Methods and devices for treating abdominal aneurysms

Abstract

A device of this application can include (i) an improved stent graft device having a collapsible conduit to provide sealable access to an aneurysmal sac during deployment or (ii) a multiport embolization sheath configured to be used conjunction with a stent graft device.

Description

METHODS AND DEVICES FOR TREATING ABDOMINAL ANEURYSMSRELATED APPLICATION S

[0001] This application is an international application that claims priority to US Provisional Patent Application serial number 63 / 662,275 filed June 20, 2024 which is incorporated herein by reference in its entirety.STATEMENT REGARDING FEDERALLY FUNDED RESEARCH

[0002] None.FIELD OF THE INVENTION

[0003] The present invention relates to devices and methods for the treatment of diseases in the vasculature, and more specifically, devices and methods for treatment of arterial aneurysms.BACKGROUND

[0004] Aneurysms can occur in various areas of the cardiovascular system, but are commonly found in the abdominal aorta, thoracic aorta, and cerebral vessels. Aneurysms are unusual ballooning of the vessel due to loss of strength and / or elasticity of the vessel wall. With the constant pulsating pressure exerted on the vessel wall, the diseased or weakened wall can expand out and potentially rupture, which is frequently fatal. Methods of treating aneurysms have consisted of invasive surgical techniques. The technique involves a major cut to access the vessel, and the diseased portion of the vessel is replaced by a synthetic tubular graft. Accordingly, this invasive surgical procedure has high mortality and morbidity rates.

[0005] Due to the inherent risks and complexities of the surgical procedures, various attempts have been made to develop minimally invasive methods to treat these aneurysms. For treatment of abdominal and thoracic aortic aneurysms, most of the attempts are catheter-based delivery of an endoluminal synthetic graft with some metallic structural member integrated into the graft, commonly called stent-grafts. One of the primary deficiencies of these systems is the formation or development of endoleaks. Endoleaks arising after grafting may be caused by incomplete sealing between the endovascular prosthesis and the aortic wall or by defects within the endovascular prostheses. In addition, retrograde bleeding from patent lumbar and inferior mesenteric arteries following placement of the endovascular prostheses in the aorta has also beenrecited as a potential cause of endoleaks. There is uniform agreement that large endoleaks that lead to aneurysm enlargement necessitate treatment in order to prevent aneurysm rupture.

[0006] There are a variety of treatment regimens for endoleaks reported in the literature including endovascular repair by placement of additional stents within the prostheses as well as insertion of metallic coils into the aneurysm space to induce thrombosis therein. The goal of such treatments is complete exclusion of the aneurysm from systemic blood flow. While complete exclusion is desirable, a secondary goal is to reduce intraaneursymal pressure (IAP) from blood flow into the aneurysm to acceptable levels thereby inhibiting the likelihood of rupture. In cases where no endoleaks arose after endovascular grafting, the mean IAP has been reported to be reduced by about 65%. However, when endoleaks arise, it is reported that the mean IAP, while initially decreasing significantly, stabilized after a week at a reduction of only 22%. Moreover, the use of coils to induce thrombosis and thereby reduce IAP did not have any significant impact on the IAP.

[0007] In view of existing problems associated with endovascular repair of endoleaks, the accepted treatment for these endoleaks is open surgery. However, the mortality rates for open surgery of endoleaks is higher than either initial open surgery for the abdominal aortic aneurysm or for the initial endovascular repair of the aneurysm.

[0008] While the above methods have shown some promise with regard to treating aortic aneurysms with minimally invasive techniques, there remains a need for a treatment system to remedy endoleaks and associated pathology. The present invention describes various embodiments and methods to address the shortcomings of current minimally invasive devices and to meet clinical needs.SUMMARY

[0009] A solution to the above described endoleak problems is an improved endoluminal stent or embolization sheath / catheter, and associated methods.

[0010] Certain embodiments are directed to a multiport abdominal aortic aneurysm sac embolization apparatus comprising sheath / catheter comprising an elongated body forming a lumen having a maximal external diameter of 7 french, the body having a proximal end and a distal end, the distal end having 2 or more ports fluidly coupled to 2 or more internal lumens and the proximal end configured to receive embolization material to be delivered to the abdominalaortic aneurysm sac during use; wherein the sheath is configured to be inserted along the external surface of an endovascular stent.

