U.S. patent application number 10/742280 was filed with the patent office on 2004-10-21 for devices and methods for the delivery and injection of therapeutic and diagnostic agents to a target site within a body.
This patent application is currently assigned to SCIMED LIFE SYSTEMS, INC.. Invention is credited to Glines, Robert C., Weller, Gary B..
Application Number | 20040210188 10/742280 |
Document ID | / |
Family ID | 32031090 |
Filed Date | 2004-10-21 |
United States Patent
Application |
20040210188 |
Kind Code |
A1 |
Glines, Robert C. ; et
al. |
October 21, 2004 |
Devices and methods for the delivery and injection of therapeutic
and diagnostic agents to a target site within a body
Abstract
The present invention includes systems, devices and methods for
delivering and injecting a solution or agent into a target site
within the body for the purpose of treating or diagnosing the
target site. The target site may be bodily tissue (such as an
organ, vessel or bodily lumen), bodily substances (such as a tumor,
plaque and thrombus) or synthetic material attached to bodily
tissue (such as an artificial graft). The systems and devices of
the present invention include injection systems and components for
accurately and precisely delivering, injecting and perfusing a
therapeutic or diagnostic agent, preferably in a fluid form,
directly into the target site without the need to penetrate the
tissue with anything other than the agent itself. More
specifically, none of the embodiments employ a needle or other
penetrating device for creating a space within which the agent is
injected. The injection systems include embodiments for use in
intraoperative and interventional clinical settings, and generally
comprise, at least in part, a propulsion apparatus, a reservoir,
often called a syringe or ampule, for receiving and holding the
solution or agent, and a dispersion means for transporting the
solution or agent from the reservoir to the target site and for
perfusing or dispersing it within the target site. The surgical and
endovascular methods of the present invention include methods for
injecting an agent into a target site within the body for the
purpose of treating and/or diagnosing a target site or tissue
adjacent a target site. Various therapeutic applications in which
the invention may be employed include but are not limited to the
treatment of cardiac, cardiovascular, peripheral vascular, and
neurovascular diseases, AV access graft stenosis and thrombus
formation, cancer, rheumatoid arthritis, etc. More specific
examples of the types of applications that can be accomplished by
the present invention include, for example, the administration of
angiogenic solutions to an ischemic area of myocardium, the
delivery of a thrombolytic drug to a thrombus within a chamber of
the heart or to the peripheral or neuro vasculature, administration
of a solution to a portion of the atria contributing to atrial
fibrillation, or the delivery of an anti-angiogenic solution to a
solid tumor or through the vasculature supplying blood to a
malignancy.
Inventors: |
Glines, Robert C.; (Cameron
Park, CA) ; Weller, Gary B.; (Los Gatos, CA) |
Correspondence
Address: |
JONES DAY
222 EAST 41ST ST
NEW YORK
NY
10017
US
|
Assignee: |
SCIMED LIFE SYSTEMS, INC.
|
Family ID: |
32031090 |
Appl. No.: |
10/742280 |
Filed: |
December 18, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10742280 |
Dec 18, 2003 |
|
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09552401 |
Apr 19, 2000 |
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6716190 |
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Current U.S.
Class: |
604/68 |
Current CPC
Class: |
A61M 5/3007
20130101 |
Class at
Publication: |
604/068 |
International
Class: |
A61M 005/30 |
Claims
What is claimed is:
1. A system for injecting an agent into a target site within the
body, comprising: an ampule having a reservoir for holding a volume
of agent, the reservoir having at least one reservoir orifice; a
dispersion means distal to the ampule and having at least one
dispersion orifice; at least one pathway in fluid communication
between the at least one reservoir orifice and the at least one
dispersion orifice; and a propulsion mechanism operatively coupled
to the reservoir for propelling the agent from within the
reservoir, through the at least one reservoir orifice, the at least
one pathway, and the at least one dispersion orifice and into the
target site at a pressure sufficient to cause the agent to
penetrate the target site without penetrating the target site with
the dispersion means; wherein: the dispersion means comprises a
fixture having an atraumatic target-facing surface within which the
at least one dispersion orifice is located; and the target-facing
surface is smooth and substantially planar.
2. The system of claim 1, wherein the fixture has a cylindrical cap
configuration
3. The system of claim 1 wherein the target-facing surface has a
circular shape.
4. The system of claim 1 wherein the target-facing surface has an
oval shape.
5. The system of claim 1 wherein the target-facing surface has an
elliptical shape.
6. The system of claim 1 wherein the target-facing surface has an
arched cone configuration having a vertex and an arched
portion.
7. The system of claim 1 wherein the target-facing surface has a
single dispersion orifice.
8. The system of claim 1 wherein the target-facing surface has a
plurality of dispersion orifices in a quadrangle arrangement.
9. The system of claim 1 wherein the target-facing surface has a
plurality of dispersion orifices arranged along the perimeter of
the target-facing surface.
10. The system of claim 1 wherein the target-facing surface has a
plurality of dispersion orifices arranged in an annular array.
11. The system of claim 6 wherein the target-facing surface has a
plurality of dispersion orifices arranged along the perimeter of
the arched portion.
12. The system of claim 7 having a single pathway in fluid
communication between the single reservoir orifice and the single
dispersion orifice.
13. The system of claim 1 wherein the dispersion means has a
profile sufficient to be delivered through a less invasive
opening.
14. The system of claim 13 wherein the less invasive opening is a
port positioned within the patient's body.
15. The system of claim 13 further comprising an endoscope
integrally coupled with the system.
16. The system of claim 8 wherein the dispersion means comprises a
cannula having a proximal end and a distal end having an atraumatic
distal tip, and having a lumen extending there between.
17. The system of claim 16 wherein the atraumatic distal tip
comprises a target-facing surface.
Description
FIELD OF THE INVENTION
[0001] This invention includes various medical devices and systems
for use in surgical and interventional procedures. More
particularly, the invention relates to devices and systems for the
delivery and injection of therapeutic and diagnostic agents,
solutions or injectates into bodily tissue, bodily substances or
synthetic materials attached to bodily tissue, such as an
artificial graft. Additionally, the invention relates to methods of
delivering and injecting a solution at a target site within the
body for the treatment or diagnosis of that target site.
BACKGROUND OF THE INVENTION
[0002] Despite the continual advances in medical technology,
particularly in the treatment of heart disease, vascular disease,
cancer, pain, allergies, orthopedic repair and many other diseases
and conditions, there are a significant number of patients for whom
conventional surgical and interventional therapies are not feasible
or are insufficient to treat the disease or condition. For many
patients, medical treatment with drugs and the like is the only
feasible treatment available.
[0003] There have been many recent advances in drug therapies,
particularly with regard to cell or site-specific therapeutics (as
opposed to systemic therapeutics) such as pharmacologic agents
(e.g., anesthetics and analgesics) and biologic agents (e.g.,
genetically engineered material). Unlike the systemic
administration of therapeutics, typically taken orally or given
intravenously, much of the effectiveness of cell- or site-specific
therapeutics is based on the ability to accurately and precisely
deliver the therapeutics to the targeted site within the body.
[0004] Needle injection devices are the most commonly used means
for the site-specific administration of agents or solutions.
Although there have been advances in needle-based drug delivery
injection systems, these systems have significant shortcomings and
disadvantages. These shortcomings and disadvantages are
exemplified, for example, in gene therapy applications--the
implantation of genetic material or engineered cells in specific
targets in the human anatomy to create a therapeutic or
preventative effect.
[0005] Depending on the disease being treated, gene therapy can be
angiogenic or anti-angiogenic. The intended result of angiogenic
therapy is the promotion of angiogensis--a complex biological
process that results in the growth of new blood vessels. Angiogenic
therapy has been used experimentally for treating, for example,
cardiac ischemia, coronary artery disease (e.g., atherosclerosis),
and ischemia in peripheral vascular beds. Conversely,
anti-angiogenic therapy involves the reduction in the proliferation
of blood vessels, for example, to cut-off the supply of blood to a
tumor or to proliferating pannus-type tissue, and to inhibit the
abnormal growth of retinal vessels that leads to blindness.
[0006] An important factor in achieving the desired result of gene
therapy is direct exposure of the genetic material to a specific
target site for a sustained period of time. This is particularly
challenging for gene therapies that require delivering genetic
material to the nuclei of cells. Depending on the location of the
targeted tissue and the type of condition being treated, exposure
of the genetic material to the target site may involve direct
approaches, such as an open or less invasive surgical approach, or
endovascular approaches by means of a catheter. With any approach,
there are significant challenges in the delivery of genetic
material to the appropriate cells of the patient in a way that is
specifically targeted, efficient and safe.
[0007] For optimum "up regulation" of the gene therapy agent, the
agent must undergo some atomization in order to be effectively
perfused within the target site. If the gene therapy drug is not
sufficiently atomized (i.e., broken up into very small
micro-particles), dispersion and then absorption of the drug may be
greatly reduced, resulting in minimal to no positive affect on the
patient. Needle-based syringes are not capable of such atomization
and, instead, deliver the injectate in the form of a bolus, which
is less likely to be effectively dispersed and absorbed within
tissue.
[0008] Moreover, in certain applications of gene therapy, it is
important to minimize the systemic exposure of the gene therapy
agent in order to avoid unwanted side-affects. The use of a needle
or other penetrating means to inject the targeted tissue area
unavoidably involves making a hole into the target site. This
results in much of the injectate leaking back out of the hole, and
being released systemically throughout the body or being wasted.
This also results in increased treatment costs and requires more
injections, time and agent to achieve the desired affect.
[0009] Gene therapy has been used, for example, to create
angiogenesis in hypoxic (i.e., oxygen-deprived) heart tissue. In a
cardiac surgical procedure, the angiogenic solution is typically
delivered by making a number of syringe injections, typically in a
grid-like pattern, directly through the epicardium (i.e., the outer
surface of the heart) at the ischemic portion of the myocardium. An
equivalent endocardial approach (i.e., through the inside surface
of the heart) involves delivering a catheter employing a distal
needle to within a ventricular chamber and injecting the angiogenic
solution through the endocardium to the myocardium. The intent of
both approaches is to cause the cells in the target tissue to
express the desired growth factor protein continuously for a
desired time period. Other means of delivering cardiac angiogenesis
agents include injecting the agent within the pericardial sac
(i.e., intrapericardial), within the coronary arteries (i.e.,
intracoronary) or directly into the myocardium (i.e., the middle
layer of the heart wall).
[0010] Although some recent clinical studies have suggested that
there is some marginal resulting angiogenic response with
syringe/needle-based injection, there are definite disadvantages of
employing a syringe/needle-based injector or other
tissue-penetrating device. For example, myocardial ischemia
typically involves an affected surface area in the range of
approximately 3 mm.sup.2 to 10 mm.sup.2. A single needle injection
in ischemic tissue can only provide a solution dispersion in a much
smaller area defined by the size of the needle and the limited
ability of the agent to diffuse through the tissue. Thus, multiple
needle-based injections may be required in order to sufficiently
disperse the solution over the entire affected area. As the number
of injections increases, the procedure time is increased and a
greater volume of the gene therapy agent is required to effectively
treat the ischemic area. More time and greater drug volume increase
the cost of the procedure.
[0011] Furthermore, it is known that needle injections or
penetration into the tissue can traumatize or destroy tissue cells
and, as a result, increase a patient's risk of post-operative
arrhythmia. This is particularly due to the difficulty in precisely
controlling the penetration of the needle during injection. The
more injections or penetrations, the greater the cell destruction
and risk of arrhythmia. Still another disadvantage of multiple
needle-based injections of growth factor is the need to carefully
track the location of each injection site so as to prevent the
accidental delivery of growth factor to non-diseased tissue.
[0012] There are some gene therapies that do not involve
needle-based drug delivery. Instead, indwelling catheters and
drug-infused stents have been used for releasing the therapeutic
agent in a steady, controlled-release fashion. These approaches
present a greater risk of releasing the agent systemically.
Additionally, it is more difficult to assess the actual dosing of
the target area that takes place. Thus, these approaches have the
disadvantages of being less effective, not as safe, and more costly
than injections.
[0013] Another condition in which site-specific or local drug
delivery is commonly employed is in the treatment of peripheral
vascular disease (such as deep vein thrombosis and embolisms). One
such treatment is venous lytic therapy, the dissolving of blood
clots (thrombus) in the peripheral vasculature (e.g., femoral and
illiac arteries and veins). Lytic therapy involves systemically
infusing thrombolytics, such as urokinase, streptokinase, reteplase
and tPA. Other more recently developed procedures involve directly
delivering the thrombolytics into the thrombus site through the use
of indwelling infusion catheters. In order to effectively lyse the
thrombus, the thrombolytics are typically infused for many hours,
even as much as a day or more, increasing the necessary length of
hospital stay and the overall cost of the procedure.
[0014] Still another area in which the localized delivery of
therapeutics is indispensable is in the treatment of
arterial-venous (AV) access routes for renal dialysis. There are
several ways in which AV access is established. One is by means of
an AV graft, a tube made of a synthetic material such as teflon
(e.g., PTFE), which is implanted to connect an artery and vein in
the arm, for example. The graft takes approximately two weeks to
mature and should be placed at least a few weeks before use for
hemodialysis. Unfortunately, these grafts are prone to stenosis and
the spreading of infection, and typically only survive for not more
than about 11/2 years. Another type of AV access route is an AV
fistula. This is a surgical connection made between an artery and a
vein. The fistula, once surgically placed, takes around twelve
weeks to mature, and thus must be placed several months before
hemodialysis is anticipated. Although the infection and stenosis
rate of fistulas is far less than that of AV grafts, infection and
stenosis are not uncommon.
