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WO1999004850A1 - Aiguille pour l'injection iontophoretique d'une substance active - Google Patents

Aiguille pour l'injection iontophoretique d'une substance active Download PDF

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Publication number
WO1999004850A1
WO1999004850A1 PCT/US1998/015050 US9815050W WO9904850A1 WO 1999004850 A1 WO1999004850 A1 WO 1999004850A1 US 9815050 W US9815050 W US 9815050W WO 9904850 A1 WO9904850 A1 WO 9904850A1
Authority
WO
WIPO (PCT)
Prior art keywords
needle
agent
shaft
target area
delivery zone
Prior art date
Application number
PCT/US1998/015050
Other languages
English (en)
Inventor
Robert G. Walsh
John C. Vanden Hoek
Deena Conrad-Vlasak
John Dockter
Original Assignee
Emed Corporation
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 Emed Corporation filed Critical Emed Corporation
Priority to EP98936936A priority Critical patent/EP0932427A1/fr
Priority to JP50997399A priority patent/JP2001506172A/ja
Priority to AU85770/98A priority patent/AU8577098A/en
Publication of WO1999004850A1 publication Critical patent/WO1999004850A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/20—Applying electric currents by contact electrodes continuous direct currents
    • A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
    • A61N1/303—Constructional details
    • A61N1/306—Arrangements where at least part of the apparatus is introduced into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/46—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests having means for controlling depth of insertion