[0011] Certain embodiments are directed to methods of treating an abdominal aortic aneurysm sac comprising: (i) inserting the embolization sheath described herein along the external surface of a stent graft positioned in the abdominal aorta with the distal end of the sheath positioned at the apex of the abdominal aortic aneurysm sac; (ii) injecting an embolization material into the abdominal aortic aneurysm sac through the at least 2, 3, 4, or more ports of the sheath (in certain aspects injection uses one set of ports / pathway at a time); (iii) optionally bending, rotating, or bending and rotating the distal portion of the sheath to locate the distal end of the sheath at a second location; (iv) injecting an embolization material into the abdominal aortic aneurysm sac through the at least one of the 2, 3, 4, or more ports of the sheath(in certain aspects injection uses one set of ports / pathway at a time); and (v) repeating the procedure; wherein, the sheath can optionally be withdrawn a distance prior to optionally bending, rotating, or bending and rotating the distal portion of the sheath. In certain aspects one of the internal lumens / pathways can be used at a time wherein embolization material is delivered through a selected outlet, pathway, or direction. The internal lumens can have a flexible diameter that expands when injection pressure applied to the embolization material. The embolization catheter can have a distal end comprising 2, 3, 4, or more outlet ports. The ports can be positioned at various angles relative to other ports. In certain aspects a first port is oriented at the tip of the embolization catheter with second or third ports being positioned at a 90 degree angle with respect to the long axis of the embolization catheter and 180 degrees with respect to each other. In other aspects the ports can project radially from the long axis of the embolization catheter. Other configurations can have a first port at the end of the embolization catheter and additional ports positioned radially with angles of 20 , 20, 30, 50, 60, 70, 80, to 90 degrees (with ports being in a distal, proximal, or a mixture of both distal and proximal directions) with respect to the long axis of the embolization catheter.

[0012] As used herein a fluid path, path, or pathway refers to an inlet and an outlet port coupled by a lumen forming the fluid path or pathway.

[0013] Certain embodiments are directed to a stent graft for treatment of an aortic aneurysm comprising a main tubular body having a top portion and at least one bottom portion with a collapsible conduit or secondary lumen (formed by a secondary wall) along the internal surfaceof the tubular stent body with an inlet position at the bottom of the stent graft and an outlet configured to traverse the stent wall and provide access to an aneurysm sac, the outlet providing access to the lumen of an aortic aneurysm sac during use, the conduit or secondary lumen configured to (i) receive an embolization sheath and (ii) to seal the outlet by collapse of the secondary wall under the arterial or venous pressure when the stent graft is deployed in a subject.

[0014] Certain embodiments are directed to methods of treating an abdominal aortic aneurysm sac comprising: (i) inserting an embolization sheath prior to fixing an aortic stent graft, the embolization sheath being inserted along a collapsible conduit of the stent graft wall, the conduit having an inlet positioned proximal to an iliac portion of the stent graft and an outlet position in the portion of the stent graft traversing a stent wall into abdominal aortic aneurysm sac, a distal tip of the embolization sheath being positioned in the abdominal aortic aneurysm sac to be treated; (ii) injecting an embolization material into the abdominal aortic aneurysm sac through the embolization sheath; (iii) removing the embolization sheath; and (iv) fixing the stent graft in the aorta, collapsing to the conduit and sealing the outlet.

[0015] Other embodiments of the invention are discussed throughout this application. Any embodiment discussed with respect to one aspect of the invention applies to other aspects of the invention as well and vice versa. Each embodiment described herein is understood to be embodiments of the invention that are applicable to all aspects of the invention. It is contemplated that any embodiment discussed herein can be implemented with respect to any method or composition of the invention, and vice versa. Furthermore, compositions and kits of the invention can be used to achieve methods of the invention.

[0016] The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and / or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”

[0017] Throughout this application, the term “about” is used to indicate that a value includes the standard deviation of error for the device or method being employed to determine the value.

[0018] The use of the term “or” in the claims is used to mean “and / or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and / or.”

