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

• US 8,764,733 B2
• Filed: 06/29/2012
• Issued: 07/01/2014
• 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): Acevedo, James H Alstrum
• Assistant Examiner(s): REYNOLDS, FRED H
• Application Number:
  US13/538,852
• Publication Number:
  US 20130164372A1
• Time in Patent Office: 732 Days
• Field of Search: None
• US Class Current: 604/890.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; 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 9/0097 Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• 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 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
• CPC Class Codes: C07K 7/16 Oxytocins; Vasopressins; Related peptides

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 vasopressin or a peptide vasopressin 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 vasopressin or a peptide vasopressin analog into the blood stream from the intestinal wall, the tissue penetrating member having a proximal and distal portion, the proximal portion configured to be detachably coupled to an advancement means disposed in a swallowable capsule.

2. The preparation of claim 1, wherein the preparation is adapted for insertion into the wall of the small intestine.

3. The preparation of claim 1, wherein the advancement means comprises a piston or a plunger.

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

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

6. The preparation of claim 5, 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.

7. The preparation of claim 6, 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.

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

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

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

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

12. The preparation of claim 11, wherein the binder comprises PEG.

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

14. The preparation of claim 13, wherein the biodegradable material comprises maltose or PGLA.

15. The preparation of claim 1, wherein a eight percent of vasopressin or peptide vasopressin analogue in the tissue penetrating member comprises between about 0.1 to 1%.

16. 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.

17. The preparation of claim 16, wherein the retaining feature comprises at least one of a barb or an inverse taper shape of the tissue penetrating member.

18. The preparation of claim 1, wherein tissue penetrating member includes a shaped section in which the vasopressin or peptide vasopressin analogue is contained.

19. The preparation of claim 18, wherein the shaped section has a cylinder or pellet shape.

20. 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.

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

22. The preparation of claim 21, wherein the preparation is configured produce a long-term release of vasopressin or peptide vasopressin analogue to produce a selectable t_1/2.

23. The preparation of claim 22, wherein the t_1/2 is about 10 hours.