[0015] Double lumen catheters are another type of AV access means.
The may be used for long-term or temporary applications. Those used
long term are surgically placed in a tunneling fashion under the
skin. AV access catheters are typically placed into either the
subclavian or jugular vein. Occasionally, they are temporarily
placed in the femoral vein. Short-term AV access catheters are
generally placed when dialysis is needed emergently either when the
referral of the patient to dialysis is unduly delayed, or when a
permanent AV access fails and the patient is too unstable to have
it revised until after an emergency treatment. AV access catheters
may develop serious infections, or may thrombose, ultimately
leading to failure of the device. Moreover, the veins they are
placed in-are prone to clotting.
[0016] Conventional treatments for problems (e.g., stenosis,
infection and thrombus formation) that may arise with AV access
grafts, fistulas or catheters typically involve surgical
intervention, including the repair or replacement of the AV access
device, the physical removal of stenotic plaque and the chemical or
physical removal of blood clots. Clearly the elimination of any
surgical procedure is advantageous to reducing morbidity and pain.
Thus, there is still a need for an improved means and method for
treating and preventing conditions related to the use of AV access
devices.
[0017] The disadvantages of conventional drug delivery systems also
exist in the treatment of other conditions such neurovascular
disease, cancer, rheumatoid arthritis, etc. Accordingly, there is a
need for devices and methodologies for delivering drugs and other
solutions to bodily tissue which are more precise, efficient, and
effective, and less costly than conventional devices and methods.
Additionally, it is highly desirable to have devices and methods
for delivering solutions to bodily tissue that are safer and less
invasive than current devices and methods. There is also a need for
medical agent delivery devices that are packaged and supplied in
ways that make their use convenient and easy for self-application
and institutional use. Thus, there still exists a need for enabling
technology for the more effective and safe local delivery of
therapeutic agents.
SUMMARY OF THE INVENTION
[0018] The present invention includes novel means and methods for
delivering and injecting a solution or agent into a target site
within the body for the purpose of treating or diagnosing the
target site. The target site may be an area of tissue or a
substance affixed or adjacent to the tissue area or its cells. More
specifically, the target site may be an organ, a body lumen, a
vessel lumen, a solid tumor, a synthetic graft, plaque, thrombus,
etc.
[0019] The devices of the present invention include injection
systems and components for accurately and precisely delivering,
injecting and perfusing a therapeutic or diagnostic agent,
preferably in a fluid form, directly into the target site without
the need to penetrate the tissue with anything other than the agent
itself More specifically, none of the embodiments employ a needle
or other penetrating device for creating a space within which the
agent is injected.
[0020] The injection systems of the present invention include
embodiments for use in intraoperative and interventional clinical
settings as well as in certain non-clinical settings in which the
patient injects himself or herself. More specifically, they are
configured for delivering a solution from an ampule and injecting
it into a target site within the body or within an artificial graft
affixed to the body through either a surgical opening, a less
invasive surgical opening (such as through a trocar port), or
endovascularly.
[0021] Generally, the injection systems comprise, at least in part,
a propulsion apparatus, an ampule reservoir, often called a syringe
or ampule, for receiving and holding the solution or agent, and a
dispersion means distal to the ampule for transporting the solution
or agent from the reservoir to the target site and for perfusing or
dispersing it within the target site.
[0022] The propulsion devices of the present invention produce
pressures great enough to inject a solution or agent within the
target site without the need for a needle or any other penetrating
device. These devices may be powered by any appropriate propulsion
mechanism or energy, such as a spring-loaded member or a
self-contained inert gas (such as a cartridge containing carbon
dioxide, nitrogen, argon, etc.) for ejecting or propelling an agent
out of a reservoir. The propulsion apparatus is operatively coupled
to the reservoir and is used to propel the agent out of the
reservoir at a desired pressure such as in the range from about
1800 psi to about 2300 psi. The propulsion devices of the present
invention further comprises means for selecting the volume of agent
to be propelled from the reservoir as well as means for selecting a
pressure at which the agent is propelled from the reservoir.
Preferably, the propulsion devices are ergonomically configured to
be held and actuated by one hand of the user.
[0023] The ampule reservoirs of the present invention are intended
to hold at least one dose, but may, however, have any appropriate
volume for containing any appropriate dose of solution. The ampule
may be reusable or disposable after a single use. The ampule sits
within the housing of the propulsion device with its distal end in
sealed engagement with the dispersion means and its proximal end in
operative engagement with a piston which forces the agent out of
the reservoir upon activation of the propulsion device.
Alternately, the ampule may be modular form which can be releasably
coupled to the dispersion means to form a nozzle assembly which is
attachable to the propulsion device. The ampule may come pre-filled
from the supplier or may refillable by the physician.
[0024] The ampule reservoir and dispersions means of the present
invention each have at least one orifice through which the agent
can pass through as it is propelled. The dispersion orifice(s) most
preferably has a diameter in the range from about 0.1 mm to about
0.3 mm. The dispersion means is comprised of material(s) that are
capable of withstanding the forces of the pressurized fluid to the
extent that the pressure of the agent is substantially maintained
as it passes through the dispersion means.
[0025] The most significant difference between the injection
devices for use in surgical applications and those for use in
interventional applications is their respective configurations of
the dispersion means. In the surgical devices, the dispersion
fixture is in the form of a fixture attached distally to the ampule
reservoir. In the endovascular devices, it is in the form of a
catheter assembly attached distally to the ampule reservoir. It
follows that the means by which the respective dispersion means
attach to the ampule reservoir are also different.
[0026] The various dispersion fixtures for use with the surgical
devices, for both direct surgical and less-invasive surgical
approaches, have an atraumatic surface which, when operatively
positioned, faces the target site. The one or more dispersion
orifices are located in this target-facing surface, which, for most
of the surgical embodiments of the present invention, is smooth and
substantially planar. The target-facing surface has a selected
shape, size, and number and arrangement of dispersion orifices for
defining a selected pattern of dispersion at the target site. The
target-facing surface and/or the orifice arrangement may have a
shape or configuration, for example, in the form of a circle, oval,
ellipse, linear array, an annular array or an arched cone. In some
less-invasive procedures, the dispersion means has a lower profile
sufficient to be delivered through a less invasive opening. For
some less-invasive devices of the present invention, the
target-facing surface is not necessarily planar, but be a rounded,
tapered or flat tip of a cannula.
[0027] To enhance the precision and accuracy of dispersion of the
agent through the dispersion orifices, a jewel having an orifice
may be coaxially aligned on the proximal side of each dispersion
orifice. The jewel is made of a very hard material such as
stainless steel or a precious stone such as sapphire. The
dispersion orifice(s) are in fluid communication with the reservoir
orifice(s) by means of one or more pathways situated between them.
In the surgical embodiments and some less-invasive embodiments of
the present invention, each pathway is defined by a channel formed
either within the dispersion fixture or within the distal end of
the ampule. In other less-invasive embodiments, the pathway is the
lumen of a tube, such as a cannula or other tubular piece. The tube
may be malleable and steerable to facilitate delivery through a
narrow, sometimes tortuous path to the target site. Additionally,
these less-invasive embodiments may further comprise an
endoscope.
[0028] The injection devices for use in interoperative or
endovascular procedures employ a catheter as the means for
dispersing the injectate into the target site. The catheters of the
present invention are made of material(s) having physical
properties sufficient to maintain the pressure of the injectate as
it travels from the reservoir to the dispersion orifice. They each
have a proximal end, a distal end having a distal tip, and a lumen
there between. The distal tip has at least one dispersion orifice.
The proximal end of the catheter is in sealed engagement with a
distally tapering reservoir nozzle terminating in a reservoir
orifice. The engagement is accomplished by means of a coupler
mechanism, such as a leur fitting. A retainer means is then seated
over the ampule reservoir to further ensure that the coupler
mechanism is securely affixed to the ampule. Collectively, these
components provide a sealed, fluid pathway from the reservoir to
the catheter, and ensure the integrity of the pathway under
pressurized conditions.
[0029] The preferred location of the catheter dispersion orifice(s)
varies from embodiment to embodiment, depending on the
intraoperative application at hand. Generally, the dispersion
orifice(s) are located on the sidewall of the distal tip or at the
distally facing end of the tip. Catheters having the dispersion
orifice(s) within the sidewalls eject the agent laterally of the
catheter tip and define an injection vector path that is
substantially transverse or perpendicular to the longitudinal axis
of the catheter. The dispersion orifices may be arranged in a
circumferential pattern, a helical array, a number of linear arrays
running parallel to the longitudinal axis of the catheter, or any
other pattern that is suitable for the application. Catheters
having the dispersion orifice(s) within the distally facing end of
the catheter tip eject the agent distally of the catheter tip and
define an injection vector path that is substantially coaxial or
parallel to the longitudinal axis of the catheter.
[0030] The present invention further includes various surgical,
less invasive surgical and endovascular methods for delivering and
injecting a solution or agent to a target site within the body or
within a graft affixed to the body without the need to penetrate
the target site with other than the solution or agent itself. The
present invention also includes methods for treating or diagnosing
a target site within the body by means of a precisely delivered
solution or agent. These methods may be standalone procedures or
may be employed in the context of or as an adjunct to other
intraoperative or interventional procedures and therapies. For
example, a method of injecting a therapeutic agent into the heart
may be performed in conjunction with a CABG surgery or a
catheter-based, stent placement procedure.
[0031] The surgical and endovascular methods of the present
invention include methods for injecting an agent into a target site
within the body for the purpose of treating and/or diagnosing a
target site or tissue adjacent a target site. Generally, these
methods first involve accessing the target site within the body.
The access site can be either a direct surgical opening, a
less-invasive opening through which a port is placed, or a
percutaneous opening through which a catheter is delivered. An
ampule having a reservoir containing a volume of the therapeutic or
diagnostic agent is provided. The volume of agent is then propelled
from the reservoir at a selected pressure to a location proximate
the target site. This involves exerting a force on the agent
contained within the reservoir to provide the selected pressure.
The selected pressure has a value such that the pressure of the
agent as it makes contact with and disperses within the target site
is sufficient to cause the agent to disperse within the target site
without penetrating the target site with any other means. The agent
is then dispersed into the target site in a substantially
predefined pattern. When using a disposable ampule with a prefilled
volume of agent, the ampule may be replaced with a second ampule
containing a volume of the same or a different agent, and then
repeating the remaining steps with the second ampule and any
additional ampules necessary to complete the procedure.
[0032] As the physician deems appropriate, the step of positioning
may involve either contacting a surface of the target site with the
end effector or bringing it to within a selected distance from a
surface of the target site. In the context of a surgical procedure,
an end effector or dispersion means is-delivered through the
surgical opening and positioned proximate the target site. In a
less-invasive surgical procedure, this involves delivering the end
effector through a smaller opening such as a one made by a trocar
port and steering the end effector towards the target tissue area.
The less-invasive method may also involve the use of an endoscope
to view some of the steps of the procedure. Similarly, in an
endovascular procedure, a catheter is inserted into a percutaneous
opening and the catheter tip is delivered proximate to the target
site. The percutaneous opening may also be the external opening of
an AV access graft.
[0033] The present invention also includes methods of diagnosing a
target site. These methods generally involve percutaneously
accessing the vasculature of a patient. A catheter having a
non-penetrating catheter tip is provided and placed in fluid
communication an ampule reservoir containing a volume of a
diagnostic agent. The catheter is then inserted into the
percutaneous access site, and its non-penetrating tip is then
delivered proximate to the target site. A volume of the diagnostic
injectate is then injected through the catheter and into the target
site in a substantially predefined dispersion pattern at a pressure
sufficient to cause the agent to disperse within the target site.
The dispersion occurs without penetrating the target site with the
catheter. Finally, the area proximate the target site is then
viewed under fluoroscopy in order to determine the optimal location
and tissue depth for injecting a therapeutic agent.
[0034] The invention is useful in the delivery and injection of
precise, predetermined volumes of a therapeutic agents or solution
directly to a target tissue site most commonly through a parenteral
route. The more common parenteral routes and target sites are
identified below in the following chart as well as agents commonly
administered via these routes. It should be noted that this chart
is intended to be illustrative only, and not intended to be a
complete, comprehensive listing.