Definitions

  • the present invention relates to delivery of an agent using iontophoresis, and more particularly, to a needle configured for iontophoretic delivery of an agent directly into a target area of tissue.
  • One of these current techniques is to deliver the agent through the systemic circulatory system.
  • the problem is that systemic delivery requires the administration of an artificially high dose of agent in order to have a therapeutic amount reach the target area.
  • Much of the agent is delivered to healthy tissue, which is inefficient and expensive.
  • a related problem is that exposing the agent to healthy tissue may result in serious side effects, especially if the agent is toxic or otherwise dangerous.
  • Iontophoresis is the use of electrical energy to transport an agent.
  • These techniques are inefficient in delivering an agent if the target area of tissue is deep within the body and remote from the delivery device. Part of the reason for this limited effect is that the agent must pass through the specific physiologic structures such as the skin; the endothelium, which is a layer of cells that line the blood vessels and similar cavities of the body; or the epithelium, which is a layer of cells that line internal surfaces of the body such as the urethra and bladder. All of these structures may serve as barriers limiting the passage of molecules.
  • skin has a high electrical resistance, relative to other tissue such as muscle, that reduces the efficiency of iontophoretic delivery of tissue.
  • Another delivery technique is to directly inject the agent into the body.
  • the problem is that diffusion and convection of the agent are limited by factors such as the viscosity of the delivery fluid, the local concentration gradient of the agent, the diffusion coefficient of the delivery agent, and the amount of pressure applied to the 2 0 delivery fluid.
  • Many treatments may require delivery of the agent to a relatively large, but discrete, area of tissue.
  • Angiogenesis which is the generation of new blood vessels, is an example of such a treatment.
  • These situations may require multiple injections in order to ensure that the agent is distributed throughout the target area.
  • some tissue is so dense that pressure is not an adequate force to aid convection and diffusion of agent throughout the target area. Bone is an example of such a tissue.
  • Cellular uptake is a factor that also may affect efficiency of the agent delivery. Once the agent is delivered to the target, it must be absorbed into the cells. The difficulty is that the cellular uptake for certain agents is often slow and inefficient. Therefore, there is a need for an apparatus for and method of directly delivering an agent to a target area of tissue deep within the body. There is another need for an apparatus for and method of distributing an agent throughout a target area. There is a further need for an apparatus for and method of efficiently delivering an agent to a target area while minimizing waste of the agent. There is still a further need for an apparatus for and method of delivering an agent to a target area of tissue while minimizing exposure of the agent to tissue outside of the target area. Another need exists for a system that can enhance cellular uptake.
  • the present invention is directed to an apparatus for iontophoretically delivering an agent.
  • the apparatus comprises a hollow needle having a shaft and a delivery zone.
  • the hollow needle defines at least one outlet port located in the delivery zone.
  • the needle is formed with an electrically conductive material.
  • the needle is configured to be in electrical communication with a power supply wherein the needle forms a first electrode.
  • An insulting material covers at least a portion of the shaft.
  • a second electrode is configured to be in electrical communication with the power supply.
  • the present invention is also directed to a method of delivering an agent to a target area of tissue within a patient.
  • the method comprises the steps of inserting a hollow needle into the target area, the needle defining at least one outlet port and being formed from an electrically conductive material, the needle forming a first electrode; injecting an agent into the target area through the hollow needle; placing an electrode into electrical communication with the patient's body; and passing an electrical current between the first and second electrodes, thereby transporting the agent to tissue in the target area.
  • Figure I is a cross-sectional view of an iontophoretic needle that embodies the present invention.
  • Figure 2 is a side view of an alternative embodiment of the iontophoretic needle shown in Figure 1.
  • Figure 3 is a cross-sectional view of another alternative embodiment of the iontophoretic needle shown in Figure 1.
  • Figure 4 is a side view of another alternative embodiment of the iontophoretic needle shown in Figure 1.
  • Figure 5 is a side view of another alternative embodiment of the iontophoretic needle shown in Figure 1.
  • Figure 6 is a side view of another alternative embodiment of the iontophoretic needle shown in Figure 1.
  • the present invention is directed to an apparatus and method for directly delivering an agent into a target area and then iontophoretically transporting the agent to tissue in the target area.
  • the delivery apparatus includes a needle formed of an electrically conductive material and forms a first electrode.
  • a second electrode is configured to be placed into electrical communication with the patient's body. In use, the caregiver inserts the needle either into or proximal to the target area, and injects an agent through the needle.
  • the caregiver then passes an electrical current between the first and second electrodes to iontophoretically transport the agent to tissue within the target area, iontophoresis can occur while the agent is being injected or after injection of the agent is complete. Additionally, the caregiver can pass an electric current between the first and second electrodes before an agent is introduced through the needle.
  • the present invention has many advantages. For example, the present invention provides for direct delivery of an agent to a target area while minimizing exposure of the agent to tissue outside the target area. As a result, the risk of side effects is minimized. Additionally, the agent is used more efficiently, which minimizes the cost of treatment. There is also increased efficiency because the agent is not transported through a substantially impervious and high resistance barrier such as the skin. Another advantage is that the present invention can enhance cellular uptake of the agent, which enhances efficiency of the delivery even further. The present invention also provides for greater and more uniform distribution of the agent throughout the target area.
