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

• US 10,350,163 B2
• Filed: 03/22/2017
• Issued: 07/16/2019
• 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): Weiler, Karen S.
• Assistant Examiner(s): Hissong, Bruce D.
• Application Number:
  US15/466,434
• Publication Number:
  US 20170189659A1
• Time in Patent Office: 846 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 38/21 Interferons [IFN]
• 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 2210/106 Small intestine
• 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 interferon to a patient, the method comprising:

providing a solid interferon dosage as a tissue penetrating member shaped and configured to penetrate and be inserted into the intestinal wall, the tissue penetrating member enclosed in a swallowable capsule comprising materials which protect the solid interferon dosage from degradation within the intestinal tract;

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

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

,

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

2. The method of claim 1, wherein the interferon 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 interferon.

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

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

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

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

7. The method of claim 6, wherein penetrating comprises expanding at least one expandable balloon from the first to the second configuration.

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

9. The method of claim 8, wherein the at least one pharmaceutical excipient comprises at least one of a binder, a preservative or a disintegrant.

10. The method of claim 1, wherein a weight percent of interferon in the tissue penetrating member comprises between about 0.1 to 3%.

11. The method of claim 1, wherein a weight percent of interferon in the tissue penetrating member comprises between about 0.05 to 0.2%.

12. 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.

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

14. The method of claim 1, wherein the solid dosage interferon produces a long-term release of interferon.

15. The method of claim 14, wherein the solid dosage interferon produces a long-term release of interferon to produce a selectable t_1/2.

16. The method of claim 15, wherein the t_1/2 is about 12 hours.

17. The method of claim 1, wherein a dose of interferon in the solid dosage is in a range of about 0.03 to 25 mg.

18. The method of claim 1, wherein a dose of interferon in the solid dosage is in a range of about 6 to 20 μ

g.

19. 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 interferon to be inserted into the intestinal wall.

20. The method of claim 19, wherein the pH is in a range from about 7 to 8.