Methods for delivering insulin preparations into a lumen of the intestinal tract using a swallowable drug delivery device

• US 9,956,178 B2
• Filed: 08/30/2016
• Issued: 05/01/2018
• 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:
  US15/252,193
• Publication Number:
  US 20170049708A1
• Time in Patent Office: 609 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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 25/04 in the body, e.g. expansible A61M25/10, A61M16/0488 take precedence
• 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 insulin to a patient, said method comprising:

providing an oral solid insulin dosage shaped as a tissue penetrating member having a pointed tip, the tissue penetrating member configured to be carried by a swallowable capsule and penetrate and be inserted into an intestinal wall, wherein upon ingestion the capsule advances to the small intestine of the patient; and

delivering the solid insulin dosage into the wall of the small intestine by an application of mechanical force upon a surface of the tissue penetrating member from an actuator operably coupled to the tissue penetrating member wherein upon insertion into the intestinal wall, the tissue penetrating member remains to release insulin into the blood stream from the intestinal wall by degradation of the of the tissue penetrating member.

2. A method as in claim 1, wherein actuator comprises an expandable member or an expandable balloon.

3. A method as in claim 1, wherein the insulin reaches a Cmax in a shorter time period than a time period to achieve a Cmax for an extravascularly injected dose of insulin.

4. A method as in claim 3, wherein a tmax for the insulin released from the therapeutic preparation is less than about 50% of a tmax for the extravascularly injected dose of insulin.

5. A method as in claim 3, wherein a tmax for the insulin released from the therapeutic preparation is less than about 30% of a tmax for the extravascularly injected dose of insulin.

6. A method as in claim 3, wherein a tmax for the insulin released from the preparation is less than about 10% of a tmax for the extravascularly injected dose of insulin.

7. A method as in claim 1, wherein the solid dosage insulin comprises a biodegradable material which degrades within the intestinal wall to release insulin into the blood stream.

8. A method as in claim 7, wherein the biodegradable material comprises PGLA, a sugar or maltose.

9. A method as in claim 7, wherein the solid dosage insulin comprises at least one pharmaceutical excipient.

10. A method as in claim 9, wherein the at least one pharmaceutical excipient comprises at least one of a binder, a preservative or a disintegrant.

11. A method as in claim 10, wherein the binder comprises PEG.

12. A method as in claim 1, wherein a weight per cent of insulin in the solid dosage insulin comprises between about 2 to 15%.

13. A method as in claim 1, further comprising retaining the solid dosage within the intestinal wall after insertion.

14. A method as in claim 1, wherein the solid dosage insulin produces a long-term release of insulin.

15. A method as in claim 14, wherein the solid dosage insulin produces a long-term release of insulin to produce a selectable t½

.

16. A method as in claim 15, wherein the t½

is about 12 hours.

17. A method as in claim 1, wherein the solid dosage insulin carries about 1 to 50 units of insulin.

18. A method as in claim 17, wherein the solid dosage insulin carries about 4 to 9 units of insulin.

19. A method as in claim 1, wherein the solid dosage insulin further comprises a therapeutically effective dose of an incretin for the treatment of diabetes or a glucose regulation disorder.

20. A method as in claim 19, wherein the incretin comprises a glucagon-like peptide-1 (GLP-1), a GLP-1 analogue, exenatide, liraglutide, albiglutide, taspoglutide or a gastric inhibitory polypeptide (GIP).

21. A method as in claim 20, wherein the incretin comprises exenatide and the dose is in a range from about 1 to 10 μ

g.

22. A method as in claim 20, wherein the incretin comprises liraglutide and the dose is in a range from about 0.1 to 1 mg.