Enhanced radioactive stent for reduction of restenosis

An ablation apparatus system for treating tissues or atherosclerosis on a patient having a stent or a metallic implant, wherein said stent or metallic implant comprises a coating layer including a carrier composed of a biocompatible material and having dispersed therein a radioactive substance, the ablation apparatus system comprising an electrical conducting wire that is coupled to an external radiofrequency generator for delivering the radiofrequency current to the stent or the metallic implant for the purposes of thermally enhanced irradiation capability for tissue therapeutic treatment.

TECHNICAL FIELD OF THE INVENTION
 The present invention generally relates to improved medical apparatus and
 methods for treating vascular tissues. More particularly, the invention
 relates to enhanced radioactive stents and methods for use in maintaining
 a lumen of a blood vessel in which the stent is implanted to expand and
 maintain the enlarged vessel in a patient by delivering therapeutic RF
 energy through a metallic stent containing radioactive element for
 enhanced reduction of restenosis.
 BACKGROUND OF THE INVENTION
 Balloon angioplasty is a nonsurgical method of clearing coronary and other
 arteries, blocked by atherosclerotic plaque, fibrous and fatty deposits on
 the walls of arteries. A catheter with a balloon-like tip is threaded up
 from the arm or groin through the artery until it reaches the blocked
 area. The balloon is then inflated, flattening the plaque and increasing
 the diameter of the blood vessel opening. The arterial passage is thus
 widened. The benefits of angioplasty of arteries have been amply
 demonstrated.
 There are limitations, however, to this technique's application, depending
 on the extent of the disease, the blood flow through the artery, and the
 part of the anatomy and the particular vessels involved. Plaque build-up
 and/or severe re-stenosis recur at about 40-50 percent of those treated. A
 huge number of patients experiencing a successful primary angioplasty
 procedure are destined to require a repeat procedure. Balloon angioplasty
 can only be characterized as a moderate-success procedure.
 Recently, a newer technique of inserting a metallic stent is used to
 permanently maintain the walls of the vessel treated at its extended
 opening state. Vascular stents are typically composed of a biocompatible
 material such as a biocompatible metal wire of tubular shape, a metallic
 perforated tube, or a tiny mesh tube used by heart surgeons to prop open
 the weak inner walls of diseased arteries. The stent should be of
 sufficient strength and rigidity to maintain its shape after deployment,
 and to resist the elastic recoil of the artery that occurs after the
 vessel wall has been stretched. The stents are often used in conjunction
 with balloon angioplasty to prevent restenosis after the clogged arteries
 are treated. Despite of its considerable benefits, coronary stenting alone
 is not a panacea, as studies have shown that about 30% of the patient
 population subjected to that procedure will still experience restenosis.
 Risks of inflammation of the vessel walls are exacerbated by the presence
 of the stent.
 When a clogged artery is widened, the plaque is broken up and the
 underlying collagen or damaged endothelium is exposed to the blood flow.
 Collagen has a prothrombotic property which is part of a body healing
 process. Unless collagen or the damaged endothelium is passivated,
 treated, or modulated, the chance for blood vessel clotting as well as
 restenosis still exists. Several U.S. patents disclose incorporation of
 drugs or radioactive elements onto the stent for slow release into the
 blood stream. One example is U.S. Pat. No. 5,843,163 to Wall who discloses
 an expandable stent having radioactive treatment means. Another example is
 U.S. Pat. No. 5,882,291 to Bradshaw et al. who discloses a device and
 methods for controlling dose rate during intravascular radiotherapy. U.S.
 Pat. No. 5,871,436 to Eury discloses radiation therapy method by immersing
 the device in a solution of the radioisotope just prior to device
 implantation. However, none of the above-mentioned patents disclose
 releasing therapeutic agents into the tissue, instead to the blood stream,
 at the stent contact site.
