WO2000067647A1 - Injection array apparatus and method - Google Patents

Injection array apparatus and method Download PDF

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Publication number
WO2000067647A1
WO2000067647A1 PCT/US2000/011274 US0011274W WO0067647A1 WO 2000067647 A1 WO2000067647 A1 WO 2000067647A1 US 0011274 W US0011274 W US 0011274W WO 0067647 A1 WO0067647 A1 WO 0067647A1
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WO
WIPO (PCT)
Prior art keywords
tubular member
injection
lumen
fluid
distal end
Prior art date
Application number
PCT/US2000/011274
Other languages
French (fr)
Inventor
Maria Palasis
Original Assignee
Boston Scientific Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boston Scientific Limited filed Critical Boston Scientific Limited
Priority to JP2000616680A priority Critical patent/JP2002543868A/en
Priority to DE60025345T priority patent/DE60025345T2/en
Priority to AU46687/00A priority patent/AU4668700A/en
Priority to CA002373034A priority patent/CA2373034C/en
Priority to EP00928446A priority patent/EP1176914B1/en
Publication of WO2000067647A1 publication Critical patent/WO2000067647A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/32Surgical cutting instruments
    • A61B17/3205Excision instruments
    • A61B17/3207Atherectomy devices working by cutting or abrading; Similar devices specially adapted for non-vascular obstructions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0067Catheters; Hollow probes characterised by the distal end, e.g. tips
    • A61M25/0082Catheter tip comprising a tool
    • A61M25/0084Catheter tip comprising a tool being one or more injection needles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14Probes or electrodes therefor
    • A61B18/1477Needle-like probes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/00234Surgical instruments, devices or methods, e.g. tourniquets for minimally invasive surgery
    • A61B2017/00238Type of minimally invasive operation
    • A61B2017/00243Type of minimally invasive operation cardiac
    • A61B2017/00247Making holes in the wall of the heart, e.g. laser Myocardial revascularization
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22072Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an instrument channel, e.g. for replacing one instrument by the other
    • A61B2017/22074Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an instrument channel, e.g. for replacing one instrument by the other the instrument being only slidable in a channel, e.g. advancing optical fibre through a channel
    • A61B2017/22077Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an instrument channel, e.g. for replacing one instrument by the other the instrument being only slidable in a channel, e.g. advancing optical fibre through a channel with a part piercing the tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22082Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00053Mechanical features of the instrument of device
    • A61B2018/00273Anchoring means for temporary attachment of a device to tissue
    • A61B2018/00291Anchoring means for temporary attachment of a device to tissue using suction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00315Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00345Vascular system
    • A61B2018/00351Heart
    • A61B2018/00392Transmyocardial revascularisation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14Probes or electrodes therefor
    • A61B2018/1405Electrodes having a specific shape
    • A61B2018/1425Needle
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2218/00Details of surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2218/001Details of surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body having means for irrigation and/or aspiration of substances to and/or from the surgical site
    • A61B2218/002Irrigation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0067Catheters; Hollow probes characterised by the distal end, e.g. tips
    • A61M25/0082Catheter tip comprising a tool
    • A61M25/0084Catheter tip comprising a tool being one or more injection needles
    • A61M2025/0085Multiple injection needles protruding axially, i.e. along the longitudinal axis of the catheter, from the distal tip
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0067Catheters; Hollow probes characterised by the distal end, e.g. tips
    • A61M25/0082Catheter tip comprising a tool
    • A61M25/0084Catheter tip comprising a tool being one or more injection needles
    • A61M2025/0093Catheter tip comprising a tool being one or more injection needles wherein at least one needle is a microneedle
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles

Definitions

  • the present invention generally relates to delivering and injecting fluid into heart tissue. More specifically, the present invention relates to delivering and injecting fluid into heart tissue utilizing an injection array.
  • Injection catheters may be used to inject therapeutic or diagnostic agents into a variety of organs, such as the heart.
  • 27 or 28 gauge needles are generally used to inject solutions carrying genes, proteins, or drugs directly into the myocardium.
  • a typical volume of an agent delivered to an injection site is about 100 microliters.
  • a limitation to this method of delivering therapeutic agents to the heart is that the injected fluid tends to leak and/or disperse from the site of the injection after the needle is disengaged from the heart. In fact, fluid may continue to leak over several seconds. In the case of dynamic organs such as the heart, there may be more pronounced leakage with each muscle contraction.
  • Therapeutic and diagnostic agents may be delivered to a portion of the heart as part of a percutaneous myocardial revascularization (PMR) procedure.
  • PMR percutaneous myocardial revascularization
  • Assuring that the heart muscle is adequately supplied with oxygen is critical to sustaining the life of a patient.
  • the heart muscle To receive an adequate supply of oxygen, the heart muscle must be well perfused with blood.
  • blood perfusion is accomplished with a system of blood vessels and capillaries. However, it is common for the blood vessels to become occluded (blocked) or stenotic (narrowed).
  • a stenosis may be formed by an atheroma which is typically a harder, calcified substance which forms on the walls of a blood vessel.
  • Coronary bypass surgery typically involves utilizing vascular tissue from another part of the patient's body to construct a shunt around the obstructed vessel.
  • Angioplasty techniques such as percutaneous transluminal angioplasty (PTA) and percutaneous transluminal coronary angioplasty (PTCA) are relatively non-invasive methods of treating a stenotic lesion.
  • PTA percutaneous transluminal angioplasty
  • PTCA percutaneous transluminal coronary angioplasty
  • These angioplasty techniques typically involve the use of a guide wire and a balloon catheter. In these procedures, a balloon catheter is advanced over a guide wire such that the balloon is positioned proximate a restriction in a diseased vessel.
  • a third technique which may be used to treat a stenotic lesion is atherectomy. During an atherectomy procedure, the stenotic lesion is mechanically cut or abraded away from the blood vessel wall.
  • Coronary by-pass, angioplasty, and atherectomy procedures have all been found effective in treating individual stenotic lesions in relatively large blood vessels.
  • the heart muscle is perfused with blood through a network of small vessels and capillaries.
  • a large number of stenotic lesions may occur in a large number of locations throughout this network of small blood vessels and capillaries.
  • the torturous path and small diameter of these blood vessels limit access to the stenotic lesions.
  • the sheer number and small size of these stenotic lesions make techniques such as cardiovascular by-pass surgery, angioplasty, and atherectomy impractical.
  • PMR percutaneous myocardial revascularization
  • a PMR procedure generally involves the creation of holes, craters or channels directly into the myocardium of the heart. In a typical PMR procedure, these holes are created using radio frequency energy delivered by a catheter having one or more electrodes near its distal end. After the wound has been created, therapeutic agents are sometimes ejected into the heart chamber from the distal end of a catheter.
  • PMR improves a patient's condition through denervation.
  • Denervation is the elimination of nerves.
  • the creation of wounds during a PMR procedure results in the elimination of nerve endings which were previously sending pain signals to the brain as a result of hibernating tissue.
  • the present invention provides an improved apparatus and method for delivering and injecting fluid into heart tissue, or other organ tissues such as liver tissue, bladder tissue, etc.
  • the present invention addresses the problems associated with retention of the fluid in the tissue by utilizing an injection array, such as a plurality of microneedles or a plurality of injection lumens.
  • the present invention may be used to deliver genes, proteins, or drugs directly into the myocardium for purposes of myocardial revascularization.
  • the present invention provides a fluid delivery system including an injection catheter disposed in an elongate sheath.
  • a fluid source is connected to the proximal end of the injection catheter and is in fluid communication with the lumen of the catheter.
  • a nozzle is disposed adjacent the distal end of the injection catheter.
  • the nozzle includes a plurality of microneedles each defining an injection lumen in fluid communication with the lumen of the catheter.
  • the nozzle defines a plurality of injection lumens in fluid communication with the lumen of the catheter.
  • the first embodiment may be referred to as the "microneedle” embodiment and the second embodiment may be referred to as the "needle-less" embodiment.
  • the microneedles may each have a diameter in the range of approximately 0.005 to 0.05 inches, and a penetrating length in the range of approximately 0.5 to 5 mm.
  • the injection lumens in the microneedle embodiment may have a diameter in the range of approximately 0.00005 to 0.005 inches.
  • the injection lumens in the needle-less embodiment may have a diameter in the range of approximately 0.00005 to 0.005 inches.
  • the injection lumens collectively form an injection array terminating in a plurality of injection orifices. Fluid is transferred to the injection lumen array from the fluid source through the lumen in the catheter.
  • the injection lumen array distributes the fluid at the injection site over a greater area than would otherwise be achieved with a single needle injection. Thus, the injection lumen array improves fluid retention in the tissue at the injection site.
  • the catheter and/or sheath may be equipped with an anchor disposed adjacent the distal end thereof.
  • the anchor may comprise a vacuum orifice in fluid communication with a vacuum source via a lumen in the catheter and/or sheath.
  • the vacuum orifice is adapted to stabilize the distal end of the injection catheter and/or the distal end of the sheath.
  • the sheath may include a hood portion disposed at its distal end.
  • the distal end of the injection catheter may be retracted within the hood of the sheath to reduce the probability that tissue damage will occur when the catheter is advanced through the vasculature of the patient.
  • the present invention also provides a method of delivering a fluid to heart tissue comprising the following steps.
  • An injection catheter substantially as described above is inserted into a patient's body and navigated to the desired target site, for example, heart tissue such as the myocardium.
  • the injection catheter may be navigated intravascularly or transthoracicly to the heart tissue.
  • a sheath substantially as described above may also be advanced until its distal end is proximate the target site.
  • the injection catheter is then advanced until the injection array is proximate the target tissue. Fluid is then urged out from the fluid source, through the lumen of the injection catheter, and into the heart tissue via the injection array.
  • the injection lumen array distributes the fluid at the target site over a greater area thereby increasing retention of fluid in the heart tissue at the injection site.
  • Approximately 0.1 to 20 microliters of fluid may be injected into the heart tissue via each injection lumen of the array. Due to the distribution of the injection array, a substantial amount if not all of the injected fluid is retained in the heart tissue.
  • Figure 1 is a perspective view of a fluid delivery system in accordance with the present invention
  • Figure 2 is a perspective view of a first (microneedle) embodiment of the distal end of the injection catheter for use with the fluid delivery system illustrated in Figure 1 ;
  • Figure 3 is a perspective view of a second (needle-less) embodiment of the distal end of the injection catheter for use with the fluid delivery system illustrated in Figure 1 ;
  • Figure 4 is a schematic view of the fluid delivery system and a human patient
  • Figure 5 is a perspective view of the distal end of the injection catheter incorporating an anchor for stabilization
  • Figure 6 is a schematic view of the fluid delivery system and a human patient utilizing an anchor for stabilization
  • Figure 7 is a cross sectional view of the distal portion of the fluid delivery system incorporating a hood, shown in the extended position;
  • Figure 8 is a cross sectional view of the fluid delivery system of Figure 7, shown in the retracted position.
  • FIG. 1 is a perspective view of a fluid delivery system 20 in accordance with the present invention.
  • fluid delivery system 20 includes a sheath 22 comprising an elongate tubular member 24 defining a sheath lumen 26.
  • Sheath 22 also includes a distal end 28 and a proximal end 30.
  • a hub 32 is disposed at proximal end 30 of sheath 22.
  • sheath 22 may be comprised of many materials without deviating from the spirit and scope of the present invention. Likewise, sheath 22 may be comprised of a single material, or a combination of materials.
  • sheath 22 may include an inner tube 34.
  • inner tube 34 is comprised of PTFE (polytetrafluoroethylene).
  • PTFE is a preferred material because it creates a smooth, low-friction surface for the passage of other devices through the sheath 22.
  • Sheath 22 may also include a support member 36 wound or braided around inner tube 34. In a presently preferred embodiment, support member 36 is comprised of a plurality of filaments 38.
  • Filaments 38 may be stainless steel wire.
  • support member 36 may be comprised of a woven polymer fabric.
  • support member 36 may be comprised of polymer fibers arranged in a braided pattern.
  • Sheath 22 may be comprised of polyether block amide (PEBA) using an extrusion process.
  • PEBA polyether block amide
  • Polyether block amide is commercially available from Atochem Polymers of Birdsboro, Pennsylvania under the trade name PEBAX.
  • molten PEBA is extruded onto the combined layers of inner tube 34 and support member 36. When this process is used, the extruded material fills interstitial spaces in support member 36.
  • Sheath 22 may also be comprised of other materials without departing from the spirit of scope of this invention. Examples of materials which may be suitable in some applications include: polyethylene (PE), polypropylene (PP), polyvinylchloride (PVC), polyurethane, and polytetrafluoroethylene (PTFE).
  • PE polyethylene
  • PP polypropylene
  • PVC polyvinylchloride
  • PTFE polytetrafluoroethylene
  • Fluid delivery system 20 also includes an injection catheter 40 which is slidingly disposed in sheath lumen 26 of sheath 22.
  • Injection catheter 40 includes an elongate tubular member 44 defining a lumen 46, a distal end 48, and a proximal end 50.
  • a fluid source 52 is releasably connected to the proximal end 50 of injection catheter 40.
  • Fluid source 52 is in fluid communication with lumen 46 of elongate tubular member 44.
  • Fluid source 52 is capable of injecting fluid 54 into lumen 46 of elongate tubular member 44.
  • fluid source 52 includes a variable volume chamber 56 in fluid communication with lumen 46 of elongate tubular member 44. Fluid source 52 further includes a plunger 58 slidingly disposed within variable volume chamber 56. Urging plunger 58 distally has the effect of urging fluid 54 into lumen 46 of elongate tubular member 44.
  • a number of energy sources may be utilized to urge plunger 58 distally. Energy sources which may be suitable in some applications include springs, compressed gas, electricity, and manual forces.
  • Fluid source 52 may alternatively comprise, for example, a conventional syringe or a high pressure injection system as disclosed in U.S. Patent No. 5,520,639 to Peterson et al. which is hereby incorporated by reference.
  • Elongate tubular member 44 is moveable between a retracted position and an extended position wherein the distal end 48 of the injection catheter 40 extends beyond the distal end 28 of sheath 22.
  • a plurality of microneedles 60 are disposed proximate the distal end 48 of injection catheter 40.
  • Each microneedle 60 defines an injection lumen 62 in fluid communication with lumen 46 of elongate tubular member 44.
  • Injection lumens 62 collectively form an injection lumen array 64.
  • FIG. 2 is a detailed perspective view of the distal end 48 of the injection catheter 40 illustrating the mircroneedle embodiment in detail.
  • a nozzle member 70 is disposed within lumen 46 proximate the distal end 48 of injection catheter 40.
  • the microneedles 60 are disposed on a distal surface 72 of nozzle member 70.
  • Microneedles 60 may be separate members inserted into holes defined in nozzle 70 or may be an integral part of nozzle 70.
  • Nozzle member 70 and microneedles 60 define a plurality of injection lumens 62.
  • Injection lumens 62 collectively form an injection lumen array 64.
  • Each injection lumen 62 is in fluid communication with lumen 46 of elongate tubular member 44.
  • microneedles 60 and nozzle member 70 are both comprised of silicon.
  • An example fabrication technique is described in U.S. Patent No. 5,697,901 to Eriksson, which is hereby incorporated by reference.
  • the microneedles 60 may each have a diameter in the range of approximately 0.005 to 0.05 inches, and a penetrating length in the range of approximately 0.5 to 5 mm.
  • the injection lumens 62 in the microneedles 60 may have a diameter in the range of approximately 0.00005 to 0.005 inches.
  • the microneedles 60 may be generally circular in cross section as shown. Those of skill in the art will appreciate that microneedles 60 may be other shapes without departing from the scope of the present invention.
  • Microneedles 60 and nozzle member 70 may be comprised of a variety of metallic and non-metallic materials.
  • metallic materials which may be suitable in some applications include stainless steel, and nickel-titanium alloys, although it is recognized that any suitable metal or alloy may be utilized.
  • non-metallic materials which may be suitable in some applications include silicon as described above and rigid polymers.
  • rigid polymers include: polycarbonate, poly(L-lactide) (PLLA), poly(D,L-lactide) (PLA), polyglycolide (PGA), poly(L-lactide-co-D,L-lactide) (PLLA/PLA), poly(L-lactide-co-glycolide) (PLLA/PGA), poly(D, L-lactide-co-glycolide) (PLA/PGA), poly(glycolide-co- trimethylene carbonate) (PGA PTMC), polyethylene oxide (PEO), polydioxanone (PDS), polycaprolactone (PCL), polyhydroxylbutyrate (PHBT), poly(phosphazene), polyD,L-lactide-co-caprolactone) (PLA/PCL), poly(glycolide-co-caprolactone) (PGA/PCL), polyanhydrides (PAN), poly(ortho esters), poly(phosphate ester), poly(amino acid), poly(hydroxy-
  • FIG. 3 is a perspective view of the distal end 48 of an alternative embodiment of an injection catheter 140 illustrating the needle-less embodiment.
  • Injection catheter 140 is the same in form and function as catheter 40 and may be used in a similar manner, except as described below.
  • injection catheter 140 includes an elongate tubular member 144 defining a lumen 146.
  • a nozzle member 170 is disposed within lumen 146 proximate distal end 148 of injection catheter 140.
  • Nozzle member 170 defines a plurality of injection lumens 162.
  • Injection lumens 162 collectively form an injection lumen array 164.
  • Each injection lumen 162 is in fluid communication with lumen 146 of elongate tubular member 144.
  • the injection lumens 162 may each have a diameter in the range of approximately 0.00005 to 0.005 inches.
  • Injection catheter 140 may be used in conjunction with the fluid delivery system 20 including the fluid source 52.
  • the fluid source 52 is disposed proximate the proximal end of injection catheter 140 and is in fluid communication with lumen 146 of elongate tubular member 144.
  • the fluid source 52 is capable of injecting fluid into lumen 146 of elongate tubular member 144 at high pressure.
  • the injection of fluid into lumen 146 of elongate tubular member 144 results in fluid 54 being ejected from injection lumens 162.
  • fluid is ejected from injection lumens 162 with a velocity which is sufficient to inject the fluid into tissue disposed proximate the distal end 148 of injection catheter 140. This technique is commonly referred to as needle-less injection.
  • a number of energy sources may be utilized to urge fluid into lumen 146 of elongate tubular member 144.
  • Energy sources which may be suitable in some applications include springs and compressed gas.
  • a high pressure system is utilized as described in U.S. Patent No. 5,697,901 to Eriksson, which is incorporated by reference.
  • FIG 4 is a schematic view of the fluid delivery system 20 and a patient 74.
  • Fluid delivery system 20 includes the injection catheter 40, the sheath 22, and the fluid source 52.
  • Injection catheter 140 may be used in place of an injection catheter 40.
  • An access catheter 80 is positioned with a distal end 88 thereof positioned within a blood vessel 76. Access catheter 80 aids in the introduction of sheath 22 into blood vessel 76.
  • Injection catheter 40/140 is disposed within lumen 26 of sheath 22.
  • the distal end 48 of injection catheter 40/140 is positioned within the heart 78 of patient 74.
  • a method of injecting a fluid into tissue of the heart 78 of patient 74 is described with reference to Figure 4.
  • the fluid delivery system 20 may be navigated intravascularly or transthoracicly to heart tissue, but is described with reference to an intravascular approach for purposes of illustration only.
  • Those of skill in the art will appreciate that the methods and devices of the present invention may be used to deliver therapeutic and/or diagnostic agents to other areas of the body without departing from the spirit and scope of the invention.
  • devices and methods in accordance with the present invention may be used to deliver fluid agents to esophageal varicies or to ulcers in the stomach lining.
