Abstract:
A device for placement within a capsule. The device includes a unit to encode information in a current signature, the unit including a partial power source. The device further including a flexible membrane secured to the unit. The membrane engages the wall of the capsule and holds the device in place within the capsule.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a divisional application of U.S. patent application Ser. No. 13/521,993, titled INGESTIBLE DEVICE WITH PHARMACEUTICAL PRODUCT, now U.S. Patent Application Publication No. 2012/0302999, published on Nov. 29, 2012 which application claims priority to International Patent Application No. PCT/US2011/061478, titled INGESTIBLE DEVICE WITH PHARMACEUTICAL PRODUCT, filed Nov. 18, 2011, which application, pursuant to 35 U.S.C. §119 (e), claims priority to the filing date of U.S. Provisional Patent Application Ser. No. 61/416,150 titled INGESTIBLE DEVICE WITH PHARMACEUTICAL PRODUCT filed Nov. 22, 2010, the disclosure of which applications are herein incorporated by reference. 
       RELATED APPLICATIONS 
       [0002]    This application is related to and incorporates the following applications by reference: U.S. patent application Ser. No. 14/570,673, now published as U.S. Patent Application Publication No. 2015/0182463 and titled CONTROLLED ACTIVATION INGESTIBLE IDENTIFIER, U.S. Pat. No. 8,945,005 issued on Feb. 3, 2015 and titled CONTROLLED ACTIVATION INGESTIBLE IDENTIFIER; U.S. Provisional Application 60/862,925 filed on Oct. 25, 2006 and titled CONTROLLED ACTIVATION PHARMA-INFORMATICS SYSTEM; PCT Patent Application Publication No. WO 2008/052136 and published on Oct. 23, 2008 and titled CONTROLLED ACTIVATION INGESTIBLE IDENTIFIER. 
     
    
     FIELD OF INVENTION 
       [0003]    The present invention relates to electronic devices and, more specifically, to electronic devices with a particle power source that are secured to a pharmaceutical product. 
       BACKGROUND 
       [0004]    Capsules are made of a material that becomes gel-like once in contact with fluids. Such gel-like materials can interfere with the operation of an ingestible device, which is carried inside the capsule, with dissolvable components and electronic components. For example, gelatinous materials have low conductivity and, hence, if the device operates using conduction through fluids, then it will not operate properly. Thus, it is important to prevent the gel-like material of the capsule, as it is dissolving, from coming into contact with the device&#39;s components. 
         [0005]    Additionally, capsules contain pharmaceutical materials that can interact with or damage the device during long term storage. For example, the product inside the capsule may be acidic and harmful to the electronic components. Alternatively, the content may be too basic, which can also harm the electronics. Furthermore, the material or product within the capsule will start to interact with the surrounding fluids, once the capsule is ingested and the capsule starts to disintegrate. The content of the capsule may include material, such as a drug or excipient or compound, that when dissolved at high concentrations, will interfere with the operation of the ingested device placed within the same capsule. As the material enters the solution at the site where the capsule is dissolving, there is a high concentration localized around the device. The stomach motion and diffusion disperses the capsule content throughout the stomach and reduces the concentration. During this time, the device will not operate properly if activated in the localized high concentration areas. Thus, the activation of the device needs to be delayed and the device should be protected from the capsule dissolving or disintegrating. 
         [0006]    Thus, the devices need to be protected from the surrounding environment, including the content of the capsule as well as moisture. Furthermore, a manufacturing solution is needed to allow for manufacturing of these devices and placement of same within a capsule in such a manner that does not damage the device. Therefore, what is needed is suitable system and manufacturing process that protects the devices. 
       SUMMARY 
       [0007]    The present disclosure includes a system and a manufacturing process that protects the device and allows for placement or combination of the device within a pharmaceutical product or capsule. The system includes circuitry and components that can be placed within certain environments. The device includes an assembly including an electronic unit, a flexible membrane secured to the unit, and a protective coating. 
         [0008]    Notwithstanding the claims, the present invention is also defined by the following clauses. 
         [0009]    Clause 1: A process for creating a pharmaceutical product, the process comprising the steps of: 
         [0000]    creating a device sheet including a plurality of devices;
 
securing an upper sheet to one side of the device sheet to produce a partially coated device sheet;
 
securing a lower sheet to another side of the partially coated device sheet, to produce a protected device sheet, wherein the upper sheet and the lower sheet form a protective layer;
 
separating a protected device from the protected device sheet; and
 
combining the protected device with a pharmaceutical agent to produce the pharmaceutical product.
 
