WO1993021860A1 - Non-thrombogenic vascular prosthesis - Google Patents
Non-thrombogenic vascular prosthesis Download PDFInfo
- Publication number
- WO1993021860A1 WO1993021860A1 PCT/US1993/004213 US9304213W WO9321860A1 WO 1993021860 A1 WO1993021860 A1 WO 1993021860A1 US 9304213 W US9304213 W US 9304213W WO 9321860 A1 WO9321860 A1 WO 9321860A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- heparin
- vascular prosthesis
- prosthesis
- compounded
- vascular
- Prior art date
Links
Classifications
-
- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0005—Use of materials characterised by their function or physical properties
- A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
- A61L33/0017—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate using a surface active agent
-
- 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
- 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
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
Definitions
- This invention relates to vascular prostheses and more particularly to a vascular prosthesis having a coating of ionically bonded heparin to act as an anticoagulant.
- vascular graft implants are those which are formed from a biologically compatible material which retains an open lumen to permit the flow of blood through the graft after implantation.
- Vascular prosthesis made of knitted or woven
- Dacron ® polyester have been used for many years in a variety of constructions.
- Common textile prostheses, made from Dacron ® polyester, are very porous and require pre- clotting with the patient's blood prior to surgery in order to prevent hemorrhaging after implantation.
- Recent developments have employed coating the prosthesis, which enables the prosthesis to be implanted without pre- clotting.
- Coatings of different materials have been used, including biodegradable materials such as albumin, collagen and gelatin, as well as non-biodegradable materials such as elastomeric polymers.
- vascular grafts with a coating, respectively, of an anionic or cationic surfactant and an oppositely charged drug bound to the surfactant.
- the surfactant and" oppositely charged drug are ionically bound.
- Greco et al, U.S. patent 4,444,133 and Greco et al, U.S.. patent 4,740,382 disclose vascular grafts coated with a cationic surfactant (TDMAC) and a negatively charged antibiotic.
- TDMAC cationic surfactant
- vascular grafts having a coating of thermoplastic fluorinated polyurethane urea (FPUU) having free a ino groups which are then reacted with heparin or other antithrombogenic agent to covalently bond the compound to the FPUU coating.
- FPUU thermoplastic fluorinated polyurethane urea
- vascular grafts having a coating of polyethyleneimine that has been water-insolubilized by cross-linking with heparin ionically bound to the polyethylemeimine.
- vascular graft having an anticoagulant substance such as heparin bound to the inner surface and a porous elastomer coating on the outside of the graft which contains a substance which counteracts the anti-coagulant substance.
- an anticoagulant substance such as heparin bound to the inner surface
- a porous elastomer coating on the outside of the graft which contains a substance which counteracts the anti-coagulant substance.
- vascular prosthesis which exhibits low porosity at the time of implantation of the prosthesis in order to obviate the need for pre-clotting which does not require a substance that counteracts an anti-coagulant, but which aiso allows for rapid build up of natural tissue within the interstices of the fabric of the prosthesis to promote good healing and prevent clotting.
- the present invention provides a vascular prosthesis free of any substance that counteracts an anti- coagulant comprising a base material, the base material having inner and outer surfaces, wherein the outer surface has a layer of a material capable of reducing the porosity of the prosthesis to blood or body fluid and a layer of compounded heparin bound thereon, and the inner surface has a layer of compounded heparin bound thereon.
- the compounded heparin employed in the grafts of the present invention preferably comprises heparin ionically bonded with the cationic surfactant.
- the coating of compounded heparin reduces thrombogenicity of the prosthesis by preventing or slowing down clotting, and promotes the build up of a thin, even, well-defined and well-adhered pseudo-intima on the inner surface of the vascular prosthesis.
- the material capable of reducing the porosity of the prosthesis obviates the need for pre-clotting procedures prior to implantation of the prosthesis.
- the present invention also provides a method of forming a vascular prosthesis comprising a base material having inner and outer surfaces, comprising the steps of applying a material capable of reducing porosity of the vascular prosthesis to the outer surface of the base material to form a layer of the material capable of reducing the porosity of the vascular prosthesis on the outer surface; and applying compounded heparin to the layer of material from step (a) and to the inner surface of said vascular prosthesis, the compounded heparin comprising heparin and a cationic surfactant, to form a layer of the compounded heparin on the layer of the material capable of reducing porosity of the vascular and a layer of compounded heparin on the inner surface of the vascular prosthesis.
- the vascular grafts of the invention may also be formed by applying the compounded heparin prior to applying the material capable of reducing porosity of the vascular graft such that the layer of compounded heparin is formed on the inner and outer surfaces of the base material and the layer of material capable of reducing porosity of the vascular prosthesis is formed on the layer of compounded heparin on the outer surface of the prosthesis.
- FIG. la is a schematic of a longitudinal cross- sectional view of a vascular prosthesis of the invention having a collagen layer bound on the outer surface and a coating of heparin on the inner surface and on the collagen layer.
- Figure lb is a schematic of a cross-sectional view of the same vascular prosthesis of the invention having a collagen layer bound on the outer surface and a coating of heparin on the inner surface and on the collagen layer.
- the vascular prostheses of the present invention are free of any substance that counteracts an anti ⁇ coagulant and exhibit low porosity at the time of implantation of the prosthesis thereby obviating the need for pre-clotting the prosthesis to avoid leakage or hemorrhaging of blood through the prosthesis.
- the compounded heparin coating of the vascular prostheses of the invention prevents or slows down blood clotting which leads to the build up of natural tissue within the interstitial spaces of the prosthesis and the build-up of a thin, even, well-defined and well-adhered pseudo-intima on the inner surface of the prosthesis.
- the vascular prostheses of the invention are convenient to use and provide a good substrate for regrowth of blood vessel tissue.
- the base material of the prosthesis is preferably a bio-compatible polymeric material that can be fabricated into a porous structure which will permit tissue ingrowth and maintain an open lumen for blood flow.
- Preferred base materials include polyethylene terephthalate (Dacron ® polyester) .
- the base material may be woven, knitted, or cast into the desired shape for the prosthesis, depending on the type of material selected for use. Knitted prostheses are used mainly to replace diseased sections of arteries in the abdominal and peripheral areas of the body, while woven prosthesis are used mainly in the higher pressure thoracic areas.
- the vascular grafts of the invention can have any shape suital: :.X ⁇ .
- patch grafts for implantation into an animal such as a tubular shape, ⁇ f bifurcated tubular shape, or be in the form of a sheet of material.
- Such flat sheets of material are known in the art as "patch grafts".
- patch grafts may have any size and configuration.
- Patch grafts are generally employed for repairing large blood vessels which do not require complete removal of tubular sections.
- a specialist form of patch graft is a thin strip of material having selvedged edges. The selvedged edge allows sutures to be placed at the very edge of the patch in order to make a very small neat suture line without risk of the sutures pulling out of the fabric.
- This specialist patch is generally used to close the carotid artery following a carotid endorectomy.
- Such carotid patches are typically about 75mm long and from about 4mm to 16mm in width.
- bio- compatible refers to material that is suitable for implantation into the body of an animal, particularly the human body. Materials may be formed into vascular grafts according to the methods known in the art, or suitable grafts may be obtained from commercial suppliers such as InterVascular, Clearwater, FL (InterVascular Knitted Micron and InverVascular Woven LP) .
- the vascular prostheses of the invention may optionally be radially supported by a synthetic polymeric material.
- the synthetic polymer is formed around the outer surface along the length of the graft to form a spiral or sleeve of material to support the prosthesis.
- the radial supporting material may also be formed integrally into the wall of the prosthesis itself.
- a preferred synthetic polymer for support of the vascular prosthesis is a polypropylene onofilament.
- the inner surface of the graft is the surface that is in contact with the flow of blood
- the outer surface of the graft is the surface not in contact with the flow of blood and is in contact with other body tissues.
- the inner surface is the surface in the lumen of the graft that will be in contact with the flow of blood
- the outer surface is the opposite surface on the outside of the graft that will be in contact with other body tissues when implanted into an animal.
- the inner surface is the surface in contact with the flow of blood and the outer surface is the surface in contact with other body tissues.
- the prostheses are coated with a layer or coating of a material capable of reducing the porosity of the prosthesis to blood or other body fluids.
