U.S. patent number RE48,181 [Application Number 16/233,134] was granted by the patent office on 2020-09-01 for capsule device having variable specific gravity.
This patent grant is currently assigned to CAPSOVISION INC. The grantee listed for this patent is CapsoVision, Inc.. Invention is credited to Mark Hadley, Ganyu Lu, Phat Trinh, Mikael Trollsas, Kang-Huai Wang, Gordon Cook Wilson.
View All Diagrams
United States Patent |
RE48,181 |
Trollsas , et al. |
September 1, 2020 |
Capsule device having variable specific gravity
Abstract
An endoscopy capsule having an image collecting capacity
includes a deformable member configured to inflate when exposed to
body liquid. The deformable member includes an effervescent
material. When the effervescent reacts with water the resulting
Carbon-Dioxide gas reduces the specific gravity of the endoscopy
capsule. The capsule is contained within a shell or dome when
swallowed. The shell or dome is configured dissolve in either a low
or high pH environment.
Inventors: |
Trollsas; Mikael (San Jose,
CA), Trinh; Phat (San Jose, CA), Hadley; Mark
(Newark, CA), Wang; Kang-Huai (Saratoga, CA), Wilson;
Gordon Cook (San Francisco, CA), Lu; Ganyu (Palo Alto,
CA) |
Applicant: |
Name |
City |
State |
Country |
Type |
CapsoVision, Inc. |
Saratoga |
CA |
US |
|
|
Assignee: |
CAPSOVISION INC (Saratoga,
CA)
|
Family
ID: |
1000004867400 |
Appl.
No.: |
16/233,134 |
Filed: |
December 27, 2018 |
Related U.S. Patent Documents
|
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
Reissue of: |
14659832 |
Mar 17, 2015 |
10098526 |
Oct 16, 2018 |
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B
1/041 (20130101); A61B 5/14539 (20130101); A61B
1/041 (20130101); A61B 1/2736 (20130101); A61B
1/00147 (20130101); A61B 5/6861 (20130101); A61B
1/2736 (20130101); A61B 5/14539 (20130101); A61B
1/00147 (20130101); A61B 1/00082 (20130101); A61B
5/073 (20130101); A61B 5/073 (20130101); A61B
1/00082 (20130101); A61B 5/6861 (20130101) |
Current International
Class: |
A61B
1/00 (20060101); A61B 5/07 (20060101); A61B
1/04 (20060101); A61B 1/273 (20060101); A61B
5/145 (20060101); A61B 5/00 (20060101) |
Field of
Search: |
;600/114-117,160,164,170,171 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
|
|
|
|
|
|
02/095351 |
|
Nov 2002 |
|
WO |
|
2015/060814 |
|
Apr 2015 |
|
WO |
|
Other References
E-Z-Gas.RTM. II Effervescent Granules Antiacid/Antiflatulent,
[retrieved from internet on Oct. 4, 2019 at
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=4e12e1cb-b-
033-076d-e054-00144ff8d46c&type=display]. cited by
examiner.
|
Primary Examiner: Flanagan; Beverly M
Attorney, Agent or Firm: B;airtech Solution LLC
Claims
What is claimed is:
1. A capsule endoscope, comprising: a sensor system comprising a
light source, an image sensor for capturing image frames of a scene
illuminated by the light source; a housing adapted for being
swallowed, wherein the housing encloses the sensor system; and at
least one pouch containing an effervescent, the pouch being
attached to the housing and being semi-permeable or porous.[.,
permeable.]. to body liquid .[.but not to gas.]. so that the
effervescent is able to generate gas upon contact with the body
liquid; wherein at least the pouch is encapsulated within a
dissolvable shell, dome or coating, and wherein specific gravity
(SG) of the capsule endoscope is greater than 1 when the pouch is
encapsulated within the dissolvable shell, dome or coating and
wherein the SG of the capsule endoscope corresponds to a specific
gravity of all .[.the.]. components of the capsule endoscope
collectively together; and wherein .[.the capsule endoscope.].
.Iadd.said at least the pouch .Iaddend.is configured to control
.[.estimated.]. inflation and deflation periods of .[.the capsule
endoscope.]. .Iadd.said at least the pouch .Iaddend.such that the
capsule endoscope has the SG of the capsule endoscope greater than
1 for a first period of time, and less than 1 for a second period
of time following the first period of time; .Iadd.and .Iaddend.
wherein .[.the capsule endoscope.]. .Iadd.said at least the pouch
.Iaddend.is configured to control .[.estimated.]. inflation
.Iadd.and deflation periods .Iaddend.of .[.the capsule endoscope.].
.Iadd.said at least the pouch .Iaddend.by .[.properly.]. selecting
parameters from a parameter group comprising a combination of pouch
membrane type and pouch wall thickness .Iadd.to affect a rate of
diffusion of body liquid into the pouch.Iaddend..
2. The capsule endoscope of claim 1, wherein at least the pouch is
encapsulated within an enteric shell, dome or coating.
3. The capsule endoscope of claim 2, wherein the enteric shell,
dome or coating is designed to dissolve a pH in range of 5.0-7.4 so
that the enteric shell, dome or coating is intended to disintegrate
in the small intestine or the cecum.
4. The capsule endoscope of claim 2, wherein the capsule endoscope
is configured to cause the specific gravity (SG) of the capsule
endoscope drops below 1 in about 2-6 hours after the capsule
endoscope is exposed to bodily fluids by swallowing the capsule
endoscope.
5. The capsule endoscope of claim 2, wherein the endoscope is
configured such that the specific gravity (SG) of the capsule
endoscope is more than 1 for more than about six hours after the
capsule endoscope is exposed to bodily fluids by swallowing
.Iadd.the capsule endoscope.Iaddend..
6. The capsule endoscope of claim 2, wherein the pouch has a wall
thickness of less than 2 mils for .[.one.]. .Iadd.a first
.Iaddend.group of pouch materials or less than 5 mils for
.[.another.]. .Iadd.a second .Iaddend.group of pouch materials.
7. The capsule endoscope of claim 2, wherein the pouch is
configured such that the specific gravity (SG) of the capsule
endoscope is more than 1 for more than 1.5 hours after the pouch is
exposed to bodily liquids by swallowing the capsule endoscope.
8. The capsule endoscope of claim 2, wherein the pouch is
configured such that the specific gravity (SG) of the capsule
endoscope is less than 1 for more than .Iadd.2 or .Iaddend.4 hours
after the pouch is exposed to bodily liquids by swallowing the
capsule endoscope.
9. The capsule endoscope of claim 1, wherein the endoscope is
configured such that the specific gravity (SG) of the capsule
endoscope drops below 1 in about 2-6 hours after the capsule
endoscope is exposed to bodily fluids by swallowing.
10. The capsule endoscope of claim 1, wherein the endoscope is
configured such that the specific gravity (SG) of the capsule
endoscope is less than 1 for more than about six hours after the
capsule endoscope is exposed to bodily fluids by swallowing
.Iadd.the capsule endoscope.Iaddend..
11. The capsule endoscope of claim 1, wherein the pouch
.[.comprises.]. .Iadd.is selected from a set consisting of
.Iaddend.polyetherblockamide copolymers, thermoplastic
polyurethanes, polyamides, polyamide block copolymers, polyamide
elastomers, polyurethanes, polyesters, polyester copolymers,
polyamide copolymers, polyurethane copolymers, polyether
copolymers, polyesteramides, polyesteramide copolymers, polyvinyl
chloride, polyvinyl chloride copolymers, polyvinylidene dichloride,
polyvinylidene dichloride copolymers, fluoropolymers, polyvinyl
fluoride, polyvinyl fluoride copolymers, polyvinylidene difluoride,
polyvinylidene difluoride copolymers, polyvinylpyrrolidone
copolymers, .[.or.]. .Iadd.and .Iaddend.polyvinylalcohol
copolymers.
12. The capsule endoscope of claim 1, wherein the pouch has a wall
thickness of less than 5 mils or less than 10 mils.
13. The capsule endoscope of claim .[.1.]. .Iadd.12.Iaddend.,
wherein the pouch water uptake in 12 hours relative to a pouch and
effervescent dry weight is less than 200% for .[.one.]. .Iadd.a
first .Iaddend.group of pouch materials or 50% for .[.another.].
.Iadd.a second .Iaddend.group of pouch materials.
14. The capsule endoscope of claim 13, wherein the pouch material
is selected from a set consisting of polyetherblockamide
copolymers, .[.thermoplastic polyurethanes,.]. polyamides,
polyamide block copolymers, polyamide elastomers,
.[.polyurethanes,.]. polyesters, polyester copolymers, polyamide
copolymers, .[.polyurethane copolymers,.]. polyether copolymers,
.[.polyvinyl chloride, polyvinyl chloride copolymers,.].
polyvinylidene dichloride, polyvinylidene dichloride copolymers,
fluoropolymers, polyvinyl fluoride, polyvinyl fluoride copolymers,
polyvinylidene difluoride, .[.or.]. .Iadd.and
.Iaddend.polyvinylidene difluoride copolymers.
15. The capsule endoscope of claim 1, wherein the Young's modulus
of the pouch is: high enough to create a non-conformal pouch; or
low enough to create a slightly conformal pouch, such that the
pouch can reach a maximum size 25% above the nominal size with a
maximum of 40 mg effervescent.
16. The capsule endoscope of claim 1, wherein the pouch is
configured such that the specific gravity (SG) of the capsule
endoscope is more than 1 for more than 1.5 hours after the pouch is
exposed to bodily liquids by swallowing the capsule endoscope.
17. The capsule endoscope of claim 1, wherein the pouch is
configured such that the specific gravity (SG) of the capsule
endoscope is less than 1 for more than .Iadd.2 or .Iaddend.4 hours
after the pouch is exposed to bodily liquids by swallowing the
capsule endoscope.
18. The capsule endoscope of claim 1, wherein the pouch is
configured such that the specific gravity (SG) is of the capsule
endoscope is less than 1 for more than 4 hours but less than 12
hours after the pouch is exposed to bodily liquids by swallowing
the capsule endoscope.
19. The capsule endoscope of claim 1, wherein the effervescent is
coated.
20. The capsule endoscope of claim .[.16.]. .Iadd.19.Iaddend.,
wherein the effervescent coating is an enteric coating designed to
a pH in the range of 5.0-7.4 such that the effervescent is intended
to react with water after the endoscope has reached the small
intestine.
21. The capsule endoscope of claim 1, wherein the pouch further
comprises a desiccant.
22. The capsule endoscope of claim 21, wherein the ratio of
desiccant to effervescent is 1:10 to 2:1 by weight.
23. The capsule endoscope of claim 1, wherein the pouch has a total
exterior surface area of about 300 and 1,000 mm.sup.2.
