Swallowable Drug Delivery Device and Method of Delivery

• US 20120010590A1
• Filed: 12/23/2010
• Published: 01/12/2012
• Est. Priority Date: 12/24/2009
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc.
• Original Assignee: InCube Labs LLC. (In-Cube, Inc.)
• Inventors: Imran, Mir
• Granted Patent: US 8,562,589 B2
• Time in Patent Office: Days
• US Class Current: 604/503
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/2235 Secretins
• 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• 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 2005/1401 Functional features
• CPC Class Codes: A61M 2005/14284 with needle insertion means
• CPC Class Codes: A61M 2210/106 Small intestine
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• 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 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/168 Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body flow control in general G05D7/00
• CPC Class Codes: A61M 5/1723 : using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61M 5/20 : Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically A61M5/142 , A61M5/46 take precedence; hypodermic projectiles F42B12/54
• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 3/08 : for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 5/18 : of the parathyroid hormones

Abstract

Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Some embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. The device comprises a capsule sized to be swallowed and pass through the intestinal tract. The capsule can include at least one guide tube, one or more tissue penetrating members positioned in the guide tube, a delivery member, an actuating mechanism and a release element. The release element degrades upon exposure to various conditions in the intestine so as to release and actuate the actuating mechanism. 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 inserting a therapeutic agent preparation into the 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 including an aperture;

at least a portion of the capsule wall comprising a material or coating which overlies the aperture and protects the capsule from degradation in the stomach and degrades in response to the pH in the small intestine;

a tissue penetrating member including a therapeutic agent preparation; and

means for advancing the tissue penetrating member from the capsule through the aperture and into the intestinal wall of the patient responsive to a selected pH in the intestine.

2. The swallowable device of claim 1, wherein the means for advancing the tissue penetrating member comprises an expandable member expandable responsive to a pH in the intestine.

3. The swallowable device of claim 2, wherein the expandable member is a balloon.

4. The swallowable device of claim 2, wherein the expandable member is expanded by a chemical reaction.

5. The swallowable device of claim 4, wherein the expandable member includes a pH sensitive valve for initiating the chemical reaction responsive to a pH in the intestine.

6. The swallowable device of claim 4, wherein the reactants for the chemical reaction are contained within the expandable member.

7. The swallowable device of claim 4, wherein the expandable member comprises at least a first portion and a second portion, the portions separated by a separation means, the first portion containing, a liquid, the second portion containing a reactant, upon mixing, the reactant and liquid produce a gas which expands the expandable device.

8. The swallowable of claim 7, wherein the separation means comprises a valve which opens in response to a force from a peristaltic contraction in the small intestine.

9. A swallowable device for delivering a therapeutic agent preparation into the 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 including an aperture;

an expandable member disposed within the capsule in at least a partially non-expanded state, the expandable member including a first portion and a second portion separated by a separation valve which degrades upon exposure to a selected pH in the intestine, the first portion including a liquid, the second portion including a reactant configured to react with the liquid to produce a gas which expands the expandable member, wherein when the valve degrades, the liquid from the first portion mixes with the reactant in the second portion, to produce the gas which expands the expandable member; and

a tissue penetrating member formed at least in part from a therapeutic agent preparation, the tissue penetrating member including a proximal and distal portion, the proximal portion detachably coupled to the expandable member, the tissue penetrating member including at least one retaining feature for retaining the tissue penetrating member within the intestinal wall, wherein upon expansion of the expandable member, the tissue penetrating member is advanced through the aperture into the intestinal wall where it is retained by the at least one retaining feature so as to detach from the expandable member.

10. The device of claim 9, wherein at least a portion of the capsule includes a coating which seals the aperture and degrades in response to a selected pH in the intestine;

and wherein upon opening of the aperture, intestinal fluid enters an interior space of the capsule and comes into contact with the separation valve.