- vascular prostheses are typically permeable to blood and other body fluids, especially in applications where the pressure of the blood within the prosthesis is high, and blood or other fluid leaks through the prosthesis into surrounding tissues.
- the material capable of reducing porosity of the vascular prosthesis acts as a barrier to the seeping of blood or other fluid through the walls of the prosthesis into surrounding tissue and renders them impermeable or substantially impermeable to the blood or other body tissue.
- the material capable of reducing the porosity of the prosthesis may be selected from biodegradable and non- biodegradable materials.
- a preferred biodegradable material is collagen.
- Suitable non-biodegradable materials include silicon based elastomeric polymers such as Silastic ® materials, and polyurethane.
- the material capable of reducing the porosity is applied to the inner or outer surface or both of the prosthesis such that a layer of material is formed that is effective to obviate the need for pre-clotting the prosthesis before it is inserted into an animal, i.e. the thickness of the layer formed renders the prosthesis impermeable or substantially impermeable to blood or other body fluid.
- the thickness of the layer of material capable of reducing porosity of the vascular prosthesis is preferably from about 0.05mm to about 0.1mm in thickness; more preferably from about 0.06 to about 0.09mm in thickness; most preferably from about 0.06 to about 0.08mm in thickness.
- the collagen When collagen is employed as the material capable of reducing porosity of the vascular prosthesis, the collagen may be applied such that it impregnated intimately into the interstitial spaces of the fabric of the base material. Alternatively, the collagen may be formed into a thin membrane or film adhered to the surface of the base material and not extending into the interstitial spaces of the base material.
- the porosity reducing coating comprising a biodegradable material may be adhered to the outer surface of the base material, the inner surface of the base material, or both the inner and outer surfaces.
- the biodegradable material may also be applied to the inner surface of the base material, or on top of an underlayer of compounded heparin.
- the layer of biodegradable material on the interior of the prosthesis is preferably thinner than the layer on the outer surface.
- the layer on the inner surface of the base material can be thinner than the layer on the outer surface since the blood pressure forces the inner layer against the base material of the prosthesis.
- the layer on the outer surface is prevented from separating from the base material only due to adhesive bonds.
- the porosity reducing coating is a non-bio-degradable material
- the porosity reducing coating is applied only to the outer surface of the base material and is preferably applied to the base material before the heparin coating is applied.
- collagen is employed as the biodegradable material capable of reducing porosity of the vascular graft.
- the collagen is selected to be compatible with the species of animal into which the prosthesis will be inserted.
- bovine collagen is preferred since it is widely available and causes few adverse reactions.
- a preferred type of bovine collagen is derived from the achilles tendon.
- Collagen is preferably obtained in the form of compressed collagen fiber sheets made from highly purified, insoluble, type 1, bovine achilles tendon collagen fiber, which may be obtained commercially from suppliers such as Bioplex, Vaals, Holland.
- the collagen in the sheet form is not cross-linked and is similar to that used as a hemostat sponge.
- the sheets of collagen are chopped into small pieces and made into an aqueous fine dispersion or slurry containing from about 5 grams per liter to about 12 grams of collagen per liter of dispersion. More preferably, collagen is present in the aqueous dispersion in the amount of about 10 grams per liter ⁇ 10%.
- a wetting agent is added to the dispersion in an amount effective to wet the collagen.
- a suitable wetting agent is polyoxyethylene- sorbitan monolaurate (Tween 20 ® , Fisher Scientific Corp, Springfield, NH) which is added in amounts of about twelve grams per liter of dispersion.
- a plasticizer is also added to the dispersion.
- a suitable plasticizer is glycerol (Fisher Scientific Corp., Springfield, NH which is added in amounts of about ten grams per liter of dispersion. This process results in a gel like slurry.
- the collagen may be applied to the base material such that it is intimately impregnated into the interstitial spaces of the base material by dipping the prosthesis into an aqueous dispersion of collagen and subsequently cross-linking the collagen with a cross- linking agent such as glutaraldehyde.
- an aqueous dispersion of collagen is cross-linked prior to application to the prosthesis.
- the collagen in the aqueous dispersion is cross-linked by adding a cross-linking agent such as glutaraldehyde and mixing for a length of time effective to cross-link the collagen but still provide a pliable aqueous dispersion that can be used for coating the vascular prosthesis.
- the aqueous dispersion is stirred for about 20 hours with the glutaraldehyde (about 0.6 grams per liter of dispersion) and the cross-linking process can be terminated by the addition of glycine (about 1.0 grams per liter of dispersion) .
- the inner layer of collagen is preferably substantially thinner than the outer layer. Differential thickness may be achieved by dipping the prosthesis one or more times in the aqueous dispersion of collagen to coat both the inner and outer surfaces or layers of compounded heparin and form a layer of collagen of a desired thickness, sewing shut the ends of the prosthesis, and redipping the closed-end prosthesis into collagen for further applications to form a thicker layer of collagen of desired thickness on the outer surface or layer of compounded heparin.
- Compounded heparin is applied to the base material either over or under a layer of biodegradable material capable of reducing the porosity of the vascular graft.
- the layer of compounded heparin is applied after or on top of the layer of non-biodegradable material.
- Compounded heparin as used in the present invention comprises heparin and a cationic surfactant.
- the heparin is preferably ionically bound to the cationic surfactant.
- Suitable cationic surfactants include tridodecylmethylammonium chloride (TDMAC) heparin and benzalkonium chloride.
- the coating of compounded heparin is ionically bound to either the base material or the layer of material capable of reducing the porosity of the prosthesis, depending on the embodiment of the invention.
- the compounded heparin penetrates into the interstices of the base material and coats the individual fibers of knitted or woven base materials and coats the pores of cast base materials.
- a coating of heparin on the inner or outer surface of the base material refers to compounded heparin deposited on the individual fibers of knitted or woven base materials or in the pores of case base materials in amounts sufficient to coat the individual fibers or pores on the surface and in the interior of the base material, at least those fibers or pores adjacent to the surface, but not in amounts sufficient to form a film or layer on the surface of the base material.
- the compounded heparin is not soluble in either water or blood plasma, so that it stays bonded to the inner surface of the base material, also referred to as the luminal wall.
- Compounded heparin is applied to the prosthesis in amounts sufficient to serve as an anti-coagulant, however, the amount preferably should not be sufficient to promote platelet clots and/or leukocyte reactions. Effective concentrations of compounded heparin range from about 2.5 to about 15 grams per square meter, which provides approximately 15 to 100 USP units of heparin per square centimeter of prosthesis surface. More preferably the compounded heparin is applied at a concentration of about 7 grams per square meter, providing 45 USP units per square centimeter.
- Compounded heparin can be prepared by ionically bonding heparin to a cationic surfactant using methods known in the art, or it can be obtained commercially through suppliers such as CIA Labs, St. Joseph, Missouri.
- Compounded heparin is applied to the vascular prosthesis by dipping the prosthesis into a solution containing compounded heparin for about 30 to about 60 seconds and then air drying the prosthesis.
- the solvent used for the solution will vary depending on the cationic surfactant used.
- the compounded heparin comprises TDMAC and heparin
- the solvent is a mixture of 50% toluene and 50% petroleum ether.
- the compounded heparin comprises benzalkonium chloride and heparin
- the solvent may be one of a number of different types known in the art, including ethylene chlor:' ::' ⁇ or ethyl alcohol.
- the compounded heparin solution may"foe made in a variety of concentrations from about 0.5% to about 6% weight per volume. Since the amount of compounded heparin that will adhere to the base material or material capable of reducing porosity of the vascular prosthesis is proportional to the concentration of compounded heparin in the solution, the amount of compounded heparin may be controlled by solution strength, i.e. the greater the amount of compounded heparin in the solution, the greater the amount of compounded heparin applied to the surface of the base material or the material capable of reducing the porosity of the vascular prosthesis. The evaporation of the solvent leaves the solute (i.e.
- the present invention provides vascular prostheses free of any substance that counteracts an anti ⁇ coagulant and comprising a base material wherein the outer surface has a layer of a material capable of reducing the porosity of the prosthesis to blood or body fluid and a layer of compounded heparin bound thereon, and the inner surface has a layer of compounded heparin bound thereon.
- the layer of material capable of reducing the porosity of the prosthesis is bound to the outer surface of the vascular prosthesis and the layer of compounded heparin is bound to the layer of material capable of reducing the porosity of the vascular prosthesis.
