WO2016141288A1

WO2016141288A1 - Platform for delayed drug release within the gastrointestinal tract

Info

Publication number: WO2016141288A1
Application number: PCT/US2016/020886
Authority: WO
Inventors: Florin M. Selaru
Original assignee: The Johns Hopkins University
Priority date: 2015-03-04
Filing date: 2016-03-04
Publication date: 2016-09-09

Abstract

A system according to the present invention provides for drug delivery without requiring the patient to maintain a drug dosage schedule. The system includes a capsule that contains a medical reservoir, a medication pump, a battery, a wireless communication module, and sensors for monitoring pH, temperature, etc. The system also includes a control unit in the form of a handheld device or software component for a personal computer or handheld computing device. The control unit communicates with the capsule and is also capable of receiving communication from the capsule. Additionally, a mechanical system is included with the capsule to confine the capsule to a predetermined region of the gastrointestinal tract. From the physician perspective, this system offers the benefit of compliance, and of fine-tuning medication delivery without patient involvement.

Description

PLATFORM FOR DELAYED DRUG RELEASE WITHIN THE

GASTROINTESTINAL TRACT

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 62/127,859 filed March 4, 2015, which is incorporated by reference herein, in its entirety.

FIELD OF THE INVENTION [0002] The present invention relates generally to medical devices. More particularly, the present invention relates to a device platform for delayed drug release within the gastrointestinal tract.

BACKGROUND OF THE INVENTION

[0003] The oral or rectal route of medication administration is superior in terms of patient acceptability than the intravenous or intramuscular route. In addition, the ideal drug will be delivered to the human body just once and will act for the duration of the disease. However, the vast majority of oral or rectal drugs are currently administered 1-3 times daily. This high frequency of administration contributes significantly to low medication compliance. In addition, for patients who need to take multiple drugs, the drug schedule is oftentimes overwhelming and mistakes are made, with potentially catastrophic results due to medication interaction, overdosing or underdosing. Certain categories of patients, such as elderly or patients with chronic diseases (e.g., renal failure, HIV infection, psychiatric patients) would particularly benefit from a drug delivery platform that would be administered infrequently, and would manage the complex medication schedule without any patient input. [0004] Accordingly, it would be beneficial to provide a drug delivery system that would require infrequent oral administration. SUMMARY OF THE INVENTION

[0005] The foregoing needs are met, to a great extent, by the present invention which provides a system for drug delivery that includes a capsule having a housing defining an interior space wherein a drug reservoir and a drug distributor are disposed within the housing. The system also includes a system for securing the drug delivery device in a gastrointestinal tract of a subject. Additionally, the system includes a control unit for monitoring and changing drug delivery via the drug distributor.

[0006] In accordance with an aspect of the present invention, the system includes one or more drug reservoirs. A wireless communication module can be housed within the capsule housing and configured to communicate with the control unit and to receive communication from the control unit. The system further includes sensors disposed on the control unit such that the sensors can determine biologic parameters at the capsule. The sensors can take the form of a pH sensor. The system for securing the drug delivery device also includes a device for increasing the size of the capsule, a magnetic dock and corresponding magnetic components, telescoping arms, and/or rotating arms. The magnetic dock is disposed between the mucosa and muscularis. The magnetic dock further includes docking extensions, and the docking extensions can be configured to extend through the mucosa.

[0007] In accordance with another aspect of the present invention, the drug distributor takes the form of a pump. The system can include a battery for providing power to the pump. The drug distributor is configured to use osmosis to deliver the drug and can included an osmotic layer and a semi-permeable layer. A flow moderator is disposed in the drug reservoir. A fluid flow channel is defined by the housing between the drug reservoir and the drug distributor. The fluid flow channel can take the form of a flow moderator. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The accompanying drawings provide visual representations, which will be used to more fully describe the representative embodiments disclosed herein and can be used by those skilled in the art to better understand them and their inherent advantages. In these drawings, like reference numerals identify corresponding elements and:

[0009] FIGS. 1-5 illustrate a drug delivery capsule according to an embodiment of the present invention.

[0010] FIG. 1 illustrates a top down view of the drug delivery capsule according to an embodiment of the present invention.

[0011] FIG. 2 illustrates a top down view of an osmotic pump according to an embodiment of the present invention.

[0012] FIG. 3 illustrates a top down view of a battery operated pump according to an embodiment of the present invention.

[0013] FIG. 4 illustrates a top down view of a communicative drug delivery device according to an embodiment of the present invention.

