U.S. patent application number 11/050214 was filed with the patent office on 2005-06-16 for ultrasonic surgical instrument for intracorporeal sonodynamic therapy.
Invention is credited to Makin, Inder Raj S., Mensch, Jurgen, Noppe, Marcus Joannes Maria, Slayton, Michael H..
Application Number | 20050131339 11/050214 |
Document ID | / |
Family ID | 26876572 |
Filed Date | 2005-06-16 |
United States Patent
Application |
20050131339 |
Kind Code |
A1 |
Makin, Inder Raj S. ; et
al. |
June 16, 2005 |
Ultrasonic surgical instrument for intracorporeal sonodynamic
therapy
Abstract
The present invention relates, in general, to ultrasonic
surgical instruments and, more particularly, to an intracorporeal
ultrasonic surgical instrument for sonodynamic therapy. Disclosed
is an ultrasonic surgical system comprising: a generator and an
instrument comprising: a housing; a transducer; a semi-permeable
membrane; a pharmaceutical agent; and an agent delivery system. The
transducer is adapted to convert the electrical energy of the
generator into mechanical energy. The pharmaceutical agent,
delivered into a chamber of the semi-permeable membrane, is driven
through the semi-permeable membrane by the mechanical energy. A
method in accordance with the present invention comprises the steps
of: providing a surgical instrument comprising: a housing; a
transducer connected to the housing; a semi-permeable membrane; a
pharmaceutical agent; and an agent delivery system; inserting the
surgical instrument into a patient; delivering a drug to the
patient; and locally activating the drug with the surgical
instrument.
Inventors: |
Makin, Inder Raj S.;
(Loveland, OH) ; Mensch, Jurgen; (Vorst-Laadal,
BE) ; Noppe, Marcus Joannes Maria; (Kalmthout,
BE) ; Slayton, Michael H.; ( Tempe, AZ) |
Correspondence
Address: |
PHILIP S. JOHNSON
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
26876572 |
Appl. No.: |
11/050214 |
Filed: |
February 3, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11050214 |
Feb 3, 2005 |
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10180702 |
Jun 26, 2002 |
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60302070 |
Jun 29, 2001 |
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Current U.S.
Class: |
604/22 |
Current CPC
Class: |
A61M 37/0092 20130101;
A61N 7/00 20130101 |
Class at
Publication: |
604/022 |
International
Class: |
A61B 017/20 |
Claims
What is claimed is:
1. An ultrasonic surgical system comprising: a housing; a
transducer connected to said housing; a membrane surrounding said
transducer; and a pharmaceutical agent within the membrane; and an
agent delivery system.
2. The ultrasonic surgical system of claim 1, wherein said
transducer operates within the range of about 500 kilohertz to
about 50 megahertz.
3. The ultrasonic surgical system of claim 2, wherein said
transducer operates within the range of about 500 kilohertz to
about 2 megahertz.
4. The ultrasonic surgical system of claim 3, wherein said membrane
is porous or semi-permeable.
5. The ultrasonic surgical system of claim 1, further comprising a
feedback device selected from the group consisting of a non-thermal
response monitor, a thermal response monitor, a cavitation monitor,
a streaming monitor, an ultrasonic imaging device, a drug
activation monitor, an infusion rate control, a source control, a
duty cycle control, a piezo sensor, a piezo receiver, a
thermocouple, and a frequency control.
6. An ultrasonic instrument comprising: a housing; a transducer
connected to said housing; a membrane surrounding said transducer;
a pharmaceutical agent; and an agent delivery system; wherein said
agent delivery system delivers said pharmaceutical agent into a
chamber of said membrane; and whereby said pharmaceutical agent is
driven through said membrane by ultrasonic energy delivered from
said transducer.
7. A method of treating tissue comprising the steps of: a)
providing a surgical instrument, said instrument comprising: a
housing; a transducer connected to said housing; b) inserting said
surgical instrument into the patient; c) delivering a drug to said
patient; and d) locally activating said drug with said surgical
instrument.
8. The method of claim 7 further comprising the step of: e)
ablating tissue of said patient with said surgical instrument.
9. An ultrasonic surgical system comprising: a) a generator; b) an
instrument comprising: i) a housing; ii) an electromechanical
element contained in an interior portion of said housing; iii) a
waveguide originating at said electromechanical element and
terminating at an end-effector extending out of said housing; iv) a
membrane surrounding said end-effector; v) a pharmaceutical agent;
and vi) an agent delivery system; wherein said generator is adapted
to provide electrical energy to said electromechanical element;
wherein said transducer is adapted to convert said electrical
energy into mechanical energy; and whereby said pharmaceutical
agent is driven through said membrane by said mechanical
energy.
10. The ultrasonic surgical system of claim 9, wherein said
electromechanical element operates within the range of about 10
kilohertz to about 200 kilohertz.
