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

• US 9,861,683 B2
• Filed: 06/29/2012
• Issued: 01/09/2018
• 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): Tran, Susan
• Application Number:
  US13/538,793
• Publication Number:
  US 20130171245A1
• Time in Patent Office: 2,020 Days
• Field of Search: None
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• 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: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• 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

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 growth hormone, the preparation shaped as a solid tissue penetrating member having a shaft and tissue penetrating end shaped and configured to penetrate and be inserted into an intestinal wall after oral ingestion by the application of force onto a surface of the tissue penetrating member, wherein upon insertion, the preparation releases growth hormone 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 growth hormone.

2. The preparation of claim 1, wherein a t_max for the growth hormone released from the therapeutic preparation is about 80% of a t_max for the extravascularly injected dose of growth hormone.

3. The preparation of claim 1, wherein a t_max for the growth hormone released from the therapeutic preparation is about 50% of a t_max for the extravascularly injected dose of growth hormone.

4. The preparation of claim 1, wherein a t_max for the growth hormone released from the therapeutic preparation is about 30% of a t_max for the extravascularly injected dose of growth hormone.

5. The preparation of claim 1, wherein a t_max for the growth hormone released from the therapeutic preparation is about 10% of a t_max for the extravascularly injected dose of growth hormone.

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, wherein 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 a 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 growth hormone into the blood stream.

13. The preparation of claim 12, wherein the biodegradable material comprises 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 PEG.

17. The preparation of claim 1, wherein the force is a mechanical force.

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

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

20. The preparation of claim 1, wherein a weight percent of growth hormone in the tissue penetrating member comprises between about 2 to 10%.

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 growth hormone 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 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 10 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 growth hormone.

29. The preparation of claim 28, wherein the preparation is configured produce a long-term release of growth hormone 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 growth hormone in the preparation is in a range from about 0.1 to 4 mg.

32. The preparation of claim 31, wherein the dose of growth hormone is in a range from about 0.2 to 1 mg.

33. The preparation of claim 1, wherein the growth hormone is somatropin.

34. A therapeutic preparation comprising growth hormone, the preparation shaped as a solid tissue penetrating member having a shaft and tissue penetrating end shaped and configured to penetrate and be inserted into an intestinal wall after oral ingestion by the application of force onto a surface of the tissue penetrating member, wherein upon insertion, the preparation releases growth hormone into the bloodstream from the intestinal wall to achieve a t_1/2 that is greater than a t_1/2 for orally ingested growth hormone that is not inserted into the intestinal wall.

35. The preparation of claim 34, wherein the t_1/2 of the growth hormone inserted into the intestinal wall is at least about 10 times greater than the t_1/2 for the orally ingested growth hormone that is not inserted into the intestinal wall.