U.S. patent application number 14/957234 was filed with the patent office on 2016-03-31 for methods and devices for controlling biologic microenvironments.
The applicant listed for this patent is P Tech, LLC. Invention is credited to Justin E. Beyers, Peter M. Bonutti.
Application Number | 20160089487 14/957234 |
Document ID | / |
Family ID | 39275528 |
Filed Date | 2016-03-31 |
United States Patent
Application |
20160089487 |
Kind Code |
A1 |
Bonutti; Peter M. ; et
al. |
March 31, 2016 |
Methods and Devices for Controlling Biologic Microenvironments
Abstract
A microenvironment of a biological body is controlled, and more
particularly, is measured, changed, and monitored with respect to
temperature, pH level, moisture and other tissue parameters of a
region of the body while, optionally, administering a therapeutic
agent to that region.
Inventors: |
Bonutti; Peter M.;
(Manalapan, FL) ; Beyers; Justin E.; (Effingham,
IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
P Tech, LLC |
Effingham |
IL |
US |
|
|
Family ID: |
39275528 |
Appl. No.: |
14/957234 |
Filed: |
December 2, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14161210 |
Jan 22, 2014 |
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14957234 |
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11867679 |
Oct 4, 2007 |
8641660 |
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14161210 |
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60828084 |
Oct 4, 2006 |
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Current U.S.
Class: |
604/24 ; 604/503;
604/504; 604/66 |
Current CPC
Class: |
A61N 1/30 20130101; A61B
2050/0016 20160201; A61M 2205/3303 20130101; A61M 2202/0225
20130101; A61M 2205/3324 20130101; A61F 7/00 20130101; A61B
2050/0018 20160201; A61F 2007/0052 20130101; A61B 90/40 20160201;
A61B 50/00 20160201; A61B 2090/401 20160201; A61M 5/1723 20130101;
A61M 3/0208 20140204; A61B 2090/0813 20160201; A61M 2005/1726
20130101; A61F 7/007 20130101 |
International
Class: |
A61M 3/02 20060101
A61M003/02 |
Claims
1-19. (canceled)
20. A system for controlling an environment of a patient undergoing
a surgical procedure, said system comprising: a conduit configured
to direct a fluid stream toward the environment; a sensor
configured to measure at least one parameter of one of the
environment; an effector comprising a reservoir operatively
connected to the conduit and containing an agent in selective
communication with the conduit, wherein the agent is configured to
change the at least one parameter of the environment; and a
controller configured to selectively activate the effector based on
a signal received from the sensor to deliver the agent into the
conduit.
21. A system as set forth in claim 20, wherein the agent is a fluid
agent.
22. A system as set forth in claim 21, wherein the controller
comprises a reservoir controller configured to selectively release
the fluid agent into the conduit to change the parameter of the
environment.
23. A system as set forth in claim 22, wherein the fluid agent is
fluidly separated from the conduit until the reservoir controller
releases the fluid agent into the conduit.
24. A system as set forth in claim 20, wherein the sensor comprises
a pH sensor.
25. A system as set forth in claim 24, wherein the fluid agent
comprises a pH controlling substance, whereby release of the agent
into the conduit adjusts a pH of the fluid stream.
26. A system as set forth in claim 25, wherein the pH controlling
substance is configured to make the fluid stream more basic.
27. A system as set forth in claim 26, wherein the pH controlling
substance comprises a calcium-based substance.
28. A system as set forth in claim 26, wherein the pH controlling
substance comprises at least one of sodium chloride, potassium
chloride, calcium carbonate, and calcium sulfate.
29. A system as set forth in claim 25, wherein the pH controlling
substance is configured to make the fluid stream more acidic.
30. A system as set forth in claim 29, wherein the pH controlling
substance comprises carbon dioxide.
31. A system as set forth in claim 20, further comprising
temperature effector, a temperature sensor, and a temperature
controller.
32. A method of controlling an environment of a patient undergoing
a surgical procedure, said method comprising: positioning a conduit
to direct a fluid stream toward the environment; directing the
fluid stream through the conduit toward the environment; sensing at
least one parameter of the environment with a sensor; receiving a
sensor signal from the sensor with a controller, the sensor signal
being indicative of the at least one parameter of the environment;
sending a control signal from the controller to an effector
operatively connected to the conduit based on the received sensor
signal; and activating, in response to the control signal, the
effector to deliver an agent from a reservoir of the effector into
the conduit to change the parameter of the environment.
33. A method as set forth in claim 32, wherein the sensor comprises
a pH sensor, and the agent adjusts the pH of the fluid stream.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Patent Application 60/828,084 to the same inventor, filed Oct. 4,
2006, entitled METHODS AND DEVICES FOR CONTROLLING BIOLOGIC
MICROENVIRONMENTS, the entire contents of which are incorporated
herein by reference.
FIELD OF THE INVENTION
[0002] The invention relates to controlling a microenvironment of a
biological body, and more particularly, to measuring, changing, and
monitoring the temperature, pH level, moisture and other tissue
parameters of a region of the body while, optionally, administering
a therapeutic agent to that region.
BACKGROUND OF THE INVENTION
[0003] The human body and bodies of other mammals naturally
maintain a certain level of temperature, pH, humidity, etc. The
normal temperature of the human body is, for example, 98.6 degrees
Fahrenheit. This temperature level, however, is not consistent
throughout the entire body. Different body regions may be higher or
lower than 98.6 degrees. Acidity levels also vary. Certain body
parts, such as the stomach or intestines may have a different pH
level than the brain or heart. Also, temperature and acidity levels
vary in the body throughout the day, depending on the level of
activity of a particular person. A person sleeping will have
different pH levels than the same person exercising.
[0004] Other factors that determine the microenvironment of the
body is disease, damage, and injury to tissue. The body may
somewhat fluctuate the microclimate of tissue during healing, to
fight infection, and to resist or kill a foreign object. However,
augmenting the body's ability to control the microenvironment
enhances tissue healing. Some patent documents disclose various
methods, devices, and reasons for controlling the body's
temperature, pH level, moisture, and other microclimate
parameters.
[0005] U.S. Pat. No. 7,056,318 entitled "Temperature Controlled
Heating Device and Method to Heat a Selected Area of a Biological
Body" discloses a heating device and method for controlling a
temperature in a selected area of a body part to obtain a
temperature effect within the selected area for therapeutic or
medical purposes. It includes temperature generating means to
generate a temperature in the selected area. It also includes
temperature detecting means to detect the generated temperature
from the selected area. It further includes temperature controlling
means to control the temperature generating means to maintain the
generated temperature within a range of a desired temperature. The
device and method prevent irreversibly damaging or overheating the
selected area or the tissue surrounding the selected area. It is
advantageous to applications where there is a need to accurately
control the temperature in a selected area in a biological body,
for instance, to activate or evaporate a temperature sensitive
agent in the selected area.
[0006] U.S. Pat. No. 7,004,961 entitled "Medical Device and Method
for Temperature Control and Treatment of the Brain and Spinal Cord"
discloses a medical device having a thermostat for temperature
measurement, irrigation/aspiration ports for fluid exchange and
application of therapeutic modalities, a pressure manometer for
pressure measurement, and an external system for control of
temperature, pressure, and flow rate. When applied to the central
nervous system (CNS), this device can be used in hypothermia or
hyperthermia applications, the exchange of cerebral spinal fluid
(CSF), the application of treatment modalities, and the insertion
of a ventriculostomy or ventriculostomy-like unit. When applied to
spinal cord applications, this device can provide temperature
control and a method for application of treatment modalities by
using a venting device placed in the space surrounding the spinal
cord, a device with similar instrumentation to measure temperature
and pressure.
[0007] U.S. Pat. No. 7,004,933 entitled "Ultrasound Enhancement of
Percutaneous Drug Absorption" discloses a system for enhancing and
improving the transcutaneous or transdermal delivery of topical
chemicals or drugs. A disposable container contains a substantially
sterile unit dose of an active agent adapted for a single use in a
medical treatment. The unit dose is formulated to enhance transport
of the active agent through mammalian skin when the active agent is
applied to the skin and the skin is exposed to light and/or
ultrasound defined by at least one specific parameter.
[0008] U.S. Pat. No. 6,961,620 entitled "Apparatus and Methods for
Assisting Ablation of Tissue Using Magnetic Beads" discloses a
system for treating tissue includes a source of conductive and/or
magnetic beads, a first member, e.g., a catheter or cannula,
coupled to the source of magnetic beads, and a second member, e.g.,
a catheter or cannula, carrying a magnet on its distal end. The
system is used for ablating or otherwise treating tissue within a
target tissue region including a blood vessel contacting or passing
therethrough. Magnetic beads are introduced into the target tissue
region, e.g., using the first member, and a magnetic field is
generated within the target tissue region, e.g., using the second
member, to cause the magnetic beads to migrate towards a wall of
the vessel. Energy is delivered into the target tissue region,
e.g., to heat tissue therein, and the magnetic beads may attenuate
or enhance treatment of tissue adjacent to the vessel.
[0009] U.S. Pat. No. 6,600,941 entitled "Systems and Methods of pH
Tissue Monitoring" discloses the use of pH measurements of tissue
as a system for controlling diagnostic and/or surgical procedures.
The invention also relates to an apparatus used to perform tissue
pH measurements. Real time tissue pH measurements can be used as a
method to determine ischemic segments of the tissue and provide the
user with courses of conduct during and after a surgical procedure.
When ischemia is found to be present in a tissue, a user can affect
an optimal delivery of preservation fluids to the site of interest
and/or effect a change in the conduct of the procedure to raise the
pH of the site.
[0010] U.S. Patent Publication No. 2005/0267565 entitled
"Biodegradable Medical Implant with Encapsulated Buffering Agent"
discloses a medical device for placement at a site in a patient's
body and for controlling pH levels at the site in the patient's
body includes one or more structural components made of a first
biodegradable and/or bioabsorbable material or, alternatively, one
or more structural components having a coating thereon made of a
first biodegradable and/or bioabsorbable material. The device also
includes a buffering agent and at least one second biodegradable
and/or bioabsorbable material on or in the one or more structural
components, or alternatively, on or in the coating on the one or
more structural components. The at least one second biodegradable
and/or bioabsorbable material encapsulates the buffering agent and
the buffering agent is dispersed from the at least one second
biodegradable and/or bioabsorbable material in response to
hydrolysis of the first biodegradable and/or bioabsorbable
material. Additionally, the device can include a drug that is
either also encapsulated by the at least one second biodegradable
and/or bioabsorbable material or is included with the first
biodegradable and/or bioabsorbable material
[0011] There exists a need for apparatus and methods for
controlling the biologic microenvironment of a body region by
measuring, changing, and monitoring the temperature, pH level,
moisture level, and other microenvironment parameters and
simultaneously delivering a pharmaceutical/therapeutic agent.
SUMMARY OF THE INVENTION
[0012] The present invention relates to devices and methods for
controlling microenvironments in living organisms. The
microenvironment (or microclimate) of a region of the body is
defined as those characteristics which create the conditions
necessary for cells to function. Such characteristics may include
temperature, pH level, moisture, humidity, oxygen tension,
oxygenase, carbon dioxide tension, rate of blood flow,
nutrient-content, osmolarity, pressure, vascular permeability,
electrical charge, and the presence of pharmaceutical agents. Some
of these characteristics, like temperature, may be naturally
controlled by the body. However, as a result of disease, age,
injury, or surgery, the body may require augmentation for
controlling the microenvironment of a body region. The present
invention provides for measuring, changing, and monitoring
microenvironment parameters. Through the use of sensors, implanted
or externally positioned, the parameters may be measured. A
physician or sensors/microprocessor determines whether the measured
levels are appropriate for the selected body region. If not, the
levels may be adjusted. Continuous monitoring of the
microenvironment creates a feedback loop so that the
microenvironment characteristics may be selectively controlled,
manually or automatically.
[0013] Optimizing the microenvironment with the devices and methods
of the present invention may be used to enhance or improve the
effect of therapeutic/pharmaceutical agents, improve the outcome of
a surgical procedure or intervention, enhance the results of a
surgical implant, optimize cell or tissue ingrowth when using cell
therapy or gene therapy, and other advantages which are described
in relation to the exemplary embodiments. Controlling the
microenvironment with this multimodal approach may be performed
preoperatively, during surgical treatment, and postoperatively.
[0014] Other benefits for controlling the microenvironment include
effecting cell receptors, effecting hormone release, effecting
tissue healing, effecting the ability of bacteria to multiple or
reduce, effecting virus activity, stimulating white blood cells
enzyme release, stimulating white blood cell phagocytosis or
migration, and managing pain.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] A more complete understanding of the present invention, and
the attendant advantages and features thereof, will be more readily
understood by reference to the following detailed description when
considered in conjunction with the accompanying drawings
wherein:
[0016] FIG. 1 illustrates an endoscope positioned in a body region
for controlling the microclimate thereof;
[0017] FIG. 2 shows a multi-lumen catheter inserted in a body
region and having an endoscope and sensors extending therefrom;
[0018] FIG. 3 illustrates an intramedullary rod designed for
controlling the microenvironment of a bone fracture;
[0019] FIG. 4 is a cross sectional view of a fastener configured
for controlling the microenvironment;
[0020] FIG. 5 shows a bone plate designed for controlling the
microenvironment of a bone fracture;
[0021] FIG. 6 illustrates a spinal implant constructed to control
the microenvironment of a spinal region;
[0022] FIG. 7 is a perspective view knee replacement components
designed for controlling the microenvironment of a knee joint;
[0023] FIGS. 8A and 8B show an acetabular implant configured to
control the microenvironment of a joint area;
[0024] FIG. 9 is a top view of a mesh sheet having integral,
microenvironment-controlling means;
[0025] FIG. 10 is a cross sectional view of a tubular mesh
constructed for controlling the microenvironment of a vessel;
[0026] FIG. 11 is a partial cut away view of an implant designed to
control the microenvironment of a blood vessel;
[0027] FIG. 12 shows apparatus for controlling the microenvironment
of a joint during joint replacement surgery;
[0028] FIG. 13 illustrates devices connected with a stomach for
controlling the microenvironment thereof and thereby controlling
the appetite of the person;
[0029] FIG. 14 is a cross sectional view of a device for correcting
vision defects of an eye;
[0030] FIG. 15 shows a tissue patch having
microenvironment-controlling devices;
[0031] FIG. 16 illustrates a device for controlling the
microenvironment of skin;
[0032] FIGS. 17A and 17B show an apparatus for iontophoretic
treatment of tissue;
[0033] FIG. 18 is a perspective view of a hat for controlling
microenvironments of the head;
[0034] FIG. 19 is a perspective view of a collar for controlling
microenvironments of the neck;
[0035] FIG. 20 is a front view of a suit for controlling one or
more microenvironments of the human body;
[0036] FIG. 21 shows a glove for controlling microenvironments of
the hand;
[0037] FIG. 22 shows a filter of the present invention having
integrated microenvironment-controlling means;
[0038] FIG. 23 illustrates another filter having an external
controller;
[0039] FIG. 24 illustrates an aerosol drug delivery system of the
present invention;
[0040] FIG. 25 shows a compressed gas drug delivery system;
[0041] FIG. 26 is a cross sectional view of a distraction drug
delivery system;
[0042] FIG. 27 is a cross sectional view of another distracting
drug delivering system of the present invention;
[0043] FIGS. 28A and 28B illustrate a omni-directional drug
dispersal system;
[0044] FIG. 29A shows a partially implanted drug delivery apparatus
of the present invention;
[0045] FIG. 29B illustrates a fully implanted, externally
controlled drug delivery device;
[0046] FIG. 30A is a top view of a generator joint; and
[0047] FIG. 30B is a side view of the generator joint of FIG.
