U.S. patent application number 14/478218 was filed with the patent office on 2016-03-10 for systems, methods, and devices addressing the gastro-intestinal tract.
This patent application is currently assigned to Elwha LLC, a limited company of the State of Delaware. The applicant listed for this patent is Elwha LLC. Invention is credited to Roderick A. Hyde, Tony S. Pan, Dennis J. Rivet.
Application Number | 20160067466 14/478218 |
Document ID | / |
Family ID | 55436370 |
Filed Date | 2016-03-10 |
United States Patent
Application |
20160067466 |
Kind Code |
A1 |
Hyde; Roderick A. ; et
al. |
March 10, 2016 |
SYSTEMS, METHODS, AND DEVICES ADDRESSING THE GASTRO-INTESTINAL
TRACT
Abstract
Various embodiments disclosed herein relate to an implantable
device, systems, and methods related thereto, that includes at
least one sensor and/or therapeutic agent delivery depot. In one
embodiment, the system and device include means for detecting
general or specific biological agents in a subject's intestinal
tract, and utilizing the information from the detection for
determining the timing and content of any therapeutic treatment
needed by the subject.
Inventors: |
Hyde; Roderick A.; (Redmond,
WA) ; Pan; Tony S.; (Bellevue, WA) ; Rivet;
Dennis J.; (Chesapeake, VA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Elwha LLC |
Bellevue |
WA |
US |
|
|
Assignee: |
Elwha LLC, a limited company of the
State of Delaware
|
Family ID: |
55436370 |
Appl. No.: |
14/478218 |
Filed: |
September 5, 2014 |
Current U.S.
Class: |
600/301 ;
600/300; 604/65; 604/66; 604/95.01; 604/99.01 |
Current CPC
Class: |
A61B 5/14539 20130101;
A61B 5/686 20130101; A61B 5/1076 20130101; A61B 8/12 20130101; A61B
5/14503 20130101; A61M 31/002 20130101; A61B 5/1107 20130101; A61B
5/14507 20130101; A61B 8/488 20130101; A61B 5/4255 20130101; A61B
5/073 20130101; A61B 5/4839 20130101; A61B 5/6887 20130101; A61B
5/6853 20130101; A61B 5/036 20130101; A61B 5/01 20130101 |
International
Class: |
A61M 31/00 20060101
A61M031/00; A61B 5/00 20060101 A61B005/00 |
Claims
1. A device, comprising: at least one reversibly inflatable bladder
less than or approximately equal to 10 mm in size; at least one
depot including one or more therapeutic or nutraceutical agent
reservoirs; and at least one activatable switch operably coupled to
at least one actuator configured to deflate the reversibly
inflatable bladder upon activation of the switch.
2. (canceled)
3. The device of claim 1, wherein the reversibly inflatable bladder
is exterior to the depot.
4. The device of claim 1, wherein the reversibly inflatable bladder
is configured, when at least partially inflated, to secure the
device within a lumen of the gastro-intestinal tract of a subject's
body.
5. The device of claim 1, further including at least one
sensor.
6.-7. (canceled)
8. The device of claim 1, wherein the one or more therapeutic or
nutraceutical agent reservoirs include at least one valve.
9. The device of claim 8, wherein the at least one valve is
operably coupled to control circuitry and configured to dispense at
least one therapeutic or nutraceutical agent from the one or more
therapeutic or nutraceutical agent reservoirs.
10. The device of claim 1, wherein each therapeutic or
nutraceutical agent reservoir includes a different agent than at
least one other agent reservoir.
11. The device of claim 1, wherein each therapeutic or
nutraceutical agent reservoir includes a different agent than any
other agent reservoir.
12. The device of claim 11, wherein the one or more therapeutic or
nutraceutical agent reservoirs include control circuitry directed
by at least one of a timer, external command, continuous flow, or
signal from at least one sensor.
13. The device of claim 12, wherein the at least one sensor
includes a sensor internal to the device.
14. The device of claim 12, wherein the at least one sensor
includes a sensor external to the device.
15.-18. (canceled)
19. The device of claim 1, further including control circuitry
operably coupled to at least one of component of the device.
20. The device of claim 19, wherein at least one component of the
device includes at least one of the depot, actuator, reservoir,
switch, sensor, light source, power source, or pump.
21. The device of claim 1, wherein the device is configured for at
least one of insertion into a subject's body or removal therefrom
by way of a catheter.
22. (canceled)
23. The device of claim 1, wherein the device is configured for
insertion into a subject's body by way of self-propulsion.
24. The device of claim 23, wherein the device includes at least
one fin, mobile leg, or revolving belt for self-propulsion.
25. The device of claim 1, further including at least one drainage
channel continuous with the outer surface of the device.
26. (canceled)
27. The device of claim 1, further including at least one drainage
channel comprising an interior lumen of the device.
28.-29. (canceled)
30. The device of claim 1, further including at least one outer
membrane enclosing the reversibly inflatable bladder.
31. The device of claim 1, wherein the reversibly inflatable
bladder is insertable in a collapsed state, and inflated subsequent
to insertion into a subject's body.
32.-34. (canceled)
35. The device of claim 1, further including at least one receiver,
transmitter, or transceiver.
36.-40. (canceled)
41. The device of claim 1, wherein at least one agent reservoir of
the depot is refillable.
42. The device of claim 41, wherein the at least one refillable
agent reservoir of the depot includes at least one inlet for refill
of at least one agent by way of catheter, capsule, or pill.
43. The device of claim 1, further including at least one
intestinal wall-attachment component.
44. The device of claim 43, wherein the intestinal wall-attachment
component includes at least one of mechanical or chemical means for
attachment to the intestinal wall of a subject.
45. The device of claim 43, wherein the intestinal wall-attachment
component includes at least one of a screw, suture, staple, clip,
anchor, hook, brace, reversibly inflatable bladder, projection,
umbrella connector, barb, latch, or adhesive.
46. The device of claim 1, further including at least one power
source.
47. The device of claim 1, further including at least one light
source.
48. The device of claim 1, further including a port configured for
inflating the reversibly inflatable bladder.
49. The device of claim 1, further including at least one rigid or
semi-rigid frame.
50. The device of claim 49, wherein the rigid or semi-rigid frame
includes at least one collapsible joint.
51. The device of claim 50, wherein the at least one collapsible
joint is operably coupled to control circuitry.
52. The device of claim 50, wherein the at least one collapsible
joint is operably coupled to at least one receiver.
53. The device of claim 50, wherein the at least one collapsible
joint is operably coupled to at least one transmitter.
54. A system, comprising: a device including at least one
reversibly inflatable bladder less than or approximately equal to
10 mm in size; at least one depot including one or more therapeutic
or nutraceutical agent reservoirs; at least one activatable switch
operably coupled to at least one actuator configured to deflate the
reversibly inflatable bladder upon activation of the switch; and in
operable communication with at least one computing device.
55. The system of claim 54, further including at least one
sensor.
56. The system of claim 54, wherein the at least one sensor
includes a sensor external to the device.
57. The system of claim 54, wherein the at least one sensor is
located in a second section of the gastro-intestinal tract of a
subject's body.
58. The system of claim 54, wherein the at least one sensor is
located in the subject's body outside of the gastro-intestinal
tract.
59. The system of claim 54, wherein the at least one sensor is
located in a room where the subject is also located.
60. A method, comprising: inserting at least one device into the
gastro-intestinal tract of a subject, the device including at least
one sensor configured to sense at least one biochemical or
biophysical parameter of the subject and at least one actuator
operably coupled to at least one depot including one or more
therapeutic or nutraceutical agents; sensing at least one
biochemical or biophysical parameter of the subject; responsive to
sensing the at least one biochemical or biophysical parameter of
the subject, actuating at least one actuator operably coupled to
the at least one depot for release of one or more therapeutic or
nutraceutical agents when a threshold has been satisfied.
Description
[0001] If an Application Data Sheet (ADS) has been filed on the
filing date of this application, it is incorporated by reference
herein. Any applications claimed on the ADS for priority under 35
U.S.C. .sctn..sctn.119, 120, 121, or 365(c), and any and all
parent, grandparent, great-grandparent, etc. applications of such
applications, are also incorporated by reference, including any
priority claims made in those applications and any material
incorporated by reference, to the extent such subject matter is not
inconsistent herewith.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0002] The present application claims the benefit of the earliest
available effective filing date(s) from the following listed
application(s) (the "Priority Applications"), if any, listed below
(e.g., claims earliest available priority dates for other than
provisional patent applications or claims benefits under 35 USC
.sctn.119(e) for provisional patent applications, for any and all
parent, grandparent, great-grandparent, etc. applications of the
Priority Application(s)).
PRIORITY APPLICATIONS
[0003] None.
[0004] If the listings of applications provided above are
inconsistent with the listings provided via an ADS, it is the
intent of the Applicant to claim priority to each application that
appears in the Domestic Benefit/National Stage Information section
of the ADS and to each application that appears in the Priority
Applications section of this application.
[0005] All subject matter of the Priority Applications and of any
and all applications related to the Priority Applications by
priority claims (directly or indirectly), including any priority
claims made and subject matter incorporated by reference therein as
of the filing date of the instant application, is incorporated
herein by reference to the extent such subject matter is not
inconsistent herewith.
SUMMARY
[0006] Various embodiments disclosed herein relate to systems,
methods, and devices including a semi-permanently mounted device
with one or more sensors and/or at least one therapeutic agent
release depot. In an embodiment, the device is mounted in the
gastro-intestinal (GI) tract of a subject. In an embodiment, the
device is mounted in the appendix of a subject.
[0007] The foregoing summary is illustrative only and is not
intended to be in any way limiting. In addition to the illustrative
aspects, embodiments, and features described above, further
aspects, embodiments, and features will become apparent by
reference to the drawings and the following detailed
description.
