WO2013090878A1 - Pontages aorto-coronariens et conduits vasculaires - Google Patents

Pontages aorto-coronariens et conduits vasculaires Download PDF

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Publication number
WO2013090878A1
WO2013090878A1 PCT/US2012/070003 US2012070003W WO2013090878A1 WO 2013090878 A1 WO2013090878 A1 WO 2013090878A1 US 2012070003 W US2012070003 W US 2012070003W WO 2013090878 A1 WO2013090878 A1 WO 2013090878A1
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Prior art keywords
vascular tissue
cross
tissue
linked
para
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PCT/US2012/070003
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English (en)
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Kemal Schankereli
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Vascudyne, Llc
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Publication of WO2013090878A1 publication Critical patent/WO2013090878A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A61F2/062—Apparatus for the production of blood vessels made from natural tissue or with layers of living cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3625—Vascular tissue, e.g. heart valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels

Definitions

  • This invention relates to coronary artery bypass grafts and vascular conduits, and in particular, to specially modified vascular tissue used to create an anastomosis.
  • Anastomosis is a procedure where two separate tubular or hollow organs are surgically grafted together to form a continuous fluid channel between them.
  • Vascular anastomosis involves creating an anastomosis between blood vessels to create or restore blood flow.
  • CAD coronary artery disease
  • an occlusion or stenosis in a coronary artery restricts blood flow to the heart muscle.
  • the area where the occlusion occurs is bypassed to reroute blood flow by grafting a vessel in the form of a harvested artery or vein, or a prosthesis.
  • Anastomosis is performed between a graft vessel and one or more target vessels in order to bypass the blocked coronary artery, circumvent the occlusion and restore adequate blood flow to the heart muscle.
  • This treatment is known as a coronary artery bypass graft procedure (CABG).
  • CABG coronary artery bypass graft procedure
  • vascular grafts and in particular coronary artery bypass grafts, that do not result in thrombosis, stenosis, or other complications caused by vascular injury, that may be used in conjunction with, but do not require, the use of pharmaceutical or therapeutic agents or drugs to achieve such affects.
  • the invention relates to the preparation of animal vascular tissue, arteries or veins, in which the tissue is cleaned, chemically cross-linked using cross-linking agents, and surface- coated with an anhydride compound using a non-aqueous method of exposing tissue to the anhydride, resulting in an improved bioprosthetic or implantable surgical material that is substantially non- antigenic, non-thrombogenic, resistant to calcification, and durable enough to be used in surgical applications, such as the creation of an anastomosis.
  • a process for the preparation of bioprosthetic animal vascular tissue comprising the step of coating at least one surface of a cross-linked vascular tissue with an anhydride compound using a non-aqueous process of exposing the vascular tissue to the anhydride, wherein the cross-linked vascular tissue is an artery or vein obtained from an animal source, and wherein the vascular tissue is cross-linked by cross-linking agents to establish chemical cross-links within collagen of the vascular tissue.
  • additional alternative non- limiting features including:
  • non-aqueous process of exposing the vascular tissue to the anhydride is washing the vascular tissue in an anhydride solution
  • anhydride solution is substantially non-aqueous
  • non-aqueous anhydride solution is a mixture of an organic acid anhydride and an organic acid
  • non-aqueous anhydride solution is a mixture of succinic anhydride and succinic acid
  • non-aqueous anhydride solution is succinic anhydride in dry pyridine
  • animal source is human, bovine, porcine, ovine, or equine
  • bovine, porcine, ovine, or equine source is an animal 30 days old or less;
  • bovine, porcine, ovine, or equine source is an animal 5 days old or less;
  • vascular tissue is cross-linked using a 0.1% to 2.0% solution of a cross-linking agent selected from the group consisting of aldehydes, epoxides, isocyanates, carbodiimides, isothiocyanates, glycidalethers, and acyl azides;
  • a cross-linking agent selected from the group consisting of aldehydes, epoxides, isocyanates, carbodiimides, isothiocyanates, glycidalethers, and acyl azides
  • vascular tissue is cross-linked using about a 0.2% glutaraldehyde solution and the cross-linked vascular tissue is radially compliant;
  • vascular tissue is cross-linked using about a 1.0% to 2.0% glutaraldehyde solution and the cross-linked vascular tissue is radially non-compliant.
  • pre-treating is comprised of dehydrating and digesting with a surfactant.
  • dehydrating comprises subjecting the vascular tissue to a hyperosmotic salt solution.
