EP1156759A1 - Biodegradable polymeriprotein based coils for intralumenal implants - Google Patents

Biodegradable polymeriprotein based coils for intralumenal implants

Info

Publication number
EP1156759A1
EP1156759A1 EP99951622A EP99951622A EP1156759A1 EP 1156759 A1 EP1156759 A1 EP 1156759A1 EP 99951622 A EP99951622 A EP 99951622A EP 99951622 A EP99951622 A EP 99951622A EP 1156759 A1 EP1156759 A1 EP 1156759A1
Authority
EP
European Patent Office
Prior art keywords
coil
biocompatible
protein
growth factor
providing
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP99951622A
Other languages
German (de)
French (fr)
Other versions
EP1156759A4 (en
Inventor
Yuichi Murayama
Fernando Vinuela
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of California
Original Assignee
University of California
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/US1999/001790 external-priority patent/WO1999044538A1/en
Application filed by University of California filed Critical University of California
Publication of EP1156759A1 publication Critical patent/EP1156759A1/en
Publication of EP1156759A4 publication Critical patent/EP1156759A4/en
Ceased legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022Occluding by internal devices, e.g. balloons or releasable wires
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12131Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
    • A61B17/1214Coils or wires
    • A61B17/1215Coils or wires comprising additional materials, e.g. thrombogenic, having filaments, having fibers, being coated
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/14Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30003Material related properties of the prosthesis or of a coating on the prosthesis
    • A61F2002/3006Properties of materials and coating materials
    • A61F2002/30062(bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30003Material related properties of the prosthesis or of a coating on the prosthesis
    • A61F2002/3006Properties of materials and coating materials
    • A61F2002/3008Properties of materials and coating materials radio-opaque, e.g. radio-opaque markers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2210/00Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0004Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2250/00Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0096Markers and sensors for detecting a position or changes of a position of an implant, e.g. RF sensors, ultrasound markers
    • A61F2250/0098Markers and sensors for detecting a position or changes of a position of an implant, e.g. RF sensors, ultrasound markers radio-opaque, e.g. radio-opaque markers

