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

• US 9,205,127 B2
• Filed: 05/20/2014
• Issued: 12/08/2015
• Est. Priority Date: 12/23/2010
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc.
• Original Assignee: RaNA Therapeutics Inc.
• Inventors: Imran, Mir A.
• Primary Examiner(s): Audet, Maury
• Assistant Examiner(s): REYNOLDS, FRED H
• Application Number:
  US14/282,448
• Publication Number:
  US 20140256631A1
• Time in Patent Office: 567 Days
• Field of Search: None
• US Class Current: 1/1
• 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 method for delivering vasopressin or a peptide vasopressin analogue to a patient, said method comprising:

providing a solid vasopressin or a peptide vasopressin analogue (VOPVA) dosage shaped as a tissue penetrating member that is detachably coupled to an advancement means;

penetrating the;

penetrating the solid dosage VOPVA into an intestinal wall after oral ingestion, wherein the vasopressin or peptide vasopressin analogue is released into the blood stream from the solid dosage VOPVA in the intestinal wall.

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

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

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

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

6. The method of claim 2, wherein a tmax for the vasopressin or peptide vasopressin analogue released from the solid dosage VOPVA is less than about 10% of a tmax for the extravascularly injected dose of vasopressin or peptide vasopressin 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 the tissue penetrating member is orally delivered in a swallowable capsule.

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

10. The method of claim 9, wherein penetrating the solid dosage VOPVA into the intestinal wall comprises expanding at least one expandable balloon from the first to the second configuration.

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

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

13. The method of claim 1, wherein the solid dosage VOPVA comprises at least one pharmaceutical excipient.

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

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

16. The method of claim 1, wherein a weight per cent of vasopressin or peptide vasopressin analogue in the solid dosage VOPVA comprises between about 0.1 to 1%.

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

18. The method of claim 17, wherein retaining comprises anchoring at least one of a barb or an inverse taper shape of the solid dosage VOPVA in the intestinal tissue.

19. The method of claim 1, wherein penetrating the solid dosage VOPVA comprises applying a force to the solid dosage VOPVA, wherein the solid dosage VOPVA has sufficient stiffness to be advanced completely into the intestinal wall by such application of force.

20. The method of claim 1, wherein the solid dosage VOPVA produces a long-term release of vasopressin or peptide vasopressin analogue.