[0019] As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as“have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

[0020] As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains”, “containing,” “characterized by” or any other variation thereof, are intended to encompass a non-exclusive inclusion, subject to any limitation explicitly indicated otherwise, of the recited components. For example, a chemical composition and / or method that “comprises” a list of elements (e.g., components or features or steps) is not necessarily limited to only those elements (or components or features or steps), but may include other elements (or components or features or steps) not expressly listed or inherent to the chemical composition and / or method.

[0021] As used herein, the transitional phrases “consists of’ and “consisting of’ exclude any element, step, or component not specified. For example, “consists of’ or “consisting of’ used in a claim would limit the claim to the components, materials or steps specifically recited in the claim except for impurities ordinarily associated therewith (i.e., impurities within a given component). When the phrase “consists of’ or “consisting of’ appears in a clause of the body of a claim, rather than immediately following the preamble, the phrase “consists of’ or “consisting of’ limits only the elements (or components or steps) set forth in that clause; other elements (or components) are not excluded from the claim as a whole.

[0022] As used herein, the transitional phrases “consists essentially of’ and “consisting essentially of’ are used to define a chemical composition and / or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel character! stic(s) of the claimed invention. The term “consisting essentially of’ occupies a middle ground between “comprising” and “consisting of’.

[0023] Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.DESCRIPTION OF THE DRAWINGS

[0024] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of the specification embodiments presented herein.

[0025] FIG. 1A. Illustration of A stent graft for treatment of an abdominal aortic aneurysm deployed in an abdominal aorta.

[0026] FIG. IB. Illustration of a stent with secondary lumen.

[0027] FIG. 1C. Illustration of a longitudinal cross section of a stent with secondary lumen.

[0028] FIG. ID. Illustration of a cross section a stent with secondary lumen and inserted embolization catheter.

[0029] FIG. IE. Illustration of a cross section a stent with secondary lumen with embolization catheter removed.

[0030] FIG. IF. Illustration of a side view of a stent with secondary lumen.

[0031] FIG. 2A. Illustration of a multiport abdominal aortic aneurysm sac embolization sheath deployed in an abdominal aneurysm.

[0032] FIG. 2B. Illustration of the distal end of a multiport abdominal aortic aneurysm sac embolization sheath.

[0033] FIG. 2C. Illustration of a cross section of the distal end of a multiport abdominal aortic aneurysm sac embolization sheath.DESCRIPTION

[0034] The following discussion is directed to various embodiments of the invention. The term “invention” is not intended to refer to any particular embodiment or otherwise limit the scope of the disclosure. Although one or more of these embodiments may be preferred, the embodiments disclosed should not be interpreted, or otherwise used, as limiting the scope of the disclosure, including the claims. In addition, one skilled in the art will understand that the following description has broad application, and the discussion of any embodiment is meant only to be an example of that embodiment, and not intended to imply that the scope of the disclosure, including the claims, is limited to that embodiment.

[0035] Aspects of the invention are directed to novel devices and methods for inhibiting endoleaks associated with endovascular repair of abdominal aortic aneurysms, in particular devices to facilitate aneurysm embolization. Particular aspects are directed to devices designed to provide access to the aneurysmal sac and accompanying methods for inhibiting the formation of or sealing endoleaks. Methods are directed to the in situ embolization of the aneurysmal sac associated with the placement of an endovascular prostheses (stent graft) in an aorta, e.g., abdominal aorta. Endoleaks in abdominal aortic aneurysms (AAAs) can be repaired using various embolization materials. These materials are chosen based on their ability to occlude blood flow into the aneurysm sac, thereby preventing further expansion and reducing the risk of rupture. Common types of embolization materials used for repairing endoleaks includes but is not limited to: (i) Coils: These are often made of platinum or stainless steel and come in various shapes and sizes. Coils are effective in fdling the endoleak channels within the aneurysm sac, promoting clot formation and sealing off the leak, (ii) Liquid Embolic Agents: Substances such as cyanoacrylate glue or ethylene-vinyl alcohol copolymer (Onyx) can be injected into the endoleak to block the flow of blood. These materials solidify upon contact with blood, creating a durable plug, (iii) Thrombin Injection: Thrombin can be directly injected into the endoleak cavity to promote clot formation, effectively sealing the leak. This method is particularly useful for Type II endoleaks where the source is from a branch vessel, (iv) Polymer-Based Embolic Agents: These include materials like polyvinyl alcohol (PVA) particles or N-butyl cyanoacrylate (NBCA) mixed with a lipiodol contrast agent. These agents can be delivered via catheter into the endoleak site to block blood flow and induce thrombosis, (v) Onyx (Ethylene-vinyl Alcohol Copolymer): This liquid embolic agent solidifies rapidly upon contact with blood and forms a durable cast within the endoleak cavity, effectively sealing off the leakage, (vi) Gelatin Sponges: These are absorbable and can be used to fill the endoleak space, promoting clot formation and sealing the leak. Gelatin sponges are biocompatible and eventually resorb over time. Each type of embolization material has its advantages and indications depending on the type and location of the endoleak within the aneurysm sac. The choice of material is typically determined by factors such as the anatomy of the aneurysm, the size and type of endoleak, and the patient's overall health and anatomy. Embolization procedures for repairing endoleaks are generally minimally invasive and can often be performed using image-guided techniques and devices describedherein under local anesthesia, resulting in reduced recovery times and lower risks compared to traditional open surgery.