24. The capsule endoscope of claim 23, wherein between about 10 mg
and 50 mg of effervescent are contained within the pouch.
25. The capsule endoscope of claim 1, wherein specific gravity (SG)
of the capsule endoscope is greater than 1 again for a third period
of time following the second period of time after the capsule
endoscope is swallowed by a human subject.
26. The capsule endoscope of claim 1, wherein the pouch is
configured such that the specific gravity (SG) of the capsule
endoscope is less than 1 for more than 4 hours but less than 12
hours after the pouch is exposed to bodily liquids by swallowing
the capsule endoscope.
.Iadd.27. A capsule endoscope, comprising: a sensor system
comprising a light source, an image sensor for capturing image
frames of a scene illuminated by the light source; a housing
adapted for being swallowed, wherein the housing encloses the
sensor system; and at least one pouch containing an effervescent,
the pouch being attached to the housing and being semi-permeable or
porous to body liquid so that the effervescent is able to generate
gas upon contact with the body liquid, wherein the effervescent
comprises anhydrous acid; wherein said at least the pouch is
encapsulated within a dissolvable shell, dome or coating, and
wherein specific gravity (SG) of the capsule endoscope is greater
than 1 when the pouch is encapsulated within the dissolvable shell,
dome or coating and wherein the SG of the capsule endoscope
corresponds to a specific gravity of all components of the capsule
endoscope collectively together; and wherein said at least the
pouch is configured to control inflation and deflation periods of
said at least the pouch such that the capsule endoscope has the SG
of the capsule endoscope greater than 1 for a first period of time,
and less than 1 for a second period of time following the first
period of time, and wherein said at least the pouch is configured
to control inflation and deflation periods of said at least the
pouch by selecting parameters from a parameter group comprising a
combination of pouch membrane type and pouch wall thickness to
affect a rate of diffusion of body liquid into the pouch..Iaddend.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
The present invention is related to PCT Patent Application Series
No. PCT/US13/66011 entitled "System and Method for Capsule Device
with Multiple Phases of Density", filed on Oct. 22, 2013, PCT
Patent Application Series No. PCT/US13/39317, entitled "Optical
Wireless Docking System for Capsule Camera", filed on May 2, 2013
and PCT Patent Application Series No. PCT/US13/42490, entitled
"Capsule Endoscopic Docking System", filed on May 23, 2013. The
U.S. Patent and PCT Patent Applications are hereby incorporated by
reference in their entireties.
BACKGROUND OF THE INVENTION
Field of the Invention
The present invention relates to diagnostic imaging inside the
human body. In particular, the present invention relates to a
capsule device with a variable specific gravity for diagnostic
imaging of the Gastrointestinal (GI) tract.
Description of the State of the Art
Devices for imaging body cavities or passages in vivo are known in
the art and include endoscopes and autonomous encapsulated cameras.
Endoscopes are flexible or rigid tubes that pass into the body
through an orifice or surgical opening, typically into the
esophagus via the mouth or into the colon via the rectum. An image
is formed at the distal end using a lens and transmitted to the
proximal end, outside the body, either by a lens-relay system or by
a coherent fiber-optic bundle. A conceptually similar instrument
might record an image electronically at the distal end, for example
using a CCD or CMOS array, and transfer the image data as an
electrical signal to the proximal end through a cable. Endoscopes
allow a physician control over the field of view and are
well-accepted diagnostic tools. However, they do have a number of
limitations, present risks to the patient, are invasive and
uncomfortable for the patient. Additionally, patient costs
typically associated with imaging body cavities with an endoscope
prohibits their use as a routine health-screening tool.
Because of the difficulty traversing a convoluted passage,
endoscopes cannot easily reach the majority of the small intestine.
Special techniques and precautions are needed to reach the entirety
of the colon. Endoscopic risks include the possible perforation of
bodily organs traversed and complications arising from anesthesia.
A trade-off is often made between the extent of imaging taken of
body cavities and patient pain during the procedure, health risks
and/or post-procedural down time associated with the use of
anesthesia. Also, a large number of patients are uncomfortable with
the concept of traditional endoscopy and are therefore refusing the
procedure resulting in an increased risk of colorectal cancer.
An alternative in vivo image sensor that addresses many of these
problems is the capsule endoscope. A camera is housed in a
swallowable capsule, along with a radio transmitter for
transmitting data, primarily comprising images recorded by the
digital camera, to a base-station receiver or transceiver and data
recorder outside the body. The capsule may also include a radio
receiver for receiving instructions or other data from a
base-station transmitter. Instead of radio-frequency transmission,
lower-frequency electromagnetic signals may be used. Power may be
supplied inductively from an external inductor to an internal
inductor within the capsule or from a battery within the
capsule.
An autonomous capsule camera system with on-board data storage was
disclosed in the U.S. Pat. No. 7,983,458, entitled "In Vivo
Autonomous Camera with On-Board Data Storage or Digital Wireless
Transmission in Regulatory Approved Band," granted on Jul. 19,
2011. This patent describes a capsule system using on-board storage
such as semiconductor nonvolatile archival memory to store captured
images. After the capsule passes from the body, it is retrieved. A
capsule housing is opened and the images stored are transferred to
a computer workstation for storage and analysis. For capsule images
either received through wireless transmission or retrieved from
on-board storage, the images are displayed and examined by a
diagnostician to identify potential anomalies. Alternatively, the
nonvolatile archival memory may be located separately or remotely
from the capsule and the images transmitted to this memory over a
wireless data link.
FIG. 1 illustrates an exemplary capsule sensing system with
on-board storage. The sensing system 110 includes illuminating
system 12 and a camera that includes optical system 14 and image
sensor 16. A semiconductor nonvolatile archival memory 20 may be
provided to allow the images to be stored and later retrieved at a
docking station outside the body, after the capsule is recovered.
The sensing system 110 includes battery power supply 24 and an
output port 26.
Sensing system 110 may be propelled through the GI tract by
peristalsis. Illuminating system 12 may be implemented by LEDs. In
FIG. 1, the LEDs are located adjacent to the camera's aperture,
although other configurations are possible. A light source may also
be provided, for example, behind the aperture. Other light sources,
such as laser diodes, may also be used. Alternatively, white light
sources or a combination of two or more narrow-wavelength-band
sources may also be used. White LEDs are available that may include
a blue LED or a violet LED, along with phosphorescent materials
that are excited by the LED light to emit light at longer
wavelengths. The portion of capsule housing 10 that allows light to
pass through may be made from bio-compatible glass or polymer.
Optical system 14, which may include multiple refractive,
diffractive, or reflective lens elements, provides an image of the
lumen walls on image sensor 16. Image sensor 16 may be provided by
charged-coupled devices (CCD) or complementary
metal-oxide-semiconductor (CMOS) type devices that convert the
received light intensities into corresponding electrical signals.
Image sensor 16 may have a monochromatic response or include a
color filter array such that a color image may be captured (e.g.
using the RGB or CYM representations). The analog signals from
image sensor 16 are preferably converted into digital form to allow
processing in digital form. Such conversion may be accomplished
using an analog-to-digital (A/D) converter, which may be provided
inside the sensor (as in the current case), or in another portion
inside capsule housing 10. The A/D unit may be provided between
image sensor 16 and the rest of the system. LEDs in illuminating
system 12 are synchronized with the operations of image sensor 16.
Processing module 22 may be used to provide processing required for
the system such as image processing and video compression. The
processing module may also provide needed system control such as to
control the LEDs during image capture operation. The processing
module may also be responsible for other functions, such as
managing image capture and coordinating image retrieval.
After traveling through the GI tract and exiting from the body, the
capsule camera is retrieved. Its images stored in an archival
memory are read out through an output port. The received images are
usually transferred to a base station for processing and for a
diagnostician to examine. The accuracy as well as efficiency of
diagnostics is most important. A diagnostician is expected to
examine all images and correctly identify all anomalies.
As the capsule device travels through the gastrointestinal (GI)
tract, the capsule device will encounter different environments. It
is desirable to manage the capsule device to travel at a relatively
steady speed so that sufficient sensor data (e.g., images) is
collected along the desired portion of the GI tract and without
wasting power or excessive data collection.
Naturally, the density of the capsule can affect its motion through
a body liquid. If the capsule density is greater than the body
liquid in which it is found, the capsule will tend to move in the
direction of gravity. If the capsule density is less than the body
liquid density and in the absence of peristalsis, the capsule will
tend to move against gravity or remain at its location, since the
volume of fluid displaced by the capsule weighs more than the
capsule. Thus, for a capsule intended for collecting images in the
colon including the ascending colon it is desirable to have a
density ratio (i.e., (capsule density)/(body liquid)) or Specific
Gravity (SG)<1, but also have SG>1 before the capsule reaches
the large intestine, such as when the capsule is passing through
the stomach.
SUMMARY OF THE INVENTION
The present invention discloses a capsule device capable of having
its density change or vary as it travels through the
gastrointestinal (GI) tract. The capsule device comprises a sensor
system and a density control. The sensor system may include a light
source, an image sensor for capturing image frames of a scene
illuminated by the light source, an archival memory, and housing.
The light source and image sensor are enclosed within the housing.
The archival memory may be enclosed within the housing, or separate
from the housing. In the latter case the archival memory may be
accessed remotely by a wireless link with the capsule device. The
capsule device is intended for being swallowed by a patient.
Embodiments of the capsule device's density control include a pouch
containing an effervescent mixture. In some embodiments there is
one pouch containing an effervescent. In other embodiments there
can be more than one pouch, each containing an effervescent. The
pouch is made at least partially from a fluid-permeable membrane
material. Body fluid diffuses through the membrane to mobilize and
initiate the effervescent reaction, which tests show has the effect
of reducing the SG of the capsule device from between well above
and slightly below 1, for the purpose of facilitating passage of
the capsule through different regions of the GI tract. In some
embodiments the capsule SG can vary between about 1.1 and 2.0
(SG>1) and equal to and less than 1, such as between 1.0 and
about 0.84, or between about 0.98 and 0.87 (SG.ltoreq.1).
Preferably a pouch or deformable member, or at least a portion
thereof, is made from a material or materials that prevent or
minimize diffusion of the effervescent gas. Preferably, the at
least a portion of the pouch or deformable member is made from a
material or materials that are permeable but minimally permeable to
CO2 gas and water.