  • an iontophoretic device consists of two electrodes in intimate electrical contact with some portion of a patient's tissue and a reservoir containing an agent that is to be introduced into the patient's body or tissue.
  • One electrode called the delivery electrode
  • the other electrode called the return electrode
  • the target area that is the tissue to which it is desired to deliver the agent, is in the electrical path between the delivery and return electrodes.
  • the circuit is completed by connecting the delivery and/or return electrodes to a source of electrical energy, such as a battery or a direct current power supply.
  • a source of electrical energy such as a battery or a direct current power supply.
  • the source of electrical energy can be controlled by a signal generator or other circuitry that is electrically connected to the energy source in order to shape or otherwise control the signal used to energize the electrodes.
  • the agent In iontophoresis, the agent either has a natural ionic charge or is combined with a charged carrier molecule. If the agent or carrier molecule is positively charged, then the positive electrode (the anode) is the delivery electrode. If the agent or carrier molecule is negatively charged, then the negative electrode (the cathode) is the delivery electrode. In this configuration, the agent is transported away from the energized delivery electrode and into the target area. Alternatively, if the agent is neither charged nor combined with a carrier molecule, delivery can rely on electroosmosis, which is a form of iontophoresis and describes the movement of water molecules placed within an electric field and the agent that is either suspended or in solution.
  • An agent can include any type of composition.
  • agents include drugs such as antiseptics and fixatives; compositions useful for diagnostic purposes such as dyes; genetic materials such as DNA, RNA, genes, ribozymes, antisense oligonucleotides, and other antisense materials; therapeutic agents such as cytotoxic, chemotherapeutic, antiviral agents, antibiotics, and antifungal agents; adjuvants; penetration enhancers; and other substances that have medical applications.
  • agent can mean an agent in any form. Examples of various forms of agents include solutions, solids, liquids, liposomes, dehydrated masses, and gels. Although the term is often used in a singular form, it can connote either a single agent or a combination of agents.
  • a needle 100 is formed with an electrically conductive material and forms a first electrode.
  • the material can be either sacrificial or non-sacrificial.
  • sacrificial materials include silver/silver chloride, copper, tin, nickel, iron, lithium, and amalgams thereof.
  • non-sacrificial materials include platinum, gold, and other noble metals.
  • the needle 100 also can be formed with zirconium, iridium, titanium, certain carbons, and stainless steel, which may oxidize under certain circumstances. The grade of stainless steel is one factor that determines whether stainless steel oxidizes. Another factor that determines whether there are obvious signs of oxidation is the surface area of the delivery zone.
  • the needle I 00 is formed with a solid material.
  • the needle 100 is formed with a base material that is plated. Plating is advantageous because some of the conductive materials such as gold and platinum are relatively expensive.
  • the needle 100 is straight, has a shaft 102, and has a delivery zone
  • the length of the delivery zone 104 is between about 0.25 inches and about 7 inches.
  • the needle 100 has a distal tip 106 that is beveled and aids insertion into the target site. Other configurations of the distal tip 106 of the needle 100 are possible. Examples include pointed and a squared configurations.
  • An opposite end of the needle (not shown) is configured to be connected to a source of the agent such as a syringe or a drug Pump.
  • the needle is rigid. In another possible configuration, the needle is flexible or pliable. In yet another possible configuration, the needle is steerable similar to a cardiovascular catheter so that a caregiver can guide the direction of the needle as it is inserted into a patient.
  • the needle 100 defines a lumen 108 that provides a passage for the flow of fluid, and at least one outlet port 110 that is in fluid communication with the lumen 108.
  • the distal tip 106 of the needle 100 is closed. Other configurations will have a distal tip that is open.
  • the outlet ports 110 are defined along the. delivery zone 104, and have a diameter of about lOOO ⁇ or less.
  • the number of outlet ports 110 can range from 1 to 1000 or more. One factor affecting the number of outlet ports is whether it is desirable to diffuse the agent in one direction or entirely around the circumference of the needle 100. Another factor affecting the number of outlet ports 110 is the size of the needle 100 and the size of the outlet ports 110. In one possible embodiment, the area of the outlet ports is maximized, which allows quick and even distribution of the agent.
  • Possible manufacturing methods to form the outlet ports 1 10 include laser drilling, electrical discharge machining, photolithography, and chemical etching.
  • outlet ports 110 are distributed around the entire circumference of the delivery zone 104. Distributing the outlet ports 110 in this manner is advantageous because it distributes the current density in order to minimize the risk of burning tissue adjacent to the outlet ports 110.
  • the outlet ports 110 are defined in only a portion of the circumference around the delivery zone 104. An advantage of this alternative embodiment is that it provides increased precision over the direction that the agent is transported.
  • the needle 100 has a gauge ranging from about 27 to about 20. These gauges provide flexibility while still having enough structural rigidity to be inserted into tissue. Additionally, these gauges are large enough to define multiple outlet ports 110. An advantage of using a gauge as small as 27 is that the needle 100 is small enough that the patient will experience only a minimal amount of pain when inserted.
  • the shaft 102 is covered with an insulating material 1 12 that is substantially non-conductive.