30A.
[0048] FIG. 31 illustrates a device in accordance with the
invention for controlling a microclimate;
[0049] FIG. 32 is an alternative to the device of FIG. 31, having a
grounded case;
[0050] FIG. 33 illustrates a waveform illustrating a change in
magnetic waveform operative to generate heat;
[0051] FIG. 34 illustrates a circuit to create and control a
sinusoidal signal;
[0052] FIG. 35 illustrates a circuit for monitoring
temperature;
[0053] FIG. 36 illustrates a control circuit for magnet control,
with heart rate input, and controls;
[0054] FIG. 37 illustrates heart monitor and control signals;
[0055] FIG. 38 illustrates a radio frequency energy delivery
circuit;
[0056] FIG. 39 illustrates an ultrasonic generator circuit; and
[0057] FIG. 40 illustrates a resistive heater circuit.
DETAILED DESCRIPTION OF THE INVENTION
[0058] The present invention relates to devices and methods for
controlling microenvironments in living organisms. Characteristics
of the microenvironment that may be controlled include temperature,
pH, moisture, humidity, oxygen-content, oxygenase, carbon
dioxide-content, rate of blood flow, nutrient-content, osmolarity,
pressure, vascular permeability, electrical charge, and the
presence of pharmaceutical or therapeutic agents. These
characteristics may be measured, changed, and monitored
automatically and/or selectively by a physician to obtain the
optimal environment for a particular body region. Continuous
monitoring of the microenvironment creates a feedback loop so that
the microenvironment characteristics may be continuously
controlled.
Implanted Systems
[0059] Referring to FIG. 1, a surgical instrument is shown
positioned in a region of a living body. The region naturally
includes tissue which requires certain levels of environmental
parameters for proper function. These parameters may include
temperature, pH level, moisture, humidity, oxygen tension, carbon
dioxide tension, rate of blood flow, nutrient-content, the presence
of pharmaceutical agents, etc. Through the use of various surgical
instruments, these parameters may be measured, changed, and
monitored.
[0060] An endoscope 10, shown in FIG. 1, includes a viewing port 12
such as a camera lens, a sensor 14, a delivery port 16, and a
heating/cooling unit 18. Cooling units may include a Peltier
cooler, optionally including means to dissipate or redirect heat
generated, including a heat sink, and or a liquid circulation
system. The viewing port 12 allows the physician to precisely
insert the endoscope 10 in the region 20 and provides visualization
of the microenvironment region. The sensor 14 is designed to
respond to physical stimuli and transmit resulting impulses for
interpretation, recording, or operating control. A display screen
(not shown) may be positioned outside the living body and in view
of the physician. The screen and related electronic components
process and display the sensor readings. The sensor 14 may be a
temperature sensor, pH level sensor, moisture sensor, oxygen
sensor, carbon dioxide sensor, or any other sensor to measure
microenvironment characteristics. The delivery port 16 is in fluid
communication with a lumen within the endoscope and a reservoir
(not shown). The delivery port and reservoir 16 are configured for
delivering a liquid, gas, gel, powder, and/or solid to affect the
microenvironment of the region 20.
[0061] Therapeutic substances to control the microenvironment may
include antibiotics, hydroxypatite, anti-inflammatory agents,
steroids, antibiotics, analgesic agents, chemotherapeutic agents,
bone morphogenetic protein, demineralized bone matrix, collagen,
growth factors, autogenetic bone marrow, progenitor cells, calcium
sulfate, immu-suppressants, fibrin, osteoinductive materials,
apatite compositions, fetal cells, stem cells, enzymes, proteins,
hormones, germicides, non-proliferative agents, anti-coagulants,
anti-platelet agents, Tyrosine Kinase inhibitors, anti-infective
agents, anti-tumor agents, anti-leukemic agents, and combinations
thereof
[0062] The heating/cooling unit 18 of the endoscope permits the
physician to adjust the temperature of the microenvironment. The
unit 18 may be a resistive heater, an ultrasonic heater, IR heater,
RF heater, microwave heater, or a convection/conduction cooling
device. By controlling the temperature of the region, other
parameters, such as pH, blood flow rate, etc., may be controlled as
a result. For example, raising the temperature of the
microenvironment region, the pH level may be increased.
[0063] In FIG. 2, another embodiment for controlling the
microenvironment is shown. A multi-lumen catheter or cannula 22
includes an endoscope channel 24, a surgical instrument channel 26,
and a plurality of microenvironment-control channels 28. The
endoscope channel 24 is configured to receive an endoscope 10 like
that of FIG. 1. The instrument channel 26 provides access for a
physician to insert medical instruments into the region 20 of the
body. The microenvironment-control channels 28 are configured for
insertion of sensors 14 and heating/cooling units 18 into the
microenvironment region 20. The sensors 14 and heating/cooling
units 18 are of the types previously described. The
microenvironment-control channels 28 may also be configured for
delivery of gases, liquids, gels, and solids. Therapeutic agents
may be delivered via the microenvironment-control channels.
[0064] To control the microenvironment of the region, a physician
may utilize the devices of FIGS. 1 and 2 as follows. A small
incision may be made in the skin of the patient, and soft tissue
may be distracted with a trocar or guidewire to create a path to
the region 20 requiring microenvironment adjustment. The cannula
may be inserted through the incision and in the path. For a region
accessible through an orifice of the body, the cannula may be
positioned through the orifice without needing to make an incision
in the skin. With the cannula positioned in the body, the endoscope
10 may be inserted in the endoscope channel of the cannula. The
endoscope 10 may be steered by the physician to locate and analyze
the desired body region. A sensor 14 and/or heating/cooling unit 18
may be inserted into the microenvironment-control channels 28 of
the cannula.
[0065] As shown in FIG. 2, a sensor 14 is deployed from the cannula
22 and positioned against tissue in the body region 20. Also, a
heating/cooling unit 18 is deployed from the cannula 22 and
positioned against the tissue. A connection member 30 such as a
wire or plastic rod carries the sensor 14 and/or heating/cooling
unit 18. Electrical or optical wiring may be located within or
adjacent the connection member 30 to carry signals between a
control unit (not shown) and the sensor 14 and heating/cooling unit
18. Based on the measured microenvironment parameters of the
region, the physician may selectively change one or more of the
parameters and/or administer one or more therapeutic agents to the
region.
[0066] The surgical instruments of FIGS. 1 and 2 may be utilized
with minimally invasive surgery techniques disclosed in U.S. Pat.
Nos. 6,702,821; 6,770,078; and 7,104,996. These patent documents
disclose, inter alia, apparatus and methods for minimally invasive
medical procedures. U.S. Pat. Nos. 6,702,821; 6,770,078; and
7,104,996 are hereby incorporated by reference.
[0067] Referring now to FIG. 3, another apparatus for controlling
the microenvironment of a body region is shown. In FIGS. 1 and 2,
the microenvironment of soft tissue was manipulated, while in FIG.
3 the microenvironment of hard tissue, such as bone 32, is
controlled. The bone 32 has a fracture 34 or other injury therein.
The implant of FIG. 3 is an intramedullary rod 36 which stabilizes
the fractured bone. The IM rod 36 may be made of metallic, ceramic,
or polymeric material. The IM rod 36 may include thermoplastic
material which is formable with the application of heat. Patent
documents which further describe such thermoplastic implants
include U.S. patent application Ser. No. 11/416,618 filed May 3,
2006 and U.S. Provisional Patent Application Nos. 60/765,857 filed
Feb. 7, 2006; 60/784,186 filed Mar. 21, 2006; and 60/810,080 filed
Jun. 1, 2006, all of which are hereby incorporated by
reference.
[0068] The IM rod 36 of the present invention includes sensors 14,
heating/cooling units 18, and an electronic controller 38. The
sensors 14 may be temperature sensors, pH sensors, moisture
sensors, oxygen sensors, carbon dioxide sensors, or other sensors
to measure microenvironment characteristics. The heating/cooling
units 18 may be resistive heaters, ultrasonic heaters, IR heaters,
RF heaters, microwave heaters, or convection/conduction cooling
devices. Both the sensors 14 and heating/cooling units 18 may be
controlled by the electronic controller 38, either automatically
based on predetermined measurements or manually via remote control.
Manual control of the implanted electronic processor may be
achieved through IR, RF, or microwave energy or through an
implanted wire.
[0069] The IM rod 36 also includes delivery ports 16, a reservoir
40, and a reservoir controller 42. Each delivery port 16 is in
fluid communication with the reservoir 40 by way of piping 44. The
delivery ports 16 and reservoir 40 are configured for delivering a
liquid, gas, gel, and/or solid to affect the microenvironment of
the region. The substance administered through the delivery ports
may be any of the agents or substances disclosed herein. The
reservoir controller 42 manipulates the release rate and release
period of the substance(s) in the reservoir 40. The reservoir
controller 42 and electronic processor 38 may be linked together to
function as a single system. That is, the reservoir controller and
electronic processor work together to control the microenvironment
of the body region. Alternatively, the reservoir controller and
electronic processor may be physically integrated into one
assembly.
[0070] The microenvironment of a fracture 34 of a bone 32 may be
controlled with the IM rod 36 of FIG. 3 by the following method.
The medullary canal of the fractured bone 32 is cleared out and
formed to receive the IM rod 36. The rod 36 is inserted into the
medullary canal such that the sensors 14, heating/cooling units 18,
and delivery ports 16 are adjacent the fracture 34. If the bone
includes multiple fractures, then the sensors, units, and delivery
ports may be located at various locations along the length of the
rod. The IM rod 36 is secured to the bone with fasteners 45. The
fasteners 45 may lock mechanically in the bone and/or may thermally
bond to the bone and rod. Examples of mechanical and thermal
fasteners are disclosed in the thermoplastic implant documents
already incorporated by reference.
[0071] With the rod 36 implanted, the microclimate may be
controlled to create an optimal healing environment. For example, a
sensor 14 may measure a microenvironment parameter and based on
predetermined levels, the electronic processor 38 may instruct the
reservoir controller 42 to release a substance from the reservoir
40. Substances which may be beneficial to a fractured bone may
include bone morphogenetic proteins, antibiotics, hydroxyapitate,
and other bone healing agents. Agents that increase or decrease the
pH level may also be delivered. The electronic processor 38 may
also instruct a heating/cooling unit 18 to change the temperature
of the body region. Controlling the microenvironment may be
performed automatically by microprocessors based on preset
parameter levels and input signals from the sensors. The
microenvironment may alternatively, or additionally, be controlled
by a physician via remote control. The physician may use RF,
microwave, or IR energy to transmit instructions to the
microprocessors in the IM rod.
[0072] For use with the IM rod 36 of FIG. 3 or any other implant, a
microenvironment-controllable fastener 46 is provided in FIG. 4.
The fastener 46 may be made of metallic, ceramic, polymeric,
composite, or thermoplastic material. The fastener 46 includes
sensors 14, heating/cooling units 18, and electronic controllers 38
similar to those of FIG. 3. The sensors 14 may be temperature
sensors, pH sensors, moisture sensors, oxygen sensors, carbon
dioxide sensors, or other sensors to measure microenvironment
characteristics. The heating/cooling units 18 may be resistive
heaters, ultrasonic heaters, IR heaters, RF heaters, microwave
heaters, or convection/conduction cooling devices. Both the sensors
14 and heating/cooling units 18 are controlled by the electronic
controller 38, either automatically based on predetermined
measurements or manually via remote control. Manual control on the
implanted electronic processor may be achieved through IR, RF, or
microwave energy or through an implanted wire.
[0073] The fastener 46 also includes delivery ports 16, a reservoir
40, and a reservoir controller 42. Each delivery port 16 is in
fluid communication with the reservoir 40 via piping 44. The
delivery ports 16 and reservoir 40 are configured for delivering a
liquid, gas, gel, and/or solid to affect the microenvironment of
the region. The substance administered through the delivery ports
may be any of the substances disclosed herein. The reservoir
controller 42 manipulates the release rate and release period of
the substance(s) in the reservoir. The reservoir controller 42 and
electronic processor 38 may be linked together to function as a
single system. That is, the reservoir controller and electronic
processor work together to control the microenvironment of the body
region. Alternatively, the reservoir controller and electronic
processor may be physically integrated into one assembly.
[0074] In use, the microenvironment of soft or hard tissue may be
controlled with the fastener 46 of FIG. 4. A bore may be created in
the tissue, and the fastener 46 positioned in the bore.
Alternatively, the fastener 46 may include a tissue-piercing tip 48
which eliminates the need to create a bore before implanting the
fastener in the tissue. If the tissue includes multiple areas for
climate control, then the sensors 14, units 18, and delivery ports
16 may be located at various locations along the length of the
fastener. With the fastener implanted, the microclimate may be
controlled to create an optimal healing environment.
[0075] In an exemplary embodiment, a sensor 14 may measure a
microenvironment parameter and based on predetermined levels, the
electronic processor 38 may instruct the reservoir controller 42 to
release one or more substances from the reservoir 40. The
electronic processor 38 may also instruct a heating/cooling unit 18
to change the temperature of the tissue. Controlling the
microenvironment around the fastener 46 may be performed
automatically by microprocessors based on preset parameter levels
and input signals from the sensors. The microenvironment may
alternatively, or additionally, be controlled by a physician via
remote control. The physician may use RF, microwave, or IR energy
to transmit instructions to the microprocessors in the
fastener.
[0076] The fractured bone of FIG. 3 may alternatively, or
additionally, be stabilized by a microenvironment-controlling rigid
plate 50 of FIG. 5. The fastener 46 of FIG. 4 and IM rod 36 of FIG.
3 utilized internal microprocessors, sensors, and units. The
implant 50 of FIG. 5 may include externally mounted
microenvironment-controlling devices. The rigid fixation plate may
be made of metallic, ceramic, composite, polymeric, or
thermoplastic material. The plate 50 includes sensors 14,
heating/cooling units 18, and an electronic controller 38. The
sensors 14 may be temperature sensors, pH sensors, moisture
sensors, oxygen sensors, carbon dioxide sensors, or other sensors
to measure microenvironment characteristics. The heating/cooling
units 18 may be resistive heaters, an ultrasonic heaters, IR
heaters, RF heaters, microwave heaters, or convection/conduction
cooling devices. Both the sensors 14 and heating/cooling units 18
are controlled by the electronic controller 38, either
automatically based on predetermined measurements or manually with
a wire or wireless (IR, RF, or microwave energy).