[0036] Embodiments include (i) an improved stent graft device having a collapsible conduit to provide sealable access to an aneurysmal sac during deployment (FIG. 1A-1F) and (ii) a stent graft a multiport embolization sheath configured to be used conjunction with a stent graft device (FIG. 2A-2C).

[0037] Endovascular repair of aneurysms involves the introduction of an endovascular prosthesis into the aortic aneurysm which is an art recognized procedure. This procedure as it relates to abdominal aneurysms typically consists of dissection of the femoral artery at the groin and introduction of an endovascular prosthesis inside the abdominal aortic aneurysm. Upon insertion, the prosthesis excludes the aneurysm sac thereby repairing or by passing the aneurysm (see FIG. 1A for example). Suitable endovascular prostheses for endovascular repair of abdominal aortic aneurysms are well known in the art. Similarly, catheters or sheaths for delivering such endovascular prostheses to the site of the abdominal aortic aneurysm are also well known in the art and are commercially available.

[0038] In the methods of this invention a fluid composition is introduced into the aneurysmal sac via a sheath or catheter. The specific amount of fluid composition employed is dictated by the total size of the aneurysmal sac, and other factors such as the concentration of polymer / prepolymer or thrombotic agent in the composition, the rate of solids formation, etc. Such factors are well within the skill of the art.

[0039] Prior to sealing the potential endoleak in the manner described above, the clinician would first identify the site or sites of the potential endoleak. Access to these sites of treatment can be achieved during the initial stent deployment through a deployment catheter or by endovascular catheter access via the femoral artery which is well known in interventional radiology practice. After access is achieved, delivery of the fluid composition proceeds as described herein.I. Endovascular Aneurysm Repair (EVAR) Stent Graft

[0040] Referring to FIG. 1A-1F, an aorta 100 is shown with a right renal artery 102a, a left renal artery 102b, an aneurysm 104 in the wall of the aorta, a right iliac artery 106a and a left iliac artery 1066. Stent 110, having a primary tubular member 120 bifurcating into two branches 121a and 121b which enter each of the iliac arteries 106a and 106b. Stent 110 comprisessecondary lumen I l la formed by a secondary wall 111b that is fluid communication with an aneurysm access port 112 and an external access port 113. Secondary lumen 112 is configured to receive an embolization sheath 114 which can optionally be positioned over a removable guidewire 115. Embolization sheath 114 is configured to provide access for introducing an embolization agent or other material into aneurysm 104. Embolization sheath 114 can be a catheter, which is temporarily introduced to the aneurysmal target site for treatment. The catheter comprises a catheter body, typically which is introduced over a steerable guidewire 115. Secondary lumen 112 is configured to collapse upon removal of embolization sheath 114, sealing the access to the aneurysm. Access sheath / port 116 is shown with a side port for providing access to secondary lumen 112. Access sheaths are typically used in providing access to the arterial lumen and providing access to place and deploy a stent graft. The secondary lumen is formed by a secondary wall that can be comprised of a flexible material that can stretch when sheath or catheter is deployed in the secondary lumen and retract or fold against the stent wall sealing the embolization port when the catheter is removed (see for example FIG. ID and FIG. IE).

[0041] Embodiments may be used or adapted for use in blood vessels other than the abdominal aorta, such as the carotid arteries, coronary arteries, cerebral vessels, and / or the like.