- the layer of compounded heparin is bound to the outer surface of the vascular graft and the layer of material capable of reducing the porosity of said vascular prosthesis is bound to the layer of compounded heparin.
- the inner surface of the prosthesis has a layer of compounded heparin and a layer of a biodegradable material capable of reducing porosity of the vascular prosthesis.
- the prosthesis in Figures la and lb has a tubular shape and an inner lumen 20 extending through the length of the prosthesis.
- the inner surface 16 of the prosthesis 10 is in contact with the flow of blood when the prosthesis is implanted into an animal.
- the outer surface 14 of the prosthesis 10 has a collagen layer 18 bound thereon.
- the collagen layer is on the outer surface 14 and does not extend into the walls 12 of the prosthesis.
- the prosthesis 10 is shown with crimps 22 that strengthen the walls 12 of the prosthesis 10.
- a coating of compounded heparin 24 is bound to the inner surface 16 of the prosthesis 10 such that it coats the individual fibers of the prosthesis at the inner surface 16 and in the walls 12 of the prosthesis.
- a coating of compounded heparin 24 is also bound to the outer surface 14 of the prosthesis 10 such that it coats the individual fibers of the prosthesis at the outer surface of the prosthesis and in the walls 12 -of the prosthesis.
- a Dacron ® polyester fabric prosthesis is coated on its inner and outer surfaces with compounded heparin. Then a layer of cross-linked collagen is applied to the outer layer of compounded heparin, or both the inner and outer layers of compounded heparin so that the collagen forms a thin membrane or film.
- the inner layer is preferably substantially thinner than the outer layer.
- the collagen layer on the inner surface or inner compounded heparin layer is absorbed first, and the blood is allowed to permeate slowly into the interstices of the fabric of the base material.
- the outer layer of collagen prevents leakage of blood or other fluid from the prosthesis into surrounding tissue.
- the Dacron ® fiber surface is mildly thrombogenic, which means that the blood would normally form a surface clot.
- the base material of the prosthesis of the present invention has been coated frith compounded heparin so the clotting process is initially prevented and later controlled at a slow rate.
Abstract
The invention provides vascular prostheses (10) free of any substance that counteracts an anti-coagulant comprising a base material having inner (16) and outer (14) surfaces, wherein the outer surface has a layer of a material capable of reducing the porosity of said prosthesis to blood or body fluid and a coating of compounded heparin (24) bound thereon, and the inner surface (16) has a coating of compounded heparin (24) bound thereon, the compounded heparin (24) comprising heparin and a cationic surfactant. The present invention also provides a method for forming a vascular prosthesis. The vascular prostheses (10) exhibit an initial low porosity thereby obviating the need for pre-clotting the prosthesis. The compounded heparin (24) coating of the vascular prostheses prevents or slows down blood clotting which leads to the build up of natural tissue within the interstitial spaces of the prosthesis (10) and the build-up of a thin, even, well-defined and well-adhered pseudo-intima on the inner surface of the prosthesis (10).
Description
NON-THROMBOGENIC VASCULAR PROSTHESIS
This is a continuation of application Serial No. 07/879,345 filed May 7, 1992.
FIELD OF THE INVENTION This invention relates to vascular prostheses and more particularly to a vascular prosthesis having a coating of ionically bonded heparin to act as an anticoagulant.
BACKGROUND OF THE INVENTION
The replacement of segments of human blood vessels with vascular grafts is well known in the art.
Among the accepted and successful vascular graft implants are those which are formed from a biologically compatible material which retains an open lumen to permit the flow of blood through the graft after implantation. Vascular prosthesis made of knitted or woven
Dacron® polyester have been used for many years in a variety of constructions. Common textile prostheses, made from Dacron® polyester, are very porous and require pre- clotting with the patient's blood prior to surgery in order to prevent hemorrhaging after implantation. Recent developments have employed coating the prosthesis, which enables the prosthesis to be implanted without pre- clotting. Coatings of different materials have been used, including biodegradable materials such as albumin, collagen
and gelatin, as well as non-biodegradable materials such as elastomeric polymers.
Greco et al. , U.S. patent 4,879,135 issued
November 7, 1989 discloses vascular grafts with a coating, respectively, of an anionic or cationic surfactant and an oppositely charged drug bound to the surfactant. The surfactant and" oppositely charged drug are ionically bound. Greco et al, U.S. patent 4,444,133 and Greco et al, U.S.. patent 4,740,382 disclose vascular grafts coated with a cationic surfactant (TDMAC) and a negatively charged antibiotic.
Hu et al, U.S. patent 5,032,666 issued July 16,
1991 discloses vascular grafts having a coating of thermoplastic fluorinated polyurethane urea (FPUU) having free a ino groups which are then reacted with heparin or other antithrombogenic agent to covalently bond the compound to the FPUU coating.
Mano et al., U.S. patent 4,229,838 issued October
28, 1980 discloses vascular grafts having a coating of polyethyleneimine that has been water-insolubilized by cross-linking with heparin ionically bound to the polyethylemeimine.
Mano et al. , U.S. patent 4,321,711 issued March
30, 1982 discloses a vascular graft having an anticoagulant substance such as heparin bound to the inner surface and a porous elastomer coating on the outside of the graft which contains a substance which counteracts the anti-coagulant substance.
However, these various coating approaches do not solve the problem of reducing the porosity of the prosthesis at the time of implantation so as to obviate the need for pre-clotting procedures, while at the same time reducing the thrombogenicity of the prosthesis to prevent clotting after implantation and promote the build up of a thin, even, well-defined and well-adhered pseudo-intima in the prosthesis. Therefore, there is a need for a vascular prosthesis which exhibits low porosity at the time of
implantation of the prosthesis in order to obviate the need for pre-clotting which does not require a substance that counteracts an anti-coagulant, but which aiso allows for rapid build up of natural tissue within the interstices of the fabric of the prosthesis to promote good healing and prevent clotting.
SUMMARY OF THE INVENTION The present invention provides a vascular prosthesis free of any substance that counteracts an anti- coagulant comprising a base material, the base material having inner and outer surfaces, wherein the outer surface has a layer of a material capable of reducing the porosity of the prosthesis to blood or body fluid and a layer of compounded heparin bound thereon, and the inner surface has a layer of compounded heparin bound thereon. The compounded heparin employed in the grafts of the present invention preferably comprises heparin ionically bonded with the cationic surfactant.
The coating of compounded heparin reduces thrombogenicity of the prosthesis by preventing or slowing down clotting, and promotes the build up of a thin, even, well-defined and well-adhered pseudo-intima on the inner surface of the vascular prosthesis. The material capable of reducing the porosity of the prosthesis obviates the need for pre-clotting procedures prior to implantation of the prosthesis.
The present invention also provides a method of forming a vascular prosthesis comprising a base material having inner and outer surfaces, comprising the steps of applying a material capable of reducing porosity of the vascular prosthesis to the outer surface of the base material to form a layer of the material capable of reducing the porosity of the vascular prosthesis on the outer surface; and applying compounded heparin to the layer of material from step (a) and to the inner surface of said vascular prosthesis, the compounded heparin comprising
heparin and a cationic surfactant, to form a layer of the compounded heparin on the layer of the material capable of reducing porosity of the vascular and a layer of compounded heparin on the inner surface of the vascular prosthesis. The vascular grafts of the invention may also be formed by applying the compounded heparin prior to applying the material capable of reducing porosity of the vascular graft such that the layer of compounded heparin is formed on the inner and outer surfaces of the base material and the layer of material capable of reducing porosity of the vascular prosthesis is formed on the layer of compounded heparin on the outer surface of the prosthesis.
This invention is more particularly pointed out in the appended claims and is described in its preferred embodiments in the following description.
BRIEF DESCRIPTION OF THE DRAWINGS FIG. la is a schematic of a longitudinal cross- sectional view of a vascular prosthesis of the invention having a collagen layer bound on the outer surface and a coating of heparin on the inner surface and on the collagen layer. Figure lb is a schematic of a cross-sectional view of the same vascular prosthesis of the invention having a collagen layer bound on the outer surface and a coating of heparin on the inner surface and on the collagen layer.
