Swallowable drug delivery device and methods of drug delivery

• US 10,179,228 B2
• Filed: 08/30/2016
• Issued: 01/15/2019
• Est. Priority Date: 12/24/2009
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc. (Sanofi )
• Original Assignee: RaNA Therapeutics Inc. (Sanofi )
• Inventors: Imran, Mir
• Primary Examiner(s): OSINSKI, BRADLEY JAMES
• Application Number:
  US15/250,937
• Publication Number:
  US 20170050005A1
• Time in Patent Office: 868 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 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/2235 Secretins
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• 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 2005/1401 Functional features
• CPC Class Codes: A61M 2005/14284 with needle insertion means
• CPC Class Codes: A61M 2210/106 Small intestine
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• 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 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/168 Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body flow control in general G05D7/00
• CPC Class Codes: A61M 5/1723 : using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61M 5/20 : Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically A61M5/142 , A61M5/46 take precedence; hypodermic projectiles F42B12/54
• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 3/08 : for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 5/18 : of the parathyroid hormones

Abstract

Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Some embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. The device comprises a capsule sized to be swallowed and pass through the intestinal tract. The capsule can include at least one guide tube, one or more tissue penetrating members positioned in the guide tube, a delivery member, an actuating mechanism and a release element. The release element degrades upon exposure to various conditions in the intestine so as to release and actuate the actuating mechanism. 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. An ingestible device suitable for swallowing into a lumen of a gastrointestinal tract of a patient, the lumen having a lumen wall, the device comprising:

a capsule sized to pass through the intestinal tract;

a preparation comprising a solid therapeutic agent comprising a protein or polypeptide disposed in the capsule, the preparation shaped as a tissue penetrating member and configured to be inserted into a wall of a small intestine, the preparation comprising at least one protein or polypeptide which would chemically degrade if released within the lumen of the gastrointestinal tract; and

a release element operably coupled to the therapeutic agent preparation, the release element configured to release the solid therapeutic agent from the capsule into the wall of the small intestine responsive to a condition in the small intestine, wherein when the preparation is released into the wall of the small intestine, chemical degradation of the protein or polypeptide in the lumen is inhibited.

2. The device of claim 1, wherein the tissue penetrating member comprises a biodegradable material configured to biodegrade in tissue to release the therapeutic agent into the wall of the small intestine.

3. The device of claim 2, wherein the biodegradable material comprises a sugar, a biodegradable polymer or PGLA.

4. The device of claim 1, wherein the release element comprises a material configured to degrade upon exposure to a selected pH in the gastrointestinal tract.

5. The device of claim 4, wherein the selected pH is greater than about 7.4.

6. The device of claim 1, further comprising an actuator coupled to the release element for advancing the tissue penetrating member into the wall of the small intestine, the actuator configured to be actuated by release of the release element.

7. The device of claim 6, wherein the actuator comprises

an expandable member disposed within the capsule, the expandable member having a first and second compartment separated by a releasable valve which releases upon exposure to fluid in the intestinal tract;

a first reactant contained in one of the compartments and a second reactant contained in the other compartment, wherein when the valve release, the reactants mix to produce a gas which expands the expandable member; and

a delivery member for advancing the tissue penetrating member into the wall of the small intestine, the delivery member operably coupled to the expandable member and the tissue penetrating member.

8. The device of claim 7, wherein the delivery member comprises a piston or a plunger.

9. The device of claim 7, wherein the release element comprises the releasable valve.

10. The device of claim 1, wherein the protein or polypeptide preparation comprises a therapeutic agent.

11. The device of claim 10, wherein the therapeutic agent comprises a therapeutically effective dose of insulin for the treatment of diabetes or a glucose regulation disorder.

12. The device of claim 10, wherein the therapeutic agent comprises a therapeutically effective dose of an incretin for the treatment of diabetes or a glucose regulation disorder.

13. The device of claim 12, 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).

14. The device of claim 10, wherein the therapeutic comprises a combination of therapeutic agents for the treatment of diabetes or a glucose regulation disorder.

15. The device of claim 14, wherein the combination comprises a therapeutically effective dose of an incretin and a therapeutically effective dose of a biguanide.

16. The device of claim 15, wherein the incretin comprises exenatide and the biguanide comprises metformin.

17. The device of claim 15, wherein the dosages of the incretin and the biguanide are matched to produce an improved level of blood glucose control for an extended period.

18. The device of claim 10, wherein the therapeutic agent comprises a therapeutically effective dose of growth hormone.

19. The device of claim 10, wherein the therapeutic agent comprises a therapeutically effective dose of parathyroid hormone for the treatment of osteoporosis or a thyroid disorder.

20. The device of claim 10, wherein the therapeutic agent comprises a therapeutically effective dose of antibiotic.

21. The device of claim 10, wherein the therapeutic agent comprises a therapeutically effective dose of an antiviral compound.

22. The device of claim 21, wherein the antiviral compound comprises a protease inhibitor.

23. The device of claim 1, wherein the protein or polypeptide comprises a gamma globulin.

24. The device of claim 23, wherein the gamma globulin comprises an antibody and the antibody is delivered is delivered into the wall of the small intestine with minimal or no loss in binding affinity or specificity to a target antigen site.