In respect to transit through the GI tract, there are at least two
designated regions where the capsule SG can differ. In one
embodiment, the capsule SG is greater than one for the stomach and
less than one for the ascending colon. In another embodiment the
capsule SG is less than one for the ascending colon and greater
than one for the stomach and descending colon in order to have the
capsule device assume a desired specific gravity within the GI
tract, it is helpful to have a good understanding of transit times
through regions of the GI tract. These transit times will of course
vary from person to person and depend on such factors as the age,
gender, race, health and anatomy of the patient. In some
embodiments the capsule SG may be configured to change, i.e.,
increase or decrease, based on an elapsed time from when the
patient swallows the capsule to when the capsule should have
reached the region of interest, e.g., time from swallowing the
capsule to when it has passed through the pyloric valve.
Other embodiments of a capsule device with deformable member (e.g.,
a tethered pouch containing an effervescent mixture) include a
deformable member coated with a biodegradable, bio-erodible or
bioresorbable coating to prevent body liquid from diffusing into an
interior of the deformable member for a limited period of time,
e.g., prior to the capsule device passing through the stomach.
Other embodiments include a capsule device encased or encapsulated
within a biodegradable shell that encloses the entire capsule
device, or a dome that only partially encloses the capsule device.
The coating, dome or shell embodiments prevent body liquid from
coming into contact with the deformable member until the coating,
dome or shell has fully or partially degraded within the body
liquid. The coating, shell or dome is configured to degrade after
the capsule device has passed through a portion of the GI tract. As
such, a capsule device with a SG>1 is maintained until after
essentially all of the biodegradable coating, shell or dome has
degraded or resorbed and a fluid-permeable membrane material comes
into contact with body liquid. The coating material, or material or
the shell or dome, may be essentially water soluble, enzymatic or
enteric material.
A sensing system of the capsule device may have electrical contacts
fixedly disposed on the housing, wherein the electrical contacts
are coupled to the archival memory so that an external device is
allowed to access image data stored in the archival memory through
the electrical contacts. The electrical contacts may include power
pins to provide power to the capsule device for data retrieval of
image data stored on the archival memory. Alternatively, inductive
powering can be used to provide power to the capsule device for
data retrieval of image data stored on the archival memory. In yet
another embodiment, the capsule device further comprises an optical
transmitter to transmit an optical signal through a clear window,
wherein image data from the archival memory is transmitted to an
external optical receiver.
According to one aspect of the invention, there is a capsule
device, a capsule endoscope, a method for making such a capsule
device/endoscope, a method for assembly of a capsule
device/endoscope, a system or a method for imaging of the GI Tract
including but not limited to the colon using the capsule device
having one or more, or any combination of the following items (1)
through (8): (1) Enteric coating, dome or shell; time-controlled
coating, dome or shell; water-soluble coating, dome or shell;
and/or enzymatic coating, dome or shell. (2) The Embodiment A
including one or more or, or any combination of the parameters (a)
through (i) associated with Embodiment A. (3) The Embodiment B
including one or more or, or any combination of the parameters (a)
through (i) associated with Embodiment B. (4) Any of the
embodiments of a pouch disclosed in FIG. 7A (5) Non-volatile,
archival memory for storing images, located on device or accessed
remotely by the system. (6) A capsule endoscope, comprising: a
sensor system comprising a light source, an image sensor for
capturing image frames of a scene illuminated by the light source,
and an archival memory; a housing adapted for being swallowed,
wherein the sensor system is enclosed in the housing; and a pouch
containing an effervescent, the pouch being attached to the
housing; wherein at least the pouch is encapsulated within a
dissolvable shell, dome or coating; and wherein the endoscope
specific gravity (SG) is greater than 1 when the pouch is not
submerged in water. (7) Item (6) in combination with one or more,
or any combination of the following items (6.a) through (6.$) with
item (6): (6.a) wherein at least the pouch is encapsulated within
an enteric shell, dome or coating; (6.b) wherein the enteric
coating, dome or coating is designed to a pH in the range of
5.0-7.4 so that the coating, dome or shell is intended to dissolve
in the small intestine; (6.c) wherein the endoscope is configured
such that the specific gravity (SG) drops below 1 in about two
hours after the pouch is exposed to water; (6.d) wherein the
endoscope is configured such that the specific gravity (SG) is less
than 1 for more than about six hours after the pouch is exposed to
water; (6.e) wherein the pouch comprises polyetherblockamide
copolymers, thermoplastic polyurethanes, polyamides, polyamide
block copolymers, polyamide elastomers, polyurethanes, polyesters,
polyester copolymers, polyamide copolymers, polyurethane
copolymers, polyether copolymers, polyesteramides, polyesteramide
copolymers, polyvinyl chloride, polyvinyl chloride copolymers,
polyvinylidene dichloride, polyvinylidene dichloride copolymers,
fluoropolymers, polyvinyl fluoride, polyvinyl fluoride copolymers,
polyvinylidene difluoride, polyvinylidene difluoride copolymers,
polyvinylpyrrolidone copolymers, or polyvinylalcohol copolymers;
(6.f) wherein the pouch has a wall thickness of less than 5 mils or
less than 10 mils; (6.g) wherein the pouch water uptake in 12 hours
relative to a pouch and effervescent dry weight is less than 200%
or 50%; (6.h) wherein the pouch material is selected form the set
consisting of polyetherblockamide copolymers, thermoplastic
polyurethanes, polyamides, polyamide block copolymers, polyamide
elastomers, polyurethanes, polyesters, polyester copolymers,
polyamide copolymers, polyurethane copolymers, polyether
copolymers, polyvinyl chloride, polyvinyl chloride copolymers,
polyvinylidene dichloride, polyvinylidene dichloride copolymers,
fluoropolymers, polyvinyl fluoride, polyvinyl fluoride copolymers,
polyvinylidene difluoride, or polyvinylidene difluoride copolymers;
(6.i) wherein the Young's modulus of the pouch is: high enough to
create a non-conformal pouch; or low enough to create a slightly
conformal pouch, such that the pouch can reach a maximum size 25%
above the nominal size with a maximum of 40 mg effervescent; (6.j)
wherein the endoscope pouch is configured such that the specific
gravity (SG) is more than for more than 1.5 hours after the pouch
is exposed to water; (6.k) wherein the endoscope pouch is
configured such that the specific gravity (SG) is <1 for more
than 6 hours after the pouch is exposed to water; (6.l) wherein the
endoscope pouch is configured such that the specific gravity (SG)
is <1 for more than 4 hours after the pouch is exposed to water;
(6.m) wherein the endoscope pouch is configured such that the
specific gravity (SG) is <1 for more than 4 hours but less than
12 hours; (6.n) wherein the effervescent is coated; (6.o) wherein
the effervescent coating is an enteric coating designed to a pH in
the range of 5.0-7.4 such that the effervescent is intended to
react with water after the endoscope has reached the small
intestine; (6.p) wherein the pouch further comprises a desiccant;
(6.q) wherein the ratio of desiccant to effervescent is 1:10 to
2:1; (6.r) wherein the pouch has a total exterior surface area of
about 300 and 1,000 mm2 and where the active exterior surface area
is between about 50 and 1,000 mm2; and/or (6.s) wherein between
about 10 mg and 50 mg of effervescent are contained within the
pouch. (8) One, two, three or more pouches attached to the
capsule.
INCORPORATION BY REFERENCE
All publications and patent applications mentioned in the present
specification are herein incorporated by reference to the same
extent as if each individual publication or patent application was
specifically and individually indicated to be incorporated by
reference. To the extent there are any inconsistent usages of words
and/or phrases between an incorporated publication or patent and
the present specification, these words and/or phrases will have a
meaning that is consistent with the manner in which they are used
in the present specification.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows schematically a capsule camera system in the GI tract,
where archival memory is used to store captured images to be
analyzed and/or examined.
FIGS. 2A through 2D illustrate a capsule device having an attached
pouch. FIGS. 2A and 2B show the capsule device before and after
placing the device in a dissolvable shell, such as an enteric or
non-enteric shell. FIG. 2C illustrates the device after the shell
has dissolved and the pouch is exposed to water. FIG. 2D
illustrates the state of the device after the pouch has accumulated
water and the CO2 has substantially diffused out of the pouch.
FIGS. 3A through 3B illustrate another embodiment of a capsule
device. The pouch of the device is enclosed or encapsulated within
a dome in FIG. 3A.
FIGS. 4A-4E illustrate an assembly process for the pouch of FIG.
3A.
FIG. 5 is a graph showing changes in SG and inflation for pouches
of capsule devices according to two embodiments of the disclosure.
Shown are plots for a change in SG for a capsule device according
to an Embodiment A and an Embodiment B, respectively. The
Embodiment A capsule device has no enteric coating, or no shell or
dome made from an enteric material when the capsule device is
swallowed. The Embodiment B capsule device having an enteric
coating, or shell or dome made from an enteric material when the
capsule device is swallowed. The abscissa is time (t), where t=T0
represents the time when the capsule device is swallowed or placed
or placed in body fluid. There are two ordinates in FIG. 5. The
first (leftmost) ordinate refers to the percentage change in
inflation for the pouch where 100% inflation means the highest
amount of inflation or gas pressure achieved within the interior of
the pouch. This ordinate corresponds to the solid curve in the
graphs. The adjacent ordinate refers to the capsule device SG and
corresponds to the dashed curves. Time t=T1 represents the time
when the reaction between the effervescent and water starts to take
place. Time t=T2 represents the time when the SG of the device has
reached about 1 and is becoming buoyant. SG is above 1 for the
period t=T2-T0. The period t=T2-T1 may correspond to a period of
between 0.05 to 3 hours. The capsule device has an SG less than or
equal to about 1 SG for the period t=T4-T2, which may correspond to
a period of between 1 to 12 hours.
FIG. 6 is a plot showing changes in pouch inflation over time among
six different configurations of a pouch containing an effervescent.
The ordinate refers to a normalized inflation amount where "1"
means the highest amount of inflation or volume increase for the
respective pouch.
FIG. 7A summarizes results from bench tests of inflation periods
for several different pouch configurations according to the
disclosure.
FIG. 7B report statistics (mean and standard deviation) for some of
the bench tests in FIG. 7A.
FIG. 7C is a table showing the percent and amount of weight
increase for different pouch configurations. The change in weight
is measured after the pouch was submerged for 12 hours. The weight
percentage change is measured with respect to the dry weight of the
pouch with effervescent and desiccant inside. For three of the
cases PEG was added as a desiccant, polyacrylic acid sodium salt
homo- and co-polymers are also effective polymer desiccants.
FIGS. 8A-8E illustrate an example of various specific gravity or
density states for a capsule device incorporating density
control.
FIGS. 9A-9B illustrate an example of various specific gravity or
density states for a capsule device incorporating a biodegradable
plug.
FIG. 10 illustrates an example of a capsule device incorporating
density control according to an embodiment of the present
invention, where the housing includes a flexible section to expand
or contract.
FIGS. 11A-11B illustrate an example of a capsule device
incorporating density control according to an embodiment of the
present invention, where the housing comprises two closely coupled
parts.