[0014] FIG. 5 illustrates a top down view of a multi-reservoired drug delivery device, according to an embodiment of the present invention.

[0015] FIGS. 6-9 illustrate mechanical systems to restrict the capsule to a defined region of the gastrointestinal tract for the desired duration of treatment, according to an embodiment of the present invention.

[0016] FIG. 6 illustrates a top down view of a drug delivery capsule according to an embodiment of the present invention.

[0017] FIG. 7 illustrates a top down view of a drug delivery capsule of FIG. 6 with the arms of the restriction system in an open position. [0018] FIG. 8 illustrates a top down view of a drug delivery capsule according to an embodiment of the present invention.

[0019] FIG. 9 illustrates a top down view of a drug delivery capsule of FIG. 8 with the arms of the restriction system in an open position.

[0020] FIGS. 10 and 11 illustrate a docking station in the gastrointestinal tract for a device, according to an embodiment of the present invention.

[0021] FIGS. 12 and 13 illustrate docking the device between the mucosa and the muscularis, preferably with extensions that hold the device in place. DETAILED DESCRIPTION

[0022] The presently disclosed subject matter now will be described more fully hereinafter with reference to the accompanying Drawings, in which some, but not all embodiments of the inventions are shown. Like numbers refer to like elements throughout. The presently disclosed subject matter may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Indeed, many modifications and other embodiments of the presently disclosed subject matter set forth herein will come to mind to one skilled in the art to which the presently disclosed subject matter pertains having the benefit of the teachings presented in the foregoing descriptions and the associated Drawings. Therefore, it is to be understood that the presently disclosed subject matter is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims.

[0023] A system according to the present invention provides for drug delivery without requiring the patient to maintain a drug dosage schedule. The system includes a capsule that contains a medical reservoir, a medication pump, a battery, a wireless communication module, and sensors for monitoring pH, temperature, etc. The system also includes a control unit in the form of a handheld device or software component for a personal computer or handheld computing device. The control unit communicates with the capsule and is also capable of receiving communication from the capsule. Additionally, a mechanical system is included with the capsule to confine the capsule to a predetermined region of the

gastrointestinal tract. From the physician perspective, this system offers the benefit of compliance, and of fine-tuning medication delivery without patient involvement.

[0024] FIGS. 1-5 illustrate a drug delivery capsule according to an embodiment of the present invention. The drug delivery platform includes a capsule that contains one or more medication reservoirs, a medication pump, a battery, a wireless communication module, and sensors for monitoring pH, temperature or other physiologic conditions.

[0025] FIG. 1 illustrates a top down view of the drug delivery capsule according to an embodiment of the present invention. The drug delivery capsule 10 is small enough in dimension to traverse the GI tract. The example illustrated in FIG. 1 shows a drug delivery capsule 10 with exemplary dimensions of 8-12 mm by 20-30 mm. These dimensions are included by way of example and are not meant to be considered limiting. Any dimensions known to or conceivable by one of skill in the art can also be used.

[0026] FIG. 2 illustrates a top down view of an osmotic pump according to an embodiment of the present invention. The osmotic pump takes the form of a drug delivery capsule 10. In the embodiment illustrated in FIG. 2, the drug delivery device 10 takes the form of an osmotic pump. The drug delivery device 10 includes a semi -permeable membrane 12 to facilitate the osmotic nature of the embodiment of FIG. 2. An osmotic layer 14 is disposed within the semipermeable membrane 12, between the semipermeable membrane 12 and the medication reservoir 16. A flow moderator 18 can be disposed within the medication reservoir 16 in order to ensure a desired or predetermined flow of medication through the osmotic pump.

[0027] FIG. 3 illustrates a top down view of a battery operated pump according to an embodiment of the present invention. The drug delivery capsule 100 takes the form of a battery operated pump. The drug delivery capsule 100 includes a medication reservoir 102 and a pump 104. The medication reservoir 102 and pump 104 are in fluid communication via first channel 106. The first channel 106 can also take the form of a flow regulator. A second channel 108 allows for the pump to transmit the medication from the medication reservoir 102 to the patient. The second channel 108 can also take the form of a flow regulator to limit the amount of medication delivered to the patient. A battery 110 is used to power the pump 104.