  • the distal end of fluid delivery system 20 may enter the patient's vasculature at a convenient location such as a blood vessel in the neck or near the groin. Ideally, the distal end of fluid delivery system 20 will be atraumatic to reduce the probability that vascular tissues will be damaged as the catheter is advanced through the vascular system. To prevent damage to the vasculature, the distal end of injection catheter 40/140 may be retracted into lumen 26 of sheath 22.
  • the physician may urge distal end 28 of sheath 22 forward by applying longitudinal forces to hub 32 of sheath 22.
  • the path taken by sheath 22 through the vascular system is tortuous requiring sheath 22 to change direction frequently.
  • the physician may apply torsional forces to the hub 32 to aid in steering sheath 22.
  • the distal portion of sheath 22 may include a plurality of bends or curves. In some embodiments, it may be desirable to include a distal portion of sheath 22 which can be heated and bent to a desired shape, then allowed to cool.
  • radiopaque contrast solution may be dispensed from distal end 28 of sheath 22 to enhance fluoroscopic visualization.
  • radiopaque contrast solution is urged through lumen 26 of sheath 22.
  • Sheath 22 and injection catheter 40/140 may also include radiopaque markers.
  • a radiopaque marker is a band of radiopaque material disposed proximate the distal end of injection catheter 40/140 and/or sheath 22. Radiopaque bands of this type aid the physician in determining the location of the distal end of the device relative to the patient's anatomy.
  • the radiopaque band may be comprised of a number of materials.
  • radiopaque filler examples include barium sulfate, bismuth subcarbonate, bismuth trioxide, bismuth oxychloride, bismuth subcarbonate, tungsten powder, and depleted uranium.
  • injection catheter 40/140 may be advanced so that nozzle member 70 contacts the bodily tissue at the target site. If injection catheter 40 with mircroneedles 60 is used, the microneedles 60 are advanced to penetrate the heart tissue. If injection catheter 140 with injection lumens 162 is used, the distal end of the injection array 164 is positioned adjacent the heart tissue surface. Force may then be applied to plunger 58 urging fluid out of fluid source 52 and into lumen 46/146 of injection catheter 40/140. The addition of fluid from fluid source 52 results in the injection of fluid into the target tissue via the injection array 64/164. The total fluid injected into the target tissue may be referred to as a dose.
  • the dose is more readily retained in the heart tissue by utilizing the injection array 64/164.
  • a portion of the dose is dispensed from each injection lumen 62/162.
  • the volume of fluid dispensed from each injection lumen 62/162 may be pre-selected.
  • the pre-selected volume dispensed from each injection lumen may be a volume which can be rapidly absorbed and/or retained by the target tissue.
  • a dose of 100 microliters may be delivered via the injection array 64/164.
  • the volume of fluid injected by each microneedle or injection lumen may be 0.1 to 20 microliters.
  • a low volume (several microliters but less than 100 microliters by a single injection) of solution is delivered to the heart such that it may absorb the delivered solution within the time frame of the injection.
  • the heart is more capable of absorbing these low volumes.
  • the effect of the low volume injection is to minimize expulsion by the tissue.
  • it may be desirable or necessary to concentrate the injection i.e., deliver the same number of viral particles or micrograms of protein, typically delivered in lOO ⁇ l, in a volume of lO ⁇ l) or keep the concentration of virus the same as that typically used, but increase the number of injections from 10 (typical) to 20, 30, or more.
  • Each injectate may also be delivered in a prolonged manner such that the heart can absorb the solution as it is being injected (rate of delivery ⁇ rate of tissue absorption).
  • the injection can be delivered at a defined flow rate using a syringe pump.
  • the time of injection will depend on the volume to be delivered. For example, low volumes (a few microliters) may be delivered in under a minute while higher volumes (10 to lOO ⁇ l or more) may be delivered over several minutes. In this instance, it may be beneficial to include a method which gently attaches the injection catheter to the wall of the heart, for instance suction or vacuum.
  • the microneedles 60 may be left in the tissue for a period of time after the dose has been delivered to allow the fluid to be absorbed by the tissue.
  • the amount of time required for the fluid to be absorbed by the tissue will vary depending on the volume of fluid delivered and the absorption characteristics of the tissue.
  • the time period may be relatively short or prolonged, ranging, for example, from about 5 seconds to 2 minutes. Preferably, the time period ranges from about 5 seconds to about 30 seconds.
  • the fluid injected into the tissue at the target area may include any number of therapeutic or diagnostic agents.
  • therapeutic agents include genes, proteins, drugs, and caustic solutions.
  • a radiopaque solution is an example of a diagnostic agent. Radiopaque solution may be used to mark an area. For example, when performing PMR, it may be desirable to mark the locations of wound formation.
  • fluid may be injected into the myocardium either from the epicardial or endocardial surface.
  • the epicardial surface was accessed intravascularly by advancing a catheter through the vascular system.
  • Other methods of have been envisioned in which the endocardial surface of the heart is accessed using surgical techniques such as transthoracic minimally invasive surgery.
  • FIG. 5 is a perspective view of distal end 48 of an alternative embodiment of an injection catheter 240.
  • Injection catheter 240 is the same in form and function as injection catheter 40 and may be used in the same manner, except as described below.
  • Injection catheter 240 includes an elongate tubular member 244 defining a lumen 246.
  • a plurality of anchors 290 are disposed proximate distal end 248 of injection catheter 240. During a procedure to inject a therapeutic agent into body tissue, anchors 290 may be utilized to retain distal end 248 of injection catheter 240 proximate the targeted tissue.
  • each anchor 290 is comprised of a vacuum orifice 292.
  • each vacuum orifice 292 is in fluid communication with a vacuum lumen 294 defined by elongate tubular member 244.
  • anchors 290 are possible without deviating from the spirit or scope of the present invention.
  • each anchor 290 may be comprised of an elongate wire with a helix disposed proximate its distal end. The helical end of the elongate wire may be "threaded" into the heart wall by rotating the wire. Additional examples, of anchors 290 which may be appropriate in some applications include hooks and barbs.
  • a nozzle member 270 is disposed within lumen 246 proximate distal end 248 of injection catheter 240.
  • a plurality of microneedles 260 are disposed on a distal surface 272 of nozzle member 270.
  • Nozzle member 270 and microneedles 260 define a plurality of injection lumens 262.
  • Injection lumens 262 collectively form an injection lumen array 264. Each injection lumen 262 is in fluid communication with lumen 246 of injection catheter 240.
  • FIG. 6 is a schematic view of a fluid delivery system 220, including the injection catheter 240 of Figure 5. Except as described below, fluid system 220 is the same in form and function as fluid system 20 and may be used in a similar manner.
  • Fluid delivery system 220 includes the injection catheter 240, a sheath 222, a vacuum source 100, and a fluid source 252.
  • a hub 232 is disposed at proximal end 230 of sheath 222, and a multi-port adapter 296 is disposed at the proximal end of injection catheter 240.
  • Multi-port adapter 296 includes a plurality of ports 298.
  • Fluid source 252 is in fluid communication with one port 298 of multi-port adapter 296.
  • Vacuum source 100 is also in fluid communication with one port 298 of multi-port adapter 296.
  • An access catheter 280 positioned with a distal end 288 positioned within blood vessel 276. Access catheter 280 may aid in the introduction of sheath 222 into blood vessel 276.
  • Injection catheter 240 is disposed within lumen 226 of sheath 222. The distal end 248 of injection catheter 240 is positioned within the heart 278 of patient 274.
  • a method of injecting a fluid into heart 278 of patient 274 is described with reference to Figure 6.
  • Sheath 222 is introduced into the vasculature of the patient 274 and it is urged forward until it's distal tip is proximate the target tissue.
  • injection catheter 240 may be advanced so that nozzle member 270 contacts the bodily tissue at the target site.
  • Anchors 290 may then be activated to stabilize distal end 248 of injection catheter 240 during injection.
  • Each anchor 290 is comprised of a vacuum orifice 292 in fluid communication with a vacuum lumen 294.
  • anchors 290 are activated by applying vacuum from vacuum source 100 to vacuum orifices 292 via vacuum lumens 294 and multi-port adapter 296.
  • the vacuum orifaces apply suction to the surface of the tissue to stabilize the catheter 240 relative to the tissue.
  • FIG. 7 is a cross sectional view of the distal portion of an alternative embodiment of fluid delivery system 320. Except as described below, fluid delivery system 320 is the same in form and function as fluid delivery system 220, and may be used in a similar manner.
  • Fluid delivery system 320 includes a sheath 322 comprising an elongate tubular member 24 defining a lumen 326. Sheath 322 also includes a distal end 328 and a proximal end 330. In the embodiment of Figure 7, sheath 322 includes a hood portion 102 disposed proximate its distal end 28.
  • Fluid delivery system 320 also includes an injection catheter 340 which is slidingly disposed in lumen 326 of sheath 322.
  • Injection catheter 340 includes a distal end 348, a proximal end 350, and an elongate tubular member 344 defining a lumen 346.
  • a fluid source (not shown) is connected to proximal end 350 of injection catheter 340.
  • a nozzle 370 is disposed proximate the distal end 348 of injection catheter
  • Nozzle 370 includes a plurality or microneedles 360. Each microneedle 360 defines an injection lumen 362 in fluid communication with lumen 346 of elongate tubular member 344. Injection lumens 362 collectively form an injection lumen array 364. Sheath 322 and injection catheter 340 define an annular passage 108 disposed about injection catheter 340. Annular passage 108 terminates at an annular opening 1 10. Vacuum may be applied to annular passage 108 in order to anchor distal end 348 of injection catheter 340 to the bodily tissue at a desired target site. By doing so, the distal end of the sheath 322 and thus the distal end of the catheter 340 is stabilized relative to the heart tissue.
  • Figure 8 is a cross sectional view of the distal portion of the fluid delivery system 320 illustrated in Figure 7, shown in the retracted position.
  • the distal end of injection catheter 40 has been retracted within hood portion 102 of sheath 322.
  • the distal end 348 of injection catheter 340 is retracted within hood portion 102 of sheath 322 to reduce the probability that vascular damage will occur when fluid delivery system 320 is advanced through the vasculature of the patient.
  • the catheter 340 may be advanced to the extended position as shown in Figure 7.
  • the fluid injected into the target area may include any therapeutic or diagnostic agents needed to treat the medical condition which the physician is treating. It is to be appreciated that methods in accordance with the present invention may be used in the treatment of a number of medical conditions. For example, methods and devices of performing percutaneous myocardial revascularization (PMR) in accordance with the present invention have been envisioned.
  • PMR percutaneous myocardial revascularization
  • a PMR procedure involves creating a plurality of wounds in hibernating tissue of the heart. These wounds are created by injecting a fluid into the tissue of the heart. As a result of these wounds, there will be increased blood flow to the myocardium caused in part by the body's healing response to the wounds. One healing response of the body is sometimes referred to as angiogenisis. In addition to promoting increased blood flow, it is also believed that PMR improves a patient's condition through denervation. Denervation is the elimination of nerves. The creation of wounds during this procedure may result in the elimination of nerve endings which were previously sending pain signals to the brain as a result of hibernating tissue.
  • Suitable wounds may be created by injecting a fluid such as water or saline into the heart tissue. Wound formation and revascularization of myocardial tissue may enhanced by injecting a fluid including a therapeutic agent into the tissue of the heart. Examples, of therapeutic agents which may be suitable include growth factors, drugs and caustic agents.
  • the fluid injected into the heart tissue may also include a radiopaque material. Injecting a radiopaque material into the wound effectively marks the locations which have been treated. This will aid the physician in procedures which are being performed percutaneously using fluoroscopic equipment.
  • injection catheters 40/140/240/340 may be used in the treatment of a number of medical conditions.
  • injection catheters 40/140/240/340 may be used in the treatment of esophageal varicies, a condition where blood vessels of the esophagus are enlarged and may potentially burst.
  • the array of injection orifices is disposed proximate the enlarged varix and an appropriate agent is injected into the varix.
  • the agent may be a coagulant such as sodium morrhuate.
  • a coagulant When a coagulant is injected into a varix, it causes the occlusion thereof.
  • the medical devices of the present invention are useful for treating any mammalian tissue or organ.
  • tumors include tumors; organs including but not limited to the heart, lung, brain, liver, kidney, bladder, urethra and ureters, eye, intestines, stomach, pancreas, ovary, prostate; skeletal muscle; smooth muscle; breast, cartilage and bone.
  • therapeutic agents and “drugs” are used interchangeably herein and include pharmaceutically active compounds, cells, nucleic acids with and without carrier vectors such as lipids, compacting agents (such as histones), virus, polymers, proteins, and the like, with or without targeting sequences.
  • therapeutic agents used in conjunction with the present invention include, for example, proteins, ohgonucleotides, ribozymes, anti-sense genes, DNA compacting agents, gene/vector systems (i.e., anything that allows for the uptake and expression of nucleic acids), nucleic acids (including, for example, recombinant nucleic acids; naked DNA, cDNA, RNA; genomic DNA, cDNA or RNA in a non-infectious vector or in a viral vector which may have attached peptide targeting sequences; antisense nucleic acid (RNA or DNA); and DNA chimeras which include gene sequences and encoding for ferry proteins such as membrane translocating sequences ("MTS") and herpes simplex virus-1 ("VP22”)), and viral, liposomes and cationic polymers that are selected from a number of types depending on the desired application.
  • nucleic acids including, for example, recombinant nucleic acids; naked DNA, cDNA, RNA; genomic DNA, cDNA or
  • anti-thrombogenic agents such as heparin, heparin derivatives, urokinase, and PPACK (dextrophenylalanine proline arginine chloromethylketone); antioxidants such as probucol and retinoic acid; angiogenic and anti-angiogenic agents; agents blocking smooth muscle cell proliferation such as rapamycin, angiopeptin, and monoclonal antibodies capable of blocking smooth muscle cell proliferation; anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, acetyl salicylic acid, and mesalamine; calcium entry blockers such as verapamil, diltiazem and nifedipine; antineoplastic / antiproliferative / anti-mitotic agents such as paclitaxel, 5-fluorouracil, methotrexate, doxorubicin, daun
  • polynucleotide sequences useful in practice of the invention include DNA or RNA sequences having a therapeutic effect after being taken up by a cell.
  • therapeutic polynucleotides include anti-sense DNA and RNA; DNA coding for an anti-sense RNA; or DNA coding for tRNA or rRNA to replace defective or deficient endogenous molecules.
  • the polynucleotides of the invention can also code for therapeutic proteins or polypeptides.
  • a polypeptide is understood to be any translation product of a polynucleotide regardless of size, and whether glycosylated or not.
  • Therapeutic proteins and polypeptides include as a primary example, those proteins or polypeptides that can compensate for defective or deficient species in an animal, or those that act through toxic effects to limit or remove harmful cells from the body.
  • the polypeptides or proteins useful in the present invention include, without limitation, angiogenic factors and other molecules competent to induce angiogenesis, including acidic and basic fibroblast growth factors, vascular endothelial growth factor, hif-1, epidermal growth factor, transforming growth factor ⁇ and ⁇ , platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor ⁇ , hepatocyte growth factor and insulin like growth factor; growth factors; cell cycle inhibitors including CDK inhibitors; anti-restenosis agents, including pl5, pl6, pl 8, pl9, p21, p27, p53, p57, Rb, nFkB and E2F decoys, thymidine kinase ("TK”) and combinations thereof and other agents useful for interfer
  • MCP-1 monocyte chemoattractant protein
  • BMP's the family of bone morphogenic proteins
  • the known proteins include BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16.
  • BMP's are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7.
  • dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules.
  • molecules capable of inducing an upstream or downstream effect of a BMP can be provided.
  • Such molecules include any of the "hedgehog" proteins, or the DNA's encoding them.
  • the present invention is also useful in delivering cells as the therapeutic agent.
  • Cells can be of human origin (autologous or allogeneic) or from an animal source (xenogeneic), genetically engineered if desired to deliver proteins of interest at a delivery or transplant site.
  • the delivery media is formulated as needed to maintain cell function and viability.

