Drug Delivery Catheter

This application incorporates by reference copending U.S. patent applications Ser. No. 08,149,587, filed Nov. 9, 1993 entitled "Improved Cutter Device," now U.S. Pat. No. 5,507,760.

1. Field of the Invention

This invention relates to a device and method for the treatment of specific areas of inner surfaces of biological conduits with medicaments.

2. Previous Art

Atherosclerosis is a progressive disease wherein fatty, fibrous, calcific, or thrombotic deposits produce atheromatous plaques within and beneath the intima which is the innermost layer of arteries. The most commonly affected vessels are the aorta, iliac, femoral, coronary and cerebral arteries. Untreated coronary artery disease can lead to angina, hypertension, myocardial infarction, strokes and the like. Atherosclerotic blockages can occur anywhere within the thicket of vessels and arteries that service the heart. Regions of blood vessels that are blocked by atheroma (plaque) or other materials are generally referred to herein as stenotic regions, and the blocking material as stenotic material. The composition of the stenotic material can vary from hard calcium-containing lesions to fatty lipid-based coatings on the inside of the coronary arteries. Stenotic materials deposited on blood vessel walls are often relatively soft and tractable. However, in many cases, the stenotic material may contain a significant amount of calcified and hardened material. A number of methods such as coronary artery bypass graft (CABG) surgery, percutaneous transluminal coronary angioplasty, (PCTA), directional coronary atherectomy (DCA), energetic ablation, and stenting, are used in attempts to restore the narrowed blood vessels to as close as is possible, to their original diameters. In percutaneous transluminal coronary angioplasty, sometimes called balloon angioplasty, during coronary catheterization, an inflatable balloon is inserted in a coronary artery in the region of coronary stenosis. Inflation of the balloon for 15-30 seconds results in an expansion of the narrowed lumen or passageway. Devices suitable for PCTA have been described is U.S. Patents such as 4,323,071. Directional Coronary Atherectomy is a procedure which has been developed for excising and removing stenotic material from the vascular system. DCA procedures employ a variety of special catheters having tissue cutting members (cutters) located at the distal end of the catheter. In use, the catheter is inserted into a biological conduit so that the cutter housing is placed adjacent to the stenotic region with the housing window aligned to the stenotic material. Stenotic material is invaginated into an opening in the cutter housing by inflating a balloon opposed to the housing window. Simultaneous rotation and translation of the cutter sever the stenotic material which is retained in the nosecone at the distal end of the catheter. Examples of such devices can be found in U.S. Pat. Nos. 5,312,425; 5,250,059; 5,181,920; 5,071,425; 4,979,951; 4,781,186; and 4,669,469 (reissued as Re. 33,569), herein incorporated by reference in their entirety. Ablative methods such as the application of laser energy to the atheroma or high speed abrasive buns are also used to widen the blood vessel at the point of stenosis. Another method of treatment of cardiac insufficiency employs stents. (mechanical supports) Stents are placed at the site of the stenosis and expanded to widen the blood vessel. The stent remains in place as an arterial implant. All of these techniques are used to open blocked areas of blood vessels in an attempt to restore the original lumen diameter or provide an alternative path for blood flow. Although these methods of treatment are distinct different methods, they share one common problem, restenosis. A certain percentage of the treated blood vessels will reocclude (restenose) after a period of time. Restenosis can occur in as many as 30-40% of the cases. In such restenotic instances, the original procedure may be repeated or an alternative method for achieving blood flow may be tried. The common factor in all of these treatment methods is that they all traumatize the blood vessel to some extent. There are several reasons why restenosis can occur. One is that small clots form on the arterial wall. Tears in the wall expose blood to foreign material and proteins, such as collagen, which are highly thrombogenic. Resulting clots can grow gradually, or can contain growth hormones which are released by platelets within the clot. Additionally, growth hormones released by other cells, such as macrophages, can cause smooth muscle cells and fibroblasts in the region to multiply. Further, there is often complete loss of the normal single layer of cells constituting the endothelial lining following angioplasty. This layer normally covers the internal surface of all vessels, rendering that surface compatible, i.e., non-thrombogenic and non-reactive with blood. Mechanically, when as angioplasty balloon is inflated, the endothelial cells are torn away. Prior art procedures also produce injuries in the arterial wall which become associated with inflammation. Any kind of inflammatory response may cause the growth of new tissue. In order to address such problems, the cardiology community needs to administer drugs which are biocompatible and in such concentration that they do not induce a toxic reaction.