11. The ultrasonic surgical system of claim 9, wherein said
membrane is porous or semi-permeable.
12. An ultrasonic surgical instrument comprising: a) a housing; b)
a transducer connected to said housing; c) a membrane adjacent said
transducer; d) a pharmaceutical agent; and e) an agent delivery
system; wherein said agent delivery system delivers said
pharmaceutical agent into a chamber of said membrane.
13. The ultrasonic surgical system of claim 12, wherein said
transducer operates within the range of about 500 kilohertz to
about 50 megahertz.
14. The ultrasonic surgical system of claim 12, wherein said
transducer operates within the range of about 10 kilohertz to about
200 kilohertz.
15. The ultrasonic surgical system of claim 12, wherein said
membrane is porous or semi-permeable.
Description
CROSS REFERENCE TO RELATED PATENT INFORMATION
[0001] This application is related to, and claims the benefit of,
U.S. provisional patent application Ser. No. 60/302,070 filed Jun.
29, 2001, which is hereby incorporated by reference herein in its
entirety.
FIELD OF THE INVENTION
[0002] The present invention relates, in general, to ultrasonic
surgical instruments and, more particularly, to an ultrasonic
surgical instrument for intracorporeal sonodynamic therapy.
BACKGROUND OF THE INVENTION
[0003] Ultrasonic instruments, including both hollow core and solid
core instruments, are used for the safe and effective treatment of
many medical conditions. Ultrasonic instruments, and particularly
solid core ultrasonic instruments, are advantageous because they
may be used to cut and/or coagulate organic tissue using energy in
the form of mechanical vibrations transmitted to a surgical
end-effector at ultrasonic frequencies. Ultrasonic vibrations, when
transmitted to organic tissue at suitable energy levels and using a
suitable end-effector, may be used to cut, dissect, or cauterize
tissue. Ultrasonic instruments utilizing solid core technology are
particularly advantageous because of the amount of ultrasonic
energy that may be transmitted from the ultrasonic transducer
through the waveguide to the surgical end-effector. Such
instruments are particularly suited for use in minimally invasive
procedures, such as endoscopic or laparoscopic procedures, wherein
the end-effector is passed through a trocar to reach the surgical
site.
[0004] Ultrasonic vibration is induced in the surgical end-effector
by, for example, electrically exciting an electromechanical
element, which may be constructed of one or more piezoelectric or
magnetostrictive elements in the instrument handpiece. Vibrations
generated by the electromechanical element are transmitted to the
surgical end-effector via an ultrasonic waveguide extending from
the transducer section to the surgical end-effector.
[0005] Another form of ultrasonic surgery is performed by High
Intensity Focused Ultrasound, commonly referred to as "HIFU". HIFU
is currently used for lithotripsy procedures where kidney stones
are broken up into small pieces by ultrasonic shock waves generated
through ultrasound energy focussed into the body from an
extracorporeal source. HIFU is also under investigational use for
treating ailments such as benign prostatic hyperplasia, uterine
fibroids, liver lesions, and prostate cancer.
[0006] Examples of uses of ultrasound to treat the body can be
found in U.S. Pat. Nos. 4,767,402; 4,821,740; 5,016,615; 6,113,570;
6,113,558; 6,002,961; 6,176,842 B1; PCT International Publication
numbers WO 00/27293; WO 98/00194; WO 97/04832; WO 00/48518; WO
00/38580; WO 98/48711; and Russian Patent number RU 2152773 C1.
[0007] Although the aforementioned devices and methods have proven
successful, it would be advantageous to provide an intracorporeal
instrument for sonodynamic therapy, and methods of sonodynamic
treatment capable of improved outcomes for patients. This invention
provides such an intracorporeal instrumennt and method for
sonodynamic therapy.
SUMMARY OF THE INVENTION
[0008] The present invention relates, in general, to ultrasonic
surgical instruments and, more particularly, to an ultrasonic
surgical instrument for intracorporeal sonodynamic therapy.
Specifically, the invention relates to an intracorporeal surgical
instrument capable of enhanced/controlled delivery and activation
of pharmaceutical agents as well as to achieve tissue ablation.
Representative pharmaceutical agents include analgesics,
anti-inflammatories, anti-cancer agents, bacteriostatics, neuro
active agents, anticoagulants, high-molecular weight proteins, for
example, for gene delivery, among others. The instrument is
designed to operate in the kHz and/or MHz frequency ranges.
[0009] Disclosed is an ultrasonic surgical system comprising a
generator and an instrument comprising a housing; a transducer
connected to the housing; a depot for chemicals including a
semi-permeable membrane, bio-degradable packet, drug impregnated
depots and liposomes among others; a pharmaceutical agent; and an
agent delivery system. The generator is adapted to provide
electrical energy to the transducer. The transducer is adapted to
convert the electrical energy into mechanical energy. The agent
delivery system delivers the pharmaceutical agent into a chamber of
the semi-permeable membrane; and the pharmaceutical agent is driven
through the semi-permeable membrane by the mechanical energy.