Definitions

  • the invention relates generally to the field of surgical and endovascular interventional instruments and specially to Intraluminal implants for occlusion of vessels or aneurysms.
  • Brain aneurysms are the commonest cause of nontraumatic subarachnoid hemorrhage (SAH) which is a significant life-threatening disease in adults. Annually in North America, the rupture of saccular aneurysms accounts for 25000 new cases of SAH. Microsurgical clipping of an aneurysm has been considered the gold standard for the treatment of this disease. Recently, intravascular treatment of aneurysms has become an accepted alternative technique. With the availability of microcatheters capable of accessing the intracranial circulation it has become possible to obliterate an aneurysm by filling it with soft platinum detachable coils (Guglielmi Detachable Coils; GDC).
  • GDC Global System for Delivery and detachment of platinum coils within an aneurysm.
  • Recent advances in endovascular techniques have proved valuable in the treatment of cerebral saccular aneurysms.
  • GDCs have contributed especially to improvements in the endovascular management of cerebral aneurysms.
  • the size of an aneurysm neck has an important effect on the anatomic results of aneurysm obliteration. It has been reported that in one study complete obliteration of aneurysms was achieved in 85% of small-necked aneurysms and 15% of wide-necked aneurysms.
  • GDCs Guglielmi detachable coils
  • Occlusion coils are used to occlude a site within a body lumen, such as a blood vessel, brain aneurysm, or vascular malformation.
  • the coils are typically placed at a desired site within the lumen by means of a microcatheter.
  • the coils are normally made of a radioopaque, biocompatible metals such as platinum, gold, or tungsten.
  • the coils occlude the aneurysm by posing a physical barrier to blood flow and by promoting thrombus formation.
  • the formation of the neo-endothelium and mature intra-aneurysmal thrombus is necessary prior to subsequent organization and scar formation that, in turn, yields a permanently occluded aneurysm.
  • metallic coils can be insufficiently thrombogenic to promote the establishment of firm and mature thrombus within the aneurysm. They have difficulty in promoting endothelialization across the wide neck of an aneurysm. Therefore, it is advantageous to tightly pack the aneurysm with coils for complete cure of the aneurysms. This may cause a mass effect on adjacent the brain parenchyma or cranial nerves.
  • Bioabsorbable polymers such as polyglycolic acid and polyglycolic/poly-L-lactic acid copolymers, or bioabsorbable proteins, such as collagen and gelatins, have been used to make Intraluminal implants. These bioabsorbable polymers or proteins are also used to provide a the drug delivery vehicle (such as for continuous local delivery of growth factors). It is necessary to modify biological cellular response in preparation for acceleration of wound healing.
  • Coil thrombogenicity was enhanced previously by increasing the surface area of the coils with fabric strands, such as Dacron, and by placing such coils into a thrombin solution. More recently, some investigators have modified the surfaces of platinum coils by coating them with collagen or polyurethane. This has resulted in some advantages, such as an increase in thrombogenicity of these coils.
  • protein coatings on platinum surfaces are usually weak and may be removed easily during the delivery of the coils. Additionally, weakly coated proteins may be washed off by high-velocity arterial flow and may be a potential source of distal thromboemboli.
  • polyurethane coatings in particular also have the disadvantage of producing unfavorable changes in GDC performance, affecting their softness, thinness, smoothness,
  • GDCs and surrounding thrombus within an aneurysm are continuously exposed to and interact with circulating blood at the neck of the aneurysm.
  • Coil compaction resulting from the force of pulsatile arterial blood flow is one of the reasons for incomplete obliteration of aneurysms. When this occurs, there is a potential risk of aneurysm recanalization and (re)rupture.
  • Re- endothelialization and the promotion of wound healing in the aneurysmal sac and across its neck are necessary for complete aneurysm cure.
  • the invention is an intravascular device that modifies either accelerating or decreasing biological cellular response comprising a separable tip or coil comprised at least in part of at least one biocompatible and absorbable polymer or protein, and a placement device associated with the separable coil adapted to dispose the coil into a selected body lumen.
  • the biocompatible and absorbable polymer or protein promotes an intra-aneurysmal inflammatory response and healing of the aneurysms.