[0077] The rigid plate 50 also includes delivery ports 16, a
reservoir 40, and a reservoir controller 42. Each delivery port 16
is in fluid communication with the reservoir 40 by way of piping
44. The delivery ports 16 and reservoir 40 are configured for
delivering a liquid, gas, gel, and/or solid to affect the
microenvironment of the region. The substance administered through
the delivery ports 16 may be any of the substances disclosed
herein. The reservoir controller 42 manipulates the release rate
and release period of the substance(s) in the reservoir. The
reservoir controller 42 and electronic processor 38 may be linked
together to function as a single system. That is, the reservoir
controller and electronic processor work together to control the
microenvironment of the body region. Alternatively, the reservoir
controller and electronic processor may be physically integrated
into one assembly.
[0078] The microenvironment of the bone fracture 34 may be
controlled with the rigid plate 50 alone, or with a combination of
the IM rod 36, rigid plate 50, and/or fastener 46. In use, the
rigid plate 50 may be positioned against the bone 32 such that the
sensors 14, heating/cooling units 18, and delivery ports 16 are
adjacent the fracture 34. If the bone 32 includes multiple
fractures, then the sensors, units, and delivery ports may be
located at various locations along the length of the plate. The
plate 50 may be secured to the bone with fasteners 45/46. The
fasteners may lock mechanically in the bone and/or may thermally
bond to the bone and rod. Examples of mechanical and thermal
fasteners are disclosed in the thermoplastic implant documents
already incorporated by reference.
[0079] Where multiple implants are employed, it is contemplated
that various components of the system, as described herein, may be
distributed among the implanted elements. For example, each
fastener may comprise a reservoir and controllable port, and an
intramedullary implant may contain a controller, receiver,
transmitter, and port controller, connected to the ports in the
fasteners. A plate may further contain an energy source in
communication with the other implants, or may support or contain
any of the other components mentioned. Additional combinations and
permutations for distributing components in accordance with the
invention are contemplated, while serving the objects of the
invention.
[0080] With the plate 50 implanted, the microclimate may be
controlled to create an optimal healing environment. For example, a
sensor 14 may measure a microenvironment parameter and based on
predetermined levels, the electronic processor 38 may instruct the
reservoir controller 42 to release an agent or substance from the
reservoir 40. Substances which may be beneficial to a fractured
bone may include bone morphogenetic proteins, antibiotics,
hydroxyapitate, and other bone healing agents. The electronic
processor 38 may also instruct a heating/cooling unit 18 to change
the temperature of the body region. Controlling the
microenvironment may be performed automatically by microprocessors
based on preset parameter levels and input signals from the
sensors. The microenvironment may alternatively, or additionally,
be controlled by a physician via remote control. The physician may
use RF, microwave, or IR energy to transmit instructions to the
microprocessors on the plate.
[0081] In addition to controlling the microenvironment of a bone
fracture, a microenvironment-controlling implant may be utilized to
heal tissue following joint replacement surgery. FIG. 6 shows an
intervertebral disc replacement component 60. The disc implant 60
may be advantageously made of a biocompatible material, including
metallic, ceramic, composite, polymeric, or thermoplastic material.
Various intervertebral implants and other implants which may
include microenvironment-controlling devices are disclosed in U.S.
patent application Ser. No. 11/258,795 filed Oct. 26, 2005, which
is hereby incorporated by reference. The intervertebral implant 60
of the present invention may include sensors 14, heating/cooling
units 18, and an electronic controller 38. The sensors 14 may be
temperature sensors, pH sensors, moisture sensors, oxygen sensors,
carbon dioxide sensors, or other sensors to measure
microenvironment characteristics. The heating/cooling units 18 may
be resistive heaters, an ultrasonic heaters, IR heaters, RF
heaters, microwave heaters, or convection/conduction or electronic
cooling devices. Both the sensors 14 and heating/cooling units 18
are controlled by the electronic controller 38, either
automatically based on predetermined measurements or manually via
remote control. Manual control on the implanted electronic
processor may be achieved through IR or RF energy or through an
implanted wire.
[0082] The intervertebral implant 60 also includes delivery ports
16, a reservoir 40, and a reservoir controller 42. Each delivery
port 16 is in fluid communication with the reservoir 40 via piping
44. The delivery ports 16 and reservoir 40 are configured for
delivering a liquid, gas, gel, and/or solid to affect the
microenvironment of the intervertebral region. The substance
administered through the delivery ports 16 may be any of the
substances disclosed herein. The reservoir controller 42
manipulates the release rate and release period of the substance(s)
in the reservoir. The reservoir controller 42 and electronic
processor 38 may be linked together to function as a single system.
That is, the reservoir controller and electronic processor work
together to control the microenvironment of the body region.
Alternatively, the reservoir controller and electronic processor
may be physically integrated into one assembly.
[0083] The microenvironment of adjacent vertebral bodies 62 may be
controlled with the implant 60 of FIG. 6 as follows. After the
vertebral bodies 62 have been prepared/cut, the implant 60 is
positioned against the superior and inferior bones such that the
sensors 14, heating/cooling units 18, and delivery ports 16 are
adjacent the bone. The implant 60 may be secured to the bone with
fasteners. The fasteners may lock mechanically in the bone and/or
may thermally bond to the bone and rod. Examples of mechanical and
thermal fasteners are disclosed in the thermoplastic implant
documents already incorporated by reference.
[0084] With the disc component 60 implanted, the microclimate may
be controlled to enhance tissue healing. For example, a sensor 14
may measure a microenvironment parameter and based on predetermined
levels, the electronic processor 38 may instruct the reservoir
controller 42 to release a substance from the reservoir 40.
Substances which may be beneficial to a fractured bone may include
bone morphogenetic proteins, antibiotics, hydroxyapitate, and other
bone healing agents. The electronic processor 38 may also instruct
a heating/cooling unit 18 to change the temperature of the body
region. Controlling the microenvironment may be performed
automatically by microprocessors based on preset parameter levels
and input signals from the sensors. The microenvironment may
alternatively, or additionally, be controlled by a physician via
remote control. The physician may use RF, microwave, or IR energy
to transmit instructions to the microprocessors in the disc
implant.
[0085] In addition to intervertebral implants, other joint
replacement components may include microenvironment-controlling
devices. FIG. 7 shows a total knee replacement implant 70 with
climate adjusting means of the present invention. The knee implant
70 may be made of metallic, ceramic, composite, polymeric, or
thermoplastic material. Other materials and structural
characteristics for knee replacement components are disclosed in
U.S. Pat. No. 7,104,996 issued Sep. 12, 2006 and its continuations
and divisionals, all of which are hereby incorporated by reference.
The knee components 70 include sensors 14, heating/cooling units
18, and an electronic controller 38. The sensors 14 may be
temperature sensors, pH sensors, moisture sensors, oxygen sensors,
carbon dioxide sensors, or other sensors to measure
microenvironment characteristics. The heating/cooling units 18 may
be resistive heaters, an ultrasonic heaters, IR heaters, RF
heaters, microwave heaters, or convection/conduction cooling
devices. Both the sensors 14 and heating/cooling units 18 are
controlled by the electronic controller 38, either automatically
based on predetermined measurements or manually via remote control.
Manual control on the implanted electronic processor may be
achieved through IR, RF, or microwave energy or through an
implanted wire.
[0086] The knee replacement components 70 also include delivery
ports 16, a reservoir 40, and a reservoir controller 42. Each
delivery port 16 is in fluid communication with the reservoir 40 by
way of piping 44. The delivery ports 16 and reservoir 40 are
configured for delivering a liquid, gas, gel, and/or solid to
affect the microenvironment of the region. The substance
administered through the delivery ports 16 may be any of the agents
or substances disclosed herein. The reservoir controller 42
manipulates the release rate and release period of the substance(s)
in the reservoir. The reservoir controller 42 and electronic
processor 38 may be linked together to function as a single system.
That is, the reservoir controller 42 and electronic processor 38
work together to control the microenvironment of the body region.
Alternatively, the reservoir controller and electronic processor
may be physically integrated into one assembly.
[0087] In use, the microenvironment parameters of adjacent bones of
the knee may be controlled with the knee replacement components 70
of FIG. 7. After the femur, tibia, and/or patella have been
prepared/cut, the components 70 are positioned against the joint
bones such that the sensors 14, heating/cooling units 18, and
delivery ports 16 are adjacent a cut surface of the bone. The
components 70 may be secured to the bones with fasteners. The
fasteners may lock mechanically in the bone and/or may thermally
bond to the bone and rod. Examples of mechanical and thermal
fasteners are disclosed in the thermoplastic implant documents
already incorporated by reference.
[0088] With the knee components 70 implanted, the microclimate may
be controlled to create an enhanced healing environment. For
example, a sensor 14 may measure a microenvironment parameter and
based on predetermined levels, the electronic processor 38 may
instruct the reservoir controller 42 to release a substance from
the reservoir. Substances which may be beneficial to a fractured
bone may include bone morphogenetic proteins, antibiotics,
hydroxyapitate, and other bone healing agents. The electronic
processor 38 may also instruct a heating/cooling unit 18 to change
the temperature of the body region. Controlling the
microenvironment may be performed automatically by microprocessors
based on preset parameter levels and input signals from the
sensors. The microenvironment may alternatively, or additionally,
be controlled by a physician via remote control. The physician may
use RF, microwave, or IR energy to transmit instructions to the
microprocessors in the knee components.
[0089] Referring now to FIGS. 8A and 8B, a hip implant 80 may
include microenvironment-controlling devices. An acetabular implant
80 is generally a half-spherical socket apparatus dimensioned to
receive a ball joint of the femur or femoral implant. The
acetabular/ball joint implant 80 may be made of metallic, ceramic,
composite, polymeric, or thermoplastic material. Other materials
and structural characteristics for acetabular component are
disclosed in U.S. Provisional Application No. 60/810,080 filed Jun.
1, 2006, which is hereby incorporated by reference. The acetabular
implant and/or ball joint implant 80 may include sensors 14,
heating/cooling units 18, and an electronic controller 38. The
sensors 14 may be temperature sensors, pH sensors, moisture
sensors, oxygen sensors, carbon dioxide sensors, or other sensors
to measure microenvironment characteristics. The heating/cooling
units 18 may be resistive heaters, an ultrasonic heaters, IR
heaters, RF heaters, microwave heaters, or convection/conduction
cooling devices. Both the sensors 14 and heating/cooling units 18
are controlled by the electronic controller 38, either
automatically based on predetermined measurements or manually via
remote control. Manual control on the implanted electronic
processor may be achieved through IR or RF energy or through an
implanted wire.
[0090] The hip implants 80 of the present invention may also
include delivery ports 16, a reservoir(s) 40, and a reservoir
controller 42. Each delivery port 16 is in fluid communication with
the reservoir 40 via piping 44. The delivery ports 16 and reservoir
40 are configured for delivering a liquid, gas, gel, and/or solid
to affect the microenvironment of the hip region. The substance(s)
administered through the delivery ports may be any of the
substances disclosed herein. The reservoir controller 42
manipulates the release rate and release period of the substance(s)
in the reservoir. The reservoir controller 42 and electronic
processor 38 may be linked together to function as a single system.
That is, the reservoir controller and electronic processor work
together to control the microenvironment of the body region.
Alternatively, the reservoir controller and electronic processor
may be physically integrated into one assembly.
[0091] In use, the microenvironment of adjacent hip bones 82 may be
controlled with the hip implant components 80 of FIGS. 8A and 8B.
After the femur and/or hip bone 82 have been prepared/cut, the
component(s) 80 are positioned against the joint bones 82 such that
the sensors 14, heating/cooling units 18, and delivery ports 16 are
adjacent a cut surface of the bone. The component(s) 80 may be
secured to the bones with fasteners. The fasteners may lock
mechanically in the bone and/or may thermally bond to the bone and
rod.
[0092] With the acetabular/ball joint component(s) 80 implanted,
the microclimate may be controlled to create an optimal healing
environment. For example, a sensor 14 may measure a
microenvironment parameter and based on predetermined levels, the
electronic processor 38 may instruct the reservoir controller 42 to
release a substance from the reservoir 40. Substances which may be
beneficial to a fractured bone may include bone morphogenetic
proteins, antibiotics, hydroxyapitate, and other bone healing
agents. The electronic processor 38 may also instruct a
heating/cooling unit 18 to change the temperature of the body
region. Controlling the microenvironment may be performed
automatically by microprocessors based on preset parameter levels
and input signals from the sensors. The microenvironment may
alternatively, or additionally, be controlled by a physician via
remote control. The physician may use RF, microwave, or IR energy
to transmit instructions to the microprocessors in the hip
implants.
[0093] In FIGS. 9 and 10, a sheet-like implant 90 is configured for
controlling the microenvironment of tissue. The sheet 90 of FIG. 9
includes integrated devices for controlling microenvironment
parameters, while the sheet 92 of FIG. 10 includes externally
mounted devices. The sheets of FIGS. 9 and 10 may include a
permeable mesh-like structure or may include an impermeable
structure. The sheets 90 and 92 may be made of metallic, ceramic,
composite, polymeric, or thermoplastic material. Other materials,
structural characteristics, and methods of manufacture/use for
sheets are disclosed in U.S. Provisional Application 60/810,080
filed Jun. 1, 2006, which was previously incorporated by reference.
The sheets of FIGS. 9 and 10 may include sensors 14,
heating/cooling units 18, and an electronic controller 38. The
sensors 14 may be temperature sensors, pH sensors, moisture
sensors, oxygen sensors, carbon dioxide sensors, or other sensors
to measure microenvironment characteristics. The heating/cooling
units 18 may be resistive heaters, an ultrasonic heaters, IR
heaters, RF heaters, microwave heaters, or convection/conduction
cooling devices. Both the sensors 14 and heating/cooling units 18
are controlled by the electronic controller 38, either
automatically based on predetermined measurements or manually via
remote control. Manual control on the implanted electronic
processor may be achieved through IR or RF energy or through an
implanted wire.
[0094] The sheets 90 and 92 may also include delivery ports 16, a
reservoir 40, and a reservoir controller 42. Each delivery port 16
is in fluid communication with the reservoir 40 by way of piping
44. The delivery ports 16 and reservoir 40 are configured for
delivering a liquid, gas, gel, and/or solid to affect the
microenvironment of the region. The substance administered through
the delivery ports 16 may be any of the substances disclosed
herein. The reservoir controller 42 manipulates the release rate
and release period of the substance(s) in the reservoir 40. The
reservoir controller 42 and electronic processor 38 may be linked
together to function as a single system. That is, the reservoir
controller and electronic processor work together to control the
microenvironment of the body region. Alternatively, the reservoir
controller and electronic processor may be physically integrated
into one assembly.
