the expandable member is shaped to conform to an
anatomic structure.
[0114] Optionally, the shape of said expandable member positions
said nascent holes towards a target.
[0115] In an exemplary embodiment of the invention, there is
provided an apparatus for injecting a therapeutic agent into a
target tissue. The apparatus comprising: [0116] (a) an expandable
member characterized by at least one protrusion adapted for
engagement by a lumen and at least a portion not engageable by said
lumen and including an outer wall, said outer wall defining an
inner cavity; [0117] (b) a fill mechanism adapted to introduce a
therapeutic agent into said inner cavity at a desired pressure; and
[0118] (c) a plurality of injection ports.
[0119] Optionally, the outer wall is characterized by a plurality
of nascent holes therein and the device includes a release
mechanism adapted to transform said nascent holes into injection
ports.
[0120] Optionally, the shape of said expandable member positions at
least one injection port facing axially with respect to said
device.
[0121] In an exemplary embodiment of the invention, there is
provided an apparatus for injecting a therapeutic agent into a
target tissue, the apparatus comprising: [0122] (a) an expandable
member including an outer wall, said outer wall defining an inner
cavity; [0123] (b) a fill mechanism adapted to introduce a
therapeutic agent into said inner cavity at a desired pressure; and
[0124] (c) at least one injection port facing axially with respect
to said device.
[0125] Optionally, the outer wall is characterized by a plurality
of nascent holes therein and the device includes a release
mechanism adapted to transform said nascent holes into injection
ports.
[0126] There is thus provided in accordance with an exemplary
embodiment of the invention, a balloon for injecting material into
a wall of a hollow organ of a human, comprising:
[0127] an expandable balloon body having a surface and having an
axis;
[0128] at least one predefined ejection port on said body adapted
for ejection of fluid therefrom, in a transaxial direction; and
[0129] an impulse source configured for and adapted to eject
material out of said point at a velocity and shape suitable for
mechanically penetrating tissue adjacent said port.
[0130] Optionally, the balloon is adapted for a blood vessel.
Alternatively or additionally, the balloon is compliant.
Alternatively, the balloon is non-compliant.
[0131] In an exemplary embodiment of the invention, said body is
adapted to be pressurized during said ejection.
[0132] In an exemplary embodiment of the invention, said impulse
source comprises a laser source located remote from said body and a
light guide adapted to guide said source into said body to generate
a mechanical impulse thereat when said laser source is
activated.
[0133] In an exemplary embodiment of the invention, said impulse
source comprises a target to which energy is provided from outside
to generate said impulse. Optionally, said target releases energy
stored in the balloon in response to said energy. Optionally, said
target converts said outside energy into said impulse.
[0134] In an exemplary embodiment of the invention, said impulse
source comprises a source of electricity.
[0135] In an exemplary embodiment of the invention, said impulse
source comprises a mechanical pressure generator adapted to be
located outside a human body containing the wall and a fluid column
connecting said generator with said balloon body.
[0136] In an exemplary embodiment of the invention, said impulse
source is inside said balloon body. Optionally, said impulse source
comprises a mechanical impulse source.
[0137] In an exemplary embodiment of the invention, the balloon
comprises at least one axial port predefined and adapted for axial
ejection of fluid therefrom.
[0138] In an exemplary embodiment of the invention, said at least
one port comprises a valve adapted to pass fluid under certain
pressure conditions. Optionally, said body and said at least one
valve are adapted so that said balloon is operable as a PTCA
balloon prior to said ejection.
[0139] In an exemplary embodiment of the invention, said port
comprises a weakening in said body. Optionally, said body is
strengthened adjacent to said weakening.
[0140] In an exemplary embodiment of the invention, the balloon has
a stent mounted thereon and adapted to deliver said stent.
[0141] In an exemplary embodiment of the invention, said at least
one port comprises a plurality of ports arranged on said body.
[0142] In an exemplary embodiment of the invention, said at least
one port comprises a plurality of ports arranged and configured
with said impulse source to generate a non-uniform fluid ejection
pattern.
[0143] In an exemplary embodiment of the invention, said at least
one port comprises a plurality of ports arranged and configured
with said impulse source to generate a uniform fluid ejection
pattern over at least a predetermined axial length of the body.
[0144] In an exemplary embodiment of the invention, said fluid
comprises a structural material adapted to affect at least one
mechanical property of human tissue when ejected into the
tissue.
[0145] In an exemplary embodiment of the invention, said fluid
comprises an anti-proliferation bio-active component.
[0146] In an exemplary embodiment of the invention, said fluid is
stored within said body.
[0147] In an exemplary embodiment of the invention, said fluid
expands said body.
[0148] In an exemplary embodiment of the invention, said body
comprises at least one tube on an outside of said body and wherein
said at least one port is defined on said tube.
[0149] There is also provided in accordance with an exemplary
embodiment of the invention, a method of treating a hollow organ,
comprising:
[0150] (a) contacting an outer surface of said balloon with the
inside walls of said organ; and
[0151] (b) ejecting fluid away from said balloon in a radial
direction and into said walls, without the use of a needle for said
penetration.
[0152] There is also provided in accordance with an exemplary
embodiment of the invention, a treatment balloon, comprising:
[0153] (a) an expandable body adapted for use in a lumen of a given
range of diameters; and
[0154] (b) a plurality of ports formed in said body and adapted to
eject fluid responsive to pressure conditions in said balloon, said
conditions being met only after said balloon is expanded to said
ranges. Optionally, said balloon is adapted to apply PTCA prior to
said ports opening. Alternatively or additionally, said plurality
of ports comprises weakened portions of said body. Alternatively or
additionally, said weakenings have an outside surface that is not
flush with an outside surface of said balloon. Alternatively or
additionally, said weakenings have an inside surface that is not
flush with an inside surface of said balloon.
[0155] In an exemplary embodiment of the invention, said body
comprises at least one strengthening element adjacent to said
weakenings.
[0156] In an exemplary embodiment of the invention, said plurality
of ports are adapted to close once a pressure on them is below a
threshold value.
[0157] In an exemplary embodiment of the invention, said plurality
of ports are arranged to eject material radially to an axis of said
balloon.
[0158] In an exemplary embodiment of the invention, the balloon
comprises an impulse source in or near said balloon and adapted to
generate an impulse sufficient to open said ports.
[0159] In an exemplary embodiment of the invention, said ports are
adapted to remain closed at a pressure below 15 atmospheres.
[0160] There is also provided in accordance with an exemplary
embodiment of the invention, a treatment balloon, comprising:
[0161] (a) an expandable body adapted for use in a lumen of a given
range of diameters;
[0162] (b) a plurality of weakenings in said body adapted to tear
or open in a controlled manner under certain pressure conditions;
and
[0163] (c) at least one strengthening element adjacent to said
weakenings.
[0164] There is also provided in accordance with an exemplary
embodiment of the invention, a kit, comprising:
[0165] an ejector adapted to inject material into an organ wall,
in-vivo; and
[0166] an amount of structural material adapted to effect a
structural change of said vessel wall without disrupting its
operational integrity. Optionally, said structural material is a
setting material that sets to a hardened condition. Alternatively,
said structural material is a non-setting material.
[0167] In an exemplary embodiment of the invention, said structural
material is mixed with a bioactive material.
[0168] In an exemplary embodiment of the invention, said ejector is
a needle-less ejector.
[0169] There is also provided in accordance with an exemplary
embodiment of the invention a method of treating a vessel wall,
comprising:
[0170] (a) contacting a port to said wall; and
[0171] (b) injecting a structural material into said wall, such
that a mechanical property of said wall is mechanically affected by
said structural material. Optionally, said structural material is a
setting material.
BRIEF DESCRIPTION OF THE DRAWINGS
[0172] Exemplary non-limiting embodiments of the invention will be
described with reference to the following description of
embodiments in conjunction with the figures. Identical structures,
elements or parts which appear in more than one figure are
generally labeled with a same or similar number in all the figures
in which they appear, in which:
[0173] FIG. 1 is a flowchart of a method of treating blood vessels,
in accordance with an exemplary embodiment of the invention;
[0174] FIGS. 2A-2E are a series illustrating an exemplary process
of treating a blood vessel or another tubular organ, following the
flowchart of FIG. 1;
[0175] FIG. 3 is a trans-axial cross-sectional view of a treated
blood vessel, in accordance with an exemplary embodiment of the
invention;
[0176] FIG. 4 is a schematic diagram of a vessel wall treatment
system, in accordance with an exemplary embodiment of the
invention;
[0177] FIGS. 5A-5G illustrate pressure sensitive holes, in
accordance with exemplary embodiments of the invention;
[0178] FIGS. 6A-6H illustrate alternative catheter designs, some of
which are suitable for prostate treatment, in accordance with
exemplary embodiments of the invention;
[0179] FIG. 7 is a graph summarizing experimental results showing
penetration depth as a function of pressure and amount of delivery
material;
[0180] FIG. 8 is a graph showing a pressure waveform measured
inside a delivery system in accordance with an exemplary embodiment
of the invention;
[0181] FIGS. 9A and 9B and 9C illustrate additional exemplary
embodiments of the invention.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
Overview
[0182] FIG. 1 shows a flowchart of a method and FIGS. 2A-2E
illustrate the acts of the method, of applying material(s) to
and/or driving material(s) into the walls of a blood vessel, in
accordance with an exemplary embodiment of the invention. FIGS.
2A-2E are discussed in parallel with the description of FIG. 1.
Variations on the devices and/or methods are described
following.
Exemplary Method
[0183] FIG. 1 is a flowchart 100 of a method of treating blood
vessels, in accordance with an exemplary embodiment of the
invention.
[0184] At 102, a narrowing or other problem in a wall 204 of a
blood vessel 200 (FIG. 2A) is identified. Optionally, the narrowing
is a plaque deposit 206, for example, a deposit with a calcified
filling 202.
[0185] At 104, a catheter treatment system 210 (FIG. 2B) is
inserted into the body and guided to the narrowing. Optionally,
system 210 is used also to identify the problem, for example,
including a contrast material port (not shown) or an imager (not
shown).
[0186] A treatment balloon 212 (FIG. 2B) is shown, including a
plurality of apertures (optionally initially sealed) 214, for
providing treatment to walls 204.
[0187] At 106, Balloon 212 is optionally inflated with pressure
sufficient to perform PTCA on deposits 206 (FIG. 2C). The deposits
are shown as schematically cracking. Optionally, apertures 214 leak
only a small amount or are configured to remain sealed at pressures
used for PTCA (e.g., 15-20 atmospheres inside the balloon).
[0188] Alternatively or additionally to PTCA, balloon 212 is
optionally used to deliver (108) a stent 220 (FIG. 2D).
[0189] Optionally, the stenting and/or PTCA are performed using a
different balloon from balloon 212 and/or performed after provision
of material to the vessel. Optionally, the material delivery method
(e.g., high pressure pulse, described below) is also used to
deliver the stent and/or fix it in place.
[0190] At 110, a pulse of high pressure is provided to create holes
in the balloon so that one or more plumes 236 (FIG. 2E), are
ejected therefrom (described below) and preferably penetrate wall
204 and/or a deposit 206 on or in the wall. In an exemplary
embodiment of the invention, at least a portion of the plume is
injected intracellularly. Optionally, the balloon remains inflated
prior to this injection, so that contact with the wall and/or a
sealing pressure, is assured. Sealing and/or contact optionally
helps deliver the material at a high pressure to the wall and/or
aids in its penetration into the wall.