  • bioprosthetic vascular tissue material is trimmed and configured to an appropriate shape for a surgical purpose selected from the group consisting of: coronary artery bypass grafting; creation of a therapeutic fistula e.g. for hemodialysis vascular access; carotid endarterectomy; endoscopic coronary surgery; and peripheral surgery.
  • FIGURE 1 is a flowchart showing Process 1 of the present invention and the steps of obtaining the collagenous tissue source, washing, dehydration, vapor cross-linking, liquid-bath cross- linking, non-aqueous anhydride surface coating, and processing into surgically usable tissue material
  • FIGURE 2 is a flowchart showing Process 2 of the present invention and the steps of obtaining the collagenous tissue source, washing, dehydration, vapor cross-linking, liquid-bath cross- linking, non-aqueous anhydride surface coating, tissue chelation, and processing into surgically usable tissue material.
  • FIGURE 3 is a flowchart showing Process 3 of the present invention and the steps of obtaining the collagenous tissue source, washing, dehydration, vapor cross-linking, liquid-bath cross- linking, non-aqueous anhydride surface coating, carbon sputter-coating, and processing into surgically usable tissue material.
  • FIGURE 4 is a flowchart showing Process 4 of the present invention and the steps of obtaining the collagenous tissue source, washing, dehydration, vapor cross-linking, liquid-bath cross- linking, non-aqueous anhydride surface coating, both chelating and carbon sputter-coating, and processing into surgically usable tissue material.
  • FIGURE 5 is an illustration of one preferred anhydride-collagen chemical reaction according to the present invention.
  • FIGURE 6 is an illustration of two examples of coronary artery bypass grafts that can be formed using the modified tissue material of the present invention.
  • FIGURE 7 is an illustration of one example of an anastomosis / vascular conduit between adjacent vascular structures.
  • FIGURE 8 is an illustration of one example of a peripheral, non-coronary use of the modified tissue material of the present invention, here showing a vascular graft to the kidney from the iliac artery.
  • the human body has numerous vessels carrying fluid to essential tissues and areas for recirculation or excretion. When vessels become damaged, severed or wholly occluded due to physiological problems, certain sections must be bypassed to allow for the free and continuous flow of fluids. Anastomosis is performed for the purpose of connecting different conduits together to optimize or redirect flow. In cardiac surgery, anastomosis is done to bypass the occluded vessel by harvesting a member of an unobstructed vessel and joining it to the occluded vessel below the point of stenosis, [para 34] The common procedure for performing the anastomosis during bypass surgery requires the use of very small sutures, loupes and microsurgical techniques. Surgeons must delicately sew the vessels together being careful not to suture too tightly so as to tear the delicate tissue, thereby injuring the vessel which may then result in poor patency of the anastomosis.
  • An anastomosis may be compliant or noncompliant.
  • a noncompliant anastomosis is one in which the anastomosis opening in the target vessel is not substantially free to expand or contract radially.
  • a noncompliant anastomosis may be formed with a one-piece or multiple-piece anastomosis device that compresses or otherwise controls tissue in the vicinity of the anastomosis to hold the graft vessel in place relative to the target vessel. Noncompliant anastomoses have been successful in certain situations.
  • a compliant anastomosis is one in which the target vessel is substantially free to expand or contract circumferentially and longitudinally in proximity to the anastomosis site.
  • a traditional sutured anastomosis is compliant, and for this reason some surgeons would prefer to utilize an anastomosis system that provides a compliant anastomosis, particularly between a graft vessel and the aorta or other source of arterial blood.
  • blood vessels are very complex structures that perform a wide array of functions beyond moving blood from point A to point B. They must not leak. They must avoid thrombosis. They must avoid stenosis. They control blood pressure. And, they perform the exchange of nutrients, ions, oxygen, and other biologically important molecules.
  • An artery is composed of three main layers of tissue. These layers, in cross-section, from outside to inside, comprise the tunica externa (formerly known as the tunica advantitia) (outer), tunica media (middle), and tunica intima (inner).
  • the tunica externa is made up of connective tissue, e.g. collagen and elastin.
  • the tunica media is made up of smooth muscle cells and elastic tissue. The muscle fibers run both longitudinally and radially.
  • the tunica intima is made up of laminin and endothelial cells, [para 39] "Thrombosis" is caused when the smooth muscle cells are exposed to flowing blood which triggers the release of Tissue Factor, also called Platelet Tissue Factor, and which initially is responsible for the biochemical cascade resulting in coagulation. Accordingly, vascular grafts must take this into account. Common stapling, suturing, puncturing and other manipulation by surgeons during the deployment of the anastomosis are sufficiently traumatic to the graft or adjacent tissues that they can cause thrombosis.