[0095] In use, the microenvironment of tissue may be controlled
with the sheets of FIGS. 9 and 10. As shown in FIG. 10, a sheet 92
is wrapped around a body conduit 94 such that the sensors 14,
heating/cooling units 18, and delivery ports 16 are adjacent the
tissue of the conduit. The conduit 94 may be a vessel, an
intestine, an esophagus, or other tubular body part. The
microenvironment-controlling sheet 90 and 92 of the present
invention may be used to treat diseased blood vessels. In FIG. 10,
a blood vessel 94 is illustrated with an aneurysm 96 therein. The
sheet 92 may be secured to the conduit with fasteners, and/or the
sheet may be fastened to itself to hold the sheet around the
conduit 94. A sheet with thermoplastic material may be heated to
shrink wrap the sheet to the body conduit. Further disclosure on
heat shrink implants may be found in U.S. Provisional Application
No. 60/810,080 filed Jun. 1, 2006 which was previously incorporated
by reference.
[0096] With the sheet 92 of the present invention implanted, the
microclimate may be controlled to enhance healing. For example, a
sensor 14 may measure a microenvironment parameter and based on
predetermined levels, the electronic processor 38 may instruct the
reservoir controller 42 to release a beneficial agent or substance
from the reservoir 40. The electronic processor 38 may also
instruct a heating/cooling unit 18 to change the temperature of the
body region. Controlling the microenvironment may be performed
automatically by microprocessors based on preset parameter levels
and input signals from the sensors. The microenvironment may
alternatively, or additionally, be controlled by a physician via
remote control. The physician may use RF, microwave, or IR energy
to transmit instructions to the microprocessors in the sheets.
Magnetism/Charged Particles
[0097] In addition to the microenvironment-controlling devices
described with respect to FIG. 10, the implant 100 of FIG. 11 may
include magnets and/or electromagnets 102. The magnets 102 attract
magnetically charged particles from adjacent tissue, such as
particles in blood. It is contemplated that any of the apparatus
and methods disclosed herein may include and use magnets and
electromagnets. Other magnet/charged particle systems are disclosed
in U.S. Pat. No. 6,820,614 entitled "Tracheal Intubination" and
issued Nov. 23, 2004, which is hereby incorporated by
reference.
[0098] Currently, there is no practical way to concentrate a
pharmaceutical agent to a local site. By charging pharmaceutical
agents, cells, gene therapy agents, RNA, DNA, BMP, tissue inductive
factors, etc., these substances may be concentrated at a
microenvironment region by a magnet. The charged substances would
flow through the blood stream until an externally mounted or
internally implanted magnet draws the charged particle to a local
region. The magnetic energy may also pull the changed substances
from the blood stream, through the vessel wall, and into adjacent
tissue.
[0099] Magnets may also be used to optimize blood flow by charging
the iron ion in hemoglobin. The charged ion in hemoglobin could be
concentrated at a specific local microenvironment for improved
oxygen flow. Nutrient delivery, vasodilatation, vasoconstriction,
cell membrane passage, cell receptor activity may also be
controlled by the magnetic charge and iron molecules in the blood.
Copper molecules/particles may also be charged and concentrated at
a local site with magnets.
[0100] The magnets used to attract charged particles may be placed
in any of the microenvironment-controlling implants disclosed
herein. In addition, the nano magnets or biodegradable magnets may
be integrally formed into a biodegradable polymeric or ceramic
implant to form magnetic sinks. The magnets may be disposed in
polylactic acid or PEEK, for example, and implanted in the body
adjacent damaged tissue. The magnets may be fragments of cobalt or
samarium encapsulated by a polymer. A magnetometer may be used to
monitor and control the magnetic field of the sink. Increasing or
decreasing the magnetic field, either internally with a
microprocessor and battery or externally with an external energy
source, would control the blood flow of the vessel and/or
concentrate therapeutic agents in the microenvironment region. The
magnetic field may be pulsed to compensate or represent heart
pulses. Using a heart beat sensor, the magnetic field pulses may be
synchronized based on the heart rate.
[0101] Generally, the implant 100 of FIG. 11 may be cylindrical or
tubular in shape to fit around a body conduit 94 such as a blood
vessel. The inner diameter D.sub.1 of the cylindrical implant 100
may be less than the outer diameter D.sub.2 of the conduit 94 so
that fluid flowing through the conduit it is inherently accelerated
at the region of the implant. The accelerated flow of the fluid
allows an increased amount of therapeutic agents to be delivery
through the conduit wall and into the fluid stream. This
characteristic is analogous to the Bernoulli's principle: flowing
fluid accelerates at a region of decreased area/volume.
Cylindrical Implant
[0102] The implant 100 of FIG. 11 may be made of metallic, ceramic,
composite, polymeric, or thermoplastic material. The cylindrical
implant 100 may include sensors 14, heating/cooling units 18,
magnets 102, and an electronic controller 38. The sensors 14 may be
temperature sensors, pH sensors, moisture sensors, oxygen sensors,
carbon dioxide sensors, or other sensors to measure
microenvironment characteristics. The heating/cooling units 18 may
be resistive heaters, ultrasonic heaters, IR heaters, RF heaters,
microwave heaters, or convection/conduction cooling devices. The
magnets 102 may be earth magnets or electromagnets. The sensors 14,
heating/cooling units 18, and magnets 102 are controlled by the
electronic controller 38, either automatically based on
predetermined measurements or manually via remote control. Manual
control on the implanted electronic processor may be achieved
through IR or RF energy or through an implanted wire.
[0103] The cylindrical implant 100 may also include port holes 16,
a reservoir(s) 40, a reservoir controller 42, and a suction means,
such as an electric or manual pump. The port hole 16 may be in
fluid communication with the reservoir 40 by way of piping 44. The
port hole 16 and reservoir 40 are configured for delivering a
liquid, gas, gel, and/or solid to affect the microenvironment of
the region. The substance(s) administered through the delivery
ports 16 may be any of the substances disclosed herein. The
reservoir controller 42 manipulates the release rate and release
period of the substance(s) in the reservoir. The reservoir
controller 42 and electronic processor 38 may be linked together to
function as a single system. That is, the reservoir controller and
electronic processor work together to control the microenvironment
of the body region. Alternatively, the reservoir controller and
electronic processor may be physically integrated into one
assembly.
[0104] A port hole 16 may instead, or in addition to, be connected
to the suction means. The suction at the port hole would create a
negative pressure (Venturi effect) on the surrounding tissue. The
suction could increase blood flow by vasodilatation or draw blood
away from a certain tissue area causing vasoconstriction. The
negative pressure may also aid in the delivery and/or concentration
of pharmaceutical substances. It is contemplated that the other
embodiments of the present invention may also include suction port
holes, a suction pump, and associated tubing. For example, the knee
replacement components 70 of FIG. 7 may include port holes and a
suction pump. This could improve vascular flow of knee tissue. The
pump could be integrated into the implant such that as the knee is
moved back and forth suction is created.
[0105] In use, the microenvironment of tissue may be controlled
with the cylindrical implant 100. As shown in FIG. 11, the implant
100 is positioned around a body conduit 94 such that the sensors
14, heating/cooling units 18, magnets 102, and delivery ports 16
are adjacent the tissue of the conduit. The conduit 94 may be a
vessel, an intestine, an esophagus, or other tubular body part. For
the sake of drawing simplicity, the inner diameter of the implant
is generally the same as the outer diameter of the conduit.
However, as previously described, a smaller inner diameter of the
implant would create increased fluid flow thereby increasing the
administration rate of therapeutic agents. The
microenvironment-controlling implant 100 of FIG. 11 may be used to
treat diseased blood vessels or other body lumens. The implant 100
may be secured to the conduit with fasteners and/or, the implant
may be fastened to itself to hold the implant around the conduit. A
cylindrical implant with thermoplastic material may be heated to
shrink wrap the implant to the body conduit. Further disclosure on
heat shrink implants may be found in patent document already
incorporated by reference.
[0106] With the cylindrical implant 100 of the present invention
positioned, the microclimate may be controlled to create an optimal
medical climate. For example, a sensor 14 may measure a
microenvironment parameter and based on predetermined levels, the
electronic processor 38 may instruct the reservoir controller 42 to
release a substance from the reservoir 40. The electronic processor
38 may also instruct a heating/cooling unit 18 to change the
temperature of the body region and/or instruct the magnets 102 to
energize thereby drawing charged particles to the conduit wall. The
diameter of the cylindrical implant 100 may be increased or
decreased with the electronic processor 38 and the heating/cooling
units 18. Heating the implant may expand the implant diameter and
cooling the implant may decrease the diameter, or vice versa.
Controlling the microenvironment may be performed automatically by
microprocessors based on preset parameter levels and input signals
from the sensors. The microenvironment may alternatively, or
additionally, be controlled by a physician via remote control. The
physician may use RF, microwave, or IR energy to transmit
instructions to the microprocessors in the implant.
[0107] It is contemplated that other known surgical implants may
include the microenvironment-controlling devices described herein.
For example, the present invention provides a
microenvironment-controlling stent; cannula; catheter; spinal rod,
plate, or pin; face and head reconstruction implant; shoulder
replacement component; elbow replacement implant; hand and foot
implant, and other similar implants.
Climate Controlled Surgery
[0108] In addition to the apparatus previously described to control
the microenvironment of a living body, the present invention
provides methods and apparatus for performing climate-controlled
surgery. During a surgical procedure, the body region being
operated on is exposed to the operating room environment. This is
especially relevant during maximally invasive procedures but also
relevant during minimally invasive surgery, endoscopic surgery, and
insufflation. Usually, the operating room is dry, and tissue
response is affected by desiccation. The room temperature often
varies between 60 and 65 degrees Fahrenheit, and the local tissue
is cooled significantly. Also, when tissue is cut it releases
enzymes which change the local pH. Bleeding changes the local pH as
well. Irrigation is often used at the surgical region, but the
irrigation is not isotonic to decrease osmolarity and drug tension.
Moreover, coolness and change in pressure effect vascular flow,
causing vasoconstriction, therefore, fewer nutrients enter the
wound site and less oxygen is delivered to the site which can
further damage the tissue.
[0109] Using climate-controlled surgery, the local body
temperature, not just the core body temperature, may be regulated.
Desiccation may be minimized, and vascular flow may be maintained.
Also, oxygen tension and nutrient delivery may be optimized. The
local pH level may be controlled, and tissue osmolarity may be
maintained.
[0110] Although a limited number of examples are provided herein,
it is contemplated that any type of surgery may be combined with
the climate-controlling methods herein. For example, the present
invention may be applied to surgery of the foot and ankle, hand and
wrist, elbow, knee, hip, shoulder, genitalia, head, etc. As will
become clearer subsequently, surgery on a region of an extremity is
most conducive for the methods of climate-controlled surgery.
[0111] Referring now to FIG. 12, a system for climate-controlled
knee surgery is illustrated. The surgical system includes a hollow
structure, such as an expanding cannula, or trocar 110, a
microprocessor controller 112, sensors 14, heating/cooling units
18, magnets 102, reservoirs 40, pumps 114 and related fluid conduit
116. The trocar 110 is dimensioned to enter the body region of the
patient that is to be operated on. The sensors 14 may be
temperature sensors, pH sensors, moisture sensors, oxygen sensors,
carbon dioxide sensors, or other sensors to measure
microenvironment characteristics. The heating/cooling units 18 may
be resistive heaters, an ultrasonic heaters, IR heaters, RF
heaters, microwave heaters, or convection/conduction cooling
devices. The magnets 102 may be earth magnets or electromagnets.
The sensors 14, heating/cooling units 18, magnets 102, reservoirs
40, and pumps 114 are controlled by the electronic controller 112,
either automatically based on predetermined measurements or
manually via remote control. Manual control on the implanted
electronic processor may be achieved through wire or wireless
remote control. Wireless control may be performed with IR, RF, or
microwave energy.
[0112] To perform climate-controlled knee surgery, a patient 118
may be placed in the prone position with the patient's leg to be
operated on positioned adjacent an edge of the support table 120. A
leg cuff and strap 122 may be connected with the patient's foot or
ankle. The strap 122 may be connected with an attachment point
which may be movable up/down, left/right, or forward/backward.
[0113] Sensors 14 and/or magnets 102 may be attached to the
patient's tissue in or around the incision area, positioned through
trocar 110, or adjacent to the entry area. The sensors 14 and
magnets 102 may be connected to the controller via wires or
wireless IR or RF energy. Fluid, such as saline, water, plasma, or
other biocompatible fluid may be added to the trocar 110 through
the inlet pipe 116 via the pump 114. Alternatively, for
insufflation, a gas may be added to trocar 110. The heating/cooling
unit 18 may vary the temperature of the fluid during filling and
throughout the surgical procedure. Based on signals from the
sensors 14 and/or on the physician's direction, pharmaceutical or
therapeutic agents stored in the reservoirs 40 may be selectively
released into the fluid stream. The combination of agent reservoirs
40, heating/cooling units 18, sensors 14, magnets 102, pumps 114,
and fluid 126 forms a means for creating, maintaining, and changing
the environment of the surgical region. During and after the
operation, the fluid 126 may be extracted from the submersion tank
110 via the outlet pipe 116b and valve 128. The valve 128 may be
controlled by the microprocessor controller and/or by the physician
(shown).
[0114] One of reservoir 40 may advantageously contain a substance
which may be used to control pH. It is advantageous to use a
calcium based substance due to a potentially beneficial effect on
bones, although a wide variety of substances may be used, as
described above. The pH controlling substance may be a gas, liquid,
or powder, and may enter the surgical field through a pipe 116c and
be collected through a separate pipe 116d. Adjustment of pH and
temperature may advantageously be carried out to reduce
postoperative pain.
Pump Implant
[0115] The present invention also provides an implantable pump for
controlling the microenvironment of a body region. The pump may
control the microenvironment parameters such as temperature, pH
level, moisture, humidity, oxygen tension, carbon dioxide tension,
rate of blood flow, nutrient-content, and the presence of
pharmaceutical agents. Through the use of pumps, reservoirs,
sensors, and controllers, these parameters may be measured,
changed, and monitored, externally or internally.
[0116] In an exemplary embodiment, a pump system would control the
local regulation of pH. pH-changing agents could be placed in an
implantable pump which may be externally or internally controlled.
The pump/reservoir may include pH controlling agents such as
calcium carbonate or calcium sulfate. The pump could have valves
which release the agents to the local circulation, or it could have
an osmotic membrane covering, another type of salt such as sodium
chloride, potassium chloride, calcium carbonate, calcium sulfate.
Calcium based compounds may be used because they are easily
metabolized by the body and can help with issues of osteoporosis.
Some salts, because of their ability to bind to proteins, may also
be efficacious with pH control. The pH control system could also be
ionic anionic. Certain salts that are released may have an affinity
to bind to proteins and affect the local microclimate.
[0117] Alternatively, a body region may be made more acidic. This
can be accomplished, for example, be delivering carbon dioxide (or
a liquid carbon dioxide) to tissue. As this agent is released it
would create carbonic acid which could make the pH more acidic. The
pH level may be automatically or manually controlled with sensors
and a microprocessor. The sensors positioned locally in the tissue
could detect the pH level and could turn on and off the delivery of
a pH-changing agent. The pH level could be varied during the course
of the day, or during a time when one wants improved tissue
effect.