FIG. 12 illustrates an example of a capsule device incorporating
density control according to an embodiment of the present
invention, where an extendable part is attached to the sensor
system.
DETAILED DESCRIPTION
It will be readily understood that the components of the present
invention, as generally described and illustrated in the figures
herein, may be arranged and designed in a wide variety of different
configurations. Thus, the following more detailed description of
the embodiments of the systems and methods of the present
invention, as represented in the figures, is not intended to limit
the scope of the invention, as claimed, but is merely
representative of selected embodiments of the invention.
Reference throughout this specification to "one embodiment," "an
embodiment," or similar language means that a particular feature,
structure, or characteristic described in connection with the
embodiment may be included in at least one embodiment of the
present invention. Thus, appearances of the phrases "in one
embodiment" or "in an embodiment" in various places throughout this
specification are not necessarily all referring to the same
embodiment.
Furthermore, the described features, structures, or characteristics
may be combined in any suitable manner in one or more embodiments.
One skilled in the relevant art will recognize, however, that the
invention can be practiced without one or more of the specific
details, or with other methods, components, etc. In other
instances, well-known structures, or operations are not shown or
described in detail to avoid obscuring aspects of the
invention.
The illustrated embodiments of the invention will be best
understood by reference to the drawings, wherein like parts are
designated by like numerals throughout. The following description
is intended only by way of example, and simply illustrates certain
selected embodiments of apparatus and methods that are consistent
with the invention as claimed herein.
In the description like reference numbers appearing in the drawings
and description designate corresponding or like elements among the
different views.
For purposes of this disclosure, the following terms and
definitions apply:
The terms "about" or "approximately" mean 30%, 20%, 15%, 10%, 5%,
4%, 3%, 2%, 1.5%, 1%, between 1-2%, 1-3%, 1-5%, or 0.5%-5% less or
more than, less than, or more than a stated value, a range or each
endpoint of a stated range, or a one-sigma, two-sigma, three-sigma
variation from a stated mean or expected value (Gaussian
distribution). For example, d1 about d2 means d1 is 30%, 20%, 15%,
10%, 5%, 4%, 3%, 2%, 1.5%, 1%, 0% or between 1-2%, 1-3%, 1-5%, or
0.5%-5% different from d2. If d1 is a mean value, then d2 is about
d1 means d2 is within a one-sigma, two-sigma, or three-sigma
variance from d1.
It is understood that any numerical value, range, or either range
endpoint (including, e.g., "approximately none", "about none",
"about all", etc.) preceded by the word "about," "substantially" or
"approximately" in this disclosure also describes or discloses the
same numerical value, range, or either range endpoint not preceded
by the word "about," "substantially" or "approximately."
An "enteric" coating, or coated shell or dome, or a dome or shell
made from an enteric material dissolves when immersed in a pH
environment of greater than about 5, or that dissolves in the small
intestine but not in the stomach.
A shell or dome not coated with an enteric coating, or a
"non-enteric" coating, or a shell or dome not made from an enteric
material dissolves when immersed in bodily fluids at physiological
temperatures. A water soluble coating or material made from gelatin
or hydroxyl propyl methyl cellulose (HPMC) are examples.
A "water soluble" or "time-released" coating, shell or dome is a
water soluble coating, dome or shell that dissolves in gastric
juices or water. The coating, shell or dome can be made to dissolve
from between about 3, 5, or 10 minutes to 4 hours from the time
when it is put in contact with body fluid.
An "enzymatic" coating, shell or dome is a coating, shell or dome
constructed to dissolve when it comes in contact with enzymes in
the body.
A "time controlled" coating, shell or dome is a coating, shell or
dome constructed to dissolve within a predetermined amount of time.
A time-controlled coating may be water soluble.
"Body liquid" means a gastric liquid, liquid present in the GI
tract when the capsule device is in transit, water or a liquid in
the GI tract that is substantially water.
"Specific Gravity" or SG means the ratio of the density of a body
to the density of water at 37 Deg. Celsius. A body that is buoyant
or floats on the surface of water has its SG equal to about one or
less than one. A body that sinks in water has an SG greater than
one.
"a deformable member" means a body including a pouch, balloon,
sack, or bag made at least partially from a fluid-permeable
membrane material. In a preferred embodiment at least a portion of
the deformable member is made from a fluid-permeable membrane
material that is permeable but minimally permeable to water and CO2
gas.
In preferred embodiments the deformable member includes a pouch
made entirely from a fluid-permeable membrane material that
prevents or minimizes diffusion of the effervescent gas, a tether
for attaching the pouch to a capsule housing, and an effervescent
contained within the pouch. The pouch is sealed so that a fluid can
enter its interior only by diffusion through the membrane. In some
embodiments there can be more than one pouch.
A "desiccant" is a solid that absorbs water and does not release a
gas when it encounters water. A desiccant may be silica gel, sodium
chloride, CaCl2, MgSO4, Na2SO4, CaSO4, K2CO3, Na2CO3, NaHCO3, CaO,
BaO, Al2O3, P2O5, polymers and super absorbing polymers such as
polyethylene glycol (PEG), polyvinylalcohol (PVA),
polyvinylpyrrolidone (PVP), cellulose, alginate, polyacrylonitrile
starch graft copolymers, acylic acid acrylamide copolymers,
polyvinyl alcohol copolymers, polyacrylate polyacrylamide
copolymers, sodium polyacylate or polyacrylic acid sodium salt
(works with potassium as well), polyacryl amide copolymer, ethylene
malic anhydride copolymer, crosslinked carboxymethylclulose, and
crosslinked polyethylene oxide. The polymers can be of any
molecular weight from about 3,000 to 500,000 Daltons, or have any
structure such as linear, branched, star, dendritic, or a
combination of these structures.
An "effervescent" or "gas generating material" is a bio-compatible
material that when placed in aqueous solution generates carbon
dioxide (CO2) or another gas. A mixture of anhydrous sodium
bicarbonate and anhydrous citric acid is one example of an
effervescent, a mixture of potassium bicarbonate and anhydrous
citric acid is another example, a mixture of two or more
bicarbonate salts and anhydrous citric acid is another example. In
another embodiment citric acid is replaced by another anhydrous
solid state acid such as ascorbic acid or succinic acid. In
preferred embodiments an effervescent mixture is used.
U.S. Pat. No. 7,192,397 and U.S. Pat. No. 8,444,554 disclose a
capsule device. If the capsule SG is about 1 the device will
suspend or float in the liquid in the gastrointestinal (GI) tract
such as in the stomach or in the colon. As disclosed in U.S. Pat.
No. 7,192,397 and U.S. Pat. No. 8,444,554, the capsule device will
be carried through the small and large intestine by backpressure of
a flow of liquid through the body lumen when the capsule SG is
about 1. However, a capsule SG of about 1 or less than 1 may float
in the stomach for some time, rather than passing through the
pyloric valve. Thus, on the one hand, it is desirable to have the
capsule SG>1 so that the capsule device will pass through the
stomach without much difficulty. On the other hand, a capsule
device with SG>1 will not will easily ascend the colon, or may
sit stationary in the cecum for a long period of time. Capsule
devices according to one aspect of the disclosure can, however,
traverse the ascending colon by having the capsule device SG become
less than 1 by the time the capsule device reaches the cecum.
For a capsule device with an image sensor, it is desirable to have
a steady and consistent travelling velocity inside different
regions of the GI tract, e.g. stomach, small bowel, ascending and
descending colons so that smooth and stable images and video can be
obtained. The travelling velocity of the capsule camera depends on
many factors including regional gastrointestinal motility,
gravitational force, buoyancy and viscous drag of the surrounding
fluids. After the capsule device is swallowed, it is propelled into
the esophagus. Peristaltic waves in the esophagus move the capsule
device into the stomach. After the capsule device passes the cardia
and enters the stomach fluid, the balance among gravitational
force, buoyancy and drag from the gastric fluids starts to affect
its travelling velocity and transit time. Travel through the
stomach for the capsule device may be understood through the
migrating myoelectric complex or cycle (MMC). The MMC can be
divided into four phases. Phase 1 lasts between 30 and 60 minutes
with rare contractions. Phase 2 lasts between 20 and 40 minutes
with intermittent contraction. Phase 3, or housekeeping phase,
lasts between 10 and 20 minutes with intense and regular
contractions for short period. The housekeeping wave sweeps all the
undigested material out of the stomach to the small bowel. Phase 4
lasts between 0 and 5 minutes and occurs between phase 3 and phase
1 of two consecutive cycles. In the small intestine, the BER (basic
electrical rhythm) is around 12 cycles/minute in the proximal
jejunum and decreases to 8 cycles/minutes in the distal ileum.
There are three types of smooth muscle contractions: peristaltic
waves, segmentation contractions and tonic contractions. Normally,
peristalsis will propel the capsule device towards the large
intestines.
While the large intestine is one organ, it demonstrates regional
differences. The right or proximal (ascending) colon serves as a
reservoir and the distal (transverse and descending) colon mainly
performs as a conduit. The character of the luminal contents
impacts the transit time. Liquid passes through the ascending colon
quickly, but remains within the transverse colon for a long period
of time. In contrast, a solid meal is retained by the cecum and
ascending colon for longer periods than a liquid diet. In the
ascending colon, retrograde movements are normal and occur
frequently. In order for the buoyant force to overcome the
gravitational force and retropulsion, the specific gravity of the
capsule device may be decreased to less than one (e.g., about 0.94
or less) by the time the capsule device enters the large intestine.
Additionally, the capsule device may have its SG increased back to
above 1 by the time it reaches the transverse or descending colon
to shorten the transit time to the rectum, and/or to facilitate or
more smooth and steady motion to the rectum.
In order to properly set the specific gravity of a capsule device,
one of course needs to know when the capsule device will arrive (or
has arrived) at specific regions of the GI tract. There are various
known region detection methods in the literature. The region
detection methods include estimated transit time (e.g., about 1
hour in stomach and about 3-4 hours in small bowel), identification
of image contents based on captured images by the capsule device,
motion detection based on the captured images by the capsule
device, pH detection (pH value increasing progressively from the
stomach (1.5-3.5) and the small bowel (5.5-6.8) to the colon
(6.4-7.0), pressure sensor (higher luminal pressure from
peristaltic motion in the colon than that in the small bowel) and
colonic microflora. The ascending colon has a larger diameter than
other regions besides the stomach. The size may be detected by the
methods disclosed in U.S. Patent Publications, Series No.
2007/0255098, published on Nov. 1, 2007, U.S. Patent Publications,
Series No. 2008/0033247 published on Feb. 7, 2008 and U.S. Patent
Publications, Series No. 2007/0249900, published on Oct. 25,
2007.
