Swallowable Drug Delivery Device and Methods of Drug Delivery

• US 20110160699A1
• Filed: 12/23/2010
• Published: 06/30/2011
• Est. Priority Date: 12/24/2009
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc. (Sanofi )
• Original Assignee: InCube Labs LLC. (In-Cube, Inc.)
• Inventors: Imran, Mir
• Granted Patent: US 8,721,620 B2
• Time in Patent Office: Days
• US Class Current: 604/514
• 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. An ingestible device suitable for swallowing into a lumen of a gastrointestinal tract of a patient, the lumen having a lumen wall, the device comprising:

a capsule sized to pass through the intestinal tract;

a therapeutic agent preparation disposable in the capsule, the preparation comprising at least one therapeutic agent, wherein the therapeutic agent preparation would chemically degrade or impose a deleterious effect on the patient if released within the lumen of the gastrointestinal tract; and

an actuator coupled to the therapeutic agent preparation and having a first configuration and a second configuration, the preparation being retained within the capsule when the actuator is in the first configuration, wherein the preparation is advanced from the capsule and into the lumen wall by movement of the actuator from the first configuration to the second configuration such that the deleterious effect or chemical degradation of the therapeutic agent in the lumen is inhibited.

2. The device of claim 1, wherein a therapeutic dose of the therapeutic agent is included in the capsule, and wherein the actuator is configured to advance substantially all of the therapeutic dose of the therapeutic agent into the lumen wall so as to minimize the deleterious effect.

3. The device of claim 1, wherein the actuator includes a release element comprising a material configured to degrade upon exposure to a selected pH in the gastrointestinal tract such that upon degradation, the preparation is advanced into the lumen wall.

4. The device of claim 3, wherein the selected pH is greater than about 7.4.

5. The device of claim 3, wherein the actuator comprises a spring, the release element being coupled to the spring to retain the spring in a compressed state and release the spring upon degradation of the release element.

6. The device of claim 5, wherein the actuator comprises an actuating mechanism including a first motion converter and a second motion converter, a tissue penetrating member having a lumen in which the therapeutic agent preparation is disposed, a delivery member and a track member, the first motion converter configured to convert motion of the spring to advance and withdraw the tissue penetrating member into and out of the lumen wall, the second motion converter configured to convert motion of the spring to advance the delivery member into the tissue penetrating member lumen to advance therapeutic agent preparation from the tissue penetrating member lumen into the lumen wall, the first and second motion converters riding along the track member.

7. The device of claim 6, wherein the tissue penetrating member comprises a biodegradable material configured to degrade so as to release the tissue penetrating member from the gastrointestinal wall.

8. The device of claim 6, wherein the tissue penetrating member comprises a needle.

9. The device of claim 6, wherein the delivery member comprises a plunger.

10. The device of claim 1, wherein the therapeutic agent preparation comprises a solid, a pellet, a powder or a liquid.

11. The device of claim 1, wherein the therapeutic agent preparation comprises a tissue penetrating member that is advanceable into the lumen wall.

12. The device of claim 1, wherein the therapeutic agent preparation includes at least a first therapeutic agent and a second therapeutic agent.

13. The device of claim 1, wherein the therapeutic agent preparation comprises a therapeutically effective dose of insulin for the treatment of diabetes or a glucose regulation disorder.

14. The device of claim 1, wherein the therapeutic agent preparation comprises a therapeutically effective dose of an incretin for the treatment of diabetes or a glucose regulation disorder.

15. The device of claim 14, wherein the incretin comprises a glucagon like peptide-1 (GLP-1), a GLP-1 analogue, exenatide, liraglutide, albiglutide, taspoglutide or a gastric inhibitory polypeptide (GIP).

16. The device of claim 1, wherein the therapeutic agent preparation comprises a combination of therapeutic agents for the treatment of diabetes or a glucose regulation disorder.

17. The device of claim 16, wherein the combination comprises a therapeutically effective dose of an incretin and a therapeutically effective dose of a biguanide.

