Devices, Systems and Methods for Acute or Chronic Delivery of Substances or Apparatus to Extravascular Treatment Sites

• US 20080058759A1
• Filed: 10/30/2007
• Published: 03/06/2008
• Est. Priority Date: 01/17/2002
• Status: Abandoned Application

• Current Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Original Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Inventors: Flaherty, J., Chang, John, Makower, Joshua, Tholfsen, David, Lamson, Theodore, Catanese, Joseph, Reggie, John
• Application Number:
  US11/927,874
• Publication Number:
  US 20080058759A1
• Time in Patent Office: Days
• US Class Current: 604/509
• CPC Class Codes: A61B 6/12 Arrangements for detecting or locating foreign bodies
• CPC Class Codes: A61M 2025/0086 the needles having bent tips, i.e. the needle distal tips are angled in relation to the longitudinal axis of the catheter
• CPC Class Codes: A61M 2025/0087 Multiple injection needles protruding laterally from the distal tip
• CPC Class Codes: A61M 2025/009 the needle having a bent tip, i.e. the needle distal tip is angled in relation to the longitudinal axis of the catheter
• CPC Class Codes: A61M 2210/12 Blood circulatory system
• CPC Class Codes: A61M 25/0084 being one or more injection needles
• CPC Class Codes: A61M 25/0108 using radio-opaque or ultrasound markers
• CPC Class Codes: A61M 5/007 for contrast media

Abstract

Methods and apparatus for delivery of substances or apparatus to target sites located outside blood vessels within the body of a human or animal patient. A vessel wall penetrating catheter is inserted into the vasculature, positioned and oriented within a blood vessel near the target extravascular site and a penetrator is advanced from the catheter so as to penetrate outwardly through the wall of the blood vessel in the direction of the target site. Thereafter, a delivery catheter is passed through a lumen of the penetrator to the target site. A desired substance or apparatus is then delivered to or obtained from the target site. In some applications, the penetrator may be retracted into the vessel wall penetrating catheter and the vessel wall penetrating catheter may be removed, leaving the delivery catheter in place for chronic or continuous delivery of substance(s) to and/or obtaining of information or samples from the target site. Alternatively, a delivery catheter having an occlusion member or balloon may be advanced into a vein or venule and the occlusion member or balloon may be used to occlude the lumen of the vein or venule during and after injection of a substance through the catheter, such that the substance will not be carried away by normal venous blood flow and will remain in the vein or venule for a sufficient period of time to have its intended effect (e.g. to enter adjacent tissues through capillary beds drained by that vein or venule).

Claims

1. A method for delivering a substance or apparatus to an extravascular target site within the body of a human or veterinary patient, said method comprising the steps of:

(A) providing a vessel wall penetrating catheter that is insertable into the vasculature of the patient, said vessel wall penetrating catheter having a penetrating member that is advanceable through the wall of a blood vessel in which the catheter body is positioned, said vessel wall penetrating member having a lumen extending longitudinally therethrough;

(B) inserting the vessel wall penetrating catheter into the vasculature of the patient;

(C) positioning the vessel wall penetrating catheter within the vasculature of the patient such that the penetrator, when advanced, will pass through the wall of a blood vessel to a location near the target site;

(D) advancing the penetrator through the wall of a blood vessel and to a location near the target site;

(E) advancing through the lumen of the penetrator and to the target site, a second apparatus selected from the group consisting of;

i. an elongate delivery catheter having a lumen through which a substance may be injected or withdrawn;

ii. an elongate member that comprises a therapeutic apparatus operative to deliver a therapy to the target site;

iii. an elongate member that comprises an information-obtaining apparatus operative to obtain information from the target site; and

,

iv. possible combinations thereof.

2. A method according to claim 1 wherein the vessel wall penetrating catheter further comprises a guidance element useable by the operator to position the vessel wall penetrating catheter body within the vasculature of the patient such that when the vessel wall penetrating member is passed from the catheter body it will penetrate through the wall of the blood vessel in the direction of the intended extravascular target site, and wherein Step C further comprises using said guidance element to position the vessel wall penetrating catheter body within the vasculature of the patient such that when the vessel wall penetrating member is passed from the catheter body it will penetrate through the wall of the blood vessel in the direction of the intended extravascular target site.

3. A method according to claim 2 wherein the guidance element comprises an imaging apparatus and wherein Step C further comprises using the imaging apparatus to image at least the target site and using such image to guide the positioning of the vessel wall penetrating catheter.

4. A method according to claim 3 wherein the imaging apparatus is an ultrasound imaging apparatus and the image used in Step C is an ultrasound image.