DETAILED DESCRIPTION OF THE INVENTION
The vascular prostheses of the present invention are free of any substance that counteracts an anti¬ coagulant and exhibit low porosity at the time of implantation of the prosthesis thereby obviating the need for pre-clotting the prosthesis to avoid leakage or hemorrhaging of blood through the prosthesis. The compounded heparin coating of the vascular prostheses of the invention prevents or slows down blood clotting which leads to the build up of natural tissue within the interstitial spaces of the prosthesis and the build-up of a thin, even, well-defined and well-adhered pseudo-intima on
the inner surface of the prosthesis. Thus, the vascular prostheses of the invention are convenient to use and provide a good substrate for regrowth of blood vessel tissue. The base material of the prosthesis is preferably a bio-compatible polymeric material that can be fabricated into a porous structure which will permit tissue ingrowth and maintain an open lumen for blood flow. Preferred base materials include polyethylene terephthalate (Dacron® polyester) . The base material may be woven, knitted, or cast into the desired shape for the prosthesis, depending on the type of material selected for use. Knitted prostheses are used mainly to replace diseased sections of arteries in the abdominal and peripheral areas of the body, while woven prosthesis are used mainly in the higher pressure thoracic areas. The vascular grafts of the invention can have any shape suital: :.X÷. for implantation into an animal such as a tubular shape, Εf bifurcated tubular shape, or be in the form of a sheet of material. Such flat sheets of material are known in the art as "patch grafts". Such patch grafts may have any size and configuration. Patch grafts are generally employed for repairing large blood vessels which do not require complete removal of tubular sections. A specialist form of patch graft is a thin strip of material having selvedged edges. The selvedged edge allows sutures to be placed at the very edge of the patch in order to make a very small neat suture line without risk of the sutures pulling out of the fabric. This specialist patch is generally used to close the carotid artery following a carotid endorectomy. Such carotid patches are typically about 75mm long and from about 4mm to 16mm in width. As used herein, the term bio- compatible refers to material that is suitable for implantation into the body of an animal, particularly the human body. Materials may be formed into vascular grafts according to the methods known in the art, or suitable grafts may be obtained from commercial suppliers such as
InterVascular, Clearwater, FL (InterVascular Knitted Micron and InverVascular Woven LP) .
The vascular prostheses of the invention may optionally be radially supported by a synthetic polymeric material. Preferably the synthetic polymer is formed around the outer surface along the length of the graft to form a spiral or sleeve of material to support the prosthesis. The radial supporting material may also be formed integrally into the wall of the prosthesis itself. A preferred synthetic polymer for support of the vascular prosthesis is a polypropylene onofilament.
As used herein, the inner surface of the graft is the surface that is in contact with the flow of blood, whereas the outer surface of the graft is the surface not in contact with the flow of blood and is in contact with other body tissues. In the case of a tubular shaped graft the inner surface is the surface in the lumen of the graft that will be in contact with the flow of blood, and the outer surface is the opposite surface on the outside of the graft that will be in contact with other body tissues when implanted into an animal. In the case of a patch graft, the inner surface is the surface in contact with the flow of blood and the outer surface is the surface in contact with other body tissues. The prostheses are coated with a layer or coating of a material capable of reducing the porosity of the prosthesis to blood or other body fluids. Vascular prostheses are typically permeable to blood and other body fluids, especially in applications where the pressure of the blood within the prosthesis is high, and blood or other fluid leaks through the prosthesis into surrounding tissues. Thus the material capable of reducing porosity of the vascular prosthesis acts as a barrier to the seeping of blood or other fluid through the walls of the prosthesis into surrounding tissue and renders them impermeable or substantially impermeable to the blood or other body tissue. The material capable of reducing the porosity of
the prosthesis may be selected from biodegradable and non- biodegradable materials. A preferred biodegradable material is collagen. Suitable non-biodegradable materials include silicon based elastomeric polymers such as Silastic® materials, and polyurethane. The material capable of reducing the porosity is applied to the inner or outer surface or both of the prosthesis such that a layer of material is formed that is effective to obviate the need for pre-clotting the prosthesis before it is inserted into an animal, i.e. the thickness of the layer formed renders the prosthesis impermeable or substantially impermeable to blood or other body fluid. The thickness of the layer of material capable of reducing porosity of the vascular prosthesis is preferably from about 0.05mm to about 0.1mm in thickness; more preferably from about 0.06 to about 0.09mm in thickness; most preferably from about 0.06 to about 0.08mm in thickness.
When collagen is employed as the material capable of reducing porosity of the vascular prosthesis, the collagen may be applied such that it impregnated intimately into the interstitial spaces of the fabric of the base material. Alternatively, the collagen may be formed into a thin membrane or film adhered to the surface of the base material and not extending into the interstitial spaces of the base material. The porosity reducing coating comprising a biodegradable material may be adhered to the outer surface of the base material, the inner surface of the base material, or both the inner and outer surfaces. The biodegradable material may also be applied to the inner surface of the base material, or on top of an underlayer of compounded heparin. In embodiments of the invention having the biodegradable material on both the inner and outer surfaces of the base material, the layer of biodegradable material on the interior of the prosthesis is preferably thinner than the layer on the outer surface. The layer on the inner surface of the base material can be thinner than the layer on the outer surface since the blood pressure
forces the inner layer against the base material of the prosthesis. The layer on the outer surface is prevented from separating from the base material only due to adhesive bonds. For embodiments of the invention where the porosity reducing coating is a non-bio-degradable material, the porosity reducing coating is applied only to the outer surface of the base material and is preferably applied to the base material before the heparin coating is applied. In preferred embodiments of the invention, collagen is employed as the biodegradable material capable of reducing porosity of the vascular graft. The collagen is selected to be compatible with the species of animal into which the prosthesis will be inserted. For use in humans, bovine collagen is preferred since it is widely available and causes few adverse reactions. A preferred type of bovine collagen is derived from the achilles tendon. Collagen is preferably obtained in the form of compressed collagen fiber sheets made from highly purified, insoluble, type 1, bovine achilles tendon collagen fiber, which may be obtained commercially from suppliers such as Bioplex, Vaals, Holland. The collagen in the sheet form is not cross-linked and is similar to that used as a hemostat sponge. The sheets of collagen are chopped into small pieces and made into an aqueous fine dispersion or slurry containing from about 5 grams per liter to about 12 grams of collagen per liter of dispersion. More preferably, collagen is present in the aqueous dispersion in the amount of about 10 grams per liter ± 10%. A wetting agent is added to the dispersion in an amount effective to wet the collagen. A suitable wetting agent is polyoxyethylene- sorbitan monolaurate (Tween 20 ®, Fisher Scientific Corp, Springfield, NH) which is added in amounts of about twelve grams per liter of dispersion. A plasticizer is also added to the dispersion. A suitable plasticizer is glycerol (Fisher Scientific Corp., Springfield, NH which is added in amounts of about ten grams per liter of dispersion. This process results in a gel like slurry.
The collagen may be applied to the base material such that it is intimately impregnated into the interstitial spaces of the base material by dipping the prosthesis into an aqueous dispersion of collagen and subsequently cross-linking the collagen with a cross- linking agent such as glutaraldehyde.
Alternatively, when the collagen is applied as a thin membrane or film adhered to the surface of the base material and not extending into the interstitial spaces of the base material, or when it is applied over a layer of compounded heparin as a thin membrane or film, an aqueous dispersion of collagen is cross-linked prior to application to the prosthesis. The collagen in the aqueous dispersion is cross-linked by adding a cross-linking agent such as glutaraldehyde and mixing for a length of time effective to cross-link the collagen but still provide a pliable aqueous dispersion that can be used for coating the vascular prosthesis. When glutaraldehyde is used as the cross- linking agent, the aqueous dispersion is stirred for about 20 hours with the glutaraldehyde (about 0.6 grams per liter of dispersion) and the cross-linking process can be terminated by the addition of glycine (about 1.0 grams per liter of dispersion) .
When layers of collagen are applied to both the inner and outer surfaces or layers of compounded heparin, the inner layer of collagen is preferably substantially thinner than the outer layer. Differential thickness may be achieved by dipping the prosthesis one or more times in the aqueous dispersion of collagen to coat both the inner and outer surfaces or layers of compounded heparin and form a layer of collagen of a desired thickness, sewing shut the ends of the prosthesis, and redipping the closed-end prosthesis into collagen for further applications to form a thicker layer of collagen of desired thickness on the outer surface or layer of compounded heparin.