[0028] FIG. 4 illustrates a top down view of a communicative drug delivery device according to an embodiment of the present invention. As illustrated in FIG. 4 the

communicative drug delivery device 200 includes a medication reservoir 202 and a pump 204. The medication reservoir 202 and pump 204 are in fluid communication via first channel 206. The first channel 206 can also take the form of a flow regulator. A second channel 208 allows for the pump to transmit the medication from the medication reservoir 202 to the patient. The second channel 208 can also take the form of a flow regulator to limit the amount of medication delivered to the patient. The communicative drug delivery device 200 also includes a wireless communication module 210 and a pH sensor 212.

[0029] FIG. 5 illustrates a top down view of a multi-reservoired drug delivery device, according to an embodiment of the present invention. As illustrated in FIG. 5, the drug delivery device 300 can include multiple medication reservoirs 302, 304, 306, 308. While 4 reservoirs are shown in FIG. 5 any number of reservoirs known to or conceivable by one of skill in the art could be used. It should also be noted that each of the reservoirs does not need to be filled with medication. The drug delivery device 300 of FIG. 5 also includes a pump 310. The pump 310 can be battery powered or powered by any other means known to or conceivable by one of skill in the art. First channel 312 puts the first reservoir 302 in fluid communication with the pump 310. Second channel 314 puts the second reservoir 304 in fluid communication with the pump 310. Third channel 316 puts the third reservoir in fluid communication with the pump 310, and fourth channel 318 puts the fourth reservoir in fluid communication with the pump 310. The reservoirs 302, 304, 306, 308, can be engaged for dispensing medicine simultaneously, separately, or in combination. Fluid channel 320 dispenses medication from the pump 310 to the patient. It should also be noted that the first, second, third, and fourth channels can also be flow regulators as well as the fluid channel between the pump and the patient.

[0030] The system also includes a control unit, that is a handheld device, or a software program for an existing hand held device that communicates with the capsule bi- directionally. The control unit system is used to report functioning parameters of the capsule, to control (increase, decrease, stop or begin) medication release from the capsule, to control the release of the capsule from the area of the GI tract where it was restricted. The control unit also allows for the physician to monitor and alter dosage and drug delivery without having to change the parameters engaged in by the patient.

[0031] In some embodiments the device can also include a loading station, which is a device that is utilized to load the capsule with medications that are uniquely tailored for the specific patients.

[0032] The pump included in the capsule will be either of the osmotic type (that does not require a battery), as illustrated in FIG. 2, or electric type (requires a battery), as illustrated in FIG. 3. The capsule will include one to several drug compartments that will be loaded with medications. FIGS. 2-4 illustrate a device with a single drug compartment, while FIG. 5 illustrates a device with multiple drug compartments. The capsule can also include a battery as illustrated in FIG. 3. A wireless communication module will also be included, as illustrated in FIG. 4. This module engages in bi-directional communication with an outside device. This module is instrumental in transmitting functioning parameters of the capsule, triggering alarms in the case of malfunctioning, as well as receiving commands from the outside device, such as changes in drug release (increasing the rate, decreasing the rate, starting or stopping a medication). The capsule also includes sensors (such as pH or temperature) that could be used to induce the restriction of the capsule to a certain area of the GI tract or to monitor certain disorders (such as gastric acid hyperactivity).

[0033] Further, with respect to the control unit, it is a handheld device or software to be installed on existing handheld devices (such as smartphones) that is used to report information from the capsule, as well as for modulating the functioning of the capsule (changes in medication delivery rates, stopping or starting medications, changing the conformation of the capsule to promote its elimination from the GI tract).

[0034] FIGS. 6-9 illustrate mechanical systems to restrict the capsule to a defined region of the gastrointestinal tract for the desired duration of treatment. In some embodiments, the mechanical system increases the size of the capsule after the capsule reaches the stomach and thus prevents it from moving further downstream within the GI tract (restriction to the stomach). The trigger for this system could be pH (the stomach has a uniquely low pH, of approximately 1), as determined by the sensor in the capsule. After a predetermined duration of time (for example 1 week), or in response to a command from the control unit, the mechanical system changes conformation to allow the capsule to progress through the GI tract and be eliminated through feces. In other embodiments, the mechanical system can take the form of an electromagnetic system to restrict the capsule to the desired location within the GI tract.

[0035] FIG. 6 illustrates a top down view of a drug delivery capsule according to an embodiment of the present invention. FIG. 6 illustrates an embodiment of a system for restricting the drug delivery capsule, with the rotational arms of the restriction system in the closed position. As illustrated in FIG. 6. The drug delivery capsule 400 includes arms 402, 404, 406 that rotate out from a body 408 of the capsule 400. The arms 402, 404, and 406 are in the closed position in FIG. 6. While three arms 402, 404, and 406 are illustrated in FIG. 6 any suitable number of arms known to or conceivable by one of skill in the art could be used.