[0191] Optionally, the delivery is at a delay after stenting and/or
PTCA, for example, to allow the vessel tissue to adapt and/or to
ensure the stenting and/or PTCA completed successfully. Exemplary
delays are 30-90 seconds, for example, 60 seconds.
[0192] In an exemplary embodiment of the invention, an optical
fiber 230 delivers a pulse of light which is absorbed in a filling
238 (e.g., saline) or a target (406 in FIG. 4), causing an
explosion 232. The pulse may include a series of sub-pulses, each
sub-pulse optionally characterized by a different energy. Shock
and/or pressure waves 234 from explosion 232 travel to the walls of
balloon 212, create holes, and cause the ejection of plumes 236.
Various mechanisms which may be used are described below. In an
exemplary embodiment of the invention, the plumes comprise the
filling which may be, for example, saline mixed with a drug or a
cement material. Optionally, the filling includes a dark (e.g.
black) dye to increase energy absorbtion.
[0193] In an exemplary embodiment of the invention, the total
volume of the balloon is not increased very much by the explosion,
for example, the balloon diameter increasing no more than 1%, 5%,
10% or smaller, intermediate or larger values. Optionally, increase
is avoided (e.g., by using a non-compliant balloon) to prevent
and/or reduce pain and/or damage which may be caused by over
expansion, for example, by overstenting and/or expansion of the
urethra.
[0194] In alternative methods, a significant increase in balloon
volume occurs, for example, 10%, 20%, 30% or a smaller,
intermediate or larger value. This increase may or may not decrease
after plumes 236 flow. In an exemplary embodiment of the invention,
varying or cycling of the balloon diameter and/or pressure are used
to assist in material penetration and/or maintenance in the tissue.
In an exemplary embodiment of the invention, increased pressure
after or during injection prevents leakage from the penetration
points. In an exemplary embodiment of the invention, decreased
pressure before injection, relaxes the vessel wall. In an exemplary
embodiment of the invention, increased pressure (or waves) after
penetration is used to cause sideways (e.g., circumferential)
dispersion of the injected material. In an exemplary embodiment of
the invention, the degree of pressure during injection controls the
tissue thickness and thus the effective penetration depth.
[0195] In an exemplary embodiment of the invention, the inflation
of balloon 212 guarantees that the balloon portions surrounding
apertures 214 are in good contact with walls 204 of the blood
vessel, possibly ensuring less leakage and/or better penetration.
Optionally, a minimal contact pressure is provided, for example,
0.5, 1, 3 atmosphere or intermediate values or greater.
[0196] If a stent 220 is provided, some of apertures 214 may be
created beneath a surface of the stent. However, most of the newly
formed apertures will not be covered by the stent. Optionally, the
apertures are arranged to fit between stent struts, however this is
not essential in some embodiments, for example, due to the presence
of many apertures.
[0197] If the material injection is not complete, balloon 212 may
be repositioned (e.g., axially or by rotation), optionally assisted
by a slight deflation to reduce contact pressure, and then
additional injections carried out. Second injections may also be
used if a different material is to be injected. Optionally, the
same balloon is used for both injections. Alternatively, the
balloon may be replaced. Optionally, two balloons are provided in
tandem, for example on a same balloon catheter and/or on a same
guidewire.
[0198] At 112, balloon 212 is deflated for removal 114. Optionally,
some leakage occurs through the apertures during removal.
Optionally, the apertures are designed to seal again when the
pressure goes below a threshold, possibly a threshold lower than
the injection pressure, for example, 20 atmospheres (e.g., 25% or
50% lower). Optionally, the apertures are formed of a rubber-like
material that self seals when the pressure goes down. A puncture in
the rubber material expands when pressure is increased.
Alternatively or additionally, one or more flaps are provided on
the apertures. Optionally, the flaps serve as a one way valve,
allowing the flap to open outwards, but not inwards.
[0199] FIG. 3 is a trans-axial cross-section of vessel 200 showing
plumes 236 in walls 204 and deposits 206. If, for example, a
structural material such as a glue is injected, it can be seen that
the plumes can serve to hold the vessel open. In some embodiments
of the invention, at least some of the material is provided outside
of the wall. In one example, the balloon has ridges, for example in
an axial or helical pattern and holes are provided at the bases of
the ridges for material injection. Some or all of this injected
material may remain trapped between the balloon and the vessel
walls.
Exemplary System
[0200] FIG. 4 illustrates an exemplary system 400, such as may be
used to carry out the method illustrated with the aid of FIGS. 1-3,
in accordance with an exemplary embodiment of the invention.
[0201] Referring first to portions of system 400 typically outside
of the body, a laser source 410 is used to provide a pulse of light
for explosion 232. Optionally, a controller 427 is used to control
one or more parameters of the pulse, such as total power, peak
power, duration and/or repetition rate, which may serve to control
the depth of penetration of plume 236 and/or an amount of material
thereof, for example.
[0202] In an exemplary embodiment of the invention, temperature
control of the balloon is provided. Optionally, a closed loop
control, for example using a temperature sensor in the balloon
coupled with fluid circulation through the balloon is used.
Optionally, a heat exchanger is provided in the balloon, so the
actual contents of the balloon need not be changed. Optionally, the
heat exchanger is in the form of one or more coils in a lumen or a
heat conducting web, such as gold. Alternatively, open loop cooling
is used, for example, pre-cooling of the fluid and/or the balloon.
Optionally, when a temperature of the balloon increases above a
desired amount, a safety is used to warn a user and/or prevent
additional energy provision. Optionally, the lumen used to provide
cooling fluid is used to cool an energy providing conduit (e.g.,
fiber, wire).
[0203] A saline source 412 is optionally used to inflate balloon
212. Optionally, an impulse source 418 is used to generate a
pressure wave in balloon 212 instead of or in addition to laser
source 410.
[0204] In an exemplary embodiment of the invention, source 418 is
used to generate pressure waves in the balloon, for example, to
provide a massaging effect. Alternatively or additionally,
vibrations are provided to the balloon, for example, to prevent
adherence of the injected material to the apertures.
[0205] It should be noted that an external pressure impulse source
and a laser impulse source may provide different types of effects.
A laser source can provide a very sharp impulse, albeit possibly
reduced volume of expulsion and/or reduced power. A pressure
source, for example, a source that is outside the body, is
typically capable only of less sharp impulses, however, such
impulses can include considerable power and/or volume.
[0206] Optionally, both types of sources are used simultaneously,
optionally in synchronization and/or with a delay between them.
Each source may be used to provide one or more pulses, only some of
which are synchronized.
[0207] In an exemplary embodiment of the invention, the type of
source used depends on the length of the catheter. For example, in
a prostate case, where the catheter is short (and volume
requirements may be large) a pressure source such as a syringe,
pump or gas powered system, may be used. In a coronary vessel,
where the lumen delivering the pressure is long and narrow (and
volume requirements are low), a laser based solution may be most
appropriate.
[0208] Other impulse sources are described below.
[0209] A source of contrast material 416 may be used to provide
saline 412 with contrast and/or may be used for assistance in
imaging vessel 200. Optionally, other tools as known in the art are
used, for example, an embolism filter.
[0210] A source of drug or other material 420 to be provided as
plume 236 is optionally used as well and may feed, for example into
saline source 412 or downstream therefrom. Alternatively or
additionally, material 420 is used instead of and/or in addition to
saline to inflate the balloon.
[0211] In an exemplary embodiment of the invention, material 420
includes a concentrated solution of a drug that optionally contains
solvents and/or stabilizers. Optionally, the concentrated solution
is provided as a stock solution. The stock solution is optionally
provided in ampoules or syringes or vials or other sealed
containers.
[0212] In an exemplary embodiment of the invention, the stock
solution is diluted with saline 412 and/or contrast 416 in mixing
rations of 1:50, 1:40, 1:25 or less to achieve a desired
concentration. Optionally, the solution a will used to inflate
balloon 212 under certain pressure.
[0213] In some embodiments, the material to be delivered,
optionally including contrast material, is provided directly into
balloon 212, for example by needle injection while the balloon is
outside the body instead of or in addition to providing using
saline (or other fluid).
[0214] In an exemplary embodiment of the invention, balloon 212 is
formed of two or more layers, with one or more future aperture
sites 414 formed thereon. Optionally, the future aperture sites are
formed only in an inner layer and/or only in an outer layer. More
details are provided below. A strengthening element 404 is
optionally provided, for example, a fiber or cord. Optionally,
element 404 is non-elastic and prevents over-expansion of balloon
212 above that needed for PTCA. Alternatively or additionally,
element 404 is placed near future apertures 414, to prevent tears
from propagating from the apertures and rupturing balloon 212.
[0215] In an exemplary embodiment of the invention, element 404
comprises a grid and the future apertures are formed in cells of
the grid. Optionally, the grid is non-uniform. Optionally, a
non-grid arrangement is used, for example a random felt-like
arrangement or a spiral arrangement.
[0216] In an exemplary embodiment of the invention, a metal
stent-like frame is used to prevent over inflation of the balloon.
In one example, the stent-like cage is designed to stop expanding
radially once a certain radius is reached. The balloon is inflated,
and the cage prevents inflation of the balloon past that point, but
still allows ejection of fluids therefrom. Optionally, the cage
remains and serves as a stent. Optionally, the cage is of a
spring-back type, for example formed of Nitinol.
[0217] In an exemplary embodiment of the invention, two tubes lead
into balloon 212, an inflation lumen 402 and optical fiber 230.
Optionally, a fluid removal lumen is provided as well (not shown)
and used for replacing the contents of balloon 212 (e.g., saline by
a glue material), optionally without deflating balloon 212.
Optionally the optical fiber passes through the inflation lumen
402. Optionally, a separate lumen is used for the guiding wire.
[0218] Optionally, a plurality of fibers 230 are provided in the
balloon, or a plurality of laser exiting points are provide on
fiber 230, for example, to better distribute laser energy in
balloon 212, for example, 2, 3, 4 or 5 exit points or more. FIG. 6A
shows a system 600, in which a fiber 602 branches to multiple
branches 604, each of which may serve as a local energy source.
This arrangement may be used to control the distribution of
shock/pressure waves in the balloon. In an exemplary embodiment of
the invention, fiber 602 has a diameter of 200-220 microns and
fibers 604 have a diameter of 100-120 microns each. Optionally, the
diameter of fiber 602 is set by a need to transmit a sufficient
amount of power. Alternatively or additionally, the diameter is
determined by a need to allow bending of the fiber in blood vessels
leading to the therapy area. Also visible in FIG. 6A are other
parts which may be provided in a treatment system, namely a
guide-wire 608 which optionally travels in its own channel 610, a
balloon 606 optionally including pressure-responsive apertures 612
and a guide sheath 614.
[0219] In an exemplary embodiment of the invention, an interior
framework, for example, of fibers, or a rigid attachment to the
base of the balloon are provided to prevent the fiber from pointing
in random directions. Optionally, the fiber is made stiff so that
it stays axial. Alternatively or additionally, the fiber is
attached to an inner lumen used for the guide wire and which
remains generally axial. Optionally, the fiber is aimed away from
any surfaces of the balloon to prevent inadvertent penetration.