[0042] Embolization materials and / or other therapeutic agents or combinations thereof may be delivered according to the methods of the present invention using a catheter introducible over a guidewire (GW).II. Multiport Aortic Abdominal Aneurysm Embolization Sheath

[0043] Referring to FIG. 2A-2C, an aorta 200 is shown with a right renal artery 202a, a left renal artery 2026, an aneurysm 204 in the wall of aorta 200, a right iliac artery 206a and a left iliac artery 2066. Stent 210, having a primary tubular member 220 bifurcating into two branches 221a and 221b which enter each of the iliac arteries 206a and 206b. One embodiment is a device to be used to treat / prevent leakage from the aneurysm and includes multiport embolization device 230 comprising multiport embolization catheter 231 positioned in the lumen of a delivery sheath 232. In certain embodiments sheath 232 can be withdrawn from embolization catheter 231 to expose multiport terminus 235, or catheter 231 can be extended beyond the sheath 232 to expose multiport terminus 235. Multiport embolization catheter 231 comprises multiple delivery lumens (see FIG, 2C) coupled to a distal multiport terminus 235 having 2, 3, or moreembolization outlets that are fluidly connected to an inlet port that is configured to be positioned externally to a subject during use. The inlet port(s) can be coupled to an valving mechanism for selecting which pathway is used. Alternatively, the inlet can be coupled to or include a multiport inlet with an inlet for each individual pathway. Inlet port 233 can be a multiport inlet port having individual inlets in fluid communication to distal outlet 235. Each fluid path between the inlet to the outlet can be independent. Each fluid path can be formed by a flexible tube that expands in response to the pressure exerted by an embolization material being injected into the embolization pathway. In certain aspects one embolization path is used at a time with the non-used embolization paths collapsing and the inner diameter of the embolization path in use expanding. The pathways can be a flexible or braided tube that can expand and contract its diameter. Characteristics and features of such a tube can include but is not limited to one or more of (i) Material Composition: It is often made from materials like silicone, polyurethane, or a combination of polymers that provide flexibility and elasticity. These materials are chosen for their biocompatibility and ability to withstand mechanical stresses, (ii) Braided Construction: Many expandable tubes feature a braided design. This involves a network of interwoven fibers or wires (often made from materials like stainless steel or nitinol) embedded within the tube wall. This braiding provides structural support while allowing for radial expansion and contraction, (iii) Expandability: The tube can expand and contract its diameter while maintaining its structural integrity. This capability is crucial for navigating through anatomical pathways that vary in diameter or require different dimensions for different stages of a procedure, (iv) Flexibility: Despite the braided or reinforced structure, the tube remains flexible. This flexibility enables it to bend and conform to the natural curves of the body, facilitating easier insertion and maneuverability during medical procedures. The expandability and collapsibility provide the ability to transfer a volume of embolization material or other materials to the aneurysm sack and maintain a small diameter (7 french or less) and still provide directional deployment through each of the multiport outlets. Multiport embolization termination 235 when deployed is in fluid communication with an aneurysm sac 204. Multiport embolization device 230 is configured to be inserted between stent graft 210 and artery 200 wall into aneurysm sac 204, or alternatively through the secondary lumen of the Endovascular Aneurysm Repair (EVAR) Stent Graft described herein. In certain aspects the embolization sheath 232 is at most 7 french in diameter. The fluid paths can have a maximal diameter of 4, 5, 6, to 7 french. Embolization sheath 232 isconfigured to provide access for introducing an embolization agent or other material into aneurysm 204. Sheath 232 can have tip 240, which can be beveled, rounded, or shaped for easing insertion and reducing damage to the internal arterial wall as well facilitate insertion of the device. Multiport embolization device 230 can be temporarily introduced to the aneurysmal target site for treatment, distal outlet 235 exposed, embolization or other materials inject via a selected catheter pathway 241 which determines the direction of flow from distal outlet 235.III. Methods of Aneurysm Repair

