Swallowable drug delivery device and methods of drug delivery

• US 8,721,620 B2
• Filed: 12/23/2010
• Issued: 05/13/2014
• 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): Mehta, Bhisma
• Assistant Examiner(s): OSINSKI, BRADLEY JAMES
• Application Number:
  US12/978,233
• Publication Number:
  US 20110160699A1
• Time in Patent Office: 1,237 Days
• Field of Search: 6048901-8921, 604500-503, 604/57, 604 65- 67, 604/103.01, 604/59, 604/60
• US Class Current: 604/503
• 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. A method for delivering a therapeutic agent into the wall of a small intestine of a patient, the method comprising:

swallowing a drug delivery device comprising a release element and a solid therapeutic agent shaped as a tissue penetrating member configured to be inserted into the wall of a small intestine;

wherein the solid therapeutic agent would chemically degrade if released within a lumen of the gastrointestinal tract;

wherein the release element releases the solid therapeutic agent from the device into the wall of the small intestine responsive to a condition in the small intestine; and

wherein the solid therapeutic agent penetrates into the wall of the small intestine such that the chemical degradation of the therapeutic agent in the lumen is inhibited.

2. The method of claim 1, wherein a dose of the therapeutic agent in the capsule does not include an amount to compensate for chemical degradation and/or lack of absorption of the therapeutic agent in the gastrointestinal tract.

3. The method of claim 1, wherein the dose of therapeutic agent is reduced in an amount between about 10 to 50 percent compared to a standard oral dosage.

5. The method of claim 1, wherein the deleterious effect comprises one of gastric cramping, diarrhea, irritable bowel or hemorrhage within the GI tract.

6. The method of claim 1, wherein the deleterious effect comprises a toxic effect on non-target tissue.

7. The method of claim 1, wherein the therapeutic agent comprises a chemotherapeutic agent for the treatment of cancer and the deleterious effect comprises at least one of a toxic effect on non-target tissue or the development of resistance to the therapeutic agent by cancerous tissue within the patient.

8. The method of claim 1, wherein the therapeutic agent comprises an antibiotic and the deleterious effect comprises the development of bacterial resistance to the antibiotic.

9. The method of claim 1, wherein the therapeutic agent comprises an antiviral agent and the deleterious effect comprises the development of a viral resistance to the antiviral agent.

10. The method of claim 1, wherein the therapeutic agent comprises an anti-seizure compound and the deleterious effect comprises a neuromuscular, cardiovascular or gastro-intestinal effect.

11. The method of claim 10, wherein the therapeutic agent comprises furosemide.

12. The method of claim 1, wherein the therapeutic agent comprises an antibody that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in the binding affinity or specificity to a target antigen site.

13. The method of claim 1, wherein the therapeutic agent comprises a polypeptide that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in binding affinity or specificity to a target binding site.

14. The method of claim 1, wherein the therapeutic agent comprises a cytokine or interferon that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in immune stimulating ability.

15. The method of claim 1, wherein the therapeutic agent comprises growth hormone that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in growth stimulating effect.

16. The method of claim 1, wherein the therapeutic agent comprises a chemotherapeutic agent for the treatment of cancer that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in cancer treatment effect.

17. The method of claim 1, wherein the therapeutic agent comprises a glucose regulating agent that is chemically degraded in the GI tract and the agent is delivered into the wall of the small intestine with minimal or no loss in glucose regulating ability.

18. The method of claim 17, wherein the glucose regulating agent comprises an insulin compound.

19. The method of claim 17, wherein the glucose regulating agent comprises an incretin compound, a GLP-1 compound or exenatide.

20. The method of claim 1, wherein the condition in the small intestine is a pH above about 7.1.

21. The method of claim 1, wherein the release element degrades in response to a chemical condition in the small intestine.

22. The method of claim 21, wherein the condition is a selected pH.

23. The method of claim 1, wherein the release element comprises an enteric material.

24. The method of claim 1, further comprising:

delivering a first therapeutic agent and a second therapeutic agent, wherein the first therapeutic agent is delivered using a first tissue penetrating member and the second therapeutic agent is delivered using a second tissue penetrating member.

4. The method of 1, wherein the patient has a shortened section of small intestine and a dose of the therapeutic agent in the capsule does not include a portion to compensate for lack of absorption of the therapeutic agent in the small intestine.

25. A method of drug delivery, the method comprising, swallowing a drug delivery device comprising a capsule, a drug shaped as a tissue penetrating member configured to be inserted into a wall of the small intestine an actuating mechanism, and a release element;

releasing the release element in the small intestine responsive to a condition in the small intestine; and

actuating the actuation mechanism to deliver the drug into the wall of the small intestine by inserting the tissue penetrating member into the wall of the small intestine.

26. The method of claim 25, wherein the drug comprises a chemotherapeutic agent, interferon, an antibody, an antibiotic, growth hormone, parathyroid hormone, a glucose regulating agent, an insulin compound, an incretin hormone, a GLP-1 compound or exenatide.

27. The method of claim 25, wherein the release element degrades in response to a chemical condition in the small intestine.

28. The method of claim 25, wherein the release element comprises an enteric material.

29. The method of claim 25, wherein the actuating mechanism comprises a spring, a cam, an electromechanical mechanism, a solenoid, or a piezoelectric material.