U.S. patent application number 11/619091 was filed with the patent office on 2007-06-21 for system and method for delivering thermally sensitive and reverse-thermal gelation materials.
This patent application is currently assigned to BioCardia, Inc.. Invention is credited to Daniel C. Rosenman.
Application Number | 20070142774 11/619091 |
Document ID | / |
Family ID | 22521912 |
Filed Date | 2007-06-21 |
United States Patent
Application |
20070142774 |
Kind Code |
A1 |
Rosenman; Daniel C. |
June 21, 2007 |
System and Method for Delivering Thermally Sensitive and
Reverse-Thermal Gelation Materials
Abstract
A catheter for injecting a thermally sensitive gelation material
to remote sites within a patient's body by maintaining the
thermally sensitive gelation material in a liquid state until it is
delivered to a target area within the body.
Inventors: |
Rosenman; Daniel C.; (South
San Francisco, CA) |
Correspondence
Address: |
CROCKETT & CROCKETT
24012 CALLE DE LA PLATA
SUITE 400
LAGUNA HILLS
CA
92653
US
|
Assignee: |
BioCardia, Inc.
|
Family ID: |
22521912 |
Appl. No.: |
11/619091 |
Filed: |
January 2, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10832040 |
Apr 26, 2004 |
7156824 |
|
|
11619091 |
Jan 2, 2007 |
|
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|
10308344 |
Dec 2, 2002 |
6726654 |
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10832040 |
Apr 26, 2004 |
|
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|
09632865 |
Aug 4, 2000 |
6488659 |
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10308344 |
Dec 2, 2002 |
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60147523 |
Aug 5, 1999 |
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Current U.S.
Class: |
604/113 |
Current CPC
Class: |
A61B 2017/005 20130101;
A61M 2205/3633 20130101; A61B 2017/00243 20130101; A61M 25/0084
20130101; A61B 17/00491 20130101; A61M 5/44 20130101; A61M
2025/0004 20130101; A61M 2025/0089 20130101 |
Class at
Publication: |
604/113 |
International
Class: |
A61F 7/12 20060101
A61F007/12 |
Claims
1. A method of treating a target area within the body of a patient,
said method comprising the steps of: providing an insulated
catheter, said catheter adapted to deliver a reverse thermal
solution within the body of the patient; inserting the insulated
catheter into the body of the patient; and delivering the reverse
thermal solution to the target area.
2. The method of claim 2 wherein the step of delivering the reverse
thermal solution to the target area comprises delivering the
reverse thermal solution to the heart of the patient.
Description
[0001] This application is a continuation of U.S. application Ser.
No. 10/832,040, filed Apr. 26, 2004, now U.S. Pat. No. 7,156,824,
which is a continuation of U.S. application Ser. No. 10/308,344
filed Dec. 2, 2002, now U.S. Pat. No. 6,726,654, which is a
continuation of U.S. application Ser. No. 09/632,865, filed Aug. 4,
2000, now U.S. Pat. No. 6,488,659, which claims priority to
provisional application 60/147,523 filed Aug. 5, 1999.
FIELD OF THE INVENTIONS
[0002] This application relates generally to catheters, and more
specifically to catheters and methods for delivering thermally
sensitive gelation materials and reverse-thermal gelation materials
to remote sites in the body.
BACKGROUND OF THE INVENTIONS
[0003] In many disease states, doctors want to deliver a
therapeutic agent to a target area and have the agent remain in the
target area to treat the tissue for an extended period of time. If
the therapeutic agent has the consistency of liquid, the body
quickly and efficiently carries it away from the target area. As a
result, the duration of time that the agent has to treat the target
area is short.
[0004] In order to reduce the body's ability to carry the
therapeutic agent away from the target area others have increased
the viscosity of the therapeutic agent such that it has the
consistency of gel. Using gels is effective because the diffusion
rates of gels are slower than the diffusion rates of liquids. Thus
the gel elutes the therapeutic agent over a longer time course
treating the target area for a greater period of time. There are
many types of gels that can incorporate therapeutic agents. Each
type of gel changes viscosity in response to different
environments. Those environments include pH, temperature, catalyst,
chemical reaction, solvent, or reaction with compounds in the
body.