1 Route/Target Site Commonly Administered Agents Intravenous
Antibiotics, anti-inflammatory agents, analgesics, (Within vessel)
antineoplastics, vasoactive agents, electrolyte solutions,
corticosteroid solutions, thrombolytics, anticoagulants,
anticoagulant antagonists, antiarrythmics, beta blockers,
vasodilators, etc. Intra-arterial Antineoplastic agents,
antithrombolytics, gene therapy agents (Arteries; commonly
(clinical testing) the coronary arteries) Intra-articular
Corticosteroid suspensions (Joint: ankle, elbow, knee, shoulder,
hip, digits) Intracardiac (Heart: Vasoconstricors, calcium, gene
therapy agents (clinical myocardium, ventricle, testing),
antibiotics pericardial sac) Intradermal Antibiotics, tuberculin,
allergens (Dermal layer of skin: forearm, back, scapula)
Intraspinal or epidural Anesthetics, analgesics (Spinal column)
Intrathecal Anesthetics, analgesics (Spinal fluid) Intramuscular
Sedatives, vitamins, vaccines, narcotics, antitoxins (Muscle:
deltoid, gluteous medius, gluteous minimus) Subcutaneous Insulin,
narcotics, vaccines, vitamins (Beneath the skin)
[0035] Various therapeutic applications in which the invention may
be employed include but are not limited to the treatment of
cardiac, cardiovascular, peripheral vascular, and neurovascular
diseases, AV access graft stenosis and thrombus formation, cancer,
rheumatoid arthritis, etc. More specific examples of the types of
applications that can be accomplished by the present invention
include, for example, the administration of angiogenic solutions to
an ischemic area of myocardium, the delivery of a thrombolytic drug
to a thrombus within a chamber of the heart or to the peripheral or
neuro vasculature, administration of a solution to a portion of the
atria contributing to atrial fibrillation, or the delivery of an
anti-angiogenic solution to a solid tumor or through the
vasculature supplying blood to a malignancy. Although only a few
specific examples of target sites, delivery routes and therapeutic
and diagnostic agents are specifically discussed here, any target
site, any appropriate delivery route to a target site and any type
of injectate may be delivered by the present invention. The
injectates can include all classes of drugs, such as biological
agents, pharmaceuticals and biopharmaceuticals, as well as
solutions, such as saline and ethanol, which are not considered to
be drugs. In addition to the primary function of delivering and
dispersing the injectate, the catheters of the present invention
may also perform adjunct functions, such as dilation of a vessel by
means of an expandable member such as a balloon.
DESCRIPTION OF THE DRAWINGS
[0036] FIG. 1A is a schematic representation of an embodiment of a
prior art injection system having an externally attached syringe or
ampule.
[0037] FIG. 1B is a schematic representation of an embodiment of a
prior art injection system having an internally housed syringe or
ampule.
[0038] FIG. 2A is a perspective view of one embodiment of a nozzle
assembly for coupling to a delivery injection system of the present
invention for use in a direct surgical application.
[0039] FIG. 2B is a lengthwise cross-sectional view of one
configuration of a nozzle body of the present invention.
[0040] FIG. 2C is a perspective view of the nozzle body of FIG. 2B
wherein channels located on the distal end of the nozzle body
facilitate delivery of an injected solution from an ampule
reservoir to dispersion orifices
[0041] FIG. 3 shows a scaled view of the distal end configuration
of an injection device of the present invention.
[0042] FIG. 4A is a view of the distal end of one embodiment of a
dispersion fixture of the present invention having a plurality of
dispersion orifices.
[0043] FIG. 4B is an underside view of the dispersion fixture of
FIG. 4A illustrating the location and configuration of channels
which facilitate delivery of an injected solution from an ampule
reservoir to dispersion orifices.
[0044] FIG. 4C is a cross-sectional side view of the dispersion
fixture of FIGS. 4A and 4B.
[0045] FIG. 4D is a magnified view of the cut-away portion of FIG.
4C defined by circular line D, illustrating the details of the
configuration of a particular embodiment of a dispersion orifice
having a jewel operatively positioned within it.
[0046] FIG. 4E is a magnified cut-away view similar to that of FIG.
4C, illustrating another embodiment of a dispersion orifice
suitable for use with the present invention.
[0047] FIG. 5 is a magnified cross-sectional view of the nozzle
body of FIG. 2A operatively coupled with another embodiment of a
dispersion fixture of the present invention.
[0048] FIG. 6A is a view of the underside of another embodiment of
a dispersion fixture of the present invention having circular shape
and a plurality of dispersion orifices symmetrically aligned along
the perimeter of the fixture and being equidistant from the focal
point of the fixture.
[0049] FIG. 6B is a view of the underside of another embodiment of
a dispersion fixture of the present invention also having circular
shape and a plurality of dispersion orifices but with the orifices
having varying distances from the focal point of the fixture.
[0050] FIG. 6C is a view of the underside of another embodiment of
a dispersion fixture of the present invention having an oval shape
and a plurality of dispersion orifices with varying distances from
the focal point of the fixture.
[0051] FIG. 6D is a view of the underside of yet another exemplary
embodiment of a dispersion fixture of the present invention having
the shape of a baseball diamond. The plurality of dispersion
orifices are equidistant from the focal point and are aligned along
the perimeter but only along the length of the arched side.
[0052] FIG. 7A is a cross-sectional front view of another
embodiment of the present invention having a dispersion fixture
that provides a solution flow path transverse to the tissue surface
being targeted. This embodiment also features malleable tubing
connecting the dispersion fixture to the ampule to provide for more
flexibility and range of motion.
[0053] FIG. 7B is a magnified bottom view of the dispersion fixture
of FIG. 7A.
[0054] FIG. 7C is a view of the jewel plate of the dispersion
fixture of FIG. 7B.
[0055] FIG. 7D is a cross-sectional side view of the jewel plate of
FIG. 7C.
[0056] FIG. 7E is a top view of an alternate embodiment of a jewel
plate for use with the present invention.
[0057] FIG. 8A is a perspective view illustrating an embodiment of
a solution injection system of the present invention in use in a
cardiac surgical procedure.
[0058] FIG. 8B illustrates use of an embodiment of a solution
injection system of the present invention operatively positioned on
the epicardium to treat an ischemic portion of the myocardium
(shown in cross-section) affected by a subendocardial infarct.
[0059] FIG. 8C is a cross-sectional view illustrating use of the
dispersion fixture of FIG. 6A operatively positioned on the
epicardium to treat an ischemic portion of the myocardium affected
by a transmural infarct.
[0060] FIG. 8D is a cross-sectional top view of another embodiment
of a solution injection system of the present invention employing
the dispersion fixture of FIG. 6D operatively positioned on the
epicardium to treat a ischemic portion of the myocardium affected
by a transmural infarct
[0061] FIG. 9 is a perspective view illustrating an embodiment of a
solution injection system of the present invention in use in a less
invasive cardiac surgical procedure.
[0062] FIG. 10 is a perspective view illustrating another
embodiment of a solution injection system of the present invention
in use in a less invasive cardiac surgical procedure.
[0063] FIG. 11A is a longitudinal view of the general configuration
of a catheter dispersion means and ampule nozzle assembly for an
embodiment of a solution dispersion means for use in endovascular
applications.
[0064] FIG. 11B is a cross-sectional view along the length of the
nozzle assembly of FIG. 11A.
[0065] FIG. 11C is a perspective view of the coupler of FIG.
11B.
[0066] FIG. 11D is a cross-sectional view along the length of the
coupler of FIG. 11C.
[0067] FIG. 11E is a magnified cross-sectional view of the hypotube
tip of the coupler of FIGS. 11C-D.
[0068] FIG. 11F is a perspective view of an embodiment of a
retainer for use with the dispersion means of FIG. 11A.
[0069] FIG. 11G is a perspective view of another embodiment of a
retainer for use with catheter-based solution dispersion means of
the present invention.
[0070] FIG. 12 is a side view of one embodiment of a side-shooting
catheter tip for use with catheter-based solution dispersion means
of the present invention.
[0071] FIG. 13A is a top view of a portion of cardiac vasculature
in which another embodiment of a side-shooting catheter tip is
shown in use in a transvascular application.
[0072] FIG. 13B is a cross-sectional view of FIG. 13A taken
transverse to the longitudinal axis of the catheter and
vessels.
[0073] FIG. 14A is a top view of a portion of a coronary artery
affected by atherosclerotic stenosis having another embodiment of a
side-shooting catheter tip of the present invention operatively
positioned proximally of the stenotic region.
[0074] FIG. 14B is a top view of a portion of a coronary artery
affected by atherosclerotic stenosis having the catheter tip of
FIG. 14A operatively positioned distally of the stenotic
region.
[0075] FIG. 15 is a top view of a portion of a coronary artery
affected by atherosclerotic stenosis having another embodiment of a
side-shooting catheter tip comprising angioplasty capabilities, and
which is operatively positioned at a stenotic region.
[0076] FIG. 16A is a perspective view of an embodiment of an
end-shooting catheter tip for use with a catheter-based solution
dispersion means of the present invention.
[0077] FIG. 16B is a longitudinal cross-sectional view of the
catheter tip of FIG. 16A.
[0078] FIG. 16C is a longitudinal cross-sectional view of the
catheter tip of FIG. 16A operatively positioned in the end of a
catheter for use with a solution dispersion means of the present
invention.
[0079] FIG. 17 illustrates an end-shooting catheter-based
dispersion means of the present invention in use in an
intra-chamber application for delivering a solution to the
endocardium.
[0080] FIG. 18A illustrates a multi-orifice embodiment of a
multi-orifice, end-shooting catheter-based dispersion means of the
present invention in use in an intravascular application for
delivering a solution to within a peripheral vessel.
[0081] FIG. 18B is a magnified cut-out view of the catheter tip of
the dispersion means of FIG. 18A ejecting a solution to treat a
thrombus.
[0082] FIG. 19A is a cross-sectional view of a medial portion of a
human brain wherein a multi-orifice, end-shooting catheter-based
dispersion means has been to delivered to a site within the
neurovasculature.
[0083] FIG. 19B is a magnified cut-out view of the catheter tip of
the dispersion means of FIG. 19A ejecting a solution to treat a
thrombus.
DETAILED DESCRIPTION OF THE INVENTION
[0084] With reference to the accompanying drawings (wherein like
numbers reference like elements), certain preferred embodiments of
the devices and methods of the present invention will now be
described in greater detail.
[0085] As mentioned above, the present invention includes injection
systems and methods for injecting and delivering an agent or
solution to a target site in the body for the treatment or
diagnosis of that target site. The injection systems comprise, at
least in part, a propulsion device, a reservoir, often called a
syringe or ampule, for receiving and holding the agent or solution,
and dispersion means for transferring the agent or solution from
the reservoir to the target site.
[0086] The propulsion device of the present invention may have a
configuration similar to current needle-free injection devices,
commonly referred to as jet injectors. Some of these devices
include those made by National Medical Products, Inc., BioJect,
Inc., Medi-Ject, Inc., Weston Medical Ltd. Visionary, Medical
Products Corp. and Equidyne Systems, Inc. that are primarily
designed for hypodermic applications, such as for the delivery of
insulin for the treatment of diabetes. PowderJect Pharmaceuticals
PLC is another manufacturer specializing in the needle-free
injection of atomized solid materials. These injection devices are
capable of injection in the range from about 2000 to about 4500
psi. Examples of such injection devices are disclosed in U.S. Pat.
Nos. 5,383,851, 5,399,1635,520,639, 5,730,723, 5,746,714, and
5,782,802, which are hereby incorporated by reference.
[0087] FIGS. 1A and 1B are schematic drawings of exemplary prior
art injection or propulsion devices which, with certain
modifications, can be used with the present invention as a
propulsion device. In FIG. 1A, propulsion device 10 has a syringe
or ampule 18 attached to the distal end 12 of injection device 10.
Ampule 18 may be reusable (refillable) or may be disposable and
replaceable with other sterilized ampules. FIG. 1B illustrates
another embodiment of a propulsion device 20 of the present
invention which has an ampule 28 (shown in phantom) housed within
the distal end 22 of injection device 20. With this internal ampule
design, an entirely disposable injection device is feasible. The
ampules of both embodiments may be supplied pre-filled with a
selected volume of the injectable solution.
[0088] Propulsion devices 10, 20 each include a housing 14, 24,
respectively, which is preferably made of biocompatible plastic,
and preferably have a general shape, size and weight so as to
readily fit in a users hand. Housing 14, 24 houses a propulsion
mechanism (not shown), typically either a spring-loaded mechanism
or self-contained volume of gas, such as carbon dioxide, helium,
argon or nitrogen. The gas is contained within a sealed cartridge
that may be interchangeable with other cartridges. Other propulsion
mechanisms, such as those driven by electromechanical or hydrolic
power may also be used with the present invention. When triggered,
the propulsion mechanism releases its potential force to supply an
appropriate amount of pressure or force to the proximal end of a
piston (also not shown). The distal end of the piston is typically
positioned within the proximal end of an ampule and impinges on the
volume of solution within the ampule reservoir causing its contents
to be forced out the reservoir.
[0089] The propulsion devices of the present invention may employ
any appropriate propulsion mechanism capable of providing a force
having a pressure preferably in the range from about 1800 psi to
about 5000 psi. With respect to some of the specific applications
discussed below, acceptable pressures may be in the range from
about 1800 psi to about 2300 psi. It should be noted, that the most
appropriate pressure for a given application will primarily be
dictated by the viscosity of the injectate, the desired depth of
penetration, and the type and thickness of the tissue or substance
being injected, i.e., muscular tissue, vascular tissue (e.g.,
cardiovascular, peripheral and neuro), collagen, ocular tissue,
cartilage, a tumor, fibrous substances (e.g., thrombus),
blood-borne substances (e.g., plaque), etc. Too low of an injection
pressure will result in a lack of penetration and dispersion of the
injectate while too great of an injection pressure may result in
trauma to the tissue site, possibly to the point of puncturing or
rupturing the tissue, and overshooting the injectate beyond the
desired penetration depth.