  • Steps (narrowing) of re-stenosis of a blood vessel is the secondary consequence of damage to a blood vessel. After the initial damage and clotting has occurred, a secondary response results in the proliferation of cells in the tunica intima.
  • Intimal hyperplasia is the universal response of a vessel to injury and is an important reason of late bypass graft failure, particularly in vein and synthetic vascular grafts.
  • multiple processes including thrombosis, inflammation, growth factor and cytokine release, cell proliferation, cell migration and extracellular matrix synthesis each contribute to the restenotic process. Accordingly, it would be advantageous to avoiding stenosis in a newly deployed vascular graft.
  • Proliferation/migration usually begins within one to two days' post-injury and peaks several days thereafter.
  • inflammatory cells may persist at the site of vascular injury for at least thirty days.
  • Inflammatory cells therefore are present and may contribute to both the acute and chronic phases of restenosis.
  • Collagen is the most abundant protein in all animal tissue, and is the primary component of connective tissue. Collagen consists of a protein with three polypeptide chains, each containing approximately 1000 amino acids and having at least one strand of repeating amino acide sequence Gly- X-Y, where X and Y can be any amino acid but usually are proline and hydroxyproline, respectively. Collagen assembles into different supramolecular structures and has exceptional functional diversity.
  • Vascular tissue sources contemplated as within the scope of the present invention include porcine, ovine, or bovine animals 30 days old or less. In one preferred embodiment, the tissue specimen is taken from an porcine, ovine, or bovine animal that is not more than about 10 days old, and in a preferred embodiment about 5 days old.
  • Vascular tissue refers to an artery or vein.
  • Crosslinks are bonds that link one polymer chain to another. They can be covalent bonds or ionic bonds.
  • Polymer chains can refer to synthetic polymers or natural polymers, including proteins such as collagen. Examples of some common crosslinkers are the dimethyl suberimidate, formaldehyde and glutaraldehyde. Each of these crosslinkers induces nucleophilic attack of the amino group of lysine and subsequent covalent bonding via the crosslinker.
  • surfactants are wetting agents that lower the surface tension of a liquid, allowing easier spreading, and lower the interfacial tension between two liquids.
  • the term surfactant is a blend of "surface active agent”.
  • Surfactants are usually organic compounds that are amphiphilic, meaning they contain both hydrophobic groups (their "tails") and hydrophilic groups (their "heads”). Therefore, they are soluble in both organic solvents and water.
  • Surfactants are also often classified into four primary groups: anionic, cationic, non-ionic, and zwitterionic (dual charge).
  • a non- limiting preferred surfactant contemplated herein is sodium laurel sulfate, although various other surfactants known to a person of ordinary skill in the art are also contemplated as within the scope of the invention,
  • the term "exposing” refers to soaking the tissue in a fluid comprising the treatment agent for a period of time sufficient to treat the tissue.
  • the soaking may be performed by, but is not limited to, incubation, swirling, immersion, mixing, or vortexing.
  • Collagen content is not limited to, incubation, swirling, immersion, mixing, or vortexing.
  • BC tissue is known to be extremely thin and has a very high natural collagen content, providing the tissue both high strength and a variety of biocompatibility benefits, including low antigenicity,
  • adult tissue may also be subjected to the steps of the present invention for the manufacturing of a source of surgical tissue.
  • Bovine, ovine, equine, and porcine sources are used to provide the base material.
  • the tissue source is bovine.
  • the tissue source is ovine.
  • the tissue source is equine.
  • the tissue source is porcine.
  • Treatment of vascular tissue for use in surgical transplantation may optionally begin with an isotonic saline wash at room temperature. Washing a tissue sample with a surfactant/water solution for a period of up to 24 hours can result in a 99: 1 post-treatment ratio of collagen to non-collagenous proteins in the tissue. Such a high ratio greatly enhances the effectiveness of later collagen cross- linking to further improve biocompatibility of the sample.
  • Thinness of tissue used for surgical implants and grafts provides many benefits in surgery as the thickness of such material directly affects the size of any product or device made with such a material, for example an anastomosis. Further, the smaller size impacts the ease with which the material may be introduced into the human body, through catheterization or otherwise, as well as the ease of manipulation of the material after placement.
  • a thinner sample means a lower gauge catheter, and easier intravenous or percutaneous insertion, and thus the ability to treat a higher percentage of the patient population requiring such an intervention.