BRIEF DESCRIPTION OF THE FIGURES
[0008] FIG. 1 shows a partial view of an embodiment of a
tubular-like device described herein.
[0009] FIG. 2 shows a partial view of an embodiment of a cage-like
structured device described herein.
[0010] FIG. 3 shows a partial view of an embodiment of an
umbrella-like structured device described herein.
[0011] FIG. 4 shows a partial view of an embodiment of a tent-like
structured device described herein.
[0012] FIG. 5 shows a partial view of an embodiment of a coiled
structured device described herein.
[0013] FIG. 6A shows a bottom view of an embodiment of a reversibly
inflatable bladder device as described herein.
[0014] FIG. 6B shows a bottom view of an embodiment of a reversibly
inflatable bladder device as described herein.
[0015] FIG. 6C shows a bottom view of an embodiment of a reversibly
inflatable bladder device as described herein.
[0016] FIG. 6D shows a bottom view of an embodiment of a reversibly
inflatable bladder device as described herein.
[0017] FIG. 7 shows a partial view of an embodiment of a tent-like
device described herein.
[0018] FIG. 8A shows a side view of an embodiment of a reversibly
inflatable bladder device described herein.
[0019] FIG. 8B shows a side view of an embodiment of a reversibly
inflatable bladder device described herein.
[0020] FIG. 8C shows a side view of an embodiment of a reversibly
inflatable bladder device described herein.
[0021] FIG. 8D shows a side view of an embodiment of a reversibly
inflatable bladder device described herein.
[0022] FIG. 8E shows a side view of an embodiment of a reversibly
inflatable bladder device described herein.
[0023] FIG. 9 shows optional locations for device components on
various embodiments.
[0024] FIG. 10A shows a partial view of an embodiment of a
microfluidic component optionally included in various embodiments
of devices described herein.
[0025] FIG. 10B shows a partial view of an embodiment of a
microfluidic component optionally included in various embodiments
of devices described herein.
[0026] FIG. 10C shows a partial view of an embodiment of a
microfluidic component optionally included in various embodiments
of devices described herein.
[0027] FIG. 11 shows a partial view of a system described
herein.
[0028] FIG. 12A shows a partial view of a depot configuration for
one or more therapeutic and/or nutraceutical agent reservoirs.
[0029] FIG. 12B shows a partial view of a depot configuration for
one or more therapeutic and/or nutraceutical agent reservoirs.
[0030] FIG. 12C shows a partial view of a depot configuration for
one or more therapeutic and/or nutraceutical agent reservoirs.
DETAILED DESCRIPTION
[0031] In the following detailed description, reference is made to
the accompanying drawings, which form a part hereof. In the
drawings, similar symbols typically identify similar components,
unless context dictates otherwise. The illustrative embodiments
described in the detailed description, drawings, and claims are not
meant to be limiting. Other embodiments may be utilized, and other
changes may be made, without departing from the spirit or scope of
the subject matter presented here.
[0032] Various embodiments disclosed herein relate to systems,
methods, and devices including a semi-permanently mounted device
with one or more sensors and at least one actuator operably coupled
to at least one therapeutic agent and/or nutraceutical agent
release depot. In an embodiment, the device is mounted in the
gastro-intestinal (GI) tract of a subject. In an embodiment, the
device is mounted in the appendix of a subject. In an embodiment,
the device is inserted into the subject's GI tract by a health care
worker (e.g., during a colonoscopy). In an embodiment, the subject
has previously had its naturally occurring appendix removed, and
the device disclosed herein functions as a "synthetic" or
"artificial" appendix. In an embodiment, the device is mounted in
the cecum of the subject. In an embodiment, the device is mounted
in a gastric bypass anastomosis, or a cavity formed by surgical
resection.
[0033] The average human appendix can range from about 2 cm to
about 20 cm in length, and is usually from about 7 mm to about 8 mm
in diameter. An appendix can also be found in various other
animals, including but not limited to, other primates, opossum,
wombat, rodents, and others.
[0034] Various other animals (e.g., herbivores including cows,
dogs, and others) have a cecum, that varies in size, depending on
the animal. The cecum in most animals contains various types of
bacteria for colonizing the GI tract for both digestion as well as
pathogen control and/or immune surveillance.
[0035] The appendix includes gut associated lymphoid tissue, which
is also found elsewhere in the GI tract and provides immune
function. For example, the gut associated lymphoid tissue provides
a haven for useful bacteria, cell signaling molecules, and immune
system cells (e.g., lymphocytes such as T cells and B cells; plasma
cells; and macrophages), similarly to the thyroid, breast, lung,
salivary glands, eye, skin, tonsils, adenoids, Peyer's Patches, and
other lymphatic organs.
[0036] In an embodiment, the device and system set forth herein
include means for manipulating at least one component of the gut
associated lymphoid tissue (GALT). In an embodiment, the device
includes at least one therapeutic agent or nutraceutical agent that
binds to at least a portion of the mucosal adressin MAdCAM-1 or a
receptor thereof. In an embodiment, the device includes at least
one therapeutic or nutraceutical agent that binds to IgA (e.g.,
IgA1, IgA2, etc.). In an embodiment the device includes a
therapeutic agent or nutraceutical agent that binds at least one of
a subject's chemokine, cytokine, lymphocyte, antibody, M cell,
natural killer cell, or microorganism. In an embodiment, the device
includes at least one therapeutic agent or nutraceutical agent that
binds to at least a portion of at least one of L-selectin, CLA,
E-selectin, or VCAM-1.
[0037] The GALT in humans is an important early site for human
immunodeficiency virus (HIV) replication and severe CD4+ T cell
depletion, however in patients that receive highly active
antiretroviral therapy (HAART), the CD4+ T cell restoration is
incomplete, as is viral suppression (when compared to peripheral
blood). See Guadalupe, et al., J. Virol., Vol. 80, No. 16, Aug.
2006, which is incorporated herein by reference. In an embodiment,
the device disclosed herein includes a therapeutic or nutraceutical
agent conducive to reducing HIV infection or for boosting T cell
restoration or sustenance in the GALT of a subject. For example,
the one or more therapeutic or nutraceutical agents can include at
least one anti-retroviral drug, anti-inflammatory agent, cytokine,
chemokine, biological cell (e.g. blood cell, stem cell, fungal or
bacterial cell, etc.), vitamin (e.g., vitamin C, vitamin D, vitamin
E, vitamin A, beta carotene, etc.), mineral (e.g., zinc, potassium,
sodium, etc.), fat, protein (including amino acids, enzymes, etc.),
sugar (e.g., glucose, sucrose, fructose, simple chain sugars or
complex sugars, etc.), insulin, chemotherapy agents, anti-viral
agents (including anti-retroviral agents), anti-fungal agents, or
other therapeutic or nutraceutical agent for assisting in HIV
infection in a subject.
[0038] In an embodiment, a system and related device are mounted in
the appendix lumen of a subject. In an embodiment, the device
includes at least one housing unit. In an embodiment, the housing
unit includes at least one permeable, semi-permeable, or
impermeable membrane (depending on the full configuration of the
device, see Figures for more details). In an embodiment, the
membrane provides for containment of the electronic and other
components of the device. In an embodiment, one or more electronic
or other components is includes on an external side of the membrane
of the device.
[0039] In an embodiment, the housing unit further includes at least
one rigid or semi-rigid frame for support of the membrane. In an
embodiment, the rigid or semi-rigid frame includes at least one
configuration including, but not limited to, coil, tent, square,
triangle, pentagon, hexagon, octagon, decagon, etc. depending on
the alignment and spacing of the rigid frame components. See
Figures for further details.
[0040] In an embodiment, at least one portion of the rigid or
semi-rigid frame includes a collapsible or "breakable" portion that
allows for the entire device to be collapsed if needed or desired.
For example, a breakable portion can include a weakened place on
the rigid or semi-rigid frame, a notched leg, a collapsible leg, or
similar "break-away" mechanism that passively or actively allows
for collapse of the rigid or semi-rigid frame. In an embodiment,
upon one or more sensors of the device detecting inflammation
(e.g., by detecting IL-4, an increase in temperature, or an
increase in white blood cells, etc.) the device will optionally
verify that it should collapse (either with an external database,
an internal checking system, or command from the user), and it will
collapse for expulsion from the GI tract.
[0041] In an embodiment, the device includes at least one
therapeutic agent delivery depot. In an embodiment, the therapeutic
agent delivery can be open loop, for example, by a schedule, by
continuous elution or diffusion, or by external command (e.g.,
remote control). In an embodiment, the therapeutic agent delivery
can be closed loop, for example, based on an input from one or more
sensors. In an embodiment, the one or more sensors are configured
for monitoring at least one GI tract condition (e.g., temperature,
pH, motion, strain/dimensions, inflammation, bacterial type or
number of one or more populations, presence/type/motion of food or
fluid, etc. Such monitoring can include, in an embodiment, terminal
ileum flora monitoring, nutritional monitoring, neoplastic cells,
verification of drug metabolites to monitor enteral passage or even
compliance or other samples of interest. In an embodiment, a level
sensor is utilized to tell when the reservoir is empty. In an
embodiment, strain and pressure sensors are either for cases where
the bladder is the depot (will indicate when it becomes empty), or
tell when the bladder is too inflated or pressing too hard on
tissue.
[0042] In an embodiment, one or more sensors include optical
sensors that are configured for measuring opacity or scattering in
the GI tract. In an embodiment, a light source in the appendix
senses reflections, and two components (e.g., one in the appendix
and one in another GI location) measures transmission or
scattering. In an embodiment, one or more sensors can measure
conductivity or permittivity of the GI tract fluid. In an
embodiment, one or more sensors include ultrasound, that allows for
measuring of opacity, scattering, or velocity (e.g., via Doppler)
in the GI tract. In an embodiment, detection includes a
cross-channel component.