 A metallic stent is generally coated with a biodegradable or non-degradable
 coating which incorporates a radioactive source. One particular example is
 U.S. Pat. No. 5,871,437 to Alt who discloses a radioactive stent for
 treating blood vessels to prevent restenosis. Said patent discloses that
 not only the restenosis triggered by the proliferation of smooth muscle
 cells is inhibited by a radioactive material, but the restenosis triggered
 by thrombus formation is also inhibited, by incorporating into the coating
 carrier hirudin, iloprost or other anti-coagulant. However, due to
 continuous blood flow to wash away the active ingredient inside the
 coating layer from the coated stent, the anti-restenosis effect diminishes
 quickly or compromised greatly. There is a clinical need to diffuse or
 embed the active ingredient, such as radioactive elements, anti-coagulant
 and the like, into the lesion site where the stent contacts the tissue of
 the arterial wall. An appropriate thermal energy plays a critical role in
 enhancing the diffusion process of an active ingredient into the tissue
 wall.
 Radiofrequency therapeutic protocol has been proven to be highly effective
 when used by electrophysiologists for the treatment of tachycardia; by
 neurosurgeons for the treatment of Parkinson's disease; and by
 neurosurgeons and anesthetists for other RF procedures such as Gasserian
 ganglionectomy for trigeminal neuralgia and percutaneous cervical
 cordotomy for intractable pains. A stent deployed within a vessel, such as
 a coronary stent, has excellent metal-to-tissue contact surface. It
 becomes an ideal medium for applying thermal energy to the tissue needed
 for impregnation or embedding of active ingredients, such as radioactive
 substances or anti-coagulants. Radiofrequency protocol, which exposes a
 patient to minimal side effects and risks, is generally applied precisely
 to the stent-to-tissue contact site to obtain the desired thermal effect
 to accelerate the diffusion and embedding of an active ingredient into the
 local stent-contact tissue for prolonged therapeutic effects.
 SUMMARY OF THE INVENTION
 In general, it is an object of the present invention to provide a method
 and an improved medical apparatus for generating heat, to treat the
 atherosclerosis, vascular vessels, or other tissues, such as intestine,
 colon, ureter, uterine tube, and the like. It is another object of the
 present invention to provide a vascular stent having radioactive
 substances on the exposed surface of the stent. It is a further object of
 the present invention to provide a metallic implant having radioactive
 substances on its surface for enhanced irradiation. It is still another
 object to provide a medical apparatus system having radiofrequency energy
 to accelerate diffusing or embedding the radioactive substance into the
 tissue. It is another object of the present invention to provide a method
 and an apparatus for monitoring the temperature of the ablated tissue, and
 to control the temperature by utilizing a temperature control mechanism
 and/or algorithm for radiofrequency energy delivery. The location of the
 temperature sensor means is preferably at close proximity of the exposed
 surface of the stent apparatus or at a distal end of detachable conducting
 wire means. It is still another object of this invention to provide a
 method and an apparatus for treating atherosclerosis, vascular walls, or
 tubular cellular tissues in a patient by applying RF current to a stent
 having radioactive substance and consequently to the underlying tissues
 for enhanced irradiation.
 Briefly, heat is generated by supplying a suitable energy source to an
 apparatus, which comprises electrical conductor means, in contact with the
 body tissues through a stent. A stent is defined in this invention as any
 metallic stenting element, in mesh form, coil form, perforated form, or
 other appropriate form, used to enlarge and maintain the enlarged tissues
 or vessels. Examples include coronary stent, peripheral stent, uterine
 stent and the like. A suitable energy source may consist of radiofrequency
 energy, microwave energy, ultrasonic energy, alternating current energy,
 or laser energy. The energy can be applied to the stent and consequently
 to the atherosclerosis, vascular walls, or cellular tissues through the
 electrode means. A DIP (dispersive indifferent pad) type returning pad or
 electrode, that contacts the patient, is connected to the Indifferent
 Electrode Connector on the RF generator. Therefore, the RF energy delivery
 becomes effective when a close circuit from a RF generator through a
 patient and returning to the RF generator is formed. The tissue behaves
 like a "resistor" to the RF circuit, whereby heat is generated at the
 stent-to-tissue contact site. The coating layer at the exposed surface of
 the stent is thereafter heated and releases the active ingredient inside
 the coating layer to the tissue via diffusion or embedding process with
 assistance of enhanced thermal energy. The thermally enhanced active
 ingredient could not diffuse to the metal side of the stent.