Stomach Irritator
[0118] In a more specific embodiment, the pump system may be used
as a stomach irritator. The pump system may be used for irritable
bowel and bladder problems as well. The stomach irritator could be
used in place of or in addition to gastric bypass surgery. The
irritator could be a pH irritator or electromagnetic irritator. An
electromagnetic irritator may include electromagnets and a
microprocessor for delivering magnetic energy to the stomach
thereby decreasing the patient's appetite. The pH irritator system
could create nausea by releasing viral agents or irritating agents
to the stomach which would cause stomach muscle spasm and therefore
decrease the patient's interest or desire to eat. The system
illustrated in FIG. 13 may include an electronic controller 38,
sensors 14, magnets 102, heating/cooling units 18, delivery ports
16, a reservoir 40, a battery 129, and related wire and conduit.
These components may be made of a biodegradable material. The
batteries may be recharged with tissue flow, tissue movement, heat
changes, thermal changes, or pH changes. Other electrical
generators and battery recharging devices and methods are described
subsequently.
[0119] The irritator systems could be used as a temporary obesity
treatment. The systems could be implanted transcutaneously,
percutaneously, endoscopically, and/or minimally invasively. The
implanted systems may be fastened in place with thermoplastic
bands, stapling, and/or ultrasonic welding techniques described in
patent documents incorporated herein. The irritator systems of the
present invention do not operate by reducing the volume of the
stomach, rather the systems function like arrhythmia of the heart
where an arrhythmia pattern in the stomach wall musculature is
created. This arrhythmia then inhibits normal mechanical operation
of the stomach, and contributes to a feeling of bloatedness or
fullness. The system may affect one or more locations of the
stomach, it would thus be diffuse affect, similar to creating
gastric fibrillation. As previously described, the system may
function electrically or electromagnetically. It may also function
ultrasonically where an ultrasonic generator transmits vibratory
energy to the stomach. Furthermore, the system may function
thermally using heating units described herein to create
irritation-type spasm in the stomach.
[0120] In addition to the pH irritator and electromagnet irritator,
the present invention provides a metallic ion irritator. This
system may include metallic ions to conduct temperatures of the
stomach, bowel, bladder, etc. The metallic ions may be
percutaneously implanted and activated with an electrical
transmitter which may be external to the body, battery operated,
and wearable by the patient. Thus, the patient or physician may
control the temperature of the stomach, etc. by changing the signal
of the transmitter.
Microenvironment Controlled Surgery of the Eye
[0121] Another embodiment of microenvironment-controlling surgery
is illustrated in FIG. 14. The microenvironment-controlling devices
of the present invention may be used to correct vision of the eye.
The surgical apparatus 130 includes a concave body 132, sensors 14,
heating/cooling units 18, delivery ports 16, reservoirs 40, and a
microprocessor controller 38. The concave body 132 may be made of
metallic, ceramic, or polymeric material. In a specific embodiment,
the concave body 132 is an ultrasonic end effector capable of
producing vibratory energy. The sensors 14 may be temperature
sensors, pH sensors, moisture sensors, oxygen sensors, carbon
dioxide sensors, or other sensors to measure microenvironment
characteristics. The heating/cooling units 18 may be resistive
heaters, an ultrasonic heaters, IR heaters, RF heaters, microwave
heaters, or convection/conduction cooling devices. The sensors 14,
heating/cooling units 18, and end effector (concave body) 132 may
be controlled by the electronic controller 38, either automatically
based on predetermined measurements or manually via remote
control.
[0122] The apparatus of FIG. 14 also includes port holes 16, a
reservoir(s) 40, a reservoir controller 42, and a suction means,
such as an electric or manual pump. The port hole 16 may be in
fluid communication with the reservoir 40 by way of piping 44. The
port hole 16 and reservoir 40 are configured for delivering a
liquid, gas, gel, and/or solid to affect the microenvironment of
the region. The substance(s) administered through the delivery
ports 16 may be any of the substances disclosed herein. The
reservoir controller manipulates the release rate and release
period of the substance(s) in the reservoir 40. The reservoir
controller 42 and electronic processor 38 may be linked together to
function as a single system. That is, the reservoir controller and
electronic processor work together to control the microenvironment
of the body region. Alternatively, the reservoir controller and
electronic processor may be physically integrated into one
assembly.
[0123] A port hole 16 may instead, or in addition to, be connected
to the suction means. The suction at the port hole 16 would create
a negative pressure (Venturi effect) on the surrounding cornea
tissue 134. The negative pressure may aid in the delivery and/or
concentration of pharmaceutical substances.
[0124] The microenvironment of the cornea 134 may be controlled
during vision correction surgery with the apparatus 130 of FIG. 14
by the following method. Initially, a physician will measure the
uncorrected shape of the patient's cornea 134 and determine the
amount and location of reshaping necessary to improve vision in the
eye 136. With the calculations completed, the concave body 132 may
be place in contact with the cornea 134. Using the body 132 as an
ultrasonic horn, vibration energy may be emitted to raise the
temperature of the cornea 134 and reshape the outer surface.
Before, during, and after reshaping, pharmaceutical agents may be
delivered to the cornea via the port openings 16, piping, and
reservoir 40. The port openings 16 may also provide suction to the
cornea 134 to draw the pharmaceutical agents to a specific location
or depth of the cornea. The sensors 14 may measure any of the
microenvironment parameters, such as temperature, acidity, etc. and
provide the measurements to the electronic controller. The
heating/cooling units 18 may be used to change the temperature of
the cornea to optimize the reshaping and healing processes.
Moreover, magnets 102 as described in early embodiments may be used
to control the microenvironment parameters of the cornea as well.
All the microenvironment-controlling devices (sensors, units, port
openings, magnets, reservoir, etc.) may be automatically controlled
by the microprocessor, manually controlled by the physician, or a
combination of manual and automatic control.
Transdermal or Topical Delivery
[0125] Certain embodiments described thus far have been
microenvironment-controlling implants or surgical procedures. The
embodiments of FIGS. 15, 16, 17A, and 17B provide
microenvironment-controlling apparatus which are positioned against
skin. A topical pharmaceutical delivery system may administer drugs
locally and transcutaneously and/or percutaneously. The system uses
poloxamer lecithin organogel (PLO), lecithin isopropyl palmitate,
polypropylene glycol, ethyl propylene glycol, ethoxydiglycol,
and/or liposomal components to help dissolve or transport
pharmaceutical agents through the skin. While lecithin is a
preferred substance, ketoprofen, licocaine, and steroids in
concentrations of about 20 percent may also be resorbed through the
skin.
[0126] Generally, as therapeutic agents are delivered topically,
the diffusion coefficient remains the same thereby releasing an
agent at a constant rate. Physicians, however, may prefer that some
pharmaceutical agents be topically administered at different rates
depending on the need of the patient or desire of the physician.
The microenvironment-controlling devices of the present invention
may be used to selectively delivery topical agents at various rates
and periods. Raising the temperature or pH level, for example, may
increase the diffusion coefficient, while cooling the skin or
lowering the pH level may slow drug delivery. Suction applied to
the skin may also vary the drug flow rate. The negative pressure
would create a Venturi effect in the skin which would enhance
penetration through the skin and into an adjacent artery or vein.
For example, a topical delivery system may be placed on the hand to
concentrate drug administration over the radial artery.
[0127] The types of pharmaceutical substances which may be
delivered topically are well known in the art. These substances may
be combined by the manufacturer in the factory or by the physician
in the hospital/operating room to create a specific mixture, or
cocktail of drugs that meet the patient's needs. These cocktails
may be placed or incorporated into a gelatin, biologic foam, or
biodegradable foam to absorb through the skin and into the body.
One type of gelatin which may be used is pluronic gel. Pluronic gel
or any other carrier may be combined with steroids, thrombolytic
agents, pain relieving agents, opioids, lidocaine,
anti-inflammatory agents, or chemotherapeutic agents for controlled
topical local administration. Other pharmaceutical agents disclosed
herein may be used with the topical system as well.
[0128] It is contemplated that the topical delivery system of the
present invention may be combined with electroshock wave energy, RF
energy, and electromagnetic energy.
[0129] A topical pharmaceutical delivery patch 140 is illustrated
in FIG. 15. The patch 140 may include a base sheet 142, sensors 14,
heating/cooling units 18, magnets 102, and microprocessor
controllers 38. The base sheet 142 may be similar to known patches
such as the nicotine patch or birth control patch. The sheet 142
may include an adhesive on the skin facing surface. The sensors 14
may be temperature sensors, pH sensors, moisture sensors, oxygen
sensors, carbon dioxide sensors, or other sensors to measure
microenvironment characteristics. The heating/cooling units 18 may
be resistive heaters, an ultrasonic heaters, IR heaters, RF
heaters, microwave heaters, or convection/conduction cooling
devices. The magnets 102 may be earth magnets or electromagnets.
The sensors 14, heating/cooling units 18, and magnets 102 are
controlled by the electronic controller 38, either automatically
based on predetermined measurements or manually via remote control.
Manual control of the electronic processor may be achieved through
IR or RF energy or through an implanted wire.
[0130] The topical delivery system may also include port holes 16,
a reservoir(s) 40, a reservoir controller 42, and a suction means,
such as an electric or manual pump. The port hole 16 may be in
fluid communication with the reservoir by way of piping 44. The
port hole 16 and reservoir 40 are configured for delivering a
liquid, gas, gel, and/or solid to affect the microenvironment of
the region. The substance(s) administered through the delivery
ports 16 may be any of the substances disclosed herein. The
reservoir controller 42 manipulates the release rate and release
period of the substance(s) in the reservoir. The reservoir
controller 42 and electronic processor 38 may be linked together to
function as a single system. That is, the reservoir controller and
electronic processor work together to control the microenvironment
of the body region. Alternatively, the reservoir controller and
electronic processor may be physically integrated into one
assembly.
[0131] A port hole 16 may instead, or in addition to, be connected
to the suction means. The suction at the port hole 16 would create
a negative pressure on the surrounding tissue. The suction could
increase blood flow by vasodilatation or draw blood away from a
certain tissue area cause vasoconstriction. The negative pressure
may also aid in the delivery and/or concentration of
pharmaceutical/therapeutic substances.
[0132] In an exemplary method of use, the patch of FIG. 15 may
control the microenvironment of soft tissue, such as skin. The
patch 140 is positioned against the skin such that the sensors 14,
heating/cooling units 18, magnets 102, and delivery ports 16 are
adjacent the tissue. The patch 140 may be secured to the skin with
adhesive. With the patch positioned, the microclimate may be
controlled to create an optimal topical drug delivery. For example,
a sensor 14 may measure a microenvironment parameter and based on
predetermined levels, the electronic processor 38 may instruct the
reservoir controller 42 to release a substance from the reservoir
40. The electronic processor 38 may also instruct a heating/cooling
unit 18 to change the temperature of the body region, instruct the
magnets 102 to energize thereby drawing charged particles to the
skin, and/or instruct increased or decreased flow rate of the
therapeutic agent. Controlling the microenvironment may be
performed automatically by microprocessors based on preset
parameter levels and input signals from the sensors. The
microenvironment may alternatively, or additionally, be controlled
by a physician via remote control. The physician may use RF,
microwave, or IR energy to transmit instructions to the
microprocessors in the implant.
Ultrasonic Topical Drug Delivery
[0133] Referring now to FIG. 16, an ultrasonic topical drug
delivery system 144 may control the microenvironment of soft
tissue. The ultrasonic system 144 may include a main body 146,
sensors 14, heating/cooling units 18, delivery ports 16, reservoirs
40, and a microprocessor controller 38. In a specific embodiment,
the body 146 is an ultrasonic end effector capable of producing
vibratory energy. The sensors 14 may be temperature sensors, pH
sensors, moisture sensors, oxygen sensors, carbon dioxide sensors,
or other sensors to measure microenvironment characteristics. The
heating/cooling units 18 may be resistive heaters, an ultrasonic
heaters, IR heaters, RF heaters, microwave heaters, or
convection/conduction cooling devices. The sensors 14,
heating/cooling units 18, and end effector (concave body) 146 may
be controlled by the electronic controller 38, either automatically
based on predetermined measurements or manually via remote
control.
[0134] The ultrasonic topical system 144 also includes port holes
16, a reservoir(s) 40, a reservoir controller 42, and a suction
means, such as an electric or manual pump. The port hole 16 may be
in fluid communication with the reservoir 40 by way of piping. The
port hole 16 and reservoir 40 are configured for delivering a
liquid, gas, gel, and/or solid to affect the microenvironment of
the region. The substance(s) administered through the delivery
ports may be any of the substances disclosed herein. The reservoir
controller 42 manipulates the release rate and release period of
the substance(s) in the reservoir. The reservoir controller 42 and
electronic processor 38 may be linked together to function as a
single system. That is, the reservoir controller and electronic
processor work together to control the microenvironment of the body
region. Alternatively, the reservoir controller and electronic
processor may be physically integrated into one assembly.
[0135] A port hole 16 may instead, or in addition to, be connected
to the suction means. The suction at the port hole 16 would create
a negative pressure (Venturi effect) on the surrounding tissue 148.
The negative pressure may aid in the delivery and/or concentration
of pharmaceutical substances.
[0136] The microenvironment of skin may be controlled during
topical administration of a pharmaceutical substance. In use, the
ultrasonic drug delivery system 144 of FIG. 16 may be positioned
against soft tissue, such as skin 148. To administer a
pharmaceutical agent 150 to the skin 148, the operator/physician
may utilize any of the microenvironment-controlling devices. For
example, the end effector 146 may transmit vibratory energy to the
skin 148, and the heat/cooling units 18 may change the temperature
of the skin. A substance 150 may be delivered from the reservoir
via the port openings 16. The substance 150 may be any of the
agents disclosed herein, such as a pH-changing agent. The port
openings 16 may alternatively, or additionally, provide negative
pressure to the skin. The magnets 102 of the system may attract
changed particles to the skin for drug concentration. All of these
microenvironment-controlling devices permit the microenvironment
parameters to be measured, changed, and monitored. A microprocessor
may automatically control the devices, or a physician may control
the devices and parameters manually.
Blood Loss
[0137] It is contemplated that the apparatus and methods of FIGS.
15 and 16 may further be used to stop bleeding. The systems may
deliver individual drugs or drug cocktails to the bleeding tissue
while changing and monitoring the microenvironment parameters.
Examples of substances the systems may used to control bleeding
include epinephrine, sucrose products as a vasoconstrictor,
tetracycline to increase or decrease scarring, and soluble
gels.
