Method for delivering gonadotropin releasing hormone into a lumen of the intestinal tract

• US 9,808,510 B2
• Filed: 02/19/2016
• Issued: 11/07/2017
• Est. Priority Date: 06/29/2011
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc. (Sanofi )
• Original Assignee: RaNA Therapeutics Inc. (Sanofi )
• Inventors: Imran, Mir
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US15/048,085
• Publication Number:
  US 20160166650A1
• Time in Patent Office: 627 Days
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• 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 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0065 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 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2210/1042 Alimentary tract A61M2210/0618 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
• CPC Class Codes: A61M 37/0015 by using microneedles
• 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 method for delivering a gonadotropin releasing hormone (GnRH) or a GnRH analogue dosage to a patient in need thereof, the method comprising:

orally delivery in a capsule a solid GnRH or GnRH analogue dosage shaped as a tissue penetrating member; and

penetrating the tissue penetrating member into an intestinal wall from the capsule after oral ingestion of the capsule, wherein the GnRH or GnRH analogue is released into the blood stream from the solid dosage GnRH or GnRH analogue in the intestinal wall.

2. The method of claim 1, wherein the GnRH or GnRH analogue released into the blood stream from the solid dosage GnRH or GnRH analogue reaches a Cmax in a shorter time period than a time period to achieve a Cmax for an extravascularly injected dose of GnRH or GnRH analogue.

3. The method of claim 2, wherein a tmax for the GnRH or GnRH analogue released from the solid dosage GnRH or GnRH analogue is less than about 80% of a tmax for the extravascularly injected dose of GnRH or GnRH analogue.

4. The method of claim 2, wherein a tmax for the GnRH or GnRH analogue released from the solid dosage GnRH or GnRH analogue is less than about 50% of a tmax for the extravascularly injected dose of GnRH or GnRH analogue.

5. The method of claim 2, wherein a tmax for the GnRH or GnRH analogue released from the solid dosage GnRH or GnRH analogue is less than about 30% of a tmax for the extravascularly injected dose of GnRH or GnRH analogue.

6. The method of claim 2, wherein a tmax for the GnRH or GnRH analogue released from the solid dosage GnRH or GnRH analogue is less than about 10% of a tmax for the extravascularly injected dose of GnRH or GnRH analogue.

7. The method of claim 1, wherein the tissue penetrating member is inserted into a wall of the small intestine.

8. The method of claim 1, wherein penetrating the tissue penetrating member into the intestinal wall comprises operably coupling the tissue penetrating member to a delivery means having a first configuration wherein the tissue penetrating member is within the capsule, and a second configuration wherein the tissue penetrating member is advanced out of the capsule and into the intestinal wall.

9. The method of claim 8, wherein penetrating the tissue penetrating member into the intestinal wall comprises expanding at least one expandable balloon from the first to the second configuration.

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

11. The method of claim 10, wherein the biodegradable material comprises PGLA, a sugar or maltose.

12. The method of claim 10, wherein the solid dosage GnRH or GnRH analogue comprises at least one pharmaceutical excipient.

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

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

15. The method of claim 1, wherein a weight per cent of GnRH or GnRH analogue in the solid dosage GnRH or GnRH analogue comprises between about 2 to 15%.

16. The method of claim 1, wherein a dose of GnRH or GnRH analogue in the solid dosage GnRH or GnRH analogue is in a range from about 0.1 to 2.0.

17. The method of claim 16, wherein the dose of GnRH or GnRH analogue in the solid dosage GnRH or GnRH analogue is about 0.2 to 1.0 mg.

18. The method of claim 1, further comprising retaining the solid dosage GnRH or GnRH analogue within the intestinal wall after insertion.

19. The method of claim 18, wherein retaining comprises anchoring at least one of a barb or an inverse taper shape of the solid dosage GnRH or GnRH analogue in the intestinal tissue.

20. The method of claim 1, wherein penetrating the tissue penetrating member comprises applying a force to the tissue penetrating member, wherein the tissue penetrating member has sufficient stiffness to be advanced completely into the intestinal wall by such application of force.

21. The method of claim 1, wherein the solid dosage GnRH or GnRH analogue produces a long-term release of GnRH or GnRH analogue to produce a selectable t_1/2.

22. The method of claim 21, wherein the t_1/2 is about 12 hours.

23. The method of claim 1, wherein the Cmax achieved by delivering the solid dosage GnRH or GnRH analogue into the intestinal wall is at least about 10 times greater than the Cmax achieved when the preparation is delivered orally without insertion into the intestinal wall.

24. The method of claim 1, wherein the GnRH analogue is leuprorelin.

25. The method of claim 24, wherein a dose of leuprorelin in the preparation is in a range from about 0.1to 2 mg.

26. The method of claim 25, wherein, a dose of leuprorelin in the preparation is in a range from about 0.2to 1.0 mg.