Optionally, nearby areas are covered with a reflective coating.
[0220] Referring back to FIG. 4, optionally, a target or mirror 406
is provided for fiber 230, to distribute and/or otherwise control
the location and/or spatial extent of explosion 232. A target is
optionally used to absorb the energy at the target location and a
mirror is optionally used to assist in redistributing the energy in
the fluid filling the balloon. In an exemplary embodiment of the
invention, the target is formed of carbon or aluminum oxide.
Optionally, the target heats and boils fluid near it. Alternatively
or additionally, the target itself explodes or evaporates at least
in part. Optionally, the wavelength used by laser 410 is absorbed
by the fluid used and/or by one or more impurities (e.g., dye or
suspended particles) mixed therein. Optionally, the impurity is
selected to selectively absorb the laser energy. Optionally, the
concentration is selected so that the depth of penetration of the
laser energy is a known amount and has a known effect (e.g.,
impulse sharpness and spatial distribution of foci). Optionally,
the impurity used is the one used in eye photo-treatment, for
example Indocyanine green and/or India ink. In an exemplary
embodiment of the invention India ink (e.g. Spot Indian ink from GL
supply company) is employed at a concentration of 2%, optionally
5%, optionally 10% or greater or lesser or intermediate
concentration in order to increase energy absorption. Optionally,
this increased energy absorbtion causes a more rapid pressure
increase inside the balloon.
[0221] Target 406 is optionally a metal element. Alternatively or
additionally, target 406 is a decomposing element, such as silver
azide.
[0222] In an exemplary embodiment of the invention, the target is
made of a material that absorbs the laser energy and forms a known
volume of gas when hit by the laser light. Optionally, the target
itself explodes. Optionally, the target comprises multiple target
layers and/or a significant thickness, so that additional laser
pulses will also cause evaporation of parts of the target.
[0223] Optionally, the target comprises a capsule whose shell is
transparent to the wavelength used and whose contents are not.
[0224] Optionally, the target is formed on the fiber tip that
delivers the laser energy, for example, as a layer of dye or metal
coating.
[0225] In an exemplary embodiment of the invention, the laser
source is a Nd: YAG laser and a dopant capable of absorbing at the
wavelength of 1.064 microns is used. Example dopants are carbon and
metal particles. Other materials that absorb between 0.800 and
1.100 microns may be used, for various laser wavelengths, for
example diode lasers. Optionally, India ink may be used as
described above.
[0226] In an exemplary embodiment of the invention, the laser
source provides wavelengths that are absorbed in water, for example
Holmium pulsed laser 2.1 microns, from an Erbium pulsed laser at
2.9 microns, or other wavelengths above 1.9 microns (for example
the 1940 nm). The absorption spectrum of water is well known and
wavelengths for which the absorption coefficient is high (and
transmission means available) may be used. Optionally, the
shock/pressure waves may be shaped by selecting a lower or higher
absorption coefficient and/or different shapes for the beam.
Optionally, a protective barrier is provided to prevent material
affected by the laser from being injected outside of the balloon.
In an exemplary embodiment of the invention, a balloon or membrane
is provided around the fiber tip. Optionally, a membrane is
provided inside the balloon. Optionally, while there is a fluid
path between the fiber tip and the apertures, this path is indirect
and significantly reduces the ejection of heat-affected material.
Filling the balloon is not necessarily hampered. Optionally, the
fiber tip is distanced from the apertures, for example, being
outside the balloon. Optionally, a pre-defined capsule for
absorbing energy and remaining sealed, is provided.
[0227] Optionally, one or more internal baffles 408 are used to
guide the effects of explosion 232, for example, setting paths
lengths for the shock/pressure waves, aiming the shock/pressure
waves, to impinge on the balloon wall at desired angles and/or for
absorbing energy and/or slowing down an impulse attack rate, in
some directions. Optionally, the guiding comprises distributing the
waves more evenly spatially and/or temporally.
[0228] While explosion 232 has been shown inside balloon 212, it
may be provided outside the balloon, for example, within 30, 20,
15, 10, 5 or fewer mm from the inflatable part of balloon 212, for
example, distally or proximally. Optionally, the area of the
explosion is surrounded by a strengthening layer, for example, a
layer of plastic or metal, optionally rigid, which may serve to
prevent rupturing of catheter 210 and/or assist in guiding
explosion waves 234 towards the balloon.
[0229] In an exemplary embodiment of the invention, the balloon is
formed of standard materials, such as Nylon 12 or PET. In an
exemplary embodiment of the invention, the balloon is sized for its
application, for example, 1, 2, 2.5, 3 or 4 mm for relatively small
vessels such as the coronaries or brain vessels. Larger diameters
may be used, for example, in veins and in the prostate (e.g., 7-10
mm). A balloon may also be sized for treating the aorta or the
abdominal aorta, for example, to treat calcifications or an aortic
stenosis.
Exemplary Provided Materials
Structural Materials
[0230] In an exemplary embodiment of the invention, the injected
material is a structural material which changes the structural
(e.g., mechanical) properties of the tissue it is injected into. An
example of a structural material is a glue or cement which hardens,
for example, Bioglue Surgical Adhesive, Dermabond cyanoacrylate or
collagen (in certain forms). Optionally, a non-hardening material
is used, for example, silicon gel, carbon nano tubes, collagen (in
certain forms), carbon fibers, plastic fibers and/or glass fibers.
It is noted that the purposes of stiffening and/or strengthening
blood vessels to prevent collapse and/or dissection thereof may be
served even if the entire wall 204 is not made rigid. Various
amounts of material may be injected based on the material used
and/or effect desired. For example the injected material may
comprise 5%, 10%, 20%, 30%, 50% or a smaller, intermediate or
larger percentage of the volume of the tissue. Optionally, the
injection is not spatially dense, for example, there being
non-injected areas, for example of dimensions of 0.3 mm, 0.5 mm, 1
mm, 2 mm in minimum or maximum extent. Optionally, the injection
fills only part of a thickness of the tissue, for example, not
reaching substantially to within 10% of the edge of the tissue.
Optionally, the injected material collects in certain spatial
forms, for example elongate needle, where the length (radial) to
width ratio is less than 1:1 or 1:2. Another exemplary arrangement
is a flat arrangement, where a plume has a height to width ratio of
2:1, 3:1 or more. Generally, a smaller amount of injected material
is desired provided the desired mechanical and/or biological
changes are achieved.
[0231] In an exemplary embodiment of the invention, after
injection, wall 204 changes elasticity, for example, increasing if
an elastic material was injected or decreasing if a malleable
material was injected.
[0232] Optionally, the structural material is mixed in with a
bioactive or other material, for example of a type described
below.
[0233] In an exemplary embodiment of the invention, the structural
material is of a type not normally present in the tissue into which
it is injected, at least not in significant amounts.
[0234] Optionally, the structural material is provided instead of
or in addition to a stent. Optionally, a less stiff stent is used
due to the provision of structural material. Optionally, the stent,
accompanied by the glue injection, is at least 50%, 70%, 80% or
more flexible that a standard suitable stent and/or there is
reduction in metal content of 50%, 70%, 80% or more. In an
exemplary embodiment of the invention, reduction in metal thickness
allows stenting in small ducts, for example, smaller than 2 mm, 1
mm, 0.7 mm, 0.5 mm or smaller intra body ducts. Optionally, the
amount of material in the stent is reduced as compared to an
indication assumed to be correct by a physician. Optionally, a
softer material is used for the stent, for example thin (as opposed
to thick) plastic. Optionally, the stent is made
biodegradable/absorbable, for example, biodegradable plastic or
sugar. Optionally, a biodegradable stent is made more safe by the
stent adhering to structural material (e.g., glue) injected by the
balloon into or near the vessel walls, so that as the stent
decomposes, the vessel wall prevents larger pieces of the stent
from going with the blood flow.
[0235] Optionally, the reduction in stent material amount may
reduce complications.
[0236] Optionally, the structural material comprises fibers,
optionally fibers that are curled shut and coated with a material,
such as sugar or certain plastics, which will dissolve and release
the fibers after time.
[0237] Optionally, the material is dissipated when not in solid
tissue (e.g., when in a blood flow) and/or dissolves. Optionally,
the material is biodegradable. Optionally, these properties are
used to reduce danger if the glue penetrates tissue past the blood
vessel wall.
[0238] Optionally, the material hardens in contact with tissue
and/or blood.
[0239] Optionally, the injected material comprises a suspension of
particles. Optionally, the suspended particles will conglomerate
and have a structural effect when inside the tissue, where fluid
may be squeezed out and/or migration is in narrow channels. In the
blood, such particles will disperse. Optionally, the particles set
after time, once they meet. Optionally, the particles are selected
to be of a size comparable to endothelial pores (or larger) and/or
comparable in size to inter cellular spaces.
[0240] Optionally, a two part material (for example PMMA) is used,
in which a first component material is injected into the walls and
then a second component material (e.g., a catalyst or hardener) is
injected. It is expected that such materials will dissipate in the
blood stream, preventing sufficient concentrations of the materials
from meeting and/or interacting with each other. Optionally, the
heat provided during such a reaction is used to further prevent
restenosis.
[0241] In an exemplary embodiment of the invention, balloon 212 is
moved after injection of the material, to prevent sticking of the
material thereto. Optionally, the balloon is rotated during a
setting time of the material. Alternatively or additionally, a
clean saline (or other physiologically acceptable) solution is
"sweated" out of balloon 212, at a low pressure, which sweating
cleans out apertures 414 and/or removes any surface residue of the
injected material. Optionally, the sweated material includes a
catalyst or solvent that prevents hardening of the injected
material. Optionally, the balloon is coated with a material to
which the structural material does adhere, for example Teflon or a
silicon oil coating. Optionally, the balloon is removed before the
material completes a setting process, for example, using a material
with a 30 minute setting process and removing the balloon after 5
minutes. Optionally, a timer is provided with kit for using the
system, which timer indicates when it is time to remove the balloon
and prevent setting.
[0242] Optionally, the balloon is kept inflated while the glue
hardens or semi-hardens. Optionally a blood flow bypass pathway is
provided in the balloon, for example, a conduit, as known in the
art.
[0243] In an exemplary embodiment of the invention, the balloon
includes a pressure sensor, used to measure the response of the
wall of the vessel to applied pressure and thus assess the effect
of the treatment.
Dye and/or Radio-Opaque
[0244] Alternatively or additionally to a structural material, a
dye/marker is injected. Optionally, the dye is used to identify
regions in a later treatment (e.g., an extent of cancer, for
surgery). Alternatively or additionally, the dye/marker is a
radio-opaque material, which serves as an indication of stent
position or treatment location. Optionally, the injection is
patterned, for example so that a particular treatment and/or
parameters thereof can be read from an image of the treated
vessel.
[0245] Optionally, a dye component is used to estimate the amount
of material injected into the vessel walls and/or lumen.
Softening Materials
[0246] In an exemplary embodiment of the invention, a material that
softens plaque and/or other tissue is injected. Optionally, this
injection is made prior to a PTCA procedure, so that the PTCA
procedure will not only flatten the plaque but also drain it.
