JP2004516067A - Bioactive drug delivery device and method - Google Patents

Abstract

A prosthesis (122) for use in a hollow body structure of a patient has a coiled body (105) with a radially extending opening (113), the coiled body being in a radially contracted state and in a radial direction. It is movable to and from the extended state. A material (124) extends along a coiled path along the coiled body. An administrable bioactive agent (M, 147) is bound to at least one of the coil and the material. The material may be configured as a coiled sleeve of material having an inner surface and an outer surface (124B, 124A), the inner surface forming the interior of the coiled body sleeve (124C). The dispensable agent may be provided, for example, on the outer surface of the material, or incorporated into the material to form a drug / material matrix, or on the inner surface of the material, or the sleeve. It can be provided inside the interior. Structures can be used to delay the transfer of the drug to the patient.

Description

[0001]
Background of the Invention
The present invention provides for the use of coiled prostheses, typically coated coiled stents, to deliver bioactive agents within a patient's hollow body structure, particularly cardiovascular and peripheral vascular diseases such as vascular stenosis and restenosis. Provided are devices and methods for delivery to a target site in the vasculature for incision and other tissue dissection, treatment of aneurysms, and the like.
[0002]
Research is being conducted to find out the causes of coronary restenosis after balloon angioplasty and its possible treatment. Restenosis following balloon angioplasty is believed to result from a number of causes, including elastic recoil of the blood vessels, thrombus formation, and cell wall growth. Chan, AW, Chew, DP and Lincoff, AM, Update on Pharmacology for Restenosis, Current Interventional Cardiology Reports 2001, 3: 149-155, with perennial lesions with restenosis and percutaneous coronary artery with restenosis unchanged. Although drug eluting stents may prove effective, they conclude that larger clinical trials are needed.
[0003]
However, the devices and methods of the present invention benefit from introducing a bioactive agent into a hollow body structure, such as the ureter, urethra, bronchus, biliary tract, gastrointestinal tract, etc., along with a reinforcing or protective structure within its body cavity. It is also useful to be placed for treatment of other conditions that may result in The prosthesis is placed endoluminally. As used herein, "endoluminally" means placement via a percutaneous or phlebotomy procedure, wherein the prosthesis is transluminally translocated through the body cavity from a remote location to a target site within the body cavity. Sent to. In vascular procedures, a prosthesis is introduced "endovascularly" using a catheter over a guidewire, usually with the guidance of a fluorescence or other imaging system. The catheter and guidewire can be introduced through the normal site of access to the vasculature, such as the femoral artery or the brachial artery, the subosseous artery, for access to the target site.
Endoluminal prostheses typically have at least one radially expandable, usually cylindrical segment. Here, “radially expandable” means that the cylindrical segment is expanded from a small diameter shape (for intraluminal placement) to a radially expanded state (usually when a prosthesis is implanted at a desired target site). (A cylindrical shape achieved when done). The prosthesis can be inelastic (eg, malleable) and thus require internal force to expand it at the target site. Typically, this dilating force can be provided by a balloon catheter, such as an angioplasty balloon for vascular procedures. Alternatively, the prosthesis can be self-expanding. Such a self-expanding structure can be provided by a temperature-sensitive superelastic material (eg, Nitinol) that will naturally expand radially once the appropriate temperature is reached. The appropriate temperature can be, for example, slightly below normal body temperature, and if the appropriate temperature is above normal body temperature, use any method for heating the structure. There must be. Another type of self-expanding structure uses an elastic material, such as stainless steel or a superelastic alloy, to hold the body segment in an unconstrained state (eg, when released from the sheath's radial constraint). , So as to obtain the desired radially expanded diameter. To remain fixed within the body cavity, the prosthesis remains partially restrained by the body cavity. The self-expanding prosthesis can be delivered in its radially constrained state, for example, by placing the prosthesis in a delivery sheath or tube and retracting the sheath at the target site. Such general aspects of construction and mode of delivery are well known in the art.
[0004]
The dimensions of a typical endovascular prosthesis will depend on its intended use. Typically, prostheses will have a length in the range of 0.5 cm to 10 cm, usually 0.8 cm to 5 cm, for blood vessels. The small diameter (in a radially buckled state) of the tubular prosthesis is typically about 1 mm to 10 mm, more usually 1.5 mm to 6 mm for blood vessels. Its expanded diameter is usually about 2 mm to 50 mm, preferably about 3 mm to 15 mm for blood vessels and about 25 mm to 45 mm for aorta.
[0005]
One type of endovascular prosthesis has both a stent member and a graft flap type cover member. These endovascular prostheses are often referred to as stent-grafts. Stent-grafted flaps are typically introduced using a catheter with both the stent and the graft flap in contracted and reduced diameter. Upon reaching the target site, the stent and graft are expanded. After expansion, the catheter is withdrawn from the vessel, leaving the stent-graft at the target site. Graft flaps can be formed, for example, from PTFE, ePTFE or Dacron® polyester.
[0006]
Implant flaps are used in the body for a variety of reasons, including treating blood vessels or treating diseased sites, such as those that may result from injury, disease or aneurysm. It has been found that it is advantageous to provide holes in the wall of the graft flap to provide tissue ingrowth on the wall of the graft flap. For larger diameter graft flaps, woven graft flap material is often used. For small and large vessels, porous fluoropolymers such as ePTFE have been found to be useful.
[0007]
The coiled stent can be wound in a twisted and compressed state about the catheter axis for deployment. The coiled stent can be maintained in this torsionally compressed state by fixing both ends of the coiled stent on the catheter shaft. Upon reaching the target site, the ends are released, for example, by pulling on a wire. See, for example, U.S. Patent Nos. 5,372,600 and 5,476,505. Alternatively, the endovascular prosthesis can be held in its reduced state by a sleeve, which can be selectively retracted to release the prosthesis. The third approach is to expand the prosthesis at the target site using a balloon, which is the most common. The stent is typically expanded beyond its elastic limit so that it remains in its expanded state after the balloon has been deflated and removed. One example of a balloon expandable stent is the Palmaz-Schatz stent, commercially available from Cordis Divison of Johnson & Johnson. Stents are also commercially available from Medtronic AVE of Santa Rosa, Calif. And Guidant Corporation of Indianapolis, Indiana.
[0008]
Summary of the invention
In the sense as used herein, bioactive agents are diagnostic and therapeutic agents such as radiation-emitting agents used for imaging and / or therapy, anti-inflammatory agents, anti-thrombotic / antiplatelet agents, and anti-proliferative agents and the like. A composition used to help prevent restenosis, an apoptotic agent, intercalating into DNA or RNA chains (8-methoxypsoralen), cross-linking into DNA or RNA chains (8-methoxypsoralen and ultraviolet light), Alternatively, it includes a light-activated agent that, when activated by light, causes apoptosis (phtalocynine) or necrosis (tin-ethyl ethiopurpurin). The following are some specific examples of these groups of drugs.
