Method for delivery of somatostatin into a lumen of the intestinal tract

• US 9,814,763 B2
• Filed: 01/28/2016
• Issued: 11/14/2017
• Est. Priority Date: 12/23/2010
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc.
• Original Assignee: InCube Labs LLC. (In-Cube, Inc.)
• Inventors: Imran, Mir
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US15/009,601
• Publication Number:
  US 20160144000A1
• Time in Patent Office: 656 Days
• 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 38/31 Somatostatins
• 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: 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 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 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 somatostatin compound to a patient, said method comprising:

providing a solid somatostatin or somatostatin analogue dosage shaped as a tissue penetrating member;

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

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

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

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

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

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

9. The method of claim 8, 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.

10. The method of claim 9, wherein penetrating the tissue penetrating member 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 somatostatin or somatostatin analogue comprises a biodegradable material which degrades within the intestinal wall to release somatostatin or somatostatin 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 11, wherein the solid dosage somatostatin or somatostatin analogue 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 somatostatin or somatostatin analogue in the solid dosage somatostatin or somatostatin analogue is the range between about 0.3 to 8%.

17. The method of claim 1, wherein a dose of somatostatin or somatostatin analogue in the solid dosage somatostatin is in a range from about 50 to 600 mg.

18. The method of claim 1, wherein the somatostatin analogue is octreotide.

19. The method of claim 18, wherein a dose of octreotide in the preparation is in a range from about 10 to100 μ

g.

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

21. The method of claim 20, wherein retaining comprises anchoring at least one of a barb or an inverse taper shape of the solid dosage somatostatin or somatostatin analogue in the intestinal tissue.

22. 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.

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

24. The method of claim 1, wherein the Cmax achieved by delivering the solid dosage somatostatin or somatostatin 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.

25. The method of claim 24, wherein the condition is a pH.

26. The method of claim 24, wherein the somatostatin or somatostatin analogue dosage is in solid form.

27. A method for delivering a somatostatin or somatostatin analogue to a patient, said method comprising:

providing a somatostatin or somatostatin analogue dosage within a swallowable capsule having at least one tissue penetrating member having a lumen;

delivering the somatostatin or somatostatin analogue dosage into a wall of the small intestine from the capsule via the tissue penetrating member lumen and an application of force on the somatostatin or somatostatin analogue dosage, the delivery of the somatostatin or somatostatin analogue being effectuated responsive to a condition unique to the small intestine, and wherein the somatostatin or somatostatin analogue is released into the blood stream from the dosage of somatostatin or somatostatin analogue in the wall of the small intestine.