Optionally, a structural material is injected after PTCA and/or
softening. Optionally, a drainage hole is formed in the plaque for
draining the softened plaque, for example, using an advancable
sharp tip in the catheter, for example, provided along the
guidewire or extending out of the balloon. Optionally, a suction
lumen is provided to suck out the plaque. Optionally, the sharp tip
is provided along the suction lumen.
Bioactive Materials
[0247] In an exemplary embodiment of the invention, the injected
material is a bioactive material, for example, a material which
prevents inflammation and/or tissue proliferation, such as
Rapamycin taxol, immune-sensitizing or desensitizing drugs and/or
gene therapy substances. Optionally, the material is encapsulated,
for example, in nanoparticles, so that a slow release over a period
of time such as 1-3 months is provided. Other exemplary periods are
less than a week, between a week and a month and between three and
six months or more.
[0248] Optionally, the bioactive materials supplement the
structural material, for example, the structural material having a
short term effect before the structural material dissipates, while
the bioactive materials have a longer effect, such as causing
fibrosis. An example of such a pair is PLA and Rapamycin.
Optionally, the short term effect is immediate or starts within a
few minutes or hours, for example up to a day or two. A long term
effect, for example, lasts several months or years and may start,
for example, after a day or a week.
[0249] In an exemplary embodiment of the invention, the methods
and/or apparatus in accordance with some embodiments of the
invention allow a reduction in volume of drug and/or other material
used. In an exemplary embodiment of the invention, insertion
directly into the tissue, and optionally with a small penetration
hole which may self-seal, reduces leakage into the blood and
possible side effects thereof. Optionally, the balloon remains
inflated after ejection of the material, to prevent further
leakage. In an exemplary embodiment of the invention, the surface
to volume ratio of the material is better than for surface
application, due to the high pressure which can, for example,
ensure multiple narrow and deep insertions of the material into the
vessel. In an exemplary embodiment of the invention, the use of
needleless injection using short impulses may cause less pain to
the patient and/or shorten treatment time.
[0250] In an exemplary embodiment of the invention, the bio-active
material is DNA or other genomic material, such as RNA (of various
types), viruses, and plasmids.
[0251] In an exemplary embodiment of the invention, the amount of
injected material is less than 10 cc, for example, less than 1 cc,
for example, 0.01-0.03 cc for a coronary blood vessel.
[0252] In an exemplary embodiment of the invention, the injected
material is prepared and/or provided near or at the treatment time,
for example, for pharmaceuticals with a short life time.
Cytotoxic Materials
[0253] In some exemplary embodiments of the invention, the injected
material is a material. Examples of cytotoxic materials include,
but are not limited to, chemotherapeutic agents, organic solvents
(e.g. alcohols), fibrotic agents and metals (e.g. gold). Fibrotic
agents may include, but are not limited to, formalin, papavain and
curare. Fibrosis in the target tissue may block an electrical
signal. Cytotoxicity may be desirable, for example in tumor
treatment or other targeted tissue ablation. Targeted tissue
ablation may have applications, for example, in treatment of atrial
fibrillation and/or to mimic the effects of intestinal
resection.
Aperture Manufacturing Methods
[0254] Various methods may be used to manufacture the apertures
(214, 414). FIGS 5A-5D illustrate various designs which assure that
the future apertures remain sealed until a desired pressure is
reached within the balloon. In an exemplary embodiment of the
invention, a PTCA procedure is performed by inflating the balloon
to a pressure below the desired pressure which creates apertures.
Optionally, apertures are created when material injection is
provided. Optionally, the apertures are 20 microns, 30 microns, 50
microns, 100 microns or other smaller intermediate or greater,
dimension, in size. Optionally, the center-to center distance is
0.3 mm, 0.5 mm 0.7 mm or a smaller, intermediate or greater
distance.
[0255] In some embodiments of the invention, a balloon is formed
first and then the apertures are formed. In other embodiments, a
first layer is formed with apertures and then a second layer,
without apertures is provided on top of it or beneath it (see FIG.
5E).
[0256] FIG. 5A shows a balloon design 500 with these later set of
properties, in which an inner layer 502 has a plurality of nascent
apertures 504 formed therein and an outer layer 506 is continuous.
Optionally, this design prevents negative interaction (such as
clotting) between apertures 502 and surrounding blood. According to
this embodiment of the invention, apertures are created when layer
506 is ruptured at points corresponding to nascent apertures
504.
[0257] FIG. 5B shows an alternative design 510 in which a solid
layer 516 is provided between nascent aperture layers 512 and 518.
Optionally, the outer apertures are provided with a material that
prevents clotting. According to this embodiment of the invention,
apertures are created when solid layer 516 is ruptured at points
corresponding to the nascent apertures in layers 512 and 518.
[0258] The strength of the solid layer and/or depth of the
apertures are configured to have desired properties of tearing only
above a desired threshold pressure.
[0259] FIG. 5C shows a design 520, in which a plurality of nascent
apertures 524 are formed in a single layer 522 of a balloon.
Optionally, the thickness of the layer at the hole is 20-95% of the
wall thickness of the balloons. Optionally, the layer at the hole
is pre-weakened, for example, being punctured.
[0260] In an exemplary embodiment of the invention, an Eximer or
other laser type is used to ablate material from the balloon,
thereby forming the nascent apertures. Optionally, a light
reflecting layer is provided between two balloon layers, to control
laser penetration. Alternatively or additionally, the absorption
properties of the two layers may be different. Optionally,
different layers are formed of different materials.
[0261] In an exemplary embodiment of the invention, hot needles are
used to form through or blind apertures in balloon 212.
[0262] In an exemplary embodiment of the invention, a water jet is
used to drill the nascent apertures.
[0263] Optionally, a mask is used during nascent aperture formation
to prevent damaging the balloon except at areas where a nascent
aperture is desired.
[0264] In an exemplary embodiment of the invention a mold, used to
manufacture the balloons, contains micro protrusions that make
nascent holes, for example, when forming the balloon by blowing a
plastic tube in the mold. Alternatively or additionally, the mold
and/or the blown tube are covered with grains of salt or another
water-soluble and/or biocompatible material, which is later washed
off, leaving pores.
[0265] FIG. 5D shows a balloon design 530, in which a plurality of
apertures 534 are filled with a temporary filling 536. When filling
536 goes away (on its own or is removed), the apertures are
created. In an exemplary embodiment of the invention, filling 536
is a material the dissolves in body fluids. Optionally, the
dissolution takes time, so that a PTCA procedure can be carried out
before dissolution and weakening of balloon 530. Alternatively or
additionally, filling 536 weakens at body temperatures. Optionally,
it is not filling 536 that weakens, but an adhesive that attaches
it to the rest of balloon 530 which weakens. Optionally, a
non-weakening section is provided so the filling will remain
attached to the balloon.
[0266] In an exemplary embodiment of the invention, filling 536 is
dissolved using a solution inside balloon 530, for example, a
gelatin filling or a polyspridine filling. Optionally, clot
dissolving material is used to dissolve a filling made of clot-like
device. Any leaking material may be useful to prevent clotting
caused by the procedure (if any). Optionally, filling 536 is
weakened by the inflation of balloon 530 to a maximum diameter.
[0267] In an exemplary embodiment of the invention, filling 536
does not fail due to time and/or material issues, but is weaker
than the rest of balloon 530, so that while a smooth balloon
surface may be presented, once a threshold pressure and/or pressure
change rate is achieved, filling 536 fails and allows ejection of
material.
[0268] The apertures may have various shapes. For example, the
radial profile can be straight as shown. Optionally, the radial
profile is cone like, which may assist in aiming the ejected
material. Optionally, an hourglass or an inverted cone profile are
provided.
[0269] The surface form of the aperture is optionally circular or
square. Optionally, an aspect ratio other than 1:1 is provided, for
example, for elongated apertures that eject a plume that has a
significant width (and a relatively small thickness).
[0270] FIG. 5E shows a balloon design 540, with an additional
exemplary mechanism for creation of nascent apertures 504 in main
balloon wall 502. According to design 540, an inner balloon 526
expands from a deflated state (dotted lines) to an inflated state
(solid lines) to seal apertures 504 by covering them from inside
thereby transforming them to nascent apertures. Balloon 526 is
filled with contents via lumen 503 and remains contained within
balloon 502, optionally after advancing along or inside guidewire
501. Optionally, the filling of balloon 526 causes inflation of
balloon 526 and/or balloon 502. In an exemplary embodiment of the
invention, balloon 502 is positioned in proximity to a stenosis
which is optionally crushed by an initial inflation of the
balloons.
[0271] In an exemplary embodiment of the invention, an optical
fiber 230 deployed through lumen 503 conducts an optical energy
pulse 232 which generates shockwaves through the interior of
balloons 526 and 502. Shockwaves 232, optionally from a laser
energy pulse, increase the pressure within inner balloon 526
suddenly to a desired level. At most points, inner balloon 526 is
supported by outer balloon 502. However, at points where inner
balloon 526 is in contact with a nascent aperture 504, the sudden
increase in pressure causes rupture of inner balloon 526 creating
an actual aperture from the nascent aperture. Rupture of inner
balloon 526 causes it to shrink to its original un-inflated
diameter. This shrinking optionally occurs in about 0.03 seconds or
less. In an exemplary embodiment of the invention, rupture of inner
balloon 526 causes ejection of the contents outwards through
apertures 504 of balloon 502 as described hereinabove. In an
exemplary embodiment of the invention, inner balloon 526 is
resistant to rupture at pressures of 15 atmospheres, optionally 30
atmospheres, optionally, 40 atmospheres, optionally, 50
atmospheres, optionally, 60 atmospheres, optionally 68 atmospheres
optionally 75 atmospheres, optionally 100 atmospheres or
intermediate or lesser or greater pressures. Optionally, outer
balloon 502 does not rupture at these pressures. Optionally, the
sudden release of high pressure through newly unmasked apertures
504 creates an ejection velocity of liquid of 60 m/s or more.
[0272] In an exemplary embodiment of the invention (FIG. 5E), inner
balloon 526 ruptures without an applied energy pulse. One of
ordinary skill in the art of engineering will be able to construct
inner balloon 526 and outer balloon 502 so that inner balloon 526
is adapted to burst at a desired inflation diameter and/or volume
within outer balloon 502. Construction considerations include
Young's modulus, tensile strength and thickness of the materials
employed to construct balloons 526 and 502. Operation of this
embodiment is similar to the embodiment described above in the
context of FIG. 5E except that no energy pulse is employed.
According to this embodiment, inflation of balloon 526 expands it
within balloon 502 transforming holes 504 to nascent holes by
sealing them. At a predetermined diameter or volume, balloon 526
bursts and balloon 502 does not. This bursting of balloon 526
exposes holes 504 in balloon 502. The liquid content of balloon 526
exits through holes 504.
[0273] FIG. 5F shows an exemplary variation of balloon design 540
which permits rupturing inner balloon 526 separately from ejection
of material via newly unmasked apertures 504. In the pictured
embodiment, a portion of inner balloon 526 is stretched away from
outer balloon 502 to one or more attachment points 233. Attachment
points 233 are optionally radio opaque markers of the type commonly
included in a conventional angioplasty balloon. Stretching brings a
portion of inner balloon 526 into proximity with a distal tip of
optical fiber 230. Optionally, a localized shockwave 232 is applied
from distal tip of fiber 230 and ruptures inner balloon 526.