[0044] Certain embodiments are directed to methods for inhibiting the formation of potential endoleaks or seal existing endoleaks associated with endovascular repair of abdominal aortic aneurysms. In one embodiment, this invention is directed to methods for inhibiting endoleaks arising either from retrograde bleeding from blood vessels associated with the aneurysmal sac such as the lumbar and inferior mesenteric arteries into the aneurysm sac or from defects within the endovascular prosthesis which permit blood flow through it or around it after endovascular repair of abdominal aortic aneurysms. Specifically, the methods of this invention involves the in situ embolization of the aneurysmal sac. Embolization is achieved by injection of either a biocompatible polymer or prepolymer fluid composition (i.e., a filler) or other embolic agent (embolization material) into the sac in a sufficient amount such that upon in situ solidification of this composition leakage into the aneurysmal sac ceases or is reduced. In certain aspects the filler comprises a contrast agent to allow the clinician to visualize the embolization process.

[0045] One method of delivering filler into the aneurysm sac is by an embolization sheathbased delivery system. The sheath can deliver the filler through its lumen, injecting the filler into the aneurysm sac. The sheath can be a curved or steerable delivery sheath where the tip is placed along the exterior of a stent structure or through a collapsible conduit in a stent with filler being deployed into the aneurysm sac. An inflatable anchor can be incorporated into the sheath to ensure that the delivery sheath tip stays inside the aneurysm sac when anchor is inflated after the tip is within the aneurysm sac it will prevent the sheath tip from backing out of the aneurysm sac. The anchor can be a balloon or expandable mesh.

[0046] A delivery sheath can be tracked over a guidewire which has been placed into the aneurysm sac external to a stent as described above or through a collapsible conduit described above.

[0047] Materials can be injected into the aneurysm sac. The injected material can be an epoxy, a UV-curable epoxy, silicone, urethane or other type of biocompatible materials such as albumin, collagen, and gelatin glue. Optionally, the injected material can be cured in situ.

[0048] The term "embolizing" refers to a process wherein a biocompatible fluid composition is injected into lumen such that upon in situ solidification of this composition, fluid flow from an aneurysmal sac ceases or is reduced.

[0049] The compositions used in the methods of this invention are biocompatible fluid compositions characterized by the fact that these compositions form a mass in vivo to cease or reduce leaks from an aneurysmal sac. The fluid compositions employed in the described methods can be polymer or prepolymer compositions. Fluid polymer compositions preferably comprise a biocompatible polymer, a biocompatible solvent and optionally a contrast agent. Such compositions can be prepared by adding sufficient amounts of the biocompatible polymer to the biocompatible solvent to achieve the effective concentration for the polymer composition. The polymer composition can comprise from about 2.5 to about 12.0 weight percent of the biocompatible polymer composition based on the total weight of the polymer composition and more preferably from about 4 to about 5.4 weight percent.

[0050] When employed, sufficient amounts of the contrast agent are then added to the biocompatible solvent to achieve the effective concentration for the complete composition. Preferably, the composition will comprise from about 10 to about 40 weight percent of the contrast agent and more preferably from about 20 to about 40 weight percent and even more preferably about 30 weight percent. Insofar as the contrast agent may not be soluble in the biocompatible solvent (e.g., a water insoluble contrast agent).

[0051] When no contrast agent is employed, the biocompatible solvent is preferably employed at a concentration of from 80 to about 98 weight percent of the embolic agent (e.g., a biocompatible polymer) composition based on the total weight of the embolic agent composition and more preferably from about 90 to about 95 weight percent.

[0052] When a contrast agent is employed, the biocompatible solvent is preferably employed at a concentration of from 50 to 90 weight percent based on the total weight of the composition.

[0053] Polymers are commercially available but can also be prepared by methods well known in the art. For example, polymers are typically prepared by conventional techniques such as radical, thermal, UV, y irradiation, or electron beam induced polymerization employing, asnecessary, a polymerization catalyst or polymerization initiator to provide for the polymer composition. The specific manner of polymerization is not critical and the polymerization techniques employed do not form a part of this invention.

[0054] Prepolymer compositions preferably comprise a biocompatible prepolymer and optionally a contrast agent. When a contrast agent is employed, such compositions can be prepared by adding sufficient amounts of the contrast agent to the solution (e.g., liquid prepolymer) to achieve the effective concentration for the complete composition.

[0055] The compositions described above can then be employed in methods for the catheter assisted embolization of the aneurysmal sac thereby inhibiting endoleaks after endovascular repair of abdominal aortic aneurysms by an endovascular prosthesis.

