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

• US 9,402,806 B2
• Filed: 06/29/2012
• Issued: 08/02/2016
• 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): Tran, Susan
• Application Number:
  US13/538,875
• Publication Number:
  US 20130195970A1
• Time in Patent Office: 1,495 Days
• Field of Search: None
• US Class Current: 1/1
• 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 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• 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: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• 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 25/1011 Multiple balloon catheters
• CPC Class Codes: A61M 31/00 Devices for introducing or retaining media, e.g. remedies, in cavities of the body A61M25/00 takes precedence ; introducing or retaining ophthalmic products into the ocular cavities A61F9/0008
• 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 therapeutic preparation comprising PTH or PTH analogue, the preparation shaped as a solid tissue penetrating member shaped and configured to penetrate and be inserted into an intestinal wall after oral ingestion, wherein upon insertion, the preparation releases PTH or PTH analogue into the blood stream from the intestinal wall by degradation of the tissue penetrating member 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 PTH or PTH analogue, 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.

2. The preparation of claim 1, wherein all of the preparation is in solid form.

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

4. The preparation of claim 3, 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.

5. The preparation of claim 4, 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.

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

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

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

9. The preparation of claim 8, wherein the at least one pharmaceutical excipient comprises at least one of a binder, a preservative or a disintegrant.

10. The preparation of claim 9, wherein the binder comprises PEG.

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

12. The preparation of claim 11, wherein the biodegradable material comprises maltose or PGLA.

13. The preparation of claim 1 wherein a weight percent of PTH or PTH analogue in the tissue penetrating member comprises between about 1 to 2%.

14. 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.

15. The preparation of claim 14, wherein the retaining feature comprises at least one of a barb or an inverse taper shape of the tissue penetrating member.

16. The preparation of claim 1, wherein the PTH or PTH analogue is contained in the tissue penetrating member in a shaped section.

17. The preparation of claim 16, wherein the shaped section has a cylinder or pellet shape.

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

19. The preparation of claim 18, wherein the long-term release of PTH or PTH analogue is about 12 hours.

20. The preparation of claim 1, wherein a dose of PTH or PTH analogue in the preparation is in a range from about 10 to 30 μ

g.

21. The preparation of claim 1, wherein the PTH analogue is teriparatide.

22. The preparation of claim 21, wherein a dose of teriparatide in the preparation is in a range from about 0.1 to 10 μ

g.

23. A therapeutic preparation comprising PTH or PTH analogue, the preparation shaped as a solid tissue penetrating member shaped and configured to penetrate and be inserted into an intestinal wall after oral ingestion, wherein upon insertion, the preparation releases PTH or PTH analogue into the blood stream from the intestinal wall by degradation of the tissue penetrating member to achieve a t_1/2 that is greater than a t_1/2 for orally ingested PTH or PTH analogue that is not inserted into the intestinal wall, 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.