Device, system and methods for the oral delivery of therapeutic compounds

• US 8,734,429 B2
• Filed: 03/15/2013
• Issued: 05/27/2014
• Est. Priority Date: 12/23/2010
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc. (Sanofi )
• Original Assignee: RaNA Therapeutics Inc. (Sanofi )
• Inventors: Imran, Mir, Herrmann, Peter, Syed, Baber, Williams, Timothy H., Ong, Chang Jin, Method, Greg
• Primary Examiner(s): Bosworth, Kami A
• Application Number:
  US13/837,025
• Publication Number:
  US 20130274659A1
• Time in Patent Office: 438 Days
• Field of Search: 604/82, 604/87, 604/89, 604/93.01, 604/103.01, 604/103.02, 604131-133, 604140-145, 604/153, 604/173, 604/890.1, 604/891.1, 604/892.1, 604/500, 604506-508, 604514-516, 128897-899
• US Class Current: 604/890.1
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• CPC Class Codes: A61K 38/55 Protease inhibitors
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61M 2205/3331 Pressure; Flow
• CPC Class Codes: A61M 2210/1042 Alimentary tract A61M2210/0618 takes precedence
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61M 37/0069 Devices for implanting pellets, e.g. markers or solid medicaments for introducing of radioactive sources for interstitial radiation therapy, i.e. brachytherapy A61N5/1027
• CPC Class Codes: A61M 5/14244 adapted to be carried by the patient, e.g. portable on the body
• CPC Class Codes: A61M 5/155 pressurised by gas introduced into the reservoir

Abstract

Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Particular embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. Embodiments also provide various drug preparations that are configured to be contained within the capsule, advanced from the capsule into the intestinal wall and degrade within the wall to release the drug to produce a therapeutic effect. The preparation can be coupled to a delivery mechanism having one or more balloons or other expandable devices which are expandable responsive to a condition in the small intestine or other GI lumen to advance the preparation out of the capsule into the intestinal wall. Embodiments of the invention are particularly useful for the delivery of drugs which are poorly absorbed, tolerated and/or degraded within the GI tract.

Claims

1. A swallowable device for delivering a therapeutic agent preparation into an intestinal wall of a patient'"'"'s intestinal tract, the swallowable device comprising:

a swallowable capsule sized to pass through the intestinal tract, the capsule having a capsule wall, a least a portion of which degrades upon exposure to a selected pH in an intestine while protecting the capsule wall from degradation in a stomach of the patient;

at least one expandable member assembly disposed within the capsule comprising a first compartment in at least a partially non-expanded state and a second compartment in at least a partially non-expanded state, the first and second compartments being fluidically separated by a degradable valve which degrades upon exposure to fluid in the intestinal tract;

a liquid contained in one of the compartments;

a reactant contained in the other compartment, wherein when the valve degrades, the liquid and the reactant mix to produce a gas which expands at least the second compartment;

a delivery mechanism coupled to the second compartment, the delivery mechanism comprising at least one piston-cylinder assembly; and

at least one tissue penetrating member comprising;

a. a proximal portion detachably coupled to the delivery mechanism; and

b. a tissue penetrating distal portion;

c. and a therapeutic agent preparation for delivery into the intestinal wall, the at least one tissue penetrating member configured to be retained in the intestinal wall; and

wherein upon expansion of the second compartment, the at least one tissue penetrating member is advanced into the intestinal wall by the delivery mechanism where it is retained in the intestinal wall so as to deliver the therapeutic agent into the intestine.

2. The swallowable device of claim 1, wherein the at least one piston-cylinder assembly comprises a piston slidably disposed inside a cylinder, the cylinder coupled to a wall of the second compartment and the piston having a proximal face exposed to an interior of the second compartment so as to have the piston be driven by the gas produced in the second compartment, and

wherein the piston is configured to advance the at least one tissue penetrating member into the intestinal wall as it slides inside the cylinder.

3. The swallowable device of claim 2, the piston-cylinder assembly further comprising a needle lumen coupled to the cylinder, wherein the needle lumen provides access to an exterior of the second compartment, and

wherein the at least one tissue penetrating member is disposed inside the needle lumen and coupled to the piston by a piston rod, the piston rod sized to be advanced through the needle lumen as the piston slides inside the cylinder.

