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

• US 10,335,463 B2
• Filed: 11/28/2017
• Issued: 07/02/2019
• 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): Tran, Susan T
• Application Number:
  US15/824,976
• Publication Number:
  US 20180221452A1
• Time in Patent Office: 581 Days
• Field of Search: None
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• 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: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes 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

Abstract

Embodiment 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 growth hormone into a wall of an intestine, the method comprising:

swallowing a drug delivery device comprising a capsule, an actuator having a first configuration and a second configuration and a growth hormone preparation operably coupled to the actuator, the growth hormone preparation comprising a therapeutically effective dose of growth hormone, the preparation being contained within the capsule in the first configuration and advanced out of the capsule and into the intestinal wall in the second configuration; and

actuating the actuator responsive to a condition in the intestine to deliver the growth hormone preparation into the wall of the small intestine.

2. The method of claim 1, wherein the condition is a selected pH.

3. The method of claim 2, wherein the pH is above about 7.1.

4. The method of claim 1, wherein the intestine is the small intestine.

5. The method of claim 1, wherein a weight per cent of Growth hormone in the Growth hormone preparation comprises between about 2 to 10%.

6. The method of claim 1, wherein a dose of growth hormone in the Growth hormone preparation is in a range from about 0.1 to 4 mg.

7. The method of claim 6, wherein the dose of growth hormone is in a range from about 0.2 to 1 mg.

8. The method of claim 1, wherein the growth hormone is somatropin.

9. The method of claim 1, wherein the growth hormone preparation further comprises at least one pharmaceutical excipient.

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

11. The method of claim 10, wherein the binder comprises PEG.

12. The method of claim 1, further comprising retaining the growth hormone preparation within the intestinal wall after insertion.

13. The method of claim 12, wherein retaining comprises anchoring at least one of a barb or an inverse taper shape of the growth hormone preparation in the intestinal wall.

14. The method of claim 1, wherein delivering the growth hormone preparation comprises applying a force to the growth hormone preparation.

15. The method of claim 14, wherein the growth hormone preparation is advanced completely into the intestinal wall by such application of force.

16. The method of claim 1, wherein the growth hormone preparation produces a long-term release of growth hormone.

17. The method of claim 16, wherein the long term release of growth hormone is in a range of about 12 to 48 hours.

18. The method of claim 1, wherein the release of grown hormone is used to treat growth hormone deficiency in a child.

19. The method of claim 18, wherein the growth hormone deficiency is associated with growth failure in the child.

20. The method of claim 1, wherein the release of grown hormone is used to treat growth hormone deficiency in an adult.

21. The method of claim 1, wherein upon insertion, the preparation releases growth hormone into the bloodstream from the intestinal wall to achieve a t½

that is greater than a t½

for orally ingested growth hormone that is not inserted into the intestinal wall.

22. The preparation of claim 21, wherein the t½

of the growth hormone inserted into the intestinal wall is at least about 10 times greater than the t½

for the orally ingested growth hormone that is not inserted into the intestinal wall.

23. A method for treating a growth hormone deficiency in a patient, the method comprising:

swallowing a drug delivery device comprising a capsule, an actuator having a first configuration and a second configuration and a growth hormone preparation operably coupled to the actuator, the growth hormone preparation comprising a therapeutically effective dose of growth hormone, the preparation being contained within the capsule in the first configuration and advanced out of the capsule and into the intestinal wall in the second configuration;

actuating the actuator responsive to a condition in the intestine to deliver the growth hormone preparation into the wall of the small intestine; and

utilizing the released growth hormone to treat the condition associated with growth hormone deficiency.

24. The method of claim 23, wherein the released growth hormone is used to treat growth hormone deficiency in a child.

25. The method of claim 24, wherein the growth hormone deficiency is associated with growth failure in the child.

26. The method of claim 23, wherein the released growth hormone is used to treat growth hormone deficiency in an adult.

27. A method for delivering growth hormone into a wall of an intestine, the method comprising:

swallowing a drug delivery device comprising a capsule, an actuator having a first configuration and a second configuration and a growth hormone preparation comprising a therapeutically effective dose of growth hormone, the grown hormone preparation positioned to be moved be actuation of the actuator, the preparation being contained within the capsule in the first configuration and advanced out of the capsule and into the intestinal wall in the second configuration; and

actuating the actuator responsive to a condition in the intestine to deliver the growth hormone preparation into the wall of the small intestine.