[0043] In an embodiment, the housing unit includes one or more
reversibly inflatable bladders utilized as "bumpers," that, when
inflated, act as intestinal wall-attachment components to secure
the device between the walls of the appendix by outward pressure.
In an embodiment, a switch is operably coupled to at least one
actuator that is operably coupled to the one or more reversibly
inflatable bladders and upon activation, will deflate the "bumpers"
in whole or in part. In an embodiment, the deflation is only
partial, for example to allow movement of fluid or other biological
material through or around the device, to decrease any
inflammation, or relieve pressure in the appendix. In an
embodiment, the deflation is complete and the device is collapsed
and actively or passively expelled from the appendix (and carried
through the intestinal tract and out of the subject's body). In an
embodiment, the deflation event is performed when the device has
exhausted itself (e.g., sensor or therapeutic agent depot is
depleted), when the device has malfunctioned, or if the appendix
becomes inflamed.
[0044] In an embodiment, the switch includes an electromagnetic
switch (relay) that is activated when a signal is received. In an
embodiment, the signal includes a wireless signal. Thus, in an
embodiment, the device is remotely controlled such that when a
signal is sent to deflate the device, the switch activates one or
more actuators that deflate the device and allow for expulsion from
the appendix. In an embodiment, the device can be induced to
release at least a portion of the one or more therapeutic or
nutraceutical agent by way of a wireless signal. Thus, the device,
in an embodiment, the device can be turned on and off by way of
remote control. For example, the one or more reservoirs containing
the at least one therapeutic agent or nutraceutical agent include,
in an embodiment, a titanium and/or platinum seal. Passing an
electric current through the seal form an internal battery melts
the seal, thus allowing for a dose to diffuse out of the reservoir.
See Kinkead, MIT Tech. Rev., Jul. 4, 2014, accessed online Jul. 25,
2014 at the worldwide web and technologyreview.com/news, the
content of which is incorporated herein by reference.
[0045] In an embodiment, one or more electronic control units are
operably connected to the one or more reversibly inflatable bladder
"bumpers" that regulate (optionally in real-time) the level of
inflation/deflation of the device, and thus adjust the pressure
that the device exerts against the walls of the appendix. In an
embodiment, the one or more electronic control units are regulated
by one or more signals from one or more sensors of the device.
[0046] In an embodiment, one or more reversibly inflatable bladder
"bumpers" are arranged in a configuration for optimal mounting in a
particular subject's GI tract (e.g., appendix), or to fulfil a
specific purpose. For example, one or more reversibly inflatable
bladder "bumpers" can form extension tube rows, columns, zig-zags,
circles (including concentric circles), "S" shape, squares,
triangles, rectangles, or any combination of these. Likewise, in an
embodiment, two or more inflatable bladder "bumpers" can be spaced
apart at various distances, depending on the desired configuration
and/or purpose. In an embodiment, the one or more reversibly
inflatable bladders are configured to form a helical device for
insertion into the subject's body. See Figures for details.
[0047] In an embodiment, the one or more reversibly inflatable
bladder "bumpers" are integrally formed as an extension tube of a
single bladder such that the increased pressure of inflating the
bladder provides feedback (e.g., to one or more sensors) as to how
much the bladder is or should be inflated. See Figures for details.
In this way, in an embodiment, the reversibly inflatable bladder is
able to self-regulate volume of the bladder. In an embodiment, the
reversibly inflatable bladder is self-inflating. Various modes of
self-inflating bladders can be adapted for use with one or more
embodiments described herein. For example, inserting the device
into a subject's body can cause an internal rigid frame to which
empty (deflated) bladders are affixed to create a physical space
within the frame, such that a vacuum is generated and air is taken
in (e.g., by way of the inlet valve) to fill the space. Upon
pressure equalization, the self-inflating bladder stops inflating
and the valve can be closed. In an embodiment, the reversible
inflatable bladder utilizes a combination of self-inflating and
external inflating (e.g., pump, pressure or temperature
differential driven, etc.).
[0048] In an embodiment, the device includes at least one
inflatable bladder that is irreversible. For example, in an
embodiment an inner lining inflatable bladder.
[0049] In an embodiment, the reversibly inflatable bladder is in a
collapsed state prior to, during, or after positioning into a
subject's appendix. In an embodiment, the reversibly inflatable
bladder is inflated before, during, or after positioning of the
device into a subject's appendix. In an embodiment, the device is
positioned in a subject's appendix while the bag is in a collapsed
state and inflated once the bag is positioned securely in the
subject's appendix. Various means for securing the device in the
subject's appendix are described herein. In an embodiment, the bag
is inflated by way of a small cartridge of gas or a small pump
within the device itself. In an embodiment, the bag is inflated by
way of a tube or other means external to the subject's body. In an
embodiment, the device includes a valve operably coupled to the
bag.
[0050] In an embodiment, the reversibly inflatable bladder includes
a flexible material and optional rigid fame. In an embodiment, one
or more actuators are operably coupled to the rigid frame. In an
embodiment, the one or more actuators operably coupled to the rigid
frame are coupled with control circuitry. In an embodiment, the one
or more actuators are configured to collapse the rigid frame upon
command via the control circuitry. In an embodiment, the command to
collapse the rigid structure is transmitted by at least one of
remote control, as a result of direct sensor feedback, based on a
timed schedule, or as a result of indirectly by way of
determination by associated circuitry based on sensor derived
information. In an embodiment, the control circuitry is housed
within the reversibly inflatable bladder of the device, and upon
external command, or internal command, the electronic components
are extruded from the device. In an embodiment, the extrusion of
the electronic components occurs before, during, or after collapse
of the rigid frame. See Figures herein.
[0051] As described elsewhere herein, the system includes a control
system operably coupled to at least one of the various sensors
described herein, and/or at least one actuator. In an embodiment,
the control system is wirelessly operably coupled to at least one
sensor and/or at least one actuator. In an embodiment, the control
system is operably coupled to at least one sensor and/or at least
one actuator by way of a wired connection.
[0052] In an embodiment, the control system further includes
control electrical circuitry configured to direct at least one
actuator or other regulatory component by way of one or more
signals, responsive to at least one sensing signal from at least
one sensor. In an embodiment, the control system includes a power
supply (e.g., battery, etc.) for powering at least some of the
components of the system, for example the control electrical
circuitry, at least one sensor, and/or at least one actuator.
[0053] In an embodiment, instructions directing the control
electrical circuitry of the control system that controls the
operation of at least one sensor and/or at least one actuator can
be programmed by the subject or third party (e.g., healthcare
worker, non-medical care giver, computer, etc.), or pre-programmed
in the control electrical circuitry. In an embodiment, the
programming of the control electrical circuitry is carried out by
at least one of software, firmware, logic devices, etc.
[0054] In an embodiment, the control electrical circuitry directs
one or more components of the system to operate (e.g., to allow a
reversibly inflatable bladder to inflate or deflate, to allow a
collapsible joint to collapse, to allow for release of at least one
therapeutic and/or nutraceutical agent, etc.), in response to at
least one sensor that senses one or more physiological parameters
of the subject, or one or more parameters of operation of the
device or system itself.
[0055] In an embodiment, the system includes memory operably
coupled to the control electrical circuitry and a user interface
that the subject, a healthcare worker, or other non-medical care
giver utilizes to program the operation of the system and/or
device. See Figures for details. In an embodiment, the memory can
be programmed by the user interface so that instructions for the
operation of the system are stored therein. In an embodiment, a
user interface includes a keyboard, mouse, touch screen, monitor,
voice command recognition, iris scan, fingerprint scan, or other
interactive device that is operably coupled to the control
electrical circuitry of the control system. In this manner, in an
embodiment the system can be programmed into memory with
instructions as needed or desired. In an embodiment, the memory is
configured to store sensed data corresponding to at least one
sensed signal from at least one sensor, and can be optionally
downloaded by the subject or another party for analysis or
decision-making.
[0056] In an embodiment, a method includes invoking an action in
the system, responsive to sensing at least one parameter of the
subject or one parameter of operation of the device via at least
one sensor. For example, in an embodiment, a sensor detects blood
glucose levels which triggers release of glucose or insulin, as
needed. In another example, a sensor detects that one of the
therapeutic/nutraceutical reservoirs has malfunctioned and triggers
a shut down of that reservoir and/or depot, and optionally sends a
signal to the user or another party (e.g., healthcare worker,
computer system, non-medical care giver, etc.).
[0057] In an embodiment, the method includes receiving input from
at least one sensor of the system. In an embodiment, at least one
component of the system is responsive to receiving input and/or
responsive to an operational program of the control system to drive
the necessary components.
[0058] In an embodiment, the method includes transmitting input
from at least one sensor of the system. In an embodiment, the
method includes providing output from at least one sensor of the
system to another party (e.g., subject, computer, healthcare
worker, non-medical care giver, etc.).
[0059] In an embodiment, one section of the device communicates
with another section of the device by way of the various electronic
and/or mechanical components described herein. For example, the
inner surface of the device can provide feedback from sensors
located there to the depot for dispensing of an agent, or for
increasing inflation in the reversibly inflatable bladder (if one
is present).
[0060] In an embodiment the device includes an inlet valve for
inflating the reversibly inflatable bladder. In an embodiment, the
device includes a release valve for rapid deflation of the
reversibly inflatable bladder. In an embodiment, the device further
includes means for expediting expulsion of the device from its
location (e.g., appendix) in the subject's body. In an embodiment,
the device further includes a pumping means for inflating the
reversibly inflatable bladder. In an embodiment, the device
includes one or more means for mobility, which may be
pre-programmable and/or controllable by way of remote control.
[0061] In an embodiment, the rigid frame and/or reversibly
inflatable bladder is shaped to fit the size of the subject's
appendix. For example, various sizes of rigid frames can be
employed, and the reversibly inflatable bladder can be inflated or
deflated in order to provide a custom fit (e.g., based on sensors
on the surface or inside of the device that sense external contact
or pressure from the subject's appendix that provides feedback to
the device with regard to level of inflation of the bag).