  • the insulating material 112 can be a sheath, coating, covering, or similar structure. In one possible configuration, the entire shaft 102 is covered with the insulating material 112. In another possible configuration, only a portion of the shaft 102 is covered with the insulating material 112. In this configuration, there is a portion of the shaft 102 between the delivery zone 104 and the insulating material 112 that is configured for direct electrical communication with, the tissue. When using this configuration, the caregiver will insert the needle 100 so that the insulating material 112 extends partially into the tissue. In yet another possible embodiment, the insulating material 1 12 extends partially along the shaft 102 from a point directly adjacent to the delivery zone 104. An advantage of the insulting material 112 is that it prevents burning at the interface where the needle 100 initially passes into the tissue.
  • the insulating material 112 can be shrink tubing that shrinks securely around that shaft 102 upon heating.
  • the insulating material can be painted onto the shaft 102 and cured, or the shaft 102 can be dipped into a reservoir of the insulating material and cured.
  • materials that can be used to form the insulating material 112 include polyester, nylon, and Teflon®, although any suitable insulating material can be used.
  • the delivery zone 104 is covered with a spacer 114 that minimizes direct contact between the outer surface 116 of the needle 100 and the tissue of the target area 104. As a result, burning of tissue that is directly adjacent to the delivery zone 104 of the needle 100 is minimized.
  • the spacer 114 is a sheath or coating 118 that covers the delivery zone 104. Examples of material that can be used to form the sheath 118 include nylon and Teflon®. If a material such as nylon or Teflon® is used, the sheath 1 1 8 has the form of a mesh, or some similar configuration, that will allow agent and electrical current to flow through the sheath 118. There are several techniques to apply the mesh.
  • the mesh can be a cloth that is wrapped around the delivery zone.
  • Examples of mesh include woven materials, knitted materials, or a perforated sheet.
  • Alternative techniques for applying nylon and Teflon® mesh is to apply the material in a fluid form and either paint it on the needle 100 or dip the needle 100 into a reservoir: The fluid material is then cured by an appropriate mechanism such as heating. This coating technique can be repeated in order to achieve the desired thickness of the insulating material.
  • Teflon® is used, one possible method of creating the mesh pattern is to apply a template to the delivery zone 104 of the needle 100 and then apply the Teflon®. After the Teflon Is has cured, the template is lifted off of the needle 100 thereby creating a mesh pattern. Yet another alternative manufacturing technique is to coat the needle 100 with the insulating material and then etch the insulating material with acid.
  • the spacer 114 can be formed with hollow fibers, which are porous to the agent. Upon being wetted, the hollow fibers allow the agent and electricity to flow therethrough.
  • the hollow fibers could be wound around the delivery zone 104 or arranged in a variety of other configurations such as a mesh or a fabric.
  • One possible type of hollow fiber that could be used is the hollow fiber that is distributed by Millipore Corporation of Massachusetts.
  • An advantage of using hollow fiber is that it will absorb the agent and act as a reservoir for the agent. This reservoir effect provides for more even distribution of the agent all the way around the circumference of the needle 100.
  • Other materials and configurations can be used to form the spacer in addition to meshes and hollow fibers. Examples of other materials include polymer matrices, foams, and hollow fibers.
  • a first lead 122 provides electrical communication between the shaft 102 of the needle 100 and a power supply 124.
  • a second lead 126 provides electrical communication between a second electrode 128 and the power supply 124.
  • the second electrode 128 is a patch-type electrode configured to be applied to the surface of the patient's skin. Other configurations of the second electrode 128 are possible. For example, the second electrode 128 could be mounted on the surface 130 of the insulating material 1 12 to provide a bi-polar needle or could be configured to be otherwise positioned in the patient's body.
  • the caregiver inserts the needle 100, 132, or 136 directly into the target area.
  • the needle 100, 132, 136 is percutaneously inserted directly through the skin.
  • the needle 100, 132, or 136 is 12 inserted through an interior body surface such as a chamber in the heart, a blood vessel, or the urethra. Access to the internal body surface is made with an appropriate device such as a catheter or a cannula.
  • the agent is injected through the lumen 108 and the outlet port 110.
  • the agent will have some natural diffusion. Especially if the tissue in the target area has large intercellular spaces such as the fibers that form muscle.
  • Iontophoresis is accomplished by providing a voltage gradient, and resulting electrical current, between the needle 100, 132, or 136 and the second electrode 128.
  • the voltage gradient causes the agent to migrate within the target tissue if the needle 100, 132, or 136 is inserted directly within the target area.
  • the voltage gradient causes the agent to migrate to and within the target area if the needle 100, 132, or 136 is inserted proximal to, but outside of, the target area.
  • the current has a net flow in one direction in order to transport the agent from a position directly adjacent the needle 100, 132, or 136 to other tissue in the target area.
  • One possible range of voltage is between about 3 volts and about 8 volts depending on the resistance of the tissue between the needle 100, 132, or 136 and the second electrode 128.
  • One possible range of current density is between about 2 mA/cm 2 to about 20 mA/cm 2 .
  • the current can be direct or have a variety of waveforms. Examples of various wave forms are described in United States Patent 5,499,971, which is entitled Internal iontophoresis Drug Delivery Apparatus and Method and issued on March 19, 1996, the disclosure of which is hereby incorporated by reference. Additionally, the current can be gradually increased or ramped up to a threshold level,, which minimizes the sensation or pain experience by the patient. Ramping up the current is described in more detail in United States Patent Application 08/829,470, which is entitled Method Of Ramping Up iontophoretic Current and was filed on March 28, 1997, the disclosure of which is also incorporated by reference.
  • the current is an alternating current that has a net flow of current in one direction.
  • alternating current may enhance cellular uptake and increase efficiency of the agent delivery.
  • a direct current or other waveform is used to transport the agent to the target tissue. The current is then switched to an alternating current to enhance cellular uptake. The alternating current does not have a net flow.