  • This device may carry growth factors, such as a vascular endothelial growth factor, a basic fibroblast growth factor or a mixture of several growth factors or cytokines.
  • the separable tip which also need not be a coil, need not be comprised of a polymer or protein, but may be comprised of any material now known or later devised which is biocompatible, absorbable and which promotes an intra-aneurysmal inflammatory response and promotes healing of the aneurysm.
  • the biocompatible and absorbable polymer is in the illustrated embodiment at least one polymer selected from the group consisting of polyglycolic acid, poly ⁇ glycolic acid/poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate/hydroxyvalerate copolymers, poly-L- lactide, polydioxanone, polycarbonates, and polyanhydrides.
  • the biocompatible and absorbable protein is at least one protein selected from the group consisting of collagen, fibrinogen, fibronectin, vitronectin, laminin, and gelatin.
  • the coil is composed of the biocompatible and absorbable polymer or protein with a radio-opaque material is disposed thereon.
  • the coil is composed of a radio-opaque material, and the biocompatible and absorbable polymer or protein is disposed thereon.
  • the invention is also characterized as a method for forming a thrombus comprising the steps of providing a separable coil comprised at least in part of at least one biocompatible and absorbable polymer or protein and disposing the separable coil into a body lumen including the various combinations and examples described above.
  • the method further of comprises the step of providing the coil with a growth factor, and in particular a vascular endothelial growth factor (VEGF), a basic fibroblast growth factor (bFGF), or other growth factors.
  • a growth factor and in particular a vascular endothelial growth factor (VEGF), a basic fibroblast growth factor (bFGF), or other growth factors.
  • VEGF vascular endothelial growth factor
  • bFGF basic fibroblast growth factor
  • a biodegradable polymer (or protein) coils are used to control thrombosis or accelerate wound healing of the brain aneurysms for which platinum coils sometimes have often proven unsatisfactory.
  • Another aspect of the invention is a method of drug delivery system using biodegradable polymer (or proteins) in the combination with growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or other growth factors which promote long lasting effect of the wound healing
  • growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or other growth factors which promote long lasting effect of the wound healing
  • biodegradable coils are useful for treating giant brain aneurysms to prevent the mass effect on the brain parenchyma or cranial nerves by shrinkage of scaring aneurysm.
  • the implants of the invention may be placed within body lumens, e.g., blood vessels, Fallopian tubes, etc., of any mammalian species, including humans.
  • the implant coils are made of biocompatible and absorbable polymers or proteins.
  • bioabsorbable polymers that have been used in the illustrated embodiment to make Intraluminal implants include but are not limited to polyglycolic acid, poly ⁇ gycolic/poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate /hydroxyvalerate copolymers, poly-L-lactide, polydioxanone, polycarbonates, and polyanhydrides.
  • bioabsorbable proteins that have been used in the illustrated embodiment to make Intraluminal implants include but are not limited to collagen, fibrinogen, fibronectin, vitronectin, laminin and gelatin.
  • the bioabsorbable polymer coils may be coated or mixed with radioopaque materials such as tantalum or platinum.
  • the bioabsorbable polymer or protein itself may be mounted or coated onto coils or wires of metals such as platinum or nitonol.
  • Preferred growth factors for use in the invention are the naturally occurring mammalian angiogenic growth such as VEGF, or b-FGF. Mixtures of such growth factors may also be used if desired.
  • the biodegradable polymer coils of the invention can be placed within the body lumen, vascular system or vessels using procedures well known in the art.
  • the desired site within the vessel is accessed with a catheter.
  • the catheter may be guided to the site by the use of guide wires.
  • the catheter lumen is cleared by removing guide wire.
  • the coils are loaded by means of a pusher wire.
  • the coils may be attached to the distal end of the pusher via a cleavable joint (e.g., a joint that is severable by heat, electrolysis, electrodynamic activation or other means) or a mechanical joint that permits the coil to be detached from the distal end of the pusher wire by mechanical manipulation.
  • the coils may be free and detached from the pusher wire, simply pushed through the catheter and expelled from the distal end of the catheter.

