Apparatus for Thermally Stable Capsule Endoscope Using Effervescent Formulation for Controlling Balloon Inflation Rate

Abstract

A capsule device with thermally-stable specific gravity control is disclosed. The capsule device comprises a capsule unit adapted to be swallowable by a human subject and an inflatable balloon comprising a thermally-stable effervescent formulation inside the inflatable balloon, where the thermally-stable effervescent formulation has a particular particle size between a first mesh size and a second mesh size, and the inflatable balloon is attached to the capsule unit. After the capsule unit with the inflatable balloon attached is swallowed, the inflatable balloon starts to inflate so as to lower specific gravity of a combination of the capsule unit and the inflatable balloon when the inflatable balloon is exposed to body fluid and the body fluid gets in touch with the thermally-stable effervescent formulation inside the inflatable balloon.

Claims

1. A capsule device, comprising: a capsule unit adapted to be swallowable by a human subject; and an inflatable balloon comprising a thermally-stable effervescent formulation inside the inflatable balloon, wherein the thermally-stable effervescent formulation has a particular particle size between a first mesh size and a second mesh size, and wherein the inflatable balloon is attached to the capsule unit; and wherein after the capsule unit with the inflatable balloon attached is swallowed, the inflatable balloon starts to inflate so as to lower specific gravity of a combination of the capsule unit and the inflatable balloon when the inflatable balloon is exposed to body fluid and moisture from the body fluid gets in touch with the thermally-stable effervescent formulation inside the inflatable balloon.

2. The capsule device of claim 1, wherein the thermally-stable effervescent formulation comprises sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate or any combination of these.

3. The capsule device of claim 2, wherein the thermally-stable effervescent formulation further comprises an acid.

4. The capsule device of claim 3, wherein the acid is selected from an acid group comprising crystalline, semi-crystalline, anhydrous, low or high molecular weight, and water soluble.

5. The capsule device of claim 2, wherein the thermally-stable effervescent formulation further comprises an excess acid.

6. The capsule device of claim 5, wherein the excess acid belongs to an excess acid group comprising citric acid, tartaric acids or monocalciumphosphate (Ca(H.sub.2PO.sub.4).sub.2).

7. The capsule device of claim 6, wherein the excess acid has an acid to base functional group stoichiometric ratio of close to 1 or above.

8. The capsule device of claim 2, wherein the first mesh size is equal to 12 and the second mesh size is equal to 14.

9. The capsule device of claim 2, wherein the first mesh size is equal to 10 and the second mesh size is equal to 12.

10. The capsule device of claim 2, wherein the first mesh size is equal to 10 and the second mesh size is equal to 14.

11. The capsule device of claim 2, wherein the first mesh size is equal to 14 and the second mesh size is equal to 16.

12. The capsule device of claim 2, wherein the first mesh size is equal to 14 and the second mesh size is equal to 18.

13. The capsule device of claim 1, wherein the thermally-stable effervescent formulation comprises sodium bicarbonate.

14. The capsule device of claim 13, wherein the thermally-stable effervescent formulation further comprises an acid.

15. The capsule device of claim 14, wherein the thermally-stable effervescent formulation further comprises an excess acid.

16. The capsule device of claim 15, wherein the first mesh size is equal to 12 and the second mesh size is equal to 14.

17. The capsule device of claim 15, wherein the first mesh size is equal to 10 and the second mesh size is equal to 12.

18. The capsule device of claim 15, wherein the first mesh size is equal to 10 and the second mesh size is equal to 14.

19. The capsule device of claim 15, wherein the first mesh size is equal to 14 and the second mesh size is equal to 16.

20. The capsule device of claim 15, wherein the first mesh size is equal to 14 and the second mesh size is equal to 18.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0020] 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.

[0021] FIG. 2 illustrates an example of balloon inflation kinetics for a capsule endoscope, where the balloon volume vs time is shown.

[0022] FIG. 3 depicts the balloon inflation volume over time for a set of capsules incorporating an embodiment of the present invention exposed to higher temperature (60° C.) for 28 days and another set of baseline capsules (not exposed to 60° C. for 28 days), respectively.