Advantageously, the transducer may be combined with other surgical
instruments such as ultrasound, iopntophoretic, laser,
electrosurgical, for example RF, and eletroporative devices to
achieve tissue ablation as well as the sonodynamic therapy.
[0010] The present invention has application in endoscopic and
conventional open-surgical instrumentation as well as application
in robotic-assisted surgery.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The novel features of the invention are set forth with
particularity in the appended claims. The invention itself,
however, both as to organization and methods of operation, together
with further objects and advantages thereof, may best be understood
by reference to the following description, taken in conjunction
with the accompanying drawings in which:
[0012] FIG. 1 is a perspective view of an ultrasonic system in
accordance with the present invention;
[0013] FIG. 2 is a perspective view of an alternate agent injection
device for an ultrasonic instrument in accordance with the present
invention;
[0014] FIG. 3 is a perspective view of an ultrasonic surgical
end-effector of an ultrasonic system in accordance with the present
invention;
[0015] FIG. 4 is a sectioned view of a portion of an intense
ultrasound instrument in accordance with the present invention;
[0016] FIG. 5 is a perspective view of an alternate embodiment of
an ultrasonic system in accordance with the present invention;
[0017] FIG. 6 is a perspective view of an alternate agent injection
device for an alternate embodiment of an ultrasonic instrument in
accordance with the present invention;
[0018] FIG. 7 is a perspective view of an ultrasonic surgical
instrument end-effector of an ultrasonic system in accordance with
the present invention;
[0019] FIG. 8 is a sectioned view of a portion of an ultrasonic
surgical instrument in accordance with the present invention;
[0020] FIG. 9 is a sectioned view of a portion of an ultrasonic
surgical instrument in accordance with the present invention;
[0021] FIG. 10 is a perspective view of an alternate embodiment of
an ultrasonic system in accordance with the present invention;
[0022] FIG. 11 is a graph illustrating the transport of an agent
with and without ultrasound energy;
[0023] FIG. 12 is a graph of the response characteristics of a
transducer in accordance with the invention of FIGS. 1-4; and
[0024] FIG. 13 is a plot of the calculated acoustic intensities of
the transducer in accordance with the invention of FIGS. 1-4.
DETAILED DESCRIPTION OF THE INVENTION
[0025] Before explaining the present invention in detail, it should
be noted that the invention is not limited in its application or
use to the details of construction and arrangement of parts
illustrated in the accompanying drawings and description. The
illustrative embodiments of the invention may be implemented or
incorporated in other embodiments, variations and modifications,
and may be practiced or carried out in various ways. Furthermore,
unless otherwise indicated, the terms and expressions employed
herein have been chosen for the purpose of describing the
illustrative embodiments of the present invention for the
convenience of the reader and are not for the purpose of limiting
the invention.
[0026] It is well known to those skilled in the art that ultrasound
operating at kHz frequencies can reversibly change the permeability
of cell barriers and/or activate drugs. Most of the work in this
area describes the drug delivery applications through the skin, or
enhancement of thrombolytic activity in the blood vessels. An
approach where a surgeon performs an excision using an ultrasonic
surgical instrument, and then "delivers" a chemotherapeutic agent
in the treatment field would improve the treatment outcomes.
[0027] The attenuation coefficient for sound at kHz frequencies in
tissue is very low, even assuming a radial spread of acoustic
energy from the end effector. There is sufficient energy distal
from the end effector, from a few millimeters to a couple of
centimeters, such that the permeability of cells can be affected.
Two examples, which are not intended to limit the scope of the
invention, of intracorporeal drug delivery/enhancement are enabled
by the present invention. One, local drug delivery in the region of
surgical treatment as described earlier. Second, the therapeutic
chemical agent is given intravenously, and the drug is activated in
a region of interest during an interventional procedure using
laparoscopic kHz and/or MHz frequency ultrasound.
[0028] For management of cancers, intra-operative delivery of
chemotherapeutic agents and treatment with ultrasound energy is
provided by the present invention to increase the efficacy of
surgery and reduce recurrence rates, as well as to reduce the risk
of seeding healthy sites with cancerous cells during intervention.
Such local and site specific drug delivery approaches with kHz
and/or MHz frequency ultrasound could be applied in surgical
procedures, such as, for example, liver, colon, prostate, lung,
kidney, and breast. A surgical patient may further benefit from the
increase in treatment volume that may result from a chemical agent
used in cooperation with kHz and/or MHz ultrasonic energy as well
as from chemical agents used with the present invention that would
otherwise be adversely affected if used with other forms of energy.