  • [para 63] Suspension in a hyperosmotic solution for a period of 30 minutes will substantially thin the tissue through partial dehydration.
  • dehydration broadly refers to any method that removes the water from the tissue without denaturing the tissue. This includes, but is not limited to processes such as, by way of example, and not limitation, lyophilization, vacuum drying, air drying, or solvent- based drying such as, by way of example, and not limitation, exposing the tissue to various alcohol- based solutions.
  • An ideal primary method for cross-linking collagen in tissue comprises placing such tissue onto a pin frame such that the edges are held firmly in place. The frame and tissue sample are then placed into a chamber equipped with each of an inlet and outlet port for submission to a "vapor cross- linking" process.
  • the inlet port is attached to a stoppered flask comprising each of an inlet and outlet port and containing a bolus of polyoxymethylene, which flask is gently heated as air flow is simultaneously initiated from the flask into the chamber containing the tissue sample, thereby producing formaldehyde (cross-linking agent) vapors which flood the chamber for a period of 10 minutes, after which time such vapors are evacuated from the chamber and the pin frame and tissue sample are removed intact therefrom.
  • formaldehyde cross-linking agent
  • the tissue material is subjected to a liquid cross-linking bath.
  • this is a liquid glutaraldehyde bath.
  • Glutaraldehyde provides a further cross-linking that results in additional cross-links that formaldehyde cannot achieve.
  • the presence of two aldehyde groups for cross-linking and the ability to be cross link over a distance since glutaraldehyde has a three-carbon chain connecting the two carbonyl moieties further strengthens the tissue material.
  • the pin frame and tissue sample are then transferred into an aqueous bath containing 1% 0.01M phosphate buffered glutaraldehyde and 10% isopropyl alcohol at a temperature of approximately 40 degrees C, and gently stirred for a period of not less than 24 hours, although variations of glutaraldehyde cross-linking are well known in the art and are considered within the scope of this step of the present invention.
  • the process of creating stable, non-reactive aromatics on the exposed surface of the collagen is believed to progress by nucleophilic attack by formaldehyde on the carbonyl of the glutaraldehyde-linked amine of the lysine, histidine, and/or arginine, improving the stability of the molecular structure of the sample and reducing the antigenicity of the sample compared to a sample treated with glutaraldehyde alone.
  • a reduced inflammatory response and lower degree of capsule formation provides a distinct advantage.
  • the tissue sample is subjected to the step of coating/reacting the cross-linked vascular tissue with an anhydride compound.
  • Coating/reacting the surface with anhydride is used to chemically modify the surface of the vascular tissue to reduce or eliminate thrombosis caused by the implant.
  • succinic anhydride is contemplated in order to create a chemical bond to the amino acid residues of the collagenous tissue.
  • the present invention provides for a method for forming a surface composition comprised of the vascular tissue and an anhydride including the step of using a nonaqueous process of exposing the vascular tissue to the anhydride, wherein the cross-linked vascular tissue is an artery or vein obtained from an animal source, and wherein the vascular tissue is cross- linked by cross-linking agents to establish chemical cross-links within collagen of the vascular tissue, [para 77]
  • the pH of the solution must be raised to 10 or higher so that free amine nucleophiles are present in the reaction system.
  • amines are efficiently acylated by both cyclic and acyclic anhydrides in aqueous medium with sodium dodecyl sulfate (SDS) - without use of acidic or basic reagents.
  • SDS sodium dodecyl sulfate
  • Various amines and anhydrides were reacted with equal ease. S. Naik, G. Bhattacharjya, B. Talukdar, B. K. Patel, Eur. J. Or . Chem., 2004, 1254-1260.
  • collagen is subjected over sufficient time to 0.05% acetic acid solution, and the pH is adjusted to 10 in a NaOH solution, the temperature of the solution was maintained at 0-2 °C in an ice/water bath. Then, succinic anhydride is added, and the pH was maintained at 9-10 for lh. Succinylated collagen is then obtained. After washing several times with distilled water, succinylated collagen may be stored in PBS buffer solution. H 2 COOH
  • the present invention is also directed to a method of coating the vascular tissue with a very thin layer of carbon.
  • Methods are known in the art for coating implants with turbostratic carbon, e.g. planar graphitic carbon, see e.g. U.S. Pat. 5,370,684, Vallana et al. This carbon coating is firmly adherent to the tissue, thereby augmenting the implants biocompatible properties.
  • the method of the present invention comprises subjecting a source of carbon to a plasma beam generated by triode sputtering under vacuum conditions. Ionization of an inert gas and generation of the plasma beam therefrom is achieved utilizing the apparatus disclosed in 5,370,684 and related patents, incorporated herein by reference.