[0062] In an embodiment, a controller is operably coupled to the
reversibly inflatable bladder, with at least one setting for
determining a threshold range outside of which the bag inflates or
deflates (or attempts to do so). In an embodiment, one or more
sensors are operably coupled to the reversibly inflatable bladder
and are configured to measure the tension of the bag in order for
the controller to determine whether the device is operating with
the bag at the proper inflation level. In an embodiment, the
inflation/deflation bag includes programmable control circuitry
configured for one or more pre-programmed levels of inflation in
the inflation/deflation bag. In an embodiment, the
inflation/deflation bag is under the control of a remote
control.
[0063] In an embodiment, the device and system include one or more
sensors that provide feedback for operation of the device, delivery
of one or more therapeutic agents, or provide information to an
entity (e.g., a remote computing system or device, a healthcare
worker, the subject itself, a database or network, or other
entity). In an embodiment, the one or more sensors detect, for
example, contractions or expansion of the device, pressure,
temperature, pH, components in the blood or GI tract fluid, etc. In
an embodiment, the information received from the one or more
sensors is sent to a controller to regulate the one or more
inflatable bladders or release from a therapeutic or nutraceutical
agent depot, or other operation of the device.
[0064] In an embodiment, the device includes one or more
transmitters, receivers, or transceivers for wirelessly
transmitting and receiving reports to and from an entity, as
described herein. In an embodiment, the one or more sensors provide
feedback relating to the operation of the device or system, for
example with regard to one or more of electrical stimulators,
therapeutic or nutraceutical agent dispensing, etc.
[0065] In an embodiment, the device includes one or more drainage
channels through or across the device (e.g., laterally,
longitudinally, helically, or transversely). In an embodiment, the
drainage channel is located as an interior lumen. See the Figures
for details. In an embodiment, one or more sensors is located
within at least one of the one or more drainage channels.
[0066] In an embodiment, one or more microfluidic or nanofluidic
chips are located on the housing unit of the device, or in the one
or more drainage channels. In an embodiment, the drainage channels
themselves operate as fluidic detection components (e.g., with one
or more sensors lining the drainage channels for detection of one
or more analytes). The same is only briefly discussed herein, as
one of skill in the art can appreciate that various examples can be
modified or adapted for use herein as described for various
embodiments.
[0067] In an embodiment, at least one of the one or more drainage
channels are utilized operationally as a flow channel for a
microfluidic device, while others provide mere drainage of fluid
through or away from the device. In an embodiment, the flow channel
includes an inlet, and an outlet coupled to either end of the flow
channel. In an embodiment, thermal conductors, valves, pumps
(peristaltic, piezo-electric, electro-osmotic, pressure pumps,
etc.), stop-flow junctions, or other means are included to assist
in the proper flow control through the channels. In an embodiment,
the drainage channel designed to be part of a microfluidic device,
may have any shape and length provided that at least one section
thereof allows for flow of the fluid from the GI tract (e.g.,
digestive juices, blood, bacterial mixtures, etc.) to flow through
one or more chambers (e.g., a chamber with a sensor, a reaction
chamber for allowing the fluid to react with one or more testing
components, a mixing chamber for mixing the fluid if needed, and
measuring chamber for measuring at least one property of the fluid,
if needed), adaptable to the device depending on the size,
structure, and purpose. In an embodiment, the flow channel includes
at least one dimension (e.g., length, diameter, a maximum dimension
for example if inflated, etc.) of at least about 1 nanometer, at
least about 10 nanometers, at least about 20 nanometers, at least
about 50 nanometers, at least about 100 nanometers, at least about
10 micrometers, at least about 20 micrometers, at least about 50
micrometers, at least about 100 micrometers, at least about 200
micrometers, at least about 300 micrometers, at least about 400
micrometers, at least about 500 micrometers, or any value
therebetween.
[0068] In an embodiment, the microfluidic portion of the device
includes at least one flow control channel section. In an
embodiment, the flow control channel section has a length that is
at least about 2 times, at least about 3 times, at least about 4
times, at least about 5 times, at least about 10 times, at least
about 15 times, at least about 20 times, or any value therebetween,
longer than the fluid flow channels. In an embodiment, the flow
control channel section is at least about 90%, at least about 95%,
at least about 99% smaller than the average cross sectional area of
the fluid flow channel section (e.g., drainage channel, if used for
this purpose).
[0069] In an embodiment, the one or more sensors include at least
one sensor in the GI tract. In an embodiment, the one or more
sensors include at least one remote sensor (e.g. located elsewhere
in the subject's body, located external to the subject's body,
located in the room where the subject resides, etc.). In an
embodiment, the one or more sensors include at least one sensor
that is configured to reversibly extend into the GI tract. As
described herein, the one or more sensors may be configured to
measure at least one of temperature, pH, motion, strain/dimensions,
inflammation, bacteria or other microorganisms that make up a
microbiome or represent potential infection, presence or motion of
food in the GI tract, etc. In an embodiment, the one or more
sensors allow for surveillance of one or more of terminal ileum
flora, nutritional monitoring, neoplastic cells, verification of
drug metabolites for enteral passage or compliance, or samples of
interest along the GI tract.
[0070] In an embodiment, the device is inserted by catheter into
the subject's body (e.g., downward from the throat, upward from the
rectum, etc.). In an embodiment, the device is inserted into the
subject's body by way of self-mobile device (e.g., orally swallowed
as it travels downward, or colon crawlers that allow for it to
travel upward to the GI tract, etc.).
[0071] In an embodiment, at least one therapeutic agent is
dispensed from the device and system, and provides therapeutic
treatment for one or more of ulcerative colitis, celiac disease,
inflammatory bowel disease, general inflammation of the GI tract,
food poisoning or other GI tract infection (appendicitis, etc.), or
other GI related condition. In an embodiment, the therapeutic agent
provides a preventative agent to the GI tract (e.g., probiotics,
vitamins, minerals, other nutraceuticals, etc.). In an embodiment,
the nutraceutical agent includes at least one of vitamin A, D, C,
E.
[0072] In an embodiment, at least one component of the device
(e.g., the housing unit) includes an anti-inflammatory agent (e.g.,
an anti-inflammatory material or chemical coating) in order to
reduce potential inflammation reactions with the device. In an
embodiment, the housing unit is fabricated from or includes
anti-inflammatory magnesium hydroxide nanoparticles incorporated
into poly (D, L-lactic-co-glycolic acid) (PLGA) scaffolds with
various porogen materials. For example, freeze drying such a
preparation results in lowered IL-6 expression, a biomarker for
inflammation. See for example, Lee, et al., Macromolecular
Research, Feb. 2014, Vol. 22, No. 2, pp. 210-218, which is
incorporated herein by reference.
[0073] Likewise, housing units fabricated at least in part from
magnesium-zinc-silver biomaterials exhibit good cytocompatibility
and anti-inflammatory properties, and can be adapted for use with
various embodiments disclosed herein. See for example, Peng et al.,
J. Biomed. Mat. Res. Pt. A, Dec. 3, 2012, Abstract, which is
incorporated herein by reference.
[0074] In an embodiment, the housing unit is fabricated at least in
part with far-infrared ray-emitting ceramic materials
(bioceramics), which have been shown to promote microcirculation
and anti-inflammatory properties, and can be adapted for use with
various embodiments disclosed herein. See Leung et al., J. Med. and
Biol. Eng., 33(2):179-184, 2011, which is incorporated herein by
reference.
[0075] In an embodiment, the housing unit is fabricated at least in
part of one or more biodegradable polymers (e.g., poly(lactide),
polyglyconate, polyanhydrides, polyorthoesters, or
poly(glycolide)). In an embodiment, at least one therapeutic or
nutraceutical agent is delivered at a rate equal to the degradation
of the device itself. In addition, the device includes
biodegradable or bioresorbable electronic components (e.g., cocoon
silk, etc.) as well.
[0076] In an embodiment, the housing unit includes at least one of
a mesh or semi-permeable membrane that sits adjacent to the lumen
wall in the subject's GI tract. In an embodiment, the device
includes at least one array of mechanical or chemical "feet"
between the housing unit and the lumen wall for support. See
Figures for details. In an embodiment, the chemical feet include
gel or other polymer protrusions from the housing unit.
[0077] In an embodiment, the device is preloaded for a single use.
In an embodiment, the device is refillable. In an embodiment, the
device can be refilled via catheters, pills, etc. In an embodiment,
the device includes at least one reversibly inflatable bladder as
described herein, wherein the bladder includes a valve (e.g., at
the front of the device) that allows the device to be inflated by
injection of fluid (e.g., gas, liquid, gel, etc.) which may include
a therapeutic agent. In an embodiment, the device includes two or
more therapeutic or nutraceutical agent depots, as described
herein. In an embodiment, each of the two or more therapeutic or
nutraceutical agent depots includes a different therapeutic or
nutraceutical agent. In this manner, in an embodiment, a
combination of multiple therapeutic or nutraceutical agents can be
dispensed into the subject's body from the device.
[0078] In an embodiment, the device and/or system includes wireless
communication to report on its drug deliveries and sensed
conditions, or to receive commands, as described herein. In an
embodiment, the device is removable (e.g., via catheter, via
self-collapse, via crawling out, for example by remote
control).
[0079] In an embodiment, the intestinal wall-attachment component
includes at least one of a screw, suture, staple, clip, anchor,
hook, brace, reversibly inflatable bladder, projection, umbrella
connector, barb, latch, or adhesive.
