WO2001030429A1

WO2001030429A1 - Guided injection device

Info

Publication number: WO2001030429A1
Application number: PCT/US2000/028764
Authority: WO
Inventors: Maria Palasis
Original assignee: Scimed Life Systems, Inc.
Priority date: 1999-10-22
Filing date: 2000-10-18
Publication date: 2001-05-03
Also published as: AU8028400A

Abstract

The present invention relates to a guided injection device comprising an injection device and a guidance probe connected thereto. The guided injection device injects a therapeutic agent into mammalian tissue with excellent visualization and accuracy.

Description

GUIDED INJECTION DEVICE

FIELD OF THE INVENTION

The present invention relates to a guided injection device for accurately targeting and injecting a therapeutic agent into a mammalian tissue or organ. More particularly the present invention relates to a therapeutic agent delivery device comprising an injection device and a guidance probe connected to one another in a single device.

BACKGROUND OF THE INVENTION Drugs and therapeutic agents may be delivered directly to mammalian tissues for the treatment of various ailments. For example, therapeutic agents are routinely delivered to heart tissue endocardially for the treatment of heart disease. In one method of delivery, a catheter is placed into a chamber of the heart through arterial or venous access to directly deliver a therapeutic agentto heart tissue. In some cases, fluoroscopic guidance is used to direct the drug delivery device to a desired location to be treated. In other cases ultrasound guidance is used to direct a drug delivery device to a desired location. When fluoroscopic or ultrasound guidance is used, a fluoroscope or ultrasound probe is also placed near the tissue to be treated, which requires two invasive procedures: placement of the fluoroscope or ultrasound probe and separate placement of the drug delivery device within the patient' s body.

While the above-described method of fluoroscopic or ultrasound guidance coupled to drug delivery is excellent in many respects, it has several drawbacks. The method involves at least two invasive techniques, one for the catheter and one for the fluoroscopic or ultrasound guidance device. Furthermore, the spatial resolution of fluoroscopy is limited. Thus, the accuracy of guidance and placement of the delivery catheter is limited. Additionally, the use of a separate delivery catheter and guidance device requires a certain distance between them, which lessens the accuracy of placement of the drug delivery device.

SUMMARY OF THE INVENTION

The present invention is directed to an insertable injection device for delivering a therapeutic agent, comprising an injection device and a guidance probe connected thereto. Preferably, the injection device is an injection catheter, and more preferably, the injection catheter comprises an adjustable needle. The guidance probe is preferably an intracardiac echocardiography (ICE) or transesophageal echo, a magnetic resonance imaging (MRI) probe, or a computerized tomography (CT) probe.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a cross sectional view of a guided injection device within the scope of the present invention having a rotational transducer;

Figure 2 is a cross sectional view of a guided injection device within the scope of the present invention having a pivoting transducer;

Figure 3 is an end of a rotational inducer that results in a conical shaped image that will be displayed on a two-dimensional screen;

Figure 4 is an end of a pivoting inducer that results in a fan-shaped image; Figure 5 is a cross sectional view of a guided injection device having a rotational transducer; and

Figure 6 is a cross sectional view of a guided injection device having a pivoting transducer.

DETAILED DESCRIPTION OF THE INVENTION The guided injection device of the present invention has a guidance probe and an injection device, by which a therapeutic agent may be injected into a mammalian tissue or organ. The injection device and the guidance probe are connected to one another to form a single device. The guided injection device of the present invention provides improved visualization and hence accuracy of placement of the therapeutic agent. By providing a guidance probe and an injection device in a single system, the distance between the guidance probe and the injection site is minimized. Hence, visualization of the injection site and the location of the injection device vis a vis the target site are improved, allowing for more accurate placement of the injection device for targeting injection of the therapeutic agent. The guided injection device of the present invention utilizes a guidance probe such as an echocardiography probe, a magnetic resonance imaging (MRI) probe or a computerized tomography (CT) probe. The use of such a guidance probe provides increased spatial resolution over fluoroscopy and other guidance methods, allowing an operator to accurately target specific locations and control the distances between each application of therapeutic agent. Preferable guidance probes for use in the present device include echocardiography probes such as intracardiac echocardiography (ICE) and transesophageal echo, having high spatial resolution for visualization of the injection site.

Alternatively, MRI or CT probes may be used, which allow visualization of the target area. A preferred MRI probe would comprise a material that does not contain ferro-magnetic compounds. A suitable MRI probe for use in the present invention may include titanium, because such a probe would provide interference- free visualization.