Alternatively or additionally, optical fiber 230 heats radio opaque
marker 233 which melts or burns inner balloon 526 and causes it to
rupture. In an exemplary embodiment of the invention, the distal
tip of fiber 230 is either in contact with inner balloon 526 or a
short distance away (e.g. 0.2 to 1 mm). The location of distal tip
of fiber 230 is near the ring 233. Ring 233 can be a radio opaque
marker (e.g. gold or a gold alloy) or a restriction band or some
enlargement in inner balloon 526 itself. The amount of energy
delivered by the distal tip of fiber 230 in order to tear the
internal balloon 526 in the stretched ring region is optionally 0.5
Joules, optionally 1 Joule, optionally 2 joules, optionally 3
joules or more.
[0274] In an exemplary embodiment of the invention, distal tip of
fiber 230: delivers a second energy pulse of 3 Joules, optionally
more, to eject material outwards from apertures 504. Optionally,
energy pulses delivered by distal tip of fiber 230 last about
200-300 microseconds. Optionally, the two bursts of energy are
applied, separated by a pause of about 0.02 to 0.1 seconds.
[0275] Alternatively or additionally, a distal tip of optical fiber
230 physically ruptures inner balloon 526 (e.g. by puncture or
tearing). Rupture of inner balloon 526 causes it to shrink as
explained above with respect to FIG. 5F, and permits the contents
of the balloon to begin to exit through newly unmasked apertures
504 in outer balloon 502. The exit velocity of the contents at this
stage is determined by the internal pressure in balloon 526 at the
time of its rupture.
[0276] According to exemplary embodiments of the invention depicted
in FIG. 5F, rupture of inner balloon 526, whether from an energy
pulse, heating of radio opaque block 233 or from physical contact,
is followed by a main energy pulse 232. Main energy pulse 232
delivered after rupture of inner balloon 526 provides a high
pressure shockwave which ejects contents of balloon 502 outwards
through newly unmasked apertures 504 as described hereinabove. The
main energy pulse 232 is optionally provided by optical fiber
230.
[0277] In an additional exemplary embodiment of the invention (FIG.
5F) rupture of inner balloon 526 is facilitated by constructing
inner balloon 526 of a light sensitive material. According to this
embodiment of the invention, cumulative exposure to light weakens
balloon 526. Optionally, light energy 232 is delivered via optical
fiber 230 and weakens inner balloon 526. Optionally, light energy
232 is characterized by a first wavelength. In an exemplary
embodiment of the invention, a main energy pulse 232 (optionally
characterized by a second wavelength) causes weakened balloon 526
to rupture and permits ejection of contents through apertures 504
at high velocity as described hereinabove.
[0278] FIG. 5G shows an exemplary variation of balloon design 540
in which rupturing inner balloon 526 leads directly to ejection of
material via newly unmasked apertures 504. The pictured embodiment
is operable without a laser. In the pictured embodiment, a ring 530
with a diameter (D) constrains inner balloon 526. As inner balloon
526 inflates, it is stretched away from outer balloon 502. The
critical inflation pressure at which inner balloon 526 bursts
varies with D and/or a thickness of balloon 526 and/or a material
from which balloon 526 is constructed and/or a conformation of the
portion of ring 530 which contacts balloon 526. In an exemplary
embodiment of the invention, an increase in D causes the critical
inflation pressure at which inner balloon 526 bursts to increase.
Inflation of inner balloon 526 is optionally via holes 505 in lumen
503. In an exemplary embodiment of the invention, the critical
inflation pressure at which inner balloon 526 bursts is 10,
optionally 12, optionally 14, optionally 16, optionally 18,
optionally 20 atmospheres or lesser or greater or intermediate
values. As in embodiments described hereinabove, rupture of inner
balloon 526 transforms nascent apertures 504 into actual apertures.
Material flows outward through these apertures and is injected into
surrounding tissue.
Balloon Filling
[0279] While, in an exemplary embodiment of the invention, the
balloon is filled using lumen 402, optionally, at least the
injected material is not provided through the lumen, for example,
to prevent clogging thereof and/or to reduce waste.
[0280] In an exemplary embodiment of the invention, injection is
into the balloon via a one way valve in the balloon, for example,
injection through a rubber plug at a tip thereof.
[0281] In an exemplary embodiment of the invention, material is
provided as a layer on the inside of the balloon. Optionally, a two
layer balloon is provided, with the material to be ejected provided
between the layers and the apertures provided only in the outer
layer. Optionally, the outer layer is provided as a cap which can
be mounted on an existing balloon design, for example, being
adhered to the base of the balloon and/or catheter.
[0282] In an exemplary embodiment of the invention, two balloons
are provided in tandem on the catheter, with one balloon (for
example the distal balloon), being a PTCA balloon and the second
balloon (for example the proximal balloon), being a material
injection balloon. Optionally, different lumens are provided for
each balloon. This optionally allows for lower pressures and or a
more structured balloon to be used for material insertion.
Injection Patterns
[0283] The actual pattern of the injected material may vary. In
some embodiments of the invention, the system is manufactured to
have a desired pattern. Alternatively or additionally, the pattern
may be controlled, for example, using controller 427 or other
means, for example, by varying the balloon pressure during the
procedure or by varying the pulses of the laser thereby modifying
the shape of the pressure/shock waves.
[0284] In an exemplary embodiment of the invention, the pattern of
injection is decided based on one or more of:
[0285] (a) type and/or wall properties of blood vessel, such as
thickness;
[0286] (b) resistance of vessel to inflation (e.g., feedback to
saline source 412);
[0287] (c) type of plaque;
[0288] (d) X-Ray image of the area to be treated, from before or
during the treatment;
[0289] (e) nearby structures which may be damaged or otherwise
affected by spill of the injected material;
[0290] (f) type of mechanical modification desired for blood
vessel;
[0291] (g) previously missed (un-treated) areas; and/or
[0292] (h) length of stent vs. length of damaged area.
[0293] These may be used, for example, to decide on the type of
structural support and/or drug treatment and/or other treatment
desired for the lesion.
[0294] In an exemplary embodiment of the invention, the depth of
penetration is controlled by the power and/or duration of the
pressure pulse and/or its increase rate. Optionally, penetration
depth is controlled, for example to ensure that all desired layers
of a vessel wall and/or plaque are treated and/or to control
over-penetration past the vessel wall.
[0295] Optionally, the direction of penetration is modified by
changing the angle of the apertures relative to the balloon (e.g.,
to not be perpendicular as shown).
[0296] In an exemplary embodiment of the invention, uniformity of
material injection is controlled by one or more of non-uniform
distribution of apertures and/or non-uniform size of apertures, so
that the total amount of plume material per unit area is the same,
for example, taking into account a non-uniform pressure profile
inside the balloon. Optionally, for new materials, for example,
with different compressibility and/or acoustic velocity than water,
the sizes of the apertures are calculated by experimenting with
different apertures sizes to determine the effect of explosion on
the transport through different apertures. Optionally, instructions
are provided with a kit explaining what hole sizes and/or pressure
profiles to use for what materials and/or lesions.
[0297] In an exemplary embodiment of the invention, the aperture
sizes and/or number are such that there is no significant pressure
loss from the apertures that first start ejecting material, before
the other apertures tear and start ejecting material. Optionally,
additional material is provided through the lumen, under pressure,
to maintain the intra-balloon pressure.
[0298] In some cases, non-uniform injection is desired. Optionally,
the non-uniformity complements stent design, for example,
additional material being injected at the ends of a treated area
and/or past a stent position and/or at points where the stent (or
stent support) is weaker. In an exemplary embodiment of the
invention, injection is provided between stent struts, where
support is less.
[0299] In an exemplary embodiment of the invention, different
materials and/or amount of materials are injected for plaque and
vessel wall and/or for different plaque types. Optionally, the
balloon includes a radio-opaque marker that indicates a rotation of
the balloon on an x-ray image. Optionally, different balloons are
used for providing lobes of material in different direction.
Alternatively, the filling of the balloon may be replaced.
Optionally, a same balloon is used for multiple axial and/or
rotational positions relative to the treated area, with some
positions the balloon being activated in a manner that increases
material injection relative to other positions. Optionally, for
positions with plaque in the vessel, a layer of setting material is
provided at the plaque. Optionally, a material is squeezed between
the balloon wall and the vessel wall (e.g., using a low pressure
and optionally reduced balloon inflation pressure), so that the
material can seep into cracks and/or other damage made to the
vessel wall and/or plaque thereat. Optionally, this procedure is
applied at known plaque positions.
[0300] In an exemplary embodiment of the invention, pre-procedure
or during procedure a diagnosis of the lesion to be treated is
made. Depending on the diagnosis, a desired pattern of material
distribution is selected and is optionally implemented by selecting
a suitably apertured balloon and/or balloon cap.
[0301] In an exemplary embodiment of the invention, the apertures
are arranged in a regular grid pattern or any pattern suitable for
manufacturing. Optionally, a helical pattern is used. Optionally,
the holes sizes and/or distribution and/or source of pressure
impulse are arranged to correspond to a known or expected plaque
configuration. For example, as many vessels have a plaque lesion in
a form that is thicker at the middle than near the ends, a balloon
that ejects material more forcefully and/or in greater amounts near
the middle may be manufactured. In special cases, other balloons,
for example, which eject more at one end, are used, based on a
diagnosis of the lesion to be treated.
[0302] In one embodiment, apertures are provided only on one
segment (axial and/or radial) of the balloon. Optionally, this is
used for partial occlusion or for selective injection such as where
additional injection is needed at one side of a vessel or reduced
injection is needed at a different side of a vessel.
[0303] In an exemplary embodiment of the invention, ejection
(optionally sector-limited) of a structural material is used to
attach a graft or a patch to a blood vessel. In an exemplary
embodiment of the invention, the graft or patch to be attached is
provided on the balloon and inflation of the balloon positions the
patch/graft in place. Ejection of structural or bioactive material,
for example, plumes that skewer the patch and the vessel or
material that passes the patch and collects between the patch and
the vessel, serve to fix the patch to the vessel. Optionally, one
or more apertures are pre-formed in the patch or graft and aligned
with the apertures of the balloon, to help material provision past
the patch. Optionally, the balloon includes one or more needles
thereon, on which needles the graft may be engaged and through
which needs the material is optionally provided.
[0304] In another embodiment, an overtube (not shown) with an
opening formed in a side thereof, is optionally provided over the
balloon, so that injection can only be through apertures aligned
with the opening. Optionally, the overtube is flexible and/or
pleated, and is strong enough to resist the ejection pressure.
Optionally, this overtube is provided once the narrowing in the
vessel is expanded by the balloon.
[0305] In an exemplary embodiment of the invention, the amount of
material injected is controlled by one or more of:
[0306] (a) pulse duration (e.g., pulse of laser or of pressure
source);
[0307] (b) pulse shape (e.g., square, triangle or sinus);
[0308] (c) number of pulses;
[0309] (d) delay between pulses;
[0310] (e) contact pressure;
[0311] (f) energy in a pulse; and/or
[0312] (g) combinations of the above, for example, a long train of
short pulses as compared to a short train of longer pulses.