[0009]
Anti-inflammatory:
Aspirin or acetylsalicylic acid
Oral corticosteroid (generic name followed by a trademark in parentheses)
Prednisone (Deltasonone), methylprenisolone (Medrol), prednisolone solution (Pediapred, Prelone)
Inhaled corticosteroids (general name followed by a trademark in parentheses)
Flunisolid (AeroBid, AeroBid-M), triamcinolone (Azmacort), beclomethasone (Beclovent, Vanceril), budesonide (Pulmicort), fluticasone (fluticasone) (Flovent), nedocromilone sodium (Intal)
[0010]
Non-steroidal anti-inflammatory drug (generic name):
1. Diclofenac
2. Diflunisal§
3. Etodolac
4. Fenoprofen§
5. Flictafenin *
6. Flurbiprofen§
7. Ibuprofen§
8. Indomethacin§
9. Ketoprofen§
10. Meclofenamate † §
11. Mefenamic acid
12. Meloxicam§
13. Nabumeton
14． Naproxen§
15. Oxaprozin
16. Phenylbutazone§
17． Piroxicam§
18. Rofecoxib
19. Sulindac§
20. Tenoxicam *
21. Thiaprofenic acid *
22. Tolmetin§
* Not available in the US
い な い Not available in Canada
§ Its generic name product is available in the United States
[0011]
Antithrombotic agent (general name):
Anisindione indication: embolism, lung; embolism, lung, prophylaxis;
Thrombosis, thrombosis, prevention
Anti-trobin III (human) indication; embolism, thrombosis
Argatroban labeling: thrombosis, thrombocytopenia, second only to heparin,
Dicoumarol indication: embolism, lung; embolism, lung, prophylaxis; fibrosis, atrium, assist; obstruction, coronary artery, assist, thrombosis, thrombosis, prevention
Heparin sodium indication: abnormal blood clotting, pulmonary tuberculosis (consumption), hemodialysis, assist, embolism, lung, embolism, lung, prevention; fibrosis, atrial, assist; surgery, assist, thrombosis, thrombosis, prevention, blood transfusion ,auxiliary
Lepirudin (rDNA) display: thrombosis, second only to thrombocytopenia and heparin
[0012]
Antiproliferative(General name followed by a trademark in parentheses):
Terazosin- (Hytrin) antihypertensive, therapeutic agent for benign prostatic hyperplasia,
Finasteride (Systemic)-(propecia, Proscar) Treatment for Benign Prostatic Hyperplasia, Hair Growth Stimulant, Hair Loss Androgen (Systemic)
Doxazosin (Systemic)-(Cardura) antihypertensive, therapeutic for benign prostatic hyperplasia
Tamsulosin (Systemic)-(Flomax) A therapeutic agent for benign prostatic hyperplasia
Prazosin (Systemic)-(Minipress) Antiseptic against ergot alkaloid poisoning, antihypertensive, therapeutic agent for benign prostatic hyperplasia, vasodilator, congestive heart failure, auxiliary treatment for vasospasm
Yet another specific example of an antiproliferative agent (a generic name followed by a trademark in parentheses) is as follows.
Mitomycin for injection (Mutamycin); Bleomycin sulfate for injection (Blenoxane); Doxorubicin hydrochloride for injection (Adriamycin or Rubex or Doxorubicin hydrochloride); Daunorubicin hydrochloride (Cerubidine); ) (DaunoXome); doxorubicin hydrochloride for injection (liposome) (Doxil); epirubicin hydrochloride for injection (Ellence); idarubicin hydrochloride for injection (Idamycin); plicamycin for penicamicin; Statin (Nipent); Mitoxantrone for injection (Novan) rone) and valrubicin (valrubicin) (Valstar).
[0013]
A first aspect of the invention relates to a prosthesis for use in a hollow body structure of a patient. The prosthesis has a coiled body with a radially extending opening, the coiled body being movable between a radially contracted state and a radially expanded state. The material extends along a coiled path along the coil. An administrable bioactive agent is associated with at least one of the coil and the material. The administrable agent can be administered within the hollow body structure of the patient. The material may include a coiled sleeve of material having an inner surface and an outer surface, the inner surface forming an interior of the sleeve containing the coil. The administrable drug may be provided, for example, on the outer surface of the material, incorporated into the material to form a drug / material matrix, or on the inner surface of the material, or the sleeve. It can be provided inside the interior. The prosthesis may form a gap between them during the radially expanded state, or may include a plurality of turns that contact each other during the radially expanded state. The bioactive agent may be administered immediately or after a delay.
[0014]
Another aspect of the invention relates to a method of delivering a bioactive agent to a target site within a hollow body structure of a patient. The method includes delivering a coiled prosthesis to a target site while maintaining the coiled prosthesis in a radially contracted state, wherein the prosthesis includes a coiled body having a radially extending opening formed therethrough, and the entire coiled body. And a material that extends along a coiled path along and an administrable bioactive agent coupled to at least one of the coiled body and the material. The prosthesis is expanded into the radially expanded state to press the prosthesis against the wall of the hollow body structure. This drug is released into the hollow body structure. The prosthesis may be selected such that the material includes a coiled sleeve of material having an inner surface and an outer surface, the inner surface forming an interior sleeve that houses the entire coil. . The drug may be provided, for example, on the outer surface of the material, incorporated into the material to form a drug / material matrix, or provided on the inner surface of the material or within the sleeve. Can be. The administrable agent can be selected from the group consisting of anti-inflammatory agents, anti-thrombotic / anti-platelet agents, and anti-proliferative agents. The administrable agent can be an anti-restenotic agent.
[0015]
Yet another aspect of the present invention relates to a method of manufacturing a prosthesis for use at a target site within a hollow body structure of a patient. The method includes determining at least one therapy for the patient and selecting a suitable prosthesis for the at least one therapy. The prosthesis includes a coil having a radially extending opening, a material extending along a coiled path along the entire coil, and first and second therapeutic methods. And the first and second agents are bound to at least one of the coil and the material. The selecting step is performed such that at least a portion of the first drug can be released at the target site in the hollow body structure before the release of the second drug at the target site starts.
[0016]
Yet another aspect of the present invention relates to a method of manufacturing a prosthesis for use at a target site within a hollow body structure of a patient. The method includes contacting the elongate material with a mixture of a carrier and an administrable bioactive agent. At least a majority of the carrier has the drug removed from the mixture while still in contact with the material to form an agent-laden material. The drug-bearing material is then combined with a radially expandable stent to form a prosthesis suitable for use in a hollow body structure of a patient. The material can be a porous material such as ePTFE. The method may further include selecting, as the porous material, a longitudinal porous sleeve material, wherein the porous material sleeve comprises an inner surface and an outer surface, wherein the inner surface comprises the combination. After the step, the inside of the sleeve including the entire stent is formed. The step of placing can be performed by placing the mixture inside the sleeve, and then the step of removing removes excess of the mixture and then at least partially drying the elongate material. This can be done by causing The administrable agent can be selected from the group consisting of anti-inflammatory agents, anti-thrombotic / anti-platelet agents, and anti-proliferative agents. The administrable agent can be an anti-restenotic agent.
[0017]
One advantage of the present invention is that it is possible to coat one surface of the stent / graft with a bioactive agent while maintaining the other surface free of the bioactive agent. It is in. By coating only those surfaces of the device that are in close contact with the wall of the lumen being treated, the device can be made more efficient. For vascular applications, the bioactive material coated on the surface of the device in intimate contact with the flowing blood of the blood vessel is a waste material. Because it is "washed out" from the surface of the device and flows to the untreated body area. Coating one side of the device will increase the efficiency of delivery of the bioactive agent.
[0018]
Another advantage of the present invention is that it provides a drug delivery that uses the coated stent in a very flexible manner. This flexibility is provided, at least in part, by the coil properties of the stent used. This allows, for example, access from a tributary of a blood vessel for drug delivery that would otherwise not be possible. By using a stent body with radially extending openings covered by a graft flap, when the prosthesis is permanently implanted within the hollow body structure, compared to a solid stent body, Good tissue growth is promoted.
[0019]
Yet another advantage is that the surface area in intimate contact with the inner wall of the stent-graft flap tube is much larger than a standard stent, except that, as with a graft flap, It is not enough to cover the lateral branch pipe. This increased area allows for more drug to be delivered, and thus drug eluting stents can be more efficient than standard drug delivery stents (they can be delivered to unwanted areas). To deliver more drug to the target site).
[0020]
Yet another aspect of the invention is directed to a coated coiled drug delivery prosthesis having a coiled radially expandable prosthesis body with an outer surface. A porous cover is provided on the outer surface. The drug can be associated with the porous cover in various ways. One such method is to form a porous cover / drug matrix from the porous cover and the drug. Other methods include configuring the drug as a layer above or below the porous cover. Any type of structure for delaying the transfer of the drug to the patient can be used. One way to do this is to use the prosthesis body, a porous cover, and a protective layer covering the drug. The protective layer can be made biodegradable or removed by at least partially exfoliating from the structure. The drug may be configured as an integral part of the biodegradable material, such that the drug is only exposed when the biodegradable material biodegrades. The drug can also be contained within a biodegradable microencapsulated material.
[0021]
Yet another aspect of the present invention relates to a method for delivering an agent to a patient. The method can be performed by directing a coated coiled drug delivery prosthesis, including a drug associated with a porous cover placed on the coiled radially expandable prosthesis, to a target site. Following this, waiting for the protective material shielding the drug, it is effectively removed from the prosthesis subassembly, thereby exposing the drug. Drug is then allowed to move out of the prosthesis subassembly for interaction with the patient.
[0022]
One advantage of the present invention is that it provides a drug delivery that uses a coated prosthesis with great flexibility. This flexibility is provided, at least in part, by the coil properties of the prosthesis used. This allows, for example, access from a tributary of a blood vessel for drug delivery, which would otherwise not be possible.