4. The swallowable device of claim 3, further comprising a means of piston-cylinder assembly alignment, the means of piston-cylinder assembly alignment configured to align the piston-cylinder assembly when the second compartment expands, such that a long axis of the piston-cylinder assembly is perpendicular to a surface of the intestinal wall so that the at least one tissue penetrating member is advanced perpendicularly into the intestinal wall.

5. The swallowable device of claim 4, wherein the piston-cylinder assembly alignment means comprises a joint configured to exert a force on the piston-cylinder assembly to bias it into a vertical orientation.

6. The swallowable device of claim 3, wherein the delivery mechanism comprises an array of piston-cylinder assemblies.

7. The swallowable device of claim 6, wherein the array of piston-cylinder assemblies share a common inflation manifold, the common inflation manifold configured to direct the gas to drive each piston of the array of piston-cylinder assemblies.

8. The swallowable device of claim 2, wherein the piston-cylinder assembly further comprises a pressure sensitive release that prevents the piston from sliding inside the cylinder until a specified pressure is reached inside the at least one expandable member.

9. The swallowable device of claim 8, wherein the pressure sensitive release comprises a tab, latch or an O-ring.

10. The swallowable device of claim 8, wherein the pressure sensitive release is configured to release at a pressure in the range of about 8 to 10 psi.

11. The device of claim 2, wherein the piston-cylinder assembly further comprises an O-ring disposed around the piston that maintains a seal between the piston and the cylinder.

12. The device of claim 1, wherein the degradable valve comprises an O-ring positioned over a dissolvable pinch valve, the pinch valve configured to dissolve upon contact with fluid in the small intestine.

13. The device of claim 1, wherein the capsule comprises a first capsule portion and a second capsule portion, the first capsule portion degrading at a first pH and the second portion degrading at a second pH.

14. The device of claim 13, wherein the first capsule portion overlies at least a portion of the degradable valve, wherein when the first capsule portion degrades, intestinal fluid can enter the capsule to make contact with the degradable valve.

15. The device of claim 13, wherein the first capsule portion degrades at a pH equal to or greater than about 5.5.

16. The device of claim 13, wherein the second capsule portion degrade at a pH equal to or greater than about 6.5.

17. The device of claim 13, wherein the first capsule portion comprises a body and the second capsule portion comprises a cap which fits onto the body.

18. The device of claim 1, wherein the pH degradable portion of the capsule wall comprises a pH sensitive coating.

19. The device of claim 1, wherein the valve comprises a sugar.

20. The device of claim 19, wherein the sugar comprise maltose.

21. The device of claim 1, wherein the reactant comprises at least a first and second reactant.

22. The device of claim 21, wherein the first and second reactant comprise an acid and a base.

23. The device of claim 22, wherein the first reactant comprises potassium bicarbonate and the second reactant comprises citric acid.

24. The device of claim 1, wherein the at least one tissue penetrating member comprises a sugar.

25. The device of claim 24, wherein the sugar comprises maltose.

26. The device of claim 1, wherein the therapeutic agent preparation comprises a shaped section disposed within at least one tissue penetrating member.

27. The device of claim 1, wherein the at least one tissue penetrating member is formed at least in part from the therapeutic agent preparation.

28. The device of claim 1, wherein the at least one tissue penetrating member includes a retaining feature for retaining the at least one tissue penetrating member within the intestinal wall.

29. The device of claim 28, wherein the retaining feature comprises a barb or a hook.

30. The device of claim 29, wherein the at least one tissue penetrating member comprises a plurality of tissue penetrating members.

31. The device of claim 1, wherein the intestine is the small intestine and the capsule wall is configured to degrade in response to a selected pH in the small intestine.

32. The device of claim 1, wherein the at least one expandable member assembly comprises a polymer, a substantially non-compliant polymer, polyethylene, PET or polyimide.