[0313] In an exemplary embodiment of the invention, energy amounts
and the spatial and/or temporal density of provision is selected to
not damage the blood vessels. For example, it appears that in some
cases, a 3.5 Joule pulse is too strong for coronary vessels and the
injected material will pass through and past the wall. For example,
a 0.15 Joule pulse of 300 microsecond length, applied to 100 holes
of 30-50 micron diameter has been found to not perforate a coronary
vessel and also not penetrate the wall with the injected material.
While these numbers may depend on various factors, in an exemplary
embodiment of the invention, the energy in such a pulse scheme is
greater, for example, 0.5 or 1 Joule or possibly 2 Joule or 3 Joule
or intermediate values. If the number of holes is changed or the
pulse length varied, the energy may need to be changed in an
appropriate manner. In cases where it is desirable to pass past the
coronary vessel walls, a greater energy may be used, for example, 4
Joule, 5 Joule, 7 Joule, 10 Joule or more.
[0314] In an exemplary embodiment of the invention, one or both of
two transport mechanisms may be optionally and/or selectively used,
a pressure impulse wave mechanism, where a sharp increase in
internal balloon pressure causes part of the balloon filling to
leave through the apertures, and a fluid induced laser shockwave
transport method, where a high speed heating of fluid at a point
generate a bubble gas which causes material to be ejected with
force.
[0315] In an exemplary embodiment of the invention, in a pressure
type system, a stroke and pressure applied by an external piston is
controlled, the stroke length controlling the amount of material
ejected and the force and envelope of the stroke controlling the
penetration depth. Optionally, the stroke length is manually or
automatically settable, for example, by moving a stop.
[0316] In an exemplary embodiment of the invention, in a shock wave
(laser ablation of water) system, the volume and depth penetration
are controlled by modifying one or more of energy per pulse, pulse
duration, and number of pulses.
[0317] In some embodiments of the invention, both patterns are
used, for example, utilizing a larger volume effect of the pressure
mechanism and a lower volume but higher speed injection of the
shock effect.
Alternative Impulse Generation Methods
[0318] In an exemplary embodiment of the invention, a sudden
increase in pressure and/or generation of shock waves inside the
balloon is generated by a different mechanism than described above.
Such pressure/shock waves may also be used for other purposes, such
as surface sweating of a material.
[0319] In an exemplary embodiment of the invention, instead of a
laser source, an electrical spark method is used which generates a
spark between two conductors under high voltage, causing an
explosion and associated shock/pressure waves. While the energy may
be provided by wire along the catheter, optionally it is provided
using eddy currents induced by an outside-the-body magnetic
field.
[0320] In an exemplary embodiment of the invention, a capsule with
a compressed spring (or other mechanical element) is used as the
impulse source. In an exemplary embodiment of the invention, when
the capsule is heated by laser and/or electricity, the potential
energy stored in the spring changes to kinetic energy which results
in fast tearing or expanding of the capsule and associated waves.
Optionally, the energy is stored in the spring ahead of time, for
example, at manufacture. Optionally, the capsule is in two parts
and the heating only allows them relative motion, but no fluid
enters the capsule.
[0321] Optionally, such a capsule includes an explosive or gas
forming element, such as a lump of silver azide, that when
triggered, generates gas that expands the capsule and increases
intra-balloon pressure.
[0322] FIG. 6B shows a catheter head 620, in which a balloon 622
includes a target 624, for example, a leaf spring 624 bent to a
curved shape by a strong cord (not shown in the picture, made for
example of an electro-resistive material, a heat sensitive material
and/or a laser light absorbing material). When heating the cord it
tears, and the leaf spring jumps to a shape indicated by a
reference 626, thus causes shock/pressure waves.
[0323] In an alternative exemplary embodiment of the invention,
target 624 is a circular disc (or square) with a diameter of 400
microns, a thickness of 590 microns and a curve radius of 200
microns. Application of energy to the disc will cause distortion,
culminating in a sudden catastrophic shape change in the disc,
which change will release some of the energy provided by the laser
(or other source) and cause the shock/pressure effects. Optionally,
the energy is supplied at a rate higher than loss via mechanisms
such as heat.
[0324] In an exemplary embodiment of the invention, the balloon
and/or catheter are used as an elastic energy storage element. In
an exemplary embodiment of the invention, pressure to the catheter
is increased until the apertures tear and fluid from the balloon
rushes out. Optionally, the parts of the catheter near the balloon
and/or the balloon and/or a gas filled bladder in the balloon serve
as storage areas that are near the fluid injection, so that there
is a reduced loss of pressure
[0325] In an exemplary embodiment of the invention a small balloon
or bag encapsulate the tip of the fiber (in a laser embodiment) and
heating of a material in this small balloon will generate the
desired impulse.
[0326] It is noted that in several of the mechanisms described
above, while there is a change in pressure in the balloon that
causes material injection, the actual change in volume of material
inside the balloon is minimal or zero, so that the amount of
material actually injected may be small. Repeated pulses may
increase the total output volume. Between pulses, topping off of
the fluid pressure may be used to maintain balloon inflation.
[0327] FIG. 6C shows a system design 640, in which a balloon 642
may itself have no apertures, but one or more tubes 644 and 646 are
provided outside of balloon 642 and include apertures 648 for
material injection, therein. Tubes 644 and 646 may be attached to
each other and/or be arranged differently than shown, for example,
as a spiral around balloon 642. Optionally, balloon 642 is used to
ensure contact between apertures 648 and the surrounding blood
vessel. Optionally, a pressure pulse is provided via tubes 644 and
648, to inject material. Optionally, an optical fiber is provided
in each arm, to generate a local impulse for the arm. Optionally,
tubes 644 and 648 are compressible and the pressure pulse is
provided by balloon 642, for example using methods described above,
whereby the pressure wave travels through the wall of balloon 642
and into tubes 644 and 648. Optionally, balloon 642 is used for
rhythmically squeezing the tubes and thus pumping material out of
apertures 648. A one way valve (not shown) is optionally provided
in side tubes 644 and 646 to prevent backflow in the tubes.
[0328] Optionally, such external tubes are used for treating a
prostate, where, in general, a larger diameter catheter may be
used.
[0329] FIG. 6D is a schematic showing of a gas-powered two stage
system 650 for creating a pressure impulse in a balloon 652. A gas
pressure source, for example a compressed gas cylinder 670 with an
optional pressure regulator 668 that is used to charge a cartridge
666, is selectively released by a valve 664. Upon release a first
piston 662 is advanced, which moves a plunger 660. Plunger 660
advances a hydraulic fluid 658, optionally with a low resistance,
through some or the entire catheter to balloon 652. A filling 654
of balloon 652 (which may be high viscosity) is optionally
separated from the hydraulic fluid by a second plunger 656.
Optionally, slow advancing of fluid 658 inflates the balloon and
fast advancing causes an impulse that ejects material. The
hydraulic fluid may be a closed system filled during
manufacture.
[0330] FIG. 6E is a schematic showing of a variant system 672 in
which a filling 674 of the balloon is used instead of hydraulic
fluid 658. Filling 674 may be provided ahead of time, for example,
at manufacture. Optionally, any added drug is provided by injection
into the balloon.
[0331] FIG. 6F is a schematic showing of a system 676, in which a
two capsule 678 tears apart and thereby causes a pressure wave. In
an exemplary embodiment of the invention, pressure is provided to
the capsule via a lumen 680. Capsule 678 is provided in two parts,
682 and 684, which are coupled by a sliding seal and maintained
together by one or more tension elements 686, for example, wires.
As the pressure is increased, the tension on the wires increases
until they fail, releasing the capsule parts. Optionally, the
pressure applied by the capsule can be determined by calculating
the failing point of the wire and the cross-section of the
capsule.
[0332] FIG. 6G shows a system 688, in which a wire 690 is pulled
back to deliver a pressure impulse in a balloon 692. In an
exemplary embodiment of the invention, a plunger 694 is attached to
the distal end of wire 690 and fits inside balloon 692, such that
pulling back will force fluid movement before plunger 694.
Optionally, the catheter has a rigid body 696 (e.g., for use in a
prostate). Alternatively, a braided body or other design that
resists kinking upon axial compression is used. Optionally, the
inflation of the balloon serves to reduce or prevent movement of
the balloon during pullback of the wire (or other forces such as
applied in other embodiments).
[0333] FIG. 6H shows a system 700, in which a capsule 704 is
provided inside a balloon 702 and a spring 706 is positioned to
selectively expand capsule 704. However, a tension element 708,
such as a wire, prevents such extension. When wire 708 is released
or cut, the spring can expand the capsule and create a pressure
pulse. Optionally, wire 708 is attached to capsule 704 at a point
710, which is selectively releasable. In one example, point 710
burns or melts upon application of an electric field to wire 708
(or a light pulse to an optical fiber tension element). Optionally,
wire 708 is attached as well at a point 712 to capsule 704, such
that tension in wire 708 is mainly between points 710 and 712 and
inside the balloon element and not along the entire catheter.
[0334] In this and other embodiments, the balloon can be pre-filled
with the material to be injected.
[0335] FIG. 7 is a graph showing penetration depth of a dye into a
bovine aorta under various conditions. The injection system was a
gas powered system that applied up to 68 atmospheres to a piston
attached to a tube 4 mm in diameter and 250 mm in length. The tube
is attached to a hollow tube section with a diameter of 9.6 mm and
120 radial holes with a diameter of 50 microns and inter-hole
spacing of about 2 mm. The system provides an amplification of
pressure of a factor of 8.
[0336] In the graph, the solid line indicates the penetration depth
in mm as a function of the applied pressure, for a 0.3 cc bolus.
The large dashes are for a case of 0.184 cc and the small dashes
for 0.2446 cc. As can be seen, increasing pressure increases
penetration depth. Size of bolus also appears to increase the
penetration depth. Each point on the graph is an average of several
(e.g., 4) experiments. The aorta was firmly attached to the
ejection holes, probably with a contact pressure below 2
atmospheres.
[0337] FIG. 8 is a graph showing the peak pressure as measured in
the hollow tube section as a function of time for a 68 atmosphere
pulse (e.g., amplified by a factor of 8 during delivery). The pulse
ended when all the material was ejected from the hollow tube. The
mean velocity of the jet is estimated to be 60 m/s. It is believed
that penetration depth is affected by one or both of mean velocity
and peak velocity. In an exemplary embodiment of the invention,
other mean and/or peak velocities can be achieved, for example, 10
m/s, 40 m/s, 100 m/s, 200 m/s, 300 m/s or smaller, intermediate or
larger speeds. If a sufficiently large pressure is applied, very
high peak velocities can be achieved, for example, 1000 m/s, 1500
m/s or faster, such as above the speed of sound in tissue (e.g.,
using shock waves).
Additional Applications
[0338] The above-described system and method may be used, for
example, for coronary vessels and cerebral vessels.
[0339] The system and/or method, optionally with some variations
(e.g., balloon diameter and/or flexibility, volume of injected
material) may be adapted for other tubular organs in the body, for
example, the gall bladder duct, the urethra, the ureters, the
esophagus, air passage ways in the lungs, such as the bronchi and
various peripheral blood vessels. It should be noted that in some
of these embodiments, the above apparatus and/or methods are used
to apply treatment without making a structural change and/or
implanting a stent in the vessel being treated.
[0340] Illustrative examples are provided in some detail to
demonstrate the scope and flexibility of the invention. These
examples should not be construed to limit the invention, either
singly or collectively.