[0023]
Other features and advantages of the present invention will become apparent from the following description, in which preferred embodiments are described in detail with reference to the accompanying drawings.
[0024]
Description of specific embodiments
FIG. 1 illustrates a stent blank 104 used to construct a coiled stent similar to that illustrated in FIGS. 3, 4 and 5A. The stent blank 104 includes a main body 106 and first and second ends 108. The main body 106 has side edges or rail members 110 connected by connecting members or bar members 112 and formed through the openings 113. The cross-bar member 112 is used when the stent blank 104 is formed into a coiled stent, as shown in FIG. 1, and is tightly wrapped around the introducer catheter, as shown in FIG. 7A. , The horizontal bar members 112 are angled with respect to the rail members 110 such that they extend axially and are flat to allow them to be more tightly wound.
[0025]
The end 108 is thinner than the main body 106 and is therefore more flexible. Further, these ends 108 have an inner tapered portion 114 terminating at a blunt tip 115. The shape of the ends 108 and the low stiffness of these ends as compared to the body 106 help prevent trauma to tissue during use. This type of coiled stent, where the end 108 is less rigid than the main body 106, is particularly useful for stabilizing a traumatic site within a patient's body, such as in the case of an incision, flap or pseudo-lumen. Can be The end 108 may also be more rigid than the main body, which embodiment is useful, for example, in treating obstructive disease on either side of a tributary tube. obtain.
[0026]
FIG. 2 illustrates a stent blank 104A that is similar to the stent blank 104 of FIG. 1, but whose main body 106A has three types of radial rigidity. That is, the main body 106A has a first relatively rigid central longitudinal portion 116, and second and third longitudinal portions 118, 120 on each side of the first portion 116. Portions 118, 120 have a radially decreasing stiffness that is progressively reduced in thickness when stent blank 104A is formed into a coiled stent. End 108A acts as a fourth longitudinal portion having the lowest radial stiffness of all portions in this embodiment. Instead of generally using a separate set of radial stiffnesses, the radial stiffness is continuous along at least a portion of the length of the stent blank 104A, and thus along the final resulting stent body. It is also possible to constitute so that it may change dynamically.
[0027]
In addition to providing a less traumatic end 108, 108A, the coiled prosthesis formed from any of the stent blanks 104, 104A, when unraveled, firstly due to its higher stiffness in the center. It has a tendency to open at its center and then at both ends. This helps to reduce the extent to which the ends 108, 108A are dragged along the surface of the vessel or other hollow body structure when the prosthesis is released.
[0028]
1A-1D illustrate four different configurations of stent blanks 104B-104E. Each of these different stent blanks has at least three rail members 110 between which connecting members or bar members 112 extend. 1A-1C, the connecting members 112 are aligned, whereas in the embodiment of FIG. 1D, they are offset. The angle of these connecting members 72 is such that when the stent blank is formed into a rigid coil during introduction, the connecting members 112 extend substantially axially and flatten for more rigid winding. It is configured to be. FIG. 1E illustrates a coiled stent 105C formed from a stent blank 104C with one or more radiopaque markers 12 used to facilitate deployment. The stent blanks 104B-104E are formed relatively wide to increase the radial force that the coiled stent can exert on the walls of the hollow body organ in which they are placed. It has been found that reducing the number of turns in a stent-graft having the same axial length helps to increase the user's control of the stent-graft during placement. This is important in certain situations, such as when processing an incision, particularly a vascular incision such as the aortic incision illustrated in FIG. 11 and described below. Also, as described above, the ends of the stent blanks 104B-104E are rounded to reduce radial forces on the ends of the stent to help prevent vascular deformation at the ends of the stent. , Or a shape having a reduced thickness.
[0029]
When the stent blank is coiled, the opening 113 of the stent, as shown in FIGS. 3-5C, acts as the body of the coiled prosthesis, as shown in FIG. 1E. The opening extends in the radial direction. Although these openings 113 are illustrated as substantially quadrilateral openings, they may be other shapes such as an ellipse, a circle, or an octagon having a combination of straight and curved lines. It is possible.
[0030]
FIGS. 3, 4, 5, and 5A illustrate four stent-graft flap embodiments 122, 122A, 122B, 122C. The stent-graft 122 includes a ladder coiled stent formed from the stent blank 104 and covered by a tubular graft material 124. That is, the implanted flap material 124 (see FIG. 3A) acts as a sleeve of material having an outer surface 124A and an inner surface 124B, said inner surface forming a sleeve interior 124C that houses the entire stent 104A. . Implant flap material 124 is preferably porous PTFE or ePTFE or Dacron® polyester. The ends 126 of the implanted flap material 124 may be glued between layers of the implanted flap material 124 using an adhesive or a suitable thermal material such as FEP (fluorinated ethylene propylene) or other thermoplastic material. Sealing is performed by disposing a sealing material and applying heat and pressure. The porosity of the implantable flap material allows for such a seal despite the inert nature of PTFE. In addition, direct bonding of PTFE to itself can be used, with a process known as firing. Other methods of sealing the end 126 could be used. One or both of the outer and inner surfaces 124A, 124B may be coated or otherwise treated to render the graft flap material 124 substantially impermeable to the passage of blood thereto. It could be permeable. At this time, it is preferred that the graft flap 124 completely surround the stent, but with the graft flap as one layer along a coiled path along only one side of the coiled body of the stent. It is also possible to configure to extend.
[0031]
The stent-graft of FIGS. 3-5C can be configured to deliver a bioactive agent, if desired. Such a coated coiled drug delivery stent can be constructed in several ways. One method is to place one or more bioactive agents on one or both of the outer and inner surfaces 124A, 124B of the material sleeve 124 illustrated in FIG. 3A. The bioactive agent can also be disposed on the inner surface 124B or housed within the sleeve interior 124C, such agents can be, for example, coated on the stent or associated with the stent. It is also possible to capture between the inner surfaces 124B. Another method is to incorporate the drug into the implanted flap material 124 to form a drug / material matrix. Such a matrix can be constructed by using a porous material as the graft flap material 124. The porous graft material is then saturated with a mixture of a carrier, such as water or alcohol, and one or more drugs. One way to do this is illustrated in FIG. 3B. The implant flap sleeve 124 has one end 124F knotted to close the end 124F while using the syringe S to fill the implant M with the mixture M. . If the mixture has fully saturated graft flap material 124 (this is usually evident by the mixture oozing out of the holes in the graft flap material 124), the excess mixture is removed and the drug is immediately removed. The filled implant flap material is at least partially dried. Another method is to produce the implanted flap material with one or more drugs dispersed therein. These agents can be microencapsulated, for example, to provide a sustained release function for the agent. Sustained release can also be achieved by coating outer surface 124A with a suitable biodegradable material.
[0032]
Another method of delivering a bioactive agent is described with reference to FIGS. 5D-5I. 5D-5I are very large cross-sectional views of the coated coiled drug delivery stent 145-145E. FIG. 5D illustrates a stent wall 139 with an outer surface 139A covered by a porous cover 141, which is covered by a protective coating 143. The porous cover, in this embodiment, preferably comprises a porous cover / drug matrix using ePTFE as the porous cover. Protective coating 143 is preferably a biodegradable polymer. Once coated, the coiled drug delivery stent 145 is positioned within the patient's body and the protective coating 143 begins to degrade, and after a predetermined time, the drug begins to migrate from the matrix to the patient.
[0033]
FIG. 5E illustrates another embodiment of the coated coiled drug delivery stent 145A, wherein like reference numbers indicate like members. The porous coating 141A of the embodiment of FIG. 5E comprises ePTFE, which is covered by a drug layer 147, which is further covered by a protective coating 143. In the embodiment of FIG. 5F, the arrangement of porous coating 141A and drug layer 147 has been reversed from that of FIG. 5E so that drug layer 147 is located between stent wall 139 and porous coating 141A. are doing. In each of these cases, after the protective coating 143 has sufficiently degraded to expose the drug, the drug is allowed to migrate from the stents 145, 145A, 145B to interact with the patient. 5D and 5F, porous coating 141 has sufficient porosity to allow the drug to pass therethrough. FIGS. 5G, 5H and 5I illustrate an embodiment similar to FIGS. 5D, 5E and 5F, but with the protective coating 143 omitted.
