Implantable and sealable system for unidirectional delivery of therapeutic agents to tissues

• US 20030064088A1
• Filed: 08/28/2002
• Published: 04/03/2003
• Est. Priority Date: 08/29/2001
• Status: Active Grant

• Current Assignee: Alan Linn Murphree, Edward E. Schmitt, Ricardo Azevedo Pontes De Carvalho
• Original Assignee: Alan Linn Murphree, Edward E. Schmitt, Ricardo Azevedo Pontes De Carvalho
• Inventors: Schmitt, Edward E., Murphree, Alan Linn, Carvalho, Ricardo Azevedo Pontes de
• Granted Patent: US 7,195,774 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

A surgically implantable and sealable delivery device that upon contact of its contents via an interface window or port therein with an organ or tissue exposes a therapeutic agent to the organ or tissue surface, allowing a controlled, selective and unidirectional diffusion of the agent into the tissue or organ. The device protects adjacent organs or tissue structures from unnecessary high levels of the delivered agent. Novel methods to deliver chemotherapeutics or bioactive agents to mammalian organs or tissues through a surgically implanted device by the way of a selective and protected diffusion mechanism are disclosed as well as method to achieve the sealing properties of the device.

Claims

1. ) A sealable drug delivery system comprised of a body or reservoir containing the therapeutic agent, delineated by an external surface impermeable to the therapeutic agent, an internal surface consisting on a biodegradable polymer layer or directly by a reservoir, and a sealing base;

9. ) The agent according to 1, wherein is preferentially, but not restricted to a chemotherapeutic, antibiotic, peptide, antibody, nucleotide, antibiotic, gene vector, hormone, protein, radio, photo or chemo sensitizer, cells, virus or bacterias.

11. ) The system according to 1, wherein the reservoir carries a vehicle for the therapeutic agent that is any form of polymer, copolymer, matrix, media, solution or tissue, chemically or physically associated to the therapeutic agents;

12. ) The system according to 1, wherein the reservoir carries biological or chemical therapeutic agents, associated or not to carrier vehicles or compounds to provide a sustained release of the agent;

29. ) The system according to 1, where it may be foldable or flexible to allow insertion through small incisions, and fitting to irregular organs surfaces.

31. ) The system according to 1, wherein its target interface is with the reservoir itself or a biodegradable polymer preferentially composed of, but not restricted to gelatin, ca-prolactone, hialuronic acid, cellulose, poly-glycolic acid, polylactic acid and any of those derivatives;

32. ) The system according to 1, wherein the therapeutic agent is in an encapsulated form, such as liposomes or microspheres;

35. ) A system according to 1, wherein to achieve what is claimed in 33, it is held in apposition to the sclera through the placement of buckling sutures or through the use of biocompatible adhesives.

54. ) A system according to 1, wherein the therapeutic agent is a prophylactic agent A system according to 1, wherein the effect or diffusion of the agent may be started or enhanced after the implantation procedure through the use of a secondary agent, whether its chemical, physical or biological.

2. ) The system claimed in 1, where the tissue is myocardium and the organ is the heart;

3. ) The system claimed in 1, where the tissue is the pericardium and the organ is the heart;

4. ) The system claimed in 1, where the tissue is the sclera and the organ is the eye;

5. ) The system claimed in 1, where the tissue is the liver capsule and the organ is the liver;

6. ) The system claimed in 1, where the tissue is the peritoneum covering the uterus body and the organ is the uterus;

7. ) The system claimed in 1, where the tissue is the kidney fibrous capsule and organ is the kidney;

8. ) The system claimed in 1, wherein carries any therapeutic or prophylactic agent in its activated or non-activated form.

10. ) The system claimed in 1, wherein it carries a cytotoxic agent;

13. ) The system claimed in 1, wherein the vehicle is preferentially, but not restricted to the classes of poly-orthoester, poly-glycolic acid, poly-lactic acid, poly-caprolactone, acrylate, cellulose, polyvinil-alcohol, polyvinil-pilirridone, dextran, hialuronic acid, fibrin, collagen, gelatin, or any derivatives;

14. ) The system claimed in 1, wherein the vehicle is in a solid, gel or liquid state;

15. ) The system claimed in 1, wherein the agent is in a solid, gel or liquid state;

16. ) The system claimed in 1, wherein the therapeutic agent is associated or not to another carrier or vehicle agent;

17. ) The system claimed in 1, wherein carries a therapeutic enhancer agent, preferentially, but not limited to an enzyme or a protein, such as albumin, a co-drug or a substract for the drug;

18. ) The system claimed in 1, wherein the reservoir carries a facilitating agent to enhance the diffusion of the therapeutic agent through the tissue'"'"'s interface, preferentially but not restricted to a prostaglandin and an enzyme;

