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.
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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 said at least the pouch is configured to control estimated inflation and deflation periods of the capsule endoscope 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 the capsule endoscope said at least the pouch is configured to control estimated inflation and deflation periods of the capsule endoscope said at least the pouch by properly 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.
0. 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.
2. The capsule endoscope of
3. The capsule endoscope of
4. The capsule endoscope of
5. The capsule endoscope of
6. The capsule endoscope of
7. The capsule endoscope of
8. The capsule endoscope of
9. The capsule endoscope of
10. The capsule endoscope of
11. The capsule endoscope of
12. The capsule endoscope of
13. The capsule endoscope of claim 1 12, wherein the pouch water uptake in 12 hours relative to a pouch and effervescent dry weight is less than 200% for one a first group of pouch materials or 50% for another a second group of pouch materials.
14. The capsule endoscope of
15. The capsule endoscope of
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
17. The capsule endoscope of
18. The capsule endoscope of
20. The capsule endoscope of claim 16 19, 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.
22. The capsule endoscope of
23. The capsule endoscope of
24. The capsule endoscope of
25. The capsule endoscope of
26. The capsule endoscope of
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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.
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.
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.
Sensing system 110 may be propelled through the GI tract by peristalsis. Illuminating system 12 may be implemented by LEDs. In
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.
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≤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):
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.
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.
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
In some embodiments the pouch 140 may be rectangular when deployed, as in the case of
With reference to
Referring to
Referring to
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.
With reference to
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 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 ≤
1-4 hours*
n/a
CO2 gas generation is slow
t ≤ 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 ≤
4-12 hours*
n/a
Capsule SG <1; Device is
t ≤ 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 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 ≤
5 min-
n/a
CO2 gas generation can be fast
t ≤ 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 ≤
2-15 hours*
n/a
Capsule SG <1; Device is
t ≤ 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
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
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
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 (
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 (
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
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.
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
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.
Exp 1: a pouch membrane was made from PEBAX 4 mils and with dimensions 30×11 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 30×11 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 30×11 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 30×11 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 30×11 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 30×11 mm, wall thickness 4 mil (0.1 mm), and 20 mg of effervescent used (coarse grind, fresh).
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.
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
The embodiments of
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.
Trollsas, Mikael, Hadley, Mark, Wang, Kang-Huai, Lu, Ganyu, Trinh, Phat, Wilson, Gordon Cook
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