Method of delivering gonadotropin releasing hormone or an analogue thereof into a lumen of the intestinal tract using a swallowable drug delivery device

• US 10,322,167 B2
• Filed: 10/11/2017
• Issued: 06/18/2019
• Est. Priority Date: 12/23/2010
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc.
• Original Assignee: RaNA Therapeutics Inc.
• Inventors: Imran, Mir
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US15/730,590
• Publication Number:
  US 20180193420A1
• Time in Patent Office: 615 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 gonadotropin releasing hormone (GnRH) or GnRH analogue to a patient in need thereof, the method comprising:

providing an oral solid GnRH or GnRH analogue (OSGGA) dosage shaped as a tissue penetrating member having a pointed tip, the tissue penetrating member configured to be carried by a swallowable capsule and penetrate and be inserted into an intestinal wall, wherein upon ingestion the capsule advances to the small intestine of the patient; and

delivering the solid GnRH or GnRH analogue dosage into the wall of the small intestine by an application of mechanical force upon a surface of the tissue penetrating member from an actuator operably coupled to the tissue penetrating member wherein upon insertion into the intestinal wall, the tissue penetrating member remains to release GnRH or GnRH analogue into a blood stream from the intestinal wall by degradation of the of the tissue penetrating member.

2. The method of claim 1, wherein actuator comprises an expandable member or an expandable balloon.

3. The method of claim 1, wherein the 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.

4. The method of claim 3, wherein a tmax for the GnRH or GnRH analogue released from the OSGGA dosage is less than about 50% of a tmax for the extravascularly injected dose of GnRH or GnRH analogue.

5. The method of claim 3, wherein a tmax for the GnRH or GnRH analogue released from the OSGGA dosage is less than about 30% of a tmax for the extravascularly injected dose of GnRH or GnRH analogue.

6. The method of claim 3, wherein a tmax for the GnRH or GnRH analogue released from the preparation 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 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.

8. The method of claim 7, wherein the biodegradable material comprises PGLA, a sugar or maltose.

9. The method of claim 7, wherein the solid dosage GnRH or GnRH analogue comprises at least one pharmaceutical excipient.

10. The method of claim 9, wherein the at least one pharmaceutical excipient comprises at least one of a binder, a preservative or a disintegrant.

11. The method of claim 10, wherein the binder comprises PEG.

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

13. The method of claim 1, further comprising retaining the solid dosage within the intestinal wall after insertion.

14. The method of claim 1, wherein the solid dosage GnRH or GnRH analogue produces a long-term release of GnRH or GnRH analogue.

15. The method of claim 14, wherein the solid dosage GnRH or GnRH analogue produces a long-term release of GnRH or GnRH analogue to produce a selectable t½

.

16. The method of claim 15, wherein the t½

is about 12 hours.

17. The method of claim 1, wherein a dose of GnRH or GnRH analogue in the OSGGA dosage is in a range from about 0.3 to 1.5 mg.

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

19. The method of claim 18, wherein the dose of leuprorelin in the OSGGA dosage is in a range from about 0.1 to 2 mg.

20. The method of claim 19, wherein the dose of leuprorelin in the OSGGA dosage is in a range from about 0.2 to 1.0 mg.