[0138] Iontophoresis
[0139] Controlling the microenvironment of tissue may also be
combined with iontophoresis, a form of electro-osmosis. Currently,
physical therapists are using iontophoresis to help penetrate
cortisone into the skin. An electric charge is placed between
electrodes positioned adjacent the skin. The electric current aids
in topical drug administration. This technique may be combined with
devices and methods for controlling the microenvironment parameters
of a region of the body. Along with the electric current, the
temperature (ultrasound), pH level, moisture, humidity, porosity,
pressure, and other parameters may be changed and monitored.
Instead of having a constant current, the electric charge may be
oscillated, pulsed, or alternated during topical drug delivery, and
instead of using iontophoresis for applying therapeutic agents to
the skin, the technique may be used for intracorporeal drug
delivery to other tissue, such as bone, muscle, and cartilage, as
well.
[0140] Any of the pharmaceutical agents disclosed herein may be
combined with iontophoresis techniques. In addition, certain
cellular elements such as DNA, RNA, BMPs, protein, hormones, fetal
cells, or other cellular elements may be included in a tissue
scaffold or tissue graft which may be implanted and
iontophoretically delivered. The cellular elements may be driven
into tissue, like bone matrix, with or without an implantable
scaffold or graft. The system could be a closed system left inside
the body where electrical energy is used to drive cells, such as
mesenchymal or stem cells, or other therapeutic agents into tissue.
Alternatively, the system may be positioned partially outside the
body with only the electrodes and microenvironment-controlling
devices implanted.
[0141] FIGS. 17A and 17B illustrate an exemplary embodiment of an
iontophoretic system. In FIG. 17A, a device 160 for iontrophoretic
treatment is shown positioned on the surface of a patient's skin
162. As previously described, the iontrophoretic device 160 of the
present invention may be fully or partially implanted for delivery
of therapeutic agents intracorporeally. The device 160, as
illustrated in FIG. 17B, includes a cylindrical body 164 made of a
biocompatible material, such as metal or plastic. Electrical
components such as a microprocessor and power supply are located in
an upper compartment 166, while reservoirs are positioned in a
lower compartment 168 of the body 164. Between the upper and lower
compartments is a pair of iontophoretic electrodes 170, typically
of electrically conductive silicone/carbon material, and which are
separated from each other by a divider baffle. The electrodes 170
are connected to the electrical components. A power recharge port
or reservoir refill port 172 may be located on the cylindrical body
164. Operation of the iontophoretic device 160 may be via a control
station 174 which includes a screen and selector buttons. For an
implantable iontophoretic device, operation may be through RF,
microwave, or IR energy.
[0142] The iontophoretic device of FIGS. 17A and 17B may include
means for controlling all the microenvironment parameters. Also, it
is contemplated that the implants and methods previously disclosed
for controlling the microenvironment of the body region may also
include an iontophoretic drug delivery system.
Dementia
[0143] Microenvironment control may further be used to prevent or
treat dementias. Currently, it is believed that Alzheimer's disease
may be related to decreased temperature and decreased blood flow to
the brain. Existing pharmaceuticals such as Aricept may increase
blood flow slightly. Other studies suggest possible cognitive
function, walking exercises, or reading exercises may improve
overall cognitive function. The present invention provides control
of the microclimate of the brain, specifically vascular flow,
temperature, and other factors such as pH, electrical stimulation,
electromagnetic, etc. This relates to diurnal curve. The
temperature or blood flow would not be constant, but would be
controlled regularly. This could be related to the cortisone levels
in the body or could be a diurnal control where it might be warmest
at certain parts of the day and cooler, but could potentially track
the patient's normal temperature curves, being lowest at 8:00 AM
and highest at 8:00 PM. It could also match serum cortisol levels.
The microenvironment parameters may be changed or given multiple
spikes during the course of the day. Normally, there is not a
constant increase in temperature; rather, it could fluctuate or
vary. Controlling the temperature could also be combined with
physical exercises or cognitive function exercises.
[0144] One objective of microenvironment control is to increase the
temperature/blood flow to the brain. This could be done by
mechanical, electrical, or thermal devices for the head, neck, or
for the carotid vasculature, for example. This may be performed
with 1) electrical control--a heating/cooling unit could be
ultrasound, RF, electromagnetic, fluid controlled, convention or
conduction cooling, etc.; 2) mechanical control--a hat or a
turtleneck neck warmer could be used to warm the blood flow to the
brain, and it could be made of a material which allows
pharmaceuticals to be delivered transcutaneously (Venturi effect);
3) technique control--the location and timing of heating/cooling
units could affect the temperature curves; 4) cognitive
features--an active brain undergoing an activity, learning, study
tools, activity tools, which would also essentially increase
temperature, blood flow, but in combination with the blood flow
curves; and 5) pharmaceutical treatments which would improve
vascular flow, vasodilatation--vasodilators such as nitroglycerin
or transcutaneous medication may be transcutaneously delivered over
the carotid arteries through a Venturi type effect.
[0145] The reverse could also occur in children that may be, for
example, hyperactive or patients that are having seizures. These
conditions may be controlled by performing exactly the opposite:
cooling and decreasing the blood flow selectively, or decreasing
the overall core temperature of the brain or selective locations
with the brain. This could be done externally, internally,
transcutaneously, percutaneously, etc.
[0146] In addition to dementias and hyperactivity, it is
contemplated that other diseases or disorders such as sleep apnea,
hypothermia, and arthritis may be prevented or treated by
controlling the microenvironment parameters.
Body Suit/Worn Items
[0147] FIGS. 18-21 illustrate various, non-limiting, embodiments of
microenvironment-controlling outerwear. A cap 180 is shown in FIG.
18, while a neck scarf 190 is illustrated in FIG. 19. The cap 180
covers the patient's head from the orbital ridge to the base of the
skull medially and from the ventral aspect of the head down
laterally to the base of the skull below the ears. The scarf 190
wraps around the patient's neck. By altering the head/neck
temperature with the cap/scarf, vasoconstriction or vasodilatation
would decrease or increase blood flow. The cap 180/scarf 190
includes a microprocessor 38 and a plurality of sensors 14, magnets
102, and heating/cooling units 18. The sensors 14 may be
temperature sensors, pH sensors, moisture sensors, oxygen sensors,
carbon dioxide sensors, or other sensors to measure
microenvironment characteristics. The heating/cooling units 18 may
be resistive heaters, an ultrasonic heaters, IR heaters, RF
heaters, microwave heaters, or convection/conduction cooling
devices. The magnets 102 may be earth magnets or electromagnets.
The magnets 102 may be used to alter blood flow and increase
circulation. The cap 180 may also include ear cannel inserts to
monitor core temperature and balance the temperature with a
heating/cooling unit in the cap. The sensors 14, heating/cooling
units 18, inserts, and magnets 102 are controlled by the
microprocessor controller, either automatically based on
predetermined measurements or manually via remote control.
[0148] A microenvironment-controlling body suit 200 is shown in
FIG. 20, and a glove 210 is illustrated in FIG. 21. The suit 200
covers the patient's torso, arms, and legs. The glove 210 is
configured to cover the patient's hand and wrist. By altering the
temperature with the suit/glove, vasoconstriction or vasodilatation
would decrease or increase blood flow. The suit 200/glove 210
includes a microprocessor 38 and a plurality of sensors 14, magnets
102, and heating/cooling units 18. The sensors 14 may be
temperature sensors, pH sensors, moisture sensors, oxygen sensors,
carbon dioxide sensors, or other sensors to measure
microenvironment characteristics. The heating/cooling units 18 may
be resistive heaters, an ultrasonic heaters, IR heaters, RF
heaters, microwave heaters, or convection/conduction cooling
devices. The magnets 102 may be earth magnets or electromagnets.
The magnets 102 may be used to alter blood flow and increase
circulation. The sensors 14, heating/cooling units 18, inserts, and
magnets 102 are controlled by the microprocessor controller 38,
either automatically based on predetermined measurements or
manually via remote control.
[0149] Therapeutic Bacteria
[0150] In a related aspect of the invention, bacteria may be used
to control the microenvironment. The previously described
reservoirs associated with microenvironment-controlling devices may
further include bacteria for changing microenvironment parameters.
Alternatively, or additionally, bacteria may be placed in a
mesh-like sac, with or without other therapeutic agents. In an
exemplary embodiment, bacteria which are easily tolerated or
symbiotic with the body, such as normal flora, may be seeded in
tissue to control, for example, the pH level. Some toxic bacteria
which require controlling in the body include staph aureus or
methicillin resistant staph aureus (MRSA). If a patient has an
infection with MRSA, a physician may want to affect the pH level by
varying the level during the course of the day. Implanted bacteria
may also control local blood flow, oxygen tension, and other
microenvironment parameters.
[0151] In another exemplary embodiment, certain types of e-coli may
be very well tolerated by the body, and not toxic, or have been
made less viable. There are also various bacteroides and
bactericides which are well tolerated. These could be used to
displace staph aureus in the right pH environment. Therefore,
physicians could use therapeutic bacteria to fight off dangerous
bacteria. The therapeutic bacteria being normally tolerated by the
body could then be killed off, removed, or if the microclimate
changes the therapeutic bacteria could be eradicated. It is
contemplated that physicians could do the same with other types of
symbiotic organisms, different types of parasites or saprophytes,
as well as different types of viral approaches to fighting off an
infection by seeding the tissue with another infection and
controlling the microenvironment parameters, such as pH level,
oxygen tension, temperature, etc. Once the acute infection or the
more severe infection is resolved then the physician can more
easily manage the local infection.
[0152] To help further describe the use of bacteria to fight
diseases, an analogy is provided with respect to the processing of
sausage. During manufacture, sausage is dry cured giving it a
different smell and different flavor. During this process, bacteria
which produces lactic acid act as a fermenting agent. The bacteria
add to the flavor, but they also have preservative properties. The
acid and other compounds kill off other bacteria that spoil food.
This same principle may be applied to killing off unwanted bacteria
causing caustic infections in the body, as previously described.
The use of bacteria or other targeting substance may be combined
with control of the microenvironment parameters. The bacteria in
sausage are lactobacillus casei. These bacteria are able to
function in very low oxygen tensions, high salt concentrations, and
low oxygen conditions. A physician could induce these conditions
locally to fight off local infections then change the oxygen
tension to ultimately kill off the lactobacillus. Lactobacillus is
a facultative anaerobe and could be delivered transcutaneous,
percutaneously, etc. to the infection site of the patient.
Wicking Agent
[0153] The therapeutic bacteria, or any pharmaceutical agent, may
also place in a reservoir located in a biodegradable screw or
hollow biodegradable object. The implant could have a wicking
action which could wick the bacteria/agent over to another material
such as a scaffold or collagen. Wicking action includes capillary
action, capillarity, or capillary motion. For example, periapatite
or hydroxyapatite could be wicked through or around the exterior
surface of an implant, allowing for an increased distribution area.
The wicking agent may be a porous ceramic, polymer, composite, or
fabric. It may be biodegradable and flexible. In an exemplary
embodiment, a biodegradable porous site may be attached to a
periapatite acetabular shell so BMP, antibiotics, or other agents
may be delivered over the entire surface of the shell by simply
allowing it to wick from a hollow biodegradable implant or
reservoir.
[0154] It is contemplated that the wicking means for delivering a
therapeutic agent may be combined with the other
microenvironment-controlling devices described herein. That is, in
addition to sensors, magnets, reservoirs, and heating/cooling
units, a wicking agent may be used to deliver therapeutic agent to
control the microenvironment. The wicking action may be controlled
automatically by the microprocessor controller of the implant
and/or manually by a physician via remote control or RF, IR,
microwave energy. Wicking control includes methods described
elsewhere herein, and including ports, closable portals,
retractable or movable wicking material, and movable seals.
Implantable Filter
[0155] In another related aspect, the present invention provides
implantable filters and methods of their use. The implantable
filter may be positioned in the body to capture cellular material,
proteins, enzymes, or other body substances. A fistula may be
created between two body parts such as two organs, and a filter may
be positioned in the fistula to gather body substances. For
example, a blood filter may be placed in the vasculature or a side
channel of a blood vessel which selectively traps white cells and
immunoglobulins. The filter may be implanted for a short period of
time, i.e. minutes (during an operation), or could be left in place
for a longer period of time (between surgical procedures). The
filter could be a porous collagen filter, a porous polylactic acid,
a PGA compound, or other known filter material. When sufficient
substance has been captured, the filter may be removed, for example
percutaneously, and re-implanted in infected tissue or where
healthy tissue cells are needed.
[0156] An implantable filter may also be placed in a joint or
synovial site to harvest cartilage cells. The filter may be
connected with a tissue scaffold. The scaffold could be left
floating in the joint, and while the joint moves, cells or slough
from the joint surface may be captured in the filter. These
captured cells could then be implanted into a joint defect or in a
different joint to repair surface defects. The scaffold and cells
may be used in combination with pressed or shaped bone or bone-like
products, such as OP-1. In an exemplary use, the scaffold/cells may
be osteoinductive and/or cartilage inductive to resurface a joint.
In addition, the scaffold/cells may be sculpted or molded in situ
or in the operating room and fastened in place with different types
of thermal bonding agents, adhesives, polysaccharides, etc.
[0157] In another embodiment, the joint filter (and scaffold) may
be affixed to the joint tissue. Movement of the knee joint would
allow cells to populate this membrane to allow healing of cartilage
lesions/biologic resurfacing. Implantation of the joint filter may
be performed with computer navigation and imaging technology. The
joint tissue may be contoured to form fit the scaffold/filter. To
fasten the filter to tissue, it may be tissue welded with
biocompatible temperatures and molded to the surface of the bone
such as with ultrasonic welding. For example, the filter may
conform to the articular surface so that it would have a smooth
contour with the biologic or biodegradable filter or membrane
attached.
[0158] To induce cells into the filter, body movement may be used
to create a hydraulic effect or Venturi effect. Alternatively, or
additionally, the membrane or filter could have a suction type pump
that could be built into it which would create negative pressure,
either constantly or at variable times during the course of the
day. This could be internally or externally controlled. The suction
would deliver or pull cells into the center of the
filter/membrane/matrix to populate cells in a three dimensional
portion of the matrix. The suction could be delivered with a pump,
electrically or electromagnetically. To determine when the filter
has been sufficiently populated, a physician could use ultrasound
energy, density determination, MRI, CT scan, or other similar
volumetric measuring methods.
[0159] An implantable filter may also be placed in bone marrow. As
the bone marrow moves, either naturally or through external
pressure/suction, stem cells could be selectively harvested through
the filter. The filter and cells may be removed from the bone
marrow during the same procedure or during another surgical
procedure. The filter and/or stem cells may then be implanted at
the local tissue site (i.e. heart, brain, spinal cord, or other
organ). In an exemplary embodiment, the filter is percutaneously
implanted in bone marrow of the hip. It could be implanted and
removed during the same procedure or could be left in for a period
of hours or days and then could be removed. The harvested cells
and/or filter could be compressed or shaped and placed into a
defect, such as a damaged heart muscle.
[0160] Cells captured with a filter of the present invention may
also be used in peripheral muscle, cartilage graft, bone graft, or
other implant. The cells and/or filter could further be used on the
surface of joint replacement components.