In general, the chemical agents whose efficacy can be enhanced with
the present invention may be chemotoxic drugs such as, for example,
Paclitaxel, Docetaxel, trademark names of Bristol Meyers-Squibb or
antibiotics, bacteriostatics, or cholinesterase inhibitors such as
Galantamine, trademark name Reminyl of Johnson and Johnson, that
may be delivered locally before completion of a surgical procedure.
Chemical agents whose efficacy may be enhanced with the present
invention further include local anesthetics such as, but not
limited to, Novacaine, anti-inflammatories, corticosteroids, or
opiate analgesics.
[0029] FIG. 1 illustrates an ultrasonic system 25 for local
delivery of an agent in combination with an intense ultrasound
instrument 50 for activating or assisting transport of the agent.
Intense ultrasound instrument 50 includes an elongated portion 68,
a housing 74, a grip 69, a porous or semi-permeable membrane 55,
and a port 79. An agent 75 is contained in a container 76 for
insertion into port 79. Insertion of container 76 into port 79 may
be done mechanically, or manually by the operator. Intense
ultrasound instrument 50 includes a radiating end-effector 60.
Intense ultrasound instrument 50 is connectable to a generator 10
via cable 90, that supplies electrical energy to radiating
end-effector 60 for conversion by transducer 65 to ultrasonic
stress waves. Radiating end-effector 60 comprises a plurality of
embodiments including, but not limited to, single element,
array-based end effectors, planar transducers, shaped transducers,
or end effectors with active-passive element combinations.
[0030] A foot switch 95 is connected to generator 10 via cable 98
to control generator 10 function. A switch 96 and a switch 97 are
included with foot switch 95 to control multiple functions. For
example, switch 96 could provide a first level of energy to radiate
end-effector 60 and a switch 97 could provide a second level of
energy to radiate end-effector 60. Generator 10 may also include a
display 80 for providing information to the user, and buttons or
switches 81, 82, and 83 to allow user input into the generator such
as, for example, turning the power on, setting levels, defining
device attributes or the like.
[0031] FIG. 2 illustrates an alternate means of providing agent 75
to intense ultrasound instrument 50. In this embodiment, a syringe
77 contains agent 75 for injection to a surgical site within a
patient. A plunger 73 may be depressed by the operator to deliver
agent 75 to a surgical site via port 78.
[0032] FIG. 3 illustrates a method of using an instrument in
accordance with the present invention. End-effector 60 is inserted
into the body cavity of a patient, and located on or near tissue 40
that includes a spot or lesion 45 for treatment with agent 75. Spot
or lesion 45 may be a cancerous region, a polyp, or other area that
would benefit from treatment with agent 75. Semi-permeable membrane
55 contains agent 75 under instrument-off conditions, once agent 75
has been delivered to semi-permeable membrane 55. Agent 75 may be
delivered to semi-permeable membrane 55 by way of an agent channel
63 (FIG. 4). An alternate embodiment of intense ultrasound
instrument 50 contemplates the disposable use of intense ultrasound
instrument 50 where semi-permeable membrane 55 is manufactured
containing a pre-selected agent 75 located within semi-permeable
membrane 55. The single use embodiment of intense ultrasound
instrument 50 comprises disposal of intense ultrasound instrument
50, semi-permeable membrane 55, and/or end effector 60.
Alternatively, and not by way of limitation of the invention,
membrane 55 could take the form of a biocompatible biodegradable
layer that is impregnated with a therapeutic chemical agent with or
without the presence of cavitation nuclei. The therapeutic agent
may be preferentially delivered at the target site when the
ultrasound instrument 50 is energized.
[0033] When intense ultrasound instrument 50 is activated, agent 75
is driven through semi-permeable membrane 55, producing agent
droplets 77. A suitable semi-permeable membrane 55 may be formed
from, for example, nitrocellulose, tyvek, silicone, ethelyne vinyl
acetate, or the like. Semi-permeable membrane 55 may be
semi-permeable in specific regions and may be non-permeable in
other regions to effectuate targeted release of the agent 75
through membrane 55. Further, semi-permeable membrane 55 may be
bio-compatible and have a tissue adhesive, allowing for the
semi-permeable membrane 55 to be left within a body cavity, and/or
may be adapted to dissolve within a body cavity. Agent droplets 77
are driven preferentially into tissue 40 by ultrasound energy, as
shown below in ultrasound-mediated diffusion experiment
results.
[0034] Intense ultrasound instrument 50 may further comprise the
use of a suction system, an irrigation system, a snare, a viewing
means, a coolant means, an imaging means, a biopsy system, a gene
delivery means, and/or a number of cutting and/or coagulation means
such as, for example, laser, iontophoretics, electroporative
devices, or electrosurgical energy. The present invention further
comprises the seeding of tissue 40 to facilitate enhanced ablation
and/or agent droplet 77 delivery such as the introduction of
foreign particles, the introduction of stabilized microbubbles,
aeration, and/or a pulse profile designed to meet the needs of a
particular medical application.
