Method for delivering a therapeutic agent into the wall of the small intestine

• US 9,757,548 B2
• Filed: 05/20/2014
• Issued: 09/12/2017
• Est. Priority Date: 12/24/2009
• Status: Active Grant

• Current Assignee: RaNA Therapeutics Inc. (Sanofi )
• Original Assignee: RaNA Therapeutics Inc. (Sanofi )
• Inventors: Imran, Mir A.
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US14/282,864
• Publication Number:
  US 20140257238A1
• Time in Patent Office: 1,211 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. 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 within the wall to release the drug to produce a therapeutic effect. The preparation can be coupled to an actuator 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 a therapeutic agent into the wall of the small intestine, the method comprising:

swallowing a drug delivery device comprising a capsule, an actuator having a first configuration and a second configuration and a therapeutic preparation operably coupled to the actuator, the therapeutic preparation comprising a therapeutically effective dose of at least one therapeutic agent, the preparation being contained within the capsule in the first configuration and advanced out of the capsule and into the small intestine wall in the second configuration so as to deliver the therapeutic agent into the lumen wall, the preparation supplied in the capsule in a shaped form which can be directly delivered from inside the capsule into the wall of the small intestine by the application of force on a surface of the preparation; and

actuating the actuator responsive to a condition in the small intestine to directly deliver the therapeutic agent from the capsule 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 therapeutic agent comprises a therapeutically effective dose of insulin for the treatment of diabetes or a glucose regulation disorder.

5. The method of claim 4, further comprising:

using the dose of delivered insulin to control a blood glucose level of a patient without injecting insulin into the patient.

6. The method of claim 1, wherein the therapeutic agent comprises a therapeutically effective dose of an incretin for the treatment of diabetes or a glucose regulation disorder.

7. The method of claim 6, further comprising:

using the dose of delivered incretin to control a blood glucose level of a patient without injecting incretin into the patient.

8. The method of claim 6, 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).

9. The method of claim 6, wherein the incretin comprises exanatide and the dose is in a range from about 1 to 10 μ

g.

10. The method of claim 1, wherein the therapeutic agent comprises a combination of therapeutic agents for the treatment of diabetes or a glucose regulation disorder.

11. The method of claim 10, further comprising:

using the dose of delivered therapeutic agents to control a blood glucose level of a patient without injecting incretin into the patient.

12. The method of claim 11, wherein the combination comprises exenatide and metformin.

13. The method of claim 12, wherein the dosages of the exenatide and the metformin are matched to produce an improved level of blood glucose control for an extended period.

14. The method of claim 13, wherein the extended period is up to about a day.

15. The method of claim 13, wherein the extended period is up to about a week.

16. The method of claim 12, wherein the dose of exenatide is in a range of about 1 to 10 μ

g and the dose of metformin is in a range of about 1 to 3 grams.

17. The method of claim 10, wherein the combination comprises a therapeutically effective dose of an incretin and a therapeutically effective dose of a biguanide.

18. The method of claim 1, wherein the therapeutic agent comprises a therapeutically effective dose of growth hormone.

19. The method of claim 1, wherein the therapeutic agent comprises a therapeutically effective dose of parathyroid hormone for the treatment of osteoporosis or a thyroid disorder.

20. The method of claim 19, further comprising:

using the dose of delivered parathyroid hormone to treat the osteoporosis or a thyroid disorder without injecting parathyroid hormone into the patient.

21. The method of claim 1, wherein the therapeutic agent comprises a therapeutically effective dose of a chemotherapeutic agent for the treatment of cancer.

22. The method of claim 1, wherein the therapeutic agent comprises a therapeutically effective dose of an antibiotic.

23. The method of claim 1, wherein the therapeutic agent comprises a therapeutically effective dose of an antiviral compound.

24. The method of claim 1, further comprising:

delivering a first and a second therapeutic agent.