Compounded heparin is applied to the base material either over or under a layer of biodegradable
material capable of reducing the porosity of the vascular graft. When a non-biodegradable material is used, the layer of compounded heparin is applied after or on top of the layer of non-biodegradable material. Compounded heparin as used in the present invention comprises heparin and a cationic surfactant. The heparin is preferably ionically bound to the cationic surfactant. Suitable cationic surfactants include tridodecylmethylammonium chloride (TDMAC) heparin and benzalkonium chloride. The coating of compounded heparin is ionically bound to either the base material or the layer of material capable of reducing the porosity of the prosthesis, depending on the embodiment of the invention. The compounded heparin penetrates into the interstices of the base material and coats the individual fibers of knitted or woven base materials and coats the pores of cast base materials. Thus, as referred to herein a coating of heparin on the inner or outer surface of the base material refers to compounded heparin deposited on the individual fibers of knitted or woven base materials or in the pores of case base materials in amounts sufficient to coat the individual fibers or pores on the surface and in the interior of the base material, at least those fibers or pores adjacent to the surface, but not in amounts sufficient to form a film or layer on the surface of the base material. The compounded heparin is not soluble in either water or blood plasma, so that it stays bonded to the inner surface of the base material, also referred to as the luminal wall. Compounded heparin is applied to the prosthesis in amounts sufficient to serve as an anti-coagulant, however, the amount preferably should not be sufficient to promote platelet clots and/or leukocyte reactions. Effective concentrations of compounded heparin range from about 2.5 to about 15 grams per square meter, which provides approximately 15 to 100 USP units of heparin per square centimeter of prosthesis surface. More preferably the compounded heparin is applied at a concentration of about 7
grams per square meter, providing 45 USP units per square centimeter. Compounded heparin can be prepared by ionically bonding heparin to a cationic surfactant using methods known in the art, or it can be obtained commercially through suppliers such as CIA Labs, St. Joseph, Missouri.
Compounded heparin is applied to the vascular prosthesis by dipping the prosthesis into a solution containing compounded heparin for about 30 to about 60 seconds and then air drying the prosthesis. The solvent used for the solution will vary depending on the cationic surfactant used. For example, when the compounded heparin comprises TDMAC and heparin, the solvent is a mixture of 50% toluene and 50% petroleum ether. Where the compounded heparin comprises benzalkonium chloride and heparin, the solvent may be one of a number of different types known in the art, including ethylene chlor:' ::'ε or ethyl alcohol. The compounded heparin solution may"foe made in a variety of concentrations from about 0.5% to about 6% weight per volume. Since the amount of compounded heparin that will adhere to the base material or material capable of reducing porosity of the vascular prosthesis is proportional to the concentration of compounded heparin in the solution, the amount of compounded heparin may be controlled by solution strength, i.e. the greater the amount of compounded heparin in the solution, the greater the amount of compounded heparin applied to the surface of the base material or the material capable of reducing the porosity of the vascular prosthesis. The evaporation of the solvent leaves the solute (i.e. compounded heparin) adhered to the prosthesis. Thus, the present invention provides vascular prostheses free of any substance that counteracts an anti¬ coagulant and comprising a base material wherein the outer surface has a layer of a material capable of reducing the porosity of the prosthesis to blood or body fluid and a layer of compounded heparin bound thereon, and the inner surface has a layer of compounded heparin bound thereon.
In one of the embodiments of the present invention, the layer of material capable of reducing the porosity of the prosthesis is bound to the outer surface of the vascular prosthesis and the layer of compounded heparin is bound to the layer of material capable of reducing the porosity of the vascular prosthesis. In another embodiment, the layer of compounded heparin is bound to the outer surface of the vascular graft and the layer of material capable of reducing the porosity of said vascular prosthesis is bound to the layer of compounded heparin. In a further embodiment of the invention, the inner surface of the prosthesis has a layer of compounded heparin and a layer of a biodegradable material capable of reducing porosity of the vascular prosthesis. A vascular prosthesis constructed and arranged in accordance with the present invention is shown in Fig. 1. Figure la shows a schematic longitudinal cross-sectional view of a vascular prosthesis 10 of the invention. Figure lb shows a schematic cross-sectional view of the same prosthesis 10. The prosthesis in Figures la and lb has a tubular shape and an inner lumen 20 extending through the length of the prosthesis. The inner surface 16 of the prosthesis 10 is in contact with the flow of blood when the prosthesis is implanted into an animal. The outer surface 14 of the prosthesis 10 has a collagen layer 18 bound thereon. The collagen layer is on the outer surface 14 and does not extend into the walls 12 of the prosthesis. In Figure la the prosthesis 10 is shown with crimps 22 that strengthen the walls 12 of the prosthesis 10. A coating of compounded heparin 24 is bound to the inner surface 16 of the prosthesis 10 such that it coats the individual fibers of the prosthesis at the inner surface 16 and in the walls 12 of the prosthesis. A coating of compounded heparin 24 is also bound to the outer surface 14 of the prosthesis 10 such that it coats the individual fibers of the prosthesis at the outer surface of the prosthesis and in the walls 12 -of the prosthesis.
In a preferred embodiment of the invention a Dacron® polyester fabric prosthesis is coated on its inner and outer surfaces with compounded heparin. Then a layer of cross-linked collagen is applied to the outer layer of compounded heparin, or both the inner and outer layers of compounded heparin so that the collagen forms a thin membrane or film. In the case of the prosthesis with inner and outer collagen layers, the inner layer is preferably substantially thinner than the outer layer. The collagen layer on the inner surface or inner compounded heparin layer is absorbed first, and the blood is allowed to permeate slowly into the interstices of the fabric of the base material. The outer layer of collagen prevents leakage of blood or other fluid from the prosthesis into surrounding tissue. The Dacron® fiber surface is mildly thrombogenic, which means that the blood would normally form a surface clot. The base material of the prosthesis of the present invention, however, has been coated frith compounded heparin so the clotting process is initially prevented and later controlled at a slow rate. This result is a slow tissue build up in the interstices of the fabric of the base material which leads to the formulation of a thin, regular, well-defined and well-adhered inti a on the inner surface of the prosthesis.. Although particular embodiments of the present invention have been described and illustrated herein, it is recognized that modifications and variations may readily occur to those skilled in the art and consequently, it is intended that the claims be intended to cover such modifications and equivalents.
Claims
1. A vascular prosthesis free of any substance that counteracts an anti-coagulant comprising a base material, said base material having inner and outer surfaces, wherein said outer surface has bound thereon a coating of a compounded heparin and a layer of a material capable of reducing the porosity of said prosthesis to blood or body fluid, and said inner surface has a coating of compounded heparin bound thereon, said compounded heparin comprising heparin and a cationic surfactant.
2. The vascular prosthesis of claim 1 wherein with respect to the outer surface of said vascular prosthesis said layer of material capable of reducing the porosity of said prosthesis is bound to the outer surface of said vascular prosthesis and said coating of compounded heparin is bound on said layer of material capable of reducing the porosity of said vascular prosthesis.
3. The vascular prosthesis of claim 1 wherein with respect to the outer surface of said vascular prosthesis said coating of compounded heparin is bound to the outer surface of said vascular graft and said layer of material capable of reducing the porosity of said vascular prosthesis is bound on said coating of compounded heparin.
4. The vascular prosthesis of claim 1 wherein said material capable of reducing the porosity of said vascular ptrosthesis is a biodegradable material.
5. The vascular prosthesis of claim 4 wherein said biodegradable material is collagen.
6. The vascular graft of claim 1 wherein said material capable of reducing the porosity of said vascular graft is a non-biodegradable material.
7. The vascular graft of claim 6 wherein said non-biodegradable material is a silicon-based polymer.
8. The vascular prosthesis of claim 1 wherein said base material is a bio-compatible polymeric material.
9. The vascular prosthesis of claim 8 where said bio-compatible polymeric material is polyethylene terephthalate.
10. The vascular prosthesis of claim 9 wherein said polyethylene terephthalate is woven.
11. The vascular prosthesis of claim 9 wherein said polyethylene terephthalate is knitted.
12. The vascular prosthesis of claim 1 wherein said vascular prosthesis has a tubular shape.
13. The vascular prosthesis of claim 1 wherein said vascular prosthesis has a bifurcated tubular shape.
14. The vascular prosthesis of claim 1 wherein said vascular prosthesis has a planar shape.
15. The vascular prosthesis of claim 14 wherein said vascular prosthesis is a narrow strip with selvedged edges.
16. The vascular prosthesis of claim 12 wherein said tubular shape is radially supported by a synthetic polymer.
17. The vascular prosthesis of claim 13 wherein said bifurcated tubular shape is radially supported by a synthetic polymer.