Abstract

A fluid delivery system for delivering and injecting fluid into heart tissue, or other organ tissues. The fluid delivery system includes an injection catheter disposed in an elongate sheath. A nozzle, including an injection array, is disposed adjacent the distal end of the injection catheter. In a first (microneedle) embodiment, the injection array comprises a plurality of microneedles each defining an injection lumen in fluid communication with the lumen of the catheter. In a second (needle-less) embodiment, the injection array comprises a plurality of injection lumens in fluid communication with the lumen of the catheter. Fluid is transferred to the injection lumen array from a fluid source through the lumen in the catheter. The injection lumen array distributes the fluid at the injection site over a greater area than would otherwise be achieved with a single needle injection. Thus, the injection lumen array improves fluid retention in the tissue at the injection site.

Description

INJECTION ARRAY APPARATUS AND METHOD
Related Applications This application claims the benefit of Provisional Patent Application Serial No. 60/133,122, filed May 7, 1999, entitled INCREASED EFFICIENCY DIRECT INJECTION OF THERAPEUTIC AGENTS, which is hereby incorporated by reference.
This application is related to co-pending Patent Application Serial No. 09/457,254, filed on even date herewith, entitled LATERAL NEEDLE INJECTION APPARATUS AND METHOD; co-pending Patent Application Serial No. 09/457,193, filed on even date herewith, entitled LATERAL NEEDLE-LESS INJECTION APPARATUS AND METHOD; and co-pending Patent Application Serial No. 09/456,456, filed on even date herewith, entitled NEEDLE-LESS INJECTION APPARATUS AND METHOD.
Field of the Invention The present invention generally relates to delivering and injecting fluid into heart tissue. More specifically, the present invention relates to delivering and injecting fluid into heart tissue utilizing an injection array.
Background of the Invention
Injection catheters may be used to inject therapeutic or diagnostic agents into a variety of organs, such as the heart. In the case of injecting a therapeutic agent into the heart, 27 or 28 gauge needles are generally used to inject solutions carrying genes, proteins, or drugs directly into the myocardium. A typical volume of an agent delivered to an injection site is about 100 microliters. A limitation to this method of delivering therapeutic agents to the heart is that the injected fluid tends to leak and/or disperse from the site of the injection after the needle is disengaged from the heart. In fact, fluid may continue to leak over several seconds. In the case of dynamic organs such as the heart, there may be more pronounced leakage with each muscle contraction.
Therapeutic and diagnostic agents may be delivered to a portion of the heart as part of a percutaneous myocardial revascularization (PMR) procedure. PMR is a procedure which is aimed at assuring that the heart is properly oxygenated. Assuring that the heart muscle is adequately supplied with oxygen is critical to sustaining the life of a patient. To receive an adequate supply of oxygen, the heart muscle must be well perfused with blood. In a healthy heart, blood perfusion is accomplished with a system of blood vessels and capillaries. However, it is common for the blood vessels to become occluded (blocked) or stenotic (narrowed). A stenosis may be formed by an atheroma which is typically a harder, calcified substance which forms on the walls of a blood vessel.
Historically, individual stenotic lesions have been treated with a number of medical procedures including coronary bypass surgery, angioplasty, and atherectomy. Coronary bypass surgery typically involves utilizing vascular tissue from another part of the patient's body to construct a shunt around the obstructed vessel. Angioplasty techniques such as percutaneous transluminal angioplasty (PTA) and percutaneous transluminal coronary angioplasty (PTCA) are relatively non-invasive methods of treating a stenotic lesion. These angioplasty techniques typically involve the use of a guide wire and a balloon catheter. In these procedures, a balloon catheter is advanced over a guide wire such that the balloon is positioned proximate a restriction in a diseased vessel. The balloon is then inflated and the restriction in the vessel is opened. A third technique which may be used to treat a stenotic lesion is atherectomy. During an atherectomy procedure, the stenotic lesion is mechanically cut or abraded away from the blood vessel wall.
Coronary by-pass, angioplasty, and atherectomy procedures have all been found effective in treating individual stenotic lesions in relatively large blood vessels. However, the heart muscle is perfused with blood through a network of small vessels and capillaries. In some cases, a large number of stenotic lesions may occur in a large number of locations throughout this network of small blood vessels and capillaries. The torturous path and small diameter of these blood vessels limit access to the stenotic lesions. The sheer number and small size of these stenotic lesions make techniques such as cardiovascular by-pass surgery, angioplasty, and atherectomy impractical.
When techniques which treat individual lesion are not practical, percutaneous myocardial revascularization (PMR) may be used to improve the oxygenation of the myocardial tissue. A PMR procedure generally involves the creation of holes, craters or channels directly into the myocardium of the heart. In a typical PMR procedure, these holes are created using radio frequency energy delivered by a catheter having one or more electrodes near its distal end. After the wound has been created, therapeutic agents are sometimes ejected into the heart chamber from the distal end of a catheter.
Positive clinical results have been demonstrated in human patients receiving PMR treatments. These results are believed to be caused in part by blood flowing within the heart chamber through channels in myocardial tissue formed by PMR. Increased blood flow to the myocardium is also believed to be caused in part by the healing response to wound formation. Specifically, the formation of new blood vessels is believed to occur in response to the newly created wound. This response is sometimes referred to as angiogenesis. After the wound has been created, therapeutic agents which are intended to promote angiogenesis are sometimes injected into the heart chamber. A limitation of this procedure is that the therapeutic agent may be quickly carried away by the flow of blood through the heart.
In addition to promoting increased blood flow, it is also believed that PMR improves a patient's condition through denervation. Denervation is the elimination of nerves. The creation of wounds during a PMR procedure results in the elimination of nerve endings which were previously sending pain signals to the brain as a result of hibernating tissue.
Currently available injection catheters are not particularly suitable for accurately delivering small volumes of therapeutic agents to heart tissue. Improved devices and methods are desired to address the problems associated with retention of the agent in the heart tissue as discussed above. This is particularly true for agents carrying genes, proteins, or other angiogenic drugs which may be very expensive, even in small doses.
Summary of the Invention The present invention provides an improved apparatus and method for delivering and injecting fluid into heart tissue, or other organ tissues such as liver tissue, bladder tissue, etc. The present invention addresses the problems associated with retention of the fluid in the tissue by utilizing an injection array, such as a plurality of microneedles or a plurality of injection lumens. The present invention may be used to deliver genes, proteins, or drugs directly into the myocardium for purposes of myocardial revascularization.
In an exemplary embodiment, the present invention provides a fluid delivery system including an injection catheter disposed in an elongate sheath. A fluid source is connected to the proximal end of the injection catheter and is in fluid communication with the lumen of the catheter. A nozzle is disposed adjacent the distal end of the injection catheter. In a first embodiment, the nozzle includes a plurality of microneedles each defining an injection lumen in fluid communication with the lumen of the catheter. In a second embodiment, the nozzle defines a plurality of injection lumens in fluid communication with the lumen of the catheter. The first embodiment may be referred to as the "microneedle" embodiment and the second embodiment may be referred to as the "needle-less" embodiment.
The microneedles may each have a diameter in the range of approximately 0.005 to 0.05 inches, and a penetrating length in the range of approximately 0.5 to 5 mm. The injection lumens in the microneedle embodiment may have a diameter in the range of approximately 0.00005 to 0.005 inches. Similarly, the injection lumens in the needle-less embodiment may have a diameter in the range of approximately 0.00005 to 0.005 inches. In both embodiments, the injection lumens collectively form an injection array terminating in a plurality of injection orifices. Fluid is transferred to the injection lumen array from the fluid source through the lumen in the catheter. The injection lumen array distributes the fluid at the injection site over a greater area than would otherwise be achieved with a single needle injection. Thus, the injection lumen array improves fluid retention in the tissue at the injection site.
Also in both embodiments, the catheter and/or sheath may be equipped with an anchor disposed adjacent the distal end thereof. The anchor may comprise a vacuum orifice in fluid communication with a vacuum source via a lumen in the catheter and/or sheath. The vacuum orifice is adapted to stabilize the distal end of the injection catheter and/or the distal end of the sheath.
The sheath may include a hood portion disposed at its distal end. The distal end of the injection catheter may be retracted within the hood of the sheath to reduce the probability that tissue damage will occur when the catheter is advanced through the vasculature of the patient. The present invention also provides a method of delivering a fluid to heart tissue comprising the following steps. An injection catheter substantially as described above is inserted into a patient's body and navigated to the desired target site, for example, heart tissue such as the myocardium. The injection catheter may be navigated intravascularly or transthoracicly to the heart tissue. A sheath substantially as described above may also be advanced until its distal end is proximate the target site. The injection catheter is then advanced until the injection array is proximate the target tissue. Fluid is then urged out from the fluid source, through the lumen of the injection catheter, and into the heart tissue via the injection array. The injection lumen array distributes the fluid at the target site over a greater area thereby increasing retention of fluid in the heart tissue at the injection site.
Less than approximately 100 microliters of fluid may be injected into the heart tissue via the injection array. Approximately 0.1 to 20 microliters of fluid may be injected into the heart tissue via each injection lumen of the array. Due to the distribution of the injection array, a substantial amount if not all of the injected fluid is retained in the heart tissue.
Brief Description of the Drawings Figure 1 is a perspective view of a fluid delivery system in accordance with the present invention;
Figure 2 is a perspective view of a first (microneedle) embodiment of the distal end of the injection catheter for use with the fluid delivery system illustrated in Figure 1 ;
Figure 3 is a perspective view of a second (needle-less) embodiment of the distal end of the injection catheter for use with the fluid delivery system illustrated in Figure 1 ;
Figure 4 is a schematic view of the fluid delivery system and a human patient; Figure 5 is a perspective view of the distal end of the injection catheter incorporating an anchor for stabilization; Figure 6 is a schematic view of the fluid delivery system and a human patient utilizing an anchor for stabilization;
Figure 7 is a cross sectional view of the distal portion of the fluid delivery system incorporating a hood, shown in the extended position; and
Figure 8 is a cross sectional view of the fluid delivery system of Figure 7, shown in the retracted position.
Detailed Description of the Invention The following detailed description should be read with reference to the drawings, in which like elements in different drawings are numbered identically. The drawings which are not necessarily to scale, depict selected embodiments and are not intended to limit the scope of the invention. Examples of constructions, materials, dimensions, and manufacturing processes are provided for various elements. Those skilled in the art will recognize that many of the examples provided have suitable alternatives which may be utilized.
Figure 1 is a perspective view of a fluid delivery system 20 in accordance with the present invention. In the embodiment of Figure 1 , fluid delivery system 20 includes a sheath 22 comprising an elongate tubular member 24 defining a sheath lumen 26. Sheath 22 also includes a distal end 28 and a proximal end 30. A hub 32 is disposed at proximal end 30 of sheath 22.
Those of skill in the art will appreciate that sheath 22 may be comprised of many materials without deviating from the spirit and scope of the present invention. Likewise, sheath 22 may be comprised of a single material, or a combination of materials. For example, sheath 22 may include an inner tube 34. In a presently preferred embodiment, inner tube 34 is comprised of PTFE (polytetrafluoroethylene). PTFE is a preferred material because it creates a smooth, low-friction surface for the passage of other devices through the sheath 22. Sheath 22 may also include a support member 36 wound or braided around inner tube 34. In a presently preferred embodiment, support member 36 is comprised of a plurality of filaments 38. Filaments 38 may be stainless steel wire. Those with skill in the art will appreciate that other embodiments of support member 36 are possible without deviating from the spirit and scope of the present invention. For example, support member 36 may be comprised of a woven polymer fabric. By way of a second example, support member 36 may be comprised of polymer fibers arranged in a braided pattern. Sheath 22 may be comprised of polyether block amide (PEBA) using an extrusion process. Polyether block amide is commercially available from Atochem Polymers of Birdsboro, Pennsylvania under the trade name PEBAX. In the extrusion process, molten PEBA is extruded onto the combined layers of inner tube 34 and support member 36. When this process is used, the extruded material fills interstitial spaces in support member 36.
It is to be understood that other manufacturing processes can be used without departing from the spirit and scope of the present invention. Sheath 22 may also be comprised of other materials without departing from the spirit of scope of this invention. Examples of materials which may be suitable in some applications include: polyethylene (PE), polypropylene (PP), polyvinylchloride (PVC), polyurethane, and polytetrafluoroethylene (PTFE).
Fluid delivery system 20 also includes an injection catheter 40 which is slidingly disposed in sheath lumen 26 of sheath 22. Injection catheter 40 includes an elongate tubular member 44 defining a lumen 46, a distal end 48, and a proximal end 50. A fluid source 52 is releasably connected to the proximal end 50 of injection catheter 40. Fluid source 52 is in fluid communication with lumen 46 of elongate tubular member 44. Fluid source 52 is capable of injecting fluid 54 into lumen 46 of elongate tubular member 44.
In the illustrated embodiment, fluid source 52 includes a variable volume chamber 56 in fluid communication with lumen 46 of elongate tubular member 44. Fluid source 52 further includes a plunger 58 slidingly disposed within variable volume chamber 56. Urging plunger 58 distally has the effect of urging fluid 54 into lumen 46 of elongate tubular member 44. A number of energy sources may be utilized to urge plunger 58 distally. Energy sources which may be suitable in some applications include springs, compressed gas, electricity, and manual forces. Fluid source 52 may alternatively comprise, for example, a conventional syringe or a high pressure injection system as disclosed in U.S. Patent No. 5,520,639 to Peterson et al. which is hereby incorporated by reference.
Elongate tubular member 44 is moveable between a retracted position and an extended position wherein the distal end 48 of the injection catheter 40 extends beyond the distal end 28 of sheath 22. A plurality of microneedles 60 are disposed proximate the distal end 48 of injection catheter 40. Each microneedle 60 defines an injection lumen 62 in fluid communication with lumen 46 of elongate tubular member 44. Injection lumens 62 collectively form an injection lumen array 64.
Figure 2 is a detailed perspective view of the distal end 48 of the injection catheter 40 illustrating the mircroneedle embodiment in detail. A nozzle member 70 is disposed within lumen 46 proximate the distal end 48 of injection catheter 40. The microneedles 60 are disposed on a distal surface 72 of nozzle member 70. Microneedles 60 may be separate members inserted into holes defined in nozzle 70 or may be an integral part of nozzle 70. Nozzle member 70 and microneedles 60 define a plurality of injection lumens 62. Injection lumens 62 collectively form an injection lumen array 64. Each injection lumen 62 is in fluid communication with lumen 46 of elongate tubular member 44.
One embodiment of injection catheter 40 has been envisioned in which microneedles 60 and nozzle member 70 are both comprised of silicon. An example fabrication technique is described in U.S. Patent No. 5,697,901 to Eriksson, which is hereby incorporated by reference. The microneedles 60 may each have a diameter in the range of approximately 0.005 to 0.05 inches, and a penetrating length in the range of approximately 0.5 to 5 mm. The injection lumens 62 in the microneedles 60 may have a diameter in the range of approximately 0.00005 to 0.005 inches. The microneedles 60 may be generally circular in cross section as shown. Those of skill in the art will appreciate that microneedles 60 may be other shapes without departing from the scope of the present invention. Examples of cross sectional shapes which may be suitable in some applications include oval, triangular, rectangular, square, and hexagonal. Microneedles 60 and nozzle member 70 may be comprised of a variety of metallic and non-metallic materials. Examples of metallic materials which may be suitable in some applications include stainless steel, and nickel-titanium alloys, although it is recognized that any suitable metal or alloy may be utilized. Examples of non-metallic materials which may be suitable in some applications include silicon as described above and rigid polymers. Examples of rigid polymers include: polycarbonate, poly(L-lactide) (PLLA), poly(D,L-lactide) (PLA), polyglycolide (PGA), poly(L-lactide-co-D,L-lactide) (PLLA/PLA), poly(L-lactide-co-glycolide) (PLLA/PGA), poly(D, L-lactide-co-glycolide) (PLA/PGA), poly(glycolide-co- trimethylene carbonate) (PGA PTMC), polyethylene oxide (PEO), polydioxanone (PDS), polycaprolactone (PCL), polyhydroxylbutyrate (PHBT), poly(phosphazene), polyD,L-lactide-co-caprolactone) (PLA/PCL), poly(glycolide-co-caprolactone) (PGA/PCL), polyanhydrides (PAN), poly(ortho esters), poly(phosphate ester), poly(amino acid), poly(hydroxy butyrate), polyacrylate, polyacrylamid, poly(hydroxyethyl methacrylate), polyurethane, polysiloxane and their copolymers. Figure 3 is a perspective view of the distal end 48 of an alternative embodiment of an injection catheter 140 illustrating the needle-less embodiment. Injection catheter 140 is the same in form and function as catheter 40 and may be used in a similar manner, except as described below. As in the microneedle embodiment described previously, injection catheter 140 includes an elongate tubular member 144 defining a lumen 146. A nozzle member 170 is disposed within lumen 146 proximate distal end 148 of injection catheter 140. Nozzle member 170 defines a plurality of injection lumens 162. Injection lumens 162 collectively form an injection lumen array 164. Each injection lumen 162 is in fluid communication with lumen 146 of elongate tubular member 144. The injection lumens 162 may each have a diameter in the range of approximately 0.00005 to 0.005 inches.
Injection catheter 140 may be used in conjunction with the fluid delivery system 20 including the fluid source 52. The fluid source 52 is disposed proximate the proximal end of injection catheter 140 and is in fluid communication with lumen 146 of elongate tubular member 144. The fluid source 52 is capable of injecting fluid into lumen 146 of elongate tubular member 144 at high pressure. The injection of fluid into lumen 146 of elongate tubular member 144 results in fluid 54 being ejected from injection lumens 162. In the needle-less embodiment of Figure 3, fluid is ejected from injection lumens 162 with a velocity which is sufficient to inject the fluid into tissue disposed proximate the distal end 148 of injection catheter 140. This technique is commonly referred to as needle-less injection. A number of energy sources may be utilized to urge fluid into lumen 146 of elongate tubular member 144. Energy sources which may be suitable in some applications include springs and compressed gas. Preferably, a high pressure system is utilized as described in U.S. Patent No. 5,697,901 to Eriksson, which is incorporated by reference.
Figure 4 is a schematic view of the fluid delivery system 20 and a patient 74. Fluid delivery system 20 includes the injection catheter 40, the sheath 22, and the fluid source 52. Injection catheter 140 may be used in place of an injection catheter 40. An access catheter 80 is positioned with a distal end 88 thereof positioned within a blood vessel 76. Access catheter 80 aids in the introduction of sheath 22 into blood vessel 76. Injection catheter 40/140 is disposed within lumen 26 of sheath 22. The distal end 48 of injection catheter 40/140 is positioned within the heart 78 of patient 74.