11. The device of claim 10, wherein at least one of the coating or the separation valve comprises PGLA.

12. The device of claim 10, wherein the intestine is the small intestine and the coating is configured to degrade in response to a selected pH in the small intestine.

13. The device of claim 12, wherein the selected pH in the small intestine is greater than about 6.0.

14. The device of claim 9, wherein the tissue penetrating element is configured to detach from the expandable member upon contraction of the expandable member.

15. The device of claim 9, wherein the tissue penetrating element is configured to detach from the expandable member responsive to force exerted upon the expandable member by peristaltic contraction of the intestine.

16. The device of claim 9, wherein the expandable member is a balloon.

17. The device of claim 16, wherein the balloon has a wall thickness of less than about 0.001 inches.

18. The device of claim 9, wherein the expandable member comprises a polymer, a substantially non-compliant polymer, polyethylene PET or polyimide.

19. The device of claim 9, wherein the expandable member includes a deflation valve degradable upon exposure to at least one of the liquid in the expandable member or the liquid in the intestine so as to deflate the expandable member after expansion, the deflation valve configured to degrade a selectable time period after expansion of the expandable member so as to allow the expandable member to advance the tissue penetrating member into the intestinal wall.

20. The device of claim 19, wherein the deflation valve degrades at a slower rate than the separation valve.

21. The device of claim 19, further comprising a puncture element positioned on an interior surfaced of the capsule, the puncture element positioned and configured to puncture and deflate the expandable member.

22. The device of claim 9, wherein the capsule is configured to come apart into at least two pieces by expansion of the expandable member.

23. The device of claim 9, wherein the separation valve includes at least one pinching feature which engages a mating feature on an interior surface of the capsule to compresses and seal the expandable member between pinching feature and the mating feature.

24. The device of claim 9, wherein the separation valve comprises a beam structure attached to an interior surface of the capsule.

25. The device of claim 24, wherein the beam structure is attached to opposite radial sides of an interior surface of the capsule.

26. The device of claim 9, wherein the device includes at least two tissue penetrating members and corresponding apertures, and wherein the at least two tissue penetrating members are positioned on opposite walls of the expandable member so as to exit apertures positioned on opposite walls of the capsule.

27. The device of claim 9, wherein the device includes at least three tissue penetrating members and corresponding apertures.

28. The device of claim 9, further comprising an advancement member coupled to a surface of the expandable member and detachably coupled to the proximal portion of the tissue penetrating member, wherein upon expansion of the expandable member, the advancement member advances the tissue penetrating member into tissue,

wherein the advancement member includes an attachment feature which engages a mating feature on the proximal portion of the tissue penetrating member, and

wherein the attachment feature is a pin and the mating feature is a recess in which the pin inserts.

29. The device of claim 28, further comprising a support member for supporting the advancement member during expansion of the expandable member, the support member having a first surface attached to a surface of the expandable member and an opposing surface attached to an advancement member surface, the opposing surface attached to an advancement member surface, the opposing surface of the support member having a larger surface area than the advancement member surface to increase the pressure applied to the advancement member from expansion of the expandable member, wherein upon expansion of the expandable member, the support member pushes against the advancement member to advance the tissue penetrating member into tissue.

30. The device of claim 9, wherein the tissue penetrating member is needle shaped.

31. The device of claim 9, wherein the tissue penetrating member comprises a biodegradable polymer.

32. The device of claim 31, wherein the biodegradable polymer comprises PLGA.

33. The device of claim 31, wherein less than about 5% of the therapeutic agent in the tissue penetrating member is thermally degraded.

34. The device of claim 33, wherein less than about 1% of the therapeutic agent in the tissue penetrating member is thermally degraded.

35. The device of claim 9, further comprising:

at least one reservoir for storage of a therapeutic agent preparation, the reservoir fluidically coupled to the tissue penetrating member, the tissue penetrating member comprising a hollow tissue penetrating member having a lumen, the reservoir configured and positioned within the capsule to be collapsible by expansion of the expandable member so as to eject the therapeutic agent from the reservoir through the lumen and into the intestinal wall.