[0005] Catheters are traditionally used to deliver therapeutic
agents to remote target areas in the body. Generally catheters
traverse the vascular pathways of the body until the tip of the
catheter reaches the target area. Catheters are used in the
cardiovascular, gastric, general, urological, neurological, and
oncological fields of medicine. The target area can be a blood
vessel, an organ, or a tumor. Catheters have been used to deliver
acute therapeutic agents such as analgesic, antibacterial,
anti-restenotic, anticancer, anti-inflammatory agents and hormones,
and bulking agents such as collagen and stainless steel
micro-embolic coils. However, due to the small size and long length
of the catheters they cannot deliver viscous materials such as gels
to remote sites in the body.
[0006] One way to circumvent the problem of delivering viscous
materials is to use a special class of gels, known as
reverse-thermal gelation gels (also known by the trademarked name
PLURONIC.RTM. gels or TETRONIC.RTM. gels, available from BASF and
other suppliers). These gels are characterized by the property of
being liquid below a critical solution temperature and becoming
viscous, or gel-like, above the critical solution temperature. This
is in contrast with normal matter that is solid below a critical
temperature, for example, the freezing temperature and liquid above
that critical temperature, exhibiting decreased viscosity as the
temperature of the matter increases. The critical solution
temperature of these gels can be tailored by their chemistry such
that they are liquid at room temperature or below (0-23.degree. C.)
and gel at body temperature (37.degree. C.).
[0007] There have been many studies of the biological behavior of
sustained release of substances from PLURONIC.RTM. gels in animals.
This gel has typically been delivered to shallow tissue in animals
through a syringe. It is possible to deliver it in this manner
because the delivery path is short enough that the liquid doesn't
gel before it is delivered through the syringe tip because the
animal's body heat does not have sufficient time to heat it up.
[0008] Gels, however, cannot be delivered to remote sites in the
body such as the heart or the brain through a catheter because the
gels are too viscous to be injected.
SUMMARY
[0009] The devices and methods claimed below allow thermally
sensitive gelation materials to be injected into remote sites
within a patient's body.
[0010] The injection catheter includes a hollow needle, a catheter
body, a handle, and a syringe. The syringe is located at the
proximal end of the injection catheter and the hollow needle is
located at the distal end.
[0011] One embodiment includes a thermally insulated injection
catheter that has an insulated catheter body. The insulated
catheter body includes a catheter wall, a stainless steel mesh
layer, an insulation layer, and a solution tube. The catheter body
can also include second tube, called the alternate tube, which
extends from the distal to the proximal end of the catheter. This
alternate tube joins the solution tube at a Y-junction proximate to
the hollow needle.
[0012] Another embodiment includes a catheter body having a
catheter wall, a solution tube, an input tube and an output tube.
The input tube surrounds the solution tube and carries a fluid, gas
or liquid, along the length of the solution tube for maintaining
the therapeutic solution in a liquid state.
[0013] A further embodiment combines cooling fluid and
reverse-thermal solution into one tube by injecting reverse-thermal
solution "plugs" separated and carried by the cooling fluid. The
plugs move down the tube, pushed by the force of injected saline.
Once the discrete plugs are lodged in the target area, the saline
would be transported away by the body, leaving the reverse-thermal
solution plug in place to harden and elute its therapeutic agent
over time.
[0014] In another embodiment, therapeutic solution is in a
reservoir located at the distal end of the catheter. The
therapeutic solution is liquefied at a neck section, which is
located proximate to the hollow needle that delivers the
therapeutic solution. The input tube coils around the neck section
and the fluid flows, in the direction of the arrow D, through the
input tube liquefying the therapeutic solution, then out the output
tube.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is an isometric view of an injection catheter.
[0016] FIG. 2 is an isometric view of a cross-section of an
insulated catheter body.