[0034]
The drug layer 147 may be, for example, a NO generator, paclitaxel, statins, taxol, various forms, ie, low molecular weight heparin, thienopyridine, glycoprotein IIb / IIIb inhibitor, antiplatelet agent, fibrin It may include lytic agents, anticoagulants, thrombolytic agents, abciximab, rapamycin, hirudin, VEGF, Hirulog, ticlopidine, clopidogrel, as well as various types of therapeutic and diagnostic agents, including the bioactive agents described above. The stent 145, 145A or 145B directs the drug delivery stent to a target site within the patient and waits for the protective material initially shielding the drug to be effectively removed from the stent, thereby exposing the drug. It is configured as follows. Following this, the medicament is allowed to move from the stent to act on the patient.
[0035]
In some situations, it may be desirable to configure the prosthesis such that at least the first and second bioactive agents are carried by the prosthesis, and that the first agent may be released prior to the onset of release of the second agent. At least a portion (eg, at least half thereof) may be released. This can be achieved in several ways. A protective coating 143 can be disposed between the layers of the bioactive agent. The first medicament can be applied over the second medicament to cover the second medicament, thereby initially preventing the release of the second medicament. One or both of the agents may be encapsulated in a biodegradable cover so that they are released only after a predetermined period of time.
[0036]
The coiled stent-graft 122 has a plurality of spaced apart turns 128 forming a generally helical void 130 therebetween. The average width of the spiral gap 130 is equal to about 0% to 1200% of the average width of the turn 128. In some applications, the average width of the void 130 is about 50% to 800% of the average width of the turn 128 when the stent-graft 122 is deployed. In other applications, such as incision placement described below, the void 130 is closed, ie, about 0%.
[0037]
The stent-graft 122 has a substantially constant pitch except for its central region. The pitch of the central turn 132 of the stent-graft 122 matches the placement of the stent-graft 122 at the intersection of the main or first tube and the tributary tube, as described in more detail with reference to FIGS. 7A-7C. To be much larger than the pitch of its adjacent turns 128.
[0038]
FIG. 4 illustrates a stent-graft 122A in which the central turn 132A also has a large pitch as opposed to the adjacent turn 128A. However, one turn of the central turn 132A has a larger, fully expanded diameter than the turn on the other side to accommodate the transition between the smaller and larger vessels.
[0039]
FIG. 5 illustrates a stent-graft 122B configured to be placed with end turns 134 having a much greater pitch than its adjacent turns 128B. This stent-graft flap 122B is such that one end of the stent-graft is at the intersection between the main vessel and the tributary vessel and the stent-graft is opposite to both sides as in the embodiment of FIGS. In contrast, it is used when positioned to extend to one side of the intersection. FIG. 5A illustrates a stent-graft 122C that can be used at a location other than the bifurcation, with substantially evenly spaced turns 128C.
[0040]
FIGS. 5B and 5C illustrate stent-graft flaps 122C, 122D, each made from the stent blank 104D of FIG. 1C. These stent-grafts 122C, 122D are configured and intended to have edges 135 of adjacent turns 137 adjacent to each other. 5B and 5C are intended for treatment of an aortic incision. The combination of each turn having a relatively large width compared to its diameter in the radially expanded state, and the use of abutting or overlapping adjacent edges, results in a full surface coverage and a larger outer surface. Such stent-graft flaps are useful when radial forces are desired. The width of the turn 137 is measured perpendicular to the edge 135. Also, reducing the number of turns facilitates control of the stent-graft and reduces the number of rotations of the shafts 138, 142 required before release from the catheter 136. The stent-graft flaps 122C, 122D can be characterized by having an average diameter to turn-to-width ratio of about 0.1 to 1 to about 2.4 to 1 in their radially expanded state. The stent-graft flaps 122C, 122D can also be characterized in their radially expanded state by having an average turn-width to stent-graft flap length ratio of about 1: 1 to about 1: 4. In some situations, it may not be necessary or desirable for the connection 112 to extend axially during the tightly wound radially contracted state. In some cases, the connection 112 could be replaced by other shaped connectors, such as corrugated or undulating connectors, V-shaped connectors, x-shaped connectors, and the like.
[0041]
6A-6B illustrate a catheter 136 used to deploy the stent-graft of FIGS. 3 and 4. FIG. The catheter 136 has outer, intermediate and inner rotating telescopic shafts 138, 140, 142, each with a distal end 144, 146, 148. Each of these shafts has a prosthesis holder 150, 150A, 150B at its distal end 144, 146, 148. These prosthesis part holders 150, 150A, 150B include pull wires 152, 152A, 152B that are attached to axially extending lumens 154, 154A, 154B formed in the body of shafts 138, 140, 142. Along the exit holes 156, 156A, 156B, across the gaps 158, 158A, 158B and back to the reinsertion openings 160, 160A, 160B. The pull wires 152, 152A, 152B are engaged, for example, through different portions of the stent-graft 122 to secure those portions of the stent-graft to the shafts 138, 140, 142. As shown in FIG. 7A, the prosthesis holder 150B at the distal end 148 of the inner shaft 142 is engaged with the distal end 166 of the stent-graft 122. The holders 150, 150A at the distal ends 144, 144A of the outer and intermediate shafts 138, 140 engage the proximal end 168 and the central turn 132 of the stent-graft 122, respectively. One or more of these shafts 138, 140, 142 may be braided to increase torsional rigidity to assist rotation.
[0042]
FIG. 6C illustrates the distal end of a catheter 136A having only two axes, an outer axis 138A and an inner axis 142A. This catheter 136A typically places an endovascular prosthesis of the type that does not have a central turn with an enlarged pitch, such as those of FIGS. 5, 5A, 5B and 5C, and thus does not require a catheter with an intermediate shaft. Is what is used when
[0043]
FIG. 6D schematically illustrates the proximal end adapter 170 attached to the proximal end of the catheter 136A of FIG. 6C. The proximal end adapter 170 has a distal end and a proximal end 172, 176 through which the catheter 136A passes. The proximal end adapter 170 provides rotation of one or both of the shafts 138A, 142A by manipulating a thumbwheel 174 attached to the portion 176. From the far end 172, a flip lever 175 directs, either to fix the shafts 138A, 142A to each other or to allow them to move axially relative to each other. It is movable between a fixed position and a release position. The pull wires 152, 152B are typically secured to their respective shafts 138A, 142A by deployment knobs 178, 180, and pulling the deployment knobs 178, 180 releases the pull wires 152, 152B, respectively. Thus, the puller wires are pulled to allow the endovascular prosthesis to be released from the appropriate holder 150, 150B.
[0044]
6F and 6G illustrate a further triaxial embodiment of the present invention that is similar to the triaxial embodiment of FIGS. 6A and 6B. Instead of using the lumen 154 to house the puller wire 152, the tubular members 162, 162A, 162B, typically hypotubes, can be secured outside the shafts 138B, 140B, 142B. It is. Voids or breaks are provided at the distal ends of the hypotubes 162, 162A, 162B to form the voids 158, 158A, 185B.
[0045]
FIG. 7A illustrates the stent-graft 122 of FIG. 3 wrapped tightly around the catheter 136. The distal end 166, proximal end 168, and central turn 132 of the stent-graft 122 are secured to the distal ends 148, 144, and 146 of the inner, outer, and intermediate shafts 142, 138, 140 by the prosthesis holder 150. Have been. The stent-graft 122 is housed in the main vessel 182 with the central turn 132 aligned with the intersection 184 of the main vessel 182 and the branch vessel 186. To ensure proper placement at the intersection 184 of the central turn 132, the stent-graft 122 includes one or more remote visualization markers at or near the turn 132. . In FIG. 8, radiopaque markers 188, 190, 192 are shown at the distal, middle and proximal ends of the central turn 194 of the stent 196. Radiopaque markers can be formed to provide information regarding both the location and orientation of the stent 196 on the catheter. For example, the radiopaque marker 190A of FIG. 9 has a wide central portion 190B extending along the rail member 110 between the rail member 110 and the arm portion 190C, so that the marker 190A can be attached to the stent 196A. It is possible to provide information on both the position and orientation around the object. The direction marker 190A is configured so that a person who looks at the marker can determine whether the turn is facing the person or away from the person based on the direction of the marker. Various other marker shapes to provide both position and orientation can also be used.