36. The device of claim 9, wherein the liquid comprises water.

37. The device of claim 9, wherein the reactant comprises a solid reactant.

38. The device of claim 9, wherein the reactant comprises a first reactant and a second reactant.

39. The device of claim 38, wherein the first reactant comprises an acid and the second reactant comprises a base.

40. The device of claim 39, wherein the acid comprises citric acid and the base comprises sodium bicarbonate.

41. The device of claim 9, wherein the at least one retaining feature comprises a barb or a hook.

42. The device of claim 9, wherein the at least one retaining feature comprises two retaining features that are symmetrically positioned 180 degrees apart with respect to a longitudinal axis of the tissue penetrating member.

43. A swallowable device for delivering a therapeutic agent preparation into the 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 including an aperture;

an expandable member disposed within the capsule in at least a partially non-expanded state, the expandable member including a first portion and second portion separated by a separation valve which degrades upon exposure to a selected pH in the intestine, the first portion including a liquid, the second portion including a reactant configured to react with the liquid to produce a gas which expands the expandable member, wherein when the valve degrades the liquid from the first portion mixes with the reactant in the second portion, to produce the gas which expands the expandable member;

a tissue penetrating member having a lumen and a proximal and a distal portion, the proximal portion coupled to the expandable member such that expansion of the expandable member, the tissue penetrating member is advanced through the aperture into the intestinal wall; and

at least one reservoir for storage of a therapeutic agent preparation, the reservoir fluidically coupled to tissue penetrating member lumen, the reservoir configured and positioned within the capsule to be collapsible by expansion of the expandable member so as to eject the therapeutic agent from the reservoir through the lumen and into the intestinal wall.

44. The device of claim 43, wherein the at least one reservoir comprises a first reservoir and a second reservoir.

45. The device of claim 43, further comprising a manifold having a channel, a tissue penetrating member connector and at least one reservoir connector all in fluidic communication, the tissue penetrating member connector coupled to the tissue penetrating member lumen and the at least one reservoir connector coupled to the at least one reservoir.

46. The device of claim 45, wherein the at least one reservoir comprises a first reservoir and a second reservoir, and the at least one reservoir connector comprises a first and a second reservoir connector, the first reservoir connector coupled to the first reservoir and the second reservoir connected coupled to the second reservoir.

47. A method for delivering a therapeutic agent into the wall of the small intestine, the method comprising:

swallowing a drug delivery device comprising a capsule, an expandable member and a tissue penetrating therapeutic agent for; and

expanding the expandable member responsive to a condition in the small intestine to deliver the therapeutic agent into the intestinal wall of the small intestine.

48. The method of claim 47, wherein the condition is a selected pH.

49. The method of claim 48, wherein the pH is above about 7.1.

50. The method of claim 47, wherein the therapeutic agent comprises a therapeutically effective dose of insulin for the treatment of diabetes or a glucose regulation disorder;

the method further comprising;

using the dose of delivered insulin to control a blood glucose level of a patient without injecting insulin into the patient.

51. The method of claim 47, wherein the therapeutic agent comprises a therapeutically effective dose of an incretin for the treatment of diabetes or a glucose regulation disorder, the method further comprising:

using the dose of delivered incretin to control a blood glucose level of a patient without injecting insulin into the patient.

52. The method of claim 47, wherein the therapeutic agent comprises a therapeutically effective dose of an incretin and a therapeutically effective dose of a biguanide for the treatment of diabetes or a glucose regulation disorder, the method further comprising:

using the dose of delivered incretin and biguanide to control a blood glucose level of a patient.

53. The method of claim 52, wherein the incretin comprises exenatide and the biguanide comprises metformin.

54. The method of claim 53, wherein the dosages of the incretin and the biguanide are matched to produce an improved level of blood glucose control for an extended period.

55. The method of claim 54, wherein the extended period is up to about a day.