         [0010]    Clause 2: The process of clause 1, wherein the device sheet defines a plurality of holes surrounding each device. 
         [0011]    Clause 3: The process of clause 2, wherein the step of securing the lower sheet to another side of the partially coated device sheet includes the step of heating the lower sheet and the upper sheet such that the lower sheet comes into contact with the upper sheet through the holes, the lower sheet surrounding each device and the upper sheet and lower sheet secured to one another at the point of the contact. 
         [0012]    Clause 4: The process of any of clauses 1-3, wherein the step of separating includes the steps of: 
         [0000]    aligning the protected device sheet with an opening defined within a die such that the protected device is aligned with the opening of the die; and
 
punching the protected device using a punch through the opening and into a capsule placed within a capsule holder.
 
         [0013]    Clause 5: The process of any of preceding clauses, wherein the step of separating includes the steps of: 
         [0000]    aligning the protected device sheet with an opening defined by a tray such that the protected device of the protected device sheet is aligned with the opening of the tray;
 
separating the protected device from the protected device sheet using a punch; and
 
placing the protected device into the opening of the tray.
 
         [0014]    Clause 6: The process of clause 5, further comprising the step of aligning the opening of the tray that comprises the protected device with a capsule holder that defines a plurality of cavities that hold a first end of a capsule, wherein the capsule includes the first end and a second end. 
         [0015]    Clause 7: The process of clause 6, further comprising the step of pushing the protected device out of the opening of the tray and into the first end of the capsule placed within the cavity of the capsule holder. 
         [0016]    Clause 8: The process of clause 7, wherein the step of combining includes the steps of: 
         [0000]    filling the first end of the capsule that includes the protected device with a pharmaceutical product; and
 
securing the second end of the capsule to the first end of the capsule.
 
         [0017]    Clause 9: A device for placement within a capsule, the device comprising: 
         [0000]    an assembly including:
 
a unit to encode information in a current signature, the unit comprising a partial power source; and
 
a flexible membrane secured to the unit, wherein the membrane engages the capsule&#39;s wall and holds the device in place within the capsule.
 
         [0018]    Clause 10: The device of clause 9, further comprising a protective coating surrounding the assembly. 
         [0019]    Clause 11: The device of clause 9 or 10, further comprising a first protective sheet secured to an upper surface of the assembly and a second protective sheet secured to a lower surface of the assembly. 
         [0020]    Clause 12: The device of clause 11, wherein the first protective sheet and the second protective sheet are secured to each other through a plurality of holes defined by the flexible membrane. 
         [0021]    Clause 13: The device of clause 11 or 12, wherein the first protective sheet and the second protective sheet are secured to each other at the edge of the assembly and extend beyond the perimeter of the assembly such that the assembly is enclosed within the protective sheets. 
         [0022]    Clause 14: The device of any of clauses 9-13, wherein the unit includes: 
         [0000]    a first material secured to a support structure; and
 
a second material secured to the support structure and electrically isolated from the first material, such that the first material and second material represent a chemical voltage potential when in contact with a conducting fluid.
 
         [0023]    Clause 15: The device of clause 14, wherein the support structure comprises a control module electrically connected to the first material and the second material to control the conductance between the first material and the second material, wherein the control module encodes the information in the current signature by altering the conductance. 
         [0024]    Clause 16: The device of any of clauses 9-15, wherein the flexible membrane includes a plurality of legs that engage the capsule&#39;s wall when the assembly is pressed into the capsule. 
         [0025]    Clause 17: The device of any of clauses 9-16, wherein the flexible membrane includes a plurality of extensions shaped to fit within the capsule and hold the assembly in place. 
         [0026]    Clause 18: A pharmaceutical product comprising: 
         [0000]    a capsule having an upper end and a lower end, wherein the upper and lower ends are brought together to form a housing that defines a cavity and wherein the cavity is filled with a drug, the capsule configured to disintegrate when in contact with a surrounding fluid; and
 
an ingestible device associated with the capsule, preferably a device according to any of the clauses 9-17, to encode information in a current signature, wherein the ingestible device is placed within the housing, wherein the ingestible device includes electronic components that are surrounded by a protective layer, wherein the protective layer is configured to begin to disintegrate after the capsule has disintegrated and has exposed the content of the capsule to the surrounding fluids.
 
         [0027]    Clause 19: The product of clause 18, further comprising a flexible membrane that is secured to the ingestible device to produce an assembly wherein the flexible membrane positions the assembly within the capsule. 
         [0028]    Clause 20: The product of clause 19, further comprising a first protective sheet secured to an upper surface of the assembly and a second protective sheet secured to a lower surface of the assembly, wherein the first protective sheet and the second protective sheet are secured to each other and surround the assembly. 
     