5. A method according to claim 2 wherein the guidance element comprises indicia that indicates the path that will be followed by the penetrator when it is subsequently advanced from the catheter penetrating catheter and wherein Step C further comprises obtaining an image of the imageable marker and using such image to guide the positioning of the vessel wall penetrating catheter.

6. A method according to claim 5 wherein the guidance element comprises the combination of an imaging apparatus and at least one imageable marker on the vessel wall penetrating catheter, and wherein Step C further comprises using the imaging apparatus to obtain an image of at least the imageable marker and using that image to guide the positioning of the vessel wall penetrating catheter.

7. A method according to claim 6 wherein the imageable marker provides an indication of the direction in which the penetrator will advance and wherein Step C further comprises imaging of the imageable marker to obtain an indication of the direction in which the penetrator will advance and using said indication to rotationally orient and position the vessel wall penetrating catheter such that subsequent advancement of the penetrator will cause the penetrator to travel in the direction of the target site.

8. A method according to claim 2 wherein the guidance element comprises an emitter located on or in the catheter body, said emitter emitting a signal that is received by an extracorporeally situated signal-receiving apparatus and wherein Step C further comprises using an extracorporeally situated signal-receiving apparatus to receive a signal from the emitter and to thereby guide the placement of the vessel wall penetrating catheter.

9. A method according to claim 1 wherein the second apparatus comprises an elongate delivery catheter having a lumen through which a substance may be delivered and wherein the method further comprises the step of:

delivering a substance through the delivery catheter to the target site.

10. A method according to claim 9 wherein the delivery catheter is a delivery catheter having an outer diameter of less than 0.5 mm.

11. A method according to claim 9 wherein the delivery catheter further comprises a matter blocking member for preventing cellular ingrowth and other matter from obstructing the lumen of the delivery catheter and wherein the method further comprises the step of:

using said matter blocking member to prevent cellular ingrowth and other matter from obstructing the lumen of the delivery catheter at least during times when no substance is being infused through the delivery catheter.

12. A method according to claim 11 wherein the delivery catheter has an outflow opening through which substances may pass out of the lumen of the delivery catheter and into the target location and wherein the matter blocking member comprises a selectively permeable barrier that allows desired substances to be infused in the distal direction through the outflow opening and to the target location but prevents cellular ingrowth and other matter from entering the lumen of the delivery catheter through said outflow opening, and wherein the method further comprises the step of:

infusing a substance in the distal direction through the delivery catheter and, thereafter, allowing the substance to pass outwardly through the selectively permeable barrier.

13. A method according to claim 11 wherein the selectively permeable barrier comprises a balloon attached to the delivery catheter and wherein the method further comprises the step of:

infusing a substance the distal direction through the delivery catheter such that the substance collects within the balloon and subsequently diffuses outwardly through the balloon.

14. A method according to claim 11 wherein the matter blocking member comprises a stylet that is insertable into the lumen of the delivery catheter to block cellular ingrowth and other matter from entering thereinto and wherein the method further comprises the step of:

inserting the stylet into the lumen of the delivery catheter at least at times when no substance is being infused through said lumen, thereby blocking the entry of cellular ingrowth and other matter into the delivery catheter lumen.

15. A method according to claim 14 wherein the stylet is removable from the lumen of the delivery catheter to permit delivery of a substance or apparatus through the delivery catheter and wherein the method further comprises the step of:

removing the stylet from the delivery catheter lumen when it is desired to deliver a substance or apparatus through the delivery catheter lumen.

16. A method according to claim 9 wherein the delivery catheter comprises:

a first tube having a lumen and a sidewall in which an outflow aperture is formed; and

,

a second tube rotatably disposed in a coaxial position within the first tube, said second tube having a lumen, a closed distal end and a sidewall in which an opening is formed;

the second tube being rotatably moveable between i) a blocking position wherein the side wall of the second tube substantially blocks the outflow aperture of the first tube to prevent cellular ingrowth and other matter from entering the lumen of the second tube and ii) a delivery position wherein the opening of the second tube is aligned with the outflow opening of the first tube such that a substance that is injected into the lumen of the second tube will flow through the opening of the second tube and through the outflow opening of the first tube, and wherein said method further comprises the steps of;

placing the second tube in the blocking position when no substance or apparatus is being delivered through the delivery catheter; and

,

placing the second tube in the delivery position when a substance or apparatus is being delivered through the delivery catheter.