19. ) The system claimed in 1, wherein the facilitating agent is preferentially a collagenase or any enzyme or pro-enzyme from the matrix metalloproteinase family;

20. ) The system claimed in 1, wherein the reservoir is directly exposed to the target tissue;

21. ) The system claimed in 1, wherein the reservoir and its continent is delineated in its internal surface by a structural layer of a biodegradable and biocompatible compound;

22. ) The system claimed in 1, wherein the delineating layer claimed in 21 is preferentially a rapidly degradable layer of gelatin;

23. ) The system claimed in 1, wherein the delineating layer claimed in 21 is a monolayer of rapidly biodegradable polymer or copolymer;

24. ) The system claimed in 1, wherein the external surface or wall is composed by a polymer impermeable to the carried agent, preferentially composed but not limited to poly-ethylene, silicone, hydrogel, glycolic acid, lactic acid or any derivative;

25. ) The system claimed in 1, wherein the external surface may comprise a refilling port preferentially made of, but not restricted to a self sealing material, such as silicone rubber;

26. ) The system claimed in 1, wherein the refilling port is distinguished from the surface of the device by staining with biocompatible dyes;

27. ) The system claimed in 1, wherein the refilling port is chemically incorporated to a marker, preferentially a dye;

28. ) The system claimed in 1, wherein the refilling port extends beyond the surface of the implant to facilitate its access;

30. ) A method for selective administration to a mammal organ, tissue or system, desired levels of a therapeutic agent through a highly controlled drug permeation across the device/tissue interface through hermetical sealing its hermetical sealing to a surface;

33. ) A method of local, protected and sustained delivery of therapeutic agents directly through its tissue interface in an unidirectional way, avoiding dissipation of the agent to surrounding tissues and fluids, after surgical implantation into a mammalian organism, through a tight interposition provided by a sealable base;

34. ) A method according to 33, wherein the system claimed in 1 is in controlled apposition to the target tissue by way of a sealed base;

44. ) A method according to 33, wherein the system claimed in 1 is anchored preferentially through a sealing suture technique throughout the sealing base;

50. ) A method according to 33, wherein the interface is with an artificial organ

51. ) A method according to 33, wherein the interface is with a synthetic or biological platform for cells or biological agents

52. ) A method according to 33, wherein the interface is with a scaffold for tissue or cell regeneration

53. ) A method according to 33, wherein the interface is with a transplanted tissue or organ

36. ) The system claimed in 1, wherein its architecture comprises suture stabilizers for accomplishing what is claimed in 33;

37. ) The system claimed in 1, wherein the suture stabilizers are placed on its outer surface to allow a buckling effect;

38. ) The system claimed in 1, wherein the suture tunnels are placed in the sealing base, surrounding the reservoir to allow a sealing effect;

39. ) The system claimed in 1, wherein the outer surface has indentation(s) for holding an encircling buckle to accomplish what is claimed in 33;

40. ) The system claimed in 1, wherein carries an osmotic agent associated to the therapeutic agent;

41. ) The method claimed in 33, wherein the system claimed in 1 is placed in contact and apposition to the target tissue preferentially through, but not limited to interposition between tissues or distinct layers of a tissue;

42. ) A method claimed in 33, wherein the system claimed in 1 is inserted through a surgical procedure to expose the target tissue surface;

43. ) A system claimed in 1, wherein to accomplish the method claimed in 33 it is inserted using an ejector or a device holder;

45. ) A method claimed in 33, wherein the system claimed in 1 is sealed to a tissue, preferentially using, but not limited to an acrylate, hydrogel, hyaluronate or a fibrin adhesive;

46. ) A system claimed in 1, wherein to accomplish the method claimed in 33 it is sealed to a tissue by using a biocompatible adhesive;

47. ) A method for achieving local or systemic, phisiological or pharmacological effects in a mammalian organism, by a surgically implantable device that delivers an agent directly and preferentially through its interface with the targeted tissue or organ, keeping the rest of its surface non-permeable to the carried agent by a a sealing mechanism of its base;

48. ) A method for achieving local or systemic, phisiological or pharmacological effects in a mammalian organism, by a surgically implantable device that delivers an agent directly and preferentially through its interface with the targeted tissue or organ, keeping the rest of its surface non-permeable to the carried agent by sealing to the target tissue through the use of buckling sutures;

49. ) A method for achieving local or systemic, phisiological or pharmacological effects in a mammalian organism, by a surgically implantable device that delivers an agent directly and preferentially through its interface with the targeted tissue or organ, keeping the rest of its surface non-permeable to the carried agent and sealed to the target tissue by the use of sealing surrounding sutures;