[0090] Those skilled in the art will appreciate that the factors
affecting pressure (e.g., solution viscosity, desired depth of
solution penetration, and tissue type and thickness) will in turn
dictate certain design specifications of the injection devices,
which will necessarily need to be implemented in order to achieve
the desired injection pressure for a given application. These
design specifications include but are not limited to the size of
the dispersion orifice(s) and the columnar and wall strengths of
the dispersion means. With respect to some of the specific
applications discussed below, acceptable dispersion orifice
diameters are preferably be in the range from about 0.1 mm to about
0.3 mm.
[0091] The propulsion mechanism of propulsion devices 10, 20 is
activated by means of a trigger mechanism 16, 26, respectively,
ergonomically located for activation by a users finger. When
activated, the propulsion mechanism supplies the requisite force or
pressure to ampule 18, 28, respectively, causing the solution
within to be propelled from injection device 10, 20 through a
dispersion means or mechanism (not shown) which in turn channels
the solution to the targeted site. The propulsion devices of the
present invention may comprise components that allow the user,
prior to activation of the propulsion mechanism, to select the
desired volume of solution to be delivered to the target site and
or the desired pressure at which the solution is propelled from the
reservoir.
[0092] The dispersion means of the present invention is the
component of the injection system that directs the agent or
solution from within the syringe or ampule to the target site. Such
dispersion means is defined by the configuration of an end effector
assembled or affixed to the distal end of the propulsion device or
ampule reservoir of the injection system. The specific
configuration of the end effector primarily depends on the approach
being used to access the targeted tissue site within the body. The
various approaches include a direct surgical approach (or surgery),
a less invasive surgical approach through a small incision or port,
or an endovascular approach (sometimes referred to as a
catheter-based approach). The end effector for use in a direct or
less-invasive surgical approach is more likely to be in the form of
a fixture having openings for dispersing the injectate. Depending
on the size of the access space and the level of difficulty in
reaching a target site in a less-invasive surgical approach, the
fixture may have a very low profile fixture and an may incorporate
means for facilitating delivery through a tortuous and lengthy
access space. On the other hand, the end effector for use in an
endovascular approach is in the form of a catheter. Regardless of
the approach used, none of the end effectors of the present
invention is designed or intended to penetrate or pierce the target
site directly. Instead, only the agent or solution being injected
by the present invention is intended to penetrate the target site
with minimal trauma to tissue or adjacent substances. In fact, in
some cases it may be preferable to avoid directly contacting the
target site with the end effector. The injection systems of the
present invention are capable of achieving the desired delivery and
dispersion of an injectate to the target site without directly
contacting the tissue, if so desired.
[0093] As mentioned above, the dispersion means of the present
invention for use in a direct surgical approach for accessing a
target site on the outer surface of an organ or bodily tissue
includes a non-penetrating end effector or fixture, such as a cap,
mounted to or integral with the distal end of the propulsion device
(such as with injection system 20 of FIG. 1B). Alternatively, the
dispersion means may be assembled with an ampule in a nozzle
configuration, which in turn is functionally coupled to the distal
end of the propulsion device (such as with injection system 10 of
FIG. 1A).
[0094] FIG. 2A is a perspective view of an embodiment of an end
effector integral with a nozzle assembly 30 for attachment to a
propulsion device such as that of FIG. 1A. Nozzle assembly 30
includes an ampule body 32 and end effector 40. Ampule body 32 has
a generally cylindrical configuration, and preferably has a length
in the range from about 3 cm to about 4 cm and an outer diameter in
the range from about 1.2 cm to about 1.5 cm. Of course, these
dimensions may vary greatly depending on the clinical application,
the amount of solution to be delivered and possibly the distance
from the surgical incision to the targeted tissue. Nozzle assembly
30 and its components are preferably comprised of a biocompatible
material, preferably a plastic such as polycarbonate. Nozzle
assembly 30 may be integral with or releasably coupled to the
propulsion device.
[0095] FIG. 2B illustrates one configuration of the nozzle assembly
30 of FIG. 2A. Ampule body 32 defines an ampule reservoir 34
therein. Reservoir 34 preferably has a volume sufficient to hold at
least one dose of an agent or solution, but may have any size
volume to accommodate any number of appropriate doses for a given
application. The distal end portion 35 of reservoir 34
(approximately the most distal 10) of reservoir 34) has a distally
tapered configuration that terminates in a single reservoir orifice
36. The diameter of reservoir orifice 36 is within the range from
about 1.1 mm to about 1.3 mm. Proximal to distal end portion 35,
reservoir 34 has a diameter in the range from about 0.75 cm to
about 1 cm. Although only ampule reservoirs having a single
reservoir orifice are illustrated in the drawings, the present
invention includes ampule reservoirs configured to comprise more
than one reservoir orifice.
[0096] The proximal end 60 of nozzle body 32 has a flanged
configuration having mounting flanges 62 for mating with
corresponding flange recesses of the distal end of an injection
system (not shown) of the kinds described with reference to FIGS.
1A and 1B. FIG. 3, for example, illustrates a corresponding mating
configuration with flange recesses 72 at the distal end 74 of an
injection system 70 having a general design similar to that of the
external ampule embodiment of FIG. 1A. This mating configuration is
some times referred to as a bayonet mount configuration.
[0097] At the distal end 38 of ampule body 32 is mounted an end
effector 40 in the form of a dispersion fixture or cap, having a
generally circular shaped distal portion 44 and an annular wall
portion 46. Distal portion 44 has a smooth, generally planar,
distal target-facing surface 45. Distal portion 44 may also have a
constant, downward grade (not shown) of approximately 3% from its
perimeter to its center. This provides a slightly concave surface
to match that of the tissue surface in order to ensure equidistance
between each of the dispersion orifices (discussed below) and the
tissue surface, and if so desired, to maximize contact between
target-facing surface 45 and the tissue surface. Optionally, a
suction mechanism associated with ampule body 32 may be employed to
apply a negative pressure to the surface of the tissue in order to
help position end effector 40. The perimeter 48 of the outer
surface of distal portion 44 is beveled so as to be atraumatic to
the tissue if target-facing surface 45 comes into contact with
tissue. Dispersion fixture 40 has an external diameter in the range
from about 1.75 cm to about 1.9 cm, and an internal diameter in the
range from about 1.3 cm to about 1.6 cm.
[0098] Distal portion 44 also has a plurality of spaced-apart
dispersion orifices 37 bored through the entire thickness of distal
portion 64. Although not necessary for the performance of
dispersion fixture 40, dispersion orifices 36 have a slightly
distally tapered configuration at their distal end to facilitate
delivery of solution there through. Here, four dispersion orifices
37 are shown (see FIG. 2A) but any number of dispersion orfices may
be employed with the present invention. Dispersion orifices 37 are
oriented in a quadrangle configuration to evenly disperse the
injectate over or within a relatively broad area of the targeted
site; however, any appropriate arrangement of the dispersion
orifices, whether symmetrical or asymmetrical, and any appropriate
spacing between the orifices may be employed with the present
invention. Other possible orifice configurations are discussed
below with reference to FIGS. 6A-E.
[0099] At least one reservoir orifice and at least one dispersion
orifice are necessary for the proper functioning of the injection
systems of the present invention. However, an end effector
employing one or more dispersion orifices may be used with only a
single corresponding reservoir orifice. Alternatively, a one-to-one
correspondence between dispersion and reservoir orifices may be
employed. In fact, any suitable number of dispersion orifices may
be used with any suitable number of reservoir orifices.
[0100] As it is preferable to maintain a continuous, uninterrupted
fluid communication between the reservoir orifice(s) and the
corresponding dispersion orifice(s), the present invention may also
include the use of fluid pathways or channels between the
dispersion and reservoir orifices. These pathways are preferably
integral with either the ampule or the end effector of the present
invention.
[0101] As is more clearly illustrated in FIG. 2C, channels 52 are
milled or machined within the distal surface 54 of ampule body 32.
Dispersion orifices 37 terminate proximally at channels 52,
respectively (discussed more thoroughly below with respect to FIGS.
5A and 5B). Channels 52 define the delivery pathways through which
a solution is caused to travel as it is ejected or expelled from
reservoir orifice 36. The solution is then caused to flow through
and be ejected from respective dispersion orifices 37.
[0102] Turning to FIG. 5, there is shown a cross-sectional view of
ampule body 32 of FIG. 2A which more clearly illustrate the
location and configuration of channels 52 within distal surface 54.
Here, ampule body 32 is coupled to another embodiment of a
dispersion fixture 96. Juxtaposed between and in sealing engagement
with the annular wall 95 of dispersion fixture 96 and ampule body
32 is an annular sleeve 50 for providing a fluid-tight seal to
prevent against leakage of the solution held within ampule
reservoir 34. Annular sleeve 50 has a wall height equivalent to
that of annular wall 95, and external and internal diameters
suitable for annular sleeve 50 to be fit snuggly between annular
wall 95 and ampule body 32. Fixture 96 has dispersion orifices 98
having a configuration different from that of the dispersion
fixture 40 of FIG. 2B, and which will be more thoroughly discussed
below with respect to FIGS. 4C and D.
[0103] Turning now to FIGS. 4A-D, the details of another embodiment
of a dispersion fixture 43 are illustrated. FIG. 4A shows the
distal portion 58 of dispersion fixture 43 having four dispersion
orifices 42 bored through the entire thickness of distal portion
47. The cross-sectional cutaway view of FIG. 4D shows each orifice
42 having a proximal portion 42a, a central portion 42b and a
distal portion 42c. Proximal portion 42a has a cylindrical
configuration having a diameter in the range from about 1.0 mm to
about 1.3 mm. Central portion 42b also has a cylindrical
configuration having a diameter in the range of about 0.1 mm to
about 0.6 mm, and more preferably in the range of about 0.1 mm to
about 0.3 mm. Distal portion 42c has a cone-like configuration with
the narrow end adjacent to and contiguous with central portion 42b,
and flaring to a diameter that is approximately twice that of
central portion 42b. This orifice configuration provides a wider
range of dispersion, preferable when targeting larger areas of
tissue.
[0104] Other suitable orifice designs are contemplated for use with
the surgical injection systems of the present invention. The
cross-sectional cut-away view of FIG. 4E shows one such alternate
design. Here, dispersion fixture 49 has a dispersion orifice 80
bored through the entire thickness of dispersion fixture 49.
Orifice 80 has a funnel shape cross-section, ending in a tubular
distal portion 80a having a diameter in preferably in the range
from about 0.1 mm to about 0.3 mm. The length of tubular distal
portion 80a is approximately 2 to 5 times greater than the
diameter. This design is more suitable when dispersing solution in
a smaller area of tissue.
[0105] Another embodiment of the solution channels of the present
invention is seen in FIG. 4B, illustrating the underside 51 of
distal portion 44 of dispersion fixture 43. Here, the channels 57
are cut or milled within the dispersion fixture itself. Milled to a
depth of about 0.5 mm, channels 57 intersect at a central focal
point 56 that is concentrically aligned with the reservoir orifice
of an ampule body (not shown). Channels 57 extend radially outward
and terminate, respectively, at a corresponding dispersion orifice
42.
[0106] As is more clearly illustrated in FIGS. 4D and 4E,
positioned within the proximal portion 42a of each orifice 42 is a
jewel or crystal 66 having a disk configuration with a central bore
67. Jewel 66 is preferably made of a hard material that can be
precisely cut to form a uniform exit path for an ejected solution.
Suitable materials include stainless steel or precious stones, such
as sapphire or ruby. Although not necessary for the proper
functioning of dispersion fixture 43, a jewel is preferably used to
ensure an accurate and precise vector path of an ejected solution.
Each jewel has a diameter sufficiently sized to allow jewel 66 to
be press-fit into jewel chamber during the assembly process.
Central bore 67 preferably has a diameter from about 10 to about 15
the diameter of jewel 66. Thus, when cap 43 and ampule body 32 are
assembled, channels 57 define the delivery paths through which a
solution is caused to travel as it is ejected or expelled from a
reservoir orifice. From the respective channels 57, the ejected
solution is then caused to flow through central bore 67 of
respective jewels 66, and then through and ejected from respective
dispersion orifices 42.
[0107] As mentioned above, any suitable dispersion orifice,
reservoir orifice, and channel configuration and pattern are
contemplated for use with the present invention. The particular
dispersion orifice (and reservoir orifice) configuration to be used
may depend on several factors including the medical condition being
treated, the gross morphology of the tissue area or other target
site being treated, the type of access provided for delivery of the
device and the viscosity and dispersion characteristics of the
injectate. For example, from what is currently known about
angiogenesis, a better angiogenic outcome is more likely where the
angiogenic solution has at least some healthy tissue in which to
initiate the grown of new vessels. Thus, in the case of myocardial
infarction, the angiogenic solution is preferably injected, at
least in part, into some healthy tissue immediately adjacent the
infarcted area. The particular orifice configuration will likely
depend on whether the infarct is a subendocardial infarct or a
transmural infarct. Subendocardial infarcts are characterized by
multifocal areas of necrosis within the myocardium and are
typically confined to the inner 12 of the myocardial wall, whereas
a transmural infarct involves the entire thickness of the
myocardial wall from endocardium to epicardium.
