Methods and apparatus for acute or chronic delivery of substances or apparatus to extravascular treatment sites

• US 6,602,241 B2
• Filed: 01/17/2001
• Issued: 08/05/2003
• Est. Priority Date: 01/17/2001
• Status: Expired due to Term

• Current Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Original Assignee: TransVascular, Inc. (Medtronic Plc)
• Inventors: Catanese, Joseph III, Chang, John Y., Reggie, John A., Flaherty, J. Christopher, Makower, Joshua, Lamson, Theodore C., Tholfsen, David R.
• Primary Examiner(s): Huson, Gregory
• Assistant Examiner(s): HUYNH, KHOA D
• Application Number:
  US09/766,502
• Publication Number:
  US 20030078562A1
• Time in Patent Office: 930 Days
• Field of Search: 604/500, 604/506-510, 604/164.01, 604/164-8-1, 604/164.13, 604/96.01, 604/99-2-, 604/103.01, 604/103.06, 604/912, 604/915, 600/585, 600/433, 600/434, 600/435, 600/470, 606/167, 606/170, 606/181, 606/182, 606/184, 606/185
• US Class Current: 604/509
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61B 17/0057 Implements for plugging an opening in the wall of a hollow or tubular organ, e.g. for sealing a vessel puncture or closing a cardiac septal defect sutures A61B17/04; closing rectum or urethra near body surface A61F2/0009
• CPC Class Codes: A61B 17/12022 Occluding by internal devices, e.g. balloons or releasable wires plugging an opening in the wall of an organ A61B17/0057; occluders for the cervical canal A61F6/146; vas deferens occluders A61F6/20
• CPC Class Codes: A61B 17/12109 in a blood vessel
• CPC Class Codes: A61B 17/12122 within the heart for closing a cardiac septal defect A61B17/0057
• CPC Class Codes: A61B 17/12136 Balloons
• CPC Class Codes: A61B 17/12186 liquid materials adapted to be injected
• CPC Class Codes: A61B 18/24 with a catheter A61B18/26, A61B18/28 take precedence
• CPC Class Codes: A61B 2017/00243 cardiac
• CPC Class Codes: A61B 2017/00247 Making holes in the wall of the heart, e.g. laser Myocardial revascularization
• CPC Class Codes: A61B 2017/00575 for closure at remote site, e.g. closing atrial septum defects
• CPC Class Codes: A61B 2018/00392 Transmyocardial revascularisation
• CPC Class Codes: A61M 2025/018 Catheters having a lateral opening for guiding elongated means lateral to the catheter
• CPC Class Codes: A61M 25/0069 Tip not integral with tube
• CPC Class Codes: A61M 25/0084 being one or more injection needles
• CPC Class Codes: A61M 25/0102 Insertion or introduction using an inner stiffening member, e.g. stylet or push-rod
• CPC Class Codes: A61M 25/065 Guide needles

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 system for delivering substances or apparatus to an extraluminal target site within the body of a human or veterinary patient, said system comprising:

a. a vessel wall penetrating catheter that comprises i) a catheter body that is insertable into a blood vessel lumen of the patient and ii) a vessel wall penetrating member having a penetrator lumen extending longitudinally therethrough, said penetrating member extending from the catheter body positioned within the blood vessel lumen to a target site located outside the blood vessel lumen; and

b. a delivery catheter having a catheter lumen extending longitudinally therethrough, said delivery catheter being advanceable through the penetrator lumen to the target site;

said vessel wall penetrating member being retractable into the catheter body and the vessel wall penetrating catheter being removable from the patient'"'"'s body such that the delivery catheter remains indwelling with the distal end of the delivery catheter located at the target site.

2. A system according to claim 1 wherein the vessel wall penetrating catheter further comprises iii) a guidance element useable by the operator to position the vessel wall penetrating catheter body within the blood vessel lumen 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 target site, which is located outside the blood vessel lumen.