 When using an alternating current outlet, the generator should be grounded
 to avoid electrical interference. Heat is controlled by the power of the
 RF energy delivered, the contact surface area, and by the delivery
 duration. The standard RF energy generator means and its applications
 through the electrode means, to a patient are well known for those who are
 skilled in the art.
 In one embodiment, an ablation apparatus system comprises a vascular stent,
 wherein the vascular stent comprises a non-radioactive elongated metallic
 tube having open ends, and a sidewall containing a multiplicity of
 openings therethrough to allow said stent to be expanded radially for
 deployment in a blood vessel subjected to angioplasty so as to maintain
 the lumen of blood vessel open; wherein a thin coating on an exterior
 surface of the tube, said coating including a carrier composed of a
 biocompatible material and having dispersed therein a radioactive
 substance. The apparatus system further comprises detachable conducting
 wire means for detachably contact said tube, said detachable conducting
 wire means having a wire distal end and a wire proximal end, wherein the
 wire distal end is to contact the elongated metallic tube and the wire
 proximal end is coupled to a radiofrequency current source. The system
 further comprises a radiofrequency current generating means for generating
 radiofrequency current, wherein the radiofrequency current is transmitted
 to the vascular stent through the detachable conducting wire means so that
 the radioactive substance has thermally enhanced irradiation capability
 for tissue treatment. The biocompatible material for the coating may be a
 biodegradable material, a non-biodegradable material, or a thermally
 degradable material.
 The ablation apparatus system may further comprise at least one temperature
 sensor, wherein the temperature sensor is disposed at close proximity of
 the wire distal end or on the elongated metallic tube. The apparatus
 system may further comprise temperature control means for controlling a
 temperature sensed from the at least one temperature sensor, wherein the
 temperature measured from the temperature sensor is relayed to the
 temperature control means and is adapted to effect the radiofrequency
 current delivery to the vascular stent. The radiofrequency current is
 preferably within the range of 50 to 2,000 kHz. The detachable conducting
 wire means may be selected from the group consisting of a guidewire, a
 spiral wire, a catheter wire, a catheter probe having an electrical
 conducting wire, a combination of the above-mentioned wires thereof, and
 the like.
 In a preferred embodiment, a method of preventing restenosis of a blood
 vessel which has undergone angioplasty to open a restricted region of a
 lumen of the vessel is disclosed. The method comprises inserting a stent
 into the blood vessel and deploying the stent to contact the vessel wall
 at the site of the restricted region; irradiating the tissue in the wall
 at said site with a radioactive substance in a coated layer which is
 coated to an exterior surface of the stent; and providing radiofrequency
 current from a radiofrequency current generator to the stent through an
 electrical conducting wire so that the radioactive substance has thermally
 enhanced irradiation for tissue treatment.
 In an alternate preferred embodiment, method for treating tissues of a
 patient having a metallic implant is disclosed, said metallic implant
 having a thin coating on an exposed surface of said implant and said
 coating including a carrier composed of a biocompatible material and
 having dispersed therein a radioactive substance. The method comprises the
 steps of (a) inserting detachable conducting wire means for detachably
 contact said metallic implant, said detachable conducting wire means
 having a wire distal end and a wire proximal end, wherein the wire distal
 end is to contact the metallic implant and the wire proximal end is to be
 coupled to a radiofrequency current source; and (b) applying
 radiofrequency current from a radiofrequency current generating means to
 the metallic implant through the detachable conducting wire means so that
 the radioactive substance has thermally enhanced irradiation for tissue
 treatment.
 The metallic implant may be a stent, a heart valve, an orthopedic implant,
 and the like. The metallic implant has a coated layer composed of
 thermally degradable or biodegradable material so that the radioactive
 substance is being embedded in the tissue by the assistance of the thermal
 energy.