In addition to guiding the placement of the injection device to the injection site, the guidance probe may be used to identify diseased tissue. For example, echocardiography or MRI may be used to identify ischemic heart tissue, which may be treated with appropriate therapeutic agents. In one embodiment of the invention a guidance probe coupled to a injection device, preferably an injection catheter, is used to diagnose disease, guide the injection device to the site of disease, and inject a therapeutic agent at or near the disease site. The ability to diagnose disease is advantageous in that it allows one to move the injection device to different injection sites or to vary the dosage of therapeutic agent to be delivered, depending on the diagnosis at the time of injection. Thus, the injection site and dosage are appropriate and accurate for the diagnosis at the time of injection. Because the guided injection device has multiple capabilities within a single device it has numerous advantages over other guide/probe systems. For example, insertion of a single device into a mammal is less invasive and simpler than insertion of multiple devices. Furthermore, only one orifice is required for insertion of the guided injection device of the invention, as opposed to multiple orifices for multiple devices. Moreover, placement of the injection device at the target injection site is more accurate using the present guided injection device since the target site can be viewed immediately prior to injection.

The injection device of the present invention is an improvement over the use of ultrasound devices because it provides a clearer image of the target area. Furthermore, the injection device of the present invention is an improvement over the use of a guidance probe and injection device individually because the present device provides a clearer image of the target area and because the guidance probe is movable with the injection device.

The injection device according to the invention is insertable into a mammal for delivery of a therapeutic agent. After injection, the inserted injection device is removed from the mammal. The injection device of the present invention preferably is an injection catheter. In a preferred embodiment of the invention, the injection device is a needle-tipped injection catheter consisting of a single needle or multiple needles. The needle may have several conformations including corkscrew, straight with a side hole or holes, angled, etc. Needle-free injection catheters are also contemplated by the present invention.

The present guided injection device can be used to treat any mammalian tissue or organ. Non-limiting examples include tumors; organs, including but not limited to the heart, lung, brain, liver, kidney, bladder, intestines, stomach, pancreas, ovary, prostate; skeletal muscle; smooth muscle; cartilage and bone. The terms "therapeutic agents" and "drugs" are used interchangeably herein and include pharmaceutically active compounds, nucleic acids with and without carrier vectors such as lipids, compacting agents (such as histones), cells, virus, polymers, proteins, small and large molecule drugs, and the like, with or without targeting sequences. An injection administered in accordance with the invention includes the therapeutic agent(s) and solutions thereof.

Specific examples of therapeutic agents used in conjunction with the present invention include, for example, pharmaceutically active compounds, cells, proteins, oligonucleotides, ribozymes, anti-sense oligonucleotides, DNA compacting agents, gene/vector systems (i.e., any vehicle that allows for the uptake and expression of nucleic acids), nucleic acids (including, for example, recombinant nucleic acids; naked DNA, cDNA, or RNA; genomic DNA, cDNA or RNA in a non-infectious vector or in a viral vector and which further 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. 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 the transplant site. The delivery media can be formulated as needed to maintain cell function and viability.

In a particularly preferred embodiment of the invention, the guided injection device is an injection catheter having an outer shaft which has at least one lumen extending therethrough. In this embodiment of the invention, the outer shaft has an inner shaft which also has a lumen extending therethrough. The inner shaft is preferably movable, which allows one to control the movement and relative position of the inner shaft with regard to the outer shaft. The device also preferably has a syringe connected to the inner shaft, which is used to deliver a therapeutic agent. An adjustable needle is preferably used, which provides control of such factors as the depth of needle insertion into the tissue or organ and amount and/or rate at which therapeutic agent is delivered. The release of therapeutic agent from the syringe into the tissue is preferably controlled by a trigger of, for example, a dosage actuator gun. In another embodiment of the invention, the injection device is a needle-free catheter. In this embodiment, carbon dioxide or a therapeutically acceptable gas is used to push the therapeutic agent through the catheter and expel the therapeutic agent from the catheter to inject the therapeutic agent at a desired injection site. A spring mechanism may also be used to generate a high velocity stream.

In this embodiment, the injection device has a guidance probe connected thereto, such as an ICE, transesophageal echo, MRI, or CT probe. Preferably, the guidance probe is housed in a second lumen within the outer shaft of the injection catheter. For example, in this embodiment the guided injection device has an outer shaft which has at least two lumens extending therethrough. In one of the lumens is an inner shaft, which preferably has a syringe connected thereto to deliver a therapeutic agent. In the other lumen is a guidance probe, preferably an ICE, transesophageal, MRI, or CT echo probe.

Alternatively, the guidance probe is externally attached to the guided injection device.