[0017] FIG. 3 is an isometric view of a cross-section of a catheter
body having a Y-junction.
[0018] FIG. 4 is an isometric view of a cross-section of a catheter
body having an input tube, an output tube, and a solution tube.
[0019] FIG. 5 is an isometric view of an injection catheter having
a fluid input and fluid output.
[0020] FIG. 6 is an isometric view of a cross-section of a catheter
body having an input tube coiled around a solution tube.
[0021] FIG. 7 is an isometric view of a cross-section of a catheter
body having a reservoir, a neck section with a coil.
[0022] FIG. 8 is an isometric view of an injection catheter in
use.
[0023] FIG. 9 is an isometric view of the distal end of an
injection catheter in use in the heart.
DETAILED DESCRIPTION OF THE INVENTIONS
[0024] The devices and methods described below provide for the
delivery of controlled-release therapeutic agents to distant
locations in the body through small access areas.
[0025] A therapeutic solution is a thermally sensitive gelling
material combined with a therapeutic agent. The term "thermally
sensitive gelling material" includes both normal thermal gels and
reverse-thermal gels. A thermal gel that works in a patient's body
must gel at body temperature and be a liquid at a temperature
higher than body temperature. Examples of such materials are
collagen and PLA/PLG copolymers. As discussed above, PLURONIC.RTM.
gel is a reverse-thermal gel that can be used in a patients
body.
[0026] A thermal solution is a combination of a normal thermal gel
and a therapeutic agent, and a reverse-thermal solution is a
combination of a reverse-thermal gel and a therapeutic agent. The
term "solution" is used in its broad sense, and is meant to
encompass a solution, a suspension, and any other form of combining
a gel with a therapeutic agent.
[0027] FIG. 1 illustrates an injection catheter 1. The injection
catheter includes a hollow needle 2, a catheter body 3, a handle 4,
and a syringe 5. The syringe is located at the proximal end of the
injection catheter and the hollow needle is located at the distal
end. The term hollow needle is meant to encompass any hollow
puncturing element. The hollow needle is typically a 27 or 28-gauge
needle that is in fluid communication with the syringe. The syringe
provides the force for moving the therapeutic solution through the
catheter body.
[0028] The syringe 5 is coupled to the catheter body 3 through a
first luer 7 that can be fixed or rotating hemostatic type. The
handle 4 advances the catheter body and optionally transmits torque
to the catheter body. The catheter body carries the therapeutic
solution from the syringe, or other injection device, to a target
area within the patient's body.
[0029] FIG. 2, a preferred embodiment, shows a thermally insulated
injection catheter that has an insulated catheter body 10. The
insulated catheter body includes a catheter wall 11, a stainless
steel mesh layer 12, an insulation layer 13, and a solution tube
14. The catheter wall is typically PEBAX.RTM. thermoplastic and is
approximately 0.125'' in outside diameter. The solution tube
transports the therapeutic solution from the syringe, out of the
needle, to the target area. The insulation layer and the stainless
steel mesh layer limit the transfer of heat between the patient's
body and the therapeutic solution, thus maintaining the therapeutic
solution in the liquid state as it travels through the insulated
catheter body to the target area.
[0030] As previously mentioned, the catheter wall 11 is typically
PEBAX.RTM. resin, and typically 0.118'' in outside diameter and
0.091'' in inside diameter. It may be constructed of varying
durometers or flexibilities from proximal to distal end. The
durometer ranges for this type of catheter are typically from 75D
to 30D. The catheter may be lined with Teflon, PTFE, ETFE, FEP,
polyethylene, polypropylene, or FPA to allow the transition from
one diameter to another. The stainless steel mesh layer 12 can be
stainless steel braiding or coiling which increase torque
transmission and elastic bending properties. The diameter of the
stainless steel wires typically used in this construction is
0.0025''. The wires may be round or flat. The braiding is typically
around 90 picks per inch.
