Biodegradable polymer coils for intraluminal implants

Surgery – Instruments – Internal pressure applicator

Reexamination Certificate

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C623S001110, C623S001380

Reexamination Certificate

active

06423085

ABSTRACT:

BACKGROUND OF THE INVENTION
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, Calif., 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 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

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