Abstract

An endovascular cellular manipulation and inflammatory response are elicited from implantation in a vascular compartment or any intraluminal location of a separable coil comprised at least in part of at least one biocompatible and absorbable polymer or protein and growth factors. Typically a catheter associated with the separable coil is used to dispose the coil into a selected body lumen. The biocompatible and absorbable polymer or protein is thrombogenic. The coil further is comprised at least in part of a growth factor or more particularly a vascular endothelial growth factor, a basic fibroblast growth factor or other growth factors. The biocompatible and absorbable polymer is in the illustrated embodiment at least one polymer selected from the group consisting of polyglycolic acid, poly∩glycolic acid/poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate/hydroxyvalerate copolymers, poly-L-lactide. Polydioxanone, polycarbonates, and polyanhydrides. The biocompatible and absorbable protein is at least one protein selected from the group consisting of collagen, fibrinogen, fibronectin, vitronectin, laminin, and gelatin. In one embodiment the coil is composed of the biocompatible and absorbable polymer or protein with a radio-opaque material is disposed thereon. Alternatively, the coil is composed of a radio-opaque material, and the biocompatible and absorbable polymer or protein is disposed thereon. This apparatus may be positioned within intracranial aneurysms or any aneurysm in the body as well as within other body cavities.

Description

BIODEGRADABLE POLYMERIPROTEIN BASED COILS FOR INTRALUMENAL IMPLANTS
Background of the Invention
Related Applications
The present application is related to U.S. Provisional Patent Application ser. No. 60/072,653 filed Jan. 27, 1998 and to PCT International Appl.No. PCT/US99/01790 filed Jan. 27, 1999 upon which its priority is based.
1. Field of the Invention
The invention relates generally to the field of surgical and endovascular interventional instruments and specially to Intraluminal implants for occlusion of vessels or aneurysms.
2. Description of the Prior Art
Brain aneurysms are the commonest cause of nontraumatic subarachnoid hemorrhage (SAH) which is a significant life-threatening disease in adults. Annually in North America, the rupture of saccular aneurysms accounts for 25000 new cases of SAH. Microsurgical clipping of an aneurysm has been considered the gold standard for the treatment of this disease. Recently, intravascular treatment of aneurysms has become an accepted alternative technique. With the availability of microcatheters capable of accessing the intracranial circulation it has become possible to obliterate an aneurysm by filling it with soft platinum detachable coils (Guglielmi Detachable Coils; GDC). Use of the GDC system allows controlled delivery and detachment of platinum coils within an aneurysm. Recent advances in endovascular techniques have proved valuable in the treatment of cerebral saccular aneurysms. GDCs have contributed especially to improvements in the endovascular management of cerebral aneurysms. However, the size of an aneurysm neck has an important effect on the anatomic results of aneurysm obliteration. It has been reported that in one study complete obliteration of aneurysms was achieved in 85% of small-necked aneurysms and 15% of wide-necked aneurysms.
Early experience with experimental and clinical use of Guglielmi detachable coils (GDCs) as manufactured by Target Therapeutics, Fremont, California, points to their effectiveness in the occlusion of endovascular small- necked intracranial saccular aneurysms.
However, the anatomical results of obliteration of either wide-necked (neck size > 4 mm) or giant aneurysms using GDCs are generally unsatisfactory.
The reasons for these incomplete anatomical results in wide-necked lesions include coil compaction, aneurysmal recanalization and the potential for distal migration of detached coils, i.e. the downstream loss of the coils from the aneurysm. Early intravascular re-endothelialization at the necks of aneurysms and the acceleration of wound healing in the aneurysmal sac and dome are O 00/44306
potential solutions that may help achieve successful permanent cures of this type of aneurysm.
Some investigators have applied simple protein coatings on GDCs to enhance their thrombogenicity and wound healing properties. However, intravascular embolization techniques generally make use of small-diametered microcatheters for delivery of these coils. Simple protein coating, therefore, results in the problem of increasing the diameter of these coils which in turn causes them to stick within the lumen of a microcatheter during coil delivery.
Occlusion coils are used to occlude a site within a body lumen, such as a blood vessel, brain aneurysm, or vascular malformation. The coils are typically placed at a desired site within the lumen by means of a microcatheter. The coils are normally made of a radioopaque, biocompatible metals such as platinum, gold, or tungsten. In treating brain aneurysms the coils occlude the aneurysm by posing a physical barrier to blood flow and by promoting thrombus formation. The formation of the neo-endothelium and mature intra-aneurysmal thrombus is necessary prior to subsequent organization and scar formation that, in turn, yields a permanently occluded aneurysm.
In the presence of continued exposure of intra-aneurysmal coils to circulating blood, metallic coils can be insufficiently thrombogenic to promote the establishment of firm and mature thrombus within the aneurysm. They have difficulty in promoting endothelialization across the wide neck of an aneurysm. Therefore, it is advantageous to tightly pack the aneurysm with coils for complete cure of the aneurysms. This may cause a mass effect on adjacent the brain parenchyma or cranial nerves.