18. The vascular prosthesis of claim 16 wherein said synthetic polymer is a polypropylene monofilament, and said polypropylene monofilament is spirally wound along the length of said vascular prosthesis.
5 19. The vascular prosthesis of claim 17 wherein said synthetic polymer is a polypropylene monofilament, and said polypropylene filament is spirally wound along the length of said vascular prosthesis.
20. The vascular prosthesis of claim 1 wherein 0 said compounded heparin comprises heparin ionically bonded with tridodecylmethylammonium chloride.
21. The vascular prosthesis of claim 1 wherein said compounded heparin comprises heparin ionically bonded with benzalkonium chloride.
5 22. A method of forming a vascular prosthesis comprising a base material having inner and outer surfaces, comprising the steps of: applying compounded heparin to the inner surface of said base material, said compounded heparin comprising O heparin and a cationic surfactant, to form a coating of said compounded heparin on said inner surface, and applying to the outer surface of said base material a coating of said compounded heparin and a layer of a material capable of reducing the porosity of said 5 vascular prosthesis.
23. The method of claim 22 wherein said coating of compounded heparin is formed on both of said inner and said outer surfaces of said base material and thereafter said layer of material capable of reducing porosity of said 0 vascular prosthesis is formed on said coating of compounded heparin on said outer surface of said base material.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US87934592A | 1992-05-07 | 1992-05-07 | |
US07/879,345 | 1992-05-07 | ||
US08/047,799 US5383927A (en) | 1992-05-07 | 1993-04-15 | Non-thromogenic vascular prosthesis |
US08/047,799 | 1993-04-15 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1993021860A1 true WO1993021860A1 (en) | 1993-11-11 |
Family
ID=26725441
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1993/004213 WO1993021860A1 (en) | 1992-05-07 | 1993-05-05 | Non-thrombogenic vascular prosthesis |
Country Status (2)
Country | Link |
---|---|
US (1) | US5383927A (en) |
WO (1) | WO1993021860A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2298577A (en) * | 1995-03-09 | 1996-09-11 | Univ Bristol | Stented vein segment for use in bypass grafting |
US5693085A (en) * | 1994-04-29 | 1997-12-02 | Scimed Life Systems, Inc. | Stent with collagen |
EP0878173A1 (en) * | 1997-05-14 | 1998-11-18 | Jomed Implantate GmbH | Stent-graft |
WO1999038547A2 (en) * | 1998-01-30 | 1999-08-05 | Edwards Lifesciences Corporation | Enhanced biocompatibility coatings for medical implants |
WO2021257674A1 (en) * | 2020-06-16 | 2021-12-23 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | A self-cleaning porous layer to minimize thrombus formation on blood contacting devices |
Families Citing this family (106)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5584875A (en) * | 1991-12-20 | 1996-12-17 | C. R. Bard, Inc. | Method for making vascular grafts |
US6039749A (en) | 1994-02-10 | 2000-03-21 | Endovascular Systems, Inc. | Method and apparatus for deploying non-circular stents and graftstent complexes |
CA2147547C (en) * | 1994-08-02 | 2006-12-19 | Peter J. Schmitt | Thinly woven flexible graft |
US5527324A (en) * | 1994-09-07 | 1996-06-18 | Krantz; Kermit E. | Surgical stent |
US5707385A (en) * | 1994-11-16 | 1998-01-13 | Advanced Cardiovascular Systems, Inc. | Drug loaded elastic membrane and method for delivery |
US5628786A (en) * | 1995-05-12 | 1997-05-13 | Impra, Inc. | Radially expandable vascular graft with resistance to longitudinal compression and method of making same |
CA2178541C (en) * | 1995-06-07 | 2009-11-24 | Neal E. Fearnot | Implantable medical device |
US6774278B1 (en) * | 1995-06-07 | 2004-08-10 | Cook Incorporated | Coated implantable medical device |
US7611533B2 (en) * | 1995-06-07 | 2009-11-03 | Cook Incorporated | Coated implantable medical device |
US20070203520A1 (en) * | 1995-06-07 | 2007-08-30 | Dennis Griffin | Endovascular filter |
US7550005B2 (en) | 1995-06-07 | 2009-06-23 | Cook Incorporated | Coated implantable medical device |
US7867275B2 (en) * | 1995-06-07 | 2011-01-11 | Cook Incorporated | Coated implantable medical device method |
US7846202B2 (en) | 1995-06-07 | 2010-12-07 | Cook Incorporated | Coated implantable medical device |
US5609629A (en) * | 1995-06-07 | 1997-03-11 | Med Institute, Inc. | Coated implantable medical device |
US7896914B2 (en) * | 1995-06-07 | 2011-03-01 | Cook Incorporated | Coated implantable medical device |
WO1997009006A1 (en) | 1995-09-01 | 1997-03-13 | Emory University | Endovascular support device and method of use |
US20060025726A1 (en) * | 1996-06-04 | 2006-02-02 | Vance Products Incorporated, D/B/A Cook Urological Incorporated | Implantable medical device with pharmacologically active layer |
US20060052757A1 (en) * | 1996-06-04 | 2006-03-09 | Vance Products Incorporated, D/B/A Cook Urological Incorporated | Implantable medical device with analgesic or anesthetic |
US5645587A (en) * | 1996-06-05 | 1997-07-08 | Chanda; Jyotirmay | Prevention of calcification and degeneration of biological tissue grafts for implantation in humans |
US5851229A (en) * | 1996-09-13 | 1998-12-22 | Meadox Medicals, Inc. | Bioresorbable sealants for porous vascular grafts |
US6530951B1 (en) | 1996-10-24 | 2003-03-11 | Cook Incorporated | Silver implantable medical device |
ZA9710342B (en) * | 1996-11-25 | 1998-06-10 | Alza Corp | Directional drug delivery stent and method of use. |
US6776792B1 (en) * | 1997-04-24 | 2004-08-17 | Advanced Cardiovascular Systems Inc. | Coated endovascular stent |
US5879697A (en) * | 1997-04-30 | 1999-03-09 | Schneider Usa Inc | Drug-releasing coatings for medical devices |
US6206917B1 (en) * | 1997-05-02 | 2001-03-27 | St. Jude Medical, Inc. | Differential treatment of prosthetic devices |
US6056993A (en) * | 1997-05-30 | 2000-05-02 | Schneider (Usa) Inc. | Porous protheses and methods for making the same wherein the protheses are formed by spraying water soluble and water insoluble fibers onto a rotating mandrel |
US6070589A (en) | 1997-08-01 | 2000-06-06 | Teramed, Inc. | Methods for deploying bypass graft stents |
US6656215B1 (en) | 2000-11-16 | 2003-12-02 | Cordis Corporation | Stent graft having an improved means for attaching a stent to a graft |
US6290731B1 (en) | 1998-03-30 | 2001-09-18 | Cordis Corporation | Aortic graft having a precursor gasket for repairing an abdominal aortic aneurysm |
US20020099438A1 (en) | 1998-04-15 | 2002-07-25 | Furst Joseph G. | Irradiated stent coating |
US20030040790A1 (en) * | 1998-04-15 | 2003-02-27 | Furst Joseph G. | Stent coating |
US7967855B2 (en) * | 1998-07-27 | 2011-06-28 | Icon Interventional Systems, Inc. | Coated medical device |
US8070796B2 (en) * | 1998-07-27 | 2011-12-06 | Icon Interventional Systems, Inc. | Thrombosis inhibiting graft |
WO2000010622A1 (en) | 1998-08-20 | 2000-03-02 | Cook Incorporated | Coated implantable medical device |
US6596699B2 (en) | 1998-09-22 | 2003-07-22 | Biosurface Engineering Technologies, Inc. | Nucleic acid coating compositions and methods |
