Therapeutic Agent Preparations for Delivery Into a Lumen of the Intestinal Tract Using a Swallowable Drug Delivery Device

• US 20110160129A1
• 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 8,759,284 B2
• Time in Patent Office: Days
• US Class Current: 514/5.9
• 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. Many embodiments provide a swallowable device for delivering the agents. 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 an actuator having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced 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 therapeutic agent preparation for delivery into a lumen of the intestinal tract, the lumen having a lumen wall, the preparation comprising a therapeutically effective dose of at least one therapeutic agent, wherein the preparation has a shape and material consistency to be contained in a swallowable capsule, to be delivered from the capsule into the lumen wall and to release the dose of therapeutic agent from within the lumen wall.

2. The preparation of claim 1, wherein the lumen is the small intestine and the preparation is configured to degrade within the wall of the small intestine.

3. The preparation of claim 1, wherein the preparation comprises at least one pharmaceutical excipient.

4. The preparation of claim 1, wherein the preparation is configured to have a selectable surface area to volume ratio to achieve a selectable rate of release of the therapeutic agent in the lumen wall.

5. The preparation of claim 1, wherein an amount of the therapeutic agent within the preparation to produce a desired therapeutic effect is less than an amount to produce a corresponding effect if the agent was orally delivered without enclosure in the swallowable capsule.

6. The preparation of claim 1, wherein the preparation is configured to be coupled to an actuator having a first configuration and a second configuration, the preparation being contained within the capsule in the first configuration and advanced out of the capsule and into the lumen wall in the second configuration.

7. The preparation of claim 1, wherein the preparation is configured to be delivered within a lumen of a tissue penetrating member.

8. The preparation of claim 1, wherein at least a portion of the preparation is shaped as a tissue penetrating member advanceable into the lumen wall.

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

10. The preparation of claim 13, wherein the dose of insulin is in a range from about 4 to 9 units of insulin.

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

12. The preparation of claim 17, 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).

13. The preparation of claim 17, wherein the incretin comprises exenatide and the dose is in a range from about 1 to 10 μ

g.

14. The preparation of claim 17, wherein the incretin comprises liraglutide and the dose is in a range from about 1 to 2 mg.

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

16. The preparation of claim 25, wherein the combination comprises a therapeutically effective dose of an incretin and a therapeutically effective dose of a biguanide.

17. The preparation of claim 26, wherein the incretin comprises exenatide and the biguanide comprises metformin.

18. The preparation of claim 26, wherein the dose of incretin is in a range of about 1 to 10 μ

grams and the dose of metformin is in a range of about 1 to 3 grams.

19. The preparation of claim 26, 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 preparation of claim 1, wherein the therapeutic agent comprises a therapeutically effective dose of growth hormone.

21. The preparation of claim 20, wherein the dose of growth hormone is in a range from 0.1 to 4 mg.

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

23. The preparation of claim 22, wherein the dose is in a range from about 10-40 μ

g.

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

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

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

28. 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 actuator and the therapeutic preparation of claim 1; and

actuating the actuator responsive to a condition in the small intestine to deliver the therapeutic agent into the wall of the small intestine.

29. The method of claim 28, wherein the condition is a selected pH.

30. The method of claim 29, wherein the pH is above about 7.1

31. The method of claim 28, wherein the therapeutic agent comprises a therapeutically effective dose of insulin for the treatment of diabetes or a glucose regulation disorder.

32. The method of claim 31, further comprising:

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

33. The method of claim 28, wherein the therapeutic agent comprises a therapeutically effective dose of an incretin for the treatment of diabetes or a glucose regulation disorder.

34. The method of claim 33, further comprising:

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

35. The method of claim 33, 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).

36. The method of claim 28, wherein the therapeutic agent comprises a combination of therapeutic agents for the treatment of diabetes or a glucose regulation disorder.

37. The method of claim 50, further comprising:

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

38. The method of claim 50, wherein the incretin comprises exenatide and the biguanide comprises metformin.

39. The method of claim 50, wherein the dosages of the incretin and the biguanide are matched to produce an improved level of blood glucose control for an extended period.

40. The method of claim 39, wherein the extended period is up to about a day.

41. The method of claim 39, wherein the extended period is up to about a week.

42. The method of claim 28, wherein the therapeutic agent comprises a therapeutically effective dose of growth hormone.

43. The method of claim 28, wherein the therapeutic agent comprises a therapeutically effective dose of parathyroid hormone for the treatment of osteoporosis or a thyroid disorder.

44. The method of claim 43, further comprising:

using the dose of delivered parathyroid hormone to treat the osteoporosis or a thyroid disorder without injecting parathyroid hormone into the patient.

45. The method of claim 28, wherein the therapeutic agent comprises a therapeutically effective dose of a chemotherapeutic agent for the treatment of cancer.

46. The method of claim 28, wherein the therapeutic agent comprises a therapeutically effective dose of an antibiotic.

47. The method of claim 28, wherein the therapeutic agent comprises a therapeutically effective dose of an antiviral compound.

48. The method of claim 33, wherein the incretin comprises exanatide and the dose is in a range from about 1 to 10 μ

g.

49. The method of claim 28, further comprising:

delivering a first and a second therapeutic agent.

50. The method of claim 36, wherein the combination comprises a therapeutically effective dose of an incretin and a therapeutically effective dose of a biguanide.

51. The method of claim 38, wherein the dose of exenatide is in a range of about 1 to 10 μ

g and the dose of metaformin is in a range of about 1 to 3 grams.

27. A therapeutic agent preparation for delivery into a lumen of the intestinal tract, the lumen having a lumen wall, the preparation comprising a therapeutically effective dose of at least one therapeutic agent;

wherein the preparation is configured to be contained in a swallowable capsule and operably coupled to an actuator having a first configuration and a second configuration, the preparation being contained within the capsule in the first configuration and advanced out of the capsule and into the lumen wall in the second configuration so as to deliver the therapeutic agent into the lumen wall.