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

Patent metadata

Field	Value
Publication number	US-9283179-B2
Application number	US-201213538841-A
Country	US
Kind code	B2
Filing date	Jun 29, 2012
Priority date	Dec 23, 2010
Publication date	Mar 15, 2016
Grant date	Mar 15, 2016

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.

First claim

What is claimed is:

1. A therapeutic preparation comprising GnRH or GnRH analogue, the preparation shaped as a solid tissue penetrating member having a dart-like structure, the preparation configured to be contained in an oval shaped swallowable capsule to penetrate and be inserted into an intestinal wall after oral ingestion, wherein upon insertion, the preparation releases GnRH or GnRH analogue 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 GnRH or GnRH analogue.

2. The preparation of claim 1 , wherein a t max for the GnRH or GnRH analogue released from the therapeutic preparation is about 80% of a t max for the extravascularly injected dose of GnRH or GnRH analogue.

3. The preparation of claim 1 , wherein a t max for the GnRH or GnRH analogue released from the therapeutic preparation is about 50% of a t max for the extravascularly injected dose of GnRH or GnRH analogue.

4. The preparation of claim 1 , wherein a t max for the GnRH or GnRH analogue released from the therapeutic preparation is about 30% of a t max for the extravascularly injected dose of GnRH or GnRH analogue.

5. The preparation of claim 1 , wherein a t max for the GnRH or GnRH analogue released from the therapeutic preparation is about 10% of a t max for the extravascularly injected dose of GnRH or GnRH analogue.

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 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.

9. The preparation of claim 8 , 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.

10. The preparation of claim 1 , wherein the preparation comprises a biodegradable material which degrades within the intestinal wall to release GnRH or GnRH analogue into the blood stream.

11. The preparation of claim 1 , wherein the biodegradable material comprises PGLA, a sugar or maltose.

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

13. The preparation of claim 12 , wherein the at least one pharmaceutical excipient comprises at least one of a binder, a preservative or a disintegrant.

14. The preparation of claim 13 , wherein the binder comprises PEG.

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

16. The preparation of claim 15 , wherein the biodegradable material comprises maltose or PGLA.

17. The preparation of claim 1 , a weight percent of GnRH or GnRH analogue in the tissue penetrating member comprises between about 2 to 15%.

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

19. The preparation of claim 18 , wherein the retaining feature comprises at least one of a barb or an inverse taper shape of the tissue penetrating member.

20. The preparation of claim 1 , the release GnRH or GnRH analogue is contained in the tissue penetrating member in a shaped section.

21. The preparation of claim 20 , wherein the shaped section has a cylinder or pellet shape.

22. 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.

23. 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.

24. The preparation of claim 23 , 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.

25. The preparation of claim 1 , wherein the preparation is configured to produce a long-term release of GnRH or GnRH analogue.

26. The preparation of claim 25 , wherein the preparation is configured produce a long-term release of GnRH or GnRH analogue to produce a selectable t 1/2 .

27. The preparation of claim 26 , wherein the t 1/2 is about 12 hours.

28. The preparation of claim 1 , wherein a dose of GnRH or GnRH analogue in the preparation is in a range from about 0.3 to 1.5 mg.

29. The preparation of claim 1 , wherein the GnRH analogue is leuprorelin.

30. The preparation of claim 29 , wherein a dose of leuprorelin in the preparation is in a range from about 0.1 to 2 mg.

Assignees

• Imran Mir
• Rani Therapeutics Llc

Inventors

• Imran Mir

Classifications

• A61K38/09

  Luteinising hormone-releasing hormone [LHRH] {, i.e. Gonadotropin-releasing hormone [GnRH]}; Related peptides · CPC title

• A61M2037/0023

  Drug applicators using microneedles · CPC title

• A61K9/4891

  Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004) · CPC title

• A61M5/00

  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}) · CPC title

• A61M37/0015

  by using microneedles · CPC title