17. A method according to claim 11 wherein the delivery catheter comprises:

a tube having a lumen and a sidewall in which an outflow aperture is formed; and

,

an obturator member disposed at least partially within the lumen of the tube, said obturator member being alternately disposable in i) a blocking position wherein the obturator substantially blocks the outflow aperture of the tube to prevent cellular ingrowth and other matter from entering the lumen of the tube and ii) a delivery position wherein the obturator does not substantially block the outflow apertures such that fluid may be injected through the lumen of the tube and out of the outflow aperture; and

wherein the method further comprises the steps of;

placing the obturator in the blocking position when no substance or apparatus is being delivered through the delivery catheter; and

,

placing the obturator in the delivery position when a substance or apparatus is being delivered through the delivery catheter.

18. A method according to claim 17 wherein the obturator member is an inflatable balloon that assumes said blocking position when inflated and said infusion position when deflated, and wherein the step of placing the obturator in the blocking position comprises inflating the balloon and the step of placing the obturator in the delivery position comprises deflating the balloon.

19. A method according to claim 9 wherein the delivery catheter comprises a delivery lumen, a return lumen, an aperture through which substances or apparatus delivered through the delivery lumen may pass out of the delivery catheter and a flow diverter, said flow diverter that is alternately deployable in i) a delivery position whereby substances or apparatus may be delivered through the delivery catheter lumen and out of the aperture and ii) a recirculation position whereby fluid infused through the delivery lumen will be recirculated back through the return lumen and wherein the method further comprises the steps of:

placing the diverter in the delivery position when it is desired to deliver a substance or apparatus through the delivery lumen and out of the aperture; and

,

placing the diverter in the recirculation position and infusing a fluid through the delivery lumen and back through the recirculation lumen, when no substance or apparatus is being delivered through the delivery lumen.

20. A method according to claim 9 wherein the delivery catheter comprises a pressure increasing outflow opening configured to cause an increase the pressure of substances that are injected through the delivery catheter lumen and out of said pressure increasing outflow opening, and wherein the method further comprises the step of:

delivering a substance through the delivery catheter and out of the outflow opening such that the pressure of the substance increases as it flows out of the outflow opening.

21. A method according to claim 9 wherein the substance delivered in Step F is a therapeutic substance.

22. A method according to claim 9 wherein the substance delivered in Step F is a agent that provides an enhanced image of the target site.

23. A method according to claim 9 wherein the substance delivered in Step F is a traceable substance that may be used to determine the rate at which the substance distributes away from or is otherwise inactivated at the target site or other pharmacokinetic or biodistributive parameters or variables.

24. A method according to claim 1 wherein the therapeutic substance is selected from the group consisting of:

a drug, a protein, cells, an angiogenic substance, a myogenic substance, a neurogenic substance, a gene, a gene therapy composition, genetic material in combination with a vector for delivering the genetic material into locations within cells at which the genetic material will have a desired effect on the cells;

25. A method according to claim 21 wherein the method is carried out to improve perfusion of an ischemic target site and where the therapeutic substance delivered in Step F comprises is an angiogenic agent that increases vascularity of the ischemic target site.

26. A method according to claim 25 wherein the angiogenic agent delivered in Step F is selected from the group of angiogenic agents consisting of vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF) or scatter factor, heparin combined with an adenosine receptor agonist, nerve cell growth factor (NGF), and combinations thereof.

27. A method according to claim 21 wherein the therapeutic substance delivered in Step F comprises cells.

28. A method according to claim 27 wherein said cells are selected from the group consisting of stem cells, progenator cells, myoblasts, myocytes, secretory cells, pancreatic islet cells, dopamine secreting cells, endothelial cells, hepatocytes, cloned cells, cells grown in cell culture, genetically modified cells, and combinations thereof.

29. A method according to claim 27 wherein the method is carried out to treat a condition characterized by a deficiency of a type of cell within the patient'"'"'s body and wherein the type of cell that is deficient matures in situ from stem cells, and wherein the therapeutic substance delivered in Step F comprises stem cells of a type that mature into the deficient cell type.

30. A method according to claim 29 wherein the method is carried out to treat a condition characterized by a lack of living myocytes in or near the target site and wherein the therapeutic substance delivered in Step F comprises myocytes.

31. A method according to claim 29 wherein the method is carried out to treat parkinsonism, the target site comprises the substantia nigra of the patient'"'"'s brain and wherein the therapeutic substance delivered in Step F comprises dopamine secreting cells which when implanted will increase dopamine in the substantia nigra.

32. A method according to claim 31 wherein the dopamine secreting cells comprise fetal dopamine secreting cells.

33. A method according to claim 29 wherein the method is carried out to treat diabetes, the target site comprises the patient'"'"'s pancreas, and wherein the therapeutic substance delivered in Step F comprises insulin secreting cells which, when implanted, will increase insulin production by the patient'"'"'s pancreas.

