Patent Application
20080077070
The foregoing and other features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention as illustrated in the accompanying drawings.
The present invention is directed to improved designs in arteriovenous grafts. Arteriovenous grafts may be utilized to create shunts between arteries and veins to create areas of withdrawal and readmission of blood in patients undergoing hemodialysis and/or other methods of extracorporeal blood treatments. By utilizing an arteriovenous shunt, needles may be inserted into the graft to obtain blood for the dialysis process rather than to repeatedly puncture a patient's arteries and veins. However, arteriovenous grafts, may over time, develop a thick, robust neointima that may gradually occlude the vessel to a point where thrombosis ultimately occurs. This neointima is more prevalent on the venous side. This phenomenon causes the need for a replacement of the arteriovenous graft.
Since connecting the arterial circulation to the venous circulation with an arteriovenous graft exposes the venous side to supraphysiologic pressure, it has been hypothesized that the robust neointima that forms is an adaptive mechanism. Accordingly, one potential means of limiting venous neointima formation might be to limit some portion of the arteriovenous graft diameter or some other design feature to produce a pressure drop across the length of the graft. This may permit the venous side of the arteriovenous graft to experience a lower pressure thereby potentially lessening adaptive neointimal formation. These design modifications are preferably positioned so as not to interfere with the needle placement utilized for the withdrawal and return of blood during dialysis.
Referring to
The arteriovenous graft 100 comprises a first end 102 adapted and/or configured for attachment to an artery and a second end 104 adapted and/or configured for attachment to a vein. As illustrated, the arteriovenous graft 100 has a larger diameter at its first end 102 that continuously decreases to a smaller diameter at its second end 104 to form a frustum of a right circular cone. According to Bernoulli's Principle, as a fluid travels through a conduit that has a changing diameter, the velocity and pressure of the fluid also changes. More specifically, Bernoulli's Principle indicates that as the velocity of a fluid increases, the static pressure within the fluid decreases. Accordingly, in the exemplary embodiment illustrated in
Referring now to
As may be seen from above, any design that results in a pressure drop from the arterial end to the venous end may be suitable to control the formation of neointima. Also, the specific shapes and configurations are for illustrative purposes only as those shapes and designs may vary. In addition to these design features, therapeutic agents may be utilized to help prevent or slow the formation of neointima on the venous side. For example, a rapamycin alone or in combination with heparin, may be affixed to the arteriovenous graft directly or via a polymeric coating to inhibit neointimal growth.
While exemplary embodiments of arteriovenous grafts are described herein, it is important to note that the local delivery of drug/drug combinations may be utilized to treat a wide variety of conditions utilizing any number of medical devices, or to enhance the function and/or life of the device. For example, intraocular lenses, placed to restore vision after cataract surgery is often compromised by the formation of a secondary cataract. The latter is often a result of cellular overgrowth on the lens surface and can be potentially minimized by combining a drug or drugs with the device. Other medical devices which often fail due to tissue in-growth or accumulation of proteinaceous material in, on and around the device, such as dialysis grafts, colostomy bag attachment devices, ear drainage tubes, leads for pace makers and implantable defibrillators can also benefit from the device-drug combination approach. Devices that serve to improve the structure and function of tissue or organ, may also show benefits when combined with the appropriate agent or agents. For example, improved osteointegration of orthopedic devices to enhance stabilization of the implanted device could potentially be achieved by combining it with agents such as bone-morphogenic protein. Similarly other surgical devices, sutures, staples, anastomosis devices, vertebral disks, bone pins, suture anchors, hemostatic barriers, clamps, screws, plates, clips, vascular implants, tissue adhesives and sealants, tissue scaffolds, various types of dressings, bone substitutes, intraluminal devices, and vascular supports could also provide enhanced patient benefit using this drug-device combination approach. Perivascular wraps may be particularly advantageous, alone or in combination with other medical devices. The perivascular wraps may supply additional drugs to a treatment site. Essentially, any type of medical device may be coated in some fashion with a drug or drug combination which enhances treatment over use of the singular use of the device or pharmaceutical agent.
In addition to various medical devices, the coatings on these devices may be used to deliver therapeutic and pharmaceutic agents including: anti-proliferative/antimitotic agents including natural products such as vinca alkaloids (i.e. vinblastine, vincristine, and vinorelbine), paclitaxel, epidipodophyllotoxins (i.e. etoposide, teniposide), antibiotics (dactinomycin (actinomycin D) daunorubicin, doxorubicin and idarubicin), anthracyclines, mitoxantrone, bleomycins, plicamycin (mithramycin) and mitomycin, enzymes (L-asparaginase which systemically metabolizes L-asparagine and deprives cells which do not have the capacity to synthesize their own asparagine); antiplatelet agents such as G(GP) llb/llla inhibitors and vitronectin receptor antagonists; anti-proliferative/antimitotic alkylating agents such as nitrogen mustards (mechlorethamine, cyclophosphamide and analogs, melphalan, chlorambucil), ethylenimines and methylmelamines (hexamethylmelamine and thiotepa), alkyl sulfonates-busulfan, nirtosoureas (carmustine (BCNU) and analogs, streptozocin), trazenes—dacarbazinine (DTIC); anti-proliferative/antimitotic antimetabolites such as folic acid analogs (methotrexate), pyrimidine analogs (fluorouracil, floxuridine, and cytarabine), purine analogs and related inhibitors (mercaptopurine, thioguanine, pentostatin and 2-chlorodeoxyadenosine {cladribine}); platinum coordination complexes (cisplatin, carboplatin), procarbazine, hydroxyurea, mitotane, aminoglutethimide; hormones (i.e. estrogen); anti-coagulants (heparin, synthetic heparin salts and other inhibitors of thrombin); fibrinolytic agents (such as tissue plasminogen activator, streptokinase and urokinase), aspirin, dipyridamole, ticlopidine, clopidogrel, abciximab; antimigratory; antisecretory (breveldin); anti-inflammatory: such as adrenocortical steroids (cortisol, cortisone, fludrocortisone, prednisone, prednisolone, 6α-methylprednisolone, triamcinolone, betamethasone, and dexamethasone), non-steroidal agents (salicylic acid derivatives i.e. aspirin; para-aminophenol derivatives i.e. acetaminophen; indole and indene acetic acids (indomethacin, sulindac, and etodalac), heteroaryl acetic acids (tolmetin, diclofenac, and ketorolac), arylpropionic acids (ibuprofen and derivatives), anthranilic acids (mefenamic acid, and meclofenamic acid), enolic acids (piroxicam, tenoxicam, phenylbutazone, and oxyphenthatrazone), nabumetone, gold compounds (auranofin, aurothioglucose, gold sodium thiomalate); immunosuppressives: (cyclosporine, tacrolimus (FK-506), sirolimus (rapamycin), azathioprine, mycophenolate mofetil); angiogenic agents: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF); angiotensin receptor blockers; nitric oxide donors; antisense oligionucleotides and combinations thereof; cell cycle inhibitors, mTOR inhibitors, and growth factor receptor signal transduction kinase inhibitors; retenoids; cyclin/CDK inhibitors; HMG co-enzyme reductase inhibitors (statins); and protease inhibitors.
Although shown and described is what is believed to be the most practical and preferred embodiments, it is apparent that departures from specific designs and methods described and shown will suggest themselves to those skilled in the art and may be used without departing from the spirit and scope of the invention. The present invention is not restricted to the particular constructions described and illustrated, but should be constructed to cohere with all modifications that may fall within the scope of the appended claims.