To accelerate wound healing in the aneurysm (i.e., promotion of scar formation) and to decrease the mass effect of the aneurysm, "biologically active" bioabsorbable embolic material may be useful. Bioabsorbable polymers, such as polyglycolic acid and polyglycolic/poly-L-lactic acid copolymers, or bioabsorbable proteins, such as collagen and gelatins, have been used to make Intraluminal implants. These bioabsorbable polymers or proteins are also used to provide a the drug delivery vehicle (such as for continuous local delivery of growth factors). It is necessary to modify biological cellular response in preparation for acceleration of wound healing. Coil thrombogenicity was enhanced previously by increasing the surface area of the coils with fabric strands, such as Dacron, and by placing such coils into a thrombin solution. More recently, some investigators have modified the surfaces of platinum coils by coating them with collagen or polyurethane. This has resulted in some advantages, such as an increase in thrombogenicity of these coils. However, protein coatings on platinum surfaces are usually weak and may be removed easily during the delivery of the coils. Additionally, weakly coated proteins may be washed off by high-velocity arterial flow and may be a potential source of distal thromboemboli. There is also the potential problem of increases in the diameters of these coils; polyurethane coatings in particular also have the disadvantage of producing unfavorable changes in GDC performance, affecting their softness, thinness, smoothness,
and memory shape. In summary, GDCs and surrounding thrombus within an aneurysm are continuously exposed to and interact with circulating blood at the neck of the aneurysm. Coil compaction resulting from the force of pulsatile arterial blood flow is one of the reasons for incomplete obliteration of aneurysms. When this occurs, there is a potential risk of aneurysm recanalization and (re)rupture. Re- endothelialization and the promotion of wound healing in the aneurysmal sac and across its neck are necessary for complete aneurysm cure. Despite the many advantages of GDCs in the treatment of aneurysms, several recent clinical and experimental reports have highlighted their potential limitations in achieving an anatomic cure for wide-necked lesions. For example, two human autopsy cases treated with GDCs were reported for which the long-term (up to 6 months) histological findings revealed unorganized thrombus in the aneurysms, with no evidence of endothelialization across the aneurysmal neck in either case. Others have reported the histological findings for a patient with an anterior communicating artery aneurysm that had been previously treated with GDCs, in whom the compaction of coils resulted in an aneurysm remnant that was subsequently (6 months later) treated surgically. Histological examination of this resected aneurysm also revealed the presence of unorganized intra-aneurysmal thrombus that was exposed directly to the blood circulation without neointimal formation. It has been reported that in a long-term GDC study with experimental canine aneurysms, three of nine initially completely embolized aneurysms yielding to subsequent recanalization. Experimental GDC studies in monkey aneurysms were reported in which one of four of cases at 14 days of follow-up showed an aneurysmal "shoulder," indicative of aneurysm recanalization. More recently, in a study of experimental bifurcation aneurysms in rabbits, demonstrated the absence of organized thrombus and no neck endothelialization in treated aneurysms, even after follow-up periods of 3 to 6 months. What is needed is a method to promote an inflammatory response and healing of the aneurysm with reduction of its mass effect.
Brief Summary of the invention
The invention is an intravascular device that modifies either accelerating or decreasing biological cellular response comprising a separable tip or coil comprised at least in part of at least one biocompatible and absorbable polymer or protein, and a placement device associated with the separable coil adapted to dispose the coil into a selected body lumen. The biocompatible and absorbable polymer or protein promotes an intra-aneurysmal inflammatory response and healing of the aneurysms. This device may carry growth factors, such as a vascular endothelial growth factor, a basic fibroblast growth factor or a mixture of several growth factors or cytokines. The separable tip, which also need not be a coil, need not be comprised of a polymer or protein, but may be comprised of any material now known or later devised which is biocompatible, absorbable and which promotes an intra-aneurysmal inflammatory response and promotes healing of the aneurysm.
The biocompatible and absorbable polymer is in the illustrated embodiment at least one polymer selected from the group consisting of polyglycolic acid, poly~glycolic acid/poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate/hydroxyvalerate copolymers, poly-L- lactide, polydioxanone, polycarbonates, and polyanhydrides.
The biocompatible and absorbable protein is at least one protein selected from the group consisting of collagen, fibrinogen, fibronectin, vitronectin, laminin, and gelatin.
In one embodiment the coil is composed of the biocompatible and absorbable polymer or protein with a radio-opaque material is disposed thereon. Alternatively, the coil is composed of a radio-opaque material, and the biocompatible and absorbable polymer or protein is disposed thereon.