[0080] In an embodiment, the device is sized and shaped for
mounting in the appendix or other GI tract location. In an
embodiment, electrodes are included in the device and are separated
by insulating material, all of which can be sealed in a segment or
as part of the housing unit of the device. In an embodiment, the
device includes a controller operably coupled to a power source. In
an embodiment, the electronic components are contained in part of
the housing unit. In an embodiment, the electronic components are
contained in the walls of the housing unit, with the central
channel or cavity of the device remaining hollow to accommodate
fluid flow. See Figures for details. In this way, in an embodiment
the device should not readily induce inflammation since it allows
for fluid flow through and/or around the device itself. For
example, in an embodiment, the device may act as a stent to keep
the appendix from swelling from infection and/or closing in on
itself.
[0081] As shown in FIG. 1, a system 100 includes a device 105, with
a rigid or semi-rigid structure 180 and optionally with an outer
membrane 110 (e.g., permeable, semi-permeable, bioresorbable, or
biodegradable). In an embodiment, the outer membrane 110 does not
cover the entire device (not shown). In an embodiment, the outer
membrane 110 is reversibly inflatable. In an embodiment, the outer
membrane 110 is reversibly inflatable and only covers a portion of
the device, thus forming an inflatable collar. As shown in FIG. 1,
a tubular device 105, allows for fluid flow 101 through the device.
As shown, in an embodiment, at least one sensor 130, transmitter
150, receiver 160, power source 140, and electrical circuitry 170,
are located on the outer side of the rigid or semi-rigid structure
180. In an embodiment (not shown), the same components are located
on the inner side of the rigid or semi-rigid structure 180. In an
embodiment, as shown, a depot 120 for one or more therapeutic
agents and/or one or more nutraceutical agents is included in the
device 105. In an embodiment, the depot 120 is located on the inner
surface of the device 105. In an embodiment (not shown), the depot
120 is located on the outer surface of the device 105.
[0082] As shown in FIG. 2, a system 200 includes a device 205, with
a rigid or semi-rigid structure 280 and optionally with an outer
membrane (not shown) (e.g., permeable, semi-permeable,
bioresorbable, or biodegradable). As shown in FIG. 2, a polymer
cage-like device 205 (optionally from a biodegradable polymer),
allows for fluid flow 201 through the device. As shown, in an
embodiment, at least one sensor 230,
transmitter/receiver/transceiver 240, microfluidic component 225,
electrical circuitry (not shown), and collapsible joint 260 are
included in the device. In an embodiment (not shown) these
components are located on the outer side of the rigid or semi-rigid
structure 280. In an embodiment, the same components are located on
the inner side of the rigid or semi-rigid structure 180. In an
embodiment, a depot 220 for one or more therapeutic agents and/or
one or more nutraceutical agents is included in the device 205. In
an embodiment, the depot 220 is located on the inner surface of the
device 205. In an embodiment (not shown), the depot 220 is located
on the outer surface of the device 205. As one will appreciate, the
exact configuration of the cage-like device can include, for
example, a square, pyramid, pentagon, hexagon, octagon, circle,
oval, sphere, etc. and is not limited by number of sides or
proportion of side lengths to each other, within the confines of
the various components described herein.
[0083] As shown in FIG. 3, a system 300 includes a device 305, with
a rigid or semi-rigid structure 390 and optionally with an outer
membrane 310 (e.g., permeable, semi-permeable, bioresorbable, or
biodegradable). As shown in FIG. 3, an umbrella-like device 305
(optionally from a biodegradable polymer), allows for fluid flow
301 through the device. As shown, in an embodiment, at least one
sensor 330, transmitter 320, receiver 330, power source 340, light
source 350, microfluidic component 375, and at least one
collapsible joint 370, and electrical circuitry (not shown) are
included in the device. In an embodiment (not shown) these
components are located on the outer side of the rigid or semi-rigid
structure 390. In an embodiment, one or more wall attachment
components 380 are located such that the umbrella-like device is
opened end to end upon attachment to the GI tract wall. In an
embodiment, an opening 390 provides for fluid flow 301 through the
device. In an embodiment, a depot 320 for one or more therapeutic
agents and/or one or more nutraceutical agents is included in the
device 305. In an embodiment, the depot 320 is located on the inner
surface of the device 305. In an embodiment (not shown), the depot
320 is located on the outer surface of the device 305 (optionally
between the structure 390 and the outer membrane 310).
[0084] As shown in FIG. 4, a system 400 includes a device 405, with
a rigid or semi-rigid structure 480 and optionally with an outer
membrane 410 (e.g., permeable, semi-permeable, bioresorbable, or
biodegradable). As shown in FIG. 4, a tent-like device 405
(optionally from a biodegradable polymer), allows for fluid flow
401 through the device. As shown, in an embodiment, at least one
sensor 430, power source 440, light source 450, transmitter 460,
receiver 420, microfluidic component 425, and at least one
collapsible joint 470, and electrical circuitry (not shown) are
included in the device. In an embodiment (not shown) these
components are located on the outer side of the rigid or semi-rigid
structure 480 (optionally between the structure 480 and the outer
membrane 410).
[0085] As shown in FIG. 5 (side view and top view), a system 500
includes a device 505, with a rigid or semi-rigid structure 580 and
optionally with an outer membrane 510 (e.g., permeable,
semi-permeable, bioresorbable, or biodegradable). As shown in FIG.
5, a spiral-like or coiled device 505 (optionally from a
biodegradable polymer), allows for fluid flow 501 through the
device. As shown, in an embodiment, at least one sensor 530, power
source 540, light source 550, transmitter 560, receiver 520,
microfluidic component 575, and electrical circuitry 570, are
included in the device. In an embodiment (not shown) these
components are located on the outer side of the rigid or semi-rigid
structure 580.
[0086] As shown in FIG. 6A (bottom view), a system 600 includes a
device 605 with one or more reversibly inflatable bladders 670 with
an optional outer membrane 610 (e.g., permeable, semi-permeable,
bioresorbable, or biodegradable). As shown in FIG. 6A, a bottom
view of an reversibly inflatable bladder 670, allows for fluid flow
601 through the device. As shown, in an embodiment, a port 650 to
inflate/deflate the reversibly inflatable bladder 670 is included.
The device further includes an opening 690 that provides an inner
surface to which device components can be adhered (see FIG. 6B). In
an embodiment, a sensor 640, a transceiver 620, and a pump 630 is
located on the outer surface of the reversibly inflatable bladder
670, and optionally beneath the outer membrane 610. In an
embodiment, the reversibly inflatable bladder 670 puts pressure on
the GI tract wall 660, thereby keeping the device in place.
[0087] As shown in FIG. 6B (bottom view), a system 600 includes a
device 605 with one or more reversibly inflatable bladders 670 with
an optional outer membrane (not shown) (e.g., permeable,
semi-permeable, or biodegradable). As shown in FIG. 6B, the
reversibly inflatable bladder 670, allows for fluid flow 601
through the device. As shown, in an embodiment, a port 650 to
inflate/deflate the reversibly inflatable bladder 670 is included.
The device further includes an opening 690 that provides an inner
surface to which the device components can be adhered. In an
embodiment, a sensor 640, transceiver 630, and depot 620 for one or
more therapeutic agents and/or one or more nutraceutical agents is
included in the inner surface of the device. In an embodiment, the
components of the device are located at the outer surface of the
device. In an embodiment, the reversibly inflatable bladder 670
puts pressure on the GI tract wall 660, thereby keeping the device
in place.
[0088] As shown in FIG. 6C (bottom view), a system 600 includes a
device 605 with one or more reversibly inflatable bladders 670 with
an optional outer membrane (not shown) (e.g., permeable,
semi-permeable, or biodegradable). As shown in FIG. 6C, the
reversibly inflatable bladder 670, allows for fluid flow 601
through the device. As shown, in an embodiment, a port 650 to
inflate/deflate the reversibly inflatable bladder 670 is included.
The device further includes an opening 690 that provides an inner
surface to which the device components (not shown) can be adhered.
In an embodiment, an adhesive 695 is utilized to adhere the device
to the GI tract wall 660, thereby keeping the device in place.
[0089] As shown in FIG. 6D (bottom view), a system 600 includes a
device 605 with one or more reversibly inflatable bladders 670 with
an optional outer membrane (not shown) (e.g., permeable,
semi-permeable, or biodegradable). As shown in FIG. 6D, the
reversibly inflatable bladder 670, allows for fluid flow 601
through the device. As shown, in an embodiment, a port 650 to
inflate/deflate the reversibly inflatable bladder 670 is included.
The device further includes an opening 690 that provides an inner
surface to which the device components (not shown) can be adhered.
In an embodiment, a rigid or semi-rigid frame 680 is utilized to
adhere the device to the GI tract wall 660, thereby keeping the
device in place.
[0090] As shown in FIG. 7, a system 700 includes a device 705 with
a rigid or semi-rigid structure 790 including a hinge 780 and
optionally with an outer membrane 710 (e.g., permeable,
semi-permeable, or biodegradable). As shown in FIG. 7, a
spiral-like or coiled device 705 (optionally from a biodegradable
polymer), allows for fluid flow 701 through the device. As shown,
in an embodiment, at least one sensor 730, power source 740, light
source 750, transmitter 760, receiver 760, microfluidic component
735, and electrical circuitry (not shown), are included in the
device. In an embodiment (not shown) these components are located
on the outer side of the rigid or semi-rigid structure 790. In an
embodiment, the components are located on an inner surface of the
device, or optionally in between the rigid or semi-rigid structure
790 and the optional outer membrane 710. In an embodiment, one or
more GI wall attachment components 770 are included in the device,
such that the device is opened at the hinge 780 and the wall
attachment components 770 keep the device in place in the GI tract.
In an embodiment, the same components are located on the inner side
of the rigid or semi-rigid structure 790. In an embodiment, a depot
720 for one or more therapeutic agents and/or one or more
nutraceutical agents is included in the device 705. In an
embodiment, the depot 720 is located on the inner surface of the
device 705. In an embodiment (not shown), the depot 720 is located
on the outer surface of the device 705.