DETAILED DESCRIPTION OF THE INVENTION

[0023] 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.

[0024] 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.

[0025] 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.

[0026] 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.

[0027] This present invention discloses a capsule device with an inflatable balloon unit including an effervescent material that is stable to at least 60° C. for at least 28 days and which has a shelf-life of at least one year even after the capsule has been exposed to 60° C. for an extended period of time.

[0028] In the present invention, effervescent materials with specific particle sizes are used as candidates for thermal stability as well as satisfactory mono-modal gas inflation behavior. Typically, the effervescent materials for gas generation are in a powder form. The stability of the effervescent material in the powder form may be more susceptible to higher temperatures. Accordingly, the present invention selects effervescent materials with specific particle sizes to achieve the goal of thermal stability. The type and amount of effervescent for a target capsule depend on the particular capsule design as well as the balloon membrane material and thickness. Some balloon design considerations are disclosed in U.S. Pat. No. 10,098,526, which is assigned to the same assignee as the present invention. According to the present invention, a specific particle size or sizes are selected for the effervescent material to achieve the thermal stability. In one embodiment, NaHCO.sub.3 (sodium bicarbonate) is selected as the base (or CO.sub.2 donor) of the effervescent material for a target capsule design. The selected particle size is 12-14 mesh. In other words, the effervescent particles can pass through mesh size 12, but will not pass mesh size 14. For mesh size 12, the screen opening size is about 1.68 mm (millimeter). For mesh size 14, the screen opening size is about 1.41 mm. In other words, the effervescent material selected to assemble a thermally stable capsule endoscope during storage/transportation needs to have specific particle size.

[0029] Bench tests were conducted by aging capsules with a balloon containing the effervescent material in particle form at mesh size 12-14 at 60° C. for 28 days (which corresponds to 1 year at room temperature). Six samples (n=6) of the capsules embodying the present invention and six baseline capsules (n=6) were used in this study. The total volume and inflation kinetics for the capsules embodying the present invention are compared to the baseline capsules, Table 2. The baseline capsules are reference capsules that were stored at room temperature, i.e., not exposed to 60° C. for 28 days. All capsule devices were suspended from an arm coupled to a weighing scale. The arm overhung a basin of water heated to about 37° C. Ballast was attached to the arm. The weight of the arm and ballast was zeroed out using a weighing scale software. Next, the capsule devices were attached to the arms with the ballasts and dropped into the water. The change in weight of the capsule devices were then recorded over the next 25 hours. As moisture entered the balloons the effervescent material inside the balloons was mobilized so the CO.sub.2 (g) generating reaction could take place allowing the SG of the capsule devices to change: the SG decreased (as CO.sub.2 (gas) produced from the reaction between the acid and the base of the effervescent), the SG reached a minimum value (corresponding to a 100% inflation condition), and then the SG increased as CO.sub.2 (gas) diffused out from the balloons.

[0030] The graph in FIG. 3 depicts the balloon inflation volume over time for a set of capsules incorporating an embodiment of the present invention exposed to higher temperature (60° C.) for 28 days and another set of baseline capsules (not exposed to 60° C. for 28 days), respectively. In order to visually distinguish the curves easily, only two sets of curves are shown in FIG. 3. Inflation volumes above about 0.9 mL for these capsule devices correspond to SG<1. While inflation volumes below 0.9 mL correspond to SG>1. In FIG. 3, the dark-colored curves (310, 320) represent typical inflation kinetics of the baseline capsule, and the light-colored curves (330, 340) represent typical inflation kinetics of the capsule incorporating an embodiment of the present invention. Based on this data and the data in Table 2, it has been demonstrated that an effervescent material with larger particles (12-14 mesh) makes the capsule endoscope thermally stable at temperatures up to 60° C. As shown in FIG. 3 and Table 2, the capsule balloons (using Balloon B) incorporating an embodiment of the present invention being exposed to higher temperature (e.g., 60° C. for 28 days) still generates the same max volume and total volume (area under the curve). In addition, the capsule incorporating an embodiment of the present invention being exposed to higher temperature (e.g., 60° C. for 28 days) exhibits about the same inflation kinetics as the baseline capsule not exposed to 60° C. for 28 days, FIG. 3 and Table 2. For example, the rise time Tx for the capsule to reach SG˜1 (i. e., the volume reaching about 0.9 mL) is about the same for the baseline capsule and the capsule exposed 60° C. for 28 days incorporating an embodiment of the present invention. Also, the capsules incorporating an embodiment of the present invention 60° C. for 28 days stay afloat for about the same period of time as the baseline capsules not exposed to 60° C. for 28 days.

