Method for delivering exenatide to a patient in need thereof

• US 9,511,121 B2
• Filed: 02/12/2015
• Issued: 12/06/2016
• 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): Chandra, Gyan
• Application Number:
  US14/620,827
• Publication Number:
  US 20150238571A1
• Time in Patent Office: 663 Days
• 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 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 2037/0023 Drug applicators 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 25/10185 Valves
• 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
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

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 Exenatide to a patient in need thereof, the method comprising:

providing a solid Exenatide dosage shaped as a tissue penetrating member that is enclosed in a swallowable capsule comprising materials which protect the solid Exantide dosage from degradation within the intestinal tract;

ingesting the solid Exenatide dosage, wherein the dosage is not degraded in the intestinal tract prior to insertion into an intestinal wall;

penetrating the solid Exenatide dosage into the intestinal wall after oral ingestion by the application of mechanical force on the tissue penetrating member wherein the tissue penetrating member is retained within the intestinal wall; and

,

degrading the solid Exenatide dosage within intestinal wall to release the Exenatide into the intestinal wall and then into the blood stream.

2. The method of claim 1, wherein the Exenatide released from the solid dosage reaches a C_max in a shorter time period than a time period to achieve a C_max for an extravascularly injected dose of Exenatide.

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

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

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

6. The method of claim 2, wherein a t_max for the Exenatide released from the solid dosage is less than about 10% of a t_max for the extravascularly injected dose of Exenatide.

7. The method of claim 1, wherein the solid dosage Exenatide is inserted into a wall of the small intestine.

8. The method of claim 1, wherein penetrating comprises operably coupling the solid dosage Exenatide to a delivery means having a first configuration wherein the solid dosage Exenatide is within the capsule and a second configuration wherein the solid-dosage Exenatide is advanced out of the capsule and into the intestinal wall.

9. The method of claim 8, wherein penetrating comprises expanding at least one expandable balloon from the first to the second configuration.

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

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

12. The method of claim 1, wherein a weight percent of Exenatide in the tissue penetrating member Exenatide comprises between about 0.1 to 11%.

13. The method of claim 1, wherein the tissue penetrating member is retained in the intestinal wall by of means of at least one of a barb or an inverse tapered shape of the tissue penetrating member.

14. The method of claim 1, wherein the tissue penetrating member is advanced completely into the intestinal wall.

15. The method of claim 1, wherein the solid dosage Exenatide produces a release of Exenatide over 12 hours.

16. The method of claim 1, wherein a dose of Exenatide in the solid dosage is in a range of about 1 to 10 mcg.

17. The method of claim 1, wherein the solid dosage Exenatide further comprises a therapeutically effective dose of another incretin for the treatment of diabetes or a glucose regulation disorder.

18. The method of claim 17, wherein the incretin comprises a glucagon-like peptide-1 (GLP-1), a GLP-1 analogue, liraglutide, albiglutide, taspoglutide or a gastric inhibitory polypeptide (GIP).

19. The method of claim 17, wherein the incretin comprises liraglutide and the dose is in a range from about 0.1 to 1 mg.

20. The method of claim 1, wherein the solid dosage Exenatide further comprises a therapeutically effective dose of insulin for the treatment of diabetes or a glucose regulation disorder.

21. The method of claim 20, wherein the dose of insulin in the preparation is in a range from about 1 to 50 units of insulin.

22. The method of claim 21, wherein the dose of insulin is in a range from about 4 to 9 units of insulin.

23. The method of claim 1, further comprising degrading the capsule material in response to a selected pH in the intestinal tract so as to cause the solid dosage Exenatide to be inserted into the intestinal wall.

24. The method of claim 23, wherein the pH is in a range from about 7 to 8.

25. The method of claim 23, wherein the capsule materials comprise at least one of methacrylate or ethyl acrylate.