Orthopedic and dental implant devices providing controlled drug delivery

• US 20060093646A1
• Filed: 10/28/2005
• Published: 05/04/2006
• Est. Priority Date: 10/28/2004
• Status: Abandoned Application

• Current Assignee: MicroCHIPS Inc.
• Original Assignee: MicroCHIPS Inc.
• Inventors: Cima, Michael J., Santini, John T. Jr., Staples, Mark A., Hutchinson, Charles E.
• Application Number:
  US11/262,413
• Publication Number:
  US 20060093646A1
• Time in Patent Office: Days
• US Class Current: 424/425
• CPC Class Codes: A61B 17/0642 for bones, e.g. for osteosynthesis or connecting tendon to bone
• CPC Class Codes: A61B 17/80 Cortical plates , i.e. bone plates; Instruments for holding or positioning cortical plates, or for compressing bones attached to cortical plates
• CPC Class Codes: A61B 17/86 Pins or screws or threaded wires; nuts therefor A61B17/72 take precedence
• CPC Class Codes: A61B 17/8625 Shanks, i.e. parts contacting bone tissue
• CPC Class Codes: A61B 2017/0648 threaded, e.g. tacks with a screw thread
• CPC Class Codes: A61C 19/063 Medicament applicators for teeth or gums, e.g. treatment with fluorides
• CPC Class Codes: A61C 8/0012 characterised by the material or composition, e.g. ceramics, surface layer, metal alloy use of specific materials A61K6/00
• CPC Class Codes: A61C 8/0016 polymeric material
• CPC Class Codes: A61F 2/30744 End caps, e.g. for closing an endoprosthetic cavity
• CPC Class Codes: A61F 2/30767 Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
• CPC Class Codes: A61F 2/30771 applied in original prostheses, e.g. holes or grooves
• CPC Class Codes: A61F 2/36 Femoral heads ; Femoral endoprostheses
• CPC Class Codes: A61F 2/3662 Femoral shafts
• CPC Class Codes: A61F 2/367 Proximal or metaphyseal parts of shafts trochanteric devices connected to said proximal parts A61F2/30739
• CPC Class Codes: A61F 2/3676 Distal or diaphyseal parts of shafts
• CPC Class Codes: A61F 2/38 for elbows or knees
• CPC Class Codes: A61F 2/3804 for elbows
• CPC Class Codes: A61F 2/3859 Femoral components
• CPC Class Codes: A61F 2/389 Tibial components A61F2/3868 takes precedence
• CPC Class Codes: A61F 2/40 for shoulders
• CPC Class Codes: A61F 2/4425 : made of articulated components
• CPC Class Codes: A61F 2/446 : having a circular or elliptical cross-section substantially parallel to the axis of the spine, e.g. cylinders or frustocones
• CPC Class Codes: A61F 2002/2817 : Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/30011 : differing in porosity
• CPC Class Codes: A61F 2002/30032 : differing in absorbability or resorbability, i.e. in absorption or resorption time
• CPC Class Codes: A61F 2002/30036 : differing in release or diffusion time
• CPC Class Codes: A61F 2002/30062 : (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30064 : Coating or prosthesis-covering structure made of biodegradable material
• CPC Class Codes: A61F 2002/30075 : swellable, e.g. when wetted
• CPC Class Codes: A61F 2002/30224 : cylindrical
• CPC Class Codes: A61F 2002/30324 : differing in thickness
• CPC Class Codes: A61F 2002/30326 : differing in height or in length
• CPC Class Codes: A61F 2002/30677 : Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/3068 : the pharmaceutical product being in a reservoir
• CPC Class Codes: A61F 2002/30787 : inclined obliquely with respect to each other
• CPC Class Codes: A61F 2002/30808 : parallel
• CPC Class Codes: A61F 2002/3081 : inclined obliquely with respect to each other
• CPC Class Codes: A61F 2002/30838 : Microstructures
• CPC Class Codes: A61F 2002/30878 : with non-sharp protrusions, for instance contacting the bone for anchoring, e.g. keels, pegs, pins, posts, shanks, stems, struts
• CPC Class Codes: A61F 2002/30929 : having at least two superposed coatings
• CPC Class Codes: A61F 2002/30971 : Laminates, i.e. layered products
• CPC Class Codes: A61F 2002/3611 : Heads or epiphyseal parts of femur
• CPC Class Codes: A61F 2002/3625 : Necks
• CPC Class Codes: A61F 2002/3631 : with an integral complete or partial peripheral collar or bearing shoulder at its base
• CPC Class Codes: A61F 2002/4631 : the prosthesis being specially adapted for being cemented
• CPC Class Codes: A61F 2210/0004 : bioabsorbable
• CPC Class Codes: A61F 2210/0061 : swellable
• CPC Class Codes: A61F 2230/0069 : cylindrical
• CPC Class Codes: A61F 2250/0024 : made from both porous and non-porous parts, e.g. adjacent parts
• CPC Class Codes: A61F 2250/003 : differing in adsorbability or resorbability, i.e. in adsorption or resorption time
• CPC Class Codes: A61F 2250/0035 : differing in release or diffusion time
• CPC Class Codes: A61F 2250/0036 : differing in thickness
• CPC Class Codes: A61F 2250/0037 : differing in height or in length
• CPC Class Codes: A61F 2250/0068 : the pharmaceutical product being in a reservoir
• CPC Class Codes: A61F 2310/00017 : Iron- or Fe-based alloys, e.g. stainless steel
• CPC Class Codes: A61F 2310/00023 : Titanium or titanium-based alloys, e.g. Ti-Ni alloys
• CPC Class Codes: A61F 2310/00029 : Cobalt-based alloys, e.g. Co-Cr alloys or Vitallium
• CPC Class Codes: A61F 2310/00131 : Tantalum or Ta-based alloys
• CPC Class Codes: A61F 2310/00179 : Ceramics or ceramic-like structures
• CPC Class Codes: A61L 2300/406 : Antibiotics
• CPC Class Codes: A61L 2300/414 : Growth factors
• CPC Class Codes: A61L 2300/604 : Biodegradation
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61N 1/30 : Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis

Abstract

Implantable prosthetic devices are provided for controlled drug delivery, for orthopedic and dental applications. The device may include a prosthetic device body having at least one outer surface area; two or more discrete reservoirs located in spaced apart positions across at least a portion of the outer surface area, the reservoirs formed with an opening at the surface of the device body and extending into the device body; and a release system disposed in the reservoirs which comprises at least one therapeutic or prophylactic agent, wherein following implantation into a patient the therapeutic or prophylactic agent is released in a controlled manner from the reservoirs. The prosthetic device body preferably is a joint prosthesis or part thereof, such as a hip prosthesis, a knee prosthesis, a vertebral or spinal disc prosthesis, or part thereof. Optional reservoir caps may further control release kinetics.

Claims

1. An implantable prosthetic device for controlled drug delivery comprising:

a prosthetic device body having at least one outer surface area;

two or more discrete reservoirs located in spaced apart positions across at least a portion of the outer surface area, the reservoirs formed with an opening at the surface of the device body and extending into the device body; and

a release system disposed in the reservoirs which comprises at least one therapeutic or prophylactic agent,

wherein following implantation into a patient the therapeutic or prophylactic agent is released in a controlled manner from the reservoirs.

2. The device of claim 1, wherein the prosthetic device body is a joint prosthesis or part thereof.

3. The device of claim 2, wherein the prosthetic device body comprises a hip prosthesis or part thereof.

4. The device of claim 2, wherein the prosthetic device body comprises a knee prosthesis or part thereof.

5. The device of claim 1, wherein the prosthetic device body comprises a vertebral or spinal disc prosthesis, spinal cage, or part thereof.

6. The device of claim 1, wherein the prosthetic device body comprises a surgical staple, screw, or plate.

7. The device of claim 1, wherein the prosthetic device body and surface area in which the reservoirs are defined comprises a biocompatible material selected from metals, polymers, ceramics, and combinations thereof.