[0031] Most importantly, the max volume for the capsule balloons (using Balloon B) incorporating the effervescent material according to the present invention and exposed to 60° C. for 28 days is about 1.09 mL, which is similar to the max volume (1.11 mL) for the baseline capsule balloons (not exposed to 60° C. for 28 days), Table 2. On the other hand, as outlined in Table 1 the max volume of a capsule balloon (using Balloon B) with the conventional effervescent material (i.e., in powder form) which is not stable to increased temperatures would suffer a max volume drop of 27.2% (from 1.69 mL to 1.23 mL) even at a temperature of 50° C. The nominal size of Balloon A (1.69 mL) is larger than the nominal size of Balloon B (˜1.11 mL).

TABLE-US-00002 TABLE 2 Max Volume (mL) Tx (hour) Ttb (hour) Ta (hour) Avg. Std. Var. Avg. Std. Var. Avg. Std. Var. Avg. Std. Var. RT (25° C.) 1.11 0.07 2.95 0.4 12.02 1.26 9.07 1.25 60° C. for 28 days 1.09 0.06 3.27 0.59 13.50 2.24 10.23 2.81

[0032] While FIG. 3 illustrates an example of a thermally stable capsule endoscope using effervescent formulation according to an embodiment at 60° C., the thermal stability is achieved for all temperatures up to 60° C.

[0033] While the particular effervescent material comprising NaHCO.sub.3 as the base is selected to demonstrate the thermally stable characteristics, other effervescent materials may also be used to practice the present invention. For example, besides sodium bicarbonate (NaHCO.sub.3), other effervescent materials such as potassium bicarbonate, sodium carbonate, potassium carbonate, or any mixture of these. Furthermore, the effervescent formulation typically comprises an acid to achieve a desire inflation kinetics. The acid selected may be crystalline or semi-crystalline, anhydrous, low or high molecular weight, and water soluble. For example, the acid belongs to a group comprising citric acid, tartaric acids or monocalciumphosphate (Ca(H.sub.2PO.sub.4).sub.2) and should have an acid to base functional group stoichiometric ratio of close to 1 or above.

[0034] The definition of functional group stoichiometric ratio is for example when you mix citric acid and sodium bicarbonate the stoichiometric ratio for the reaction is:

H3C6H5O7(aq)+3NaHCO3(aq).fwdarw.Na3C6H5O7(aq)+3H2O(l)+3CO2(gas)  (I)

but since one citric acid molecule have three functional groups (—COOH)) it can donate protons to three sodium bicarbonate molecules. Thus as written in equation (I) the functional group stoichiometric ratio is 1. The reaction rate can be increased by adding excess of citric acid and still generate the same volume CO2 (gas), while if you reduce the amount of citric acid not only will the CO2 (gas) generation rate be reduced but the total volume of CO2 (gas) generated will also be less. If the excess of citric acid is significant the CO2 (gas) generation rate will also be significantly higher.

[0035] While the particle size of mesh 12-14 is selected for NaHCO.sub.3, other particle size or sizes may be required for other effervescent materials. For example, a larger particle size of mesh 10-12 may be selected to achieve a desired inflation kinetics for a particular capsule design. In another embodiment, a larger particle sizes of mesh 10-14 may be selected to achieve a desired inflation kinetics for a particular capsule design. In another example, a smaller particle size of mesh 14-16 may be selected to achieve a desired inflation kinetics for a particular capsule design. In yet another embodiment, a smaller particle sizes of mesh 14-18 may be selected to achieve a desired inflation kinetics for a particular capsule design.

[0036] The invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described examples are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.