A method of injecting a fluid into tissue of the heart 78 of patient 74 is described with reference to Figure 4. The fluid delivery system 20 may be navigated intravascularly or transthoracicly to heart tissue, but is described with reference to an intravascular approach for purposes of illustration only. Those of skill in the art will appreciate that the methods and devices of the present invention may be used to deliver therapeutic and/or diagnostic agents to other areas of the body without departing from the spirit and scope of the invention. For example, devices and methods in accordance with the present invention may be used to deliver fluid agents to esophageal varicies or to ulcers in the stomach lining.
The distal end of fluid delivery system 20 may enter the patient's vasculature at a convenient location such as a blood vessel in the neck or near the groin. Ideally, the distal end of fluid delivery system 20 will be atraumatic to reduce the probability that vascular tissues will be damaged as the catheter is advanced through the vascular system. To prevent damage to the vasculature, the distal end of injection catheter 40/140 may be retracted into lumen 26 of sheath 22.
Once the distal portion of fluid delivery system 20 has entered the patient's vascular system, the physician may urge distal end 28 of sheath 22 forward by applying longitudinal forces to hub 32 of sheath 22. Frequently, the path taken by sheath 22 through the vascular system is tortuous requiring sheath 22 to change direction frequently. While advancing sheath 22 through the torturous path of the patient's vasculature, the physician may apply torsional forces to the hub 32 to aid in steering sheath 22. To facilitate the steering process, the distal portion of sheath 22 may include a plurality of bends or curves. In some embodiments, it may be desirable to include a distal portion of sheath 22 which can be heated and bent to a desired shape, then allowed to cool.
To aid the physician in visualizing the vascular pathway, radiopaque contrast solution may be dispensed from distal end 28 of sheath 22 to enhance fluoroscopic visualization. In one method in accordance with the present invention, radiopaque contrast solution is urged through lumen 26 of sheath 22. Sheath 22 and injection catheter 40/140 may also include radiopaque markers. One example of a radiopaque marker is a band of radiopaque material disposed proximate the distal end of injection catheter 40/140 and/or sheath 22. Radiopaque bands of this type aid the physician in determining the location of the distal end of the device relative to the patient's anatomy. The radiopaque band may be comprised of a number of materials. Examples of materials which may be suitable in some applications include gold, platinum, tungsten, iron, silver, and thermoplastic material loaded with a radiopaque filler. Examples of radiopaque filler which may be suitable in some applications include barium sulfate, bismuth subcarbonate, bismuth trioxide, bismuth oxychloride, bismuth subcarbonate, tungsten powder, and depleted uranium.
Once distal end 28 of sheath 22 is positioned proximate the target site, injection catheter 40/140 may be advanced so that nozzle member 70 contacts the bodily tissue at the target site. If injection catheter 40 with mircroneedles 60 is used, the microneedles 60 are advanced to penetrate the heart tissue. If injection catheter 140 with injection lumens 162 is used, the distal end of the injection array 164 is positioned adjacent the heart tissue surface. Force may then be applied to plunger 58 urging fluid out of fluid source 52 and into lumen 46/146 of injection catheter 40/140. The addition of fluid from fluid source 52 results in the injection of fluid into the target tissue via the injection array 64/164. The total fluid injected into the target tissue may be referred to as a dose. The dose is more readily retained in the heart tissue by utilizing the injection array 64/164. A portion of the dose is dispensed from each injection lumen 62/162. The volume of fluid dispensed from each injection lumen 62/162 may be pre-selected. The pre-selected volume dispensed from each injection lumen may be a volume which can be rapidly absorbed and/or retained by the target tissue. By way of example, a dose of 100 microliters may be delivered via the injection array 64/164. The volume of fluid injected by each microneedle or injection lumen may be 0.1 to 20 microliters.
In an embodiment of the present invention, a low volume (several microliters but less than 100 microliters by a single injection) of solution is delivered to the heart such that it may absorb the delivered solution within the time frame of the injection. In contrast to higher volume injections, the heart is more capable of absorbing these low volumes. The effect of the low volume injection is to minimize expulsion by the tissue. In order to deliver the entire dose of virus, it may be desirable or necessary to concentrate the injection (i.e., deliver the same number of viral particles or micrograms of protein, typically delivered in lOOμl, in a volume of lOμl) or keep the concentration of virus the same as that typically used, but increase the number of injections from 10 (typical) to 20, 30, or more.
Each injectate may also be delivered in a prolonged manner such that the heart can absorb the solution as it is being injected (rate of delivery < rate of tissue absorption). For instance, the injection can be delivered at a defined flow rate using a syringe pump. The time of injection will depend on the volume to be delivered. For example, low volumes (a few microliters) may be delivered in under a minute while higher volumes (10 to lOOμl or more) may be delivered over several minutes. In this instance, it may be beneficial to include a method which gently attaches the injection catheter to the wall of the heart, for instance suction or vacuum.
If injection catheter 40 with mircroneedles 60 is used, the microneedles 60 may be left in the tissue for a period of time after the dose has been delivered to allow the fluid to be absorbed by the tissue. The amount of time required for the fluid to be absorbed by the tissue will vary depending on the volume of fluid delivered and the absorption characteristics of the tissue. The time period may be relatively short or prolonged, ranging, for example, from about 5 seconds to 2 minutes. Preferably, the time period ranges from about 5 seconds to about 30 seconds. When the mircroneedles 60 are subsequently withdrawn, leakage of the fluid from the tissue is further minimized or eliminated due to absorption thereof by the tissue.
The fluid injected into the tissue at the target area may include any number of therapeutic or diagnostic agents. Examples of therapeutic agents include genes, proteins, drugs, and caustic solutions. A radiopaque solution is an example of a diagnostic agent. Radiopaque solution may be used to mark an area. For example, when performing PMR, it may be desirable to mark the locations of wound formation.
Those of skill in the art will appreciate that when the organ being treated is the heart, fluid may be injected into the myocardium either from the epicardial or endocardial surface. In the exemplary embodiment of Figure 4, the epicardial surface was accessed intravascularly by advancing a catheter through the vascular system. Other methods of have been envisioned in which the endocardial surface of the heart is accessed using surgical techniques such as transthoracic minimally invasive surgery.
Figure 5 is a perspective view of distal end 48 of an alternative embodiment of an injection catheter 240. Injection catheter 240 is the same in form and function as injection catheter 40 and may be used in the same manner, except as described below. Injection catheter 240 includes an elongate tubular member 244 defining a lumen 246. A plurality of anchors 290 are disposed proximate distal end 248 of injection catheter 240. During a procedure to inject a therapeutic agent into body tissue, anchors 290 may be utilized to retain distal end 248 of injection catheter 240 proximate the targeted tissue. In the embodiment of Figure 5, each anchor 290 is comprised of a vacuum orifice 292. Each vacuum orifice 292 is in fluid communication with a vacuum lumen 294 defined by elongate tubular member 244. Other embodiments of anchors 290 are possible without deviating from the spirit or scope of the present invention. For example, each anchor 290 may be comprised of an elongate wire with a helix disposed proximate its distal end. The helical end of the elongate wire may be "threaded" into the heart wall by rotating the wire. Additional examples, of anchors 290 which may be appropriate in some applications include hooks and barbs.
In the embodiment of Figure 5, a nozzle member 270 is disposed within lumen 246 proximate distal end 248 of injection catheter 240. A plurality of microneedles 260 are disposed on a distal surface 272 of nozzle member 270. Nozzle member 270 and microneedles 260 define a plurality of injection lumens 262. Injection lumens 262 collectively form an injection lumen array 264. Each injection lumen 262 is in fluid communication with lumen 246 of injection catheter 240.
Figure 6 is a schematic view of a fluid delivery system 220, including the injection catheter 240 of Figure 5. Except as described below, fluid system 220 is the same in form and function as fluid system 20 and may be used in a similar manner. Fluid delivery system 220 includes the injection catheter 240, a sheath 222, a vacuum source 100, and a fluid source 252. A hub 232 is disposed at proximal end 230 of sheath 222, and a multi-port adapter 296 is disposed at the proximal end of injection catheter 240. Multi-port adapter 296 includes a plurality of ports 298. Fluid source 252 is in fluid communication with one port 298 of multi-port adapter 296. Vacuum source 100 is also in fluid communication with one port 298 of multi-port adapter 296. An access catheter 280 positioned with a distal end 288 positioned within blood vessel 276. Access catheter 280 may aid in the introduction of sheath 222 into blood vessel 276. Injection catheter 240 is disposed within lumen 226 of sheath 222. The distal end 248 of injection catheter 240 is positioned within the heart 278 of patient 274.
A method of injecting a fluid into heart 278 of patient 274 is described with reference to Figure 6. Sheath 222 is introduced into the vasculature of the patient 274 and it is urged forward until it's distal tip is proximate the target tissue. Once the distal end of the sheath is positioned proximate the target site, injection catheter 240 may be advanced so that nozzle member 270 contacts the bodily tissue at the target site. Anchors 290 may then be activated to stabilize distal end 248 of injection catheter 240 during injection. Each anchor 290 is comprised of a vacuum orifice 292 in fluid communication with a vacuum lumen 294. In this embodiment, anchors 290 are activated by applying vacuum from vacuum source 100 to vacuum orifices 292 via vacuum lumens 294 and multi-port adapter 296. The vacuum orifaces apply suction to the surface of the tissue to stabilize the catheter 240 relative to the tissue.
With distal end 248 of injection catheter 240 anchored, force may be applied to plunger 258 urging fluid out of fluid source 252 and into lumen 246 of injection catheter 240. The addition of fluid from fluid source 252 results in the injection of fluid into the target tissue via injection array 264.
Figure 7 is a cross sectional view of the distal portion of an alternative embodiment of fluid delivery system 320. Except as described below, fluid delivery system 320 is the same in form and function as fluid delivery system 220, and may be used in a similar manner. Fluid delivery system 320 includes a sheath 322 comprising an elongate tubular member 24 defining a lumen 326. Sheath 322 also includes a distal end 328 and a proximal end 330. In the embodiment of Figure 7, sheath 322 includes a hood portion 102 disposed proximate its distal end 28. Fluid delivery system 320 also includes an injection catheter 340 which is slidingly disposed in lumen 326 of sheath 322. Injection catheter 340 includes a distal end 348, a proximal end 350, and an elongate tubular member 344 defining a lumen 346. A fluid source (not shown) is connected to proximal end 350 of injection catheter 340. A nozzle 370 is disposed proximate the distal end 348 of injection catheter
340. Nozzle 370 includes a plurality or microneedles 360. Each microneedle 360 defines an injection lumen 362 in fluid communication with lumen 346 of elongate tubular member 344. Injection lumens 362 collectively form an injection lumen array 364. Sheath 322 and injection catheter 340 define an annular passage 108 disposed about injection catheter 340. Annular passage 108 terminates at an annular opening 1 10. Vacuum may be applied to annular passage 108 in order to anchor distal end 348 of injection catheter 340 to the bodily tissue at a desired target site. By doing so, the distal end of the sheath 322 and thus the distal end of the catheter 340 is stabilized relative to the heart tissue.
Figure 8 is a cross sectional view of the distal portion of the fluid delivery system 320 illustrated in Figure 7, shown in the retracted position. The distal end of injection catheter 40 has been retracted within hood portion 102 of sheath 322. The distal end 348 of injection catheter 340 is retracted within hood portion 102 of sheath 322 to reduce the probability that vascular damage will occur when fluid delivery system 320 is advanced through the vasculature of the patient. Upon positioning the system 320 at the target site, the catheter 340 may be advanced to the extended position as shown in Figure 7.
With all embodiments described herein, the fluid injected into the target area may include any therapeutic or diagnostic agents needed to treat the medical condition which the physician is treating. It is to be appreciated that methods in accordance with the present invention may be used in the treatment of a number of medical conditions. For example, methods and devices of performing percutaneous myocardial revascularization (PMR) in accordance with the present invention have been envisioned.
A PMR procedure involves creating a plurality of wounds in hibernating tissue of the heart. These wounds are created by injecting a fluid into the tissue of the heart. As a result of these wounds, there will be increased blood flow to the myocardium caused in part by the body's healing response to the wounds. One healing response of the body is sometimes referred to as angiogenisis. In addition to promoting increased blood flow, it is also believed that PMR improves a patient's condition through denervation. Denervation is the elimination of nerves. The creation of wounds during this procedure may result in the elimination of nerve endings which were previously sending pain signals to the brain as a result of hibernating tissue.
Suitable wounds may be created by injecting a fluid such as water or saline into the heart tissue. Wound formation and revascularization of myocardial tissue may enhanced by injecting a fluid including a therapeutic agent into the tissue of the heart. Examples, of therapeutic agents which may be suitable include growth factors, drugs and caustic agents. The fluid injected into the heart tissue may also include a radiopaque material. Injecting a radiopaque material into the wound effectively marks the locations which have been treated. This will aid the physician in procedures which are being performed percutaneously using fluoroscopic equipment.
As describe above, injection catheters 40/140/240/340 may be used in the treatment of a number of medical conditions. By way of an additional example, injection catheters 40/140/240/340 may be used in the treatment of esophageal varicies, a condition where blood vessels of the esophagus are enlarged and may potentially burst. For such a procedure, the array of injection orifices is disposed proximate the enlarged varix and an appropriate agent is injected into the varix. When treating an esophageal varice, the agent may be a coagulant such as sodium morrhuate. When a coagulant is injected into a varix, it causes the occlusion thereof. Although treatment of the heart is used as an example herein, the medical devices of the present invention are useful for treating any mammalian tissue or organ. Non-limiting examples include tumors; organs including but not limited to the heart, lung, brain, liver, kidney, bladder, urethra and ureters, eye, intestines, stomach, pancreas, ovary, prostate; skeletal muscle; smooth muscle; breast, cartilage and bone. The terms "therapeutic agents" and "drugs" are used interchangeably herein and include pharmaceutically active compounds, cells, nucleic acids with and without carrier vectors such as lipids, compacting agents (such as histones), virus, polymers, proteins, and the like, with or without targeting sequences.
Specific examples of therapeutic agents used in conjunction with the present invention include, for example, proteins, ohgonucleotides, ribozymes, anti-sense genes, DNA compacting agents, gene/vector systems (i.e., anything that allows for the uptake and expression of nucleic acids), nucleic acids (including, for example, recombinant nucleic acids; naked DNA, cDNA, RNA; genomic DNA, cDNA or RNA in a non-infectious vector or in a viral vector which may have attached peptide targeting sequences; antisense nucleic acid (RNA or DNA); and DNA chimeras which include gene sequences and encoding for ferry proteins such as membrane translocating sequences ("MTS") and herpes simplex virus-1 ("VP22")), and viral, liposomes and cationic polymers that are selected from a number of types depending on the desired application. Other pharmaceutically active materials include anti- thrombogenic agents such as heparin, heparin derivatives, urokinase, and PPACK (dextrophenylalanine proline arginine chloromethylketone); antioxidants such as probucol and retinoic acid; angiogenic and anti-angiogenic agents; agents blocking smooth muscle cell proliferation such as rapamycin, angiopeptin, and monoclonal antibodies capable of blocking smooth muscle cell proliferation; anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, acetyl salicylic acid, and mesalamine; calcium entry blockers such as verapamil, diltiazem and nifedipine; antineoplastic / antiproliferative / anti-mitotic agents such as paclitaxel, 5-fluorouracil, methotrexate, doxorubicin, daunorubicin, cyclosporine, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors; antimicrobials such as triclosan, cephalosporins, aminoglycosides, and nitorfurantoin; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; nitric oxide (NO) donors such as lisidomine, molsidomine, L- arginine, NO-protein adducts, NO-carbohydrate adducts, polymeric or oligomeric NO adducts; anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, enoxaparin, hirudin, Warafin sodium, Dicumarol, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet factors; vascular cell growth promotors such as growth factors, growth factor receptor antagonists, transcriptional activators, and translational promotors; vascular cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; cholesterol- lowering agents; vasodilating agents; agents which interfere with endogeneus vascoactive mechanisms; survival genes which protect against cell death, such as anti- apoptotic Bcl-2 family factors and Akt kinase; and combinations thereof. Examples of polynucleotide sequences useful in practice of the invention include DNA or RNA sequences having a therapeutic effect after being taken up by a cell. Examples of therapeutic polynucleotides include anti-sense DNA and RNA; DNA coding for an anti-sense RNA; or DNA coding for tRNA or rRNA to replace defective or deficient endogenous molecules. The polynucleotides of the invention can also code for therapeutic proteins or polypeptides. A polypeptide is understood to be any translation product of a polynucleotide regardless of size, and whether glycosylated or not. Therapeutic proteins and polypeptides include as a primary example, those proteins or polypeptides that can compensate for defective or deficient species in an animal, or those that act through toxic effects to limit or remove harmful cells from the body. In addition, the polypeptides or proteins useful in the present invention include, without limitation, angiogenic factors and other molecules competent to induce angiogenesis, including acidic and basic fibroblast growth factors, vascular endothelial growth factor, hif-1, epidermal growth factor, transforming growth factor α and β, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α, hepatocyte growth factor and insulin like growth factor; growth factors; cell cycle inhibitors including CDK inhibitors; anti-restenosis agents, including pl5, pl6, pl 8, pl9, p21, p27, p53, p57, Rb, nFkB and E2F decoys, thymidine kinase ("TK") and combinations thereof and other agents useful for interfering with cell proliferation, including agents for treating malignancies; and combinations thereof. Still other useful factors, which can be provided as polypeptides or as DNA encoding these polypeptides, include monocyte chemoattractant protein ("MCP-1"), and the family of bone morphogenic proteins ("BMP's"). The known proteins include BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMP's are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. Alternatively or, in addition, molecules capable of inducing an upstream or downstream effect of a BMP can be provided. Such molecules include any of the "hedgehog" proteins, or the DNA's encoding them.
The present invention is also useful in delivering cells as the therapeutic agent. Cells can be of human origin (autologous or allogeneic) or from an animal source (xenogeneic), genetically engineered if desired to deliver proteins of interest at a delivery or transplant site. The delivery media is formulated as needed to maintain cell function and viability.
Having thus described the preferred embodiments of the present invention, those of skill in the art will readily appreciate that yet other embodiments may be made and used within the scope of the claims hereto attached. Numerous advantages of the invention covered by this document have been set forth in the foregoing description. It will be understood, however, that this disclosure is, in many respects, only illustrative. Changes may be made in details, particularly in matters of shape, size, and arrangement of parts without exceeding the scope of the invention. The invention's scope is, of course, defined in the language in which the appended claims are expressed.