According to some embodiments, the capsule device is configured to
have a specific gravity (SG) larger than 1 when the device resides
in the stomach. For example, the capsule device SG is about 1.1, or
between 1.1 and 2. After the capsule device passes through the
small bowel and enters the cecum, it must traverse the ascending
colon. The capsule device SG is reduced to less than 1 (e.g., about
0.94) by the time it reaches the ascending colon. By reducing the
SG the procedure time should not unnecessarily be prolonged so that
patient does not need to fast for too long. Furthermore, the
battery life for the capsule device is limited. If the capsule
device stays in the ascending colon for too long, the battery may
be exhausted before the capsule device finishes its intended tasks,
such as capturing images of the colon. Therefore, it is preferred
that the capsule device has a specific gravity less than 1 by the
time it reaches the cecum or ascending colon. For example, the
capsule device may have an SG of about 0.94 or less. During the
intermediary period between the stomach and large intestine the
capsule device may have a SG of less than or greater than 1. In
some embodiments, the capsule device may evolve into a first state
with a specific gravity greater than 1 when the capsule device
resides in the stomach; the capsule device then evolves into a
second state with a specific gravity less than 1 by the time the
capsule device reaches the ascending colon; and the capsule device
further evolves into a third state with a specific gravity greater
than 1 or with a density heavier than the liquid by the time it
reaches the descending colon. Finally the capsule device will reach
the anus for excretion. An SG of about 1.1 or larger may be
selected for the stomach and descending colon and a specific
gravity of 0.94 or smaller may be selected for the ascending colon.
The embodiments of a deformable member where the SG slower changes
based on the rates of diffusion of gas or liquid is an example of
an evolving SG capsule device.
FIGS. 2A through 2D depict a capsule device 120 including a
deformable member 140 tethered to the housing 10 of the sensing
system 110 (FIG. 1).
FIG. 2A depicts an assembled view showing the capsule device 120
prior to being encased or encapsulated within a shell 130
configured to transport the device 120 to a target region of the GI
tract, e.g., the stomach or the duodenum. The deformable member 140
includes a pouch 141 formed from a semi-permeable or porous
membrane 222, an effervescent 224 contained within an interior of
the pouch 141 and a tether 144 connecting the pouch 140 to the
housing 10. The tether 144 is secured to a loop 146 disposed at an
end 10a of the housing 10.
FIG. 2A depicts the capsule device before the deformable member 140
expands in response to the effervescent 224 being exposed to body
liquid. The pouch 140 interior space is sealed from its exterior
environment, thereby allowing a fluid to pass in/out of the pouch
interior only through diffusion through its membrane 222 (an
assembly of the deformable member 140 is discussed in connection
with FIGS. 4A through 4E).
FIG. 2B shows the capsule device 120 within a biodegradable shell
130, which may be water soluble or enteric. The shell 130 has a
front piece or portion 130a shaped to form a space for the
deformable member 140'. The folded pouch 141' is packed within this
open space provided at the front piece/portion 130a of the shell
130. The shell 130 may be made in two pieces (i.e., a front piece
130a and rear piece 130b) that are secured together and may be
coated by a water soluble, enteric or enzymatic coating 131.
The shell 130 may be made such that it adds significant additional
weight to the capsule device to effectively increase the net SG of
the capsule device and shell; or ballast may be included within the
shell with the capsule device. In either case, the increased SG can
be favorable for reducing transit time through the stomach. After
the shell dissolves this additional weight is lost.
In the case of the shell 130 being made from an enteric material,
when the shell and capsule device of FIG. 2A approach the terminal
ileum or the cecum, the shell 130 has substantially or entirely
dissolved due to the higher pH level. At this point body liquid
begins to diffuse through the porous material 222 and enters the
pouch 141 interior space. As depicted in FIG. 2C, the diffused body
liquid reacts with the effervescent 224 therein to produce CO2.
Although a small amount of body liquid resides in the pouch
interior, the net effect of the reaction increases the volume of
the pouch 140 to a greater extent than the added pouch weight
brought on by the body liquid. As a result, the SG of the device in
FIG. 2C is less than the SG of the device in FIG. 2A.
FIG. 2D depicts the state of the device 120 after all or most all
of the effervescence has taken place and the CO2 has diffused out
of the pouch 141. For example, after about 4 to 12 hours from the
start of the reaction producing CO2 the pouch 141 interior contains
mostly but limited amounts of water 230 from body liquids, which
results in a small increase in the device 120 SG. Eventually the
device 120 SG returns to the SG it had prior to the capsule device
being placed in the shell 130.
In some embodiments the pouch 140 may be rectangular when deployed,
as in the case of FIG. 2C. In other embodiments the pouch may be
elliptical, e.g., circular, so that when it inflates with CO2 the
pouch has more rounded corners. In some embodiments the pouch 140
may be designed to be more of a hat or a sock on the housing, such
as the embodiments described in connection with FIGS. 8A-8C. In
some embodiments the shell 130 may completely encapsulate a sensing
device and deformable member, or only a portion of the sensing
device so as to allow the sensing device to acquire data prior to
the deformable member being exposed to body liquid. Any combination
of these embodiments is contemplated.
With reference to FIGS. 3A through 3B there is depicted a capsule
device 122 including a deformable member 150 tethered to the
housing 10 of a sensing system 112 according to another embodiment.
FIG. 3A depicts the device 122 with a dome 132 (shown in
cross-section) encapsulating the deformable member 150 but not the
entire sensing system 112. A sensing system according to this
embodiment may be the same as that described for the capsule
endoscope in U.S. Pat. No. 8,636,653 (the '653 patent). Referring
to the '653 patent, in FIG. 2A there is shown a field of view (FOV)
defining an imaging region 212, which is directed radially outward,
as opposed to forwardly with respect to the axis A in FIG. 3A. The
shell 130 that encloses the entire device (FIG. 2B) would prevent
images from being gathered until the shell 130 has dissolved, since
the shell 130 blocks or obscures the FOV for an capsule endoscope
configured as in the '653 patent.
Referring to FIG. 3A the sensing system 112 radially-outwardly
directed FOV is indicated by the shaded area 115. The dome 132
(enclosing a folded deformable member 150') is sized to not
obstruct this FOV for the sensing system 112. By the dome 132 not
covering the FOV it is possible for the capsule device 122 to
gather images before the dome 132 has dissolved. The dome has a
bulbous shape such that the radius of curvature of the bulbous dome
may be greater than a radius of curvature of the housing surface it
covers. The dome 132 has a straight or cylindrical shaped end 133.
The dome 132 may be secured in place by a biodegradable adhesive
applied between the end 133 and surface of the housing 10. The dome
may alternatively have about the same radius of curvature as the
housing surface it covers. In this case the dome 132 may have an
elongated cylindrical section 133 sized to provide the space
between the inner dome surface and housing surface 10 for the
folded deformable member 150'.
Referring to FIG. 3B there is shown the deformable member 150 after
the dome 132 has dissolved and the effervescent 224 begins to react
with the diffused body liquid. The pouch 151 is shaped as an
ellipse, which may be preferred over the rectangular-shaped pouch
141 from FIG. 2B.
By its construction the pouch 140 when at full inflation may tend
to form a cylindrical volume but with the seams extending around
its perimeter. In the case of the elliptical-shape pouch, the
inflated shape may to take the form of a spheroid having the seams.
In other embodiments the pouch 140 or 150 may be formed (at least
in-part) by a blow-molding or injection molding process, in which
case the pouch may more resemble a cylindrical shape or spheroid,
respectively.
FIGS. 4A through 4E depicts an assembly of the deformable member
140. In this example a length of 30 mm is chosen for the tether
144. And membrane material of 60.times.11 mm selected for the pouch
141 (FIG. 4A). The membrane 222 is folded over to make the
30.times.11 mm size for the pouch 141 (FIG. 4B). Three sides 147 of
the membrane 222 are secured together (FIG. 4C), e.g., by heat
seal. The effervescent 224 is added to the pouch 141 (FIG. 4D). The
pouch 141 is evacuated of air and heat sealed on the open side
147a, to produce the deformable member 140 of FIGS. 2A-2D. To make
the pouch of FIG. 3B a membrane 222 may be cut to have a connected
pair of ellipse shapes, so that when folded at the connection part
the pouch shape takes the form shown in FIG. 3B.
With reference to FIG. 5 there is a graph depicting inflation and
deflation periods for two types of capsule devices called
Embodiment A and Embodiment B, respectively. The Embodiments A
and/or B may correspond to any of the illustrated embodiments of a
capsule device having deformable members 140 or 150. The solid
curves refer to an inflation percentage (verses time) and the
dashed curves refer to the change in SG for the Embodiments A and
B, respectively. In these graphs the SG values of 0.94 and 1.1 are
provided only as examples. As noted earlier, the upper end of SG
may be up to 2 and the lower end may be as low as 0.8. Moreover,
the inflation percentage (80% and 100%) is exemplary only. In some
embodiments the pouch may be constructed so that a desired lower
end for SG is reached at only about 70%, or 75% inflation.
TABLE 1A, below, provides one example of a capsule device having
the characteristics of Embodiment A. In this example the capsule
device has no enteric coating, nor does it have a shell or dome
made form an enteric material. Thus, the deformable member of
Embodiment A becomes exposed to body liquid relatively soon after
the capsule is swallowed, e.g., within 5-30 minutes after being
swallowed. According to Embodiment A the deformable member may
become exposed to body liquid while the capsule resides in the
stomach. Capsule devices according to Embodiment A, which are
configured for use without an enteric coating, or enteric shell or
dome, have a deformable member that inflates more slowly than
capsule devices encapsulated within an enteric coating or material.
Embodiment B, in contrast, has a faster rise time. In the preferred
embodiments the balloon is configured so that when it reaches about
80% inflation the capsule SG is equal to or less than 1.
TABLE-US-00001 TABLE 1A (Embodiment A) Time Approximate point/ time
after Approximate interval swallowing location for FIG. 5 (hours)
patients Comment T0 n/a Mouth Capsule SG >1; camera capsule with
attached ouch encased in soluble sphere or dome T1 5-30 min Stomach
Outer sphere or dome dissolved and camera capsule with attached
pouch comes in contact with body fluids. Capsule SG starts to
decrease as water permeates the pouch and initiates reactions with
effervescent within. CO2 is generated. T2 1-4 hours small Capsule
SG becomes <1 and intestine enough CO2 gas has been produced to
make the device bouyant. T1 .ltoreq. 1-4 hours* n/a CO2 gas
generation is slow t .ltoreq. T2 enough to prevent the device from
becoming bouyant and trapped in the stomach T3 n/a Large Capsule SG
<1; SG is lowest, intestine CO2 volume and gas pressure as gas
diffuses through membrane wall faster than it is produced. T4 3-15
hours Large Capsule SG becomes >1; CO2 intestine gas has
diffused through membrane wall and the device is no longer bouyant
T2 .ltoreq. 4-12 hours* n/a Capsule SG <1; Device is t .ltoreq.