Some drugs might have a beneficial effect upon inhibition of the stenotic growth or even remove the stenotic material; however treatment of the site of vessel blockage via systemic administration of drugs has not been successful. The area in need of treatment is very small relative to the area of the vascular system. Blood flow at the stenotic region is low and variable. Localized application of some drugs could achieve the most effective result without burdening the entire system with large amounts of a drug. One attempt to localize drug delivery during an angioplasty procedure is described in U.S. Pat. No. 5,199,951. This patent is limited in the area of treatment, and method of application. There does not exist an efficient means for the localized delivery of medicaments in a biological conduit such as a blood vessel.

What is needed is a method of applying a medicament to a specific site in a biological conduit to either remove or destroy the stenotic material or to treat the site of vascular intervention to prevent restenosis.

It is an object of this invention to provide a device and method for applying a medicament to a biological conduit.

It is a further object of the invention to provide such a device and method usable in a catheter having a rotatable drive cable, such that the medicament is accepted by the device, is retained during handling and introduction of the catheter and the device into the biological conduit, and is thereafter delivered into the biological conduit upon rotation of the device by the drive cable.

It is a further object of the invention to provide such a device and method usable to apply a medicament to a biological conduit during removal of tissue from the biological conduit.

In accordance with the above objects and those that will be mentioned and that will be apparent below, a device for the application of a medicament from a rotatable drive cable-equipped catheter to a biological conduit is provided comprising:

a rotatable and axially translatable applicator including an outer surface defining a proximal end attachable to the catheter drive cable, a distal end, and a side portion; and also including an inner surface defining a reservoir for medicaments; and

at least one medicament delivery path in the side portion of the applicator, originating in the reservoir and terminating in an opening on the outer surface of the applicator;

whereby a medicament is substantially retainable within the reservoir against gravity and during introduction of the device into the biological conduit, and the medicament is substantially deliverable from the reservoir upon rotation of the applicator within the biological conduit.

Also in accordance with the same objects, a method for the application of medicaments within a biological conduit, the method comprising the steps of:

providing a catheter comprising a rotatable drive cable;

providing within the catheter a rotatable and axially translatable applicator including an outer surface defining a side portion, a distal end, a proximal end attached to the catheter drive cable; an inner surface defining a reservoir for medicaments; and at least one medicament delivery path originating in the reservoir and terminating in an opening on the outer surface of the applicator;

introducing the catheter into a biological conduit and advancing the catheter to a treatment site therein; and

rotating the applicator at a speed sufficient to force medicament from the reservoir into the biological conduit via the delivery path;

whereby the medicament is substantially retained within the reservoir against gravity and during introduction of the device into the biological conduit, and the medicament is substantially delivered from the reservoir into the biological conduit when the applicator is rotated therein.

Also provided in accordance with the same objects are embodiments of the device and method wherein the reservoir contains a porous absorbent material for retaining the medicament, embodiments wherein the delivery path is of capillary dimensions, embodiments wherein the delivery path comprises a slit of capillary dimensions, embodiments including a distal sealing plug through which a medicament is injected into the reservoir; and embodiments wherein the method is performed in a blood vessel or a coronary blood vessel in particular.

In the event that a drug is applied that is effective for removing or otherwise controlling the stenotic material without need of excising or compressing stenotic material, the housing window can be optimized to the extent required to maintain structural rigidity and permit the largest area of application.