Claims

What is claimed is:
1. A catheter for delivering a fluid to an injection site in heart tissue, comprising: an elongate tubular member having a proximal end, a distal end, and a lumen extending therethrough; a nozzle member disposed proximate the distal end of the tubular member; and a plurality of microneedles connected to the nozzle member, the microneedles defining a plurality of injection lumens in fluid communication with the lumen of the tubular member.
2. A catheter as in claim 1, further comprising an anchor disposed proximate the distal end of the tubular member.
3. A catheter as in claim 1, further comprising an outer sheath having a proximal end, a distal end, and a lumen extending therethrough, the tubular member slidingly disposed in the lumen of the sheath.
4. A catheter as in claim 3, further comprising an anchor disposed proximate the distal end of the sheath.
5. A catheter as in claim 1, wherein each of the microneedles have a diameter in the range of approximately 0.005 to 0.05 inches.
6. A system for delivering a fluid to an injection site in heart tissue, comprising: a first tubular member having a proximal end, a distal end, and a lumen extending therethrough; a second tubular member having a proximal end, a distal end, and a lumen extending therethrough, the second tubular member slidingly disposed within the lumen of the first tubular member; a nozzle member disposed proximate the distal end of the second tubular member; the nozzle member including a plurality of microneedles, each microneedle defining an injection lumen in fluid communication with the lumen of the second tubular member, the lumen of each microneedle terminating with an injection orifice; and a fluid source in fluid communication with the lumen of the second tubular member.
7. A system as in claim 6, wherein an anchor is disposed proximate the distal end of the second tubular member.
8. A system as in claim 6, wherein an anchor is disposed proximate the distal end of the first tubular member.
9. A system as in claim 8, wherein the anchor comprises a vacuum orifice.
10. A system as in claim 9, wherein the vacuum orifice is in fluid communication with a vacuum source via the lumen of the second tubular member.
11. A system as in claim 6, wherein each of the microneedles have a diameter in the range of approximately 0.005 to 0.05 inches.
12. A method of delivering a fluid to an injection site in a patient's heart tissue, comprising the steps of: providing a first tubular member having a proximal end, a distal end, and a lumen extending therethrough; providing a second tubular member having a proximal end, a distal end, and a lumen extending therethrough, the second tubular member slidingly disposed within the lumen of the first tubular member, the second tubular member including a nozzle member disposed proximate the distal end thereof, the nozzle member including a plurality of microneedles, each microneedle defining an injection lumen in fluid communication with the lumen of the second tubular member, the lumen of each microneedle terminating with an injection orifice; inserting the first tubular member into the patient; advancing the first tubular member until the distal end thereof is proximate the injection site in the patient's heart tissue; advancing the second tubular member through the first tubular member until the plurality of injection orifices are proximate the injection site; urging the fluid from the fluid source to the lumen of second tubular member; and injecting the fluid into the heart tissue at the injection site via the microneedles.
13. A method of delivering a fluid as in claim 12, further including the step of stabilizing the distal end of the first tubular member relative to the target site.
14. A method of delivering a fluid as in claim 12, wherein the microneedles are advanced into the tissue and retained in the tissue for a period of time after the fluid has been injected into the tissue in order to allow the fluid to be absorbed by the tissue.
15. A method of delivering a fluid as in claim 14, wherein the period of time ranges from about 5 seconds to about 120 seconds.
16. A method of delivering a fluid as in claim 14, wherein the period of time ranges from about 5 seconds to about 30 seconds.
17. A catheter for delivering a fluid to an injection site in heart tissue, comprising: an elongate tubular member having a proximal end, a distal end, and a lumen extending therethrough; a nozzle member disposed proximate the distal end of the tubular member; and a plurality of injection lumens defined by the nozzle member, the injection lumens terminating with an injection orifice in fluid communication with the lumen of the tubular member.
18. A catheter as in claim 17, further comprising an outer sheath having a proximal end, a distal end, and a lumen extending therethrough, the tubular member slidingly disposed in the lumen of the sheath.
19. A catheter as in claim 18, further including an anchor disposed proximate the distal end of the sheath.
20. A catheter as in claim 19, wherein the anchor comprises a vacuum orifice defined by the lumen of the sheath adjacent the distal end thereof.
21. A catheter as in claim 17, wherein each of the injection lumens have a diameter in the range of approximately 0.00005 to 0.005 inches.
22. A system for delivering a fluid to an injection site in heart tissue, comprising: a first tubular member having a proximal end, a distal end, and a lumen extending therethrough; a second tubular member having a proximal end, a distal end, and a lumen extending therethrough, the second tubular member slidingly disposed within the lumen of the first tubular member; a nozzle member disposed proximate the distal end of the second tubular member; the nozzle member including a plurality of injection lumens in fluid communication with the lumen of the second tubular member, the injection lumens terminating with an injection orifice; and a fluid source in fluid communication with the lumen of the second tubular member.
23. A system as in claim 22, wherein an anchor is disposed proximate the distal end of the first tubular member.
24. A system as in claim 23, wherein an anchor is disposed proximate the distal end of the second tubular member.
25. A system as in claim 24, wherein the anchor comprises a vacuum orifice.
26. A system as in claim 25, wherein the vacuum orifice is in fluid communication with a vacuum source via the lumen of the second tubular member.
27. A system as in claim 22, wherein each of the injection lumens have a diameter in the range of approximately 0.00005 to 0.005 inches.
28. A method of delivering a fluid to an injection site in a patient's heart tissue, comprising the steps of: providing a first tubular member having a proximal end, a distal end, and a lumen extending therethrough; providing a second tubular member having a proximal end, a distal end, and a lumen extending therethrough, the second tubular member slidingly disposed within the lumen of the first tubular member, the second tubular member including a nozzle member disposed proximate the distal end thereof, the nozzle member including a plurality of injection lumens in fluid communication with the lumen of the second tubular member, each injection lumen terminating with an injection orifice; inserting the first tubular member into the patient; advancing the first tubular member until the distal end thereof is proximate the injection site in the patient's heart tissue; advancing the second tubular member through the first tubular member until the plurality of injection orifices are proximate the injection site; urging the fluid from the fluid source to the lumen of second tubular member; and injecting the fluid into the heart tissue at the injection site via the injection lumens.
29. A method as in claim 25, further including the step of stabilizing the distal end of the first tubular member relative to the target site.
PCT/US2000/011274 1999-05-07 2000-04-26 Injection array apparatus and method WO2000067647A1 (en)

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AU46687/00A AU4668700A (en) 1999-05-07 2000-04-26 Injection array apparatus and method
CA002373034A CA2373034C (en) 1999-05-07 2000-04-26 Injection array apparatus and method
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Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002024247A1 (en) * 2000-09-22 2002-03-28 Kensey Nash Corporation Drug delivering prostheses and methods of use
WO2002024248A1 (en) * 2000-09-22 2002-03-28 Kensey Nash Corporation Systems and methods for delivering beneficial agents into targeted tissue of a living being
WO2002024271A3 (en) * 2000-09-22 2002-06-27 Kensey Nash Corp Systems for delivering agents for revascularizing accluded blood vessels
WO2002083232A1 (en) * 2001-04-13 2002-10-24 Becton, Dickinson And Company Methods and devices for administration of substances into the intradermal layer of skin for systemic absorption
WO2002083231A1 (en) * 2001-04-13 2002-10-24 Becton, Dickinson And Company A method and device for delivery of high molecular weight substances
EP1393766A1 (en) * 2002-07-31 2004-03-03 BIOTRONIK Mess- und Therapiegeräte GmbH & Co Ingenieurbüro Berlin Endovascular implant for injecting a drug into the media of a blood vessel
WO2004064645A1 (en) * 2003-01-14 2004-08-05 Medtronic, Inc. Devices and methods for interstitial injection of biologic agents into tissue
WO2004093960A1 (en) 2003-03-20 2004-11-04 Boston Scientific Limited Devices for delivering therapeutic or diagnostic agents
EP1485151A1 (en) * 2002-02-26 2004-12-15 Bioject Medical Technologies Inc. End effector for needle-free injection system
WO2005092421A1 (en) * 2004-02-26 2005-10-06 Boston Scientific Limited Antimicrobial agent delivery system
EP1623734A1 (en) * 2003-05-06 2006-02-08 Asahi Intecc Co., Ltd. Medical liquid-injecting device
WO2006045809A1 (en) * 2004-10-25 2006-05-04 Coloplast A/S Male telescope catheter
US7048723B1 (en) * 1998-09-18 2006-05-23 The University Of Utah Research Foundation Surface micromachined microneedles
WO2006063180A2 (en) * 2004-12-09 2006-06-15 Ams Research Corporation Needleless delivery systems
EP1819379A2 (en) * 2004-11-18 2007-08-22 Nano Pass Technologies Ltd. System and method for delivering fluid into flexible biological barrier
WO2007136492A1 (en) * 2006-05-17 2007-11-29 Abbott Cardiovascular Systems Inc. Needle array devices and methods
US7396351B2 (en) 2003-11-05 2008-07-08 Boston Scientific Scimed, Inc. Device and method for the delivery of viscous fluids in the body
US7481798B2 (en) 2003-03-20 2009-01-27 Boston Scientific Scimed, Inc. Devices and methods for delivering therapeutic or diagnostic agents
US7534249B2 (en) 1996-07-26 2009-05-19 Kensey Nash Corporation System and method of use for agent delivery and revascularizing of grafts and vessels
EP2068975A2 (en) * 2006-08-08 2009-06-17 Peak Biosciences, Inc. Catheter and array for anticancer therapy
US7594900B1 (en) 1999-08-05 2009-09-29 Kensey Nash Corporation Systems and methods for delivering agents into targeted tissue of a living being
US7628780B2 (en) * 2001-01-13 2009-12-08 Medtronic, Inc. Devices and methods for interstitial injection of biologic agents into tissue
WO2009150594A1 (en) * 2008-06-11 2009-12-17 Koninklijke Philips Electronics N.V. Micro-jet injection device for local submucosal drug application
US7713232B2 (en) 2005-11-04 2010-05-11 Medrad, Inc. System for washing and processing of cells for delivery thereof to tissue
US7722595B2 (en) 2002-05-06 2010-05-25 Becton, Dickinson And Company Method and device for controlling drug pharmacokinetics
US7833239B2 (en) 1996-07-26 2010-11-16 Kensey Nash Corporation System and method of use for revascularizing stenotic bypass grafts and other blood vessels
US7838222B2 (en) 1999-07-26 2010-11-23 United States of America/ NIH Methods, devices and kits for multiplex blotting of biological samples from multi-well plates
US7981129B2 (en) 1996-07-26 2011-07-19 Kensey Nash Corporation System for opening a lumen in an occluded blood vessel
US8182444B2 (en) 2005-11-04 2012-05-22 Medrad, Inc. Delivery of agents such as cells to tissue
US8192787B2 (en) 2004-08-16 2012-06-05 Innoture Limited Method of producing a microneedle or microimplant
US8465468B1 (en) 2000-06-29 2013-06-18 Becton, Dickinson And Company Intradermal delivery of substances
US9814837B2 (en) 2006-11-21 2017-11-14 Astora Women's Health Holdings, Llc Injection tube for jet injection device
US9827367B2 (en) 2008-04-29 2017-11-28 Medtronic Xomed, Inc. Surgical instrument, system, and method for frontal sinus irrigation
US10058675B2 (en) 2009-09-21 2018-08-28 Cook Regentec Llc Infusion catheter tip for biologics with reinforced external balloon valve
US10155099B2 (en) 2009-09-21 2018-12-18 Cook Regentec Llc Method for infusing stem cells
US11129961B2 (en) 2015-05-13 2021-09-28 Hollister Incorporated Telescopic urinary catheter assemblies