3. A system according to claim 2 wherein the guidance element comprises an imaging apparatus.

4. A system according to claim 3 wherein the imaging apparatus is an ultrasound imaging apparatus.

5. A system according to claim 2 wherein the guidance element comprises an imageable marker on the vessel wall penetrating catheter body.

6. A system according to claim 2 wherein the guidance element comprises the combination of an imaging apparatus and at least one imageable marker that is imageable by the imaging apparatus.

7. A system 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.

8. A system according to claim 1 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.

9. A system according to claim 8 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.

10. A system according to claim 9 wherein the selectively permeable barrier is a balloon attached to the delivery catheter such that substances infused through the lumen of the delivery catheter collect within the balloon and subsequently diffuse outwardly through the balloon.

11. A system according to claim 8 wherein the matter blocking member comprises a stylet that is insertable into the lumen of the delivery catheter to block the entry of extraneous matter thereinto.

12. A system according to claim 11 wherein the stylet is removable from the lumen of the delivery catheter to permit delivery of a substance or apparatus through the delivery catheter.

13. A system according to claim 1 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) an infusion 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.

14. A system according to claim 12 wherein a plurality of outflow apertures are formed in the sidewall of the first tube.

15. A system according to claim 1 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) an infusion 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.

16. A system according to claim 15 wherein a plurality of outflow apertures are formed in the sidewall of the tube.

17. A system according to claim 15 wherein the obturator member is an inflatable balloon that assumes said blocking position when inflated and said infusion position when deflated.

18. A system according to claim 1 wherein the delivery catheter comprises an infusion lumen, a return lumen, an outflow aperture through which infused substances may flow out of the infusion lumen and a flow diverter, said flow diverter that is alternately deployable in i) an infusion position whereby substances infused through the infusion lumen will flow out of the outflow aperture and ii) a recirculation position whereby fluid infused through the infusion lumen will be recirculated back through the return lumen.

19. A system according to claim 1 wherein the delivery catheter comprises a pressure increasing outflow opening configured to cause an increase the pressure of fluids that are injected through the delivery catheter lumen and out of said pressure increasing outflow opening.

20. A system according to claim 19 wherein said pressure increasing outflow opening is formed in the side wall of the delivery catheter.

21. A system according to claim 20 wherein a plurality of pressure increasing outflow openings are formed in the side wall of the delivery catheter.

22. A system according to claim 1 wherein the delivery catheter further comprises an anchoring member for anchoring the catheter in a substantially fixed position within the patient'"'"'s body.

23. A system according to claim 22 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.

24. A system according to claim 1 wherein the delivery catheter further comprises a backflow deterrent member for blocking backflow of substances that have been injected through the delivery catheter.

25. A system according to claim 24 wherein said backflow deterrent member comprises a backflow barrier rib formed on the delivery catheter.

26. A system according to claim 25 wherein said backflow barrier comprises an inflatable balloon on the delivery catheter.

27. A system according to claim 25 wherein said backflow barrier comprises a raised projection formed on the exterior of the delivery catheter.

28. A system according to claim 27 wherein the raised projection comprises an annular rib formed about the outer surface of the delivery catheter.

29. A system according to claim 24 wherein the backflow deterrent comprises a sealant that is implanted prior to or concurrently with removal of the delivery catheter so as to prevent the injected substance from bacflowing through the tract from which the delivery catheter is removed.

30. A system according to claim 29 wherein the sealant comprises a quantity of a flowable sealant injected into the tract upon removal of the delivery catheter.

31. A system according to claim 29 wherein the sealant comprises a detachable sealing member.

32. A system according to claim 31 wherein the detachable sealing member is formed of biodegradable material.

33. A system according to claim 32 wherein the sealing member is a collagen sponge.

34. A system according to claim 32 wherein the sealing member is a hydrogel sponge.

35. A system according to claim 1 wherein at least a portion of the delivery catheter is coated with an adhesive.

36. A system according to claim 1 wherein an anti-microbial substance is disposed on at least a portion of the delivery catheter.