T4 bouyant and SG is below 1 for at least 4 hours to make sure the
device transits well from small intestine to lage intestine. T5
4-25 hours Excreted or >90% of the generated CO2 gas in large
has diffused out of the pouch intestine *Does not reflect the times
from swallowing the device
TABLE-US-00002 TABLE 1B (Embodiment B) Approximate Approximate
Time- time after location point swallowing for most FIG. 5 (hours)
patients Comment T0 n/a Month Capsule SG >1; camera capsule with
attached pouch encased in soluble sphere or dome T1 10 min- Small
Outer sphere or dome w euteric 3 hours intestine or time controlled
coating dissolved and camera capsule with attached pouch comes in
contact with body fluids. Capsule SG starts to decrease as water
permeates the pouch and initiates reaction with effervescent within
and CO2 starts to be generated. T2 30 min- Small Capsule SG becomes
<1 and 3.5 hours intestine enough CO2 gas has been produced to
make the device bouyant. T1 .ltoreq. 5 min- n/a CO2 gas generation
can be fast t .ltoreq. T2 1 hour as the device is already in small
intestine and the risk that the device becomes bouyant and trapped
in the stomach is low. Allows for thinner pouches. T3 n/a Large
Capsule SG <1; SG is lowest. intestine CO2 volume and gas
pressure at highest and begins to decrease as gas diffuses through
membrane wall faster than it is produced T4 3-15 hours Large
Capsule SG becomes >1; CO2 intestine gas has diffused through
membrane wall and the device is no longer bouyant. T2 .ltoreq. 2-15
hours* n/a Capsule SG <1; Device is t .ltoreq. T4 bouyant and SG
is below 1 for at least 2 hours to make sure the device transits
well from small intestine to large intestine. T5 4-25 hours
Excreted or >90% of the generated CO2 gas in large has diffused
out of the pouch intestine *Does not reflect the times from
swallowing the device
TABLE 1B, below, provides one example of a capsule device having
the characteristics of Embodiment B. In this example the capsule
device has an enteric or time-controlled coating, or has a shell or
dome made from an enteric or time-controlled material. Thus, the
deformable member of Embodiment B becomes exposed to body liquid
after the capsule has passed through the pyloric valve. According
to Embodiment B the deformable member does not become exposed to
body liquid until the capsule reaches the small bowel (Once the
enteric or time-controlled coating has dissolved the body fluid
dissolvable shell or dome dissolves quickly). Capsule devices
according to Embodiment B have a deformable member that inflates
more quickly than capsule devices encapsulated without an enteric
or time-controlled coating or material (Embodiment A). Referring
once again to FIG. 5, the different curves and/or slopes of curves
for the pouch inflation pressure vs. time, and/or percent inflation
for a target SG to achieve buoyancy, may be arrived at by varying
parameters affecting the inflation rate and duration for the pouch
when exposed to body liquid. These parameters may include one or
more, or any combination of the following parameters (a) through
(i): (a) The amount (by weight or volume) of effervescent in the
pouch. In one embodiment between about 1 and 100 milligrams, and
more preferably between about 5 to 50 milligrams of an effervescent
comprising a bicarbonate salt an anhydrous acid or preferably,
sodium bicarbonate, and/or potassium bicarbonate, and anhydrous
citric acid is used. In a preferred embodiment the effervescent is
composed of about 20% by weight of sodium bicarbonate, about 40% by
weight of potassium bicarbonate, and about 40% by weight anhydrous
citric acid. (b) Coarse or fine granules of effervescent or an
effervescent tablet. And/or aged or fresh granules of effervescent
or an effervescent tablet. (c) The amount of desiccant in the pouch
vs. effervescent. In one embodiment a ratio of between about 1:25
and 1:0.04 of desiccant to effervescent, and more preferably
between about 1:10 and 1:0.1 of desiccant to effervescent is used.
In a preferred embodiment polyethylene glycol is used as a
desiccant and the ratio of effervescent to this desiccant is 0.5 to
2, or 1 to 1. A preferred molecular weight of the polyethylene
glycol is in the range of 5,000 to 50,000 Daltons with a linear, 4-
or 8-armed star structure. (d) The presence of a coating over the
effervescent, e.g., an enteric coating or water soluble coating. In
some embodiments it may be desirable to coat the effervescent
material with a coating so as to obtain a more controlled release
of CO2. The effervescent may be coated with an enteric coating, to
be used in combination with a shell or dome that dissolves in the
stomach. In some embodiments it may be desirable to have the
effervescent placed in contact with the membrane of the deformable
member so that body liquid diffused through the membrane will reach
and react with the effervescent material as quickly as possible. In
other embodiments it may be unnecessary or undesirable to place the
material in contact with the membrane because it is desirable to
delay the reaction time for reasons previously given above. (e) The
pouch size. In one embodiment a rectangular pouch has dimensions of
about 30.times.11 mm or about 2.times.330 mm.sup.2 surface area
total surface area for the outer surface of membrane material. A
rectangular pouch (FIG. 2A) may have a ratio of length to width of
2:1, 1:1, or 3:1, or between 2:1 to 3:1 for the membrane. The pouch
may alternatively have an elliptical shape (FIG. 3B). In the
embodiments the total external surface area of the pouch
(representative approximately of its internal volume capacity when
under pressure) is between 50 and 1,500 mm.sup.2 and more
preferably between 300 and 1,000 mm.sup.2. (f) The membrane wall
thickness. The wall thickness can range from between 0.2 to 10 mils
(about 5 to 254 microns) and more preferably 0.5 to 5 mils (about
12 to 125 microns). (g) The membrane may be made from any of the
following, or combinations of material: polyetherblockamide
copolymers, thermoplastic polyurethanes, polyamides, polyamide
block copolymers, polyamide elastomers, polyurethanes, polyesters,
polyester copolymers, polyamide copolymers, polyurethane
copolymers, polyether copolymers, polyesteramides, polyesteramide
copolymers, polyvinyl chloride, polyvinyl chloride copolymers,
polyvinylidene dichloride, polyvinylidene dichloride copolymers,
fluoropolymers, polyvinyl fluoride, polyvinyl fluoride copolymers,
polyvinylidene difluoride, polyvinylidene difluoride copolymers,
polyvinylpyrrolidone copolymers, polyvinylalcohol copolymers, two
layered, three layered, or multi layered films of various materials
may be used to provide a combination of barrier properties from one
material and mechanical or adhesive properties for sealing of
another. Pouches may also have one material on one side and another
material on the other or opposite side. The membrane material may
be present on the entire side, or only a portion of one side, or
only exposed on a portion of one side or both sides. Additionally,
the membrane composition may be varied by thickness, polymer type,
layering of different or the same material, or by change of
patterning. (h) An enteric, enzymatic, time-controlled (water
soluble), or body fluid-soluble (water-soluble, non-enteric)
coating. (i) An enteric, enzymatic, time-controlled (water
soluble), or body fluid-soluble (water-soluble, non-enteric) shell
or dome.
With respect to parameter (a), the more effervescent material in
the pouch, the more CO2 gas is available for inflating the pouch.
The amount of effervescent chosen may be based on the desired
amount and duration of buoyancy for the capsule. For example,
referring to FIG. 5 the duration of time for Embodiment A at or
above 80% inflation covers the period T2 to T4. During this time
the capsule has an SG no greater than 1. Thus, for this embodiment
it can be expected that the capsule will float in the body liquid
from T2 to T4. If a greater amount of effervescent is added the
duration of time where SG is less than 1 may increase.
With respect to parameter (b), the coarseness of the effervescent
particles, or choice of a tablet over particles for the
effervescent may change the reaction times, e.g., production of CO2
at a quicker rate when finely ground effervescent particles are
used in place of a tablet due to the increased surface area. In
current testing however it was found that the size of the
effervescent granules, or choosing a granule over a tablet did not
produce much change in the curves of FIG. 5.
With respect to parameter (c), the addition of desiccant to the
pouch can significantly delay or reduce the rate of CO2 production
in the pouch, because the desiccant will adsorb water, or absorb
water depending on the desiccant used (both types are contemplated
for use). Accordingly, by using a greater percentage of desiccant
material (in proportion to effervescent) the rise time for pouch
inflation can be increased. For example, all other parameters being
equal between Embodiments A and B, the Embodiment A curve (FIG. 5A)
may be achieved by adding more desiccant to the pouch of Embodiment
B (FIG. 5B), thereby making the rise time longer for Embodiment A
than Embodiment B. A slower rise time is preferred for a shell,
dome or coating that dissolves in the stomach.
Thus, with respect to parameters (b) and (c), the addition of
desiccant inside the pouch will adsorb (or absorb) the water from
the body liquid and delay production of CO2 and the coarseness of
the desiccant particles, or choice of a tablet over particles for
the effervescent combined with the desiccant may change the
reaction times, e.g., production of CO2 at a slower rate when
finely ground and well mixed as a powder or tablet effervescent and
desiccant particles are used in place of a more coarse or less well
mixed mixture due to the increased surface area.
With respect to parameter (d), the coating on the effervescent
particle (or tablet) may prevent or delay the body liquid
mobilization of the effervescent material and therefore may delay
the production of CO2 until the right time or the pH has changed.
The coating thus can effectively reduce the rate of CO2 production
within the pouch and increase the rise time. In some embodiments an
effervescent has an enteric coating. Other embodiments use instead
a coating designed to dissolve in the stomach or small bowel within
about 2-4 hours after being in contact with body fluids, unless
they are enteric, in which case they will not dissolve in the low
pH of the stomach but disintegrate in the higher pH environment of
the small bowel or colon. The coating may be made of polymers,
polysaccharides, plasticizers, methyl cellulose, gelatin, sugar, or
other materials. Hydroxypropylcellulose, hypromellose acetate
succinate and methacrylic acid co-polymer type C are examples of an
enteric polymer. These materials may also be applied as coatings to
the deformable member alone or to it and the sensing system. For
example, all other parameters being equal the Embodiment A curve
(FIG. 5A) may be achieved by using a non-coated effervescent, while
using a coated effervescent material may delay the onset of T1 from
being in the stomach to being in the small bowel (Embodiment B,
FIG. 5B) or if time controlled may delay it from 20 min after
swallowing to 2-4 hours after swallowing. A delayed T1 is preferred
for a shell or dome that dissolves in the small intestine. It also
allows the use of thinner balloon materials.