[0046]
Radiopaque markers can also be used on the placement catheter itself. For example, the radiopaque markers 191, 193, 195 may have their axes 138 B, 140 B aligned with their respective holders 150, 150 A, 150 B to indicate the position of the holders, as shown in FIG. 6F. , 142B. The radiopaque marker 193 is shown configured as an orientation marker to assist in proper placement of the prosthesis. FIG. 10 illustrates the shape of an orientation-specific radiopaque marker 197 that can be placed, for example, on axes 138, 140, 142, of one or more holders 150 of the embodiments of FIGS. 6A, 6C, and 6E. I have. Radiopaque or other remote visualization markers may also be used at other locations along the endovascular prosthesis, such as at or along each end of a placement catheter.
[0047]
FIG. 7B illustrates release of the proximal end 168 of the stent-graft 122, while FIG. 7C illustrates subsequent release of the distal end 166 of the stent-graft 122. The distal and proximal ends 166, 168 of the stent-graft 122 ensure that the open area of the central turn 122 remains opposite the intersection 184 while the central turn 132 is secured to the central shaft 140. It should be noted that it is released to help ensure substantially unrestricted fluid flow between the main vessel 182 and the branch vessel 186. It should also be noted that the number of turns can be increased or decreased by relative rotation of the shafts 138, 140, 142 prior to release of the stent-graft. Further, the length of the stent-graft 122 can be varied by relative axial sliding between the outer, middle and inner shafts 138, 140, 142. For example, instead of simply releasing the proximal end 168 of the stent-graft 122 to the position shown in FIG. 7B, the stent-graft may be properly released prior to release of the stent-graft. Rotate the outer shaft relative to the middle shaft 140 while maintaining the middle and inner shafts 140, 142 stationary so as to open the proximal end half of the stent-graft to ensure positioning. It may be desirable to let them. Similarly, prior to releasing any portion of the stent-graft, rotating both the outer and inner shafts while maintaining the intermediate shaft stationary to create the expanded diameter condition of FIG. Can be. In this way, the physician can ensure that the stent-graft 122 is properly positioned, particularly with respect to the central turn 132. If necessary or desirable, for example, the intermediate shaft 140 could be rotated with respect to the outer and inner shafts 138, 142 to assist in proper positioning or repositioning of the central turn 132.
[0048]
FIG. 7A also illustrates how, for a particular outer diameter placement catheter, by appropriately selecting the angle of the connection member 112 with respect to the side member 110, the connection member 112 is shown in phantom in FIG. 7A. Are also arranged substantially parallel to the axis of the stent-graft 122. This allows the connecting members 112 to be located closer to the catheter 136 and in its contracted reduced diameter state than in those states where these connecting members are not substantially parallel to the axis. It allows to provide a much smoother siege. This axial orientation may be in contrast to the off-axis orientation of the connecting member 112 during the enlarged diameter state of FIG. 7C. The smooth outer surface of the stent-graft 122 further facilitates insertion of the stent-graft into a hollow body organ, such as a blood vessel 182.
[0049]
FIG. 7D illustrates the stent-graft flap 122D of FIG. 5C tightly wound around the placement catheter 136A of FIG. 6C, with the proximal end of the stent-graft 122D secured to the outer catheter shaft 183A. The distal end of the stent-graft 122D is fixed to the inner catheter shaft 142A. FIG. 7E illustrates the structure of FIG. 7D after the pull wire 152B has been pulled to release the distal end of the stent-graft 122D. Immediately thereafter, pull wire 152 is pulled to release the proximal end of stent-graft 122D from outer catheter shaft 138A. Due to the width of each turn of the stent-graft 122D, each puller wire 152, 152B passes through two locations 199 along the end of the stent-graft 122D so that during delivery, the stent graft Ensure that the flap abuts against the catheter 136A.
[0050]
As described above, the stent-graft 122D is brought into a radially contracted state by rotating the inner and outer catheter shafts 138A, 142A relative to each other. Once positioned for deployment, the catheter shafts 138A, 142A are rotated relative to each other to open the stent-graft 122D. The axes 138A, 142A also allow the operator to change the pitch so that the edges 135 of the turns 137 of the stent-graft 122 are adjacent to each other when fully deployed, as is often desirable. As warranted, it is also possible to move longitudinally (axially) with respect to each other. At any time, the operator retightens the stent-graft 122D to bring it into a radially contracted state, so long as the pull wires 152, 152B have not yet been removed from the end of the stent-graft. The flap can be repositioned or the pitch can be changed. Proper placement of the graft flap 122D, including ensuring that the edges are adjacent to each other, can be aided by the use of radiopaque markers 121. See FIG. 1E.
[0051]
FIG. 11 illustrates the placement of a stent-graft 122C within the true lumen 200 of the aortic arch 202 to cover the entrance 204 to the pseudolumen 206 formed by the aortic incision 208. The aortic incisions can be of various types, all of which, together with the portal formed through the separate lining into the pseudolumen, are formed from the remainder of the wall, such as the hollow body structure wall 212. Have a false lumen caused by separation of the lining, such as the intimal lining 210. The aortic incision and other incisions may be of the type having one inlet 204 or, for example, having an inlet and an outlet. Another incision 208A is indicated by the dashed line in FIG. 11, which shows the extension of the aortic incision from the solid line portion to the outlet 214 near the bifurcation 216. It is possible to close both the inlet 204 and the outlet 214 using one or more stent-graft flaps, but that may not be necessary or desirable. Also, it may not be necessary to cover either the entrance and / or exit to the pseudolumen with a stent-graft to effectively treat the incision. The stent-graft flap 122C also has dashed lines indicating the location of the stent rail members 110 and connecting members 112.
[0052]
The stent-graft 122C is used for a thoracic level aortotomy. The stent-graft can be used for other levels of incisions along the aorta 218, such as the abdominal level 220, or along the arch 222. When a stent-graft is used in an arch 222 or other hollow body region having one or more branches, a stent-graft having one or more enlarged voids (see FIGS. 3, 4 and 7C). ) Can be used to help prevent obstruction of the branch vessels.
[0053]
5B and 5C can be used to assist in repairing various incisions other than aortic incisions. In particular, such stent-graft flaps can be used for incisions in other types of vascular incisions and other hollow body organs in which the incisions can be found. Incisions may be made as a result of non-penetrating trauma or for invasive trauma as well as biological reasons such as disease, stress, congenital disorders, and the like.
[0054]
Various modifications and variations can be made to the above-described invention without departing from the spirit of the invention as defined in the appended claims. For example, the connection member 112 may be oriented perpendicular to the rail member 110, or the graft flap material 124 may be placed only on a portion of the underlying stent or only on one side of the underlying stent. It is also possible. The number of telescopic rotatable axes of the placement catheter 136 can be increased or decreased. The telescopic shafts need not be concentric shafts slidable therein or together, but may be, for example, juxtaposed solid and / or tubular elongated members. The structure of the holder 150 can be different, for example, if the sequence of release of the prosthesis is known, one pull wire can be used instead of three separate pull wires It is.
[0055]
All patents, applications and publications mentioned above are incorporated by reference.
[Brief description of the drawings]
FIG.
FIG. 1 illustrates a stent blank used to form a coiled stent, such as the one illustrated in FIGS. 3, 4 and 5A.
FIG. 1A
FIG. 1A illustrates a stent blank of another configuration.
FIG. 1B
FIG. 1B illustrates a stent blank of another configuration.
FIG. 1C
FIG. 1C illustrates a stent blank of another configuration.
FIG. 1D
FIG. 1D illustrates a stent blank of another configuration.
FIG. 1E
FIG. 1E illustrates a coiled stent made from the stent blank of FIG. 1B.
FIG. 2
FIG. 2 illustrates a stent blank similar to that of FIG. 1, but having a different thickness along its length.
FIG. 3
FIG. 3 illustrates a stent-graft in a radially expanded state, the stent-graft having a stent similar to that shown in FIG. 1 covered by a sleeve of porous graft material. The stent-graft has a central turn with a greatly increased pitch for placement at the bifurcation.
FIG. 3A
FIG. 3A is an enlarged cross-sectional view of the prosthesis along line 3A-3A in FIG.
FIG. 3B
FIG. 3B is a simplified side view illustrating the introduction of a mixture of a carrier and a bioactive agent into the interior of a sleeve of a porous graft material.
FIG. 4
FIG. 4 is similar to that of FIG. 3, but with one end of the stent-graft having a much larger radial expansion diameter than the other end to accommodate tubes having various inner diameters. 1 illustrates a stent-graft flap.
FIG. 5
FIG. 5 shows another embodiment of the stent-graft of FIG. 3, wherein the stent-graft has a large enlarged diameter and one turn having a large pitch at one end of the stent-graft. Is illustrated.