[0161] In a further exemplary embodiment, a filter may be implanted
in a patient's eye to collect retinal cells. The captured cells may
be harvested from the filter and used to prevent or treat macular
degeneration or another eye tissue injury. The harvested retinal
cells along with the filter may be implant in the eye. In this
configuration, the filter/cells may be used to treat macular
degeneration, where the degeneration may be caused by a chlamydial
infection. To do so, antibiotics, tetracycline, doxycycline, and
other therapeutic agents may be placed on or impregnated in the
filter. The agent(s) may be time released locally to help cool off
the chlamydial infection within the eyeball/retina itself. This
embodiment is particularly beneficial because antibiotics and other
substances do not go through the blood brain barrier and do not get
into the tissue inside the eyeball.
[0162] Various methods of use are contemplated for the cell filters
of the present invention. For example, a fistula may be formed
between an artery and vein, and the filter could be placed in the
fistula to permanently harvest cells. The filter then could have
tubing which could deliver the captured cells to another site in
the body. An implanted filter could be left within bone marrow to
trap cells. Then, through a closed line which could be
subcutaneously implanted to another tissue location, the cells
could be transported to a transplant site while maintaining the
cells viable by body fluid. The simple movement of body parts,
organs, blood movement, etc., would trap these cells in the filter
and move the cells to the recipient site.
[0163] The filters of the present invention may include different
porosity to trap different types of cells. They could have
adhesives such as polysaccharide adhesives, or certain ionic or
covalent attractions for certain types of cells. The filters may
also be coated it with immunoglobulins or other pharmaceuticals or
proteins to attract or bond certain types of white cells, red
cells, or blood marrow elements.
[0164] In a further filter embodiment, an implantable filter may be
positioned in the amniotic membrane, either free floating or
attached to one surface of the membrane. As the fetus is moving,
cells are sloughed off and will be caught by the filter/mesh. The
filter/mesh could then be sent off to cell culture, be stored in a
tissue bank, or be reimplanted in the same patient or another
patient. The captured cells may include, for example,
dedifferentiated stem cells, mesenchymal cells, embryonal cells,
and fetal cells. The fetus would be untouched and would maintain
its viability. The filter may be implanted and removed through an
expandable cannula, under fluoroscopic visualization, or ultrasonic
guidance without damaging the fetus.
[0165] Similarly, a filter of the present invention could be used
to attach or grasp tissue cells on the surface of the heart. If a
person has a heart attack, the victim could lose muscle cells in
one portion of the heart, while another portion of the heart may
remain viable. An implantable filter may be positioned in that
portion of the heart that remains viable. As the heart moves,
certain cardiac cells would be trapped into the filter. The filter
and/or cells could then be removed at the same surgical time or
during another surgical procedure. The cells may be transplanted
into the area where the cardiac cells are dead to induce cardiac
cell formation. These cells could be combined with bone marrow
cells, OP-1, and other tissue inductive factors to enhance
growth.
[0166] All of the above described filters may be placed within or
on the surface of any type of tissue. The porosity, surface area,
and/or contour of filter may be used to entrap or capture cells. To
aid in cell collection, negative pressure, such as a sponge which
would apply slow negative pressure, could be applied to the filter
and surrounding area. A sponge would draw collected cells to the
center of the matrix, progressively populating the entire
matrix.
[0167] FIGS. 22 and 23 illustrate exemplary embodiments of the
filters of the present invention. In FIG. 22 the filter 220 is
generally shaped like a circular parachute or sea anchor, while the
filter 230 of FIG. 23 is generally flat. The filters may include
metallic, ceramic, composite, polymeric, or thermoplastic material.
The filters may include a mesh-like structure and may be flexible
or rigid and biodegradable or biostable. The filters may include
sensors 14, heating/cooling units 18, magnets 102, and an
electronic controller 38. The sensors 14 may be temperature
sensors, pH sensors, moisture sensors, oxygen sensors, carbon
dioxide sensors, or other sensors to measure microenvironment
characteristics. The heating/cooling units 18 may be resistive
heaters, an ultrasonic heaters, IR heaters, RF heaters, microwave
heaters, or convection/conduction cooling devices. The magnets 102
may be earth magnets or electromagnets. The sensors 14,
heating/cooling units 18, and magnets 102 are controlled by the
electronic controller 38, either automatically based on
predetermined measurements or manually via remote control. Manual
control on the implanted electronic processor may be achieved
through IR, RF, or microwave energy or through an implanted
wire.
[0168] The filters 220/230 may also include port holes 16, a
reservoir(s) 40, a reservoir controller 42, and a suction means,
such as an electric or manual pump. The port hole 16 may be in
fluid communication with the reservoir 40 by way of piping. The
port hole 16 and reservoir 40 are configured for delivering a
liquid, gas, gel, and/or solid to affect the microenvironment of
the region. The substance(s) administered through the delivery
ports may be any of the substances disclosed herein, including
bacteria. The reservoir controller 42 manipulates the release rate
and release period of the substance(s) in the reservoir. The
reservoir controller 42 and electronic processor 40 may be linked
together to function as a single system. That is, the reservoir
controller and electronic processor work together to control the
microenvironment of the body region. Alternatively, the reservoir
controller and electronic processor may be physically integrated
into one assembly.
[0169] A port hole 16 may instead, or in addition to, be connected
to the suction means. The suction at the port hole 16 would create
a negative pressure (Venturi effect) on the surrounding tissue. The
suction would increase the capture rate of cells. The negative
pressure may also aid in the delivery and/or concentration of
pharmaceutical substances.
[0170] Methods of using the filters 220/230 of the present
invention have been previously illustrated. That is, the filters
may be implanted in the vasculature, bone marrow, fistula, organ,
etc. to collect desired cells and other body substances. The filter
230 of FIG. 23 is particularly applicable to muscle, joint, organ,
or bone repair as previously described. The filter 230 may be
contoured or shape to form to the surface of tissue. With the
filters implanted, the microclimate may be controlled to create an
optimal cell/substance capturing climate. For example, a sensor 14
may measure a microenvironment parameter and based on predetermined
levels, the electronic processor 38 may instruct the reservoir
controller to release a substance from the reservoir. The
electronic processor 38 may also instruct a heating/cooling unit 18
to change the temperature of the body region and/or instruct the
magnets 102 to energize thereby drawing charged particles to the
conduit wall. Controlling the microenvironment may be performed
automatically by microprocessors based on preset parameter levels
and input signals from the sensors. The microenvironment may
alternatively, or additionally, be controlled by a physician via
remote control. The physician may use RF, microwave, or IR energy
to transmit instructions to the microprocessors in the implant.
Aerosol Delivery
[0171] In another related invention, therapeutic and pharmaceutical
agents may be delivered to body tissue in a pulsed, atomized
manner. The following description of a pharmaceutical agent
distribution system may be used in combination with and/or
integrated with the microenvironment-controlling apparatus and
methods described herein. Generally, during the course of medical
treatment, medicaments are administered to patients before, during,
and after surgery. In many medical situations it is necessary or
desirable to administer small amounts of medicaments and other
pharmaceutical agents to a patient over a relatively long period of
time.
[0172] For example, heparin is administered to a patient in need
thereof by an intravenous "drip" procedure. Other medicines which
may be administered through the "drip" process include
antiarrhythmics, vitamins, hormones, corticosteroids, anesthetics
and antibiotics. These medicines may be administered intermittently
by bolus injection or continuously by gravity dispensers. Bolus
injections may not, however, match the patient's actual
requirements and may subject the patient to larger dosages of drugs
than required as well as frequent needle insertion. Drug delivery
through gravity dispensers may limit the patient's lifestyle by
tethering the patient to the intravenous drip apparatus.
Furthermore, the dispensing rate is not always constant.
[0173] Rather than relying on the manual injection of bolus doses
of drugs using syringes or on manually setting the drip rate of
gravity-fed intravenous infusion sets, health professionals are
utilizing infusion devices that electronically or mechanically
control the infusion rate of drugs as they are being administered
to patients. Infusion pumps may include compact pump housings or
larger stationary pump housing units. The administration of
prescribed drugs has been accomplished through infusion tubing and
an associated catheter or the like, thereby introducing the drug
intravenously. Pain, tissue damage and post-op complications have
long been tolerated as negative side effects from the use of
existing hypodermic drug delivery infusion systems. The pain and
tissue damage are a direct result of uncontrolled flow rate in
conjunction with excessive pressures created during the
administration of drug solutions within the tissue spaces. Also, it
has been demonstrated that particular pressures for a specific
tissue type will cause damage. It is therefore critical that a
specific flow rate in conjunction with a specified pressure range
be maintained during the delivery of fluids (drugs) when a
subcutaneous injection is given preventing pain response as well as
tissue damage.
[0174] The most common application of infusion devices is for the
maintenance of appropriate fluid levels in patients. Fluid therapy
is commonly used in the treatment of burns, the pre- and
postoperative management of surgical patients and in the treatment
of dehydration. The administration of drugs provides the greatest
challenge to infusion devices. For a drug to be effective, the
concentration of any drug at its site of action must be
sufficiently high for the drug to be effective, yet the
concentration must not be too high for the drug to become toxic to
the patient.
[0175] Used in applications such as delivering anesthetics during
surgery, chemotherapy for cancer, and oxytocic agents for inducing
labor, continuous drug infusion reduces the fluctuations in a
drug's concentration that occurs with the more traditional modes of
drug administration such as injections and pills. Moreover,
continuous drug infusion assures a continuous therapeutic action as
long as the infusion rate is appropriate.
[0176] In contrast to continuous drug infusion pumps, some infusion
pumps deliver drugs providing intermittent, episodic or limited
drug delivery. An intermittent infusion pump is used to
automatically administer a desired amount of liquid medicant to a
patient. The liquid medicant is supplied from a reservoir and
pumped into the patient via a catheter or other injection device.
The manner in which the liquid is infused is controlled by the
infusion pump controller, which may have various modes of infusion,
such as a periodic release of medicine or a ramp mode in which the
rate of infusion gradually increases, then remains constant, and
then gradually decreases.
[0177] Additionally, many types of medications can be administered
to a patient via the respiratory tract. Delivery of drugs to the
lungs by way of inhalation is an important means of treating a
variety of conditions, including such common local conditions as
cystic fibrosis, pneumonia, bronchial asthma and chronic
obstructive pulmonary disease and some systemic conditions,
including hormone replacement, pain management, immune deficiency,
erythropoiesis, diabetes, etc. Steroids, beta agonists,
anti-cholinergic agents, proteins and polypeptides are among the
drugs that are administered to the lungs for such purposes. Such
drugs are commonly administered to the lung in the form of an
aerosol of particles of respirable size (less than about 10 .mu.m
in diameter). The aerosol formulation can be presented as a liquid
or a dry powder. In order to assure proper particle size in a
liquid aerosol, particles can be prepared in respirable size and
then incorporated into a colloidial dispersion either containing a
propellant as a metered dose inhaler (MDI) or air, such as in the
case of a dry powder inhaler (DPI). For MDI application, an aerosol
formulation is placed into an aerosol canister equipped with a
metered dose valve. In the hands of the patient the formulation is
dispensed via an actuator adapted to direct the dose from the valve
to the patient.
[0178] Delivery of medication via the respiratory tract may be
preferred in many circumstances because medication delivered this
way enters the bloodstream very rapidly. Delivery of medication to
the lungs may also be preferred when the medication is used in a
treatment of a disease or condition affecting the lungs in order to
apply or target the medication as close as physically possible to
the diseased area.
[0179] Aerosol delivery of a medication to a patient's respiratory
tract also may be performed while the patient is intubated, i.e.
when an endotracheal tube is positioned in the patient's trachea to
assist in breathing. When an endotracheal tube is positioned in a
patient, a proximal end of the endotracheal tube may be connected
to a mechanical ventilator and the distal end is located in the
trachea. An aerosol may be added to the airflow in the ventilator
circuit of the endotracheal tube and carried by the patient's
inhalation to the lungs. A significant amount of the aerosolized
medication may be deposited inside the endotracheal tube and the
delivery rate of the medicine to the lungs also remains relatively
low and unpredictable.
[0180] Another use of an insufflator is to inflate a body cavity,
like the abdominal cavity. Insufflation of the cavity is necessary
to provide a working space for a surgeon to examine the contents of
the cavity or operate within the cavity. Insufflating the abdominal
cavity with gas, normally carbon dioxide, elevates the abdominal
wall and pushes the contents of the region, such as the bowel and
the liver, away from the areas of the cavity requiring the
surgeon's attention. Various gas insufflators for use in the
operating room are known. These insufflators infuse between 4 and 6
liters of carbon dioxide into the abdomen, creating a distention
pressure of 15 mmHg (0.33 psi).
[0181] The carbon dioxide for an operating room insufflation unit
is supplied by large pressurized tanks Flow rate and pressure may
be regulated by controls located on the insufflator units, and
monitors located on the units display gas flow rate, gas pressure,
and the total infusion volume. For use in a doctor's office or
emergency room, it is desirable to have a compact hand-held
insufflation unit. Such a simplified unit would provide an adequate
volume of insufflation gas without the risk of over
insufflation.
[0182] In addition to delivering medication via gravity-fed
intravenous infusion, infusion pumps, inhalation, and insufflation,
a drug may be delivered subcutaneously by way of an aerosolized or
atomized medicament. Generally, a physician may insert a delivery
tube within an incision or body cavity of a patient to administer
the drug to the surface area of the body cavity.
[0183] As described above, there are a variety of means to
administer medicaments to a patient. That is, therapeutic agents
can be delivered intravenously, subcutaneously, or respiratorily.
However, the distribution system of the present invention provides
an apparatus and method of delivering pharmaceutical agents
percutaneously to a desired location while providing thorough
dispersion of the medicament over a large surface area.
[0184] FIG. 24 illustrates an exemplary embodiment of a drug
distribution system 240 of the present invention. The system 240
includes an aerosol canister 242 with a medicament, a control unit
244, and interconnecting tubing 246. The canister 242 may be
pressurized with a gas/medicament combination. The gas may be
carbon dioxide, nitrogen, oxygen, or other biocompatible gas. The
medicament or agent may be a gas, liquid, power, solid,
particulate, granule, crystal, or gel. An example of a
therapeutic/pharmaceutical agent includes a hemostatic agent,
antibiotic, bone morphogenic protein, chemotherapeutic agent,
anesthetic agent, agent that changes neovascularity, proteins,
immunoglobulin, steroids, anti-inflammatory agent, angiogenesis
factors, lidocaine, eqinephrine, ethrane, halofane, nitrous oxide,
carbon dioxide, nitrogen, oxygen, opiates like OxyContin, morphine,
Demerol, any agent described herein, and combinations thereof
[0185] The control unit 244 may include a microprocessor and/or
switches for controlling the release of the medicament. The
microprocessor may automatically deliver the agent(s) within the
body, while the switches allow an operator to administer agent(s)
manually. The control unit 244 may control how the medicament is
administered. That is, the medicament may be delivered in pulses,
bursts, high pressure, low pressure, spray, stream, aerosolized,
atomized, or combinations thereof. How the medicament is delivered
determines the amount of tissue surface area that is covered by the
agent. For example, stream burst delivery would cover a small
target site, while a spray burst aerosolized delivery would cover a
greater tissue area. The control unit may be remote controlled via
a wire or RF, IR, optical, or microwave energy. The control unit
may be operated by a physician, technician, and/or patient. The
control unit may be time controlled for continuous or period drug
delivery.