18. The device of claim 17 wherein the incretin comprises exenatide and the biguanide comprises metformin.

19. The device of claim 17, wherein the dosages of the incretin and the biguanide are matched to produce an improved level of blood glucose control for an extended period.

20. The device of claim 1, wherein the therapeutic agent preparation comprises a therapeutically effective dose of growth hormone.

21. The device of claim 1, wherein the therapeutic agent preparation comprises a therapeutically effective dose of parathyroid hormone for the treatment of osteoporosis or a thyroid disorder.

22. The device of claim 1, wherein the therapeutic agent preparation comprises a therapeutically effective dose of a chemotherapeutic agent for the treatment of cancer.

23. The device of claim 1, wherein the therapeutic agent preparation comprises a therapeutically effective dose of antibiotic.

24. The device of claim 1, wherein the therapeutic agent preparation comprises a therapeutically effective dose of an antiviral compound.

25. The device of claim 24, wherein the antiviral compound comprises a protease inhibitor.

26. The device of claim 1, wherein the therapeutic agent preparation comprises a therapeutically effective does of an anti-seizure compound.

27. The device of claim 26, wherein the anti-seizure compound comprises furosemide.

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

swallowing a drug delivery device comprising a therapeutic agent, a release element and a tissue penetrating member;

wherein the therapeutic agent would chemically degrade or impose a deleterious effect on the patient if released within a lumen of the gastrointestinal tract;

releasing the release element in the small intestine responsive to a condition in the small intestine; and

delivering the therapeutic agent into the wall of the small intestine using the tissue penetrating member such that the deleterious effect or chemical degradation of the therapeutic agent in the lumen is inhibited.

29. The method of claim 28, wherein a dose of the therapeutic agent in the capsule does not include an amount to compensate for chemical degradation and/or lack of absorption of the therapeutic agent in the gastrointestinal tract.

30. The method of claim 28, wherein the dose of therapeutic agent is reduced in an amount between about 10 to 50 per cent compared to a standard oral dosage.

32. The method of claim 28, wherein the deleterious effect comprises one of gastric cramping, diarrhea, irritable bowel or hemorrhage within the GI tract.

33. The method of claim 28, wherein the deleterious effect comprises a toxic effect on non-target tissue.

34. The method of claim 28, wherein the therapeutic agent comprises a chemotherapeutic agent for the treatment of cancer and the deleterious effect comprises at least one of a toxic effect on non-target tissue or the development of resistance to the therapeutic agent by cancerous tissue within the patient.

35. The method of claim 28, wherein the therapeutic agent comprises an antibiotic and the deleterious effect comprises the development of bacterial resistance to the antibiotic.

36. The method of claim 28, wherein the therapeutic agent comprises an antiviral agent and the deleterious effect comprises the development of a viral resistance to the antiviral agent.

37. The method of claim 28, wherein the therapeutic agent comprises an anti-seizure compound and the deleterious effect comprises a neuromuscular, cardiovascular or gastro-intestinal effect.

38. The method of claim 37, wherein the therapeutic agent comprises furosemide.

39. The method of claim 28, wherein the therapeutic agent comprises an antibody that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in the binding affinity or specificity to a target antigen site.

40. The method of claim 28, wherein the therapeutic agent comprises a polypeptide that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in binding affinity or specificity to a target binding site.

41. The method of claim 28, wherein the therapeutic agent comprises a cytokine or interferon that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in immune stimulating ability.

42. The method of claim 28, wherein the therapeutic agent comprises growth hormone that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in growth stimulating effect.

43. The method of claim 28, wherein the therapeutic agent comprises a chemotherapeutic agent for the treatment of cancer that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in cancer treatment effect.

44. The method of claim 28, wherein the therapeutic agent comprises a glucose regulating agent that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in glucose regulating ability.