FIG. 5A
FIG. 5A illustrates a stent-graft similar to that of FIG. 3, but with substantially uniformly spaced turns.
FIG. 5B
FIG. 5B illustrates a stent-graft made from the stent-graft of FIG. 1C.
FIG. 5C
FIG. 5C illustrates a stent-graft made from the stent-graft of FIG. 1C.
FIG. 5D
FIG. 5D is three enlarged partial cross-sectional views of three types of coated coiled drug delivery stents.
FIG. 5E
FIG. 5E shows three enlarged partial cross-sectional views of three types of coated coiled drug delivery stents.
FIG. 5F
FIG. 5F shows three enlarged partial cross-sectional views of three types of coated coiled drug delivery stents.
FIG. 5G
FIG. 5G is three enlarged partial cross-sectional views of three types of coated coiled drug delivery stents.
FIG. 5H
FIG. 5H shows three enlarged partial cross-sectional views of three types of coated coiled drug delivery stents.
FIG. 5I
FIG. 5I shows three enlarged partial cross-sectional views of three types of coated coiled drug delivery stents.
FIG. 6A
FIG. 6A is an overall view of the distal end of a triaxial deployment catheter used to deploy the stent-graft of FIGS. 3-5.
FIG. 6B
FIG. 6B is an end view of the shaft of 6A.
FIG. 6C
FIG. 6C is an embodiment similar to the catheter of FIG. 6A, but with only the inner and outer shafts.
FIG. 6D
FIG. 6D illustrates the proximal end adapter attached to the proximal end of the catheter of FIG. 6C.
FIG. 6E
FIG. 6E illustrates another embodiment of the catheter of FIG. 6C.
FIG. 6F
FIG. 6F is a simplified side view of yet another embodiment of the catheter of FIGS. 6A and 6B.
FIG. 6G
FIG. 6G is a simplified cross-sectional view of yet another embodiment of the catheter of FIGS. 6A and 6B.
FIG. 7A
FIG. 7A is a view of FIG. 3 in which the catheter of FIGS. 6A and 6B is tightly wrapped around the distal end and placed intravascularly with the middle of the stent-graft at the intersection of the main vessel and the branch vessel. 1 illustrates a stent-graft according to the present invention.
FIG. 7B
FIG. 7B illustrates the release of the proximal half of the stent-graft.
FIG. 7C
FIG. 7C illustrates release of the distal half of the stent-graft prior to removal of the catheter shaft.
FIG. 7D
FIG. 7D illustrates the stent-graft of FIG. 5C tightly wound around a placement catheter.
FIG. 7E
FIG. 7E shows the stent-graft of FIG. 7D with the distal end of the stent-graft released from the catheter and the proximal end of the stent-graft releasably secured to the catheter in two positions. Figure 2 illustrates a flap.
FIG. 8
FIG. 8 illustrates the placement of radiopaque marks at different locations along a coiled laddered stent with a central turn having a greatly increased pitch.
FIG. 9
FIG. 9 illustrates the placement of radiopaque marks at different locations along a coiled laddered stent with a central turn having a greatly increased pitch.
FIG. 10
FIG. 10 illustrates an example of a radiopaque mark formed to allow determination of the orientation of the prosthesis and further its position.
FIG. 11
FIG. 11 illustrates the stent-implant flap of FIG. 5B within the true lumen of the aortic arch at the entrance of the aortic incision, with another aortic incision indicated by dashed lines.

Claims (127)

A prosthesis for use in a hollow body structure of a patient, comprising:
A coil-shaped body having a radially extending opening formed therethrough, the coil-shaped body being movable between a radially contracted state and a radially expanded state,
A material extending along a coiled path along the entire coiled body;
A prosthesis comprising an administrable bioactive agent associated with at least one of the coil and the material, the bioactive agent being administrable into a hollow body structure of a patient. The prosthesis of claim 1, further comprising a delayed release material associated with the administrable agent for delaying release of the administrable agent into the hollow body structure. 3. The prosthesis of claim 2, wherein the delayed release material comprises a biodegradable delayed release layer. 2. The prosthesis of claim 1, wherein the administrable drug is microencapsulated using a biodegradable encapsulating material to delay migration of the drug from the prosthesis. The prosthesis of claim 1, further comprising removing a protective layer from the coil and the material, such that when removed, the administrable agent is movable from the prosthesis. 6. The prosthesis of claim 5, wherein the protective layer comprises a biodegradable material such that the protective layer is removed when biodegraded. 6. The prosthesis of claim 5, wherein the protective layer includes a sheath that can be withdrawn from the coil and a material for removing the protective layer therefrom. 2. The prosthesis of claim 1, wherein the coiled body has longitudinally extending side members and a lateral member connecting the side members. The prosthesis according to claim 1, wherein the coil is made of metal. The prosthesis of claim 1, wherein the prosthesis includes spaced turns that form a gap therebetween during the radially expanded state. 2. The prosthesis of claim 1, wherein the prosthesis has a plurality of turns, of which adjacent ones contact each other during the radially expanded state. The prosthesis of claim 1, wherein the material comprises a coiled sleeve of material having an inner surface and an outer surface, the inner surface defining an interior of the sleeve including the entire coil. 13. The prosthesis of claim 12, wherein the drug is at least in the next position, i.e., on an outer surface of the material, the outer surface being in the hollow body structure when the coil is in the radially expanded state. Prosthesis, wherein the material is disposed only at a location that is in intimate contact with the hollow body structure and is administrable from that location) and is administrable from that location. 13. The prosthesis of claim 12, wherein the drug is disposed in at least the next location, i.e., a location that is incorporated into the material and forms a drug / material matrix, and is administrable from that location. 13. The prosthesis of claim 12, wherein the medicament is disposed on at least a next location, i.e., on an interior surface of the material, and is dispensable from that location. 13. The prosthesis of claim 12, wherein the medicament is located at least in a next location, i.e., within the interior of the sleeve and is dispensable from that location. 2. The prosthesis of claim 1, wherein the material has a radially inwardly facing inner surface and a radially outwardly facing outer surface, the material having the coiled body adjacent the coiled body. A prosthesis, wherein the outer surface is positionable with respect to the hollow body structure when the coiled body is in the radially expanded state. 13. The prosthesis according to claim 12, wherein the medicament is located on the outer surface of the material and is dispensable from that location, so that it is located and located only in close contact with the hollow body structure. Prosthesis that can be administered from The prosthesis of claim 1, further comprising first and second administrable agents. 20. The prosthesis of claim 19, wherein the first agent is stacked on the two agents. 20. The prosthesis of claim 19, wherein the first medicament is administrable prior to commencement of administration of the second medicament. 20. The prosthesis of claim 19, wherein at least half of the first medicament is administrable before administration of the second medicament. The prosthesis of claim 1, wherein the material is a porous material. 24. The prosthesis of claim 23, wherein the porous material comprises porous PTFE. 24. The prosthesis of claim 23, wherein the porous material has an interior surface that is substantially impermeable to the passage of blood therethrough. 2. The prosthesis of claim 1, wherein the administrable agent is from the group consisting of anti-inflammatory agents, anti-thrombotic / anti-platelet agents, and anti-proliferative agents, apoptosis-inducing agents, photoactivators, and biological agents. Prosthesis selected. 2. The prosthesis of claim 1, wherein the administrable agent comprises an anti-restenotic agent. A prosthesis for use in a hollow body structure of a patient, comprising:
A coil-shaped body having a radially extending opening formed therethrough, the coil-shaped body being movable between a radially contracted state and a radially expanded state,
A coiled sleeve of material extending along a coiled path, said material having an inner surface and an outer surface, and forming a coiled interior of said sleeve for housing said coiled body. A prosthesis comprising a sleeve and an administrable bioactive agent provided on the outer surface of the material, the administrable agent being administrable into a hollow body structure of a patient. 29. The prosthesis of claim 28, wherein the administrable agent comprises an anti-restenotic agent. 29. The prosthesis of claim 28, further comprising a delayed release material coupled to the administrable agent to delay release of the administrable agent into the hollow body structure. 29. The prosthesis of claim 28, wherein the prosthesis has spaced turns forming a gap therebetween when in the radially expanded state. 29. The prosthesis of claim 28, wherein the material comprises porous PTFE. A prosthesis for use in a hollow body structure of a patient, comprising:
A coil-shaped body having a radially extending opening formed therethrough, the coil-shaped body being movable between a radially contracted state and a radially expanded state,
A coiled sleeve of material extending along a coiled path, said material having an inner surface and an outer surface, and forming a coiled interior of said sleeve for housing said coiled body. Sleeve and
A prosthesis comprising an administrable bioactive agent incorporated into the material to form a drug / material matrix, the administrable agent being administrable into a hollow body structure of a patient. 34. The prosthesis of claim 33, wherein the administrable agent comprises an anti-restenotic agent. 34. The prosthesis of claim 33, further comprising a delayed release material coupled to the administrable drug to delay release of the administrable drug into the hollow body structure. 34. The prosthesis of claim 33, wherein the prosthesis has spaced turns that form a gap therebetween when in the radially expanded state. 34. The prosthesis of claim 33, wherein the material comprises porous PTFE. A prosthesis for use in a hollow body structure of a patient, comprising:
A coil-shaped body having a radially extending opening formed therethrough, the coil-shaped body being movable between a radially contracted state and a radially expanded state,
A coiled sleeve of material extending along a coiled path, said material having an inner surface and an outer surface, and forming a coiled interior of said sleeve for housing said coiled body. Sleeve and
A prosthesis comprising an administrable bioactive agent disposed on the inner surface of the material or within the sleeve, the administrable agent being administrable into a hollow body structure of a patient. 39. The prosthesis of claim 38, wherein the administrable agent comprises an anti-restenotic agent. 39. The prosthesis of claim 38, further comprising a delayed release material coupled to the administrable drug to delay release of the administrable drug into the hollow body structure. 39. The prosthesis of claim 38, wherein the prosthesis has spaced turns forming a gap therebetween when in the radially expanded state. 39. The prosthesis of claim 38, wherein the material comprises porous PTFE. A method for delivering a bioactive agent to a target site within a hollow body structure of a patient, comprising:
Delivering the coiled prosthesis to a target site within the hollow body structure of the patient with the prosthesis in a radially contracted state, wherein the prosthesis comprises a coiled body having a radially extending opening formed therethrough. And a material extending along a coiled path along the entire coil, and an administrable bioactive agent coupled to at least one of the coil and the material.