Treatment of Atrial Fibrillation
[0341] In an exemplary embodiment of the invention, (FIG. 9A) a
balloon 212 according to the present invention is deployed through
a cardiac auricle 900 into vessel 200, optionally a pulmonary vein,
to treat atrial fibrillation. In an exemplary embodiment of the
invention, a cytotoxic substance is ejected radially or
transaxially outwards from balloon 212 (arrows) to contact cells
lining pulmonary vein 200. Optionally, the cytotoxic substance
causes ablation and/or reduces a metabolic activity and/or alters
an electrical property of cells lining the pulmonary vein. The
ablated tissue blocks transmission of an electrical signal, such as
an electrical signal causing Atrial Fibrillation. In an exemplary
embodiment of the invention, an alcohol, such as ethanol, serves as
a cytotoxic agent. A flow through balloon may optionally be
employed to permit uninterrupted blood flow through pulmonary vein
200.
[0342] Various atrial fibrillation embodiments of the invention
employ balloons of different physical configurations. For example,
a balloon shape which helps align the balloon in the pulmonary vein
may be employed (FIGS. 9A and/or 9B). Optionally, the balloon will
have a "flow through" design so that blood flow is not interrupted.
In some exemplary embodiments, injection into tissue is radial with
respect to the balloon (FIG. 9A). In some exemplary embodiments,
injection has an axial component with respect to the balloon but
injects in a ring shaped pattern on a tissue surface surrounding
the pulmonary vessel 200 (FIG. 9B).
Use in the Digestive Tract
[0343] Delivery of a cytotoxic substance to a selected area or
areas in the intestine as described above could be used to block
digestion of food, either temporarily or permanently. In order to
permanently block food digestion, an amount of cytotoxic substance
delivered to the intestine must be sufficient to kill progenitor
cells responsible for replenishing cells lining the intestinal
lumen. In an exemplary embodiment of the invention, this technique
offers an alternative to intestinal resection in the treatment of
obesity. Alternatively or additionally, using an agent which causes
only temporary blocking of digestion can serve as a means of
screening obese patients to identify those that are likely to
benefit from intestinal resection.
[0344] Alternatively or additionally, a balloon according to the
present invention may be employed to deliver a cytotoxic and/or
chemotherapeutic agent to a tumor located in the digestive tract.
The tumor may be located, for example, on an inner surface of a
digestive organ such as the stomach, small intestine or large
intestine. Alternatively or additionally, pancreatic tumors may be
treated by deploying a balloon according to the present invention
through the intestinal tract via the gall bladder to the
pancreas.
[0345] Balloons for use in the GI tract may have different physical
configurations depending upon their intended function. For example,
a balloon to deliver cytotoxic substances to the intestine to
prevent digestion would employ apertures spaced radially and
axially along balloon with a length corresponding to the length of
intestine to be treated. Alternatively or additionally, a balloon
to deliver cytotoxic substances to a tumor located on the
intestinal wall 088/04789 has apertures positioned along a side of
a balloon positioned proximal to the tumor to be treated.
Treatment of the Urinary Tract
[0346] In an exemplary embodiment of the invention, a tumor, or
group of tumors, on an inner surface of a urinary bladder is
treated with a balloon according to the present invention.
Treatment by direct injection of material into the tumor according
to the present invention permits delivery of a higher concentration
of a chemotherapeutic agent than would typically be achieved using
previously available alternatives (e.g. "washing" the urinary
bladder with the chemotherapeutic agent). Alternatively or
additionally, direct injection of material into the tumor according
to the present invention reduces a cytotoxic effect of the
treatment on non-tumor cells lining the urinary bladder and/or a
systemic cytotoxic effect.
[0347] FIG. 9C illustrates a balloon 212 according to the present
invention deployed through a lumen of a urinary bladder 910.
Optionally, a camera 920 is provided to permit positioning of
balloon 212 in proximity to a tumor 915 growing on an inner wall of
bladder lumen. Inflation of balloon 212 is not necessarily required
for positioning. In an exemplary embodiment of the invention, a
cytotoxic agent is ejected outwards from balloon 212 (arrows) and
injected into tumor 915. The cytotoxic agent may optionally be a
chemotherapeutic such as, for example, BCG. Injection may
optionally be axial as pictured. Use of balloons according to the
invention permits a high concentration of a therapeutic agent to be
applied directly to tumor 915. Alternatively or additionally,
direct injection using a balloon, limits dispersal of the applied
agent throughout the volume of bladder 910. The high concentration
may be, for example, 1, optionally 10, optionally 25, optionally
50, optionally 75, optionally 100 nanograms per milligram of target
tissue or lesser or intermediate or greater values.
[0348] In an exemplary embodiment of the invention, a balloon 212
with a large surface containing injection ports (as in FIG. 9B)
delivers a chemotherapeutic agent to a large area. This exemplary
configuration may be employed, for example, to inject axially into
an inner wall surface of a urinary bladder 900. In the pictured
embodiment, the tumors (not shown) are grouped around ureter 200.
Optionally, a portion of balloon 212 protrudes into ureter 200 to
correctly position the balloon. Optionally, this eliminates the
need for a camera to assist in positioning.
Treatment of Tumors in Other Lumens
[0349] The methodology described in conjunction with FIG. 9C is
generally applicable to cancer treatment at other body lumens. In
an exemplary embodiment of the invention, a balloon 212 is deployed
in any body lumen to deliver a therapeutic agent to a tumor from
outside the tumor.
[0350] The invention has clinical utility in, for example,
treatment of oral, nasal, pharyngeal, lung, esophageal, gastric,
intestinal, colonic, pancreatic, rectal, cervical, uterine and
prostate cancer. Optionally, balloon 212 may be mounted on an
endoscope, for example a colonoscope, to aid in directing it to a
desired location.
Intratumor Chemotherapy
[0351] In an additional exemplary embodiment of the invention, a
balloon 212 is guided to a position within a tumor to deliver a
therapeutic agent to a tumor from within the tumor. Optionally,
guiding is through a blood vessel. Optionally, the balloon is
guided through a capsule wall. In an exemplary embodiment of the
invention, a guidewire tip and/or a guiding catheter make a hole in
the capsule wall and a balloon according to the invention is guided
through the hole. In the context of cancer treatment, the
therapeutic agent may be, for example, a chemotherapeutic agent, a
sclerosing agent, a gene therapy agent, an anti-angiogenic agent,
an antibody or any other agent deemed useful in tumor treatment. In
an exemplary embodiment of the invention, balloon 212 is employed
to deliver therapeutic agents to tumors either on surfaces or
inside organs.
[0352] In an exemplary embodiment of the invention, a balloon
according to the invention is inserted directly into a tumor via a
channel created specifically to facilitate insertion of the
balloon. The channel may be created, for example, by insertion of a
guidewire, cannula or stylet.
Dermatologic Applications
[0353] In an exemplary embodiment of the invention, a balloon 212
may be employed to deliver a therapeutic agent intradermally to
cells of a relatively large skin surface. For applications of this
type, balloon 212 may be configured to have a substantially flat or
slightly curved aspect (as in FIGS. 9B and/or 9C) so that it
conforms to a skin surface to be treated in size and/or shape.
Optionally, a balloon constructed for dermatologic applications
will be stiff or flexible at the portion destined to be positioned
near or contact the skin. In an exemplary embodiment of the
invention, the balloon is filled with a therapeutic agent at a
pressure in the range of 1 atmosphere. Optionally air is removed
from the balloon. In an exemplary embodiment of the invention,
delivery of the therapeutic agent into the skin is driven by an
energy pulse which produces a pressure of 10, optionally 20,
optionally 50, optionally 100, optionally 150, optionally 200
atmospheres or lesser or greater or intermediate values.
[0354] Optionally, this embodiment is useful in local treatment of
a skin disease such as psoriasis, dermatitis or leprosy, acne,
tinea, pityriasis and herpes zoster. Relevant therapeutic agents
include, but are not limited to cortisone, calcipotriol, steroids
and combines including one or more of these agents. In an exemplary
embodiment of the invention, the balloon delivers cortisone and at
least one additional hormone, optionally a steroid hormone.
[0355] Intradermal, as opposed to transdermal, injection relies
upon dispersion or spreading of a small amount of a delivered agent
over a relatively large skin surface and delivering the agent at a
velocity which introduces the agent into the skin, but not through
the skin. The present invention avoids the need for topical
application or subcutaneous delivery. Previously available
needleless injection devices typically provide an injection
velocity of 100-500 m/s which causes injected material to pass
through the skin. In an exemplary embodiment of the invention, the
injection velocity for intradermal treatment is in the range of
10-50 m/s, optionally 10-40 m/s, optionally 10-25 m/s, optionally
10-15 m/s or lesser or intermediate or greater values. These lower
velocities are sufficient to propel liquid droplets into the skin
without causing penetration to subdermal tissue layers as a
standard needleless injector does.
Transmucosal Applications
[0356] In an exemplary embodiment of the invention, a balloon
according to the present invention is employed to inject
medications through mucous membranes to underlying cells. Most skin
surfaces are not covered by a mucosal layer unless they are within
a body cavity (e.g. oral cavity). Optionally, injection of
medications through mucous membranes permits treatment of any cell
layer covered by a mucosal layer. Mucosal layers line, for example,
the digestive tract, the genitourinary tract, the buccal cavity,
the nostrils, the oral cavity and the nasal sinuses.
[0357] Mucosal layers exist to protect underlying cells. Previously
available alternatives typically permitted delivery of therapeutic
agents onto a mucosal layer, but not through the mucosal layer.
Because mucosal layers in general are characterized by a high
turnover rate and/or a high non-specific binding capacity, delivery
of a therapeutic agent onto the mucosal layer using prior art
technology often effectively reduced the amount of agent delivered
to a desired target. Alternatively or additionally, mucosal
secretions are frequently re-absorbed into the body (e.g. mucous
secreted in the nasal sinuses may drip into the mouth where it is
subsequently swallowed and digested). This re-absorption can lead
to undesired systemic side effects of mucosally delivered drugs.
For at least these reasons, prior art solutions for local delivery
of therapeutic agents to a tissue covered by a mucosal layer were
characterized by a low efficacy and/or high incidence of systemic
side effects.
[0358] In an exemplary embodiment of the invention a balloon
according to the invention is inserted into at least one nostril.
Optionally, inflation causes the balloon to conform to at least a
portion of a nostril and/or nasal sinus. Delivery of a therapeutic
substance may, for example, ameliorate or relieve symptoms of
rhinitis (e.g. allergic rhinitis or rhinitis caused by infection)
and/or sinusitis and/or upper respiratory tract infections.
[0359] Useful therapeutic agents in this context include, but are
not limited to antihistamines, decongestants, steroids and
antibiotics. Alternatively or additionally, a sclerosant agent may
be employed. Sclerosants may act by shrinking an inferior turbinate
and/or other hypertrophic nasal tissue(s). Optionally, the
shrinking of hypertrophic tissue relieves nasal obstruction.
[0360] Previously available topical delivery devices for the nose
and/or sinuses delivered therapeutic agents at low pressures (e.g.
spay bottle, metered dose inhaler, nebulizer and vaporizer). The
low pressure delivery generally did not cause the delivered
agent(s) to pass through the mucous membranes into underlying
cells. Because of the high turnover of mucous, especially in acute
rhinitis, much of the active ingredient(s) was not absorbed by
target cells using these delivery methods.