With respect to parameter (e), pouch sizes may be limited to ensure
that it does not get caught on any anatomy when the pouch becomes
inflated, e.g., if the pouch were to achieve near 100% inflation
prior to reaching the cecum. A smaller pouch size for the same
amount of effervescent should produce a higher gas pressure, which
may increase the rate of diffusion of gas from the membrane. In
some embodiments a more non-compliant membrane is used, as a
measure for controlling the volume of the inflated pouch. A
compliant membrane material may be used, as a measure for
controlling internal pressure. A less or more compliant membrane
material may be understood as a membrane having a lower or higher
wall thickness, respectively, or a lower or higher elastic modulus
in general.
With respect to parameters (f) and (g), the pouch membrane material
and wall thickness can affect the rate of diffusion of body liquid
(water) into the pouch interior and as a result the rate of CO2
production, parameters (f) and (g) also affect diffusion of CO2 gas
out of the pouch. For example, if the membrane wall thickness is
increased, the rate at which body fluid diffuses into, and/or CO2
gas diffuse out of the pouch interior should decrease. As will be
appreciated from the foregoing, this effect may be somewhat
different if, for example, at the same time the amount of
effervescent used per unit volume of the pouch interior is
increased or decreased. If there is more gas produced per unit
volume the pouch internal gas pressure should increase, which may
decrease the diffusion of body fluid into the pouch thereby
increasing the buoyancy period and/or increasing the rise time.
Similarly, for a higher wall thickness the deflation period (e.g.,
from T4 to T5 in FIG. 5B) should increase. An increase or decrease
in the surface area of the pouch may be thought of as having a
similar effect as a decrease or increase, respectively, in the
effervescent per unit volume. For example, for an increase in the
surface area with no increase in the amount of effervescent used
the rise time should decrease.
With respect to parameters (h) and (i), embodiments of a capsule
device have an enteric coating, or shell or dome made from an
enteric material, or the capsule device may be coated with an
enteric, enzymatic, time-controlled (water soluble), or body
fluid-soluble (water-soluble, non-enteric) coating, or use shells
or domes devoid not made from an enteric material. FIGS. 5A and 5B
and Tables 1A and 1B illustrate these differences. The foregoing
selection of appropriate parameters to achieve a desired inflation
rate may be guided substantially by whether or not an enteric
coating or material is used. Embodiments of coatings, domes or
shells are designed to dissolve in the stomach or small bowel
within about 30 minutes of swallowing, unless they are enteric, in
which case they will not dissolve in the low pH of the stomach but
disintegrate in the higher pH environment of the small bowel or
colon. The shell or dome may be made of polymers, polysaccharides,
plasticizers, methyl cellulose, gelatin, sugar, or other materials.
Hydroxypropylcellulose, hypromellose acetate succinate and
methacrylic acid co-polymer type C are examples of an enteric
polymer These materials may also be applied as coatings to the
deformable member alone or to it and the sensing system. There may
be reasons for using one type of dome, coating or shell over
another depending on the type of application. On the one hand a
shell configured to dissolve in the stomach is reliable and should
not depend too much on the patient's condition. On the other hand,
there may be concern over whether the pouch inflates too soon and
before the capsule has passed through the stomach. In this case the
capsule may not exit the stomach and instead float in the
stomach.
An enteric shell or an enteric coated shell should not dissolve
fully until the capsule has reached the small bowel. Thus, the
pouch should ideally not start to inflate until after the capsule
has passed through the stomach. The advantage here is the pouch may
inflate rapidly and the only possible limitation or challenge may
be to keep pouch inflated long enough to stabilize its transit
through the ascending colon as well as through the transverse
colon. Another advantage is that more types and/or thinner pouch
materials may be used. And there is less need for desiccants.
However, an enteric shell or coating can be expensive and more
sensitive to changes in pH. Thus, the enteric shell may not fully
dissolve in the small bowel unless the pH level is sufficiently
high, which can make its effectiveness more dependent on a
particular patient's condition. Should the shell not dissolve, the
pouch cannot inflate and the capsule will not ascend the colon.
Thus, when choosing between an enteric shell, dome or coating
verses one that is dissolved by gastric juices, one may select a
pouch configuration that has a slower rise time when the shell,
dome or coating dissolves in the stomach. And when an enteric
shell, dome or coating is used the rise time can be decreased.
There may be advantages or disadvantages, and/or other factors to
consider. For instance, a configuration that yields a slower rise
time may also take longer to deflate, which can result in
unacceptable delay in getting the capsule through the transverse
and descending colon due to its low SG. This problem may be
overcome by using a relatively thin wall thickness, since tests
show that the deflation time is mostly a function of the wall
thickness of the membrane.
Testing
Bench tests were conducted to evaluate changes in buoyancy periods
for a variety of pouch configurations. The tests varied the amount
of effervescent material, the pouch material, pouch wall thickness
and dimensions, as well as the type and amount of desiccant. The
apparatus used to test pouch properties consisted of a pouch
(assembled as shown in FIGS. 4A-4E) suspended from an arm coupled
to a weighing scale. The arm overhung a basin of water heated to
about 37.degree. C. Ballast was attached to the pouch. The weight
of the suspended pouch and ballast were recorded (dry weight).
Next, the pouch and ballast and were dropped into the water. The
change in weight of the pouch and ballast were then recorded over
the next 10 to 20 hours.
As the reaction between the water and effervescent takes place, the
SG of the pouch and ballast changed: the SG decreased (CO2 produced
from the reaction between the water and effervescent), the SG
reached a minimum value (corresponding to a 100% inflation
condition), and then the SG increased as CO2 diffused from the
pouch.
FIG. 6 is a normalized plot showing changes in pouch inflation
volume over time among six different configurations of a pouch from
the bench tests. The ordinate refers to the percentage change in
inflation for the pouch where 100% inflation means the highest
amount of inflation or gas pressure achieved within the interior of
the pouch. The test article for each of the six test samples
depicted in FIG. 6 (labeled as "Exp 1", "Exp 2", "Exp 3", "Exp 4",
"Exp 5" and "Exp 6") are summarized below:
Exp 1: a pouch membrane was made from PEBAX 4 mils and with
dimensions 30.times.11 mm, wall thickness 4 mil (0.1 mm), and 20 mg
of effervescent used (fine grind, aged).
Exp 2: a pouch membrane was made from PEBAX 4 mils and with
dimensions 30.times.11 mm, wall thickness 4 mil (0.1 mm), and 20 mm
of effervescent used (fine grind, aged).
Exp 3: a pouch membrane was made from PEBAX 4 mils and with
dimensions 30.times.11 mm, wall thickness 4 mil (0.1 mm), and 20 mg
of effervescent used (fine grind, fresh).
Exp 4: a pouch membrane was made from PEBAX 4 mils and with
dimensions 30.times.11 mm, wall thickness 4 mil (0.1 mm), and 20 mg
of effervescent used (fine grind, fresh).
Exp 5: a pouch membrane was made from PEBAX 4 mils and with
dimensions 30.times.11 mm, wall thickness 4 mil (0.1 mm), and 20 mg
of effervescent used (coarse grind, fresh).
Exp 6: a pouch membrane was made from PEBAX 4 mils and with
dimensions 30.times.11 mm, wall thickness 4 mil (0.1 mm), and 20 mg
of effervescent used (coarse grind, fresh).
FIG. 7 shows additional results from tests. Listed are the
materials and size and wall thickness of the pouch. The amount of
effervescent used was varied from between 5 mg to 30 mg and was
either coarse or fine, and aged or new. The "n" vales refer to the
number of experiments performed. The data under the columns Ta, Tb,
Tc, Td, Te and Tf are explained below (time "T0" refers to the
moment when the pouch is placed in the water). These times are
given in units of hours.
Ta is the time elapsed from T0 to when the pouch reaches 80%
inflation.
Tb is the time elapsed from T0 to when the pouch reaches 100%
inflation.
Tc is the time elapsed from T0 to when the pouch inflation begins
to decrease from a 100% inflation state.
Td is the time the pouch maintains 100% inflation; thus,
Td=Tc-Tb.
Te is the time elapsed from T0 to when the pouch inflation begins
to decrease from a 80% inflation state.
Tf is the time the pouch maintains 80% inflation; thus,
Tf=Te-Ta.
In some cases the pouch did not reach 100% inflation or 80%
inflation. These are noted in the comments. In some cases the
rectangular-shaped pouch was modified to have a double seal or a
double bag. A double seal means there was an inner rectangular seal
made in the bag, in addition to the outer seal. A double bag means
the effervescent was placed in a sealed inner bag, and then the
inner bag was placed in a sealed outer bag.
The parameters that have the most significant effects on the
inflation/deflation periods reported are the type of polymer, wall
thickness, type and amount of desiccant, and quantity of
effervescent material in the pouch. When more effervescent was
used, the rise time decreased and the period above 80% inflation
increased. An increase in effervescent material used, however, can
also significantly increase the deflation time.
The following discloses additional embodiments of a capsule
device.
FIGS. 8A-8C depict an example of a capsule device with a deformable
member 220 integral with the housing 10 of the sensing system 110.
As in prior embodiments the device includes a pouch 221 formed from
a semi-permeable membrane material 222, and an effervescent 224
contained within an interior of the pouch 221. One difference
between this capsule device and previously discussed embodiments is
that the deformable member 220 is integral with the capsule housing
10, as opposed to being tethered to it. The membrane material 222
chosen may be more elastic than in prior embodiments since ends of
the pouch 221 is constrained to the relatively rigid surface of
housing 10 and thus less able to increase its interior volume as in
prior embodiments without stretching of the membrane. The membrane
material 222 may be attached to the surface of the housing 10 by an
adhesive so that a fluid-tight interior to the pouch 221 is formed.
As such, body liquid enters the interior of the pouch 221 only by
way of diffusion through pores of the membrane 222.
FIG. 8A depicts a capsule device before the deformable member 220
expands in response to the effervescent 224 being exposed to body
liquid. The effervescent 224 is contained within the interior of
the pouch 221 made of the porous or semi-permeable membrane
material 222.
In this particular embodiment an enteric coating 223 (as
represented by dashed lines) is applied to the exterior of the
membrane 222 to prevent diffusion of body liquid into the pouch
interior until after the capsule device has entered the small
intestine. The enteric coating may also cover the sensing device
110.
When the capsule device of FIG. 8A approaches the terminal ileum or
the cecum, the enteric coating 223 dissolves due to the higher pH
level, as depicted in FIG. 8B. With the enteric coating dissolved,
body liquid begins to diffuse through the porous material 222 and
enters the interior space. Thus, the reaction takes place producing
the gas that expands the pouch volume, as shown in FIG. 8C.