Radially expanding the prosthesis from the radially contracted state to a radially expanded state to press the prosthesis against a wall of the hollow body structure;
Releasing the drug into the hollow body structure. 44. The method of claim 43, further comprising the step of selecting a prosthesis having a coiled body having longitudinally extending side members and transverse members connecting the side members. 44. The method of claim 43, wherein the radially expanding step is performed by a prosthesis having spaced turns forming a gap therebetween during the radially expanded state. 44. The method of claim 43, wherein the radially expanding step is performed by a prosthesis having turns that contact each other during the radially expanded state. 44. The method of claim 43, wherein the material further comprises a coiled sleeve of material, the coiled sleeve of material having an inner surface and an outer surface, wherein the inner surface covers the entire coil. A method comprising the step of selecting a prosthesis to form a receiving sleeve interior. 44. The method of claim 43, further comprising the step of selecting a prosthesis wherein the agent comprises first and second administrable agents. 49. The method of claim 48, further comprising the step of selecting a prosthesis wherein said first agent is layered over said second agent. 49. The method of claim 48, wherein the releasing step is performed such that at least a portion of the first drug is released prior to initiating the release of the second drug. 49. The method of claim 48, wherein said controllable release step is performed such that at least half of said first drug is released prior to the start of release of said second drug. 44. The method of claim 43, further comprising selecting a prosthesis comprising a porous material as said material. 53. The method of claim 52, wherein said selecting is performed by selecting a prosthesis wherein said porous material comprises ePTFE. 53. The method of claim 52, wherein said selecting is performed by selecting a prosthesis wherein said porous material has a surface that is substantially impermeable to the passage of blood therethrough. 44. The method of claim 43, further comprising selecting a prosthesis having a delayed release material associated with the administrable agent. 56. The method of claim 55, wherein said selecting is performed by selecting a prosthesis wherein said delayed release material comprises a biodegradable delayed release material. 56. The method of claim 55, wherein the selecting step is performed by selecting a prosthesis wherein the delayed release material comprises a delayed release layer coating the administrable drug. 56. The method of claim 55, wherein the selecting step is performed by selecting a prosthesis wherein the delayed release material is a component of a matrix of the administrable drug and the delayed release material. 56. The method of claim 55, wherein said selecting is performed by selecting a prosthesis wherein said delayed release material comprises a biodegradable polymer. 56. The method of claim 55, wherein the delayed release material comprises a protective layer, the method further comprising removing the protective layer from the coil with the material, thereby exposing the coil with the material. A method comprising the step of: 44. The method of claim 43, further comprising an administrable selected from the group consisting of an anti-inflammatory agent, an anti-thrombotic / anti-platelet agent, an anti-proliferative agent, an apoptosis-inducing agent, a photoactivator, and a biological agent. A method comprising selecting a prosthesis having a drug. 44. The method of claim 43, further comprising selecting an anti-restenotic agent as said administrable agent. A method for delivering a bioactive agent to a target site within a hollow body structure of a patient, comprising:
Delivering the coiled prosthesis to a target site within the hollow body structure of the patient with the prosthesis in a radially contracted state, wherein the prosthesis comprises a coiled body having a radially extending opening formed therethrough. A coiled sleeve of a material extending along the coiled path and having an inner surface and an outer surface, the inner surface of which forms an interior of the sleeve that houses the entire coiled body; An administrable bioactive agent provided on the side,
Radially expanding the prosthesis from the radially contracted state to a radially expanded state to press the prosthesis against the wall;
Releasing the drug from the outer surface of the material into the hollow body structure. 64. The method of claim 63, further comprising selecting an anti-restenotic agent as said administrable agent. 64. The method of claim 63, wherein releasing comprises temporarily controllably releasing the drug into the hollow body structure. 64. The method of claim 63, wherein the radially expanding step is performed by a prosthesis having spaced turns forming a gap therebetween during the radially expanded state. 64. The method of claim 63, further comprising the step of selecting a prosthesis having porous PTFE as said material. A method for delivering a bioactive agent to a target site within a hollow body structure of a patient, comprising:
Delivering the coiled prosthesis to a target site within the hollow body structure of the patient with the prosthesis in a radially contracted state, wherein the prosthesis comprises a coiled body having a radially extending opening formed therethrough. And a coiled sleeve of a material extending along the coiled path and having an inner surface and an outer surface, the inner surface of which forms the interior of the sleeve that houses the entire coiled body, and incorporated into the material. And an administrable bioactive agent to form a drug / material matrix.