Figure 1 is a cross sectional view of a guided injection device 100 within the scope of the present invention. The injection device comprises a steering sheath 101, within which is a steering guide 102. In the embodiment shown in Figure 1, the steering guide 102 houses a needle catheter 103 and a rotary transducer 104, which is the guidance probe of the present invention. The needle catheter 103 has a needle tip 105.

Figure 2 is a cross sectional view of a guided injection device 200 within the scope of the present invention. Just as in the embodiment set forth in Figure 1, the injection device of this embodiment comprises a steering sheath 101, within which is a steering guide 102. In the embodiment shown in Figure 2, the steering guide 102 houses a needle catheter 103 and the needle catheter 103 has a needle tip 105. The transducer 201 in figure 2 is a pivoting transducer that has a fan-type motion. Figure 3 is an end of a rotational inducer that results in a conical shaped image that will be displayed on a two-dimensional screen. Figure 3 A shows the rotational transducer 104 at 0° rotation. Figure 3B shows the rotational transducer 104 at 90° rotation. Figure 3C shows the rotational transducer 104 at 180° rotation. Figure 3D shows the rotational transducer 104 at 270° rotation. Figure 3E demonstrates the conical shaped image 301 that results from the rotation of the rotational transducer 104.

Figure 4 is an end of a pivoting inducer that results in a fan-shaped image. Figure 4A shows the pivoting transducer 201 at 0° rotation. Figure 4B shows the pivoting transducer 201 at 90° rotation. Figure 4C shows the pivoting transducer 201 at 180° rotation. Figure 4D demonstrates the fan-shaped image 401 that results from the rotation of the pivoting transducer 201.

Figure 5 is a cross sectional view of a guided injection device 500 having a rotational transducer, according to one embodiment of the present invention. Just as in Figure 1, the injection device 500 in Figure 5 comprises a steering sheath 101, within which is a steering guide 102. Also as in Figure 1, in the embodiment shown in Figure 5, the steering guide 102 houses a needle catheter 103 and a rotary transducer 104, which is the guidance probe of the present invention. The needle catheter 103 has a needle tip 105. The distance "x" shown in Figure 5 may be, but is not necessarily, 0. Figure 6 is a cross sectional view of a guided injection device 600 having a pivoting transducer, according to one embodiment of the present invention. Just as in Figure 2, the injection device 600 in Figure 6 comprises a steering sheath 101, within which is a steering guide 102. Also as in Figure 2, in the embodiment shown in Figure 6, the steering guide 102 houses a needle catheter 103 and a pivoting transducer 201, which is the guidance probe of the present invention. The needle catheter 103 has a needle tip 105. The distance "x" shown in Figure 6 may be, but is not necessarily, 0.

Characteristics and 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 illustrative. It can be appreciated by those skilled in the art that there are numerous materials which can be advantageously used to construct the apparatus disclosed herein. These materials should be selected in view of the use to which the apparatus are put.

Claims

What is claimed is:

1. A guided injection device for delivering a therapeutic agent to a tissue or organ, comprising an injection device and a guidance probe connected to said injection device, wherein the guidance probe is selected from the group consisting of an intracardiac echocardiography probe, a transesophageal echo probe, a magnetic resonance imaging probe, and a computerized tomography probe.

2. The guided injection device of claim 1, wherein the injection device is a needle injection catheter or a needle-free injection catheter.

3. The guided injection device of claim 2, wherein the injection catheter is a needle-injection catheter.

4. The guided injection device of claim 2, wherein the injection catheter is a needle-free injection catheter.

5. The guided injection device of claim 1, wherein the guidance probe is a rotational transducer.

6 The guided injection device of claim 1, wherein the guidance probe is a pivoting transducer.

7. The guided injection device of claim 1 , wherein the guidance probe is an intracardiac echocardiography probe.

8. The guided injection device of claim 1, wherein the guidance probe is a transesophageal echo probe.

9. The guided injection device of claim 1, wherein the guidance probe is a magnetic resonance imaging probe.

10. The guided injection device of claim 1, wherein the guidance probe is a computerized tomography probe.

11. The guided injection device of claim 1 , wherein the guidance probe is housed within a lumen of the guided injection device.

12. A guided injection device for delivering a therapeutic agent, comprising a) an injection device comprising an elongated outer shaft having a proximal end and a distal end, and at least one lumen extending therethrough, an inner shaft having a proximal end and a distal end, the inner shaft disposed within a lumen of the outer shaft, the inner shaft having a lumen extending therethrough, and an adjustable needle attached to the distal end of the inner shaft; and b) a guidance probe connected to said injection device, wherein the guidance probe is selected from the group consisting of an intracardiac echocardiography probe, a transesophageal echo probe, a magnetic resonance imaging probe, and a computerized tomography probe.