Families Citing this family (122)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8092224B2 (en) * 1995-11-22 2012-01-10 James A. Jorasch Systems and methods for improved health care compliance
US7553234B2 (en) * 1995-11-22 2009-06-30 Walker Digital, Llc Method and apparatus for outputting a result of a game via a container
US6503231B1 (en) * 1998-06-10 2003-01-07 Georgia Tech Research Corporation Microneedle device for transport of molecules across tissue
US6689103B1 (en) * 1999-05-07 2004-02-10 Scimed Life System, Inc. Injection array apparatus and method
US6743211B1 (en) * 1999-11-23 2004-06-01 Georgia Tech Research Corporation Devices and methods for enhanced microneedle penetration of biological barriers
US6611707B1 (en) 1999-06-04 2003-08-26 Georgia Tech Research Corporation Microneedle drug delivery device
US6256533B1 (en) * 1999-06-09 2001-07-03 The Procter & Gamble Company Apparatus and method for using an intracutaneous microneedle array
US7479124B2 (en) * 1999-12-22 2009-01-20 Wisconsin Alumni Research Foundation Device for treatment of venous congestion
US8055509B1 (en) 2000-03-10 2011-11-08 Walker Digital, Llc Methods and apparatus for increasing and/or for monitoring a party's compliance with a schedule for taking medicines
US7366675B1 (en) 2000-03-10 2008-04-29 Walker Digital, Llc Methods and apparatus for increasing, monitoring and/or rewarding a party's compliance with a schedule for taking medicines
US7588554B2 (en) 2000-06-26 2009-09-15 Boston Scientific Scimed, Inc. Method and apparatus for treating ischemic tissue
US20040175360A1 (en) * 2000-06-29 2004-09-09 Pettis Ronald J. Method for altering drug pharmacokinetics based on medical delivery platform
US7108681B2 (en) 2000-10-16 2006-09-19 Corium International, Inc. Microstructures for delivering a composition cutaneously to skin
US7828827B2 (en) 2002-05-24 2010-11-09 Corium International, Inc. Method of exfoliation of skin using closely-packed microstructures
US6638246B1 (en) * 2000-11-28 2003-10-28 Scimed Life Systems, Inc. Medical device for delivery of a biologically active material to a lumen
WO2002064193A2 (en) * 2000-12-14 2002-08-22 Georgia Tech Research Corporation Microneedle devices and production thereof
US7740623B2 (en) * 2001-01-13 2010-06-22 Medtronic, Inc. Devices and methods for interstitial injection of biologic agents into tissue
US6663820B2 (en) * 2001-03-14 2003-12-16 The Procter & Gamble Company Method of manufacturing microneedle structures using soft lithography and photolithography
US6767341B2 (en) * 2001-06-13 2004-07-27 Abbott Laboratories Microneedles for minimally invasive drug delivery
US20040087992A1 (en) * 2002-08-09 2004-05-06 Vladimir Gartstein Microstructures for delivering a composition cutaneously to skin using rotatable structures
FR2830455B1 (en) * 2001-10-09 2004-06-25 Saphir Medical CATHETER WITH RETRACTABLE PERFORATING OR STITCHING TOOL
US7115108B2 (en) * 2002-04-02 2006-10-03 Becton, Dickinson And Company Method and device for intradermally delivering a substance
US20040127824A1 (en) * 2002-10-18 2004-07-01 Falahee Mark H. Radiopaque marking pen
US7578954B2 (en) * 2003-02-24 2009-08-25 Corium International, Inc. Method for manufacturing microstructures having multiple microelements with through-holes
US20070066935A1 (en) * 2003-05-09 2007-03-22 Ryuichi Morishita Needleless syringe having medical agent accomodated therein
JP2007511291A (en) * 2003-11-13 2007-05-10 シンフォニー メディカル, インコーポレイテッド Control of arrhythmias by altering neurotransmission within the fat pad of the heart
US7310722B2 (en) * 2003-12-18 2007-12-18 Nvidia Corporation Across-thread out of order instruction dispatch in a multithreaded graphics processor
WO2005094526A2 (en) * 2004-03-24 2005-10-13 Corium International, Inc. Transdermal delivery device
US20050222518A1 (en) * 2004-04-06 2005-10-06 Genocell, Llc Biopsy and injection catheters
US8636694B2 (en) * 2004-06-14 2014-01-28 Medtronic, Inc. Modular medical injection system
CA2577729C (en) 2004-08-09 2014-08-05 Tyco Healthcare Group Lp Medical skin applicator apparatus
EP1802737A4 (en) * 2004-10-12 2010-08-18 Agency Science Tech & Res Tissue system and methods of use
US20090023127A1 (en) * 2004-10-12 2009-01-22 Agency For Science, Technology And Research Tissue system and methods of use
CA2583800C (en) * 2004-10-18 2013-12-10 Tyco Healthcare Group Lp Apparatus for applying wound treatment material using tissue-penetrating needles
US7678107B2 (en) * 2005-03-10 2010-03-16 Boston Scientific Scimed, Inc. Medical needles and electrodes with improved bending stiffness
US8439867B2 (en) * 2005-06-07 2013-05-14 David R. Staskin Injection guidance system and method
EP1904158B1 (en) * 2005-06-24 2013-07-24 3M Innovative Properties Company Collapsible patch with microneedle array
US20070038181A1 (en) * 2005-08-09 2007-02-15 Alexander Melamud Method, system and device for delivering a substance to tissue
DE102005040251A1 (en) * 2005-08-24 2007-03-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg Transcorneal drug delivery system
US7819876B2 (en) * 2005-10-25 2010-10-26 Zimmer Technology, Inc. Orthopaedic pin driver
US20090312696A1 (en) * 2005-12-28 2009-12-17 Copa Vincent G Devices, Systems, and Related Methods for Delivery of Fluid to Tissue
US20070164133A1 (en) * 2006-01-18 2007-07-19 Hao-Jan Lin Low pressure gas accelerated gene gun
WO2008030578A2 (en) * 2006-09-08 2008-03-13 Symphony Medical, Inc. Intramyocardial patterning for global cardiac resizing and reshaping
US20090012413A1 (en) * 2006-09-08 2009-01-08 Sabbah Hani N Cardiac patterning for improving diastolic function
US8603138B2 (en) * 2006-10-04 2013-12-10 Ethicon Endo-Surgery, Inc. Use of an adhesive to treat intraluminal bleeding
US8821446B2 (en) * 2007-01-22 2014-09-02 Corium International, Inc. Applicators for microneedles
EP2146667A2 (en) * 2007-04-11 2010-01-27 Henry Ford Health System Cardiac repair, resizing and reshaping using the venous system of the heart
US8911749B2 (en) * 2007-04-16 2014-12-16 Corium International, Inc. Vaccine delivery via microneedle arrays
ES2820335T3 (en) 2007-04-16 2021-04-20 Corium Inc Solvent Cast Microneedle Arrays Containing Active Agent
GB2464902B (en) 2007-08-14 2011-10-19 Hutchinson Fred Cancer Res Methods for evaluating candidate therapeutic agents
US20090053673A1 (en) * 2007-08-23 2009-02-26 Zimmer, Inc. Method for localized treatment of periodontal tissue
US8465515B2 (en) * 2007-08-29 2013-06-18 Ethicon Endo-Surgery, Inc. Tissue retractors
JP5178132B2 (en) * 2007-10-11 2013-04-10 キヤノン株式会社 Image processing system and image processing method
US8517931B2 (en) * 2007-11-26 2013-08-27 Ethicon Endo-Surgery, Inc. Tissue retractors
US8128559B2 (en) * 2007-11-26 2012-03-06 Ethicon Endo-Surgery, Inc. Tissue retractors
US20090253981A1 (en) * 2008-04-03 2009-10-08 Hamilton Brian H Skin Marking Tool for Radiological Imaging Material
US8801665B2 (en) * 2008-04-10 2014-08-12 Henry Ford Health System Apparatus and method for controlled depth of injection into myocardial tissue
WO2010011930A2 (en) * 2008-07-24 2010-01-28 Boston Scientific Scimed, Inc. Various catheter devices for myocardial injections or other uses
US20100130958A1 (en) * 2008-11-26 2010-05-27 David Kang Device and Methods for Subcutaneous Delivery of High Viscosity Fluids
US7866471B2 (en) * 2009-02-04 2011-01-11 Tyco Healthcare Group Lp Medical system with skin applicator
WO2010124177A1 (en) * 2009-04-24 2010-10-28 The Trustees Of The University Of Pennsylvania Multiple-electrode and metal-coated probes
WO2010124255A2 (en) * 2009-04-24 2010-10-28 Corium International, Inc. Methods for manufacturing microprojection arrays
WO2010138001A1 (en) * 2009-05-28 2010-12-02 Simcro Tech Limited Skin gripping means, injector including the skin gripping means and method of performing a subcutaneous injection
US20110014181A1 (en) * 2009-07-20 2011-01-20 Medtronic Vascular, Inc. Microneedle Delivery Device and Methods of Using Same
WO2011011436A2 (en) * 2009-07-21 2011-01-27 The General Hospital Corporation D/B/A Peripheral blood sampling methods and devices
GB0913972D0 (en) 2009-08-10 2009-09-16 Rieke Corp Dispensers
GB0913973D0 (en) 2009-08-10 2009-09-16 Rieke Corp Dispensers
US8647311B2 (en) * 2009-09-21 2014-02-11 Translational Biologic Infusion Catheter, Llc Biologics infusion system
US8551071B2 (en) * 2010-03-19 2013-10-08 Halozyme, Inc. Gas-pressured medication delivery device
US9629979B2 (en) 2010-04-28 2017-04-25 Sanovas, Inc. Pressure/Vacuum actuated catheter drug delivery probe
JP6327852B2 (en) 2010-05-04 2018-05-23 コリウム インターナショナル, インコーポレイテッド Methods and devices for transdermal delivery of parathyroid hormone using microprojection arrays
JP5562138B2 (en) * 2010-06-24 2014-07-30 シスメックス株式会社 Micropore forming device
US9017289B2 (en) * 2010-11-03 2015-04-28 Covidien Lp Transdermal fluid delivery device
WO2012071559A2 (en) * 2010-11-23 2012-05-31 Presage Biosciences, Inc. Therapeutic methods and compositions for solid delivery
US9144450B2 (en) * 2010-12-22 2015-09-29 Boston Scientific Scimed, Inc. Fluid sealant compositions and various medical applications pertaining to the same
US9186100B2 (en) 2011-04-26 2015-11-17 Velano Vascular, Inc. Systems and methods for phlebotomy through a peripheral IV catheter
US10076272B2 (en) 2011-04-26 2018-09-18 Velano Vascular, Inc. Systems and methods for phlebotomy through a peripheral IV catheter
US8366685B2 (en) 2011-04-26 2013-02-05 Creative Vascular, Llc Systems and methods for phlebotomy through a peripheral IV catheter
SG11201401851UA (en) 2011-10-28 2014-05-29 Presage Biosciences Inc Methods for drug delivery
CN103301092B (en) * 2012-03-06 2014-12-03 中国科学院理化技术研究所 Polymer micro-needle array chip, and preparation method and application thereof
GB201209880D0 (en) 2012-05-31 2012-07-18 Rieke Corp Applicators
US9044582B2 (en) * 2012-06-26 2015-06-02 Franklin J. Chang Apparatus and method for transdermal fluid delivery
CA2885028A1 (en) * 2012-09-24 2014-03-27 Cormatrix Cardiovascular, Inc. Multi-needle injection apparatus and system for delivering pharmacological agents to biological tissue
CA2894718A1 (en) * 2012-11-21 2014-05-30 Circuit Therapeutics, Inc. System and method for optogenetic therapy
WO2014100750A1 (en) 2012-12-21 2014-06-26 Corium International, Inc. Microarray for delivery of therapeutic agent and methods of use
US20140255354A1 (en) * 2013-03-11 2014-09-11 Mi4Spine, Llc Barrier cell treatment for malignant or benign tumors
BR122020006959B1 (en) 2013-03-12 2022-04-26 Corium, Inc microprojection applicator
ES2761580T3 (en) 2013-03-15 2020-05-20 Corium Inc Microarrays for therapeutic agent delivery, methods of use and manufacturing methods
AU2014233695A1 (en) 2013-03-15 2015-10-01 Corium International, Inc. Microarray for delivery of therapeutic agent and methods of use
ES2939317T3 (en) 2013-03-15 2023-04-20 Corium Pharma Solutions Inc Multi-impact micro-spray applicators
WO2014150293A1 (en) 2013-03-15 2014-09-25 Corium International, Inc. Microarray with polymer-free microstructures, methods of making, and methods of use
WO2014149977A1 (en) * 2013-03-15 2014-09-25 Muffin Incorporated Cell injection needle
US20140350518A1 (en) 2013-05-23 2014-11-27 Allergan, Inc. Syringe extrusion accessory
US20140350516A1 (en) 2013-05-23 2014-11-27 Allergan, Inc. Mechanical syringe accessory
US10029048B2 (en) 2014-05-13 2018-07-24 Allergan, Inc. High force injection devices
EP2965779A1 (en) * 2014-07-07 2016-01-13 MT Derm GmbH Application module for a handheld device for repeated application of an application element to a human or an animal skin and hand-held device
KR101636775B1 (en) * 2014-08-19 2016-07-08 아주대학교산학협력단 Apparatus and method of regional anesthesia
WO2016036866A1 (en) 2014-09-04 2016-03-10 Corium International, Inc. Microstructure array, methods of making, and methods of use
US10226585B2 (en) 2014-10-01 2019-03-12 Allergan, Inc. Devices for injection and dosing
EP3268063A4 (en) 2015-03-10 2018-10-31 Allergan Pharmaceuticals Holdings (Ireland) Unlimited Company Multiple needle injector
US10857093B2 (en) 2015-06-29 2020-12-08 Corium, Inc. Microarray for delivery of therapeutic agent, methods of use, and methods of making
US10287543B2 (en) 2015-11-19 2019-05-14 Miltenyi Biotec, Gmbh Process and device for isolating cells from biological tissue
US20170164942A1 (en) * 2015-12-15 2017-06-15 Heartstitch, Inc. Holding Block For Multiple Catheter Needles
US10300247B2 (en) 2016-02-03 2019-05-28 Velano Vascular, Inc. Devices and methods for fluid transfer through a placed peripheral intravenous catheter
EP3439716B1 (en) 2016-04-08 2023-11-01 Allergan, Inc. Aspiration and injection device
US9744344B1 (en) 2016-06-30 2017-08-29 Velano Vascular, Inc. Devices and methods for catheter placement within a vein
EP3315156A1 (en) * 2016-11-01 2018-05-02 Sanofi-Aventis Deutschland GmbH Medicament delivery device
EP3318300A1 (en) 2016-11-02 2018-05-09 Miltenyi Biotec GmbH Perfusion device for biological tissue
AU2017378040B2 (en) 2016-12-16 2023-06-08 Sorrento Therapeutics, Inc. Application device for a fluid delivery apparatus and method of use
JP7082621B2 (en) * 2016-12-16 2022-06-08 ソレント・セラピューティクス・インコーポレイテッド How to administer drugs suitable for the treatment of migraine or cluster headache
DK3554619T3 (en) 2016-12-16 2021-11-15 Sorrento Therapeutics Inc FLUID DELIVERY APPLIANCE AND ASSEMBLY METHOD
WO2018175529A1 (en) 2017-03-21 2018-09-27 Velano Vascular, Inc. Systems and methods for controlling catheter device size
CA3052213A1 (en) 2017-03-21 2018-09-27 Velano Vascular, Inc. Devices and methods for fluid transfer through a placed peripheral intravenous catheter
USD867582S1 (en) 2017-03-24 2019-11-19 Allergan, Inc. Syringe device
US20180271589A1 (en) * 2017-03-24 2018-09-27 Shenzhen Peninsula Medical Co., Ltd. Microneedle treatment apparatus and variable frequency rf treatment system
CN106983928B (en) * 2017-04-28 2020-07-10 宁波迪创医疗科技有限公司 System for delivering therapeutic agents
US11801364B2 (en) * 2017-06-30 2023-10-31 Avectas Limited Electrospray catheter
WO2019075380A1 (en) * 2017-10-12 2019-04-18 Northwestern University Targeted delivery of biologic therapeutic agents
BR112022003098A2 (en) 2019-08-20 2022-05-17 Velano Vascular Inc Fluid transfer devices with extended-length catheters and methods of using the same
WO2021186514A1 (en) * 2020-03-16 2021-09-23 国立研究開発法人水産研究・教育機構 Device for replacing blood vessel content of fish and method for manufacturing blood vessel content-replaced fish
CA3197752A1 (en) 2020-11-26 2022-06-02 Avia Vascular, Llc Blood collection devices, systems, and methods
WO2023147535A2 (en) * 2022-01-28 2023-08-03 The Trustees Of Columbia University In The City Of New York Microneedle apparatus and system for perforation of the round window membrane

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5403311A (en) * 1993-03-29 1995-04-04 Boston Scientific Corporation Electro-coagulation and ablation and other electrotherapeutic treatments of body tissue
US5520639A (en) 1992-07-24 1996-05-28 Bioject, Inc. Needleless hypodermic injection methods and device
DE19607922A1 (en) * 1996-03-01 1997-09-04 Grund Karl Ernst Prof Method and device for endoscopically injecting at least one liquid
US5693029A (en) * 1995-07-10 1997-12-02 World Medical Manufacturing Corporation Pro-cell intra-cavity therapeutic agent delivery device
WO1998005307A1 (en) * 1996-08-08 1998-02-12 Localmed, Inc. Transmural drug delivery method and apparatus
CA2241615A1 (en) * 1997-06-26 1998-12-26 An-Go-Gen Inc. Catheters
WO1999004851A1 (en) * 1997-07-22 1999-02-04 Emed Corporation Iontophoretic delivery of an agent into cardiac tissue
US5882332A (en) * 1997-06-06 1999-03-16 Wijay; Bandula Drug infusion catheter and method
EP0934728A2 (en) * 1997-11-25 1999-08-11 Eclipse Surgical Technologies, Inc. Selective treatment of endocardial/myocardial boundary
WO1999044524A2 (en) * 1998-03-05 1999-09-10 Scimed Life Systems, Inc. Expandable pmr device and method