34. A method according to claim 33 wherein the insulin secreting cells comprise pancreatic β

islet cells.

35. A method according to claim 21 wherein the method is carried out to treat a neurogenerative disorder and wherein the substance delivered comprises nerve cells.

36. A method according to claim 21 wherein the method is carried out to treat a neurogenerative disorder and wherein the substance delivered comprises a substance that facilitates nerve growth.

37. A method according to claim 36 wherein the substance delivered is selected from the group consisting of:

glial cell line-derived neurotropic factor (GDNF), nerve growth factor, neuro-immunophilin ligand, poly ADP-Ribose polymerase, and combinations thereof.

38. A method according to claim 31 wherein the therapeutic substance comprises a gene in combination with a vector for facilitating entry of the gene into locations within cells in which the gene will have a desired therapeutic effect.

39. A method according to claim 38 wherein the vector is a virus.

40. A method according to claim 1 wherein the second apparatus further comprises an anchoring member for holding the second apparatus in a substantially fixed position within the patient'"'"'s body and wherein the method further comprises the step of:

causing the anchoring apparatus to hold the second apparatus in a substantially fixed position within the patient'"'"'s body.

41. A method according to claim 40 wherein the anchoring member is selected from the group of anchoring members consisting of:

a hook;

a barb;

a permeable surface into which tissue may grow;

an adhesive; and

,

combinations thereof;

and wherein Step F comprises causing the anchoring apparatus to engage tissue adjacent thereto so as to hold the second apparatus in said substantially fixed position.

42. A method according to claim 1 wherein the second apparatus is a delivery catheter, wherein the delivery catheter further comprises a backflow deterrent for blocking backflow of substances that have been injected through the delivery catheter and wherein the method further comprises the step of:

causing the backflow deterrent to deter backflow of a substance that has been infused through the delivery catheter to the target site.

43. A method according to claim 42 wherein the backflow deterrent comprises a backflow barrier rib formed on the delivery catheter and wherein the step of causing the backflow deterrent to deter backflow is carried out by positioning the backflow deterrent rib so that is acts as a barrier to the unwanted backflow.

44. A method according to claim 43 wherein said backflow barrier comprises an inflatable balloon on the delivery catheter and wherein the step causing the backflow deterrent to deter backflow is carried out by inflating the balloon.

45. A method according to claim 42 wherein said backflow deterrent comprises a raised projection formed on the exterior of the delivery catheter and wherein the step of causing the backflow deterrent to deter backflow is carried out by positioning the raised projection so that is acts as a barrier to the unwanted backflow.

46. A method according to claim 45 wherein the raised projection comprises an annular rib formed about the outer surface of the delivery catheter

47. A method according to claim 42 wherein the backflow deterrent comprises a sealant which, when implanted in the penetration tract through which the delivery catheter was advanced, will prevent the substance from backflowing through that tract, and wherein Step F of the method comprises implanting the sealant into the penetration tract.

48. A method according to claim 47 wherein the sealant is implanted into the tract prior to removal of the delivery catheter.

49. A method according to claim 47 wherein the sealant is implanted into the tract prior concurrently with removal of the delivery catheter.

50. A method according to claim 47 wherein the sealant comprises a quantity of a flowable sealant and wherein the step of implanting the sealant into the penetration tract comprises injecting the flowable sealant into the penetration tract.

51. A method according to claim 50 wherein the injecting of the flowable sealant into the penetration tract comprises injecting the flowable sealant through the delivery catheter.

52. A method according to claim 47 wherein the sealant comprises a detachable sealing member and wherein Step F comprises introducing the sealing member into the penetration tract and thereafter detaching the sealing member such that it will remain in the penetration tract after the delivery catheter has been removed.

53. A method according to claim 52 wherein the detachable sealing member comprises biodegradable material and wherein Step F comprises introducing the biodegradable member into the penetration tract and thereafter detaching the biodegradable member such that it will remain in the penetration tract after the delivery catheter has been removed.

54. A method according to claim 52 wherein the sealing member is a collagen sponge and wherein Step F comprises introducing the collagen sponge into the penetration tract and thereafter detaching the collagen sponge such that it will remain in the penetration tract after the delivery catheter has been removed.

55. A method according to claim 52 wherein the sealing member is a hydrogel material and wherein Step F comprises introducing the hydrogel material into the penetration tract and thereafter detaching the hydrogel material such that it will remain in the penetration tract after the delivery catheter has been removed.