[0108] The quadrangle configuration of the dispersion orifices
illustrated in FIG. 4A may be more suitable for a subendocardial
infarct than for transmural ischemia. The quadrangle configuration
will likely create a contiguous, relatively expansive dispersion
area in the myocardium, allowing the injected angiogenic solution
to disperse within the outer layers of healthy tissue confining the
subtransmural ischemia. In the case of transmural ischemia where
the hypoxic tissue spans the entire thickness of the myocardium,
leaving no healthy tissue at the epicardial or endocardial
surfaces, injecting the angiogenic solution within the perimeter of
and directly over (epicardially) the infracted area (or directly
under the infracted area in the case of an endovascular approach)
is not likely to produce the best results. A more suitable
dispersion fixture for this application is, for example, one having
a single orifice, a linear array of orifices having a in an annular
configuration (e.g., any shape ring or loop, or an arch
configuration) or a straight row(s) of orifice which can be
selectively aligned with or immediately proximal to the perimeter
of the ischemic area wherein at least some of the angiogenic
solution is dispersed within healthy tissue.
[0109] FIGS. 6A-E illustrate a few exemplary dispersion fixtures of
the present invention having various shapes, sizes, orifice
patterns and corresponding channel configurations. Unless
specifically referenced, certain dimensions (such as diameter and
angle of curvature) of the various dispersion fixtures to follow
should be assumed to be appropriately analogous to those of
previous embodiments, keeping in mind the obvious variances
attributable to the specific shape and necessary surface area of
the various dispersion fixtures.
[0110] FIG. 6A illustrates the underside of a dispersion fixture
104 of the kind discussed above with respect to FIGS. 2A-C. Here,
the orifice configuration includes twelve (12) orifices 106 aligned
in a ring close to the perimeter of orifice fixture 104. The
spacing between adjacent orifices 106 is the same throughout the
ring. Corresponding to each orifice 106 is a channel 108 extending
radially from the center 110 of dispersion fixture 104. This
particular design is advantageous for injecting an angiogenic
solution to treat a transmural infarct, for example. In use, the
user would position dispersion fixture 104 (attached to an
injection device) on the patient's myocardium such that orifices
106 surround the infracted area or are in close proximity to the
perimeter of the infracted area. As mentioned above, the present
invention includes embodiments of dispersion fixtures having any
number of orifices arranged in any suitable pattern.
[0111] FIG. 6B illustrates the underside of another embodiment of a
dispersion fixture 112 having a circular shape and having a
plurality of dispersion orifices 114 in a staggered configuration
which defines a channel pattern of two sets of symmetrical
channels, channel set 116a (the more proximal, set) and channel set
116b (the more distal set) having different lengths, i.e., the
channel length of channel set 116a is shorter than that of channel
set 116b. This embodiment provides a more even distribution of
injected solution in a defined area, and would be useful, for
example, in delivering angiogenic solution to an area of myocardium
affected by a subtransmural infarct. Due to the shorter distance
from the center of the dispersion fixture 112, the pressure and
velocity of the injectate through the dispersion orifices 114 of
channel set 116a will likely be slightly greater than that being
delivered through the dispersion orifices 114 of channel set 116b.
However, the size and path length (e.g., by means of curving) of
one channel set may be increased or decreased to compensate for the
slight deviation.
[0112] Referring now to FIG. 6C, there is shown the underside of a
dispersion fixture 118 having an oval profile. As with the
embodiment of FIG. 6A, the dispersion orifices 120 are similarly
aligned close to the perimeter of fixture 118; however, the
resulting oval pattern of orifices 120 results in varying lengths
of channels 122. Similar to the embodiment of FIG. 6B, the varying
channel lengths will result in correspondingly varying pressures,
velocities and volumes of solution exiting each orifice 120.
Continuing to use the example of myocardial infarcts, dispersion
fixture 118 is more suitable for infarcted areas that have a shape
and size corresponding to that of fixture 118. Clearly the distal
end of a nozzle body to be used with dispersion fixture 118
necessarily has a design and structure different from that of the
previously discussed embodiments. Those skilled in the art will
understand these necessary design modifications.
[0113] FIG. 6D illustrates the underside of yet another possible
embodiment of a dispersion fixture 124 of the present invention.
Here, dispersion fixture 124 has a shape in the form of a diamond
or of an arched cone. Five dispersion orifices 126 are aligned in a
single, linear array proximate the perimeter of and matching the
angle of curvature of annular or arched side 128 of dispersion
fixture 124. The included angle 125 at the vertex 123 of dispersion
fixture 124 may range from a minimum value, defined by the space
necessary to accommodate a single dispersion orifice, preferably
greater than about 5(, to a maximum value of 360(, such as in the
embodiments of FIGS. 6A-C. More typically, angle 125 will ranged
from about 20(to about 180(, and even more typically, between about
45(and about 90(, such as with the embodiment of FIG. 6D. Here,
dispersion orifices 126 are equidistant from the focal point 129 of
dispersion, and thus, result in corresponding channels 130 which
extend radially outward from focal point 129 and which have
identical lengths. As with the embodiment of FIG. 6A, the pressure,
velocity and volume of solution exiting each dispersion orifice 126
will be the same for each. Again, the requisite nozzle body design
to be used with dispersion fixture 124 will differ from those
previously discussed. Those skilled in the art will understand the
necessary design features required for a compatible nozzle
body.
[0114] FIG. 7A shows a cross-section front view of another
embodiment of a dispersion fixture 132. As is more clearly shown in
the magnified bottom view of FIG. 7B, taken along the lines B-B in
FIG. 7A, target-facing surface 138 of dispersion fixture 132 has an
atraumatic, elliptical profile having a length preferably in the
range of about 7 mm to about 10 cm and a width in the range of
about 2.5 mm to about 4 cm but will vary depending on the target
organ or tissue and the size of the tissue area being treated.
Target-facing surface 138 provides a linear array of dispersion
orifices 134 in fluid communication with their respective channels
136 which, except for the center orifice, are at varying acute
angles to tissue surface 133 when operatively positioned. Such a
dispersion fixture configuration is useful, for example, for
delivering an angiogenic solution to the epicardium along or
lateral to a portion of a coronary artery 135 affected by
atherosclerotic plaque 143. In the latter case, an angiogenic
solution, such as BFGF, may be used to promote the growth of
collateral blood vessels. This embodiment is also suitable for
delivering a solution (such as ethanol) to the epicardial tissue,
such as on the atria, for creating a linear lesion to treat atrial
fibrillation.
[0115] Additionally, as seen in FIG. 7A, target-facing surface 138
has a shallow arch configuration so as to maximize contact with the
tissue surface 133. Due to the slightly varying lengths of channels
136, the pressure, velocity and volume of solution exiting each
dispersion orifice 134 will be slightly different. More
specifically, the value of these variables will be the greatest for
solution exiting the center orifice and the lowest for solution
exiting the two outermost orifices. The value of these variables
for solution exiting the two orifices positioned in between the
central and outermost orifices fall somewhere in between the other
two sets of values.
[0116] The construct of a nozzle body 140 compatible with
dispersion fixture 132 of FIG. 7A is generally the same as that
discussed with respect to the nozzle body embodiment of FIG. 2B;
however, the means for functionally attaching dispersion fixture
132 to nozzle body 140, and thereby functionally connecting
reservoir orifice 142 to channels 136, is different. Such a means
is generally referenced as 144 and includes a length of malleable
tubing 145 extending from the very distal end 147 of nozzle body
140 to the proximal end 137 of dispersion fixture 132. Tubing 145
transports a pressurized solution from within ampule reservoir 141
to channels 136, respectively, while providing a free range of
motion and positioning of dispersion fixture 132 relative to nozzle
body 140. Tubing 145 is preferably comprised of material(s) that
allows it to be malleable. One suitable material is coated wire
mesh, which is flexible enough to be contorted and bent but ridged
enough to provide stability and to reliably maintain the position
of dispersion fixture 132 while solution is being injected into
tissue. Tubing 145 may either define its own lumen 146 or encase a
catheter (not shown) co-axially running at least the length of
tubing 145. Such a catheter is coupled to reservoir orifice 142 at
its proximal end and to channel entrance 139 at its distal end.
Tubing 145 and or a co-axial catheter are comprised of material(s)
which provide a wall strength sufficient to maintain the pressure
and velocity of an injectate being delivered through it. The
attachment and connecting means 144 just described is not limited
to this embodiment but may be employed with any embodiment of the
present invention.
[0117] Another feature of dispersion fixture 132 that is
distinguishable from those previously discussed, is that a single
jeweled substrate 148 may be used in lieu of multiple jewels, one
for each dispersion orifice as described for the previous
embodiments. Jeweled plate 148 is comprised of any suitable stone
or crystal that would be used for the multiple jewel embodiments.
As more clearly illustrated in FIGS. 7B, the bottom view of
target-facing surface 138, the magnified top (or bottom) view of
jeweled plate 148, and the cross-sectional side view of jeweled
substrate 148, jeweled substrate 148 has a plurality of bores 150
corresponding to the number of and aligned with dispersion orifices
139. A single substrate has the advantage of being easier to
fabricate and easier to handle and position within dispersion
fixture 132 during the manufacturing process.
[0118] FIG. 7E illustrates an alternative configuration of a
jeweled substrate 152. Jeweled substrate 152 has a narrow stem
portion 154 having a plurality of outposts 155 along one side of
stem portion 154. Each outpost 155 has a jewel 156 attached to its
distal end. Substrate 152 and outposts 155 may be made of the jewel
material being used or another rigid material. One skilled in the
art will recognize that other suitable embodiments of the jewel
piece(s) may be used with the present invention.
[0119] Although certain dispersion fixtures have been described for
use in surgical applications, one skilled in the art can appreciate
that other shapes and sizes of dispersion fixtures and any number
and configuration of orifices may be employed with the present
invention. For example, a dispersion fixture of the present
invention having a relatively small target-facing surface and only
a single dispersion orifice may be useful for accurately and
precisely delivering solution to small, discrete areas of tissue,
such as an area of infarcted myocardium having diffuse locations of
ischemia. An embodiment having a dispersion fixture that is
comprised of a relatively flat, thin, malleable sheath may be
useful to treat oddly shaped or difficult to reach tissue, say for
example, the back side of the liver or a tumor within the
intestinal area whose dimensions and shape are not readily known
until exposed.
[0120] The examples illustrated and discussed are not intended to
limit the invention. Those skilled in the art will appreciate that
the most useful and appropriate dispersion fixture configuration
for a particular clinical application may be dependent on a variety
of factors, including but not limited to, the location of the organ
or tissue being targeted, the size and depth of the area being
treated, and the condition being treated.
[0121] The methods of using the injection systems of the present
invention in a surgical setting will now be discussed with
reference to FIGS. 8A-D. FIGS. 8A-D illustrate various embodiments
of injection systems of the present being used in a thoracic or
cardiothoracic surgical application, for example, to deliver and
inject angiogenic growth factor for initiating angiogenesis within
the myocardium or within a coronary vessel. Typically, the solution
delivery procedure in the context of an open cardiac surgical
procedure will be adjunct to a CABG or valve replacement or repair
procedure. Also, the solution delivery procedure may be performed
prior to or after the other surgical procedure and may be done on
or off-pump.
[0122] Referring now to FIG. 8A, the patients chest is held open by
a surgical retractor 212 while a surgeon 210 is holding a solution
injection system 200 and targeting it on the myocardium of the
patient shear 214. Solution injection system 200 has an injection
portion 202, having a general structure in the form of a gun, and
an ampule 204 distally attached to injection portion 202. Ampule
204 holds the angiogenic solution to be delivered. Attached
distally to ampule 204 is a dispersion fixture 206 in the form of
cap similar to the embodiment of FIGS. 2A-C. Here, dispersion
fixture 206 is shown being held against and in direct contact with
the epicardium in an area of infarcted tissue 216 (outlined in
phantom); however, direct contact is not required for performing
the methods of the present invention with any of the devices of the
present invention. In fact, depending on the application at hand,
patient anatomy and surgeon preference, holding the injection
system 200 such that dispersion factor 206 is a selected distance
(possibly as far as 2 cm) from the surface of the tissue may be
preferable to direct contact. To ensure greater accuracy of
positioning, a robotic mechanism may be used. In either case, after
providing a solution delivery device 200 with ampule 204 filled
with a selected volume of solution and with the pressure gradient
of the injection mechanism set at the desired level, the dispersion
fixture 206 is positioned adjacent or proximate to the target
tissue area. The propulsion mechanism (such as the ones discussed
above with respect to FIGS. 1A and 1B) internal to injection
portion 202 is activated by means of a trigger mechanism (not
shown) to provide the requisite force to drive the solution out of
ampule reservoir 204, into and through dispersion fixture 206
having a suitable size and shape for the application at hand. The
internal configuration of dispersion fixture 206 channels the
solution flow through a defined path or paths which optimize the
volume and pressure of solution being injected at the desired
point(s) within the target area. Upon injection into the target
area, the highly pressurized injectate is then dispersed throughout
the selected area. This procedure may be repeated as necessary for
treating one or more targeted sites.
[0123] FIG. 8B illustrates use of solution injection system 215 of
the present invention to treat a portion of myocardium 210 affected
by subendocardial ischemia. As the affected area 212 involves
ischemic tissue 212 within the central portion of the myocardium
210, the dispersion fixture 218 of solution injection system 215 is
preferably of the type illustrated in FIGS. 2A-C and 4A-E.
Operatively positioned on epicardium 214, this configuration allows
for the jet delivery of angiogenic solution into the healthy layer
of tissue directly over ischemic area 212. This allows for the
angiogenic growth factors to initiate the creation of new vessels
within the healthy area.