Family Cites Families (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE596981C (en) * 1931-10-30 1934-05-12 Mario Demarchi Dr Injection syringe
US2551902A (en) * 1948-09-10 1951-05-08 Arthur Schaffer Dehorning fluid ejector
US4397903A (en) * 1979-01-18 1983-08-09 The West Company Molded articles
US4578061A (en) 1980-10-28 1986-03-25 Lemelson Jerome H Injection catheter and method
US4596556A (en) 1985-03-25 1986-06-24 Bioject, Inc. Hypodermic injection apparatus
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
FR2638360A1 (en) * 1988-11-03 1990-05-04 Tino Dalto AUTOMATIC INSULIN INJECTOR WITHOUT NEEDLE, PORTABLE WITH MULTIPLE INJECTION HEADS INTERCHANGEABLE TO MULTITROUS
US5262128A (en) 1989-10-23 1993-11-16 The United States Of America As Represented By The Department Of Health And Human Services Array-type multiple cell injector
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
US5697901A (en) 1989-12-14 1997-12-16 Elof Eriksson Gene delivery by microneedle injection
US5098389A (en) 1990-06-28 1992-03-24 Becton, Dickinson And Company Hypodermic needle assembly
US5843017A (en) 1990-07-24 1998-12-01 Yoon; Inbae Multifunctional tissue dissecting instrument
WO1992010142A1 (en) 1990-12-10 1992-06-25 Howmedica Inc. A device and method for interstitial laser energy delivery
US5807388A (en) * 1994-05-25 1998-09-15 The Trustees Of Columbia University In The City Of New York Myocardial revascularization through the endocardial surface using a laser
WO1994015661A1 (en) 1991-05-01 1994-07-21 Rosenberg Paul H Device and method for inhibiting intravascular device associated infection
JP3368603B2 (en) 1992-02-28 2003-01-20 オリンパス光学工業株式会社 Gene therapy treatment device
US5478328A (en) 1992-05-22 1995-12-26 Silverman; David G. Methods of minimizing disease transmission by used hypodermic needles, and hypodermic needles adapted for carrying out the method
US5236424A (en) 1992-06-05 1993-08-17 Cardiac Pathways Corporation Catheter with retractable cannula for delivering a plurality of chemicals
US5311841A (en) * 1992-07-10 1994-05-17 Thaxton J Paul Administration of medicaments of poultry
US5538504A (en) 1992-07-14 1996-07-23 Scimed Life Systems, Inc. Intra-extravascular drug delivery catheter and method
DE4235506A1 (en) 1992-10-21 1994-04-28 Bavaria Med Tech Drug injection catheter
DE4428914C2 (en) 1993-08-18 2000-09-28 Scimed Life Systems Inc Thin-walled multi-layer catheter
US5807395A (en) 1993-08-27 1998-09-15 Medtronic, Inc. Method and apparatus for RF ablation and hyperthermia
US5472441A (en) 1993-11-08 1995-12-05 Zomed International Device for treating cancer and non-malignant tumors and methods
CA2141522A1 (en) * 1994-02-16 1995-08-17 Thomas D. Weldon Electrophysiology positioning catheter
DE4408108A1 (en) 1994-03-10 1995-09-14 Bavaria Med Tech Catheter for injecting a fluid or a drug
US5457041A (en) 1994-03-25 1995-10-10 Science Applications International Corporation Needle array and method of introducing biological substances into living cells using the needle array
US5464395A (en) 1994-04-05 1995-11-07 Faxon; David P. Catheter for delivering therapeutic and/or diagnostic agents to the tissue surrounding a bodily passageway
US5607388A (en) * 1994-06-16 1997-03-04 Hercules Incorporated Multi-purpose wound dressing
EP0954244A1 (en) * 1994-07-01 1999-11-10 SciMed Life Systems, Inc. Intravascular device utilizing fluid to extract occlusive material
US5417683A (en) * 1994-07-13 1995-05-23 Shiao; I-Shen Mini-graft hair implanting device for implanting multiple clumps of hair follicles at one time
EP0892651A1 (en) * 1995-05-10 1999-01-27 Cardiogenesis Corporation System for treating or diagnosing heart tissue
DE29507987U1 (en) 1995-05-15 1996-09-19 Ferton Holding Ejection device for high pressure ejection of a liquid
US5840059A (en) 1995-06-07 1998-11-24 Cardiogenesis Corporation Therapeutic and diagnostic agent delivery
US5672174A (en) 1995-08-15 1997-09-30 Rita Medical Systems, Inc. Multiple antenna ablation apparatus and method
US6283951B1 (en) 1996-10-11 2001-09-04 Transvascular, Inc. Systems and methods for delivering drugs to selected locations within the body
ATE440559T1 (en) 1995-10-13 2009-09-15 Medtronic Vascular Inc DEVICE FOR INTERSTITIAL TRANSVASCULAR PROCEDURES
CA2197608C (en) * 1996-02-20 2000-02-01 Charles S. Taylor Surgical devices for imposing a negative pressure to stabilize cardiac tissue during surgery
US5782823A (en) 1996-04-05 1998-07-21 Eclipse Surgical Technologies, Inc. Laser device for transmyocardial revascularization procedures including means for enabling a formation of a pilot hole in the epicardium
US5766164A (en) 1996-07-03 1998-06-16 Eclipse Surgical Technologies, Inc. Contiguous, branched transmyocardial revascularization (TMR) channel, method and device
US5651774A (en) * 1996-09-11 1997-07-29 William J. Taranto Hypodermic syringe with safety shield and method of using same
DE19704261C2 (en) * 1997-02-05 1999-01-28 Aesculap Ag & Co Kg Surgical instrument
US6063069A (en) * 1997-05-19 2000-05-16 Micro Therapeutics Inc. Method and apparatus for power lysis of a thrombus
US5972013A (en) * 1997-09-19 1999-10-26 Comedicus Incorporated Direct pericardial access device with deflecting mechanism and method
DE19745488B4 (en) * 1997-10-15 2004-07-08 Richard Wolf Gmbh Endoscopic instrument for the therapy of the heart muscle
US5980548A (en) 1997-10-29 1999-11-09 Kensey Nash Corporation Transmyocardial revascularization system
US6063082A (en) 1997-11-04 2000-05-16 Scimed Life Systems, Inc. Percutaneous myocardial revascularization basket delivery system and radiofrequency therapeutic device
JP4535468B2 (en) 1998-02-05 2010-09-01 バイオセンス・ウエブスター・インコーポレーテツド Intracardiac drug delivery
US6093185A (en) 1998-03-05 2000-07-25 Scimed Life Systems, Inc. Expandable PMR device and method
AU3374799A (en) 1998-03-31 1999-10-18 Cardiogenesis Corporation Delivery of an angiogenic substance
US6302870B1 (en) 1999-04-29 2001-10-16 Precision Vascular Systems, Inc. Apparatus for injecting fluids into the walls of blood vessels, body cavities, and the like
US6689103B1 (en) * 1999-05-07 2004-02-10 Scimed Life System, Inc. Injection array apparatus and method
US6641553B1 (en) * 1999-06-02 2003-11-04 Boston Scientific Corporation Devices and methods for delivering a drug
US6613026B1 (en) * 1999-12-08 2003-09-02 Scimed Life Systems, Inc. Lateral needle-less injection apparatus and method

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5520639A (en) 1992-07-24 1996-05-28 Bioject, Inc. Needleless hypodermic injection methods and device
US5403311A (en) * 1993-03-29 1995-04-04 Boston Scientific Corporation Electro-coagulation and ablation and other electrotherapeutic treatments of body tissue
US5693029A (en) * 1995-07-10 1997-12-02 World Medical Manufacturing Corporation Pro-cell intra-cavity therapeutic agent delivery device
DE19607922A1 (en) * 1996-03-01 1997-09-04 Grund Karl Ernst Prof Method and device for endoscopically injecting at least one liquid
WO1998005307A1 (en) * 1996-08-08 1998-02-12 Localmed, Inc. Transmural drug delivery method and apparatus
US5882332A (en) * 1997-06-06 1999-03-16 Wijay; Bandula Drug infusion catheter and method
CA2241615A1 (en) * 1997-06-26 1998-12-26 An-Go-Gen Inc. Catheters
WO1999004851A1 (en) * 1997-07-22 1999-02-04 Emed Corporation Iontophoretic delivery of an agent into cardiac tissue
EP0934728A2 (en) * 1997-11-25 1999-08-11 Eclipse Surgical Technologies, Inc. Selective treatment of endocardial/myocardial boundary
WO1999044524A2 (en) * 1998-03-05 1999-09-10 Scimed Life Systems, Inc. Expandable pmr device and method

Cited By (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7534249B2 (en) 1996-07-26 2009-05-19 Kensey Nash Corporation System and method of use for agent delivery and revascularizing of grafts and vessels
US8226673B2 (en) 1996-07-26 2012-07-24 Kensey Nash Corporation System and method of use for agent delivery and revascularizing of grafts and vessels
US7981129B2 (en) 1996-07-26 2011-07-19 Kensey Nash Corporation System for opening a lumen in an occluded blood vessel
US7833239B2 (en) 1996-07-26 2010-11-16 Kensey Nash Corporation System and method of use for revascularizing stenotic bypass grafts and other blood vessels
US6569147B1 (en) 1996-07-26 2003-05-27 Kensey Nash Corporation Systems and methods of use for delivering beneficial agents for revascularizing stenotic bypass grafts and other occluded blood vessels and for other purposes
US7048723B1 (en) * 1998-09-18 2006-05-23 The University Of Utah Research Foundation Surface micromachined microneedles
US7838222B2 (en) 1999-07-26 2010-11-23 United States of America/ NIH Methods, devices and kits for multiplex blotting of biological samples from multi-well plates
US8779312B2 (en) 1999-07-26 2014-07-15 United States of America/NIH Method and device for analyzing biomolecules with track-etched polymeric layers
US7594900B1 (en) 1999-08-05 2009-09-29 Kensey Nash Corporation Systems and methods for delivering agents into targeted tissue of a living being
US8998877B2 (en) 2000-06-29 2015-04-07 Becton, Dickinson And Company Intradermal delivery of substances
US8708994B2 (en) 2000-06-29 2014-04-29 Becton, Dickinson And Company Method for altering drug pharmacokinetics based on medical delivery platform
US9005182B2 (en) 2000-06-29 2015-04-14 Becton, Dickinson And Company Intradermal delivery of substances
US8465468B1 (en) 2000-06-29 2013-06-18 Becton, Dickinson And Company Intradermal delivery of substances
US9339613B2 (en) 2000-06-29 2016-05-17 Becton, Dickinson And Company Intradermal delivery of substances
US9242052B2 (en) 2000-06-29 2016-01-26 Becton, Dickinson And Company Method for altering drug pharmacokinetics based on medical delivery platform
US8986280B2 (en) 2000-06-29 2015-03-24 Becton, Dickinson And Company Intradermal delivery of substances
WO2002024247A1 (en) * 2000-09-22 2002-03-28 Kensey Nash Corporation Drug delivering prostheses and methods of use
WO2002024248A1 (en) * 2000-09-22 2002-03-28 Kensey Nash Corporation Systems and methods for delivering beneficial agents into targeted tissue of a living being
WO2002024271A3 (en) * 2000-09-22 2002-06-27 Kensey Nash Corp Systems for delivering agents for revascularizing accluded blood vessels
US7628780B2 (en) * 2001-01-13 2009-12-08 Medtronic, Inc. Devices and methods for interstitial injection of biologic agents into tissue
WO2002083231A1 (en) * 2001-04-13 2002-10-24 Becton, Dickinson And Company A method and device for delivery of high molecular weight substances
WO2002083232A1 (en) * 2001-04-13 2002-10-24 Becton, Dickinson And Company Methods and devices for administration of substances into the intradermal layer of skin for systemic absorption
EP1485151A4 (en) * 2002-02-26 2005-12-28 Bioject Medical Technologies I End effector for needle-free injection system
EP1485151A1 (en) * 2002-02-26 2004-12-15 Bioject Medical Technologies Inc. End effector for needle-free injection system
US7722595B2 (en) 2002-05-06 2010-05-25 Becton, Dickinson And Company Method and device for controlling drug pharmacokinetics
US10322272B2 (en) 2002-05-06 2019-06-18 Becton, Dickinson And Company Method and device for controlling drug pharmacokinetics
US9192750B2 (en) 2002-05-06 2015-11-24 Becton, Dickinson And Company Method and device for controlling drug pharmacokinetics
EP1393766A1 (en) * 2002-07-31 2004-03-03 BIOTRONIK Mess- und Therapiegeräte GmbH & Co Ingenieurbüro Berlin Endovascular implant for injecting a drug into the media of a blood vessel
WO2004064645A1 (en) * 2003-01-14 2004-08-05 Medtronic, Inc. Devices and methods for interstitial injection of biologic agents into tissue
WO2004093960A1 (en) 2003-03-20 2004-11-04 Boston Scientific Limited Devices for delivering therapeutic or diagnostic agents
US8512290B2 (en) 2003-03-20 2013-08-20 Boston Scientific Scimed, Inc. Devices and methods for delivering therapeutic or diagnostic agents
US7481798B2 (en) 2003-03-20 2009-01-27 Boston Scientific Scimed, Inc. Devices and methods for delivering therapeutic or diagnostic agents
US8057459B2 (en) 2003-03-20 2011-11-15 Boston Scientific Scimed, Inc. Method for delivering therapeutic or diagnostic agents
EP1623734A1 (en) * 2003-05-06 2006-02-08 Asahi Intecc Co., Ltd. Medical liquid-injecting device
EP1623734A4 (en) * 2003-05-06 2008-09-03 Asahi Intecc Co Ltd Medical liquid-injecting device
US7172576B2 (en) 2003-05-06 2007-02-06 Asahi Intecc Co., Ltd. Medicinal-liquid injection apparatus
US7396351B2 (en) 2003-11-05 2008-07-08 Boston Scientific Scimed, Inc. Device and method for the delivery of viscous fluids in the body
US8123728B2 (en) 2004-02-26 2012-02-28 Boston Scientific Scimed, Inc. Antimicrobial agent delivery system
WO2005092421A1 (en) * 2004-02-26 2005-10-06 Boston Scientific Limited Antimicrobial agent delivery system
US8192787B2 (en) 2004-08-16 2012-06-05 Innoture Limited Method of producing a microneedle or microimplant
AU2005298618B2 (en) * 2004-10-25 2011-04-07 Coloplast A/S Male telescope catheter
EP2409722A1 (en) * 2004-10-25 2012-01-25 Coloplast A/S Male telescope cathether
EP2409723A1 (en) * 2004-10-25 2012-01-25 Coloplast A/S Male telescope cathether
EP2407201A1 (en) * 2004-10-25 2012-01-18 Coloplast A/S Male telescope catheter
WO2006045809A1 (en) * 2004-10-25 2006-05-04 Coloplast A/S Male telescope catheter
EP2407202A1 (en) * 2004-10-25 2012-01-18 Coloplast A/S Male telescope catheter
EP3446738A1 (en) * 2004-10-25 2019-02-27 Coloplast A/S Male telescope catheter
US8361057B2 (en) 2004-10-25 2013-01-29 Coloplast A/S Male telescope catheter
CN101850149A (en) * 2004-10-25 2010-10-06 科洛普拉斯特公司 Male telescope catheter
US8007466B2 (en) 2004-11-18 2011-08-30 Nanopass Technologies Ltd. System and method for delivering fluid into flexible biological barrier
EP1819379A2 (en) * 2004-11-18 2007-08-22 Nano Pass Technologies Ltd. System and method for delivering fluid into flexible biological barrier
EP1819379A4 (en) * 2004-11-18 2010-10-06 Nanopass Technologies Ltd System and method for delivering fluid into flexible biological barrier
US8808232B2 (en) 2004-12-09 2014-08-19 Ams Research Corporation Needleless delivery systems
WO2006063180A3 (en) * 2004-12-09 2006-10-19 Ams Res Corp Needleless delivery systems
US8262605B2 (en) 2004-12-09 2012-09-11 Ams Research Corporation Needleless delivery systems
US8986244B2 (en) 2004-12-09 2015-03-24 Ams Research Corporation Needleless delivery systems
WO2006063180A2 (en) * 2004-12-09 2006-06-15 Ams Research Corporation Needleless delivery systems
US8182444B2 (en) 2005-11-04 2012-05-22 Medrad, Inc. Delivery of agents such as cells to tissue
US7713232B2 (en) 2005-11-04 2010-05-11 Medrad, Inc. System for washing and processing of cells for delivery thereof to tissue
US9629780B2 (en) 2005-11-04 2017-04-25 Bayer Healthcare Llc System for processing cells and container for use therewith
US8414765B2 (en) 2005-11-04 2013-04-09 Medrad, Inc. System for processing cells and container for use therewith
US7621895B2 (en) 2006-05-17 2009-11-24 Abbott Cardiovascular Systems Inc. Needle array devices and methods
WO2007136492A1 (en) * 2006-05-17 2007-11-29 Abbott Cardiovascular Systems Inc. Needle array devices and methods
EP2068975A2 (en) * 2006-08-08 2009-06-17 Peak Biosciences, Inc. Catheter and array for anticancer therapy
EP2068975A4 (en) * 2006-08-08 2013-10-30 Peak Biosciences Inc Catheter and array for anticancer therapy
US9814837B2 (en) 2006-11-21 2017-11-14 Astora Women's Health Holdings, Llc Injection tube for jet injection device
US9827367B2 (en) 2008-04-29 2017-11-28 Medtronic Xomed, Inc. Surgical instrument, system, and method for frontal sinus irrigation
WO2009150594A1 (en) * 2008-06-11 2009-12-17 Koninklijke Philips Electronics N.V. Micro-jet injection device for local submucosal drug application
US10058675B2 (en) 2009-09-21 2018-08-28 Cook Regentec Llc Infusion catheter tip for biologics with reinforced external balloon valve
US10155099B2 (en) 2009-09-21 2018-12-18 Cook Regentec Llc Method for infusing stem cells
US10806891B2 (en) 2009-09-21 2020-10-20 Cook Regentec Llc Method for infusing stem cells
US11129961B2 (en) 2015-05-13 2021-09-28 Hollister Incorporated Telescopic urinary catheter assemblies

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CA2373034A1 (en) 2000-11-16
US6689103B1 (en) 2004-02-10
CA2373034C (en) 2009-01-27
EP1176914B1 (en) 2006-01-04
DE60025345D1 (en) 2006-03-30
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AU4668700A (en) 2000-11-21
JP2002543868A (en) 2002-12-24

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