56. A method according to claim 1 wherein at least a portion of the second apparatus is coated with an adhesive and wherein the method further comprises the step of:

causing the adhesive to adhere to adjacent tissue thereby deterring movement of the second apparatus.

57. A method according to claim 1 wherein an anti-microbial substance is disposed on at least a portion of the second apparatus and wherein the method further comprises the step of:

causing the anti-microbial substance to deter microbial growth in the area surrounding the portion of the second apparatus on which the anti-microbial substance is disposed.

58. A method according to claim 1 wherein an anti-coagulant substance is disposed on at least a portion of the second apparatus and wherein the method further comprises the step of:

causing the anti-coagulant substance to deter coagulative processes in the area surrounding the portion of the second apparatus on which the anti-coagulant substance is disposed.

59. A method according to claim 9 wherein the apparatus further comprises a tissue pocket creating apparatus and wherein the method further comprises the step of:

using the tissue pocket creating apparatus to create a pocket within tissue adjacent to the delivery catheter such that when a substance or apparatus is introduced through the delivery catheter it will be received within said pocket

60. A method according to claim 59 wherein the tissue pocket creating apparatus comprises an energy emitting member and wherein the step of using the tissue pocket creating apparatus comprises causing the tissue pocket creating apparatus to emit energy into adjacent tissue to create a tissue pocket therein.

61. A method according to claim 60 wherein the energy emitting apparatus is a radiofrequency electrode and wherein the step of using the tissue pocket creating apparatus comprises causing the electrode to emit energy of a magnitude and duration sufficient to create the tissue pocket.

62. A method according to claim 60 wherein the energy emitting apparatus is a laser.

63. A method according to claim 59 wherein the tissue pocket creating apparatus comprises a nozzle through which a stream of fluid may be injected and wherein the step of using the tissue pocket creating apparatus comprises injecting fluid through the nozzle to create the pocket in adjacent tissue.

64. A method according to claim 59 wherein the tissue pocket creating apparatus comprises an expandable cage and wherein the step of using the tissue pocket creating apparatus comprises expanding the cage to create the pocket in adjacent tissue.

65. A method according to claim 1 wherein the second apparatus is an elongate member that comprises a therapeutic apparatus operative to deliver a therapy to the target site and wherein the method further comprises the step of:

using the therapeutic apparatus to deliver therapy to the target site.

66. A method according to claim 1 wherein the delivery catheter further comprises a position indicator for indicating the position of the delivery catheter within tissue and wherein the method further comprises the step of:

using the position indicator to discern the position of the delivery catheter within the patient'"'"'s body at least one time during the procedure.

67. A method according to claim 66 wherein the position indicator comprises a radiographically visible marker and wherein the step of using the position indicator to discern the position comprises using a radiographic imaging apparatus to discern the location of the radiographically visible marker.

68. A method according to claim 1 wherein the method comprises advancing a delivery catheter through the penetrator and injecting a substance though the delivery catheter.

69. A method according to claim 68 wherein the method further comprises moving the delivery catheter while injecting the substance.

70. A method according to claim 69 wherein the delivery catheter is advanced while injecting the substance.

71. A method according to claim 69 wherein the delivery catheter is retracted while injecting the substance.

72. A method according to claim 69 wherein the substance is injected continuously while the delivery catheter is moved to deposit the substance over an elongate area or deposition.

73. A method according to claim 69 wherein boluses of the substance are injected at different times while the delivery catheter is moved to provide a plurality of discrete deposits of the substance at different locations on the path over which the delivery catheter was moved.

74. A method according to claim 1 further comprising the steps of:

obtaining a quantity of tissue or cellular matter for use as a tissue graft;

loading the tissue graft into the delivery catheter;

advancing the delivery catheter to an interstitial site; and

, delivering the tissue graft through the delivery catheter to the interstitial site.

75. A method according to claim 1 wherein a delivery catheter is advanced through the penetrator and to a location adjacent to an anatomical cavity, chamber or structure that the operator does not wish to penetrate with the delivery catheter and, wherein at least one of the penetrator and delivery catheter are of curved configuration such that the delivery catheter will advance through tissue on a path of advancement that is not directed into the anatomical cavity, chamber or structure that the operator does not wish to penetrate.

76. A method according to claim 75 wherein the delivery catheter is advanced into myocardial tissue adjacent to a chamber of the heart and at least one of the penetrator and delivery catheter are of a curved configuration that causes the delivery catheter to be advanced on a path of advancement that is generally tangential to the adjacent chamber of the heart, the delivery catheter being thereby advanced into the myocardial tissue without entering the chamber of the heart.