[0124] FIG. 8C illustrates use of another injection system 220 of
the present invention for the treatment of a portion of myocardium
222 affected by a transmural ischemic area 224, wherein the
affected area 224 spans the thickness of myocardium 222 from
endocardium 226 to epicardium 228. Solution injection system 220
has an ampule body 221 housing reservoir 223 with a dispersion
fixture 230 mounted thereto. Preferably, dispersion fixture 230 is
of the type illustrated, for example, in FIG. 6A, wherein a
plurality of dispersion orifices 232 arranged annularly and
proximate to the perimeter of dispersion fixture 230. The diameter
of the annular configuration formed by dispersion orifices 232 is
preferably slightly greater than the diameter of infracted area 224
(assuming the infarct has a generally annular shape itself,
otherwise, a more appropriate shaped dispersion fixture should be
used). Thus, with this embodiment, the angiogenic solution is
injected into or dispersed to at least some of the healthy tissue
proximate the perimeter 225 of ischemic area 224 so as to further
ensure the genesis of new blood vessels.
[0125] FIG. 8D illustrates use of yet another injection system of
the present invention. This embodiment has a dispersion fixture 234
having the configuration of the type illustrated in FIG. 6D, which
is also suitable for use in treating an ischemic area 250 of a
heart wall 252 created by a transmural infarct. FIG. 8D provides a
cross-sectional top view of dispersion fixture 234 illustrating an
annular array of dispersion orifices 236 aligned along and
proximate to the perimeter of arched portion 235 of fixture 234.
Here, dispersion fixture 234 is coupled to a rigid shaft 242 that
extends form an ampule body (not shown). Fixture 234 and shaft 242
are preferably coupled by a hinged-type joint mechanism 243 (not
shown in detail) that allows dispersion fixture 234 to be
selectively pivoted and locked in place with respect to shaft 242.
Dispersion fixture 234 has a range of motion preferably from about
30(to about 110(with respect to the longitudinal axis of shaft 242.
This range of motion allows a user more flexibility to treat
difficult to reach tissue areas, such as on the posterior side of
the heart. Various configurations of such a joint mechanism are
commonly known by those skilled in the art.
[0126] Running coaxially with the lumen of shaft 242 is flexible
tubing 240 that provides a conduit for transporting a pressurized
solution between an ampule reservoir (not shown) and dispersion
fixture 234. Tubing 240 is flexible enough and has sufficient slack
along its length to allow for the variable positioning of
dispersion fixture 234 with respect to shaft 242. Tubing 145 is
preferably comprised of high tensile strength plastic or silicone
reinforced with stainless steel ribs or wound wire in order to
maintain a desired solution pressure and velocity throughout the
injection cycle. Distal end 244 of tubing 240 terminates at an
opening to the entrance of solution channels 238 each of which
extend radially to a respective dispersion orifice 236
[0127] When using embodiments of the present invention having
dispersion means with flexible, malleable or otherwise variable
components, such as those described with respect to FIGS. 7A and
8D, the physician or other user, prior to each injection, will have
the option to adjust the position of the dispersion means with
respect to the injection device to optimize the delivery and
dispersion of a solution. This includes either adjusting (e.g.,
bending, angling, etc. as appropriate) the dispersion fixture, or
the means for coupling the dispersion fixture to the ampule, or
both. These configurations of solution delivery devices may also be
useable in less invasive surgical procedures, such as those
described below.
[0128] Although only several embodiments of injection systems for
surgical applications have been illustrated and described, those
skilled in the art will appreciate the modifications and variations
that can be made to these devices to suit a particular application.
As mentioned above, the most appropriate dispersion fixture
configuration for a particular clinical application will depend on
several factors, including but not limited to, accurately assessing
the condition to be treated (e.g., subendocardial ischemia vs.
transmural ischemia), the size, shape and thickness of the tissue
area being treated, the depth of the area from the tissues surface,
the location of the treatment area (i.e., the organ being
targeted), and the ease of access or lack thereof to the targeted
locations. Additionally, the most appropriate dispersion orifice
configuration, including the number of orifices, the size of the
orifice(s) and the arrangement of orifices, will depend on several
factors, including but not limited to, the pressure profile of the
propulsion device being used, the viscosity of the injectate, and
the size of the surface area of the target site.
[0129] The present invention can also be configured for delivering
a solution to a targeted site within the body in the context of a
less invasive surgical procedure. The means of access for less
invasive surgeries, particularly for a minimally invasive cardiac
surgery, is typically accomplished by means of a very small
incision or a positioned through the skin. For minimally invasive
cardiac surgery, the port is created within the patients chest
cavity or through a mini-thoracotomy or other minimally invasive
incision in the chest area. A port access approach may require the
use of a trocar, an elongated tubular device that provides a
conduit from outside the body to the target area within the body. A
larger but still less invasive incision may not require use of a
trocar but may still require the use of smaller and preferably
flexible or malleable tools to access the more difficult to reach
areas. Still other less invasive procedures involve the use of an
endoscope to facilitate visualization while performing the
surgery.
[0130] The injection devices described above for use in the
injection systems of the present invention for direct surgical
applications are also suitable for use in injection systems for
less invasive surgical applications. It is the configuration of the
dispersion means of the less invasive systems, as defined by the
particular end effector being used, which necessarily has a slimmer
or lower profile than those of the systems for surgical
applications. The specific design of the end effector for a less
invasive surgical approach will primarily depend on such factors,
including but not limited, the location of the treatment area
(i.e., the organ being targeted) and the ease of access or lack
thereof to the treatment area. For example, accessing an area of
tissue on the myocardium through a port between a patient's ribs
may require a different configuration than accessing a portion of
intestine in a laparoscopic procedure. Particularly in the case of
a cardiac procedure, the configuration of the dispersion means may
also depend on whether the solution delivery procedure is adjunct
to another procedure, such as a CABG or a valve repair or
replacement procedure, or is the sole procedure being performed. In
the former situation, the pericardium will have been incised to
access the heart, possibly requiring only minor modifications to
the dispersion means of the present invention, some of which are
described below. On the other hand, in the latter situation, it may
not be necessary to cut into the pericardium. For example, a
solution (e.g., such as an antibiotic for the treatment of
pericarditis or myocarditis) may be injected with the present
invention directly through the pericardium so as to fill the
pericardial space (i.e., intrapericardial injection) for prolonged
exposure to the pericardium or the myocardium. Alternately, a
solution (e.g., such as an angiogenic solution for treating
ischemic myocardial tissue), may be injected with sufficient
pressure so as to penetrate both the pericardial sac. and the
myocardium with the solution.
[0131] Turning now to FIGS. 9 and 10, exemplary configurations of
end effectors of the present invention are illustrated in use in
the context of a less invasive cardiac procedure, such as for the
treatment of an area of ischemic tissue by means of high-pressure
injection of an angiogenic solution into the target tissue. FIG. 9
is a view of a heart from within the thoracic cavity and an
embodiment of a dispersion means 260 operatively positioned to
treat an area of the myocardium 254. Dispersion means 260 includes
a cylindrical shaft 261 coaxially positioned within a trocar port
265 operatively positioned between two adjacent ribs 256. Trocar
ports suitable for use in this and other thoracic procedures are
commonly known to those skilled in the art of cardiac and thoracic
surgery. Dispersion means 260 further includes a dispersion fixture
262 attached to the distal end of shaft 261 shown here to be in
operative contact with a targeted area 258 of the hearts
epicardium. Dispersion fixture 262 has a configuration generally
similar to those illustrated in FIGS. 8A-C. However, here,
dispersion fixture 262 has a diameter (or other transverse
dimension depending on the shape of the fixture) small enough to
fit through trocar port 265 and may have any suitable shape and
dispersion orifice configuration (similar to those discussed above
with respect to embodiments for surgical applications) for the
application at hand. Shaft 261 defines an internal space comprising
either an ampule reservoir (not shown), similar to those described
above for surgical applications, or a lumen (not shown) for
transporting solution from an ampule reservoir (located either
proximally within shaft 261 or within the injection device itself)
to dispersion fixture 262. In the case where the ampule reservoir
is located within shaft 262, the reservoir has length and diameter
dimensions suitable for being housed in shaft 261 and for defining
a volume sufficient to hold at least a single dose of solution.
[0132] A method of using the embodiment of FIG. 9 will now be
discussed in the context of a minimally invasive cardiac procedure
in which a solution is being delivered to a target area 238 on the
epicardium. After a small incision is made at the desired location
(e.g., between adjacent ribs 256), trocar 265 is positioned within
the incision. Dispersion means 260 is then inserted into the
proximal end of trocar 265 and moved coaxially within trocar 265
until dispersion fixture 262 is delivered to a desired distance
from or in contact with the target tissue. With the ampule
reservoir filled with the desired amount of solution and the
injection mechanism of the injection system properly set for
firing, the system is actuated, causing the solution to be ejected
from the ampule reservoir and delivered through shaft 261 to
dispersion fixture 262. The dispersion orifices (not shown) then
directed the solution to various sites within the target area.
[0133] Turning now to FIG. 10, there is shown another embodiment of
a dispersion means 270 of the present invention in use in a less
invasive cardiac procedure in which access to the heart is
accomplished through an opening made, for example, in the region
just below the patient's xyphoid 280 (i.e., subxyphoid). Dispersion
means 270 comprises a malleable catheter or tubing 274 which, at
its proximal end, is in sealing engagement with the orifice of an
ampule reservoir (not shown), and extends distally to dispersion
fixture or catheter tip 275. Tip 275 has at least one dispersion
orifice. In the application illustrated in FIG. 10, only a single
dispersion orifice is employed, and is preferably located so as to
provide a solution path, which remains coaxial with catheter 274
after exiting the dispersion orifice. However, any appropriate
number of dispersion orifices having any suitable shape and size
and located at any suitable location on the tip region of the
catheter is contemplated. The location of such orifices is
discussed more thoroughly below in the discussion of endovascular
devices of the present invention. Tubing 274 is preferably
comprised of a strong yet flexible medical grade material, such as
nitinol, nylon, or polyimide reinforced with stainless steel or
Kevlar, and may have any suitable length for the application at
hand. Tubing 274 has outer and inner diameters suitable for
connection to an ampule reservoir orifice and for coaxial alignment
within a cannula or tubing 278.
[0134] In FIG. 10, a port 272 has been positioned within a
subxyphbid incision, for example, to provide access to within the
thoracic cavity of the patient. This port configuration is more
suitable for penetration through the diaphragm 282 rather than
between the ribs such as trocar 235 of FIG. 9. A flexible,
steerable cannula or tubing 278 extends proximally from and is in
sealing engagement with port 272. Tubing 278 is preferably
comprised of material mentioned above with respect to tubing 274 of
FIG. 10, and may have any suitable length for the application at
hand.
[0135] A method of using the embodiment of FIG. 10 will now be
discussed in the context of a minimally invasive cardiac procedure
in which a solution is being delivered to a target area 284 on the
epicardium. After a small incision is made at the desired location
in the subxyphoid region, port 272 and the attached cannula 278 are
positioned within the incision. Tubing 274 is shaped into a
desirable configuration and then inserted into the proximal end of
cannula 278. The malleability of catheter 274 allows it to be
shaped in a configuration that will more readily facilitate
navigation of catheter tip 275 to the target area(s). The
flexibility and deformability of cannula 278 allows it to comply
with the shape of the catheter being inserted into it and further
increases ease of access to the target area(s). Catheter 274 is
then steered distally through cannula 278 until catheter tip 275 is
delivered to a desired distance from or in contact with the target
tissue 284. With the ampule reservoir filled with the desired
amount of solution and the injection mechanism of the injection
system properly set for firing, the system is actuated, causing the
solution to be ejected from the ampule reservoir and delivered
through catheter 274 to the dispersion orifice at tip 275, which
precisely directs the solution to a selected site within the target
area 284. All or some of the steps of this process may be repeated
as necessary to deliver solution to other sites with the same or
different target area. Additionally, an endoscope and a light
source, either integral with system of the present invention or as
a stand-alone unit, may be used with the process just described in
order to facilitate visualization by the surgeon of the surgical
area.
[0136] The flexibility and low profile of this embodiment allows
solution to be delivered to areas that are very difficult to reach,
particularly through a less invasive incision. For example, as
shown in FIG. 10, the device is capable of delivering solution to a
target area of tissue on the posterior side of the heart. Also,
this configuration may also be suitable for injecting a solution
directly through the pericardial sac. Those skilled in the art will
appreciate the diversity of this embodiment and the many
applications for which it is suitable.
[0137] The dispersion means of the present invention for use in
endovascular applications includes a catheter assembly having an
end effector in the form of a catheter tip to access a target site
within an organ, a tumor, a body or vessel lumen, or an artificial
graft lumen. Some applications include, for example, accessing a
target area on the inside surface of the heart (i.e., the
endocardium), within the cardiac vasculature (such as the aorta, or
a coronary artery or vein), within the peripheral vasculature (such
as the iliac, femoral, popiteal and infrarenal), within the
neurovascular systems (such as the carotid artery) or to a tumor
via the vasculature from which it receives its blood supply. The
endovascular approaches involve inserting a catheter of the present
invention through a percutaneous incision made within a vessel,
such as the femoral artery, subclavian artery, the carotid artery
or other suitable vessel, and delivering the catheter tip to a
target site by means of a guide wire (e.g. over-the-wire, rapid
exchange or monorail catheter guide wire configuration) or a
guiding catheter, many of which are commonly used in the art. Such
a catheter is configured for attachment to the distal end of an
ampule (such as the embodiment of FIG. 1A) or directly to the
distal end of an injection device (such as the embodiment of FIG.