For a further understanding of the objects and advantages of the present invention, reference should be had to the following detailed description, taken in conjunction with the accompanying drawing, in which like parts are given like reference numerals and wherein:

FIG. 1 is a side view of an cutting applicator in accordance with the present invention.

FIG. 2 is an end view and the applicator of FIG. 2.

FIG. 3 is a side view of a non-cutting embodiment of the present invention.

FIG. 4 is an end view of the applicator of FIG. 3.

FIG. 5 is another embodiment of a cutting applicator in accordance with the present invention.

FIG. 6 is an end view and the applicator of FIG. 5.

FIG. 7 is a non-cutting embodiment of the applicator in accordance with the present invention.

FIG. 8 is an end view and the applicator of FIG. 7.

FIG. 9 illustrates the entry of a device constructed in accordance with the invention into a biological conduit.

FIG. 10 illustrates the positioning of a device constructed in accordance with the invention within a blood vessel in conjunction with an atherectomy catheter.

With respect to FIG. 1 is shown a medicament applicator 1 having a proximal end 5, a distal end 6, a medicament reservoir 20, delivery paths 30, openings to the exterior 31, a sealing plug 40 and a cutting edge 50. The applicator 1 is attached to a drive cable 10 at proximal end 5 which is attached to a motor drive (not shown). Reservoir 20 contains a porous absorbent material 23, such as cotton, open celled cellulosic foam, open celled polyurethane foam or the like. The drug to be delivered can be loaded through port 41 into reservoir 20 and absorbed by absorbent material 23 when the device is manufactured and sealed in place by plug 40 or injected by means of a hypodermic syringe and needle into reservoir 20 through plug 40 just prior to use. Drugs that have sufficient storage stability may lend themselves to the preloading approach. Drugs that have a limited lifetime can be prepared just prior to the treatment and injected into the reservoir 20 through sealing plug 40. In a preferred embodiment, the reservoir 20 contains an absorbent material 23 that will retain the absorbed drug by absorption until the applicator 1 is rotated above a threshold high speeds. Thus, the cutting applicator 1 is first rotated and translated axially to remove the stenotic material. Then, when the application of drug is desired, the cutting applicator 1 is rotated an a higher speed that is sufficient to express out the drug of reservoir 20 via path 30 to opening 31. In this manner, several cuts may be made in various positions, and drug may be applied to each cut after it is made. In the embodiment shown in FIG. 1, the drug delivery paths 30, are at an angle to the perpendicular of the axis of rotation of the applicator 1 and permit treatment a larger area of blood vessel that would be possible if the openings were perpendicular from the axis of rotation and equidistant from a central point. In this manner, one of ordinary skill in the art can construct applicators that apply drugs to larger or smaller areas by changing the placement and number of openings. For example, therapeutic drugs for treating an injured or diseased area in a vessel and for combination with the disclosed applicator can include antiplatelets, antithrombins, and antiproliferatives. Examples of antiplatelets and antithrombins include sodium heparin. LMW heparin, hirudin, hirulog, argatroban, forskolin, vapirprost, prostacyclin, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIB/IIIa platelet membrane receptor antibody, recombinant hirudin, thrombin inhibitor (from Biogen) and 7E-3B (antiplatelet drug form Centocor). Examples of antiproliferatives include angiopeptin (somatostatin analogue from a French company: Ibsen), angiotensin converting enzyme inhibitors (Captopril (Squibb), Cilazapril (Hoffman-LaRoche) and Lisinopril (Merk)), calcium channel blockers (Nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), low molecular weight heparin (Wyeth. Glycomed), histamine antagonists, lovastatin (inhibitor of HMG-CoA reductase, cholesterol lowering drug from Merk), methotrexate, monoclonal antibodies (to PDGF receptors. etc.), nitroprusside, phosphodiesterase inhibitors, prostacyclin analogues, prostaglandin inhibitor (Glaxo), seramin (PDGF antagonist(, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (PDGF antagonist from Japanese company). While the foregoing therapeutic agents have been used to prevent or treat restenosis and thrombosis, they are provided by way of example and not meant to be limiting, as other therapeutic drugs may be developed which are equally applicable for use with the present invention.