The invention is also characterized as a method for forming a thrombus comprising the steps of providing a separable coil comprised at least in part of at least one biocompatible and absorbable polymer or protein and disposing the separable coil into a body lumen including the various combinations and examples described above.
The method further of comprises the step of providing the coil with a growth factor, and in particular a vascular endothelial growth factor (VEGF), a basic fibroblast growth factor (bFGF), or other growth factors.
The invention having been briefly summarized by the foregoing, the invention and its various embodiments may be better visualized by turning to the following drawings wherein like elements are referenced by like numerals.
Detailed Description of the Preferred Embodiments In the present invention a biodegradable polymer (or protein) coils are used to control thrombosis or accelerate wound healing of the brain aneurysms for which platinum coils sometimes have often proven unsatisfactory.
Another aspect of the invention is a method of drug delivery system using biodegradable polymer (or proteins) in the combination with growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or other growth factors which promote long lasting effect of the wound healing
These biodegradable coils are useful for treating giant brain aneurysms to prevent the mass effect on the brain parenchyma or cranial nerves by shrinkage of scaring aneurysm.
Modes For Carrying Out The Invention
The implants of the invention may be placed within body lumens, e.g., blood vessels, Fallopian tubes, etc., of any mammalian species, including humans. The implant coils are made of biocompatible and absorbable polymers or proteins. Examples of bioabsorbable polymers that have been used in the illustrated embodiment to make Intraluminal implants include but are not limited to polyglycolic acid, poly~gycolic/poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate /hydroxyvalerate copolymers, poly-L-lactide, polydioxanone, polycarbonates, and polyanhydrides. Examples of bioabsorbable proteins that have been used in the illustrated embodiment to make Intraluminal implants include but are not limited to collagen, fibrinogen, fibronectin, vitronectin, laminin and gelatin.
To achieve radioopacity, the bioabsorbable polymer coils may be coated or mixed with radioopaque materials such as tantalum or platinum. The bioabsorbable polymer or protein itself may be mounted or coated onto coils or wires of metals such as platinum or nitonol.
Preferred growth factors for use in the invention are the naturally occurring mammalian angiogenic growth such as VEGF, or b-FGF. Mixtures of such growth factors may also be used if desired. The biodegradable polymer coils of the invention can be placed within the body lumen, vascular system or vessels using procedures well known in the art.
Generally, the desired site within the vessel is accessed with a catheter. For small diameter torturous vessels the catheter may be guided to the site by the use of guide wires. Once the site has been reached, the catheter lumen is cleared by removing guide wire. In the case of polymer occlusion coils, the coils are loaded by means of a pusher wire. The coils may be attached to the distal end of the pusher via a cleavable joint (e.g., a joint that is severable by heat, electrolysis, electrodynamic activation or other means) or a mechanical joint that permits the coil to be detached from the distal end of the pusher wire by mechanical manipulation. Alternatively, the coils may be free and detached from the pusher wire, simply pushed through the catheter and expelled from the distal end of the catheter. Many alterations and modifications may be made by those having ordinary skill in the art without departing from the spirit and scope of the invention. Therefore, it must be understood that the illustrated embodiment has been set forth only for the purposes of example and that it should not be taken as limiting the invention as defined by the following claims.
The words used in this specification to describe the invention and its various embodiments are to be understood not only in the sense of their commonly defined meanings, but to include by special definition in this specification structure, material or acts beyond the scope of the commonly defined meanings. Thus if an element can be understood in the context of this specification as including more than one meaning, then its use in a claim must be understood as being generic to all possible meanings supported by the specification and by the word itself.
The definitions of the words or elements of the following claims are, therefore, defined in this specification to include not only the combination of elements which are literally set forth, but all equivalent structure, material or acts for performing substantially the same function in substantially the same way to obtain substantially the same result. In this sense it is therefore contemplated that an equivalent substitution of two or more elements may be made for any one of the elements in the claims below or that a single element may be substituted for two or more elements in a claim.
Insubstantial changes from the claimed subject matter as viewed by a person with ordinary skill in the art, now known or later devised, are expressly contemplated as being equivalently within the scope of the claims. Therefore, obvious substitutions now or later known to one with ordinary skill in the art are defined to be within the scope of the defined elements. The claims are thus to be understood to include what is specifically illustrated and described above, what is conceptionally equivalent, what can be obviously substituted and also what essentially incorporates the essential idea of the invention.