US6342591B1 (en) | 1998-09-22 | 2002-01-29 | Biosurface Engineering Technologies, Inc. | Amphipathic coating for modulating cellular adhesion composition and methods |
US6475234B1 (en) * | 1998-10-26 | 2002-11-05 | Medinol, Ltd. | Balloon expandable covered stents |
US6464723B1 (en) | 1999-04-22 | 2002-10-15 | Advanced Cardiovascular Systems, Inc. | Radiopaque stents |
US6790228B2 (en) * | 1999-12-23 | 2004-09-14 | Advanced Cardiovascular Systems, Inc. | Coating for implantable devices and a method of forming the same |
US6585757B1 (en) | 1999-09-15 | 2003-07-01 | Advanced Cardiovascular Systems, Inc. | Endovascular stent with radiopaque spine |
US6602287B1 (en) | 1999-12-08 | 2003-08-05 | Advanced Cardiovascular Systems, Inc. | Stent with anti-thrombogenic coating |
US6251136B1 (en) | 1999-12-08 | 2001-06-26 | Advanced Cardiovascular Systems, Inc. | Method of layering a three-coated stent using pharmacological and polymeric agents |
US6296661B1 (en) | 2000-02-01 | 2001-10-02 | Luis A. Davila | Self-expanding stent-graft |
US6245100B1 (en) | 2000-02-01 | 2001-06-12 | Cordis Corporation | Method for making a self-expanding stent-graft |
US8252044B1 (en) | 2000-11-17 | 2012-08-28 | Advanced Bio Prosthestic Surfaces, Ltd. | Device for in vivo delivery of bioactive agents and method of manufacture thereof |
US6652579B1 (en) | 2000-06-22 | 2003-11-25 | Advanced Cardiovascular Systems, Inc. | Radiopaque stent |
US6783793B1 (en) * | 2000-10-26 | 2004-08-31 | Advanced Cardiovascular Systems, Inc. | Selective coating of medical devices |
US7807210B1 (en) | 2000-10-31 | 2010-10-05 | Advanced Cardiovascular Systems, Inc. | Hemocompatible polymers on hydrophobic porous polymers |
US6833153B1 (en) | 2000-10-31 | 2004-12-21 | Advanced Cardiovascular Systems, Inc. | Hemocompatible coatings on hydrophobic porous polymers |
US7314483B2 (en) * | 2000-11-16 | 2008-01-01 | Cordis Corp. | Stent graft with branch leg |
US9107605B2 (en) * | 2000-11-17 | 2015-08-18 | Advanced Bio Prosthetic Surfaces, Ltd., A Wholly Owned Subsidiary Of Palmaz Scientific, Inc. | Device for in vivo delivery of bioactive agents and method of manufacture thereof |
US6641607B1 (en) | 2000-12-29 | 2003-11-04 | Advanced Cardiovascular Systems, Inc. | Double tube stent |
US7238199B2 (en) * | 2001-03-06 | 2007-07-03 | The Board Of Regents Of The University Of Texas System | Method and apparatus for stent deployment with enhanced delivery of bioactive agents |
DE10115740A1 (en) | 2001-03-26 | 2002-10-02 | Ulrich Speck | Preparation for restenosis prophylaxis |
US7201940B1 (en) * | 2001-06-12 | 2007-04-10 | Advanced Cardiovascular Systems, Inc. | Method and apparatus for thermal spray processing of medical devices |
US6565659B1 (en) * | 2001-06-28 | 2003-05-20 | Advanced Cardiovascular Systems, Inc. | Stent mounting assembly and a method of using the same to coat a stent |
US6913626B2 (en) * | 2001-08-14 | 2005-07-05 | Mcghan Jim J. | Medical implant having bioabsorbable textured surface |
US20030077310A1 (en) * | 2001-10-22 | 2003-04-24 | Chandrashekhar Pathak | Stent coatings containing HMG-CoA reductase inhibitors |
US8740973B2 (en) * | 2001-10-26 | 2014-06-03 | Icon Medical Corp. | Polymer biodegradable medical device |
US7147661B2 (en) | 2001-12-20 | 2006-12-12 | Boston Scientific Santa Rosa Corp. | Radially expandable stent |
US8308797B2 (en) | 2002-01-04 | 2012-11-13 | Colibri Heart Valve, LLC | Percutaneously implantable replacement heart valve device and method of making same |
US7326237B2 (en) * | 2002-01-08 | 2008-02-05 | Cordis Corporation | Supra-renal anchoring prosthesis |
AU2003256540B2 (en) | 2002-07-12 | 2008-12-11 | Cook Medical Technologies Llc | Coated medical device |
US8016881B2 (en) * | 2002-07-31 | 2011-09-13 | Icon Interventional Systems, Inc. | Sutures and surgical staples for anastamoses, wound closures, and surgical closures |
DE10244847A1 (en) | 2002-09-20 | 2004-04-01 | Ulrich Prof. Dr. Speck | Medical device for drug delivery |
US6929663B2 (en) * | 2003-03-26 | 2005-08-16 | Boston Scientific Scimed, Inc. | Longitudinally expanding medical device |
CN101005812A (en) | 2003-05-07 | 2007-07-25 | 先进生物假体表面有限公司 | Metallic implantable grafts and method of making same |
US7198675B2 (en) * | 2003-09-30 | 2007-04-03 | Advanced Cardiovascular Systems | Stent mandrel fixture and method for selectively coating surfaces of a stent |
US7056337B2 (en) * | 2003-10-21 | 2006-06-06 | Cook Incorporated | Natural tissue stent |
US7211108B2 (en) * | 2004-01-23 | 2007-05-01 | Icon Medical Corp. | Vascular grafts with amphiphilic block copolymer coatings |
US20050171596A1 (en) * | 2004-02-03 | 2005-08-04 | Furst Joseph G. | Stents with amphiphilic copolymer coatings |
US20050288481A1 (en) * | 2004-04-30 | 2005-12-29 | Desnoyer Jessica R | Design of poly(ester amides) for the control of agent-release from polymeric compositions |
US8323333B2 (en) * | 2005-03-03 | 2012-12-04 | Icon Medical Corp. | Fragile structure protective coating |
US9107899B2 (en) | 2005-03-03 | 2015-08-18 | Icon Medical Corporation | Metal alloys for medical devices |
US20060264914A1 (en) * | 2005-03-03 | 2006-11-23 | Icon Medical Corp. | Metal alloys for medical devices |
WO2006110197A2 (en) * | 2005-03-03 | 2006-10-19 | Icon Medical Corp. | Polymer biodegradable medical device |
US7540995B2 (en) | 2005-03-03 | 2009-06-02 | Icon Medical Corp. | Process for forming an improved metal alloy stent |
JP5335244B2 (en) * | 2005-03-03 | 2013-11-06 | アイコン メディカル コーポレーション | Medical member using improved metal alloy |
US20060200048A1 (en) * | 2005-03-03 | 2006-09-07 | Icon Medical Corp. | Removable sheath for device protection |
US20060201601A1 (en) * | 2005-03-03 | 2006-09-14 | Icon Interventional Systems, Inc. | Flexible markers |
US20060216431A1 (en) * | 2005-03-28 | 2006-09-28 | Kerrigan Cameron K | Electrostatic abluminal coating of a stent crimped on a balloon catheter |
US7867547B2 (en) | 2005-12-19 | 2011-01-11 | Advanced Cardiovascular Systems, Inc. | Selectively coating luminal surfaces of stents |
US20070148251A1 (en) * | 2005-12-22 | 2007-06-28 | Hossainy Syed F A | Nanoparticle releasing medical devices |
US8069814B2 (en) | 2006-05-04 | 2011-12-06 | Advanced Cardiovascular Systems, Inc. | Stent support devices |
US8603530B2 (en) | 2006-06-14 | 2013-12-10 | Abbott Cardiovascular Systems Inc. | Nanoshell therapy |
US8048448B2 (en) * | 2006-06-15 | 2011-11-01 | Abbott Cardiovascular Systems Inc. | Nanoshells for drug delivery |
US8017237B2 (en) * | 2006-06-23 | 2011-09-13 | Abbott Cardiovascular Systems, Inc. | Nanoshells on polymers |
WO2008008291A2 (en) * | 2006-07-13 | 2008-01-17 | Icon Medical Corp. | Stent |
US8435283B2 (en) * | 2007-06-13 | 2013-05-07 | Boston Scientific Scimed, Inc. | Anti-migration features and geometry for a shape memory polymer stent |
US8048441B2 (en) | 2007-06-25 | 2011-11-01 | Abbott Cardiovascular Systems, Inc. | Nanobead releasing medical devices |
WO2010048052A1 (en) | 2008-10-22 | 2010-04-29 | Boston Scientific Scimed, Inc. | Shape memory tubular stent with grooves |
WO2011109450A2 (en) | 2010-03-01 | 2011-09-09 | Colibri Heart Valve Llc | Percutaneously deliverable heart valve and methods associated therewith |