37. A system according to claim 1 wherein an anti-coagulant substance is disposed on at least a portion of the delivery catheter.

38. A system according to claim 1 further comprising apparatus for creating 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.

39. A system according to claim 38 wherein the apparatus for creating a pocket comprises an energy emitting member that emits energy into adjacent tissue to create said pocket.

40. A system according to claim 39 wherein the energy emitting apparatus is a radiofrequency electrode.

41. A system according to claim 39 wherein the energy emitting apparatus is a laser.

42. A system according to claim 38 wherein the apparatus for creating a pocket comprises a nozzle through which a stream of fluid may be injected to create the pocket in adjacent tissue.

43. A system according to claim 38 wherein the apparatus for creating a pocket comprises an expandable cage which, when expanded, creates said pocket.

44. A system according to claim 1 further in combination with an infusion apparatus for infusing a substance through the delivery catheter.

45. A system according to claim 44 wherein said infusion apparatus is a syringe.

46. A system according to claim 44 wherein said infusion apparatus is a pump.

47. A system according to claim 44 wherein said infusion apparatus is a reservoir positioned for gravity drainage of the substance through the delivery catheter.

48. A system according to claim 44 wherein said infusion apparatus further comprises a quantity of a substance for infusion through the delivery catheter.

49. A system according to claim 48 wherein the substance is a drug.

50. A system according to claim 49 wherein the drug is selected from the group consisting of:

thrombolytics, platelet inhibitors, anti-restenotic agents, beta adrenergic blockers, ion channel antagonists, positive or negative ionotropic agents, anti-arrhythmics and combinations thereof.

51. A system according to claim 48 wherein the substance is a protein.

52. A system according to claim 48 wherein the substance is an angiogenic substance.

53. A system according to claim 51 wherein the angiogenic substance is selected from the group 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, and combinations thereof.

54. A system according to claim 48 wherein the substance comprises cells.

55. A system according to claim 54 wherein the substance comprises progenator cells for a type of cell that is desired to be formed at the target site.

56. A system according to claim 55 wherein said substance comprises myoblasts to form cardiac muscle cells.

57. A system according to claim 56 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.

58. A system according to claim 48 wherein the substance is a gene.

59. A system according to claim 48 wherein the substance comprises a gene and a vector for facilitating entry of the gene into locations within cells at which the gene will have a desired effect on the cells.

60. A system according to claim 59 wherein the vector is a virus.

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

(A) providing a vessel wall penetrating catheter that is insertable into a blood vessel of the patient, said vessel wall penetrating catheter having a catheter body and 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 penetrator lumen extending longitudinally therethrough;

(B) inserting the vessel wall penetrating catheter into a blood vessel lumen of the patient;

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

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

(E) advancing through the lumen of the penetrating member 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; and

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

62. A method according to claim 61 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 blood vessel lumen 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 target site, which is located outside the blood vessel lumen, and wherein Step C further comprises using said guidance element to position the vessel wall penetrating catheter body within the blood vessel lumen 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 target site.

63. A method according to claim 62 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.

64. A method according to claim 63 wherein the imaging apparatus is an ultrasound imaging apparatus and the image used in Step C is an ultrasound image.

65. A method according to claim 62 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.

66. A method according to claim 65 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.

67. A method according to claim 66 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.

68. A method according to claim 62 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.

69. A method according to claim 61 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:

(F) delivering a substance through the delivery catheter to the target site.

70. A method according to claim 69 wherein the delivery catheter is a microcatheter having an outer diameter of less than 0.5 mm.

71. A method according to claim 69 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.

72. A method according to claim 71 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.

73. A method according to claim 71 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.

74. A method according to claim 71 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.

75. A method according to claim 74 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.

76. A method according to claim 69 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.

77. A method according to claim 71 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.

78. A method according to claim 77 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.

79. A method according to claim 69 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.

80. A method according to claim 69 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.

81. A method according to claim 69 wherein the substance delivered in Step F is a therapeutic substance.

82. A method according to claim 69 wherein the substance delivered in Step F is a agent that provides an enhanced image of the target site.