  • An advantage of switching between waveforms in this manner is that a direct current will efficiently and quickly transport the agent. Once the agent is distributed throughout the desired target area, the alternating current may enhance cellular uptake.
  • the present invention is advantageous for delivering an agent to treat a variety of target areas within the body and a variety of maladies and conditions.
  • target area include muscle tissue, the prostate, the heart, the lung, the liver, bone, the bladder, and tumors.
  • treatments that can be performed or promoted include angiogenesis, apoptosis, the delivery of DNA vaccines, and plastic surgery.
  • Angiogenesis is a procedure of stimulating the growth of new blood vessels.
  • the growth of vessels is stimulated by angiogenesis agents delivered directly into target tissue using the delivery techniques outlined above.
  • the agent includes the DNA that codes for any of several growth factors that stimulates the growth of new vasculature.
  • the DNA can be delivered in various forms including naked gene plasmids, as well as lipid coforinulating and viral vectors such as adenoviruses, adenoassociated viruses, and retroviruses.
  • Agents other that DNA could also be used to promote angiogenesis. Examples of these agents include basic fibroblast growth factors, acidic fibroblast growth factors, or vascular endothelial growth factors.
  • Apoptosis is a form of programmed cell death. Most cells have an internal signaling mechanism that tells the cell when to die. One function of apoptosis is to make room for the growth of new cells. The difficulty is that this internal signaling method occasionally fails, resulting in uncontrolled proliferation of new cells. The result is often the development of a tumor.
  • the invention described herein could also be used to deliver agents, that promote apoptosis, including DNA material, directly into a tumor in an effort to promote the death of the tumor cells. An example of such agents includes DNA or reconbinate proteins such as p53 rumor suppresser.
  • the present invention is also useful for delivering DNA vaccines. Present vaccines typically consist of viable or non- viable viruses or microorganisms that are injected into the circulatory system. These foreign bodies activate the host defense mechanisms, including an immunological response directed against the microorganism or virus. The problem is that the patient is exposed to potentially deadly bacteria and viruses and may develop an infection.
  • a DNA vaccine is a DNA plasmid that codes for an antigenic protein associated with the invading microorganism or virus.
  • the cells receive the DNA plasmid, which stimulates the growth of the antigenic protein.
  • the host immunological response is then directed against the antigenic protein without exposing the patient to potentially deadly microorganisms or viruses.
  • An advantage of using the present invention to deliver the DNA vaccine is that it transports the DNA plasmid to a larger volume of cells. An increased number of cells then develop and release the antigenic protein, which results in a quicker and more thorough development of a defensive response by the host.
  • the present invention could be used to deliver the gene or genetic material that codes for the growth of collagen or other structural protein rather than injecting the collagen or other structural protein itself.
  • the needle 160 is substantially similar to the needle 100, and includes a shaft 102, an insulating material 112, a delivery zone 104, and outlet ports 110.
  • the needle 160 does not, however, include a spacer. Rather, the outer surface 116 of the needle 100 at the delivery zone 104 is exposed directly to tissue in the patient's body during use.
  • another alternative embodiment 132 is substantially similar to the needle 100, and includes a shaft 102, an insulating material 112, a delivery zone 104, and a spacer 114.
  • the outlet ports 110 are configured as a slot 134 that extends the length of the delivery zone 102.
  • the needle 132 can define multiple slots 134, depending on the size of the needle 132 and whether the caregiver desires to deliver agent around the entire circumference of the delivery zone 104.
  • yet another alternative embodiment 136 has a shaft 138, an insulating material 139 covering the shaft 138, a delivery zone 140, and a spacer 142.
  • the delivery zone 140 has a helical or corkscrew configuration. Like the other needle configurations, the needle 136 defines a delivery chamber (not shown) and at least one outlet port (not shown) in the delivery zone 140.
  • the helical needle configuration has several advantageous.
  • the helical needle 136 is screwed into the target area thus securely anchored in a delivery position.
  • the needle 136 will not readily move, which is especially advantageous if the target area is a heart that continues to beat during delivery of the agent.
  • the needle also has a larger delivery zone, which helps to distribute the iontophoretic current and thus reduces the risk of burning tissue.
  • a related advantage is that the greater delivery zone also enables the use of more delivery ports, which enables the agent to be delivered quicker and more efficiently.
  • another alternative embodiment 142 is also substantially similar to the needle 100, and includes a shaft 144, an insulating material 112, a delivery zone 104, and a spacer 114.
  • the shaft has a distal portion 146 and a proximal portion 148.
  • the diameter of the distal portion 146 is substantially equal to the diameter of the delivery zone 104.
  • the diameter of the proximal portion is greater than the diameter of the distal portion 146.
  • a radially oriented surface 150 between the distal and proximal portions 146 and 148 of the shaft 144 forms a depth guide 152 that limits how far the needle 142 can be inserted into the patient's body.
  • the distance between the distal tip 106 of the needle and the depth guide 152 can vary depending on how deep the target area is from the surface into which the needle is to be injected.
  • another alternative embodiment 154 is also substantially similar to the needle 100, and includes a shaft 102, an insulating material 112, a delivery zone 104, and a spacer 114.
  • a collar 156 slidably engages the shaft 102.
  • a flange 158 is mounted on the distal end of the collar 156.
  • the flange 158 forms a depth guide 160.
  • the distance between the distal tip 106 of the needle 154 and the flange 158 is adjustable.
  • the collar 156 can be secured in one position by a set screw or any other appropriate mechanism. In an alternative embodiment, there is no flange connected to the collar 156, and the collar 156 functions alone as the depth guide.