8. The device of claim 7, wherein the device body comprises a stainless steel, a chrome-cobalt alloy, a titanium alloy, a ceramic, or an ultra high molecular weight polyethylene.

9. The device of claim 1, wherein the prosthetic device body comprises a porous surface region.

10. The device of claim 9, wherein the prosthetic device body further comprises a non-porous region, at least part of which is located beneath the porous region.

11. The device of claim 1, wherein the therapeutic or prophylactic agent comprises an antibiotic agent.

12. The device of claim 1, wherein the therapeutic or prophylactic agent comprises one or more growth factors.

13. The device of claim 1, wherein the therapeutic or prophylactic agent is a self-propagating agent.

14. The device of claim 1, wherein the release of the therapeutic or prophylactic agent is passively controlled.

15. The device of claim 1, wherein the release of the therapeutic or prophylactic agent is actively controlled.

16. The device of claim 1, wherein the release system further comprises one or more matrix materials.

17. The device of claim 16, wherein the matrix material comprises one or more synthetic polymers.

18. The device of claim 16, wherein the one or more matrix materials comprises a biodegradable, bioerodible, water-soluble, or water-swellable matrix material.

19. The device of claim 16, wherein the therapeutic or prophylactic agent is distributed in the matrix material and the matrix material degrades or dissolves in vivo to controllably release the therapeutic or prophylactic agent.

20. The device of claim 16, wherein the release system is provided in two or more layers having different compositions.

21. The device of claim 20, wherein each of the at least two reservoirs comprises at least two layers which comprise the one or more therapeutic or prophylactic agents and at least one layer of a degradable or dissolvable matrix material which does not comprise the one or more therapeutic or prophylactic agents.

22. The device of claim 20, wherein at least a first therapeutic or prophylactic agent is contained in a first layer of the two or more layers, and wherein a second therapeutic or prophylactic agent is contained in a second layer of the two or more layers.

23. The device of claim 1, wherein the therapeutic or prophylactic agent is heterogeneously distributed in the reservoir.

24. The device of claim 1, wherein the therapeutic or prophylactic agent is homogeneously distributed in the reservoir.

25. The device of claim 1, wherein the quantity of therapeutic or prophylactic agent provided for release from at least a first of the reservoirs is different from the quantity of the therapeutic or prophylactic agent provided for release from at least a second of the reservoirs.

26. The device of claim 1, wherein the kinetics of release of one of the therapeutic or prophylactic agents from at least a first of the reservoirs is different from the kinetics of release of the therapeutic or prophylactic agent from at least a second of the reservoirs.

27. The device of claim 1, wherein a first therapeutic or prophylactic agent is in at least one of the reservoirs and a second therapeutic or prophylactic agent is in at least one other of the reservoirs, the first therapeutic or prophylactic agent and the second therapeutic or prophylactic agent being different in kind or dose.

28. The device of claim 1, further comprising one or more discrete reservoir caps positioned over or disposed in the reservoir openings, wherein the time and/or rate of release of the therapeutic or prophylactic agent is controlled by the reservoir caps.

29. The device of claim 28, wherein the reservoir caps are non-porous.

30. The device of claim 29, wherein the reservoir caps comprise a biodegradable or bioerodible polymer.

31. The device of claim 30, wherein the biodegradable or bioerodible polymer is selected from the group consisting of poly(lactic acids), poly(glycolic acids), poly(lactic-co-glycolic acids), poly(caprolactones), poly(anhydrides), and mixtures thereof.

32. The device of claim 28, wherein the reservoir caps have a thickness between 0.1 and 100 microns.

33. The device of claim 29, wherein at least one discrete reservoir cap is formed of a first material and at least one other discrete reservoir cap is formed of a second material, wherein the first material has a different degradation or dissolution rate compared to the second material.