1B).
[0138] Turning again to the drawings, FIG. 11A illustrates an
embodiment of a dispersion means 300 of the present invention for
use in endovascular applications. Dispersion means 300 includes
catheter assembly 304 integrally coupled to an ampule body 308
defining a reservoir 310 by means of a retainer 311 threaded over
the distal end 309 of ampule body 308. Proximal end 307 of ampule
body 308 defines a bayonet mount for coupling to the distal end of
an injection system (such as injection system 10 of FIG. 1A).
[0139] Retainer 311 generally has a similar shape and size as the
dispersion fixtures discussed above with respect to the
intraoperative devices illustrated; however, retainer 311 does not
provide a solution dispersion function but, instead, provides a
means for securely retaining the attachment of catheter assembly
304 to ampule body 308, particularly during an injection cycle.
Juxtaposed between and in engagement with retainer wall 303 of
retainer 311 and ampule body 308 is an annular sleeve 305, which
further ensure retention of catheter assembly 304 to ampule body
308 when under the high pressures of an injection cycle.
[0140] Another difference between this endovascular device and the
surgical devices discussed above is the configuration of distal
portion 309 of ampule body 308. As is more clearly illustrated in
the cross-sectional view of FIG. 11B, distal portion 309 terminates
in an annular wall 312 and a reservoir nozzle 313 extending from
reservoir orifice 316. Reservoir nozzle 313 is centrally and
coaxially positioned within annular wall 312, and both extend about
7.5 mm proximally of ampule body 308, and collectively define a
toroidal shaped space 315 between them. Reservoir nozzle 313 has a
centrally disposed, narrow lumen 314 in fluid communication with
reservoir orifice 316. Narrow lumen 314, as well as reservoir
orifice 316, has diameters in the range from about 0.4 mm to about
0.8 mm.
[0141] Catheter assembly 304 includes a catheter 318 attached
proximally to a coupler 320. Catheter 318 is comprised of
material(s) having columnar and wall strengths sufficient to
maintain the desired pressure and velocity of an injected solution
throughout the injection cycle. Here, for added performance,
catheter 318 is preferably comprised of two layers, an internal
conduit 321 preferably made of a braided polyimide for strength,
and an outer sheath 322 preferably comprised of thermoplastic
polyether-based polyamide (PEBAX) which provides a soft atraumatic
feel.
[0142] The length and diameter (or size in French units) of
catheter 318 will depend on the diameter of the vessel providing
the delivery path and the distance between the percutaneous entry
site and the target site(s) (e.g., coronary artery, carotid artery,
iliac artery, femoral vein, subclavian artery, cerebral artery,
renal artery, etc.). For example, a catheter delivered through a
percutaneous site in the femoral artery at the patients groin to
location within the heart preferably has a length within the range
from about 1.3 meters to about 1.7 meters, and more preferably a
length of about 1.5 meters. A catheter to be delivered to within a
coronary artery, for example, likely has an outer diameter that is
smaller than that which is delivered to a heart chamber such as the
left ventricle, and is preferably is in the range from about 1.4 mm
to about 1.8 mm, or a French size of about 4 to about 6. On the
other hand, if the target site is within an inferior portion of the
femoral vein and the catheter entry site is within the portion of
the vein located near the groin, a catheter having a shorter length
and possibly a larger outer diameter may be used.
[0143] As mentioned above, catheter assembly 304 further comprises
a coupler 320, such as a luer subassembly, for coupling catheter
304 into reservoir nozzle 313. FIGS. 11C and D more clearly
illustrate the configuration of luer subassembly 320, which
generally includes a luer fitting 324 and hypotube 326 extending
coaxially from the distal end 328 of luer fitting 324. Luer fitting
324 is preferably comprised of stainless steel. Luer fitting 324
preferably has a length within the range from about 20 mm to about
24 mm, and an outer diameter at the widest portion of the luer wall
323 is in the range from about 6 cm to about 8 mm. The cylindrical
lumen 325 has a slightly distally tapered configuration within
which it matingly receives and engages the distal end of reservoir
nozzle 315. The profile of distal end 328 of luer fitting tapers
somewhat and defines a luer shoulder 338.
[0144] Centrally disposed within distal end 328 of luer fitting
324, hypotube 326 is in fluid communication with luer lumen 325.
Hypotube 326 extends distally from its proximal end 330, flush with
the distal end 329 of luer lumen 325, to a flared distal tip 332.
Like catheter 318, hypotube 326 is comprised of material(s) that
can maintain the desired pressure and velocity of an injected
solution throughout the injection cycle, and is preferably made of
stainless steel. Hypotube 326 has a length preferably in the range
from about 1.0 cm to about 1.3 cm, an outer diameter preferably in
the range from about 0.5 mm to about 0.7 mm, and an inner diameter
preferably in the range from about 0.35 mm to about 0.5 mm. As is
more clearly illustrated in FIG. 11E, distal tip 332 of hypotube
326 flares outward at a slight angle 334 in the range of about 6%
to about 9% from the axis defined by the inside of the tubing wall.
The flared portion of distal tip 332 comprises about 3 to about 5
of the entire length of hypotube 326. The outer diameter at
burnished edge 336 of flared tip 332 is approximately about 0.01 to
about 0.2 mm greater than that of the remainder of the hypotube
326. This tip configuration helps ensures a tightly sealed fit
between hypotube 326 and the proximal end of catheter 318. More
specifically, flared tip 332 and the distal portion of hypotube 326
are inserted into the lumen of inner layer 321 at the proximal end
of catheter 318, and then sealed to it by means of an epoxy. A
short metal ferrule 340 (having a length just shy of the portion of
hypotube 326 which extends from distal end 328) is then fit over
and crimped around the distal end of hypotube 326. The outer layer
322 of catheter 318 is then slid over and sealed to the entire
length of inner layer 321, including ferrule 340.
[0145] Turning now to the perspective view of retainer 311 in FIG.
11F, retainer 311 is preferably made of a polycarbonate material
and has a centrally positioned bore through its closed end 344
beveled at its perimeter 346. Retainer 311 is assembled with nozzle
assembly 302 and catheter assembly 304 by passing the distal tip
350 of catheter 318 through the underside of retainer 311 and
through bore 342. Retainer 311 is then slide over catheter 318 and
distal end 328 of luer fitting 324 until close end 344 buttresses
against luer shoulder 338. Bore 342 allows retainer 311 to rotate
around catheter assembly 304 while it is being manually screwed
onto annular sleeve 305. As just described, catheter assembly 304
and nozzle assembly 302 are now securely engaged with each
other.
[0146] FIG. 11G shows a perspective view of another embodiment of a
retainer 352 for use with the present invention. The configuration
of retainer 352 is generally similar to that of retainer 311 of
FIG. 11; however, closed end 355 of retainer 352 has a keyhole
shaped slot 354 that runs the height of annular sidewall 356. With
the slotted configuration, retainer 352 can be seated in place
without having to slide retainer 352 over the entire length of
catheter 318. Chamber 354 is aligned along catheter assembly 304
just above distal end 328 of luer fitting 320. After proper
alignment, retainer 352 is screwed onto annular sleeve 305. Besides
ease of use, this configuration has the added advantage of avoiding
potential damage to catheter 318 and particularly catheter tip 350.
Sidewall 356 is fluted for better grip. Retainer 352 is preferably
comprised of aluminum or of another lightweight, rigid metal,
rather than of a plastic material as the slotted configuration of
retainer 352 makes it more susceptible to failure under the
injection pressure if made of plastic.
[0147] Various embodiments of catheter tips for use with the
endovascular devices of the present invention will now be described
and discussed. The particular design of a catheter tip and its
target-facing surface for use with the present invention will
depend in part on the type of treatment involved. Some applications
include, for example, accessing a target area in a chamber or lumen
within an organ, within the cardiac vasculature, the peripheral
vasculature and the neurovascular systems, or on or in a tumor via
the vasculature from which it receives its blood supply. It is also
intended that the various catheter tip embodiments be
interchangeable with each for attachment to the same catheter.
[0148] The catheter tip design, and more specifically the design of
the target-facing surface of the tip, will also depend upon the
location of the targeted site and the type of tissue or substance
being treated. For example, when treating a coronary artery
affected by artherosclerotic plaque, such as with an angiogenic
solution to promote collateral vessel growth or with another
solution such as inducible nitrous oxide synthase (iNOS) to reduce
plaque or minimize the likelihood of restenosis, it is preferable
to use a catheter tip that is able to inject the solution directly
into or through the artery wall. As a catheter is typically coaxial
with and parallel to a vessel lumen into which it has been
delivered, a suitable catheter tip for this application is
preferably one that is capable of directing the ejected solution
along a path that is lateral to the catheter wall and preferably
somewhat transverse to, and possibly directly perpendicular to, the
artery lumen. Thus, such a design dictates that the target-facing
surface, i.e., the portion of the tip comprising the dispersion
orifices, comprise at least a portion of the wall of the catheter
tip. Simply stated, such a tip design ejects the solution from the
side of the catheter.
[0149] Referring now to FIG. 12, there is shown an exemplary
embodiment of a side-shooting catheter tip for use with the
catheter-based solution dispersion means of the present invention.
Catheter tip 400 is simply a distal extension of its catheter body
sealed at its distal end 407, which facilitates atraumatic delivery
of the catheter through the vasculature. Additionally, catheter tip
400 has a linear array of six dispersion orifices 402 (formed by
means of an exymer laser process) aligned in a single path along
one side of catheter wall 404 (i.e., the target-facing surface) and
parallel to the longitudinal axis of catheter tip 400. Any suitable
number of dispersion orifices and array of orifices arranged in any
suitable pattern (e.g., helically or in a solid pattern around the
circumference of the catheter tip, etc.) may be employed with the
side-shooting catheter of the present invention. The diameter of
each dispersion orifice 402 is in the range from about 0.1 mm to
about 0.3 mm. The length of the orifice array path and the distance
between the orifices 402 will depend on the application at hand and
the surface area of the tissue site being treated. Here, dispersion
orifices 402 are preferably spaced apart in the range from about 3
mm to about 5 mm. As such, catheter tip 400 is configured, for
example, to treat a site within a vessel affected by
atherosclerotic plaque wherein the plaque-covered area (i.e., the
target site) is situated to the orifice side of catheter tip 400.
This embodiment is also useful to deliver a thrombolytic agent to
an area of thrombus within a vessel that extends along a length of
the vessel.
[0150] FIGS. 13A-B illustrate such a side-shooting catheter in a
transvascular approach to treating a stenotic area within a cardiac
vessel. By transvascular, it is meant that the target tissue or
substance site is adjacent to or otherwise outside the vessel
through which the catheter is being delivered. Here, catheter tip
410, having a dispersion orifice configuration 412 similar to that
of catheter tip 400 of FIG. 12, has been delivered endovascularly
to within a vessel 415 embedded within the myocardium, such as the
cardiac vein, which is substantially parallel with and lateral to
coronary artery 417 having a stenotic area 419. Here, the array of
dispersion orifices 412 has been positioned along the side of
cardiac vein 415 adjacent to the stenotic area 419 within artery
417. Thus, a solution 414 ejected from orifices 412 by means of a
solution injection device of the present invention would define an
injectate vector path substantially perpendicular to the axis of
catheter tip 410 and to the lumen wall of vein 415 and artery 417,
thereby targeting stenotic area 419.
[0151] Turning now to FIGS. 14A-B, there is shown another
embodiment of a side-shooting catheter tip 420 of the present
invention in use in an intracoronary application. Catheter tip 420
has a plurality of dispersion orifices 422 arranged in a dense,
circumferential pattern throughout tip 420. In FIG. 14A, catheter
tip 420 has been delivered directly to within coronary artery 425
and positioned just proximal to stenotic area 423, allowing a
solution, such as an angiogenic solution to be injected into the
artery wall proximal of stenotic are 423. Ideally, collateral
vessel growth is initiated in the myocardial bed surrounding artery
425 to allow for enhanced blood flow to the tissues.
[0152] As is shown in FIG. 14B, catheter tip 420 may be delivered
to the distal side of stenotic area 423, provided that the diameter
of the vessel lumen at stenotic area 419 is large enough for
catheter tip 420 to pass through without the risk of embolizing the
plaque. Preferably, then, collateral vessel growth is initiated on
both sides of stenotic region 419 to further enhance blood supply
to the myocardium and to reduce the risk of ischemia in case
vessel. 425 becomes significantly occluded. If, however, stenotic
area 419 is sufficiently occluded so as to make passage of catheter
tip 420 to the distal side of stenotic area 419 impossible or
highly risky, a physician may choose to widen the passage by means
of a PTCA procedure prior to the step of delivering catheter tip
420 distal of stenotic area 419. In addition to injecting
angiogenic drug into the wall of artery 425 proximally and distally
of stenotic area 419, the same or a different solution, such as an
thrombolitic (such as tissue plasminogen activator (tPA)) or a gene
therapy drug (such as inducible nitrous oxide synthase (iNOS)) may
be injected directly into stenotic area 419 itself. The latter
injection may be accomplished by means of the same catheter used
for delivery of the angiogenic solution, or by means of a second
catheter. In either situation, a change of drug ampules may be
required. It should also be noted that more than one type of
solution or more than one injection of the same solution may be
injected into the same target tissue site.