13. The guided injection device of claim 12, further comprising a syringe connected to the proximal end of said inner shaft.

14. The guided injection device of claim 12, wherein the injection device is an injection catheter.

15. The guided injection device of claim 12, wherein the guidance probe s housed within a lumen in the outer shaft

16 The guided injection device of claim 12, wherein the guidance probe s an intracardiac echocardiography probe

17 The guided injection device of claim 12, wherein the guidance probe is a transesophageal echo probe

18 The guided injection device of claim 12, wherein the guidance probe is a magnetic resonance imaging probe

19 The guided injection device of claim 12, wherein the guidance probe is a computerized tomography probe

20 The guided injection device of claim 12, wherein the therapeutic agent is selected from the group consisting of pharmaceutically active compounds, cells, proteins, oligonucleotides, ribozymes, anti-sense oligonucleotides, DNA compacting agents, gene/vector systems and nucleic acids, naked DNA, cDNA, and RNA, genomic DNA, cDNA and RNA in a non-infectious vector or in a viral vector, antisense nucleic acid, and DNA chimeras

21 The guided injection device of claim 12. wherein the injection device comprises a needle-free catheter in which carbon dioxide or a therapeutically acceptable gas pushes the therapeutic agent through the catheter and expels the therapeutic agent from the catheter at an injection site

22 A guided injection device for delivering a therapeutic agent, comprising an elongated outer shaft having a proximal end and a distal end. and at least a first lumen and a second lumen extending therethrough, an inner shaft having a proximal end and a distal end, the inner shaft disposed within the first lumen of the outer shaft, the inner shaft having a lumen extending therethrough; an adjustable needle attached to the distal end of the inner shaft; and a guidance probe housed within the second lumen of said outer shaft, wherein the guidance probe is selected from the group consisting of an intracardiac echocardiography probe, a transesophageal echo probe, a magnetic resonance imaging probe, and a computerized tomography probe.

23. The guided injection device of claim 22, further comprising a syringe connected to the proximal end of said inner shaft.

24. The guided injection device of claim 22, wherein the injection device is a needle injection catheter or a needle-free catheter.

25. The guided injection device of claim 24, wherein the injection catheter is a needle-injection catheter.

26. The guided injection device of claim 22, wherein the therapeutic agent is selected from the group consisting of pharmaceutically active compounds, cells, proteins, oligonucleotides, ribozymes, anti-sense oligonucleotides, DNA compacting agents, gene/vector systems and nucleic acids; naked DNA, cDNA, and RNA; genomic DNA, cDNA and RNA in a non-infectious vector or in a viral vector; antisense nucleic acid; and DNA chimeras.

27. The guided injection device of claim 22, wherein the guidance probe is an intracardiac echocardiography probe.

28. The guided injection device of claim 22, wherein the guidance probe is a transesophageal echocardiography probe.

29. The guided injection device of claim 22, wherein the guidance probe is a magnetic resonance imaging probe.

30. The guided injection device of claim 22, wherein the guidance probe is a computerized tomography probe.

31. A method of delivering a therapeutic agent to a tissue or organ comprising providing a guided injection device comprising an injection device and a guidance probe connected to said injection device; guiding said injection device to an injection site of a tissue or organ by viewing said injection site using said guidance probe; and injecting a therapeutic agent from said guided injection device into said injection site.

32. The method of claim 31 , wherein the injection device is a needle injection catheter or a needle-free catheter.

33. The method of claim 31, wherein the injection device is a needle injection catheter.

34. The method of claim 31, wherein the injection device is a needle-free injection catheter.

35. The method of claim 31 , wherein the guidance probe is housed within a lumen of the guided injection device.

36. The method of claim 31, wherein the injecting comprises pulling a trigger on a dosage actuator gun included as part of said guided injection device to inject said therapeutic agent from said guided injection device into said injection site.

37. The method of claim 31, wherein the injecting comprises releasing carbon dioxide or a therapeutically acceptable gas to push said therapeutic agent through the catheter and inject said therapeutic agent from said guided injection device into said injection site.

38. The method of claim 31 , wherein the guidance probe is an intracardiac echocardiography probe.

39. The method of claim 31, wherein the guidance probe is a transesophageal echo probe.

40. The method of claim 31 , wherein the guidance probe is a magnetic resonance imaging probe.

41. The method of claim 31 , wherein the guidance probe is a computerized tomography probe