34. The device of claim 29, wherein at least one discrete reservoir cap has a first thickness and at least one other discrete reservoir cap has a second thickness, wherein the first thickness is different from the second thickness, thereby providing different times of release of the one or more therapeutic or prophylactic agent from the reservoirs covered respectively by the discrete reservoir cap having the first thickness and the discrete reservoir cap having the second thickness.

35. The device of claim 1, comprising at least two rows of at least two reservoirs.

36. The device of claim 35, wherein a first release system is in each of the at least two reservoirs of a first row and a second release system is in each of the at least two reservoirs of the other of the at least two rows other of the reservoirs, the first release system releasing the one or more therapeutic or prophylactic agents at a rate or in a dosage amount different from release of the one or more therapeutic or prophylactic agents from the second release system.

37. The device of claim 1, wherein the reservoirs are micro-reservoirs.

38. The device of claim 29, wherein the reservoir caps comprise a metal film.

39. The device of claim 38, further comprising control means to actively disintegrate the reservoir cap.

40. The device of claim 1, wherein the outer surface comprises a porous region, and the release system comprises a calcium phosphate compound, a bone morphogenic protein or a recombinant version thereof, or a combination thereof.

42. The device of claim 40, wherein the reservoirs comprise macroreservoirs.

43. The device of claim 42, wherein the pores of the porous surface region comprise a bone morphogenic protein or a recombinant version thereof.

44. A method of releasing a therapeutic or prophylactic agent from a prosthetic device in vivo comprising:

implanting the prosthetic device of claim 1 at a site in a patient in need thereof; and

releasing the therapeutic or prophylactic agent from the prosthetic device.

55. The device of claim 1, wherein the prosthetic device body is a dental implant.

56. The device of claim 55, wherein the release system comprises a bone morphogenic protein, a growth factor, an anti-infective agent, or a combination thereof.

45. An implantable prosthetic device for controlled drug delivery comprising:

a prosthetic device body having at least one outer surface area;

two or more discrete microreservoirs located in spaced apart positions across at least a portion of the outer surface area, the microreservoirs formed with an opening at the surface of the device body and extending into the device body;

a release system disposed in the microreservoirs which comprises at least one therapeutic or prophylactic agent; and

a plurality of discrete, non-porous reservoir caps located over the release system in the microreservoirs,

wherein release of the therapeutic or prophylactic agent following implantation of the device into a patient is controlled by the reservoir caps.

46. The device of claim 45, wherein the release system further comprises a matrix material, which further controls release of the therapeutic or prophylactic agent in vivo.

47. An implantable prosthetic device for controlled drug delivery comprising:

a prosthetic device body having at least one outer surface area;

two or more discrete microreservoirs located in spaced apart positions across at least a portion of the outer surface area, the microreservoirs formed with an opening at the surface of the device body and extending into the device body; and

a release system disposed in the reservoirs which comprises at least one therapeutic or prophylactic agent and a biodegradable or bioerodible matrix material;

wherein release of the therapeutic or prophylactic agent in vivo following implantation of the device into a patient is controlled by the matrix material.

48. The device of claim 47, further comprising a plurality of discrete, non-porous reservoir caps located over the release system in the reservoir reservoirs, wherein the reservoir caps further control release of the therapeutic or prophylactic agent in vivo.

49. The device of claim 47, wherein the release system is provided in two or more layers having different compositions.

50. The device of claim 47, wherein at least a portion of the device body is non-porous.

51. The device of claim 47, wherein at least a portion of the device body comprises a metal.

52. The device of claim 47, wherein the device body comprises at least one porous surface region.

53. A method for in vivo local delivery of a therapeutic or prophylactic agent in the treatment of orthopedic tissues comprising:

implanting at a orthopedic tissue site a tip portion of a tube which comprises a first end and a distal second end, wherein the tip portion has located therein a plurality of discrete reservoirs containing a therapeutic or prophylactic agent, the reservoirs having openings sealed by a plurality of discrete reservoir caps; and

actively and selectively disintegrating the reservoir caps to initiate release of the therapeutic or prophylactic agent at the tissue site.

54. The method of claim 53, wherein the orthopedic tissue site is a joint or spinal disc.