[0035] Agent 75 is injectable into chamber 57 of semi-permeable
membrane 55 through port 62 under pressure from syringe 77,
container 76, or by other suitable means of delivery. Agent 75 may
be Vorozole, Paclitaxel, Docetaxel, bacteriostatics, antibiotics,
anti-coagulants, glues, genes, chemotoxic agents, or any other
agent having properties beneficial to the outcomes of the medical
treatment or surgical procedure. Chemical agents whose efficacy may
be enhanced with the present invention further include local
anesthetics such as, but not limited to, Novacaine,
anti-inflammatories, corticosteroids, or opiate analgesics.
[0036] FIG. 4 illustrates a section of elongated portion 68.
Residing inside elongated portion 68 is an agent channel 63, a
coaxial cable 66, and a lead 64. Agent channel 63 delivers the
agent 75 from the proximal end of intense ultrasound instrument 50
to the radiating end-effector 60 via port 62. Coaxial cable 66
delivers electrical energy to transducer 65. In one embodiment,
when electrically activated, transducer 65 operates preferably at
0.5-50 MHz, and more preferably at 0.5-10 MHz, and more preferably
at 0.5-2 MHz. Lead 64 may be used to transmit a feedback signal
from the radiating end-effector 60 to generator 10 such as, for
example, temperature information from a thermocouple, acoustic
noise level from a hydrophone, or the like. The present invention
further contemplates the use of a plurality of coaxial cables 66,
leads 64, and/or agent channels 63. Coaxial cable 66 may be
designed from any conductive material suitable for use in surgical
procedures. In one embodiment of the present invention, agent
channel 63 comprises at least one lumen constructed from plastic,
metal, rubber, or other material suitable for use in surgical
procedures.
[0037] A design representative of an intra-corporeal MHz-frequency
ablation and Sonodynamic therapy prototype may be, for example, a
UTX Model #0008015 (UTX, Inc., Holmes, N.Y.). This may be designed
around a 20 cm long tube that fits through a 5 mm trocar. At the
distal end of this tube, there is one spherically curved ceramic
element (4.times.15 mm, radius of curvature=25 mm). The transducer
design accomplishes narrow bandwidth operation around 2 MHz. (as
shown in FIG. 12). The acoustic output at source may be .about.20
W/cm.sup.2. The acoustic intensity around the focal zone may be on
the order of 200 W/cm.sup.2, (FIG. 13), sufficient to cause tissue
ablation in the treatment volume. In addition, there is sufficient
acoustic energy range available for accomplishing enhanced
drug-delivery or drug activation steps.
[0038] As is known in the art, the connecting cable 90 may be
shielded coax. If needed, there may be an additional electrical
matching network between the power amplifier and the transducer.
The front faces of the transducer active surfaces have acoustic
matching layers. The transducers are "air-backed." Thin, 0.125 mm,
diameter thermocouples may be attached close to the ceramic faces
that help monitor any self heating of the ultrasonic sources.
Membrane 55 may be silicone, polyurethane, or polyester-based
balloons to ensure that most of the energy radiated by the
transducer is delivered to the tissue and not reflected back from
the source tissue interface.
[0039] A further embodiment of ultrasonic system 25 comprises the
systemic delivery of agent 75 in cooperation with intense
ultrasound instrument 50. Agent 75 may be ingested, injected or
systemically delivered by other suitable means. Intense ultrasound
instrument 50 may then be activated on or near tissue 40 where the
effects of intense ultrasound are desired.
[0040] FIG. 5 illustrates an ultrasonic system 125 for local
delivery of an agent 175 in combination with an ultrasonic surgical
instrument 150 for activating or assisting transport of the agent
175. Ultrasonic surgical instrument 150 includes an elongated
portion 168, a housing 174, an electro-mechanical element 165, for
example, a piezoelectric transducer stack, a grip 169, a
semi-permeable membrane 155, and a port 179. An agent 175 is
contained in a container 176. Container 176 is insertable into port
179 of a housing 174. Alternatively, agent 175 may be delivered via
a syringe 177 through a port 178 as shown in FIG. 6. Ultrasonic
surgical instrument 150 includes a contact end-effector 160.
Ultrasonic surgical instrument 150 is connectable to a generator
200 via cable 190, that supplies electrical energy to a transducer
165 that delivers stress waves to contact end-effector 160 via a
waveguide 146 (FIG. 8). In one embodiment, when electrically
active, electromechanical element 165 operates preferably at 10-200
kHz, more preferably and more preferably at 10-75 kHz. A clamp arm
170 may be attached to elongated portion 168, to provide
compression of tissue 145 (FIG. 7) between clamp arm 170 and a
blade 147 at the distal end of waveguide 146. Blade 147 comprises a
plurality of embodiments including, but not limited to, a curved
form, a straight form, a ball form, a hook form, a short form, a
long form, or a wide form.