 The method and medical apparatus of the present invention has several
 significant advantages over other known systems or techniques to treat the
 atherosclerosis or tissues having a stent or a metallic implant. In
 particular, the apparatus system comprising the detachable conducting wire
 means, using RF energy as a heat source, in this invention results in a
 more efficient therapeutic effect, which is highly desirable in its
 intended application on the atherosclerosis or on other tissue ablation
 applications when there is a pre-implanted stent.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
 Referring to FIGS. 1 to 4, what is shown is an embodiment of the ablation
 apparatus system comprising a vascular stent and/or a metallic implant,
 wherein a thin layer is coated on its exterior surface and a radioactive
 substance dispersed inside the thin layer has thermally enhanced
 irradiation for tissue treatment.
 FIG. 1 shows a schematic diagram of a RF treatment method in relation to
 the tissues through a stent or an implant having radioactive substance at
 its exposed surface layer in a patient. A RF current generator 30 is
 connected to a stent or an implant 21 through a detachable conducting wire
 means 29. The detachable conducting wire means 29 may be selected from the
 group consisting of a guidewire, a spiral wire, a catheter wire, a
 catheter probe having an electrical conducting wire, a combination of the
 abovementioned wires thereof, and the like. The detachable conducting wire
 means comprises a wire distal end and a wire proximal end, wherein the
 wire distal end is conductive and is in an appropriate form to effect the
 easy, secure, and efficient contact to the stent or implant of the present
 invention. The conducting wire means itself, except the wire distal end,
 is electrically non-conductive.
 The detachable conducting wire means 29 is to contact a stent or an implant
 21 when the ablation apparatus system is deployed. The stent is in close
 contact with the underlying tissue 25. A thin layer 12 is coated or
 attached on the original exterior surface 13A of the non-radioactive stent
 so that the exposed surface of the thin layer 13 will contact the tissue.
 In a stent, the exposed surface having a layer of radioactive substance is
 the exterior surface 13. The thin layer contains radioactive substance 11
 for irradiation purposes. A DIP (dispersive indifferent pad) type pad 14,
 that contacts a patient, is connected to the Indifferent Electrode
 Connector on the RF generator 30 through a returning electrical wire 16.
 Therefore, the RF energy delivery becomes effective when a close circuit
 from a RF generator through a patient and returning to the RF generator is
 formed. Impedance 17 measured from the tissue contact 25 is to ensure good
 tissue contact for ablation, otherwise the RF current is cutoff when the
 impedance is unreasonably high. A temperature sensor 27 is also used to
 measure the tissue temperature and is relayed through a temperature
 sensing wire 28 and a closed-loop temperature controller 31 for
 controlling the ablative energy delivered. Heat is controlled by the power
 of the RF energy delivered and by the delivery duration. In one
 embodiment, the closed-loop temperature controller 31 is part of RF
 current generating means 30 for temperature controlling purposes.
 FIG. 2 shows an overall view of a preferred stent having radioactive
 substance at its exterior exposed surface layer, constructed in accordance
 to the principles of the present invention. In a preferred embodiment, a
 vascular stent 21 comprises a non-radioactive elongated metallic tube 1
 having open ends 2, 3, and a sidewall 4 containing a multiplicity of
 openings therethrough to allow said stent to be expanded radially for
 deployment in a blood vessel subjected to angioplasty so as to maintain
 the lumen of blood vessel open; wherein a thin coating 12 on an original
 exterior surface 13A of the tube 1, said coating including a carrier
 composed of a biocompatible material and having dispersed therein a
 radioactive substance 11. The interior surface 10 of the tube 1 may not
 contain radioactive substance because the blood stream passing the
 interior surface 10 could sweep away the substance, if any, quickly. A
 vascular stent of different constructions is well known to one who is
 skilled in the art of stent development and design.
 FIG. 3 shows a cross-sectional perspective view of the stent and its coated
 layer at the exterior exposed surface of said stent. The stent has a
 plurality of wire branches 8A, 8B, 8C or meshes coupled to each other. The
 stent may also contain multiplicity of openings therethrough. For
 illustration purposes, each wire branch 8A, 8B, 8C has an interior exposed
 surface 10 and an original exterior surface 13A, wherein a thin layer of
 less than 100 microns is adhered to the original exterior surface 13A to
 make it as an exterior exposed surface 13. The adherence of a thin layer
 to the stent wire branches may be done by coating, dip coating, adhering,
 painting, and the like. The layer may compose any biocompatible material
 selected from the group of bio-degradable polymer, thermally degradable
 material, and non-degradable material.
