Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device

• US 9,629,799 B2
• Filed: 06/29/2012
• Issued: 04/25/2017
• Est. Priority Date: 12/23/2010
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc. (Sanofi )
• Original Assignee: RaNA Therapeutics Inc. (Sanofi )
• Inventors: Imran, Mir
• Primary Examiner(s): Landsman, Robert
• Assistant Examiner(s): Hissong, Bruce D
• Application Number:
  US13/538,903
• Publication Number:
  US 20130177527A1
• Time in Patent Office: 1,761 Days
• 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 38/21 Interferons [IFN]
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• 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 2210/106 Small intestine
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• 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 5/00 Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests vaccination appliances for veterinary use A61D1/025 ; tube connectors, tube couplings, valves or branch units specially adapted for medical use A61M39/00; containers specially adapted for medical or pharmaceutical purposes A61J1/00; combinations of vial and syringe for mixing or transferring their contents A61J1/20; holders for containers for collecting, storing or administering blood or medical fluids A61J1/16

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 to release the drug into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means 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 preparation comprising interferon, the preparation shaped as a solid tissue penetrating member having a shaft and pointed tip structure configured to penetrate and be inserted into an intestinal wall after oral ingestion, wherein upon insertion, the preparation releases interferon into the blood stream from the intestinal wall to achieve a C_max in a shorter time period than a time period to achieve a C_max for an extravascularly injected dose of interferon.

2. The preparation of claim 1, wherein a t_max for the interferon released from preparation is less than about 80% of a t_max for the extravascularly injected dose of interferon.

3. The preparation of claim 1, wherein a t_max for the interferon released from the preparation is less than about 50% of a t_max for the extravascularly injected dose of interferon.

4. The preparation of claim 1, wherein a t_max for the interferon released from the preparation is less than about 30% of a t_max for the extravascularly injected dose of interferon.

5. The preparation of claim 1, wherein a t_max for the interferon released from the preparation is less than about 10% of a t_max for the extravascularly injected dose of interferon.

6. The preparation of claim 1, wherein the preparation is adapted for insertion into the wall of the small intestine.

7. The preparation of claim 1, wherein the extravascular injection is a subcutaneous injection or an intramuscular injection.

8. The preparation of claim 1, whereih at least a portion of the preparation is in solid form.

9. The preparation of claim 1, wherein the preparation is adapted to be orally delivered in a swallowable capsule.

10. The preparation of claim 9, wherein the preparation is adapted to be operably coupled to delivery means 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 intestinal wall in the second configuration.

11. The preparation of claim 10, wherein the delivery means comprises at least one expandable balloon having an expanded and a non-expanded state and the first configuration is the non-expanded state and the second configuration is the expanded state.

12. The preparation of claim 1, wherein the preparation comprises a biodegradable material which degrades within the intestinal wall to release interferon into the blood stream.

13. The preparation of claim 12, wherein the biodegradable material comprises poly lactic-co-glycolic acid (PGLA) a sugar or maltose.

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

15. The preparation of claim 14, wherein the at least one pharmaceutical excipient comprises at least one of a binder, a preservative or a disintegrant.

16. The preparation of claim 15, wherein the binder comprises polyethylene glycol (PEG).

17. The preparation of claim 1, wherein the tissue penetrating member comprises a biodegradable material which degrades within the intestinal wall to release interferon into the blood stream.

18. The preparation of claim 17, wherein the biodegradable material comprises maltose or PGLA.

19. The preparation of claim 1, wherein a weight percent of interferon in the tissue penetrating member comprises between about 0.1 to 3%.

20. The preparation of claim 1, wherein a weight per cent of interferon in the tissue penetrating member comprises between about 0.05 to 0.2%.

21. The preparation of claim 1, wherein the tissue penetrating member includes a retaining feature for retaining the tissue penetrating member within the intestinal wall after insertion.

22. The preparation of claim 21, wherein the retaining feature comprises at least one of a barb or an inverse taper shape of the tissue penetrating member.

23. The preparation of claim 1, wherein the interferon is contained in the tissue penetrating member in a shaped section.

24. The preparation of claim 23, wherein the shaped section has a cylinder or pellet shape.

25. The preparation of claim 1, wherein the tissue penetrating member has sufficient stiffness to be advanced completely into the intestinal wall by the application of a force to the tissue penetrating member.

26. The preparation of claim 1, wherein the C_max achieved by delivering the preparation by insertion into the intestinal wall is substantially greater than a C_max achieved when the preparation is delivered orally without insertion into the intestinal wall.

27. The preparation of claim 26, wherein the C_max achieved by delivering the preparation by insertion into the intestinal wall is at least about 100 times greater than the C_max achieved when the preparation is delivered orally without insertion into the intestinal wall.

28. The preparation of claim 1, wherein the preparation is configured to produce a long-term release of interferon.

29. The preparation of claim 28, wherein the preparation is configured produce a long-term release of interferon to produce a selectable t_1/2.

30. The preparation of claim 29, wherein the t_1/2 is about 12 hours.

31. The preparation of claim 1, wherein a dose of interferon in the preparation is in a range from about 0.03 to 25 mg of interferon.

32. The preparation of claim 1, wherein a dose of interferon in the preparation is in a range from about 6 to 20 μ

g of interferon.

33. The composition of claim 1, wherein the interferon is interferon alpha-2a.

34. The composition of claim 1, wherein the interferon is interferon beta-1a.

35. The composition of claim 1, wherein the interferon is interferon beta-1b.

36. The composition of claim 1, wherein the interferon is PEGylated interferon alpha-2a.

37. The composition of claim 1, wherein the interferon is PEGylated interferon alpha-2b.

38. A therapeutic preparation comprising interferon, the preparation shaped as a solid tissue penetrating having a shaft and pointed tip structure configured to penetrate and be inserted into an intestinal wall after oral ingestion, wherein upon insertion, the preparation releases interferon into the bloodstream from the intestinal wall to achieve a t_1/2 that is greater than a t_1/2, for orally ingested interferon that is not inserted into the intestinal wall.

39. The preparation of claim 38, wherein the t_1/2 of the interferon inserted into the intestinal wall is at least about 10 times greater than the t_1/2 for the orally ingested interferon that is not inserted into the intestinal wall.