Radially expanding the prosthesis from the radially contracted state to a radially expanded state to press the prosthesis against the wall; and releasing the drug from the drug / material matrix into the hollow body structure. And a method comprising: 70. The method of claim 68, further comprising selecting an anti-restenotic agent as said administrable agent. 69. The method of claim 68, wherein releasing comprises temporarily controllably releasing the drug into the hollow body structure. 69. The method of claim 68, wherein the step of radially expanding is performed by a prosthesis having spaced turns forming a gap therebetween during the radially expanded state. 69. The method of claim 68, further comprising selecting a prosthesis having porous PTFE as said material. 69. The method of claim 68, further comprising the material comprising a coiled sleeve of material, the coiled sleeve of material having an inner surface and an outer surface, the inner surface facing the coil. And a method comprising selecting a prosthesis, wherein the inner surface forms an interior of a sleeve that houses the entire coil. A method for delivering a bioactive agent to a target site within a hollow body structure of a patient, comprising:
Delivering the coiled prosthesis to a target site within the hollow body structure of the patient with the prosthesis in a radially contracted state, wherein the prosthesis comprises a coiled body having a radially extending opening formed therethrough. A coiled sleeve of a material extending along the coiled path, having an inner surface and an outer surface, the inner surface of which forms the interior of the sleeve that houses the entire coiled body; and Having an administrable bioactive agent on an inner surface or within the sleeve;
Radially expanding the prosthesis from the radially contracted state to a radially expanded state to press the prosthesis against the wall;
Releasing the drug from the interior surface of the material into the hollow body structure. 75. The method of claim 74, further comprising selecting an anti-restenotic agent as said administrable agent. 75. The method of claim 74, wherein said releasing comprises temporarily controllably releasing said drug into said hollow body structure. 75. The method of claim 74, wherein the radially expanding step is performed by a prosthesis having spaced turns forming a gap therebetween during the radially expanded state. 75. The method of claim 74, further comprising selecting a prosthesis having porous PTFE as said material. A method of making a prosthesis for use at a target site within a hollow body structure of a patient, comprising:
Determining at least one treatment for the patient;
Selecting a prosthesis suitable for the at least one treatment, wherein the prosthesis includes a coiled body having a radially extending opening formed therethrough and a coiled path along the entire coiled body. A material extending along the at least one of the coil and the material, the first and second administrable bioactive agents for the treatment. And a step coupled to
The method wherein the selecting is performed such that at least a portion of the first drug is releasable at the target site within the hollow body structure of the patient prior to initiating release of the second drug at the target site. 80. The method of claim 79, wherein said selecting is performed by selecting a prosthesis having a porous material as said material. 81. The method of claim 80, wherein said selecting is performed on said porous material comprising ePTFE. 81. The method of claim 80, wherein the selecting step is performed by selecting a prosthesis wherein the porous material comprises a surface that is substantially impermeable to the passage of blood therethrough. 80. The method of claim 79, wherein said selecting is performed by selecting a prosthesis wherein said first agent is layered over said second agent. 80. The method of claim 79, wherein the selecting step comprises: releasing the first drug in a first time period and releasing the second drug in a second time period, wherein the first and second time periods are at least partially separated. A method that is performed as if they are overlapping. 80. The method of claim 79, wherein the selecting step is performed by selecting a prosthesis having a delayed release material associated with at least one of the first and second agents. 86. The method of claim 85, wherein said selecting is performed by selecting a prosthesis wherein said delayed release material comprises a biodegradable delayed release layer. 80. The method of claim 79, wherein said selecting step is selected from the group consisting of an anti-inflammatory agent, an anti-thrombotic / anti-platelet agent, an anti-proliferative agent, an apoptosis inducer, a photoactivator, and a biological agent. Selecting a prosthesis having an administrable drug. 80. The method of claim 79, further comprising the step of selecting an anti-restenotic agent as said administrable agent. 80. The method of claim 79, wherein the selecting step comprises a coiled sleeve of a material having an inner surface and an outer surface, the inner surface forming an interior of the sleeve that houses the entire coil. Selecting a prosthesis comprising: the outer surface of the material, the location at which the drug was introduced into the material to form a drug / material matrix, the inner surface of the material. A method performed releasably from at least one location on and within the interior of the sleeve. 80. The method of claim 79, wherein the selecting step comprises selecting a prosthesis having spaced turns forming a gap therebetween during the radially expanded state. A method of making a prosthesis for use at a target site within a hollow body structure of a patient, comprising:
Placing the elongate material in contact with a mixture of the carrier and the administrable bioactive agent;
Removing at least a majority of the carrier from the mixture while the drug is in contact with the material to form a drug-filled material;
Combining the drug-filled material with a radially expandable stent to form a prosthesis suitable for use in a hollow body structure of a patient. 92. The method of claim 91, wherein said placing is performed using a porous material as said material. 93. The method of claim 92, wherein said placing step is performed on said porous material including ePTFE. 93. The method of claim 92, further comprising selecting a longitudinal porous sleeve material as the porous material, wherein the porous sleeve material has an inner surface and an outer surface, wherein the inner surface is Forming the interior of the sleeve that houses the entire stent after the combining step. 95. The method of claim 94, wherein said placing step is performed by placing said mixture inside said sleeve. 96. The method of claim 95, wherein said selecting step is performed using a sleeve material having an open end, and said placing step at least temporarily sealing one of said open ends. A method comprising the steps of: 92. The method of claim 91, wherein the removing step is performed by removing an excess of the mixture, followed by at least partially drying the elongate material. 90. The method of claim 91, further comprising an agent selected from the group consisting of an anti-inflammatory agent, an anti-thrombotic / anti-platelet agent, an anti-proliferative agent, an apoptosis-inducing agent, a photoactivator, and a biological agent. A method comprising the step of selecting. 92. The method of claim 91, further comprising selecting an anti-restenotic agent as said bioactive agent. 92. The method of claim 91, wherein the assembling step is performed by a prosthesis having spaced turns forming a gap therebetween during the radially expanded state. A coated coiled drug delivery stent, comprising:
A coiled radially expandable stent body having an outer surface;
A porous cover covering the outer surface,
A drug coupled to the porous cover,
The stent, wherein the stent, porous cover, and agent comprise a stent subassembly. 102. The stent of claim 101, wherein the stent body has spaced parallel side members joined by connecting members. 102. The stent of claim 101, wherein the stent body is made of metal. 102. The coated stent of claim 101, wherein the stent body is made of nickel titanium. 102. The coated stent of claim 101, wherein the porous cover comprises ePTFE. 102. The coated stent of claim 101, wherein the drug and the porous cover include a drug / porous cover matrix. 102. The stent of claim 101, wherein the agent is located between the outer surface and the porous cover. 102. The coated stent of claim 101, wherein the agent is disposed on the porous cover. 102. The coated stent of claim 101, further comprising means for delaying movement of the agent from the stent subassembly. 110. The coated stent of claim 109, wherein the drug transfer delay means comprises a drug / biodegradable material matrix in which the drug is dispersed in a biodegradable material. 102. The coated stent of claim 101, wherein the drug is microencapsulated using a biodegradable encapsulating material to delay migration of the drug from the stent subassembly. 102. The coated stent of claim 101, further comprising a removable protective layer covering the stent subassembly such that the drug is removable from the stent subassembly when it is removed. 1 13. The stent of claim 112, wherein the protective layer comprises a biodegradable material such that the protective layer is removed as it biodegrades. 114. The stent of claim 113, wherein the biodegradable material comprises a biodegradable polymer. 112. The coated stent of claim 112, wherein the protective layer includes a sheath that can be withdrawn from the stent subassembly to remove the protective layer from the stent subassembly. 102. The coated stent of claim 101, wherein the drug is:
NO generators, paclitaxel, statins, taxol, various forms (ie low molecular weight) of heparin, thienopyridine, glycoprotein IIb / IIIb inhibitors, antiplatelet agents, antithrombotics, fibrinolytics, anticoagulants, A stent comprising one or more of a thrombolytic agent, abciximab, rapamycin, hirudin, VEGF, Hirulog, ticlopidine, clopidogrel. 102. The coated stent of claim 101, wherein the agent comprises taxol. 102. The coated stent of claim 101, wherein the agent comprises heparin. 102. The stent of claim 101, wherein the agent comprises rapamycin. A coated coiled drug delivery stent, comprising:
A coiled radially expandable stent body having a spaced parallel side member and an outer surface joined by a connecting member;
A porous cover comprising ePTFE superimposed on the outer surface;
A drug coupled to the porous cover;
(Here, the stent body, the porous cover, and the drug constitute a stent subassembly.)
A biodegradable protective layer overlying the stent subassembly such that the drug is removable from the stent subassembly when the protective layer biodegrades. A method of delivering a drug to a patient, comprising:
Guiding a coated coiled stent subassembly including a drug coupled to a porous cover disposed on a coiled radially expandable prosthesis to a target site within a patient;
First shielding the drug for effective removal from the stent assembly, thereby waiting for a protective member to expose the drug;
Allowing the drug to move from the stent subassembly to interact with the patient. 123. The method of claim 121, wherein the guiding step comprises:
NO generators, hirudin, paclitaxel, rapmycin, statins, taxol, various forms (ie low molecular weight) of heparin, thienopyridine, glycoprotein IIb / IIIb inhibitors, antiplatelet agents, antithrombin, fibrinolytics, anticoagulants A method performed using an agent comprising at least one of a blood agent, a thrombolytic agent, abciximab, rapamycin, hirudin, VEGF, Hirulog, ticlopidine, and clopidogrel. 124. The method of claim 121, wherein the guiding step comprises the following locations: under the porous cover, over the porous cover, and incorporated into the porous cover to form a drug / porous cover matrix. A method performed by at least one of said locations with said medicament. 124. The method of claim 121, wherein the waiting step includes a waiting step, wherein the biodegradable material overlying the drug first biodegrades, thereby exposing the drug. 123. The method of claim 121, wherein said waiting step comprises waiting for a protective layer covering said subassembly to biodegrade. 124. The method of claim 121, wherein the waiting step comprises waiting for a protective cover covering the subassembly to be at least partially peeled from the stent. 123. The method of claim 121, further comprising removing the stent subassembly from the patient after the allowing step.