[0031] The insulation layer 13 is soft material that has low
thermal conductivity, such as, closed or open-celled foams of
polyurethane, silicone, polyvinyl alcohol or other thermoplastics
or thermosetting plastics. Alternatively, the insulation layer can
be made up of windings of flat materials that include these foams,
thermoplastics, papers, cellulose, and other thermally insulating
materials. The winding pattern and stiffness of these materials are
designed to allow the catheter to bend easily so that it can
negotiate curves in the patient's vasculature to advance to the
target area.
[0032] If the therapeutic solution is a reverse-thermal solution,
then the insulation layer 13 could be replaced by a high heat
capacity fluid or material. A fluid or material whose critical
temperature is near the delivery temperature of the reverse-thermal
solution keeps the reverse-thermal solution cool by taking heat
away from it. The catheter could be filled with this fluid or
material at room temperature or it could be precooled before it was
used in the catheter lab. This fluid or material (solid, gel or
liquid) is protected from the heat of the circulating blood by the
insulating properties of the catheter wall.
[0033] The solution tube 14 has an outer diameter of typically
0.030'' and the inner diameter is sized to fit over the 27or
28-gauge needle (typically 0.016'' inside diameter). The solution
tube material can be silicone, urethane, polyethylene, Teflon,
PTFE, ETFE, FEP, FPA, polyolefin, PEO or other thermoplastic that
is easily extruded. The solution tube carries the therapeutic
solution from the syringe to the hollow needle on the distal end of
the catheter. The needle is typically constructed of stainless
steel but could be insulated with a thermally insulating material
(thermoset or thermoplastic) or made of such a material.
[0034] FIG. 3 shows a second preferred embodiment which includes a
second tube, called the alternate tube 16, extending from the
distal to the proximal end of the catheter. The alternate tube
joins the solution tube at a Y-junction 17 proximate to the hollow
needle 2. The surgeon could inject radiopaque contrast through this
tube to better visualize locations in the body. This tube could
also be used to flush the distal hollow needle or helix of the
therapeutic solution after the solution had been injected into the
target area. This would ensure that no therapeutic solution resides
in the exposed hollow needle thus reducing the small likelihood
that the solution could solidify within the device.
[0035] When a reverse-thermal solution is used, heated saline could
be injected into the alternate tube 16 where the alternate tube is
insulated. The heated saline would flush the distal end of the
catheter after the reverse-thermal solution had been delivered.
Additionally, the heated saline would speed the gelling of the
reverse-thermal solution within the target area. In contrast, when
a thermal solution is used, cooled saline could be injected into
the alternate tube.
[0036] FIG. 4 shows a third preferred embodiment which includes a
catheter body 3 having a catheter wall 11, a solution tube 14, an
input tube 18 and an output tube 19. The input tube surrounds the
solution tube and carries a fluid, gas or liquid, along the length
of the solution tube through the catheter body toward the distal
end of the catheter. The output tube surrounds the input tube and
carries the fluid away from the distal end of the catheter. The
catheter wall surrounds the output tube.
[0037] An opening 21 at the distal end of the catheter connects the
input tube 18 and the output tube 19, such that the fluid flows
from the proximal end of the catheter to the distal end of the
catheter through the input tube. The fluid then flows in the
direction of the arrow A into the output tube. Once in the output
tube the fluid flows to the proximal end of the catheter. The
distal plug 22 prevents fluid from flowing out of the distal end of
the catheter into the patient's body.
[0038] The fluid is either a heating or a cooling fluid, depending
on whether the therapeutic solution is a thermal solution or a
reverse-thermal solution. A heating fluid is used if a thermal
solution is used, and a cooling fluid is used if a reverse-thermal
solution is used. The fluid keeps the therapeutic solution in the
liquid state as it travels through the catheter. The fluid
convectively cools or heats the therapeutic solution. The term
"fluid" is meant in its broad sense, and includes liquids and
gases. A compressed gas, such as, nitrogen, carbon dioxide, air,
oxygen, helium or other gas can be used as the fluid.