83. A method according to claim 69 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.

84. A method according to claim 81 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.

85. A method according to claim 81 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.

86. A method according to claim 85 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.

87. A method according to claim 81 wherein the therapeutic substance delivered in Step F comprises cells.

88. A method according to claim 87 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.

89. A method according to claim 87 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.

90. A method according to claim 89 wherein the method is carried out to treat a condition characterized by a lack of living myocytes iin or near the target site and wherein the therapeutic substance delivered in Step F comprises myocytes.

91. A method according to claim 89 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.

92. A method according to claim 91 wherein the dopamine secreting cells comprise fetal dopamine secreting cells.

93. A method according to claim 89 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.

94. A method according to claim 93 wherein the insulin secreting cells comprise pancreatic β

islet cells.

95. A method according to claim 81 wherein the method is carried out to treat a neurogenerative disorder and wherein the substance delivered comprises nerve cells.

96. A method according to claim 81 wherein the method is carried out to treat a neurogenerative disorder and wherein the substance delivered comprises a substance that facilitates nerve growth.

97. A method according to claim 96 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.

98. A method according to claim 81 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.

99. A method according to claim 98 wherein the vector is a virus.

100. A method according to claim 61 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:

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

101. A method according to claim 100 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.

102. A method according to claim 61 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.

103. A method according to claim 102 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.

104. A method according to claim 103 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.

105. A method according to claim 102 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.

106. A method according to claim 105 wherein the raised projection comprises an annular rib formed about the outer surface of the delivery catheter.

107. A method according to claim 102 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 bacflowing through that tract, and wherein Step F of the method comprises implanting the sealant into the penetration tract.

108. A method according to claim 107 wherein the sealant is implanted into the tract prior to removal of the delivery catheter.

109. A method according to claim 107 wherein the sealant is implanted into the tract prior concurrently with removal of the delivery catheter.

110. A method according to claim 107 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.

111. A method according to claim 110 wherein the injecting of the flowable sealant into the penetration tract comprises injecting the flowable sealant through the delivery catheter.

112. A method according to claim 107 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.

113. A method according to claim 112 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.

114. A method according to claim 112 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.

115. A method according to claim 112 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.

116. A method according to claim 61 wherein at least a portion of the second apparatus is coated with an adhesive and wherein the method further comprises the step of:

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

117. A method according to claim 61 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:

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

118. A method according to claim 61 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:

(F) 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.

119. A method according to claim 69 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.

120. A method according to claim 119 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.

121. A method according to claim 120 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.

122. A method according to claim 120 wherein the energy emitting apparatus is a laser.

123. A method according to claim 119 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.

124. A method according to claim 119 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.

125. A method according to claim 61 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:

(F) using the therapeutic apparatus to deliver therapy to the target site.

126. A system for delivery of a substance to a target site located a spaced distance from a blood vessel within the body of a human or animal patient, said system comprising:

a vessel wall penetrating catheter that has a vessel wall penetrator advanceable therefrom, said vessel wall penetrating catheter being insertable into the vasculature and positionable in the blood vessel near the target site and said penetrator being thereafter advanceable from the catheter and trough the wall of the blood vessel in the direction of the target site;

a delivery catheter that is advanceable through the penetrator and to the target site, said delivery catheter being of sufficient length and constructed such that, after the delivery catheter has been advanced through the penetrator and to the target site, 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 such that the delivery catheter extends through the patient'"'"'s vasculature into the blood vessel near the target site, outwardly through the wall of the blood vessel and to the target site.

127. A system according to claim 126 wherein the delivery catheter comprises a hub member that is a) not attached to the proximal end of the delivery catheter while the vessel wall penetrating catheter is being withdrawn and removed and b) attached to the proximal end of the delivery catheter after the vessel wall penetrating catheter has been withdrawn and removed.