[0091] As shown in FIG. 8A, a system 800 includes a device 805 with
one or more reversibly inflatable bladders 870 with an optional
outer membrane (not shown) (e.g., permeable, semi-permeable, or
biodegradable). As shown, in an embodiment, a port 850 to
inflate/deflate the reversibly inflatable bladder 870 is included.
In an embodiment, an adhesive 870 is utilized to adhere the device
to the GI tract wall 898, thereby keeping the device in place.
[0092] As shown in FIG. 8B, a system 800 includes a device 805 with
one or more reversibly inflatable bladders 870 with an optional
outer membrane (not shown) (e.g., permeable, semi-permeable, or
biodegradable). As shown, in an embodiment, a port 850 to
inflate/deflate the reversibly inflatable bladder 870 is included.
In an embodiment, an expandable wall attachment component 880 is
utilized to attach the device to the GI tract wall 898, thereby
keeping the device in place.
[0093] As shown in FIG. 8C, a system 800 includes a device 805 with
one or more reversibly inflatable bladders 870 with an optional
outer membrane (not shown) (e.g., permeable, semi-permeable, or
biodegradable). As shown, in an embodiment, a port 850 to
inflate/deflate the reversibly inflatable bladder 870 is included.
In an embodiment, a hinged wall attachment component 890 is
utilized to attach the device to the GI tract wall 898, thereby
keeping the device in place.
[0094] As shown in FIG. 8D, a system 800 includes a device 805 with
one or more reversibly inflatable bladders 870 with an optional
outer membrane (not shown) (e.g., permeable, semi-permeable, or
biodegradable). As shown, in an embodiment, a port 850 to
inflate/deflate the reversibly inflatable bladder 870 is included.
In an embodiment, an intra-bladder port 860, is utilized to adjust
the inflation levels of multiple reversibly inflatable bladders
870. In an embodiment, a staple wall attachment component 875, a
hook wall attachment component 895, or an anchor wall attachment
component 885 is utilized to attach the device to the GI tract wall
898, thereby keeping the device in place.
[0095] As shown in FIG. 8E, a system 800 includes a device 805 with
one or more reversibly inflatable bladders 870 with an optional
outer membrane (not shown) (e.g., permeable, semi-permeable, or
biodegradable). As shown, in an embodiment, a port 850 to
inflate/deflate the reversibly inflatable bladder 870 is included.
In an embodiment, an intra-bladder port 860, is utilized to adjust
the inflation levels of multiple reversibly inflatable bladders
870. In an embodiment, a suture attachment component 865 is
utilized to attach the device to the GI tract wall 898, thereby
keeping the device in place.
[0096] As shown in FIG. 9, various embodiments of devices 905
contacting the GI tract wall 930, are shown to illustrate a
particular embodiment where the electrical components 920 of the
devices 905 are located on each particular device. Further details
are provided in the related Figures. For example, in any of the
devices 905 with an optional outer membrane 910 as previously
described herein, the electronic components 920 is located at an
inner surface location of the device, an outer surface of the
device, or in between the device 905 and the outer membrane 910. In
an embodiment, the electronic components 920 include one or more
circuits 965, at least one microfluidic device 935, at least one
depot 955 including one or more therapeutic agents and/or one or
more nutraceutical agents, at least one light source 945, one or
more sensors 940, at least one power source 980, at least one
controller 950, at least one transmitter 970, at least one receiver
960, wherein one or more components is located on a microchip (as
shown). In an embodiment, one or more microchips of components 920
are located in a device (e.g., in a cluster, on a platform, in
multiple locations of the device, etc.) and is not limited to any
particular configuration. As shown in FIG. 10, various
configurations of microfluidic devices may be employed with
embodiments disclosed herein. For example, as shown in FIG. 10A, a
microfluidic device 1050 includes at least one inlet 1000 that is
operably connected to one or more channels 1040 that allows for
fluid flow 1020 along the one or more channels 1040, toward the
detection zone 1030 and to the outlet 1010. As shown in FIG. 10B, a
microfluidic device 1052 includes at least one inlet 1000 operably
connected to one or more channels 1040 that allows for fluid flow
1020 along the one or more channels 1040 toward the detection zone
1030 and to the outlet 1010. As shown in FIG. 10C, a microfluidic
device 1053 includes at least one inlet 1000 that is operably
connected to one or more channels 1040 that allows for fluid flow
1020 along the one or more channels 1040, toward the detection zone
1030 and to the outlet 1010.
[0097] As shown in FIG. 11, a system 1100 includes a device 1120 as
described herein, configured to send signals 1130 to and receive
signals 1130 from at least one computing system 1150. In an
embodiment, at least one user 1140 (e.g., healthcare worker,
subject itself, parent/guardian, caretaker, etc.) who can enter
information into the computing system 1150 and provide directions
back to the device 1120 in the subject. Alternatively, the device
1120 can access one or more databases directly by way of engaging
with the computing system 1150. For example, in an embodiment, the
device 1120 is able to access the subject's own personal health
records, family health records, or general health databases (e.g.,
CDC databases) by sending and receiving signals 1130 to and from
the computing system 1150. In an embodiment, the device 1120 sends
and/or receives signals 1130 relating to the function of the device
itself (microfluidic data, other sensor data, level of agent in one
or more depots for therapeutic and/or nutraceutical agents, battery
level, or other operational status, etc.).
[0098] As shown in FIG. 12A, a depot 1200 including one or more
therapeutic agents and/or one or more nutraceutical agents includes
one or more transmitters/receivers/transceivers (not shown) or
utilizes the transmitter/receiver/transceiver of the device as
described herein, to send and/or receive signals 1230 with a
computing device (not shown). Thus, in this manner, the depot 1200
is able to be operated by remote control. (See for example,
Kinkead, MIT Tech. Rev., Jul. 4, 2014 accessed online Jul. 25, 2014
at technologyreview.com/news, the content of which is incorporated
herein by reference). For example, a microchip depot includes an
outlet 1220 for the agent to pass from the depot to the subject's
body. The depot includes one or more reservoirs 1210 sealed by a
thin metal membrane 1215, such as platinum and titanium. See Id.
Upon activation of the device (e.g., by way of wireless signal),
allows for a thin electric current to pass through the thin metal
membrane seal 1215, melting the seal temporarily and releasing the
agent contained within the one or more reservoirs 1210 of the
depot.
[0099] As shown in FIG. 12B, a depot 1200 including one or more
reservoirs 1250 containing one or more therapeutic agents and/or
one or more nutraceutical agents (as described herein, the depot
can include reservoirs each with the same agent or reservoirs each
with different agents. In an embodiment, the depot includes one or
more transmitters/receivers/transceivers (not shown) or utilizes
the transmitter/receiver/transceiver of the device as described
herein, to send and/or receive signals 1230 with a computing device
(not shown). Thus, in this manner, the depot 1200 is able to be
operated by remote control. For example, a microchip depot includes
an outlet 1220 for the agent to pass from the depot to the
subject's body. In an embodiment, the one or more reservoirs 1250
are inflated with the agent contained therein and are under
pressure (e.g. from the fluid pressure of the agent), and are
activated (e.g., wirelessly) by operation of a valve 1280 operably
coupled to the reservoir 1250, which expels the agent from the
reservoir 1280 through an outlet 1260 and into the subject's body.
In an embodiment, a micropump 1270 (or microjet) is utilized to
expel the agent from the reservoir 1250 through the outlet 1240
operably coupled to the micropump/microjet 1270 and the reservoir
1250.
[0100] As shown in FIG. 12C, a depot 1200 including one or more
reservoirs 1295 containing one or more therapeutic agents and/or
one or more nutraceutical agents (as described herein, the depot
can include reservoirs each with the same agent or reservoirs each
with different agents. In an embodiment, the depot includes one or
more transmitters/receivers/transceivers (not shown) or utilizes
the transmitter/receiver/transceiver of the device as described
herein, to send and/or receive signals 1230 with a computing device
(not shown). Thus, in this manner, the depot 1200 is able to be
operated by remote control. For example, a microchip depot includes
an outlet 1275 for the agent to pass from the depot to the
subject's body. In an embodiment, the one or more reservoirs 1295
are sturdy compartments with the agent contained therein and are
under pressure (e.g. from the fluid pressure of the agent), and are
activated (e.g., wirelessly) by operation of a valve 1265 operably
coupled to the reservoir 1295, which expels the agent from the
reservoir 1295 through an outlet 1275 and into the subject's body.
In an embodiment, a micropump or microjet (not shown) is utilized
to expel the agent from the reservoir 1295 through the outlet 1275
operably coupled to the micropump/microjet and the reservoir
1295.
[0101] In an embodiment, any of the reservoirs (1250, 1295, 1210)
described are manufactured with biodegradable materials, such that
the reservoir itself can be absorbed by the subject's body
following expulsion of the therapeutic or nutraceutical agent(s)
contained therein. In an embodiment, the depot includes multiple
reservoirs, each containing a different agent. In an embodiment,
the depot includes electrical circuitry (not shown) that activates
the reservoir directly or indirectly (e.g., wireless signal from
remote control, signal from computer program as part of the system
described herein, or signal from outside of the system based on
timing or feedback from at least one of the sensors of the medical
device itself (for which the depot is a component). Thus, in this
manner, in an embodiment the medical device is "stocked" with
several therapeutic and/or nutraceutical agents before activation
(whether prior to insertion of the device, or subsequent to
insertion of the device in the subject's body) and delivery of the
one or more agents to the subject. In an embodiment, the depot is
regulated based on feedback from the one or more sensors. In an
embodiment, the depot is regulated based on external commands
(e.g., from a healthcare worker, computer database, computer
program, timed schedule, etc.). For example, if a particular agent
is needed for control of inflammation (e.g., in HIV infection,
inflammatory bowel disease, Crohn's disease, etc.) the sensed
information related to inflammation is directly or indirectly
utilized to activate at least one reservoir of the depot that
contains an anti-inflammatory agent (therapeutic or nutraceutical),
and further feedback is obtained to track the reaction following
administration of the anti-inflammatory agent. If additional
dispensing of anti-inflammatory agents is needed, another reservoir
of the depot will be activated to release the same type or a
different type of anti-inflammatory agent. Likewise, if a
particular agent is needed to enhance one or more microorganisms of
the subject's microbiome or GALT, that agent is released in
response to sensed data, and the continuous or intermittent
monitoring continues, along with release of
therapeutic/nutraceutical agents as needed.