Claims

We claim:
1. An endovascular apparatus of biodegradable and biocompatible polymers for developing a controlled inflammatory response with cellular manipulation comprising: a separable coil comprised at least in part of at least one biocompatible and absorbable polymer or protein; and an endovascular placement device associated with said separable coil adapted to dispose said coil into a selected body lumen.
2. The apparatus of claim 1 wherein said coil further is comprised at least in part of a growth factor.
3. The apparatus of claim 2 wherein said coil further is comprised at least in part of a one selected from the group of VEGF, b-FGF, or mixtures thereof.
4. The apparatus of claim 2 wherein said coil further is comprised at least in part of a basic fibroblast growth factor. „„,„ ,,„,: O 00/44306
13
5. The apparatus of claim 3 wherein said coil further is comprised at least in part of a mixture of said vascular endothelial growth factor and a basic fibroblast growth factor.
6. The apparatus of claim 1 wherein said biocompatible and absorbable polymer is at least one polymer selected from the group consisting of polyglycolic acid, poly-glycoiic acid/poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate/hydroxyvalerate copolymers, poly-L- lactide, polydioxanone, polycarbonates, and polyanhydrides.
7. The apparatus of claim 1 wherein said biocompatible and absorbable protein is at least one protein selected from the group consisting of collagen, fibrinogen, fibronectin, vitronectin, laminin, and gelatin.
8. The apparatus of claim 1 wherein said coil is composed of said biocompatible and absorbable polymer or protein, and wherein a radio- opaque material is disposed thereon.
9. The apparatus of claim 1 wherein said coil composed of a radio-opaque material, and wherein said biocompatible and absorbable polymer or protein is disposed thereon. O 00/44306
14
10. The apparatus of claim 1 wherein said biocompatible and absorbable polymer or protein promotes cellular manipulation, controlled inflammatory response and vascular healing.
11. A method for endovascular inflammatory response comprising: providing a separable coil comprised at least in part of at least one biocompatible and absorbable polymer or protein; and disposing said separable coil into a body lumen.
12. The method of claim 11 further providing said coil with a growth factor.
13. The method of claim 12 wherein providing said coil with a growth factor comprises providing said coil with a vascular endothelial growth factor.
14. The method of claim 12 wherein providing said coil with a growth factor comprises providing said coil with a basic fibroblast growth factor.
15. The method of claim 13 wherein providing said coil with a growth factor comprises providing said coil with a mixture of said vascular endothelial growth factor and a basic fibroblast growth factor.
16. The method of claim 11 wherein providing said separable coil comprised with said biocompatible and absorbable polymer comprises providing said coil with at least one polymer selected from the group consisting of polyglycolic acid, poly~glycolic acid/poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate/hydroxyvalerate copolymers, poly-L- lactide, polydioxanone, polycarbonates, and polyanhydrides.
17. The method of claim 11 wherein providing said separable coil comprised with said biocompatible and absorbable protein comprising providing at least one protein selected from the group consisting of collagen, fibrinogen, fibronectin, vitronectin, laminin, and gelatin.
18. The method of claim 11 wherein providing said coil provides a coil composed of said biocompatible and absorbable polymer or protein with a radio-opaque material is disposed thereon.
19. The method of claim 11 wherein providing said coil provides a coil composed of a radio-opaque material with said biocompatible and absorbable polymer or protein is disposed thereon.
EP99951622A 1999-01-27 1999-09-27 Biodegradable polymeriprotein based coils for intralumenal implants Ceased EP1156759A4 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
PCT/US1999/001790 WO1999044538A1 (en) 1998-01-27 1999-01-27 Biodegradable polymer/protein based coils for intralumenal implants
WOPCT/US99/01790 1999-01-27
PCT/US1999/022420 WO2000044306A1 (en) 1999-01-27 1999-09-27 Biodegradable polymeriprotein based coils for intralumenal implants

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EP1156759A1 true EP1156759A1 (en) 2001-11-28
EP1156759A4 EP1156759A4 (en) 2002-11-20

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CA2323151C (en) 2007-04-10
AU6402699A (en) 2000-08-18
JP2004223268A (en) 2004-08-12
EP1156759A4 (en) 2002-11-20
WO2000044306A1 (en) 2000-08-03
JP4751661B2 (en) 2011-08-17
JP2003524456A (en) 2003-08-19
CA2323151A1 (en) 2000-08-03
JP2006021052A (en) 2006-01-26

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