[0056] The term "biocompatible polymer" refers to polymers which, in the amounts employed, are non-toxic, chemically inert, and substantially noninmnunogenic when used internally in the patient and which are substantially insoluble in blood. Suitable biocompatible polymers include, by way of example, cellulose acetates (including cellulose diacetatel), ethylene vinyl alcohol copolymers, hydrogels (e.g., acrylics), polyacrylonitrile, polyvinyl acetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethanelcarbonate, copolymers of styrene / maleic acid, and mixtures thereof. Preferably, the biocompatible polymer does not induce chronic inflammation when employed in vivo.

[0057] The particular biocompatible polymer employed is not critical and is selected relative to the viscosity of the resulting polymer solution, the solubility of the biocompatible polymer in the biocompatible solvent, and the like. Such factors are well within the skill of the art.

[0058] Preferred biocompatible polymers include cellulose diacetate and ethylene vinyl alcohol copolymer. Cellulose diacetate polymers are either commercially available or can be prepared by art recognized procedures. In a preferred embodiment, the number average molecular weight, as determined by gel permeation chromatography, of the cellulose diacetate composition is from about 25,000 to about 100,000 more preferably from about 50,000 to about 75,000 and still more preferably from about 58,000 to 64,000. The weight average molecular weight of the cellulose diacetate composition, as determined by gel permeation chromatography, is preferably from about 50,000 to 200,000 and more preferably from about 100,000 to about 180,000. As is apparent to one skilled in the art, with all other factors being equal, cellulose diacetate polymers having a lower molecular weight will impart a lower viscosity to thecomposition as compared to higher molecular weight polymers. Accordingly, adjustment of the viscosity of the composition can be readily achieved by mere adjustment of the molecular weight of the polymer composition.

[0059] Ethylene vinyl alcohol copolymers comprise residues of both ethylene and vinyl alcohol monomers. Small amounts (e.g., less than 5 mole percent) of additional monomers can be included in the polymer structure or grafted thereon provided such additional monomers do not alter the sealing properties of the composition. Such additional monomers include, by way of example only, maleic anhydride, styrene, propylene, acrylic acid, vinyl acetate and the like.

[0060] Ethylene vinyl alcohol copolymers are either commercially available or can be prepared by art recognized procedures. Preferably, the ethylene vinyl alcohol copolymer composition is selected such that a solution of 6 weight percent of the ethylene vinyl alcohol copolymer, 35 weight percent of a tantalum contrast agent in DMSO has a viscosity equal to or less than 60 centipoise at 20° C. As is apparent to one skilled in the art, with all other factors being equal, copolymers having a lower molecular weight will impart a lower viscosity to the composition as compared to higher molecular weight copolymers. Accordingly, adjustment of the viscosity of the composition as necessary for catheter delivery can be readily achieved by mere adjustment of the molecular weight of the copolymer composition.

[0061] As is also apparent, the ratio of ethylene to vinyl alcohol in the copolymer affects the overall hydrophobicity / hydrophilicity of the composition which, in turn, affects the relative water solubility / insolubility of the composition as well as the rate of precipitation of the copolymer in an aqueous solution (e.g., blood). In a particularly preferred embodiment, the copolymers employed herein comprise a mole percent of ethylene of from about 25 to about 60 and a mole percent of vinyl alcohol of from about 40 to about 75. These compositions provide for requisite precipitation rates suitable for use in sealing endoleaks arising from endovascular repair of an abdominal aortic aneurysm.

[0062] The term "contrast agent" refers to a biocompatible (non-toxic) radiopaque material capable of being monitored during injection into a mammalian subject by, for example, radiography or fluoroscopy. The contrast agent can be either water soluble or water insoluble. Examples of water soluble contrast agents include metrizamide, iopamidol, iothalamate sodium, iodomide sodium, and meglumine.

[0063] The term "water insoluble contrast agent" refers to a water insoluble (i.e., has a water solubility of less than 0.01 mg / mil at 20° C ), radiopaque material capable of being monitored during injection into a mammalian subject by, for example, radiography or fluoroscopy. Examples of water insoluble contrast agents include tantalum, tantalum oxide and barium sulfate, which are commercially available in the proper form for in vivo use. Methods for preparing such water insoluble biocompatible contrast agents having an average particle size of about 10 pm or less are described below. Other water insoluble contrast agents include gold, tungsten and platinum.