    
     
       DESCRIPTION OF THE DRAWINGS 
         [0029]      FIG. 1  shows a capsule with a laminated device inside the capsule. 
           [0030]      FIG. 2A  shows a capsule with a table inside the capsule and the tablet includes a covered device. 
           [0031]      FIG. 2B  shows a capsule with a table inside the capsule and the tablet includes a device. 
           [0032]      FIG. 3  shows a capsule with a covered device inside one portion of the capsule. 
           [0033]      FIG. 4A  shows an example of a device that can be used in the capsule of  FIG. 3 . 
           [0034]      FIG. 4B  shows another example of a device that can be used in a capsule end for  FIG. 3  with a specific designed capsule end to mechanically hold the device in place. 
           [0035]      FIG. 5  shows a device with a cover secured onto a tablet and the tablet placed inside a capsule. 
           [0036]      FIG. 6  shows the process of laminating or covering the device. 
           [0037]      FIG. 7  shows a closer view of the assembly pieces of  FIG. 6 . 
           [0038]      FIG. 8  shows a process of inserting a device within a capsule end in accordance with one aspect of the present invention. 
           [0039]      FIG. 9  shows an advanced stage of the process of  FIG. 8 . 
           [0040]      FIG. 10  shows a perspective view of a transfer tray. 
           [0041]      FIG. 11  shows an initial stage of the process of inserting a device within a capsule end in accordance with one aspect of the present invention. 
           [0042]      FIG. 12  shows the device of  FIG. 11  within the transfer tray of  FIG. 10 . 
           [0043]      FIG. 13  shows an advanced stage of the process of  FIG. 11  in accordance with one aspect of the present invention. 
           [0044]      FIG. 14  shows an advanced stage of the process of  FIG. 13  in accordance with one aspect of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0045]    The present invention discloses multiple approaches to protecting a device from the harmful effects of a capsule and the content of the capsule when the device is placed within the capsule. The present invention also discloses multiple approaches to securing the device within the capsule that contains the product. The scope of the present invention is not limited by the type of product within the capsule. For example, the product can be a capsule, a time-release oral dosage, a powder, a gel, a sub-lingual tablet or any oral dosage product. In accordance with one aspect of the present invention, the capsule has the device positioned inside or secured to the interior. In an alternative arrangement, the device is secured to the exterior of the capsule or as part of the capsule wall. 
         [0046]    In accordance with the teachings of the present, in some embodiments, the device is placed within the capsule. In accordance with other aspects of the present invention, the device is secured with the capsule. Various methods of securing the device to the capsule are disclosed. For example, the device may be secured to the capsule using ingestible glues, pressure sensitive adhesives, thermal adhesives, mechanically attached, secured to a band that is later placed around the product. 
         [0047]    In addition to the methods used to secure the device to the product, there are various methods of coating or laminating the device, surrounding the device, or separating and isolating the device from the drug or product within the capsule to prevent a reaction between the device and the drug or product. For example, certain products contain acids that can damage the device, such as tartaric acid. Additionally, there are times when the device, upon activation may interact with the product or drug when the device is activated too quickly. Thus, as discussed in detail below, there are various lamination and packaging options that may be used in association with the device to prevent such problems. 
         [0048]    Referring now to  FIG. 1 , an ingestible device  20  is shown with a layer  20   a  surrounding electronics  20   b . The layer  20   a  is soluble and a disintegrating layer of material around the electronics  20   b . The layer  20   a  delays the exposure of the electronics  20   b  to surrounding fluids. The device  20  is placed inside the capsule  22 , which also contains a pharmaceutical product or drug. The capsule  22  has a bottom end  22   a  and a top end  22   b . The capsule  22  is made of a dissolvable material, such as gelatin. Upon ingestion, the capsule  22  walls turn into a gel-like material, due to contact with fluids. The layer  20   a  prevents contact between the gel-like material of the capsule  22  and the electronics  20   b  until the gel-like material has dissolved and no longer interferes with the operation of the device  20 . During the time the capsule  22  is dissolving, the layer  20   a  is also slowly disintegrating away to allow the electronics  20   b  to come into contact with the fluids and become activated. One example of the type of electronic components that are part of the device  20  is disclosed in U.S. patent application Ser. No. 12/564,017 filed on Sep. 21, 2009, which issued on Jul. 12, 2011 as U.S. Pat. No. 7,978,064 and is titled COMMUNICATION SYSTEM WITH PARTIAL POWER SOURCE, the entire disclosure of which is incorporated herein by reference. The capsule  22 , in all instances described herein is intended to carry a drug and includes a drug product in addition to the device. 