[0041] Referring now to FIG. 7 end-effector 160 may be inserted
into the body cavity of a patient, and located on or near tissue
140 that includes a spot or lesion 145 for treatment with agent
175. Spot or lesion 145 may be a cancerous region, a polyp, or
other area that would benefit from treatment with agent 175.
Semi-permeable membrane 155 contains agent 175 under instrument-off
conditions once agent 175 has been delivered to semi-permeable
membrane 155. Agent 175 may be delivered to semi-permeable membrane
155 by way of an agent channel 163 (FIG. 8). An alternate
embodiment of ultrasonic surgical instrument 150 comprises the
single use of ultrasonic sugical instrument 150 where
semi-permeable membrane 155 may be manufactured containing a
pre-selected agent 175 located within semi-permeable membrane 155.
The single use embodiment of ultrasonic surgical instrument 150
further contemplates disposal of ultrasonic surgical instrument
150, semi-permeable membrane 155, and/or end effector 160. When
ultrasonic surgical instrument 150 is activated, agent 175 is
driven through semi-permeable membrane 155, producing agent
droplets 177. A suitable semi-permeable membrane 155 may be formed
from, for example, nitrocellulose, tyvek, silicone, ethelyne vinyl
acetate, or the like. Agent droplets 177 are then driven
preferentially into tissue 140 by ultrasound energy, as shown below
in ultrasound-mediated diffusion experiment results. Ultrasonic
surgical instrument 150 further contemplates the use of a suction
system, an irrigation system, a snare, a viewing means, and/or a
number of cutting and/or coagulation means such as, for example,
laser, iontophoretics, electroporative devices, or electrosurgical
energy.
[0042] FIG. 8 illustrates a section of elongated portion 168.
Residing inside elongated portion 168 may be an agent channel 163,
solid waveguide 146, and a lead 164. Agent channel 163 delivers the
agent 175 from the proximal end of ultrasonic surgical instrument
150 to the contact end-effector 160. Lead 164 may be used to
transmit a signal from the radiating end-effector 160 to generator
200 such as, for example, temperature information from a
thermocouple, acoustic noise level from a hydrophone, or the like.
The present invention further contemplates the use of a plurality
of leads 164 and/or agent channels 163. In one embodiment of the
present invention, agent channel 163 comprises at least one lumen
constructed from plastic, metal, rubber, or other material suitable
for use in surgical procedures.
[0043] FIG. 9 illustrates an embodiment of the invention that
combines the disclosures of FIGS. 1 and 5 and enables operation of
a surgical instrument in both the KHz and MHz operating range.
Shown is a section of elongated portion 268 of an overall system as
shown in FIG. 5. Residing inside elongated portion 268 may be an
agent channel 263, a transducer 265 in combination with a coaxial
cable 266 for MHz operation, a solid waveguide 246 in combination
with end effector 260 for KHz operation, and a lead 264. Agent
channel 263 delivers the agent 275 from the proximal end of coupled
ultrasound instrument 250 (not shown) to the semi-permeable
membrane 255. Coaxial cable 266 delivers electrical energy to
transducer 265. In one embodiment, when electrically activated,
transducer 265 operates preferably at 0.5-50 MHz. Lead 264 may be
used to transmit a signal from the distal end of coupled ultrasound
instrument 250 to generator 10 such as, for example, temperature
information from a thermocouple, acoustic noise level from a
hydrophone, pulse-echo information from the target region, or the
like. The present invention contemplates the use of a plurality of
coaxial cables 266, leads 264, and/or agent channels 263. Coaxial
cable 266 may be designed from any conductive material suitable for
use in surgical procedures. In one embodiment of the present
invention, agent channel 263 comprises at least one lumen
constructed from plastic, metal, rubber, or other material suitable
for use in surgical procedures.
[0044] The coupled ultrasonic instrument (not shown) comprises the
use of an end effector 260 (kHz operation) connected to a waveguide
246 in cooperation with a transducer 265 (MHz) connected to a
coaxial cable 266 and a semi-permeable membrane 255 connected to
agent channel 263. Waveguide 246 may be coupled to an
electromechanical element (not shown) located at the proximal end
of the coupled ultrasonic instrument. In one embodiment of the
present invention, the electro-mechanical element connected to
waveguide 246 operates at 10-200 kHz. In one embodiment of the
present invention, transducer 265 operates preferably at 0.5-50
MHz, and more preferably at 0.5-10 MHz. Accordingly, end effector
260 may be used simultaneously or alternately with transducer 265,
or end effector 260 and transducer 265 may be used independently.