Prophetic Examples
Prophetic Example 1
An Implantable Intestinal Medicament Delivery Device with
Inflammation Sensors and a Reversibly Inflatable Anchor
[0102] An implantable medicament delivery device to prevent and
mitigate inflammatory bowel disease (IBD) is constructed as a
small, hollow tubular device with an inflatable collar to anchor
the device in the appendix and sensors to detect markers of
inflammation. The walls of the tube are hexagonal and contain
depots with reservoirs containing anti-inflammatory therapeutics to
treat inflammation in the gut and to promote a healthy gut
associated lymphoid tissue (GALT). (See Figures). The tubular
device is constructed from biocompatible materials to reside inside
the appendix and to allow free flow of mucus, cells, and fluids
into and out of the appendix through the lumen of the device. The
device, a hexagonal tube, is anchored in the appendix by an
inflatable collar, and extends distally into the ascending colon.
The device contains sensors of inflammation which signal to control
circuitry which in turn initiates release of anti-inflammatories
and prebiotics into the colon.
[0103] The device is constructed with dimensions that allow
insertion into the lumen of the appendix. For example the hexagonal
tube is approximately 6 mm in outside diameter and approximately 2
to 3 cm in length. The hexagonal tube is formed from a
biocompatible polymer, for example, polyethylene-co-vinyl acetate
(PEVA) (available from Polysciences, Inc., Warrington, Pa.; see
PEVA info sheet). Methods and materials to manufacture polymers
with a desired porosity and physical properties (e.g., flexibility,
tensile strength and biocompatibility) are described (see e.g.,
Handbook of Membrane Separations: Chemical, Pharmaceutical, Food,
and Biotechnological Applications, edited by Anil K. Pabby, Syed S.
H. Rizvi, Ana Maria Sastre, 2009, CRC Press, Boca Raton, Fla. which
is incorporated herein by reference). Alternatively a strong,
biocompatible material that slowly degrades may be used to
construct the device. For example poly(anhydride-co-imide) may be
adapted for use (see e.g., U.S. Pat. No. 6,669,683, which is
incorporated herein by reference).
[0104] The implantable device has several drug delivery reservoirs
embedded in the interior walls of the hexagonal tube. Medicaments
are released into the lumen of the device upon signaling from
control circuitry which heats thermally responsive reservoir caps.
Reservoirs are created using microelectronic manufacturing methods
and semiconductor materials. For example, reservoirs 800
.mu.m.times.800 .mu.m and approximately 500 .mu.m deep may be
created in silicon wafers using photolithography, chemical etching
and deposition technologies. Hundreds of reservoirs may be created
in arrays (also referred to as depots) approximately 2 mm.times.30
mm on the inner hexagonal walls of the tube. The reservoirs are
filled with medicaments during the manufacturing process. For
example, selected reservoirs are filled with acetaminophen to
prevent or attenuate inflammation in the appendix and the colon.
The selected reservoirs may each contain approximately 300 nL of
acetaminophen solution (e.g., acetaminophen at approximately 500
mg/ml) and deliver approximately 0.15 mg acetaminophen when each
reservoir cap is disrupted. Selected reservoirs may be filled with
a different medicament, for example, an antibody to neutralize a
proinflammatory cytokine, interferon gamma (see e.g., Hachim et
al., Saudi Med. J. 27:1815-1821, Abstract, 2006 which is
incorporated herein by reference). An antibody fragment (e.g.,
single chain variable region fragment, SCFv) that neutralizes gamma
interferon is aseptically injected into selected reservoirs of the
device. Antibody fragments to neutralize a wide variety of antigens
are described (see e.g., Pansri et al., BMC Biotechnology 9:6,
2009; available online at biomedcentral.com/1472-6750/9/6, the
subject matter of which is incorporated herein by reference).
Methods and materials to create microchips with reservoirs
containing lyophilized biologicals (e.g., proteins) are described
(see e.g., Farra et al., Sci. Transl. Med. 4, 122ra21 (2012)
available on line at:stm.sciencemag.org/content/4/122/122ra21, the
subject matter of which is incorporated herein by reference).
[0105] Microelectronic manufacturing methods are used to create
thermally responsive caps on each reservoir and corresponding
resistors for thermal disruption of each reservoir cap and delivery
of individual reservoir contents. Microcircuitry connects each
reservoir cap to a power source. Methods and materials for
constructing arrays of reservoirs with temperature responsive caps
for drug delivery are known (see e.g., U.S. Pat. No. 6,669,683
Ibid.). The device includes a microbattery to empower the control
circuitry and to heat the resistive circuits in each cap.
Rechargeable thin-film microbatteries suitable for integration with
the control circuitry of the implantable device are described (see
e.g., U.S. Pat. No. 6,669,683 Ibid.).
[0106] The device is anchored by an inflatable collar which expands
to attach to the intestinal wall of the appendix when the collar is
inflated. Anchors to retain sleeves in the gastrointestinal tract
are described (see e.g., U.S. Patent Appl. No. 2013/0281911, which
is incorporated herein by reference). The collar may be cast from
silicone and attached encircling one end of the hexagonal tube. The
collar is inflated to approximately 8-9 mm in diameter once the
device is implanted in the lumen of the appendix. The inflatable
collar contains an electronic valve to inflate or deflate the
collar. A micro air pump is incorporated on the device, and control
of the valve and air pump is mediated by control circuitry on the
device. Control circuitry on the device may respond to external
signals from a technician, computer, care-giver, or healthcare
worker. For example wireless signals from an external
radiofrequency transmitter, may direct control circuitry to
activate the air pump and inflate the collar when the device is
implanted in the appendix at the desired location. Conversely
internal signals from sensors on the device may be translated by
control circuitry to open the valve and deflate the collar, thus
releasing the device into the lumen of the colon and allowing
excretion of the device.
[0107] Sensors which detect inflammatory markers (e.g.,
proinflammatory cytokines and metabolites) near the intestinal wall
or in the lumen of the colon, send signals to the device control
circuitry which are programmed to respond by signaling release of
anti-inflammatory therapeutics and/or nutraceuticals into the lumen
of the device, or alternatively, to deflate the anchor and release
the device into the colon. For example molecular sensors may detect
elevated amounts of tumor necrosis factor (TNF) protein and/or
gamma interferon in the lumen of the device and signal the abnormal
cytokine levels to control circuitry. Sensors that detect proteins
and signal electronically may be integrated into the device along
with microfluidic components for sampling intestinal fluids. For
example, aptamer-based sensors which include microfluidic
components to measure cytokine levels in vivo and report
quantitative results electronically to a computational apparatus
are described (see e.g., U.S. Pat. No. 8,145,434, and Maehashi et
al., Anal. Chem. 79:782-787, 2007, each of which is incorporated
herein by reference).
[0108] The device control circuitry recognizes inflammation, as
indicated by elevated levels of inflammatory cytokines, and
activates release of anti-inflammatories (e.g. acetaminophen or
anti-gamma interferon antibody) from reservoirs on the device. The
dosage and schedule for release of anti-inflammatory agents is
determined by the control circuitry based on the levels of
inflammatory markers detected. For example, detection of
approximately 0.1 ng/mL of gamma interferon in intestinal fluid may
trigger release of at least equimolar amounts of anti-gamma
interferon antibodies or antibody fragments (e.g., SCFv), for
example, 0.5-1.0 ng/mL. If advanced inflammation is detected (e.g.
highly elevated levels of TNF and/or interferon gamma or clinical
indices such as abdominal pain or an elevated blood neutrophil
count) the control circuitry may automatically initiate signaling
to deflate the inflatable collar and release the device into the
colon for excretion. Alternatively, a healthcare worker, the
subject itself, or another party (including a computer programmed
for threshold determination or response to the device) may signal
with a radio frequency transmitter to the implanted device to
initiate deflation of the collar and excretion of the device.
[0109] In an embodiment, release of a therapeutic or nutraceutical
agent from a depot is based on a sensor and pre-determined
threshold. For example, if one or more sensed signals is over a
threshold level, the control electrical circuitry directs the one
or more reservoirs of a depot to release a therapeutic or
nutraceutical agent. In an embodiment, a different threshold is set
for each reservoir (and may be dictated by the contents of the
reservoir itself, that is for one particular therapeutic agent a
specific threshold is set and for another particular therapeutic
agent a different threshold is set).
[0110] The implanted intestinal device may promote a healthy
microbiome and associated GALT by delivering nutraceuticals to the
colon. For example, if low or intermediate levels of inflammatory
cytokines are detected the control circuitry may signal to
reservoirs containing prebiotics which promote the growth of
beneficial microbes. For example prebiotics, such as oligofructose
and inulin, promote the growth of beneficial bacteria, e.g.,
Lactobacilli and Bifidobacteria, and stimulate the production of
butyric acid which reduces inflammation in the colonic mucosa (see
e.g., Damaskos et al., Brit. J. Clin. Pharm. 65:453-467, 2008 which
is incorporated herein by reference). Periodic monitoring of
inflammatory markers by the device sensors informs control
circuitry which determines the dose and schedule for delivery of
prebiotics and anti-inflammatory drugs. Methods to determine the
pharmacokinetics and the dose and schedule of biologicals and
pharmaceuticals delivered by implanted devices are described (see
e.g., Farra et al., Ibid.).