[0036] FIG. 7 illustrates a top down view of a drug delivery capsule of FIG. 6 with the arms of the restriction system in an open position. As illustrated in FIG. 7, the restriction system includes arms 402, 404, 406, and 410 in an open position for restricting movement of the drug delivery capsule 400. The arms 402, 404, 406, and 410 are rotated out from the body of the capsule 400 in order to achieve the open position.

[0037] FIG. 8 illustrates a top down view of a drug delivery capsule according to an embodiment of the present invention. FIG. 8 illustrates an embodiment of a system for restricting the drug delivery capsule, with telescoping arms in a closed position. As illustrated in FIG. 8 the drug delivery capsule 500 includes arms 502, 504, 506, and 508. The arms 502, 504, 506, and 508 are configured to telescope in and out from the body 510 of the drug delivery capsule 500. Any number of arms known to or conceivable by one of skill in the art could also be used.

[0038] FIG. 9 illustrates a top down view of a drug delivery capsule of FIG. 8 with the arms of the restriction system in an open position. As illustrated in FIG. 8, the restriction system includes arms 502, 504, 506, and 508 in an open position for restricting movement of the drug delivery capsule 500. The arms 502, 504, 506, and 508 are telescoped out from the body of the capsule 500 in order to achieve the open position.

[0039] Any external capsule that is placed within the GI tract has the theoretical potential for inducing bowel obstruction, in case it blocks the flow through the GI tract. Nonetheless, the stomach is a larger cavity that will allow the presence of such a capsule without the potential for bowel obstruction. The rectum is the second region of the GI tract that would also allow the placement of such capsule without the danger of bowel obstruction.

[0040] The mechanical systems restrict the capsule to a predetermined location in the body for a predetermined amount of time. The device can be restricted to the stomach or rectum or alternately any other position in the body that is known to or conceivable to one of skill in the art. In one embodiment, presence of arms on the outside surface of the capsule that in response to a predetermined stimulus (such as low pH, characteristic for the stomach) will rotate, as illustrated in FIGS. 6 and 7. The rotation of these arms, from the inward position in FIG. 6 to the outward position in FIG. 7, will restrict the movement of the capsule through the pylorus and will restrict it to the stomach. The arms can move in the original position, or could be severed from the capsule after a predetermined amount of time (for example 1 week) or in response to other stimuli (such as a command from the control unit outside the patient's body).

[0041] In another embodiment, as illustrated in FIGS. 8 and 9, telescoping arms that extend from the capsule promote retaining the capsule in the stomach. The arms will telescope back into the capsule when the capsule is ready to leave the stomach.

[0042] In another embodiment, a layer on the outside of the capsule swells in contact with gastric juices and increase the size of the capsule restricting in to the stomach. This layer could be degraded enzymatically by enzymes contained within a reservoir within the capsule in response to a command from the control unit outside the patient's body.

[0043] As illustrated in FIGS. 10 and 11, in another embodiment, a docking station 600 is situated within the stomach. This system involves the endoscopic placement of a docking station within the stomach. This docking station can be placed at a convenient location (such as gastric fundus). The docking station can be placed in a variety of ways, including submucosal placement. This placement is currently feasible through creating a pocket underneath the mucosa (including the possible use of a dissecting gel), inserting the docking station, then closing the flap. The drug delivery capsule 602 couples to the docking station 600.

[0044] The docking station can be placed endoscopically as described above. The docking station includes an electropermanent magnet or another magnetizible device. The magnetic properties of the docking station are changed by the outside device. The docking station is magnetized, then the capsule swallowed. In this variation of the delivery system, the capsule contains metal that promotes the docking of the capsule to the docking station. After a predetermined amount of time, the docking station will de-magnitize and the capsule will be allowed to move downstream through the GI tract.

[0045] A variation of the system involves placing the pump within the docking station. The capsule then only serves the purpose of carrying drugs to the docking station and, potentially, providing the electrical power (battery) that will power the docking station to deliver medications.

[0046] A variant of the system described here is for rectal administration. This system involves the endoscopic placement of a docking station within the rectum. Once a week (or at frequencies that will be determined by specific medications and their packaging within the capsule), a capsule will be inserted through the rectum. The capsule will dock to the docking station (electropermanent magnet or electromagnet). As above, a variation is possible where the capsule will carry the medications and the battery, while the docking station will include a pump to deliver the medications. FIGS. 12 and 13 illustrate docking the device 700 between the mucosa 702 and the muscularis 704, preferably with extensions 706 and 708 that hold the device in place, as illustrated in FIG. 13.