 FIG. 4 shows an ablation apparatus system comprising a stent 21 having
 radioactive substance layer at the exterior surface of the wire branches
 of the tube 1, detachable conducting wire means 29 and a RF current
 generator 30, wherein the radioactive substance has thermally enhanced
 irradiation capability for tissue treatment.
 In one embodiment, at least one temperature sensing means 27 is disposed at
 a distal end of said conducting wire means 29. In another embodiment, a
 temperature sensor 27A is disposed on the elongated metallic tube 1 or at
 the exterior surface of the stent 21. The temperature sensor can be a
 thermocouple type or a thermister type. Insulated temperature sensing wire
 28 passes from the temperature sensing means 27, to an external
 temperature control mechanism 31. The RF energy delivery is controlled by
 using the measured temperature from the temperature sensing means 27,
 through a closed-loop temperature control mechanism 31 and/or algorithm.
 When the measured temperature rises to the preset high-limit point, the
 temperature control mechanism sends out a signal to cut off the RF current
 supply. In a similar manner, when the measured temperature drops to the
 preset low-limit point, the temperature control mechanism sends out a
 signal to activate the RF current supply.
 In one preferred embodiment, a method of preventing restenosis of a blood
 vessel which has undergone angioplasty to open a restricted region of a
 lumen of the vessel is disclosed, the method comprising (1) inserting a
 stent into the blood vessel and deploying the stent to contact the vessel
 wall at the site of the restricted region; (2) irradiating the tissue in
 the wall at said site with a radioactive substance in a coated layer which
 is coated to an exterior surface of the stent; and (3) providing
 radiofrequency current from a radiofrequency current generator to the
 stent through an electrical conducting wire so that the radioactive
 substance has thermally enhanced irradiation capability for tissue
 treatment.
 As an alternative illustration, a method for treating tissues of a patient
 having a metallic implant is disclosed, said metallic implant having a
 thin coating on an exposed surface of said implant and said coating
 including a carrier composed of a biocompatible material and having
 dispersed therein a radioactive substance. The method comprises the steps
 of (1) inserting detachable conducting wire means for detachably contact
 said metallic implant, said detachable conducting wire means having a wire
 distal end and a wire proximal end, wherein the wire distal end is to
 contact the metallic implant and the wire proximal end is to be coupled to
 a radiofrequency current source; and (2) applying radiofrequency current
 from a radiofrequency current generating means to the metallic implant
 through the detachable conducting wire means so that the radioactive
 substance has thermally enhanced irradiation capability for tissue
 treatment.
 The external RF current generating means has the capability to supply RF
 current by controlling the time, power, and temperature through an
 optional separate closed-loop temperature control means. The patient is
 connected to the RF generator means through a DIP electrode to form a
 closed-loop current system. Therefore, RF current is applied and delivered
 to the targeted atherosclerosis region, through the detachable conducting
 wire means of this invention. The radiofrequency current in this invention
 is preferably within the range of 50 to 2,000 kHz. By providing thermal
 energy to the thin layer through radiofrequency principles, the active
 ingredient, such as radioactive substance or anticoagulant, diffuses more
 quickly into the surrounding contact tissue for prolonged radiotherapy.
 In a particular embodiment, the material for the stent or metallic implant
 of this invention may be selected from the group consisting of platinum,
 iridium, gold, silver, tungsten, stainless steel, Nitinol, or an alloy of
 these metals.
 From the foregoing description, it should now be appreciated that an
 ablation apparatus system for the tubular organs, atherosclerosis, and the
 treatment of vascular tissues, comprising a suitable energy source and a
 layer of radioactive substance has been disclosed. While the invention has
 been described with reference to a specific embodiment, the description is
 illustrative of the invention and is not to be construed as limiting the
 invention. Various modifications and applications may occur to those who
 are skilled in the art, without departing from the true spirit and scope
 of the invention, as described by the appended claims.