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Radiology & Medical Imaging (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Vascular Medicine (AREA)
  • Anesthesiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Electrotherapy Devices (AREA)

Abstract

Cette invention se rapporte à un dispositif servant à l'injection par voie iontophorétique d'une substance active. Ce dispositif comprend une aiguille creuse ayant une tige et une zone d'injection. Cette aiguille creuse forme au moins un orifice de sortie situé dans la zone d'injection. Cette aiguille est constituée d'un matériau électroconducteur. Elle est conçue pour être en communication électrique avec une source de courant, pour qu'elle forme une première électrode. Un matériau isolant recouvre au moins une partie de la tige de l'aiguille. Un élément d'espacement est connecté de façon opérationnelle à la zone d'injection. Une seconde électrode est conçue pour être en communication électrique avec la source de courant.
PCT/US1998/015050 1997-07-22 1998-07-22 Aiguille pour l'injection iontophoretique d'une substance active WO1999004850A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP98936936A EP0932427A1 (fr) 1997-07-22 1998-07-22 Aiguille pour l'injection iontophoretique d'une substance active
JP50997399A JP2001506172A (ja) 1997-07-22 1998-07-22 作用物質のイオン導入法による送達のための針
AU85770/98A AU8577098A (en) 1997-07-22 1998-07-22 Needle for iontophoretic delivery of agent