[0153] FIG. 15 illustrates another embodiment of a side-shooting
catheter dispersion means of the present invention having
angioplasty capabilities integrated therein. A dilation means in
the form of an inflatable balloon 430 has been incorporated into
the catheter tip 426 for performing angioplasty at stenotic site
429. Balloon 430 is situated between proximal and distal dispersion
sections 431, 432. Dispersion sections 431, 432 have dispersion
orifice configurations similar to that of catheter tip 420 of FIGS.
12A-B but which extend over a length about twice that of catheter
420. This embodiment allows simultaneous dispersion of the
treatment solution proximally and distally of stenotic area 429
while eliminating the step of using a separate angioplasty
catheter. Those skilled in the art will recognize ways in which the
necessary angioplasty components may be incorporated into the
catheter dispersion means of the present invention.
[0154] The present invention includes another type of catheter tip
that is more suitable for injecting a solution into a targeted site
located either within or on an organ, a tumor or some other
non-tubular tissue structure, or within a vessel lumen but not
necessarily within the wall of the vessel itself. More
specifically, such a catheter tip design is capable of ejecting a
solution in a path distally of the catheter tip and substantially
coaxial or parallel to the longitudinal axis of the catheter. The
dispersion orifice(s) for such a tip design is preferably located
at the distally-facing end of the catheter tip rather than through
its sidewalls. Simply stated, such a tip design ejects the solution
from the end of the catheter.
[0155] Turning now to FIGS. 16A-C, an embodiment of such an
end-shooting catheter tip assembly 440 of the present invention
will now be described and discussed. Catheter tip assembly 440
includes a section of hypotube 442 and a dispersion fixture or cap
446 at the coupled to the distal end of hypotube 442. Hypotube 442
has a flared proximal end 444 to ensure a tightly sealed fit
between it and the distal end of catheter 462 of catheter assembly
460 (see FIG. 16C). Hypotube 442 has the same configuration and
dimensions and is comprised of the same material as hypotube
section 326 of FIG. 11D-E except that the flared end of hypotube
section 326 is its distal end rather than its proximal end.
Dispersion fixture or cap 446 has a cylindrical configuration
preferably having a wall height in the range from about 1.8 mm to
about 2.0 mm, an outer diameter in the range from about 1.5 mm to
about 1.7 mm, an inner diameter in the range from about 1.0 mm to
about 1.2 mm. The distal end of dispersion cap 446 defines a distal
surface 445, which in this embodiment is flat but may have any
appropriate shape (e.g., concave, rounded) for the application at
hand. Distal surface 445 has a dispersion orifice 447 centrally
bored there through and having a diameter in the range from about
0.1 mm to about 0.6 mm, and more preferably from about 0.1 mm to
about 0.3 mm. Dispersion orifice 447 may have any suitable size and
shape such as a circular bore, a slot, a diamond shape, etc.
Additionally, any suitable number of orifices may be used.
[0156] Seated flush within dispersion cap 446 is jewel or crystal
448 having a disk configuration with a diameter sufficiently sized
to allow jewel 448 to be slip-fit into dispersion cap 446. Jewel
448 has a central bore 449 having a diameter in the range from
about 0.1 mm to about 0.3 mm (about 30 to about 35 the diameter of
dispersion orifice 447), which is centrally aligned with dispersion
orifice 447 and the lumen of hypotube 442 when jewel 448 is
operatively seated. As with the jewels discussed with respect to
the surgical embodiments discussed above, jewel 448, although not
necessary, is preferably used to ensure an accurate and precise
vector path of an ejected solution. Coaxially disposed between
dispersion cap 446 and the distal end of hypotube 442, and abutting
the proximal side of jewel 448, is an annular sleeve 450. Annular
450 is preferably laser welded at points of contact between it and
dispersion cap 446 and hypotube 442, respectively, to provide a
fluid-tight seal to prevent against leakage of a solution as it is
being ejected and to retain jewel 448.
[0157] The cross-sectional view of FIG. 16C shows catheter tip
assembly 440 operatively coupled within the distal end of a
catheter 460, which preferably has the same two-ply configuration
as catheter 318 described above with respect to FIG. 11A. Here,
internal conduit and outer sheath are referenced as 462 and 464,
respectively. Similar to the manner in which hypotube 326 and the
proximal end of catheter 318 of FIG. 11A are coupled together,
hypotube 442 is inserted into the distal end of internal conduit
462 over which a ferrule 468 is coaxially positioned and crimped.
Outer sheath 464 is then sealed with epoxy around this composite
structure.
[0158] Endovascular methods of using such an end-shooting catheter
of FIGS. 16A-C include intrachamber and intravascular approaches.
The intrachamber approach involves delivering the catheter tip to
within a chamber or lumen in an organ. An intravascular approach
involves delivering of the catheter tip to within a selected
portion of an artery or vein, such as a coronary artery, a
peripheral vessel, or the neurovasculature.
[0159] Specific cardiac applications of the intrachamber approach
include but are not limited to the delivery of an angiogenic
solution to the endocardium, such as within the left or right
ventricle, for treatment of an ischemic area of myocardium; the
delivery of an anti-angiogenic solution to treat a tumor located
within a heart chamber (i.e., a myxoma); the delivery of a
biochemical, such as ethanol, to within the atria for treating
atrial fibrillation; and the delivery of a thrombolytic solution,
such as tPA, to break up a thrombus within the atria.
[0160] For example, FIG. 17 illustrates use of an endovascular
dispersion means of the present invention having a catheter
assembly 500 including a catheter 502 and catheter tip 504, of the
construction just described with respect to FIGS. 16A-C. Catheter
assembly 500 has been delivered endovascularly to within a chamber
of the heart, such as the left ventricle, to treat an ischemic
region 507 of the myocardium 505. Here, catheter tip 504 is shown
operatively contacting endocardium 509 for delivery of an
angiogenic solution to the targeted tissue area 507. As mentioned
above with respect to other embodiments of the dispersion means of
the present invention, it is not necessary to contact the target
area with the catheter tip; however, in this application, it may be
preferable as the flow of blood within the ventricle during the
systolic and diastolic cycle does not interfere with the delivery
path or reduce the pressure of the ejected solution prior to its
entry into the endocardium 509. Catheter tip 504 may be delivered
to within any distance from the surface of the endocardium which
will allow the delivery of a sufficient volume of solution at a
desired pressure.
[0161] Specific cardiac applications of the intravascular approach
using an end-shooting catheter tip include but are not limited to
the delivery a thrombolytic solution, such as TPA, or a non-drug
such as saline, to break up a thrombus within the coronary,
peripheral or a neuro vasculature. More specifically, when the
thrombus is more of a localized formation, such as that in FIGS.
18A-B, rather than a planar configuration along a length of a
vessel wall, the such an end-shooting embodiment is appropriate.
For example, FIGS. 18A-B illustrate an intravascular approach of
the present invention for treating deep vein thrombosis such as
within the saphenous or iliac vein 512 of a patients leg 510. Here,
an embodiment of a catheter 520 having a multi-orifice,
end-shooting catheter tip configuration 522 has been delivered
through a percutaneous incision 514 proximate the patients groin to
a location just proximal of the target site or thrombus 516
anchored to the inner wall of vessel 512. The end-shooting catheter
tip 522 is designed to direct an throbolitic solution at the
thrombus 516, but not directly into the tissue wall to which the
thrombus is anchored, thereby avoiding injuring to the vessel
wall.
[0162] FIGS. 19A-B illustrate another example of an intravascular
approach of the present invention in a neurovascular application.
FIG. 19A is a cross-sectional view of a medial portion of a human
brain 540. Here, an end-shooting catheter 530 has been delivered
through a percutaneous incision (not shown) into the carotid artery
of the patient and into the cerebral artery 542 to reach thrombus
544. Multi-orifice catheter tip 532 has been positioned just
proximal of thrombus 544 where it is ideally positioned to deliver
the thrombolytic solution to the thrombus 544.
[0163] Another application of the endovascular embodiments of the
present invention is the treatment of AV access grafts that have
plaque and/or thrombus formations within the graft lumen. Most
commonly, the injectate is a thrombolytic drug or a lysing agent.
Similar to the other intravascular applications discussed above,
the treatment of AV access grafts involves inserting the catheter
through a percutaneous opening and delivering the catheter tip
proximate the target site, e.g., an area of plaque or thrombus
formation. Here, the percutaneous opening is most typically the
external opening of the graft, but the opening may be a
percutaneous incision through the skin at a location near the
graft. Either a side-shooting or an end shooting catheter may be
used, depending on the specific location and positioning of the
formation being targeted. The therapeutic agent is then injected at
the target site. As medically dictated, the targeted formation may
be dissolved or broken up sufficiently to be released systemically
within the patient, or may otherwise be filtered or vacuumed and
then removed from the graft by the physician.
[0164] A diagnostic application of the present invention, primarily
the endovascular embodiments, involves first using the catheter to
inject contrast solution (prior to injecting a therapeutic
solution) into the general target site while examining the site
under fluoroscopy. The purpose of this diagnostic step is to
determine the landscape of microvasculature in the target tissue
site in order to avoid rupturing the healthy microvasculature.
Rupturing the microvasculature is clearly damaging to the tissue
and can also cause the injectate to enter the blood stream for
systemic distribution that may be harmful to the patient. From this
diagnostic step, the practitioner may determine the appropriate
injection penetration depth, and the appropriate size and number of
dispersion orifices.
[0165] In order to effectively treat the affected area of tissue or
the substance affecting the targeted tissue site with any
embodiment and in any application of the present invention, it is
important for the physician or user of the present invention to be
aware of potential factors that may affect the desired dispersion
pattern of the injectate. By dispersion pattern, we mean the depth
and breadth of dispersion. Factors that may affect dispersion
patterns, include the type of tissue being treated, the volume of
blood flow through the targeted tissue, the kinematics and
viscosity of the injectate, the volume of and the injection
pressure of the injectate, and the distance between the target site
and the dispersion orifice(s).
[0166] The pressure of the injectate is one of the most important
factors. It will significantly affect the depth of penetration into
a target site. The depth of penetration may be crucial for certain
applications. For example, when using a side-shooting
catheter-based injection device of the present invention in an
intravascular application, a physician may want to limit
penetration of the injectate to only the endothelial lining of the
vessel. On the other hand, he may want to penetrate through the
adventitial layer of the vessel wall and into the surrounding
tissue bed. Accordingly, the proper injection pressure should be
carefully selected for the application at hand.
[0167] Different types of tissue (e.g., myocardial, vascular,
cartilage, malignancies, etc) or substances (e.g., atherosclerotic
plaque, thrombus, etc.) have physiological differences that may
affect the dispersion characteristics of an injected solution. For
example, muscular tissue such as the myocardium has what are known
as interstitial tissue planes, i.e., parallel planes of tissue
defined by seams running between the planes. The point or line of
contact between a vessel and its adjacent tissue also define and
interstitial tissue plane. These planes may affect the path of the
injectate as it will follow the path of least resistance and run
along the seams rather than transversely penetrating the tissue
planes.
[0168] Exposure of the injected solution to a blood supply can also
effect dispersion and the intended medical outcome of the
procedure. For example, in the case of infarcted myocardium, it is
important for the injected angiogenic growth factor to be exposed
to at least some blood supply by which it is nourished in order
proliferate. Additionally, due to the individual cellular and
chemical composition of each solution, each solution is likely to
have a different kinematic response while dispersing through
tissue. The viscosity, cell size, valence bonding, and other
chemical and biological characteristics of the solution may also
affect its kinematic behavior.
[0169] For purposes of this description, the devices and methods of
the present invention have been described primarily for use in
cardiac and vascular applications, and more specifically for the
treatment of ischemia, atherosclerosis and thrombosis; however,
other applications of the present invention are contemplated. These
include but are not limited to the treatment of tumors, rheumatoid
arthritis, chronic inflammatory diseases, genital-ureteral
conditions and various retinopathies. Also, although only specific
examples of injectable solutions were mentioned in the description,
any suitable biologic, pharmaceuticals, biopharmaceuticals, or
other agents which are not necessarily categorized as a drug (e.g.,
alcohol) may be delivered and injected by the devices and methods
of the present invention.
[0170] Each of the various components of the solution
delivery/injection systems of the present invention, the injection
device, the solution ampule and the solution dispersion means, may
be supplied integrally assembled and packaged, or may be
individually packaged, or otherwise packaged in any combination of
the components. The ampules may be supplied with a pre-filled,
selected volume (one or more doses) of solution directly from the
supplier, or may be filled by the user at the time of the procedure
and then refilled with additional doses, either within the same
procedure, or in a later procedure. Additionally, any or all of the
components may be reusable, or disposable, single-use (or
procedure) units.
[0171] For all embodiments of the present invention, the end
effector of the dispersion means is designed for optimally
delivering and dispersing a solution through the surface of the
target organ or tissue or substance without using the end effector
itself or another implement to first penetrate and create a working
space within the tissue.
[0172] From the foregoing, it will be appreciated that although
embodiments of the invention have been described herein for
purposes of illustration, various modifications may be made without
deviating from the spirit of the invention. Thus, the present
invention is not limited to the embodiments described herein, but
rather is defined by the, claims which follow.
* * * * *