[0064] The term "biocompatible solvent" refers to an organic material liquid at least at body temperature of the mammal in which the biocompatible polymer is soluble and, in the amounts used, is substantially non-toxic. Suitable biocompatible solvents include, by way of example, ethanol, acetone, dimethylsulfoxide, analogues / homologues of dimethylsulfoxide, ethyl lactate, and the like. Aqueous mixtures with the biocompatible solvent can also be employed provided that the amount of water employed is sufficiently small that the dissolved polymer precipitates upon contact with the blood. Preferably, the biocompatible solvent is dimethylsulfoxide (DMSO).

[0065] The term "encapsulation" as used relative to the contrast agent being encapsulated in the polymer precipitate is not meant to infer any physical entrapment of the contrast agent within the precipitate such as a capsule encapsulates a medicament. Rather, this term is used to mean that an integral coherent precipitate forms which does not separate into individual components.

[0066] The term "adheres to" as used herein means that the composition formed in situ retains the position / location where the polymer mass formed after injection and thereby functions to seal the blood vessels. This term does not necessarily infer that the composition acts as an adhesive although in the case of, for example, a cyanoacrylate prepolymer, the solid composition formed may, in fact, be adhesive.

[0067] The term "biocompatible prepolymer" refers to materials which polymerize in situ to form a polymer and which, in the amounts employed, are non-toxic, chemically inert, and substantially non-immunogenic when used internally in the patient and which are substantially insoluble in blood. Suitable biocompatible prepolymers include, by way of example, cyanoacrylates14, 15, 16, hydroxyethyl methacrylate, silicone prepolymers, and the like. Theprepolymer can either be a monomer or a reactive oligomer16. Preferably, the biocompatible prepolymer does not induce chronic inflammation when employed in vivo.

Claims

CLAIMS1. A multiport abdominal aortic aneurysm sac embolization apparatus comprising sheath / catheter comprising an elongated body forming a lumen having an external diameter of 7 French or less, the body having a proximal end and a steerable distal end, the distal end having 2 or more ports fluidly coupled to the lumen and the proximal end configured to receive embolization material to be delivered to the abdominal aortic aneurysm sac during use; wherein the sheath is configured to be inserted along the external surface of an endovascular stent.

2. A method of treating an abdominal aortic aneurysm sac comprising:(i) inserting the embolization sheath of claim 1 along the external surface of a stent graft positioned in the abdominal aorta with the distal end of the sheath positioned at the apex of the abdominal aortic aneurysm sac;(ii) injecting an embolization material into the abdominal aortic aneurysm sac through the at least 2 ports of the sheath;(iii) bending, rotating, or bending and rotating the distal portion of the sheath to locate the distal end of the sheath at a second location;(iv) injecting an embolization material into the abdominal aortic aneurysm sac through the at least 2 ports of the sheath; and(v) repeating the procedure; wherein, the sheath can optionally be withdrawn a distance prior to bending, rotating, or bending and rotating the distal portion of the sheath.

3. A stent graft for treatment of an aortic aneurysm comprising a main tubular body having a top portion and at least one bottom portion with a collapsible conduit along the internal surface of the tubular stent body with an inlet position at the bottom of the stent graft and an outlet position in a portion of the stent graft configured to traverse an aortic aneurysm, the outlet providing access to the lumen of an aortic aneurysm sac during use, the conduit configured to (i) receive an embolization sheath and (ii) to seal the outlet when the stent graft is deployed in a subject.

4. A method of treating an abdominal aortic aneurysm sac comprising:(i) inserting the embolization sheath prior to fixing an aortic stent graft, the embolization sheath being inserted along a collapsible conduit of the stent graft wall, the conduit having an inlet positioned proximal to an iliac portion of the stent graft and an outlet position in the portion of the stent graft traversing the abdominal aortic aneurysm sac, a distal tip of the embolization sheath being positioned in the abdominal aortic aneurysm sac to be treated;(ii) injecting an embolization material into the abdominal aortic aneurysm sac through the embolization sheath;(iii) removing the embolization sheath; and(iv) fixing the stent graft in the aorta, collapsing to the conduit and sealing the outlet.

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