45. The method of claim 39, wherein the glucose regulating agent comprises an insulin compound.

46. The method of claim 39, wherein the glucose regulating agent comprises an incretin compound, a GLP-1 compound or exenatide.

47. The method of claim 28, wherein the condition in the small intestine is a pH above about 7.1.

48. The method of claim 28, wherein the release element degrades in response to a chemical condition in the small intestine.

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

50. The method of claim 28, wherein the release element comprises an enteric material.

51. The method of claim 28, further comprising:

delivering a first therapeutic agent and a second therapeutic agent,

wherein the first therapeutic agent is delivered using a first tissue penetrating member and the second therapeutic agent is delivered using a second tissue penetrating member.

31. The method of 28, wherein the patient has a shortened section of small intestine and a dose of the therapeutic agent in the capsule does not include a portion to compensate lack of absorption of the therapeutic agent in the small intestine.

52. A swallowable device for delivering a drug into the intestinal wall, the device comprising:

a capsule sized to pass through the intestinal tract;

a tissue penetrating member positioned in the capsule and configured to contain the drug, the tissue penetrating member having a tissue penetrating end for penetrating the intestinal wall;

a delivery member for delivering the drug from the tissue penetrating member into tissue;

an actuating mechanism coupled to at least one of the tissue penetrating member or the delivery member, the actuating mechanism configured to advance the tissue penetrating member into the intestinal wall and advance the delivery member to deliver the drug; and

a release element operatively coupled to the actuating mechanism, the release element comprising a material configured to degrade upon exposure to a selected pH in the intestine such that upon degradation, the actuating mechanism is actuated to release the tissue penetrating member and advance the advanceable member to deliver the drug into the intestinal wall.

53. The device of claim 52, wherein the capsule includes at least one guide tube and the tissue penetrating member is positioned in the at least one guide tube.

54. The device of claim 52, wherein the tissue penetrating member has a lumen for holding the drug, at least a portion of the delivery member being advanceable within the tissue penetrating member lumen.

55. The device of claim 52, wherein the selected pH is greater than about 7.4.

56. The device of claim 52, wherein at least a portion of the device comprises a biodegradable material configured to degrade within the intestinal tract so as to allow the device to pass atraumatically through the intestinal tract.

57. The device of claim 52, wherein the tissue penetrating member comprises a biodegradable material configured to degrade so as to release the tissue penetrating member from the intestinal wall.

58. The device of claim 52, wherein the tissue penetrating member comprises a needle.

59. The device of claim 52, wherein the advanceable member comprises a plunger.

60. A system for delivery of a drug, the system comprising:

the device of claim 52; and

a drug disposed in the capsule or the tissue penetrating member.

61. The system of claim 60, wherein the drug comprises a solid, a pellet or a powder.

62. The system of claim 60, wherein the tissue penetrating member comprises the drug.

63. The system of claim 60, wherein the drug comprises a chemotherapeutic agent, interferon, an antibody, an antibiotic, growth hormone, parathyroid hormone, a glucose regulating agent, an insulin compound, an incretin hormone, a GLP-1 compound or exenatide.

64. A method of drug delivery, the method comprising.

swallowing a drug delivery device comprising a capsule, a drug, an actuating mechanism, a release element and a tissue penetrating member;

releasing the release element in the small intestine responsive to a condition in the small intestine; and

actuating the actuation mechanism to deliver the drug into the wall of the small intestine using the tissue penetrating member.

65. The method of claim 64, wherein the drug comprises a chemotherapeutic agent, interferon, an antibody, an antibiotic, growth hormone, parathyroid hormone, a glucose regulating agent, an insulin compound, an incretin hormone, a GLP-1 compound or exenatide.

66. The method of claim 64, wherein the release element degrades in response to a chemical condition in the small intestine.

67. The method of claim 64, wherein the release element comprises an enteric material.

68. The method of claim 64, wherein the actuating mechanism comprises a spring, a cam, an electromechanical mechanism, a solenoid, or a piezoelectric material.