[0039] FIG. 5 shows the syringe 5, filled with the therapeutic
solution in the liquid state, is connected to the catheter body via
a first luer 7. Also connected to the catheter body, via a second
luer 23, is a fluid source container 24. Further connected to the
catheter body, via a third luer 25, is a fluid output container 26.
The therapeutic solution flows from the syringe 5 through the
catheter body 4 out of the needle 2 into the target area. The fluid
flows from the fluid source container 24 into the input tube,
through the opening into the output tube and finally into the fluid
output container 26.
[0040] A pump 30 draws up the fluid, which can be water, saline,
radiopaque contrast material or a gas etc., from the fluid source
container and pressurizes it into the proximal end of the input
tube of the catheter. Gravity, a pressurized reservoir, hand
pressure or other supply of pressurized fluid can also supply the
pressure to move the fluid through the catheter.
[0041] FIG. 6 shows the input tube 18 being wrapped in a spiral
fashion around the solution tube 14 forming a coil 27. Once the
coil reaches the distal end of the catheter, it changes direction
180 degrees and becomes the output tube 19 returning the fluid to
the proximal end of the catheter and into the fluid output
container.
[0042] In another alternative, there could be an input tube and no
output tube or distal plug, such that, a cooling fluid flows out
the distal end of the catheter into the body. The cooling fluid in
this case could be saline. If the cooling fluid is saline, it can
continuously empty into the bloodstream without adverse effects on
the patient.
[0043] The pressure of the fluid carries it out of the catheter and
into the fluid output container. When the driving pressure of the
fluid is higher than atmospheric pressure, the fluid will flow into
the fluid output container, if it is open to the atmosphere.
Because of the thermal capacity of the fluid and the volume of
fluid flow, the therapeutic solution is kept in the liquid state
until it exits the catheter into the target area.
[0044] One schooled in the art can envision that the pump can be
placed on the output-side of the catheter and could develop a
vacuum that would draw the fluid through the catheter instead of
pushing it from the input-side. The preferred embodiment also
includes controllers to change the rate at which the fluid is
pumped, the input temperature of the fluid, and thermocouples tied
to temperature readouts which monitor the temperature of the
therapeutic solution as it exits the catheter into the target
area.
[0045] FIG. 7 shows another preferred embodiment, which includes a
reservoir 34 filled with the reverse-thermal solution. The
reservoir is located at the distal end of the catheter. The
reverse-thermal solution is cooled at a neck section 35, which is
located proximate to the hollow needle 2 that delivers the
reverse-thermal solution. The input tube 18 coils around the neck
section and the fluid flows, in the direction of the arrow D,
through the input tube cooling the reverse-thermal solution then
out the output tube 19, in the direction of the arrow C. The
reservoir has a large, constant cross-section. The cooling of the
reverse-thermal solution occurs just proximal to the hollow needle
2 liquefying a small amount of reverse-thermal solution. This small
amount of reverse-thermal solution is dispensed by the pressure of
the reservoir of reverse-thermal solution in the gelled state which
acts like a syringe plunger when pressurized at the proximal end of
the catheter. Because the large gel reservoir is of a constant
cross-sectional area, it can be forced forward under mild pressure
(but not through the small opening of the distal needle).
[0046] The same configuration could be used wherein the reservoir
is filled with the thermal solution. The fluid carried in the input
tube heats the neck section thus liquefying the thermal solution in
the neck section in order to inject the thermal solution into the
target area.
[0047] Another embodiment combines cooling fluid and
reverse-thermal solution into one tube by injecting reverse-thermal
solution "plugs" separated and carried by the cooling fluid. The
plugs move down the tube, pushed by the force of injected saline.
Once the discrete plugs are lodged in the target area, the saline
would be transported away by the body, leaving the reverse-thermal
solution plug in place to harden and elute its therapeutic agent
over time. The proximal end of the device could have a two-position
stopcock that either feeds cool saline or cooled saline carrying
discrete plugs, depending on which input source is selected by the
stopcock position.