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US89841097A 1997-07-22 1997-07-22
US08/898,410 1997-07-22

Publications (1)

Publication Number Publication Date
WO1999004850A1 true WO1999004850A1 (fr) 1999-02-04

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PCT/US1998/015050 WO1999004850A1 (fr) 1997-07-22 1998-07-22 Aiguille pour l'injection iontophoretique d'une substance active

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JP (1) JP2001506172A (fr)
AU (1) AU8577098A (fr)
WO (1) WO1999004850A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999036563A1 (fr) * 1998-01-14 1999-07-22 Emed Corporation Expression cellulaire a mediation electrique
EP1148885A1 (fr) * 1999-02-08 2001-10-31 Chiron Corporation Augmentation electriquement induite de l'immunite et de l'efficacite de vaccins d'adn in vivo
WO2002009807A1 (fr) * 2000-08-02 2002-02-07 Elisabetta Rossi Recipient pour fluide de ionophorese muni d'un distributeur et electrode associee
EP1324802A1 (fr) * 2000-09-12 2003-07-09 Peter K. Law Catheter et methode de transfert de cellules myogenes
US6595958B1 (en) 2000-08-08 2003-07-22 Scimed Life Systems, Inc. Tortuous path injection device and method
US6613017B1 (en) 2000-08-08 2003-09-02 Scimed Life Systems, Inc. Controlled depth injection device and method
WO2004104557A2 (fr) * 2003-05-19 2004-12-02 Ventana Medical Systems, Inc. Coloration des tissus in situ par electrophorese
US6893421B1 (en) 2000-08-08 2005-05-17 Scimed Life Systems, Inc. Catheter shaft assembly
FR2872056A1 (fr) * 2004-06-24 2005-12-30 Yves Scherman Dispositif pour l'administration de principe actif aux cellules et tissus utilisant une ou deux forces physiques
WO2006010837A3 (fr) * 2004-06-24 2006-04-06 Sphergen Dispositif our le transfert de molecules aux cellules utilisant une force electrique
US10695562B2 (en) 2009-02-26 2020-06-30 The University Of North Carolina At Chapel Hill Interventional drug delivery system and associated methods
US11666550B2 (en) 2010-03-08 2023-06-06 Sloan-Kettering Institute For Cancer Research CDC7 kinase inhibitors and uses thereof

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US8066659B2 (en) 2004-06-15 2011-11-29 Ceramatec, Inc. Apparatus and method for treating and dispensing a material into tissue
US8777889B2 (en) 2004-06-15 2014-07-15 Ceramatec, Inc. Apparatus and method for administering a therapeutic agent into tissue
US8353906B2 (en) * 2005-08-01 2013-01-15 Ceramatec, Inc. Electrochemical probe and method for in situ treatment of a tissue

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EP1148885A1 (fr) * 1999-02-08 2001-10-31 Chiron Corporation Augmentation electriquement induite de l'immunite et de l'efficacite de vaccins d'adn in vivo
EP1148885A4 (fr) * 1999-02-08 2002-05-08 Chiron Corp Augmentation electriquement induite de l'immunite et de l'efficacite de vaccins d'adn in vivo
WO2002009807A1 (fr) * 2000-08-02 2002-02-07 Elisabetta Rossi Recipient pour fluide de ionophorese muni d'un distributeur et electrode associee
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US7399294B2 (en) 2000-08-08 2008-07-15 Boston Scientific Scimed, Inc. Controlled depth injection device
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US10695562B2 (en) 2009-02-26 2020-06-30 The University Of North Carolina At Chapel Hill Interventional drug delivery system and associated methods
US11666550B2 (en) 2010-03-08 2023-06-06 Sloan-Kettering Institute For Cancer Research CDC7 kinase inhibitors and uses thereof
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AU8577098A (en) 1999-02-16
EP0932427A1 (fr) 1999-08-04

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