[0361] Previously available systemic treatment modalities required
large amounts of medication to reach an effective local (e.g.
intranasal) concentration. The large amounts of medication required
for systemic treatment often caused undesirable systemic side
effects.
[0362] Optionally, a catheter may be employed to guide a balloon
212 deeply into a mucosally lined lumen. This may be useful, for
example, in treatment of chronically infected nasal sinuses or
uterine inflammation and/or infection and/or tumors.
[0363] In an additional exemplary embodiment of the invention a
balloon is inserted into a stomach or duodenum to treat gastric or
duodenal ulcers. Useful therapeutic agents in this context include,
but are not limited to, acid reducers and antibiotics.
[0364] In an additional exemplary embodiment of the invention a
balloon is inserted into an intestine to treat an inflammatory
bowel disease (e.g. Ulcerative colitis or Crohn's disease). Useful
therapeutic agents in this context include, but are not limited to,
anti-inflammatory drugs (e.g. steroids and/or non-steroid
anti-inflammatory drugs [NSAIDS]) and immunosuppressive drugs.
Buccal Cavity Treatment
[0365] In an exemplary embodiment of the invention, a balloon
according to the invention is employed to deliver a therapeutic
agent to the soft palate. Optionally, the therapeutic agent is
useful in reducing snoring and/or obstructive sleep apnea.
Optionally, the therapeutic agent is a sclerosant. Sclerosants can
increase formation of connective tissues such as collagen by
inducing fibrosis. Optionally, stiffening of the soft palate is
achieved. Injection can be applied on the surface or by
introduction of a catheter.
[0366] In an exemplary embodiment of the invention, a balloon 212
delivers a therapeutic agent to the tonsils and/or adenoids.
Optionally, the therapeutic agent is useful in reducing swelling
and/or has antibiotic properties. Optionally, the therapeutic agent
is a sclerosant. In an exemplary embodiment of the invention,
treatment with a balloon 212 obviates a need for surgical
intervention.
[0367] In an exemplary embodiment of the invention, a balloon
according to the invention injects a therapeutic agent into the
tonsils and/or adenoids and/or soft palate and/or inferior nasal
turbinates. Relevant therapeutic agents in this context include
glues, sclerosants, antihistamines, decongestants, corticosteroids
and antibiotics In an exemplary embodiment of the invention, the
therapeutic agent includes a glue which makes the tissue stiffer.
Optionally stiffening and/or shrinking caused by the therapeutic
agent reduces vibration. Optionally, a decrease in vibration
ameliorates snoring.
Scar Therapy
[0368] In an exemplary embodiment of the invention, a balloon 212
delivers a therapeutic agent which mitigates scarring. Optionally,
the scars to be treated resulted from granulation and/or tumor
growth. Optionally, treatment of scar tissue in the trachea and/or
esophagus is undertaken. Optionally, the therapeutic agent includes
a scar modifying medication. Optionally, the scar modifying
medication includes a steroid hormone and/or mithomycin C and/or
immuno-suppressant drug. In an exemplary embodiment of the
invention, treatment of airway stenosis or stenosis of the
digestive tract is achieved. Optionally, symptoms of cystic
fibrosis and/or Autoimmune diseases such as: myasthenia gravis
and/or Graves' disease and/or Rheumatoid arthritis and/or Necrotic
vasculitis and/or System lupus erythematodis and/or Scleroderma
with pulmonary fibrosis are ameliorated and/or relieved. In an
exemplary embodiment of the invention, delivery is to tissue
surrounding the scar and/or to the scar itself.
Gene Therapy
[0369] In an exemplary embodiment of the invention, a balloon with
injection ports delivers a medicament containing microparticles
and/or nanoparticles. Optionally, the medicament contains a gene
therapy reagent. In an exemplary embodiment of the invention, the
balloon facilitates somatic cell gene therapy by injecting a
nucleic acid vector into a target tissue.
Other Considerations
[0370] Optionally, the system and method are used to deliver a
material to only one side of the balloon. Exemplary applications
include the larynx, pharynx, vocal cords, voice box and/or base of
tongue.
[0371] Optionally, the system and/or method are used for cosmetic
applications, for example for stiffening tissue by injecting
structural material into the tissue, for example, using a catheter
(optionally without a balloon) inserted under the skin.
[0372] In an exemplary embodiment of the invention, injection of
structural material is used for strengthening an anastomosis
region, for example, to help support vessels damaged by the
manipulation and/or tensions associated with anastomosis.
Optionally, injection of a structural material does not prevent
further growing in diameter of the treated vessel. This may be
useful, for example, when the treated vessel is a small vessel
which may grow (e.g., to respond to additional demand), or when
treating children. Optionally, changes in diameter allow the vessel
to respond to pulse waves and/or changes in blood pressure.
[0373] The following PCT publications, the disclosures of which are
incorporated herein by reference, describes methods for anastomosis
and hole closure which may be used together with injection of
materials into the treated region, for example, to reduce the
volume of a connector used or to structurally stabilize diseased
tissue: WO 99/62408, WO 99/62415, WO 00/56226, WO 00/56223, WO
00/56227, WO 00/56228, WO 01/4162, , WO 01/41624, WO 01/70091, WO
01/70118, WO 01/70119, WO 01/70090, WO 02/47561, WO 02/30172, WO
02/47532, WO 02/074188, WO 03/026475, WO 2004/028377, WO
2004/028380, WO 2004/028376, WO 2005/027750, WO 2004/028378, WO
2004/043216, WO 2005/013836, WO 2005/055801. The disclosures of all
of these documents are incorporated herein by reference.
[0374] In an exemplary embodiment of the invention, injection of
glue or other structural material is used to aid attachment to a
wall of a blood vessel. In one example, glue is injected into a
wall to strengthen it so that it may be used for attaching an
anastomosis connector thereto. In an exemplary embodiment of the
invention, a calcified aorta is treated, to prevent breakaway of
material during anastomosis or bypass procedures. In an exemplary
embodiment of the invention, the injection is used to attach small
hooks or stubs (e.g., of the glue material) to the wall, on which
stubs a patch or a connector or other vessel may be attached.
Optionally, the stubs are created by the apertures including an
offset, for example 0.5-1 mm. Optionally, the stubs are created by
injection using a needle and pulling back the needle slowly.
[0375] In an exemplary embodiment of the invention, while injection
using needleless methods are described, needle based methods may be
used, especially for structural materials such as glue. Optionally,
a plurality of needles are provided on the outside of the balloon.
Alternatively or additionally, the needles are provided on tubes
644 and 646. Alternatively or additionally, the needles are
provided on a balloon or other expandable structure inside of
balloon 642 and then, when deployed, the needles extend through the
wall of balloon 642 (or other balloon design) and penetrate the
nearby vessel walls. In an exemplary embodiment of the invention,
the needles are 1 mm or less in length and/or diameter, for
example, less than 0.5 mm. Optionally, 5, 10, 20 or an intermediate
or larger number of needles are provided.
[0376] In a prostate application, the balloon (e.g., 642) is
optionally made more or completely rigid, for example, being a
metallic balloon. This may be useful for prostate treatments.
Optionally, the rigid balloon does not expand, and is more properly
termed a hollow element. Alternatively, the balloon expands but is
non-compliant.
[0377] While the above embodiments have focused on radial ejection
of material, optionally, axial ejection is provided. In an
exemplary embodiment of the invention, a balloon employed for
forward injecting of material holds the ejection port in a stable
orientation and may help prevent misses of the target and/or motion
of the ejection port due to the third law of motion. Optionally,
forward ejection is used to help dissolve thrombosis, for example,
by assisting in the distribution of material into the
thrombosis.
Physical Configuration of the Balloon
[0378] The above description has focused on in-vivo treatment
especially of blood vessels and that focus has led to use of the
term "tube" and other geometrical shapes which have been described
and used for generality. However, methods and/or apparatuses
described herein are suitable for use in treatment of other tissue
and/or treatment outside the body so that various embodiments of
the invention include physical configurations adapted for the
intended use.
[0379] In an exemplary embodiment of the invention, the balloon
used will have a non tubular geometry. Optionally, a balloon
according to the invention will be characterized by at least one
flat side. Optionally, a balloon according to the invention will be
in the form of a polygonal solid such as, for example, a cylinder,
a cone, a pyramid or a cube.
[0380] In an exemplary embodiment of the invention, a tube need not
have a full body nor have a circular cross-section. Alternatively
or additionally, balloon 212 may optionally be fashioned so that it
forms an inner flow through channel when inflated. A flow through
channel may be created, for example by fashioning balloon 212 as a
toroid ring or hollow cylinder. This type of design may be
advantageous, for example, when treating a major blood vessel, such
as the aorta or a carotid artery. The flow through channel prevents
ischemia when the balloon is inflated in the blood vessel.
[0381] Optionally, balloons according to the invention may be sized
for specific applications. For example, a balloon for coronary
applications might have a diameter of 2 to 3.5 mm and a length of
10 to 25 mm. A balloon intended for deployment in the prostate
might be considerably larger, for example a diameter of 6 to 11 mm
and a length of 20 to 40 mm.
[0382] Alternatively or additionally, particular modifications may
be desired for certain vessel types. For example, the aorta is
thicker, while a coronary vessel is thinner, thus suggesting
different ejection parameters, powers and/or balloon pressures and
sizes. For example, an aorta may be 3 mm thick, while a coronary
vessel may be less than 1 mm thick.
[0383] Measurements are provided to serve only as exemplary
measurements for particular cases. The exact measurements stated in
the text may vary depending on the application, the type of vessel
(e.g., artery, vein, xenograft, synthetic graft), shape of plaque
(e.g., local, elongate, thin, thick, outer remolding, vulnerable)
and/or sizes of vessels involved (e.g., 1 mm, 2 mm, 3 mm, 5 mm,
aorta sized).
[0384] It will be appreciated that the above described methods of
material injection may be varied in many ways, including, changing
the order of steps and the types of tools used. In addition, a
multiplicity of various features, both of method and of devices
have been described. In some embodiments mainly methods are
described, however, also apparatus adapted for performing the
methods are considered to be within the scope of the invention. It
should be appreciated that different features may be combined in
different ways. In particular, not all the features shown above in
a particular embodiment are necessary in every similar embodiment
of the invention. Further, combinations of the above features, also
for different embodiments, are also considered to be within the
scope of some embodiments of the invention. Also within the scope
of the invention are surgical kits which include sets of medical
devices suitable for performing, for example, a single or a small
number of tissue treatments. In some embodiments, one or more of
the devices, generally sterile, described above, are packaged
and/or sold with an instruction leaflet and/or portions of
treatment materials, describing the device dimensions and/or
situations for which the device should be applied and/or what
materials should be used. With regard to the controller, various
implementations are considered within the scope of the invention,
including hardware, firmware software, computers loaded with
suitable software and/or computer readable media having software
thereon suitable for supporting the methods described herein.
Section headings where they are provided are intended for aiding
navigation and should not be construed to limiting the description
to the headings. When used in the following claims, the terms
"comprises", "includes", "have" and their conjugates mean
"including but not limited to".
[0385] It will be appreciated by a person skilled in the art that
the present invention is not limited by what has thus far been
described. Rather, the scope of the present invention is limited
only by the following claims.
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