         [0049]    Referring now to  FIGS. 2A and 2B , in accordance with another aspect of the present invention, the capsule  22  is shown with a device  24  inside the capsule. The device  24  includes a disintegrating film or material  24   a  and components and electronics  24   b . In accordance with one embodiment, the device  24  has a laminated coating as shown in  FIG. 2A . In accordance with another embodiment, the device  24  has is surrounded by the material  24   a  as shown in  FIG. 2B . As the capsule  22  is ingested, the capsule ends  22   a  and  22   b  disintegrate or dissolve. The content of the capsule  22  comes into contact with the surrounding fluids. The material  24   a  reacts with the fluids to prevent the gel-like material of the capsule  22  from coming into contact with the electronics  24   b  as discussed with respect to  FIG. 2 . 
         [0050]    Referring now to  FIG. 3 , the capsule  22  is shown with a device  26  positioned within the capsule end  22   b  in accordance with another aspect of the present invention. The device  26  is held in position inside the capsule end  22   b  using friction or by a mechanical means as will be discussed with respect to  FIGS. 4A and 4B , respectively. In accordance with various aspects of the present invention, the device  26  may be covered in a manner similar to the device  20  or the device  24  of  FIG. 1  and  FIGS. 2A and 2B , respectively. For example, the device  26  may include a layer or lamination material or the device  26  may include a disintegration material. As noted, the device  26  is held in position using friction or mechanical attachment. 
         [0051]    Referring now to  FIG. 4A , in accordance with one aspect of the present invention, the device  26  includes tabs or legs  28  and electronics  26   b . The legs  28  are flexible and as the device  26  is pushed into the capsule end  22   b , the friction between the legs  28  and the wall of the capsule end  22   b  hold the device  26  in place. As the capsule  22  dissolves, the walls of the capsule end  22   b  change shape or collapse causing the friction between the legs  28  and walls of the capsule end  22   b  to reduce and thereby allow the device  26  to be released from the capsule end  22   b.    
         [0052]    Referring now to  FIG. 4B , in accordance with another aspect of the present invention, the device  26   a  includes tabs or legs  30  and electronics  26   b . The legs  30  are used to secure the device  26   a  into a capsule end  22   c . The capsule end  22   b  of  FIG. 3  is replaced with the capsule end  22   c . The capsule end  22   c  includes a matching number of slots or indentations  32  to the legs  30  of the device  26   a . In an alternative aspect of the present invention, the number of legs  30  may differ from the number of slots  32 . As the device  26   a  is pressed inside the capsule end  22   c , the tabs  30  engage the slots  32  and lock the device  26   a  into place mechanically. As the capsule end  22   c  dissolves, the walls of the capsule end  22   c  change shape or collapse causing the device  26   a  to be released from the capsule end  22   c.    
         [0053]    Referring now to  FIG. 5 , the capsule  22  is shown with device  34  in accordance with another aspect of the present invention. The device  34  includes a material  34   a  to which is secured electronics  34   b , similar to the electronics  24   b , and a layer or covering  34   c.    
         [0054]    Referring now to  FIG. 6  and  FIG. 7 , a process for creating a device with a covering or lamination is shown in accordance with one aspect of the present invention. Devices  40  are shown on a sheet  41  that is placed between a top lamination sheet  42   a  and a bottom lamination sheet  42   b . The sheets  42   a  and  42   b  may be made of a variety of materials or films, such as polymer films that include polyethylene oxide, hydroxypropyl cellulose, and triethyl citrate. Other films that can be used include any soluble polymer, plasticizer. The film provides a moisture barrier and dissolves under the proper conditions to delay activation of the device. The film layer is designed to provide sufficient delay in exposure of the device to the surrounding fluids relative to the disintegration and dispersion of the capsule material and the content of the capsule. The film layer may includes the soluble materials, barrier materials (such as lipids, polyvinyl alcohol), processing aids (such as plasticizers, adhesion promoters), and stabilizers. Furthermore, the film layer may be manufactured via lamination, application of a coating solution or slurry followed by a cure. In accordance with other aspects of the present invention, the film or layer may be similar to  FIG. 2  and formed using dry compression, such as a tablet press. 
         [0055]    There are a variety of active agents or pharmaceutical products that can be placed inside of a capsule. For example, there are FDA approved drugs, drugs that are disclosed chemically in a patent application or in an issued patent, there are drugs are disclosed in the Orange Book as part of the approved drug products, and generics. In accordance with the teachings of the present inventions, any one or combination of such drugs may be placed within the capsule along with the device. Each of those drugs will have a specific and unique impact on the operation of the device as well as the disintegration of the film used because of the unique chemical composition. As such, the type of material uses as the film layer will vary to be compatible to the chemical composition of the products used. Thus, the scope of the present invention is not limited by the type of content of the capsule and the film or coating layer around the electronic components of the device. 