[0048] FIGS. 8 and 9 show the catheter in use. The catheter can,
for example, deliver the therapeutic solution to the heart 38,
where it slowly releases growth factors to treat coronary artery
disease over a period of time. In this instance, the injection
catheter is routed through the aortic valve 39 to the left
ventricle 40 of the heart inside a hollow guide catheter (not
shown) specially shaped for this access. Once the distal end of the
catheter is carried to the target site, the needle of the catheter
is buried in the wall of the myocardium 41. Then the proximal
syringe 5 is depressed to dispense the physician-specified amount
of therapeutic solution into the myocardium. The injection catheter
is removed from the myocardium and repositioned to another site or
removed from the patient's body. The injected therapeutic solution
then becomes more viscous under the influence of the body
temperature of the patient and thus remains in place to elute its
therapeutic agents over a period of time. The therapeutic solution
for injection into the heart muscle includes anti-arrythmia agents,
angiogenic growth factors, and other agents having therapeutic
effects on heart tissue.
[0049] Implantation of therapeutic reverse-thermal solutions with
angiogenic agents in concert with a percutaneous transmyocardial
revascularization procedure (PTMR) may prove more efficacious than
either procedure alone. The localized heating may help start the
angiogenic response.
[0050] The devices described provide for delivery of therapeutic
agents to the myocardium of the left ventricle (retrograde access
across the aortic valve), the right atrium and ventricle of the
heart (venous access), trans-septally from the right to the left
side of the heart, from the coronary sinus into the myocardium, or
from the coronary artery vessels into the myocardium of the
heart.
[0051] There has been recent work on the development and delivery
of growth factors, or antigrowth factors to tissues in the human
body. These growth factors can be delivered to influence nerves,
blood vessels, tissues, bones, cartilage, muscles, or other cells
to grow. Gene therapy preparations can also be delivered. These
preparations enable cells to produce the therapeutic proteins that
encourage the tissues to grow. Anti-growth proteins have been
delivered to discourage growth or to kill tissues that are growing
abnormally such as anti-restenosis or antitumor drugs, cytotoxic or
chemotherapeutic drugs. The cytotoxic or chemotherapeutic drugs
include vincristine, vinblastine, cisplatin, methotrexate, and
5-FU. Gene therapies are being developed to enable the body to make
the proteins that limit growth or cause cells to die. All of these
therapeutic agents can be formulated into therapeutic
solutions.
[0052] The cooling, heating, or insulating properties of the
catheter can also encapsulate the syringe or other pressurized
source of therapeutic solution. This would keep the therapeutic
solution in its liquid state for a longer period of time. If the
therapeutic solution being used were a reverse-thermal solution
then it could be insulated it from the heat of the operating room
or doctor's body.
[0053] There are other pressurizing elements to deliver the
therapeutic solution to the target area including power injectors,
syringe pumps, roller pumps, compressed-gas-powered syringes,
in/deflators, and dosing syringes. All of these could be used with
the devices and methods described above because they can be joined
to the input tube at the luer connector at the proximal end of the
catheter.
[0054] Features could be added to the catheter to control the depth
that the needle tip penetrates the tissue at the target area.
Another possible feature is to measure the amount of therapeutic
solution that is delivered at the distal end of the catheter.
[0055] Another embodiment uses electrical, magnetic,
radiofrequency, ultrasonic, laser, ultraviolet, or other energy
source at the distal end of the catheter to speed the gelling of
reverse-thermal solutions after they have been delivered, and the
needle flushed of its contents with saline. This is particularly
useful in tumor ablation procedures. The additional heat generated
by the energy source kills some of the aberrant tumor cells and the
delivered reverse-thermal solution continues killing the tumor
cells after the acute treatment provided by the energy source.
[0056] Thus, while the preferred embodiments of the devices and
methods have been described in reference to the environment in
which they were developed, they are merely illustrative of the
principles of the inventions. Other embodiments and configurations
may be devised without departing from the spirit of the inventions
and the scope of the appended claims.
* * * * *