Prophetic Example 2
A Semi-Rigid Delivery/Sensory Device with Expandable/Collapsible
Anchors for Implantation in the Appendix
[0111] A semi-rigid, stent-like device which maintains a
flow-through opening in the appendix and provides medicaments and
nutraceuticals to the appendix and ascending colon. The device has
expandable anchors which have collapsible joints (weak points) to
allow collapsing the anchors and removing the device. The device
has sensors to detect molecules, microbes and cells in the
intestinal fluid and the intestinal wall. Control circuitry on the
device receives signals from: the device sensors, from external
sensors, and from external transmitters. Control circuitry on the
device signals to reservoirs containing medicaments, and to
collapsible anchors on the device. The device is manufactured from
biocompatible materials and reservoirs are filled with
anti-inflammatory agents and prebiotics.
[0112] The semi-rigid device is manufactured as a cylindrical tube
formed from a grid of polymer struts with an outside diameter of
approximately 6 mm. For example a semi-rigid polymer such as
polyurethane or polyethylene may be cast or molded or extruded to
form the cylindrical device (see e.g., U.S. Patent Application No.
2014/0012178, which is incorporated herein by reference). A
suitable biocompatible polymer for example, polyethylene-co-vinyl
acetate (PEVA) is available from Polysciences, Inc., Warrington,
Pa. (see PEVA info sheet incorporated by reference herein). Methods
and materials to manufacture polymers with a desired porosity and
physical properties (e.g., flexibility, tensile strength and
biocompatibility) are described (see e.g., Handbook of Membrane
Separations: Chemical, Pharmaceutical, Food, and Biotechnological
Applications, edited by Anil K. Pabby, Syed S. H. Rizvi, Ana Maria
Sastre, 2009, CRC Press, Boca Raton, Fla. which is incorporated
herein by reference). Expandable/collapsible anchors are attached
around the circumference of one end of the device. Stent-like
intestinal devices with expandable barbs to anchor the device and
endoscopic methods to implant the device are described (see e.g.,
U.S. Pat. No. 7,267,694, which is incorporated herein by
reference).
[0113] The semi-rigid cylindrical device and the expandable barb
anchors are manufactured with weak points (see FIG. 2) to allow
collapse of the barb anchors and the cylindrical device when
removal of the device is desired. Weak points may be formed from
degradable polymers (e.g., alginate hydrogels or poly
lactic-co-glycolic acid) that are composed to be subject to changes
in pH or exposure to chemicals (see e.g., Makadia et al., Polymers
3:1377-1397, 2011 and Kong et al., Biomacromolecules 5:1720-1727,
2004 which are incorporated herein by reference). Or they may be
thin metal strips that melt upon activation of a thermal or
electric pulse (similar to the drug reservoir release caps).
[0114] Chemical and enzymatic agents to accelerate degradation at
weak points may be acids, bases, or degradative enzymes (e.g.,
alginase, agarase, esterases). Reservoirs containing degradative
chemicals and enzymes are formed adjacent to weak points, and
release their contents in response to signaling from the device
control circuitry. For example, clinical symptoms may indicate
acute appendicitis and a nurse or physician may transmit a wireless
signal to the implanted device to expel the device. Control
circuitry on the device receives the expulsion signal and signals
to the reservoirs adjacent to each weak point to release
degradative chemicals and enzymes. Polymer degradation at the weak
points and collapse of the barb anchors and the cylindrical device
promotes expulsion of the device from the appendix and excretion
via the colon. Alternatively, expulsion of the device may be
initiated by control circuitry on the device based upon signaling
from sensors on the implanted device.
[0115] Sensors which detect inflammatory markers (e.g.,
proinflammatory cytokines, cells and metabolites) near the
intestinal wall or in the lumen of the cecum, send signals to the
device control circuitry which is programmed to respond by
signaling release of anti-inflammatory therapeutics and/or
nutraceuticals into the lumen of the device, or alternatively, to
initiate expulsion of the device into the colon. For example
molecular sensors may detect proinflammatory cytokines, tumor
necrosis factor (TNF) and/or gamma interferon and electronically
transmit the cytokine levels to control circuitry. Sensors that
detect proteins and cells and signal electronically may be
integrated into the device along with microfluidic components for
sampling intestinal fluids. For example, aptamer-based sensors
which include microfluidic components to measure cytokine levels in
vivo and report quantitative results electronically to a
computational apparatus are described (see e.g., U.S. Pat. No.
8,145,434, and Maehashi et al., Anal. Chem. 79:782-787, 2007, each
of which is incorporated herein by reference). Also aptamer-based
sensors may detect leukocytes or bacteria by recognition of cell
surface molecules, e.g., receptors and antigens. The device sensors
may monitor molecular and cellular markers of inflammation over
time and quantify changes in the level of cytokines (e.g., TNF,
gamma interferon, IL-1) and the number of cells (e.g., neutrophils)
in the appendix and cecum.
[0116] Moreover, the device may include an external sensor, to
monitor inflammation. An aptamer-based sensor may be implanted
intravenously in the arm of the subject to monitor the neutrophil
count over time. Elevated neutrophil numbers in the peripheral
blood, indicative of inflammation, are transmitted wirelessly to
the implanted device and received by control circuitry on the
device. Aptamer based sensors with microfluidic components and
micro-circuitry to transmit radio frequency signals are described
(see e.g., U.S. Pat. No. 8,145,434 Ibid.). Based upon sensor input,
control circuitry on the implanted device computes the levels of
inflammatory markers and microbes, as well as initiates signaling
to release therapeutics or prebiotics from reservoirs on the
device.
[0117] Reservoirs containing therapeutics, nutraceuticals,
chemicals and enzymes are formed on the interior walls of the
cylindrical tube. Therapeutics, prebiotics and degradative agents
are released into the lumen of the device or adjacent to weak
points in the cylindrical structure and the expandable anchors.
Release of agents from the reservoirs is initiated by signaling
from control circuitry which electronically heats thermally
responsive caps on the reservoirs. The reservoirs are created using
microelectronic manufacturing methods and semiconductor
materials.
[0118] For example, reservoirs 800 .mu.m.times.800 .mu.m and
approximately 500 .mu.m deep may be created in silicon wafers using
photolithography, chemical etching and deposition technologies.
Hundreds of reservoirs (organized as depots) may be created in
microchips approximately 6 mm.times.12 mm which contain thermally
sensitive caps that may be disrupted by electronic circuitry and
embedded resistors. Microelectronic manufacturing methods are used
to create thermally responsive caps on each reservoir and
corresponding resistors for thermal disruption of each reservoir
cap and delivery of individual reservoir contents. Microcircuitry
connects each reservoir cap to a power source. Methods and
materials for constructing arrays of reservoirs with temperature
responsive caps for drug delivery are known (see e.g., U.S. Pat.
No. 6,669,683, which is incorporated herein by reference).
[0119] The implanted device also includes a microbattery to empower
the control circuitry and to heat the resistive circuits in each
cap. Rechargeable thin-film microbatteries suitable for integration
with the control circuitry of the implantable device are described
(see e.g., U.S. Pat. No. 6,669,683 Ibid.). Methods and materials to
create microchips with multiple reservoirs and thermally sensitive
caps are described (see e.g., U.S. Pat. No. 6,669,683 Ibid.). The
reservoirs are filled with medicaments or chemicals during the
manufacturing process. For example, selected reservoirs are filled
with acetaminophen to prevent or attenuate inflammation in the
appendix and the colon. Selected reservoirs may each contain
approximately 300 nL of acetaminophen solution (e.g., acetaminophen
at approximately 500 mg/ml) and deliver approximately 0.15 mg
acetaminophen when each reservoir cap is disrupted. Selected
reservoirs may be filled with a different medicament, for example,
an antibody to neutralize a proinflammatory cytokine, interferon
gamma (see e.g., Hachim et al., Saudi Med. J., 27:1815-1821, 2006
which is incorporated herein by reference). An antibody fragment
(e.g., single chain variable region fragment, SCFv) that
neutralizes gamma interferon is aseptically injected into selected
reservoirs of the device. Antibody fragments to neutralize a wide
variety of antigens are described (see e.g., Pansri et al., BMC
Biotechnology 9:6, 2009; available online at
biomedcentral.com/1472-6750/9/6, the subject matter of which is
incorporated herein by reference). Methods and materials to create
microchips with reservoirs containing lyophilized biologicals
(e.g., proteins) are also described (see e.g., Farra et al., Sci.
Transl. Med. 4, 122ra21 (2012) available on line at
stm.sciencemag.org/content/4/122/122ra21, the subject matter of
which is incorporated herein by reference).
[0120] The implanted intestinal device may promote a healthy
microbiome and associated GALT by delivering nutraceuticals to the
colon. For example, if low or intermediate levels of inflammatory
cytokines are detected the control circuitry may signal to
reservoirs containing prebiotics which promote the growth of
beneficial microbes. For example prebiotics, such as oligofructose
and inulin, promote the growth of beneficial bacteria, e.g.,
Lactobacilli and Bifidobacteria, and stimulate the production of
butyric acid which reduces inflammation in the colonic mucosa (see
e.g., Damaskos et al., Brit. J. Clin. Pharm. 65:453-467, 2008 which
is incorporated herein by reference). Periodic monitoring of
inflammatory markers by the device sensors informs control
circuitry which determines the dose and schedule for delivery of
prebiotics and anti-inflammatory drugs. Methods to determine the
pharmacokinetics and the dose and schedule of biologicals and
pharmaceuticals delivered by implanted devices are described (see
e.g., Farra et al., Ibid.).
[0121] While various aspects and embodiments have been disclosed
herein, other aspects and embodiments will be apparent to those
skilled in the art. The various aspects and embodiments disclosed
herein are for purposes of illustration and are not intended to be
limiting, with the true scope and spirit being indicated by the
following claims.
* * * * *