  • Carbon atoms sputtered off the target are directed to the substrate to thereby deposit a thin biocompatible film on the substrate.
  • the desired density of the carbon deposited on the substrate (2.1 g/cm 3 preferably 2.2 g/cm 3 ) is achieved by operating the triode sputtering apparatus under the following conditions: Filament current 80-90 amps ; sputtering voltage 2000-3200 volts ; sputtering current 0.1-0.3 amp ; pressure 6xl0 ⁇ 4 to 6xl0 ⁇ 3 mbar .
  • This method of depositing the highly dense carbon may be used regardless of the configuration of the substrate, e.g. flat or curved or undulating. Here, it is used on modified vascular tissue as described herein.
  • the tissue may have its surface chemically modified to have a chelating agent affixed thereto.
  • Chelating agents are known to have an anti-coagulating effect as well as provide the possibility of reducing calcification of the glutaraldehyde cross-linked bioimplants.
  • a preferred chelating agent is a compound that contains magnesium, such as mesotetraphenylporphorin magnesium chloride.
  • EDTA ethylenediaminetetraacetic acid
  • EGTA EGTA
  • bisaminoethyl-glycolethertetraacetic acid as well as polymeric ether chelating agents such as the polyoxyethylenes, polyoxyglycols, and poly-glymes; other structural components which form similar shapes such as cyclic antibiotics, amino acid peptides, and wholly synthetic or biological compounds, such as modified fullerenes, dendrimers, polysaccharides, polynucleic acids, or other compounds capable of complexing divalent cations due to their three dimensional shape and ionic character.
  • the principal action of the agents described is complexation of metal compounds, such as calcium and magnesium, through one or more electron-donating groups.
  • the chelating agent can be monodentate (from the Latin word dentatus, meaning "toothed.”), such as the chlorides, cyanides, hydroxides, or ammonia complexes, and mixed complexes may be formed from these.
  • the ligand may be multidentate, or containing multiple teeth, which can contribute two or more electron pairs to a complex.
  • Ethylenediamine, NH2CH2CH2NH2 is an exemplary bidentate ligand.
  • aminopolycarboxylic acid family examples include DCTA (trans-diaminocyclohexanetetraacetic acid), NTA (nitrilotriacetic acid), and DTPA (diethylenetriameinepentaacetic acid).
  • DCTA trans-diaminocyclohexanetetraacetic acid
  • NTA nitrilotriacetic acid
  • DTPA diethylenetriameinepentaacetic acid
  • the product is then optionally sterilized by transferring it to an aqueous bath consisting essentially of a 2% buffered glutaraldehyde solution containing 10% isopropyl alcohol, and is soaked therein at 42 degrees C for a period of no less than 24 hours. Upon completion of sterilization, the tissue sample is removed from the pin frame.
  • tissue sample is packaged for transport in a container together with a sterilizing 0.65%, 0.01 M phosphate buffered glutaraldehyde solution, in which solution the tissue sample may either float freely or be held stationary by attachment to a mylar film.
  • tissue sample may be trimmed, sutured or otherwise manipulated to form the size and shape necessary for any vascular tissue implantation surgery for which such tissue would be appropriate.
  • agents have been suggested as anti-pro liferative agents in restenosis and have shown some activity in experimental animal models.
  • ACE angiotensin converting enzyme
  • agents with diverse mechanisms of smooth muscle cell inhibition may have therapeutic utility in reducing intimal hyperplasia
  • agents which have also been unsuccessful in the prevention of restenosis, include the calcium channel antagonists, prostacyclin mimetics, angiotensin converting enzyme inhibitors, serotonin receptor antagonists, and anti-pro liferative agents. These agents must be given systemically, however, and attainment of a therapeutically effective dose may not be possible; anti-proliferative (or anti-restenosis) concentrations may exceed the known toxic concentrations of these agents so that levels sufficient to produce smooth muscle inhibition may not be reached.

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Abstract

Cette invention concerne des pontages aorto-coronariens et des conduits vasculaires, et en particulier, un tissu vasculaire spécialement modifié utilisé pour créer une anastomose.
PCT/US2012/070003 2011-12-15 2012-12-17 Pontages aorto-coronariens et conduits vasculaires WO2013090878A1 (fr)

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Citations (4)

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EP0124659A1 (fr) * 1983-04-13 1984-11-14 Koken Co. Ltd. Matériau médical
US5800541A (en) * 1988-11-21 1998-09-01 Collagen Corporation Collagen-synthetic polymer matrices prepared using a multiple step reaction
US20080075754A1 (en) * 2002-03-29 2008-03-27 Aruna Nathan Compositions and medical devices utilizing bioabsorbable liquid polymers
US20080199506A1 (en) * 2005-05-05 2008-08-21 Roland Horres Coating of the Entire Surface of Endoprostheses

Patent Citations (4)

* Cited by examiner, † Cited by third party
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