33. A swallowable device for inserting a therapeutic agent preparation into an intestinal wall of a patient'"'"'s intestinal tract, the device comprising:

a swallowable capsule sized to pass through the intestinal tract, the capsule having a capsule wall, a least a portion of which degrades upon exposure to a selected pH in an intestine while protecting the capsule wall from degradation in the stomach;

at least one expandable member assembly disposed within the capsule comprising a first compartment in at least a partially non-expanded state and a second compartment in at least a partially non-expanded state, the first and second compartments being fluidically separated by a degradable valve which degrades upon exposure to fluid in the intestinal tract;

a liquid contained in one of the compartments;

a reactant contained in the other compartment, wherein when the valve degrades, the liquid and the reactant mix to produce a gas which expands at least the second compartment;

a delivery mechanism coupled to the wall of the second expandable compartment; and

at least one tissue penetrating member comprising;

a.) a proximal portion detachably coupled to the delivery mechanism; and

b.) tissue penetrating distal portion;

c.) and a therapeutic agent preparation for delivery into the intestinal wall,

the tissue penetrating member configured to be retained in the intestinal wall; and

wherein upon expansion of the second compartment the at least one tissue penetrating member is advanced into the intestinal wall by the delivery mechanism where it is retained in the intestinal wall so as to deliver the therapeutic agent into an intestine; and

wherein the delivery mechanism comprises a third compartment having a lower portion and an upper portion, the lower portion being coupled to a wall of the second compartment having one or more tissue penetrating members disposed thereon and directed towards the upper portion and the intestinal wall, the upper portion having one or more puncture needles disposed thereon directed towards the lower portion; and

wherein upon inflation of the second compartment, the lower portion of the third compartment is driven against the upper portion of the third compartment, the one or more tissue penetrating members being driven through the upper portion of the third compartment into the intestinal wall, and the one or more puncture needles being driven through the lower portion of the third compartment thereby puncturing the wall of the second compartment and deflating the expandable member assembly.

34. The swallowable device of claim 33, wherein the upper portion of the third compartment comprises one or more apertures configured to allow the one or more tissue penetrating members to pass through and into the intestinal wall.

35. The swallowable device of claim 33, wherein the one or more tissue penetrating members are long enough relative to the one or more puncture needles such that the expandable member assembly is not deflated until the at least one tissue penetrating members have been inserted into the intestinal wall.

36. The swallowable device of claim 33, wherein the bottom portion is fabricated from a material which does not allow penetration by the one or more puncture needles until a desired pressure is reached inside the second compartment.

37. A method of delivering a therapeutic agent preparation into an intestinal wall of a patient'"'"'s intestinal tract, the method comprising:

providing a swallowable capsule sized to pass through the intestinal tract, the capsule having;

a capsule wall, a least a portion of which degrades upon exposure to a selected pH in an intestine while protecting the capsule wall from degradation in a stomach of the patient; and

wherein, the swallowable capsule also having;

at least one expandable member assembly disposed within the capsule comprising a first compartment in at least a partially non-expanded state, a second compartment in at least a partially non-expanded state, wherein the first and second compartments are fluidically separated by a degradable valve which degrades upon exposure to fluid in the intestinal tract; and

degrading the degradable valve with fluid in the intestinal tract thereby allowing a liquid contained in one of the compartments to mix with a reactant contained in the other compartment; and

producing a gas with a reaction of the liquid and the reactant; and

inflating at least the second compartment of the expandable member assembly with the gas produced by the reaction of the liquid and the reactant; and

orienting a cylinder-piston assembly disposed inside the expandable member assembly, the cylinder-piston assembly comprising;

a piston slidably disposed inside a cylinder, an interface between the piston and the cylinder sealed with an O-ring, the cylinder coupled to a wall of the second compartment in communication with a needle lumen, the needle lumen providing access to an exterior of the second compartment; and

wherein the cylinder-piston assembly is oriented such that the needle lumen is perpendicular to the intestinal wall; and

driving the piston inside the cylinder towards the exterior of the second compartment with pressure from the gas, thereby driving a tissue penetrating member disposed in the needle lumen into the intestinal wall with a piston rod coupled between the piston and the tissue penetrating member, the piston rod sized to be slidable inside the needle lumen; and

wherein the tissue penetrating member comprises at least the therapeutic agent preparation.