[0186] The interconnecting tubing 246 of the drug delivery system
may be made of polymeric, metallic, composite, or ceramic material.
The tubing 246 may be biodegradable, biostable, and/or expandable.
Multi-lumen tubing may be used for delivery of two or more agents.
The distal tip of the delivery tube may include a needle (steerable
or curved), omni-directional ports, and an atomizing/dispersing
tip.
[0187] Referring now to FIG. 25, a multi-medicament delivery system
250 is shown. The system includes a gas container 252, a control
unit 244, two or more drug reservoirs 254, and connecting tubing
246. The container 252 includes a gas with or without a medicament.
The gas may be any of the gaseous substances disclosed herein. The
control unit 244 may include all or some of the characteristics of
the control unit of FIG. 25. The drug reservoirs 254 may be
refillable and include any of the therapeutic or pharmaceutical
agents described herein. The tubing includes a plurality of lumens
256 for delivery of the plurality of agents.
Tissue Distraction
[0188] FIGS. 26 and 27 illustrate tissue distraction systems for
use with the drug delivery systems of the present invention. The
distraction system 260 of FIG. 26 includes a multi-channel
catheter/cannula 262, an expandable balloon 264, a balloon
inflation tube 266, and a drug delivery tube 268. In use, the
system 260 is inserted in tissue adjacent a body region 272 which
require the administration of one or more medicaments. During
insertion, the balloon 264 is deflated to minimize tissue
displacement. Once positioned, the balloon 264 is inflated to
distract tissue. The distal end of the drug delivery tube 268 is
positioned proximal from the balloon 264 such that medicament may
be administered to tissue located proximal to the balloon 264.
[0189] The distraction drug delivery system 270 of FIG. 27 is
similar to the system of the FIG. 26 and includes similar
structural features. In use, the system 270 is inserted in tissue
adjacent a body region 272 which requires the administration of one
or more medicaments. During insertion, the balloon 264 is deflated
to minimize tissue displacement. Once positioned, the balloon 264
is inflated to distract tissue. The distal end of the drug delivery
tube 268 is positioned distal from the balloon 264 such that
medicament may be administered to tissue located distal to the
balloon 264. The systems 260/270 of FIGS. 26 and 27 allow
therapeutic and pharmaceutical agents to be delivered to a greater
tissue surface area since the tissue is spaced apart by the
inflated balloon.
Dispersion
[0190] FIGS. 28A and 28B illustrate a drug dispersion member 280
for administering one or more medicaments to the surface of tissue.
The dispersion member 280 includes porous material 284 for allowing
medicaments to flow therethrough. The member 280 may be made of
foam, fabric, polymer, metal, ceramic, composite, or combinations
thereof. It may be biodegradable or biostable. The dispersion
member 280 may include a channel 286 dimensioned for receiving a
delivery tube 288 of a drug delivery system previously described.
In FIG. 28B, the member 280 is implanted in tissue 282 such that
the outer surface of the member contacts the tissue surface. The
delivery tube 288 is inserted in the channel 286 of the member 280.
The tube 288 may include microenvironment-controlling devices, such
as sensors 14, magnets 102, heating/cooling units 18, drug ports
16, and pressure ports 16. With the tube positioned, one or more
medicaments may be expelled from the tube 288 and captured by the
porous material 284 of the disbursement member 280. The member and
its pores function as a wick to carry the agent(s) to the adjacent
tissue. The microenvironment of the adjacent tissue may be
measured, changed, and monitored by the dispersion member.
Internal Aerosol Delivery
[0191] The embodiments shown in FIGS. 24 and 25 were configured for
external drug administration. However, in FIGS. 29A and 29B,
implantable delivery systems are illustrated. The implantable
systems include similar structural elements as the systems of FIGS.
24 and 25. In FIG. 29A, the control unit/reservoir 38/42,
microenvironment-controlling devices, and tubing are implanted in
the patient 294. A refill port 292 is positioned in the skin and is
connected to the internal tubing. The medicament/gas canister 298
is connected to the refill port 292 for recharging the internal
reservoir 40. The embodiment of FIG. 29B is completely implanted.
The canister 298 along with the other components is positioned in
the patient. The control unit 38 of the system may be operated with
a remote 296 via RF, IR, optical, or microwave energy. The
microenvironment of internal body tissue may be measured, changed,
and monitored by the implantable delivery systems.
Generator Joint
[0192] In a related invention, a generator joint 300 is illustrated
in FIGS. 30A and 30B. A replacement component or total joint
replacement implant 302 may include magnets 304 and winding 306 for
generating electrical current. The joint may be the knee, shoulder,
hip, spine, elbow, wrist, ankle, or a joint of the foot or hand.
The electrical current may be used to power any of the
microenvironment-controlling systems described herein or to power
any other implant. In an exemplary embodiment, a total knee
replacement implant 302 is shown. The implant components include
magnets 304, windings 306, and electrical wires. As the knee is
moved or rotated naturally, the relative movement of the magnets
and windings create an electrical current. This current may be
utilized to power sensors, heating/cooling units, electromagnets,
drug pumps, or any other microenvironment-controlling device.
Fuel Cell
[0193] In a further related invention, a fuel cell may be used to
power the microenvironment-controlling apparatus of the present
invention. Fuel cells generate electricity by combining hydrogen
with oxygen. In an exemplary embodiment, the fuel cell runs on
alcohol such as methanol. The power source for the devices of the
present invention may also be a hybrid of battery power and a fuel
cell.
[0194] Heat Probe
[0195] FIGS. 31 and 32 depict a needle shaped device 400,402 for
microclimate heating in the body. Wires 404,406 convey electrical
energy to a heater at the needle tip. In needle 402, a single wire
410 provides power in combination with a chassis ground 412,
enabling the needle to have a more narrow diameter. Needles 400,402
may be combined with systems described herein, where it is
advantageous to control temperature. Wires 404,406, and 410 are
controllable by a system microcontroller, as described above.
Magnetic Heating
[0196] FIGS. 33 and 34 illustrate a method of heating magnetic
material implanted proximate the site for which microclimate
control is desired. FIG. 3 illustrates a sinusoidal waveform
representative of the change in magnetic pull. By rapidly changing
the poles, indicate as N north and S south, magnetic particles
within the body are excited and thus generate heat. Circuit 414 is
illustrative of a means for such rapid polar changing, under
microprocessor 416 control. As can be seen in FIG. 35, a circuit
415 may be used to precisely monitor the temperature generated,
incorporating thermocouple 418.
[0197] It may be advantageous to coordinate or correlate magnetic
pulses with the heart rate, for improved efficacy of a therapeutic
substance delivered as described above. With reference to FIG. 36,
a circuit 440 is shown, with a heart rate monitor 442, magnetic
field output 444, microprocessor 446, real time clock 448 for
microprocessor control and power saving, and a serial interface 450
for downloading a delivery profile. FIG. 37 illustrates a
corresponding signal profile, with trace 460 indicating the heart
beat, and trace 462 indicating the programmed delivery profile
correlated therewith.
Energy Delivery
[0198] With reference to FIG. 38, a circuit 470 is illustrated,
operative to transmit radio frequency (RF) energy. Illustrated are
frequency generator 472, pre-amplifier 474, frequency multiplier
476, power amplifiers 480, and output antenna 482. In this
application, an implant (not shown) has an antenna that would
receive the energy transmitted at 482 to power the implant, and or
to directly warm the tissue proximate the implant.
[0199] FIG. 39 illustrates and ultrasonic generator circuit having
components analogous to FIG. 38, with the inclusion of a feedback
loop 492 operative to create a phase lock loop signal. Feedback
mechanisms may be based on constant phase, mm impedance or other
methods.
[0200] FIG. 40 illustrates a resistive heater circuit 500 including
a microprocessor/microcontroller 502 and heating element 504.
[0201] It is contemplated the microenvironment-controlling systems
of the present invention may be used with and integrated with the
methods and devices disclosed in U.S. Provisional Application No.
60/765,857 entitled "Surgical Fixation Device" filed on Feb. 7,
2006. In the '857 document, various thermoplastic fixation devices
are disclosed. The fixation devices may be, but are not limited to,
degradable, biodegradable, bioerodible, bioabsorbable, mechanically
expandable, hydrophilic, bendable, deformable, malleable, riveting,
threaded, toggling, barded, bubbled, laminated, coated, blocking,
pneumatic, one-piece, multi-component, solid, hollow,
polygon-shaped, pointed, self-introducing, and combinations
thereof. Also, the devices may include, but are not limited to,
metallic material, polymeric material, ceramic material, composite
material, body tissue, synthetic tissue, hydrophilic material,
expandable material, compressible material, heat bondable material,
and combinations thereof.
[0202] The methods and devices disclosed in the '857 document may
be used in conjunction with any surgical procedure of the body. The
fastening and repair of tissue or an implant may be performed in
connection with surgery of a joint, bone, muscle, ligament, tendon,
cartilage, capsule, organ, skin, nerve, vessel, or other body
parts. For example, tissue may be repaired during intervertebral
disc surgery, knee surgery, hip surgery, organ transplant surgery,
bariatric surgery, spinal surgery, anterior cruciate ligament (ACL)
surgery, tendon-ligament surgery, rotator cuff surgery, capsule
repair surgery, fractured bone surgery, pelvic fracture surgery,
avulsion fragment surgery, shoulder surgery, hernia repair surgery,
and surgery of an intrasubstance ligament tear, annulus fibrosis,
fascia lata, flexor tendons, etc.
[0203] It is contemplated that the devices and methods of the
present invention be applied using minimally invasive incisions and
techniques to fasten muscles, tendons, ligaments, bones, nerves,
and blood vessels. A small incision(s) may be made adjacent the
damaged tissue area to be repaired, and a tube, delivery catheter,
sheath, cannula, or expandable cannula may be used to perform the
methods of the present invention. U.S. Pat. No. 5,320,611 entitled
"Expandable Cannula Having Longitudinal Wire and Method of Use"
discloses cannulas for surgical and medical use expandable along
their entire lengths. The cannulas are inserted through tissue when
in an unexpanded condition and with a small diameter. The cannulas
are then expanded radially outwardly to give a full-size instrument
passage. Expansion of the cannulas occurs against the viscoelastic
resistance of the surrounding tissue. The expandable cannulas do
not require a full depth incision, or at most require only a
needle-size entrance opening.
[0204] U.S. Pat. Nos. 5,674,240; 5,961,499; and 6,338,730 also
disclose cannulas for surgical and medical use expandable along
their lengths. The cannula can be provided with a pointed end
portion and can include wires having cores which are enclosed by
jackets. The jackets are integrally formed as one piece with a
sheath of the cannula. The cannula may be expanded by inserting
members or by fluid pressure. An expandable chamber may be provided
at the distal end of the cannula. The above mentioned patents are
hereby incorporated by reference.
[0205] In addition to using a cannula with the present invention,
an introducer may be utilized to position implants at a specific
location within the body. U.S. Pat. No. 5,948,002 entitled
"Apparatus and Method for Use in Positioning a Suture Anchor"
discloses devices for controlling the placement depth of a
fastener. Also, U.S. patent application Ser. No. 10/102,413
discloses methods of securing body tissue with a robotic mechanism.
The above-mentioned patent and application are hereby incorporated
by reference. Another introducer or cannula which may be used with
the present invention is the VersaStep.RTM. System by Tyco.RTM.
Healthcare.
[0206] The present invention may also be utilized with minimally
invasive surgery techniques disclosed in U.S. Pat. Nos. 6,702,821;
6,770,078; and 7,104,996. These patent documents disclose, inter
alia, apparatus and methods for minimally invasive joint
replacement. The femoral, tibial, and/or patellar components of a
knee replacement may be fastened or locked to each other and to
adjacent tissue using fixation devices disclosed herein and
incorporated by reference. Furthermore, the methods and devices of
the present invention may be utilized for repairing,
reconstructing, augmenting, and securing tissue or implants during
and "on the way out" of a knee replacement procedure. For example,
the anterior cruciate ligament and other ligaments may be repaired
or reconstructed; quadriceps mechanisms and other muscles may be
repaired; a damaged rotator cuff may be mended. The patent
documents mentioned above are hereby incorporated by reference.
[0207] It is further contemplated that the present invention may be
used in conjunction with the devices and methods disclosed in U.S.
Pat. No. 5,329,846 entitled "Tissue Press and System" and U.S. Pat.
No. 5,269,785 entitled "Apparatus and Method for Tissue Removal."
For example, an implant of the present invention may include tissue
harvested, configured, and implanted as described in the patents.
The above-mentioned patents are hereby incorporated by
reference.
[0208] Additionally, it is contemplated that the devices and
methods of the present invention may be used with heat bondable
materials as disclosed in U.S. Pat. No. 5,593,425 entitled
"Surgical Devices Assembled Using Heat Bondable Materials." For
example, the implants of the present invention may include
thermoplastic material. The material may be deformed to secure
tissue or hold a suture or cable. The fasteners made of heat
bondable material may be mechanically crimped, plastically crimped,
or may be welded to a suture or cable with RF (Bovie devices),
laser, ultrasound, electromagnet, ultraviolet, infrared,
electro-shockwave, or other known energy. The welding may be
performed in an aqueous, dry, or moist environment. The welding
device may be disposable, sterilizable, single-use, and/or
battery-operated. The above-mentioned patent is hereby incorporated
by reference.
[0209] Furthermore, the methods of the present invention may be
performed under indirect visualization, such as endoscopic
guidance, computer assisted navigation, magnetic resonance imaging,
CT scan, ultrasound, fluoroscopy, X-ray, or other suitable
visualization technique. The implants of the present invention may
include a radiopaque material for enhancing indirect visualization.
The use of these visualization means along with minimally invasive
surgery techniques permits physicians to accurately and rapidly
repair, reconstruct, augment, and secure tissue or an implant
within the body. U.S. Pat. Nos. 5,329,924; 5,349,956; and 5,542,423
disclose apparatus and methods for use in medical imaging. Also,
the present invention may be performed using robotics, such as
haptic arms or similar apparatus. The above-mentioned patents are
hereby incorporated by reference.
[0210] All references cited herein are expressly incorporated by
reference in their entirety.
[0211] It will be appreciated by persons skilled in the art that
the present invention is not limited to what has been particularly
shown and described herein above. In addition, unless mention was
made above to the contrary, it should be noted that all of the
accompanying drawings are not to scale. A variety of modifications
and variations are possible in light of the above teachings without
departing from the scope and spirit of the invention.
* * * * *