[0047] The present invention is advantageous because it allows for infrequent

administration of medications. The frequency of the administration will depend on how well the specific drug can be packaged within the volume of the capsule. We expect that once a week administration is feasible currently and predict that with further drug development, once a month, or longer, administration will be feasible. Therefore, compliance with medications can be increased dramatically. The present invention allows for administration of multiple medications with the same capsule, removing complexity from patients. This will further increase compliance.

[0048] The present invention also allows medication administration to select patient populations who need multiple medications or who would prefer to not manage a complex drug administration schedule. These populations include elderly (multiple medications, complex schedules), chronic diseases (renal failure, HIV infection, psychiatric patients).

[0049] It should be noted that the system described herein can include a computing device such as a microprocessor, hard drive, solid state drive or any other suitable computing device known to or conceivable by one of skill in the art. The computing device can be programmed with a non-transitory computer readable medium that is programmed with steps to execute the different stimulation levels, patterns, and configurations available. [0050] Any such computer application will be fixed on a non-transitory computer readable medium. It should be noted that the computer application is programmed onto a non- transitory computer readable medium that can be read and executed by any of the computing devices mentioned in this application. The non-transitory computer readable medium can take any suitable form known to one of skill in the art. The non-transitory computer readable medium is understood to be any article of manufacture readable by a computer. Such non- transitory computer readable media includes, but is not limited to, magnetic media, such as floppy disk, flexible disk, hard, disk, reel-to-reel tape, cartridge tape, cassette tapes or cards, optical media such as CD-ROM, DVD, blu-ray, writable compact discs, magneto-optical media in disc, tape, or card form, and paper media such as punch cards or paper tape.

Alternately, the program for executing the method and algorithms of the present invention can reside on a remote server or other networked device. Any databases associated with the present invention can be housed on a central computing device, server(s), in cloud storage, or any other suitable means known to or conceivable by one of skill in the art. All of the information associated with the application is transmitted either wired or wirelessly over a network, via the internet, cellular telephone network, or any other suitable data transmission means known to or conceivable by one of skill in the art.

[0051] The many features and advantages of the invention are apparent from the detailed specification, and thus, it is intended by the appended claims to cover all such features and advantages of the invention, which fall within the true spirit and scope of the invention.

Further, since numerous modifications and variations will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation illustrated and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention.

Claims

What is claimed is:

1. A system for drug delivery comprising:

a capsule having a housing defining an interior space wherein a drug reservoir and a drug distributor are disposed within the housing;

a system for securing the drug delivery device in a gastrointestinal tract of a subject; and

a control unit for monitoring and changing drug delivery via the drug distributor.

2. The system of claim 1 further comprising one or more drug reservoirs.

3. The system of claim 1 further comprising a wireless communication module housed within the capsule housing and configured to communicate with the control unit and to receive communication from the control unit.

4. The system of claim 1 further comprising sensors disposed on the control unit such that the sensors can determine biologic parameters at the capsule.

5. The system of claim 4 further comprising a pH sensor.

6. The system of claim 1 wherein the system for securing the drug delivery device comprises a device for increasing the size of the capsule.

7. The system of claim 1 wherein the system for securing the drug delivery device comprises a magnetic dock and corresponding magnetic components.

8 The system of claim 7 wherein the magnetic dock is disposed between the mucosa and muscularis.

9. The system of claim 7 wherein the magnetic dock further comprises docking extensions.

10. The system of claim 9 wherein the docking extensions extend through the mucosa.

11. The system of claim 1 wherein the system for securing the drug delivery device comprises telescoping arms.

12. The system of claim 1 wherein the system for securing the drug delivery device comprises rotating arms.

13. The system of claim 1 wherein the drug distributor comprises a pump.

14. The system of claim 13 further comprising a battery for providing power to the pump.

15. The system of claim 1 wherein the drug distributor is configured to use osmosis to deliver the drug.

16. The system of claim 15 further comprising an osmotic layer.

17. The system of claim 15 further comprising a semi -permeable layer.

18. The system of claim 1 further comprising a flow moderator disposed in the drug reservoir.

19. The system of claim 1 further comprising a fluid flow channel defined by the housing between the drug reservoir and the drug distributor.

20. The system of claim 19 wherein the fluid flow channel comprises a flow moderator.