US8398916B2 (en) | 2010-03-04 | 2013-03-19 | Icon Medical Corp. | Method for forming a tubular medical device |
CA2806544C (en) | 2010-06-28 | 2016-08-23 | Colibri Heart Valve Llc | Method and apparatus for the endoluminal delivery of intravascular devices |
SG10201601962WA (en) | 2010-12-14 | 2016-04-28 | Colibri Heart Valve Llc | Percutaneously deliverable heart valve including folded membrane cusps with integral leaflets |
US20140228925A1 (en) * | 2011-10-27 | 2014-08-14 | St. Jude Medical Ab | Implantable medical lead with blood seal |
CN106535826A (en) | 2014-06-24 | 2017-03-22 | 怡康医疗股份有限公司 | Improved metal alloys for medical devices |
JP6636511B2 (en) | 2014-10-09 | 2020-01-29 | ボストン サイエンティフィック サイムド,インコーポレイテッドBoston Scientific Scimed,Inc. | Pancreatic stent with drainage features |
US11766506B2 (en) | 2016-03-04 | 2023-09-26 | Mirus Llc | Stent device for spinal fusion |
WO2019045766A1 (en) | 2017-08-17 | 2019-03-07 | Incubar Llc | Prosthetic vascular valve and methods associated therewith |
WO2019051476A1 (en) | 2017-09-11 | 2019-03-14 | Incubar, LLC | Conduit vascular implant sealing device for reducing endoleak |
US11027046B2 (en) | 2017-10-31 | 2021-06-08 | Hothouse Medical Limited | Textile products having selectively applied sealant or coating and method of manufacture |
GB201717885D0 (en) | 2017-10-31 | 2017-12-13 | Hothouse Medical Ltd | Prothesis and method of manufacture |
KR102582640B1 (en) | 2019-01-07 | 2023-09-25 | 보스톤 싸이엔티픽 싸이메드 인코포레이티드 | Stent with anti-migration features |
US11918496B2 (en) | 2020-12-02 | 2024-03-05 | Boston Scientific Scimed, Inc. | Stent with improved deployment characteristics |
CN114159624B (en) * | 2021-11-24 | 2022-09-02 | 山东黄河三角洲纺织科技研究院有限公司 | Coating method of woven artificial blood vessel and artificial blood vessel |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3425418A (en) * | 1963-06-15 | 1969-02-04 | Spofa Vereinigte Pharma Werke | Artificial blood vessels and method of preparing the same |
US4321711A (en) * | 1978-10-18 | 1982-03-30 | Sumitomo Electric Industries, Ltd. | Vascular prosthesis |
WO1988000813A1 (en) * | 1986-08-05 | 1988-02-11 | St. Jude Medical, Inc. | Braided polyester vascular prosthesis and method |
US4822361A (en) * | 1985-12-24 | 1989-04-18 | Sumitomo Electric Industries, Ltd. | Tubular prosthesis having a composite structure |
US4879135A (en) * | 1984-07-23 | 1989-11-07 | University Of Medicine And Dentistry Of New Jersey | Drug bonded prosthesis and process for producing same |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4441215A (en) * | 1980-11-17 | 1984-04-10 | Kaster Robert L | Vascular graft |
JPS58180162A (en) * | 1982-04-19 | 1983-10-21 | 株式会社高研 | Anti-thrombosis medical material |
US5108424A (en) * | 1984-01-30 | 1992-04-28 | Meadox Medicals, Inc. | Collagen-impregnated dacron graft |
JPS6229532A (en) * | 1985-07-31 | 1987-02-07 | Koken:Kk | Antithrombogenetic medical material and production thereof |
JPS6238172A (en) * | 1985-08-12 | 1987-02-19 | 株式会社 高研 | Production of anti-thrombotic medical material |
-
1993
- 1993-04-15 US US08/047,799 patent/US5383927A/en not_active Expired - Lifetime
- 1993-05-05 WO PCT/US1993/004213 patent/WO1993021860A1/en active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3425418A (en) * | 1963-06-15 | 1969-02-04 | Spofa Vereinigte Pharma Werke | Artificial blood vessels and method of preparing the same |
US4321711A (en) * | 1978-10-18 | 1982-03-30 | Sumitomo Electric Industries, Ltd. | Vascular prosthesis |
US4879135A (en) * | 1984-07-23 | 1989-11-07 | University Of Medicine And Dentistry Of New Jersey | Drug bonded prosthesis and process for producing same |
US4822361A (en) * | 1985-12-24 | 1989-04-18 | Sumitomo Electric Industries, Ltd. | Tubular prosthesis having a composite structure |
WO1988000813A1 (en) * | 1986-08-05 | 1988-02-11 | St. Jude Medical, Inc. | Braided polyester vascular prosthesis and method |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5693085A (en) * | 1994-04-29 | 1997-12-02 | Scimed Life Systems, Inc. | Stent with collagen |
GB2298577A (en) * | 1995-03-09 | 1996-09-11 | Univ Bristol | Stented vein segment for use in bypass grafting |
GB2298577B (en) * | 1995-03-09 | 1999-02-17 | Univ Bristol | Arteriovenous bypass grafting |
US6071306A (en) * | 1995-03-09 | 2000-06-06 | University Of Bristol | Externally stented vein segment and its use in an arteriovenous bypass grafting procedure |
EP0878173A1 (en) * | 1997-05-14 | 1998-11-18 | Jomed Implantate GmbH | Stent-graft |
WO1999038547A2 (en) * | 1998-01-30 | 1999-08-05 | Edwards Lifesciences Corporation | Enhanced biocompatibility coatings for medical implants |
WO1999038547A3 (en) * | 1998-01-30 | 1999-09-23 | Baxter Int | Enhanced biocompatibility coatings for medical implants |
WO2021257674A1 (en) * | 2020-06-16 | 2021-12-23 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | A self-cleaning porous layer to minimize thrombus formation on blood contacting devices |
Also Published As
Publication number | Publication date |
---|---|
US5383927A (en) | 1995-01-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5383927A (en) | Non-thromogenic vascular prosthesis | |
US5632776A (en) | Implantation materials | |
JP3784798B2 (en) | Implantable tubular prosthesis made of polytetrafluoroethylene | |
US6440166B1 (en) | Multilayer and multifunction vascular graft | |
EP0118458B1 (en) | Biocompatible, antithrombogenic materials suitable for reconstructive surgery | |
US5578073A (en) | Thromboresistant surface treatment for biomaterials | |
EP0941740B1 (en) | Attachment of biomolecules to surfaces of medical devices | |
EP1471952B1 (en) | Coated vascular prosthesis and methods of manufacture and use. | |
US5980551A (en) | Composition and method for making a biodegradable drug delivery stent | |
US5037377A (en) | Means for improving biocompatibility of implants, particularly of vascular grafts | |
CA1292597C (en) | Tubular prothesis having a composite structure | |
EP1781210B1 (en) | Composite vascular graft including bioactive agent coating and biodegradable sheath | |
US20060008497A1 (en) | Implantable apparatus having improved biocompatibility and process of making the same | |
Guidoin et al. | Albumin coating of a knitted polyester arterial prosthesis: an alternative to preclotting | |
EP0512122A1 (en) | Implant material | |
EP0662805A1 (en) | Silicone/dacron composite vascular graft | |
WO1998010804A1 (en) | Improved bioresorbable sealants for porous vascular grafts | |
JP2002540854A (en) | Pipe lining | |
JPH0866469A (en) | Tubular graft which is impregnated with heparin-containing collagen sealant | |
EP0466105A2 (en) | Composite biosynthetic graft | |
EP1708764B1 (en) | Blood-tight implantable textile material and method of making | |
EP0781089B1 (en) | Thromboresistant surface treatment for biomaterials | |
EP0246638A2 (en) | Biologically modified synthetic grafts | |
WO1996008149A9 (en) | Thromboresistant surface treatment for biomaterials | |
Sigot‐Luizard et al. | Cytocompatibility of albuminated polyester fabrics |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): JP |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
122 | Ep: pct application non-entry in european phase |