The present invention comprises the method of using waveguide 246
with end effector 260 and/or transducer 265 to perform excision,
hemostasis, ablation, and/or coagulative necrosis, prior to the
delivery of agent 275 to semi-permeable membrane 255. Following
necessary excision and hemostasis, agent 275 may be delivered
through agent channel 263 into semi-permeable membrane 255, or
agent 275 may be delivered systemically.
[0045] When transducer 265 and/or end effector 260 are activated,
agent 275 is driven through semi-permeable membrane 255, producing
agent droplets 277. A suitable semi-permeable membrane 255 may be
formed from, for example, nitrocellulose, tyvek, silicone, ethelyne
vinyl acetate, or the like. Agent droplets 277 are then driven
preferentially into tissue 240 by ultrasound energy, as shown below
in ultrasound mediated diffusion experiment results. The coupled
ultrasonic instrument further comprises the use of a suction
system, an irrigation system, a snare, a viewing means, and/or a
number of cutting and/or coagulation means such as, for example,
laser or electrosurgical energy. The waveguide 246 and associated
end effector 260 may be used in cooperation with transducer 265 to
facilitate a local (omnidirectional) tissue effect or a distant
(focused) tissue effect depending on the needs of the application.
The coupled ultrasound instrument further contemplates a transducer
265 surrounded by semi-permeable membrane 255, where agent channel
263 may be within or substantially near transducer 265 to
facilitate the delivery of agent 275 into semi-permeable membrane
255 surrounding transducer 265. In a further embodiment of the
present invention, semi-permeable membrane 255 may surround end
effector 260, or may surround both end effector 260 and transducer
265.
[0046] FIG. 10 illustrates an ultrasonic system 325 for local
delivery of an agent in combination with an intense ultrasound
instrument 350 for activating or assisting transport of the agent
375 in combination with a first feedback device 366 and a second
feedback device 367. Feedback devices 366 and 367 may be one or a
plurality of piezo sensors, piezo receivers, thermocouples,
non-thermal response monitors, thermal response monitors,
cavitation monitors, streaming monitors, ultrasonic imaging
devices, drug activation monitors, infusion rate controls, source
controls, duty cycle controls, frequency controls, or other
suitable means of monitoring and/or controlling a surgical
procedure. Unless otherwise specified, all "300" series reference
numerals have the same function as the corresponding reference
numerals of FIG. 1, but it is evident that feedback devices 366 and
367 are useful in any of the embodiments of the invention presented
herein.
[0047] In one embodiment of the present invention, first feedback
device 366 is a piezo sensor attached to the distal portion of end
effector 360, is coupled via wire 370 to a feedback monitor (not
shown), in the form of a broad bandwidth pulser-receiver. Feedback
device 366 in the form of a piezo sensor may be driven and
controlled by the broad bandwidth pulser-receiver in order to
acquire standard A-line (pulse echo) data from the region of
interest, and to monitor morphological changes in the tissue 40. A
further embodiment of the present invention comprises a feedback
device 366 in the form of a piezo sensor used to estimate the
temperature of the treatment volume using ultrasonic (remote)
means, such as change in sound speed and/or the attenuation
coefficient, and to facilitate monitored therapy. A further
embodiment of the present invention contemplates feedback device
366 in the form of a piezo reciever to actively, and/or passively,
monitor the cavitational activity in the therapy zone. Used in
cooperation with a broad bandwidth pulser-receiver, this technique
can be implemented by recording and processing the broad bandwidth
acoustic emissions resulting from the bubble growth and collapse
due the therapeutic ultrasound field in the region of treatment.
Alternatively, the higher harmonic such as, for example, the
2.sup.nd or 3.sup.rd, or the sub-harmonic response due to the
high-power field in the therapeutic zone can be recorded and
correlated to the tissue therapy, or to estimate the amount of
agent 75 activated. Further, the streaming field resulting from the
therapy acoustic field may be monitored using Doppler flow
techniques. The strength of the flow signal may be correlated to
the magnitude of advection, or delivery of agent 75, within the
treatment volume.
[0048] A second feedback device 367 may be a thermocouple attached
to the elongated portion 368 comprising at least one wire 371,
where at least one wire 371 is attached to both second feedback
device 367 and to a feedback monitor (not shown). Feedback monitor
(not shown) may be for example, a broad bandwidth pulser-receiver,
or other suitable means of monitoring and/or controlling a surgical
procedure. Wire 371 may be constructed from silver, stainless
steel, or other conductive material suitable for use in surgical
procedures. Second feedback device 367 may be located at any point
along elongated portion 368 depending on the needs of a particular
medical application. In one embodiment of the present invention,
feedback device 367 may be a thermocouple attached to elongated
portion 368, where the feedback device 367, in the form of a
thermocouple, monitors the region of interest during ablation
and/or drug activation phases.
[0049] The present invention contemplates one or a plurality of
feedback devices 366 and/or feedback devices 367 used within a
system feedback loop to control, for example, the therapy source,
pulsing, treatment time, and/or rate of drug infusion, in order to
optimize the ablative and drug activation-based treatments.