         [0056]    In accordance with another aspect and benefit of the present invention, the film or coating will also prevent the interaction components of the device with the drug inside the capsule and as such the device will not alter or impact the effectiveness of the drug. 
         [0057]    As shown in  FIG. 7 , one example of the device  40  includes a skirt  40   a  with a plurality of holes  44  and electronics  40   b . As the sheets  42   a  and  42   b  are subject to heating or pressure, then the sheets  42   a  and  42   b  are secured to each other through the holes  44  and the device  40  is securely held between the sheets  42   a  and  42   b . As shown in  FIG. 7 , the device  40  is laminated between the sheets  42   a  and  42   b . In accordance with another aspect of the present invention, the sheets  42   a  and  42   b  may have the portions for each device  40  punched, cut-out, or removed first and then positioned above and below the device  40 . The portions are cut to be oversized. Thus, as the portions of the sheets  42   a  and  42   b  are exposed to heat or pressure, then the oversized portions at the edges are secured to each other forming a pocket that surrounds the device  40  as well as secured to in place through the holes  44  as noted above. In accordance with another aspect of the present invention, the holes  44  may be eliminated when the device is placed between the oversized portions and secured within a pocket that surrounds the device  40 . 
         [0058]    Referring now to  FIG. 8  and  FIG. 9 , in accordance with one aspect of the present invention, a laminated device sheet  50  is positioned above a die  52  with a hole  52   a  in the die  52 . Even though only one hole  52   a  is shown, it will be understood by those skilled in art that the die may include multiple holes and the example discussed with respect one, may be repeated for many. The hole  52   a  of the die  52  is positioned above a capsule holder  54  that contains a capsule end  56 . As the sheet  50  is positioned above the hole  52   a , a punch  58  is used to cut the device  50   a  out of the sheet  50  and insert the device  50   a  into the capsule end  56 . As noted above in accordance with various aspects of the present invention, the device  50   a  can have a variety of shapes and those shapes can be created by the punch  58 . 
         [0059]    Referring now to  FIGS. 10-14 , in accordance with one aspect of the present invention, the device  40  of  FIG. 6  may be punched out and placed inside a hole  62   a  of a transfer tray  62 . The tray  62  is shown in  FIG. 10  with a plurality of holes. As shown in  FIG. 11 , the tray  62  is positioned below a sheet of devices, such as the sheet  50  of  FIG. 8 . A punch blade  64  cuts a device  66  from the sheet of devices and inserts the device  66  into the hole  62   a . The device  66  is held in place in the hole  62  with friction as shown in  FIG. 12 . The tray  62  is then advanced to the next step of the process and a punch press  70  pushes the device  66  into a capsule end  72  held within a capsule holder  74  as shown in  FIGS. 13 and 14 . 
         [0060]    As noted above various disintegration materials may be used to surround the electronic components. For example, a disintegrant may be sodium starch glycolate or a water soluble excipient such as hydroxypropyl cellulose. It will also be apparent that the various layers disclosed can be eliminated or combined depending on the material employed and the properties thereof. 
         [0061]    As described herein, a system of the present invention is used with a conducting fluid to indicate the event marked by contact between the conducting fluid and the system. For example, the system of the present disclosure may be used with a pharmaceutical product and the event that is indicated is when the product is taken or ingested. The term “ingested” or “ingest” or “ingesting” is understood to mean any introduction of the system internal to the in-vivo. For example, ingesting includes simply placing the system in the mouth all the way to the descending colon. Thus, the term ingesting refers to any instant in time when the system is introduced to an environment that contains a conducting fluid. Another example would be a situation when a non-conducting fluid is mixed with a conducting fluid. In such a situation the system would be present in the non-conduction fluid and when the two fluids are mixed, the system comes into contact with the conducting fluid and the system is activated. Yet another example would be the situation when the presence of certain conducting fluids needed to be detected. In such instances, the presence of the system, which would be activated, within the conducting fluid could be detected and, hence, the presence of the respective fluid would be detected. 
         [0062]    It is noted that, as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. 
         [0063]    As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible. 
         [0064]    Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims. 
         [0065]    Accordingly, the preceding merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and embodiments of the invention as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. The scope of the present invention, therefore, is not intended to be limited to the exemplary embodiments shown and described herein. Rather, the scope and spirit of present invention is embodied by the appended claims.