FIG. 9 illustrates the entry of a device constructed in accordance with the invention into a biological conduit, showing a catheter 62 containing a device in accordance with the invention being inserted into a biological conduit 64 through an incision 66.

With reference to FIG. 10, a device 70 constructed in accordance with the invention is positioned within a blood vessel 64. Applicator 72 attached to cable 74 is disposed within the housing 68 of a catheter 76.

FIG. 2 shows the relative positions of the drug delivery paths 30 with respect to a plane perpendicular to the central axis of the cutting applicator 1.

FIG. 3 describes an embodiment wherein applicator 1 does not perform any cutting action. With respect to FIG. 3 is shown a medicament applicator 1 having a proximal end 5, a distal end 6, a medicament reservoir 20, delivery paths 30, exterior openings 31, and sealing plug 40. Applicator 1 is attached to drive cable 10 which is attached to a motor drive (not shown). As in the previous embodiment, the drug to be delivered can be loaded into reservoir 20 through port 41 and sealed in place by plug 40. In this preferred embodiment, reservoir 20 contains an absorbent material that will retain the absorbed drug until applicator 1 is rotated at speed high enough to overcome the absorptive forces. Once applicator 1 is positioned, drug is released when it is rotated at a suitable speed.

FIG. 4 shows the relative positions of the drug delivery paths 30 with respect to a plane perpendicular to the central axis of the cutting applicator 1.

FIG. 5 shows an embodiment of applicator 1 wherein the drug reservoir is devoid of any absorbent material and escape of the drug is controlled by the diameter of the capillary-like drug delivery paths 32 and the speed of applicator 1. The term "capillary-like" is used herein to describe the ordinary attraction between liquids and solids wherein a capillary bore will spontaneously fill when contacted with liquid and will not empty under ordinary gravitational forces. In the particular embodiment, the drug delivery paths 32 are slits of capillary dimensions. Slits 32 communicate with the surface via surface openings 33 and are wide enough to apply drug to a broader area than when a bore and a hole of capillary dimensions are used. As in the previous embodiment, the drug to be delivered can be loaded into the reservoir 22 when the device is manufactured through port 41 and sealed in place by plug 40 or alternatively, prepared just prior to treatment and injected into reservoir 31 through sealing plug 40 by means of a hypodermic syringe and needle. FIG. 6 shows the capillary nature of slits 33 more clearly. One skilled in the art can construct differently sized capillary, conduits for the delivery of distinct amounts of drug at a desired rotational speed.

FIG. 7 describes another embodiment wherein the applicator 1 does not perform any cutting action. With respect to FIG. 6 is shown a medicament applicator 1 having proximal end 5, distal end 6, medicament reservoir 22, delivery paths 32, exterior openings 33, and sealing plug 40. Applicator 1 is attached to drive cable 10 at proximal end 5 which is attached to a motor drive (not shown). The drug to be delivered can be loaded into reservoir 22 through port 41 and sealed in place by plug 40. Drug reservoir 22 is devoid of any absorbent material and delivery of the drug is controlled by the diameter of the capillary-like drug delivery path 32 and the speed of rotation of applicator 1. In this specific embodiment, drug delivery paths 32 are slits of capillary dimensions. Delivery paths 32 communicate with the surface of applicator 1 via surface openings 33 and are wide enough to apply drug to a broader area than would be possible if a single bore and hole of capillary dimensions were used.

The foregoing detailed descriptions have described preferred embodiments of the drug delivery applicator of the instant invention and are to be understood to be illustrative only and not limiting of the disclosed invention. Particularly, the specific details of the drug delivery path and the construction of the reservoir can be varied to obtain different delivery rates and area of coverage and still be within the scope of the disclosed invention. Thus, the invention is to be limited only by the claims set forth below.