[0050] Protocol for Ultrasound-Mediated Diffusion Experiments
[0051] A method for treating tissue in accordance with the present
invention comprises the steps of: providing a surgical instrument,
the instrument comprising: a housing; a transducer connected to the
housing; a semi-permeable membrane surrounding the transducer; a
pharmaceutical agent; and an agent delivery system; inserting the
surgical instrument into a body cavity of a patient; delivering a
drug to the patient; and locally activating the drug with the
surgical instrument. For purposes herein, locally is defined as
within a range of about 0.5 mm to 50 mm from the end-effector of
the instrument. Other steps in accordance with the present
invention include achieving hemostasis, excising tissue,
coagulating tissue, and cutting tissue.
[0052] Experiments were performed to determine if the present
invention could transport a chemical agent of interest to a
potential therapeutic site. An appropriate agent, Vorozole, a model
chemical agent from Janssen Pharmaceutica in Belgium was selected
as a chemical drug for permeation through biological barriers.
[0053] The representative 20 kHz and 1 MHz sources are described as
follows. The 20 kHz sonicator system is available from Cole Parmer,
Inc., Vernon Hills, Ill.--Ultrasonic Homogenizer, Model CPX 400.
The 1 MHz source was a custom designed transducer available from
UTX, Inc., Holmes, N.Y. (e.g., UTX Model #9908039). A suitable
acoustic power output ranges from 1-10 W, pulsed at 5-75% duty
cycle. A suitable source geometry ranges from 1-5 MHz, flat
geometry (19 mm diameter ceramic disks (preferably PZT-4)).
Transducers should be designed for high-power long-term operation
(up to 26 hours), air or Corporene-backed (narrow bandwidth
tuning), high-temperature epoxy front face matching. Embedded
thermocouples in close proximity of the ceramic may provide
feedback for the source surface temperature. A number of source
cooling schemes may be implemented (for example, transducer housing
with a water jacket, or circulating water at the front face of
transducer, separated from the drug reservoir by using
polymer-based membranes or stainless steel shim stock). The cable
for the transducers may be double-shielded coax, teflon coated
(high-temperature), or gold braided thin-gauge cable.
[0054] For active diffusion experiments with Vorozole, 16 ml of 5%
HP-1-CD with 0.05% NaN.sub.3 in water was added into the receptor
compartment of glass diffusion cells. A Teflon-coated magnetic
stirring bar was also added in the receptor compartment. The Franz
cells were then placed on top of a stirring plate set at about 600
rpm.
[0055] To perform the ultrasound-mediated experiments, a 20 kHz and
a 1 MHz probe were mounted in the donor compartment close to the
skin surface. The formulations were added until the probes were
immersed in the liquid and ultrasound sources were turned on.
[0056] The power setting indicated on the 20 kHz system relates to
a correspondingly increased acoustic field radiated from the horn
tip. The acoustic power radiated by the MHz frequency transducers
was nominally .about.4 W for the voltage used in our study at 1
MHz. In addition, the acoustic intensity over time (I.sub.temporal)
was a function of the pulsing regime used for a given
experiment.
[0057] The experiments were conducted over 20 hours. Samples were
collected in the following successive order: 1, 2, 3, 4, 5, 6, 7,
8, 10, 12, 14, 16, 20 hours.
[0058] After the incubation period, the receptor fluid was
collected and stored at 4.degree. C. until HPLC analysis was
performed. The formulation was removed from the donor side with a
syringe and Kleenex tissues. The diffusion cells were dismantled
and the skin was carefully removed. The surface was cleaned
consecutively with a dry Kleenex tissue, an ethanol-wetted tissue
and a dry tissue. The skin was evaluated for morphologic changes
due to the exposure to ultrasound.
[0059] Parallel experiments for passive diffusion of the drug were
conducted whereby the set-up was identical for ultrasound exposure
to the tissue, except that the skin was not exposed to any
ultrasound energy. The result of the above experiment is
illustrated in FIG. 11, illustrating that an ultrasonic surgical
instrument 50 increases the transport of Vorazol through tissue.
Specification A is 20 kilohertz ultrasound with a tip displacement
of approximately 10 micrometers peak-to-peak, 0.5 Seconds on, 12.5%
duty cycle. Specification B is 1 Megaherts ultrasound at
approximately 4 Watts power, 4 seconds on at 50% duty cycle.
Specification C is passive permeation.
[0060] While preferred embodiments of the present invention have
been shown and described herein, it will be obvious to those
skilled in the art that such embodiments are provided by way of
example only. Numerous variations, changes, and substitutions will
now occur to those skilled in the art without departing from the
invention. Accordingly, it is intended that the invention be
limited only by the spirit and scope of the appended claims.
* * * * *