128. A system according to claim 126 wherein the delivery catheter further comprises at least one anchoring element for holding the delivery at the target site.

129. A system according to claim 127 wherein the delivery catheter further comprises a barrier for deterring substances injected through the delivery catheter from backflowing around the delivery catheter through the tissue tract through which the delivery catheter extends from the blood vessel to the target site.

130. A system according to claim 126 wherein the delivery catheter further comprises apparatus for preventing cellular ingrowth and other matter from obstructing the lumen of the delivery catheter.

131. A system according to claim 126 wherein the vessel wall penetrating catheter further comprises a guidance element that facilitates positioning and orientation of the vessel wall penetrating catheter within the blood vessel such that, then the penetrator is subsequently advanced from the vessel wall penetrating catheter, the penetrator will travel substantially toward the target site.

137. A system according to claim 126 wherein the vessel wall penetrating catheter further comprises a guidance element that facilitates positioning and orientation of the vessel wall penetrating catheter within the blood vessel such that, then the penetrator is subsequently advanced from the vessel wall penetrating catheter, the penetrator will travel substantially toward the target site and wherein the method further comprises the step of:

using the guidance element to position and orient the vessel wall penetrating catheter in the blood vessel prior to performance of Step C such that when Step C is subsequently performed, the penetrator will travel through the blood vessel wall substantially in the direction of the target site.

132. A method for delivery of substances or apparatus to a target site located a spaced distance from a blood vessel within the body of a human or animal patient, said method comprising the steps of:

(A) Inserting a vessel wall penetrating catheter into the vasculature of the patient, said vessel wall penetrating catheter having a penetrator advanceable therefrom;

(B) positioning the vessel wall penetrating catheter in the blood vessel near the target site;

(C) advancing the penetrator from the vessel wall penetrating catheter and through the wall of the blood in the direction of the target site;

(D) advancing a delivery catheter through the penetrator and to the target site;

(E) retracting the penetrator into the vessel wall penetrating catheter; and

,

(F) withdrawing and removing the vessel wall penetrating catheter, leaving the delivery catheter indwelling such that it extends through the patient'"'"'s vasculature into the blood vessel near the target site, outwardly through the wall of the blood vessel and to the target site.

133. A method according to claim 132 wherein the delivery catheter comprises a hub member that is a) not attached to the proximal end of the delivery catheter while the vessel wall penetrating catheter is being withdrawn and removed and b) attached to the proximal end of the delivery catheter after the vessel wall penetrating catheter has been withdrawn and removed, and wherein the method further comprises the steps of:

causing the hub member to be detached from the delivery catheter while the vessel wall penetrating catheter is being withdrawn and removed in Step F; and

,

causing the hub member to be attached to the proximal end of the delivery catheter after the vessel wall penetrating catheter has been withdrawn and removed in Step F.

134. A method according to claim 132 wherein the delivery catheter further comprises at least one anchoring element for holding the delivery at the target site and wherein the method further comprises:

causing the anchoring element to hold the delivery catheter at the target site at least after Step F has been performed.

135. A method according to claim 132 wherein the delivery catheter further comprises a barrier for deterring substances injected through the delivery catheter from backflowing around the delivery catheter through the tissue tract through which the delivery catheter extends from the blood vessel to the target site and wherein the method further comprises:

causing the barrier to deter substances injected through the delivery catheter from backflowing around the delivery catheter through the tissue tract through which the delivery catheter extends from the blood vessel to the target site.

136. A system according to claim 132 wherein the delivery catheter further comprises apparatus for preventing cellular ingrowth and other matter from obstructing the lumen of the delivery catheter and wherein the method further comprises the step of:

causing the apparatus for preventing cellular ingrowth and other matter from obstructing the lumen of the delivery catheter to prevent cellular ingrowth or other matter from obstructing the lumen of the delivery catheter.