Although a small amount of fluid 230 resides in the pouch 221
interior, the net effect of the reaction increases the volume of
the pouch to a greater extent than the added pouch weight brought
on by the body liquid. The SG of the device in FIG. 8C is less than
the SG of the device in FIG. 8A. In some embodiments it may be
desirable to have the effervescent material 224 placed in contact
with the semipermeable membrane of the deformable member so that
body liquid diffused through the membrane will reach and react with
the effervescent material 224 as quickly as possible. In other
embodiments it may be unnecessary or undesirable to place the
material 224 in contact with the membrane because it is desirable
to delay the reaction time for reasons previously given above
FIGS. 8D-8E depict later stages of the capsule device of FIG. 8C
Compared to the state in FIG. 8C, the state in FIG. 8D shows that
more body liquid has accumulated in the pouch 224 interior and less
gas (as a result of diffusion of the gas through the membrane 222).
FIG. 8E depicts a state of the capsule device after its SG has
increased to above 1 due to the amount of body liquid that has
diffused into the pouch 224 interior.
FIGS. 9A-9B depict an example of a deformable member 320 integral
with the housing 10 (as in FIGS. 8A-8C). According to this
embodiment the deformable 320 includes a pouch 321 having the
effervescent in its interior (FIG. 9A shows the pouch 321
configuration after body liquid has diffused into its interior
space and CO2 gas released). The pouch 321 is formed by a membrane
322 that is permeable to body liquid and substantially impermeable
to gas. A biodegradable relief valve, plug or seal made of a
biodegradable (or resorbable) material 310 covers an opening in the
membrane 322. The seal 310 may be configured to degrade within a
few hours of exposure to body liquid.
FIG. 9B depicts the state of the deformable member 320 after the
seal has degraded. The gas has been released and the SG of the
capsule device has increases back to above 1. FIG. 10 depicts an
embodiment of a capsule device where a housing 450 of the capsule
device 400 includes a flexible section 430. For example, a
bellows-like structure can be used for the flexible section. The
flexible section can be expanded or compressed along a longitudinal
direction 440 of the capsule device 400. Furthermore, the capsule
device 400 comprises sensor 410 and light 420 for capturing images
inside the body lumen.
FIGS. 11A and 11B depict an embodiment of a capsule device 500
where two coupled parts 530 and 540 are biased to spring apart to
form an enlarged volume of the housing (FIG. 5B). The parts 530,
540 are held together by a biodegradable or resorbable seal. When
exposed to body liquid the seal breaks and the two parts move
apart. With the increased volume and the housing formed by parts
530, 540 moved apart and the housing being liquid impermeable, the
device 500 has a SG that decreases as the parts 530, 540 move part.
The housing may be maintained in a sealed (liquid impermeable)
condition by disposing an O-ring or gasket between the overlapping
sections of parts 530, 540. FIGS. 11A and 11B illustrate states
where the capsule device has an SG greater than 1 and less than 1,
respectively.
FIG. 12 illustrates a capsule device 600 where a main sensor system
630 is configured to accommodate an extendable attachment 640. The
extendable attachment 640 can be moved within a range indicated by
650. When fully extended (i.e., attachment 640 moved from left to
right in FIG. 12) the capsule volume increases; hence the SG
decreases.
The embodiments of FIGS. 10-12 illustrate examples of capsules with
an expandable housing. The housing may be expanded in these
embodiments by an actuator such as a motor and screw drive internal
to the housing. Such actuators may consume excessive power,
however. Another option is to spring load the housing internally.
The housing expansion may be constrained by an external
biodegradable shell or coating that dissolves after the capsule
device is swallowed.
In one or more of the aforementioned other embodiments a capsule
device may be coated with a material to decrease drag or friction
between the housing and body liquid, or anatomy encountered in the
GI track. Hydrophilic coatings are one example of a coating that
may be used to coat the capsule's housing surface.
In a wireless application, a transmitter is used to transmit image
data to a receiver system external to the body and the image data
is stored in an external recorder. In U.S. Pat. No. 5,604,531, a
wireless capsule system is disclosed and the capsule system with a
wireless transmitter is powered by the battery within the capsule.
For colon applications, the transit time is substantially longer
than for small bowel applications. Therefore, the receiver system
and external recorder may become burdensome to carry over long
hours (e.g., 10 hours or more). Since the time period for a colon
application in general takes longer than, e.g., 8-10 hours, an
out-patient procedure would require the patient to bring the
receiver/transceiver equipment with him or her. This increases
healthcare costs since additional (portable) equipment is needed to
gather data for the colon. Additionally, the signals
transmitted/received between the device and receiver can interfere
with nearby equipment, such as another implant. It may therefore be
preferred to utilize for colon applications a capsule device that
can travel through the large intestine more rapidly. This may be
achieved by having the SG return back to an SG greater than 1 after
the capsule has passed through the ascending colon, by use of an
booster protocol, or a combination of the two. In yet another
embodiment of the present invention, the density control means is
applied to a capsule system with on-board storage. Such system is
disclosed in to U.S. Pat. No. 7,983,458, entitled "in vivo
Autonomous Camera with On-Board Data Storage or Digital Wireless
Transmission in Regulatory Approved Band", granted on Jul. 19, 201.
The capsule system with on-board storage does not require the
patient to wear any external equipment. Therefore, the capsule
system with on-board storage is much preferred for procedure
requiring a prolonged time period. Furthermore, in PCT Patent
Application No. PCT/US13/42490, a docketing station to read out
archived data from a capsule system with on-board storage is
disclosed. The capsule system comprises a set of probe pads
disposed on the housing. After the capsule device is excreted and
recovered, the image data can be retrieved by probing these probe
pads without opening the capsule housing. Since the battery power
is pretty much depleted when the capsule device is retrieved, one
pair of the probe pads can be used to provide power and ground for
the data retrieval operation. Alternatively, the power can be
provided using inductive powering as disclosed in PCT Patent
Application Series No. PCT/US13/39317. After the capsule is
recovered, the data may be transmitted optically through a
transparent portion of the capsule to an external receiver.
The following additional Concepts are included as part of the
foregoing disclosure.
Concept 1. A capsule device, comprising: a sensor system
comprising: a light source; an image sensor for capturing image
frames of a scene illuminated by the light source; an archival
memory; and a housing adapted to be swallowed, wherein the light
source, the image sensor and the archival memory are enclosed in
the housing; and a density control means for causing at least two
specific gravities of the capsule device for at least two
designated regions of gastrointestinal track respectively, wherein
each of said at least two specific gravities is selected from a
first group consisting of a greater-than-one state and a
less-than-one state.
Concept 2. The capsule device of Concept 1, wherein the
greater-than-one state correspond to the specific gravity of about
1.1 or larger and the less-than-one state corresponds to the
specific gravity of about 0.94 or smaller.
Concept 3. The capsule device of Concept 1, wherein said at least
two designated regions of the gastrointestinal track are selected
from a second group comprising stomach, ascending colon and
descending colon.
Concept 4. The capsule device of Concept 1, wherein said at least
two designated regions of the gastrointestinal track correspond to
stomach and ascending colon, and wherein the corresponding said at
least two specific gravities are the greater-than-one state and the
less-than-one state respectively.
Concept 5. The capsule device of Concept 1, wherein said at least
two designated regions of the gastrointestinal track correspond to
stomach, ascending colon and descending colon, and wherein the
corresponding said at least two specific gravities are the
greater-than-one state, the less-than-one state and the
greater-than-one state respectively.
Concept 6. The capsule device of Concept 1, wherein whether the
capsule device is located in or approaching at one of said at least
two designated regions of the gastrointestinal track is determined
based on: estimated transit time after the capsule device is
swallowed; pH values measured at capsule device locations; luminal
pressure measured at the capsule device location; identification of
image contents based on captured images by the capsule device;
motion detection based on the captured images by the capsule
device; colonic microflora detected at the capsule device location;
or estimation of lumen diameter.
Concept 7. The capsule device of Concept 1, wherein said density
control means couples a deformable member to the sensor system,
wherein the deformable member contains gas generating material,
said density control means causes the deformable member to inflate
by causing fluid to enter the deformable member so that the gas
generating material generates gas and the capsule device has the
specific gravity less than one.
Concept 8. The capsule device of Concept 7, wherein the deformable
member is coated with an enteric coating before the capsule device
is swallowed to prevent the fluid to enter the deformable member
before the capsule device exits stomach.
Concept 9. The capsule device of Concept 7, wherein the deformable
member comprises a biodegradable plug, wherein the biodegradable
plug becomes separated or partially separated from rest of the
deformable member or causes leaks on the deformable member to let
the gas and the fluid to leak from the deformable member.
Concept 10. The capsule device of Concept 7, wherein the deformable
member is made of a first material which is more permeable to the
gas than to the fluid.
Concept 11. The capsule device of Concept 10, wherein the
deformable member inflates with the gas and later deflates as the
gas diffuses out of the deformable member faster than the fluid
diffuses in the deformable member.
Concept 12. The capsule device of Concept 7, wherein after a first
period of time since the capsule device reaches the specific
gravity less than one, the density control means causes the capsule
device to reach the specific gravity greater than one by allowing
the fluid to continue to enter the deformable member such that a
volume ratio of the gas to the fluid inside the member
decreases.
Concept 13. The capsule device of Concept 1, wherein the capsule
devise is coated with or made of a second material so that the
capsule devise has a reduced friction with body lumen or fluid.
Concept 14. The capsule device of Concept 1, wherein electrical
contacts are disposed fixedly on the housing, wherein the
electrical contacts are coupled to the archival memory so that an
external device is allowed to access image data stored in the
archival memory through the electrical contacts.
Concept 15. The capsule device of Concept 14, wherein the
electrical contacts include power pins to provide power to the
capsule device for data retrieval of image data stored on the
archival memory.
Concept 16. The capsule device of Concept 14, wherein inductive
powering is used to provide power to the capsule device for data
retrieval of image data stored on the archival memory.
Concept 17. The capsule device of Concept 1, wherein the capsule
device further comprises: an optical transmitter to transmit an
optical signal through a clear window, wherein image data from the
archival memory is transmitted to an external optical receiver.
Concept 18. The capsule device of Concept 17, wherein inductive
powering is used to provide power to the capsule device for data
retrieval of image data stored on the archival memory.
The above description of illustrated embodiments of the invention,
including what is described in the Abstract, is not intended to be
exhaustive or to limit the invention to the precise forms
disclosed. While specific embodiments of, and examples for, the
invention are described herein for illustrative purposes, various
modifications are possible within the scope of the invention, as
those skilled in the relevant art will recognize.
These modifications can be made to the invention in light of the
above detailed description. The terms used in claims should not be
construed to limit the invention to the specific embodiments
disclosed in the specification.
* * * * *
References