WO2013160829A1

WO2013160829A1 - Intravascular prosthesis for small vessels

Info

Publication number: WO2013160829A1
Application number: PCT/IB2013/053204
Authority: WO
Inventors: George L. De Goicoechea
Original assignee: St George Medical Inc
Priority date: 2012-04-23
Filing date: 2013-04-23
Publication date: 2013-10-31
Also published as: FR2989567A1

Abstract

The invention relates to a vascular prosthesis (10) for inserting into a vessel exhibiting a stenosis or a narrowing. In order to prevent premature restenosis, such a prosthesis comprises an essentially tubular main member consisting of a metal mesh (11) cooperating with its bioabsorbable means (12) comprising a drug and a biocompatible monomer stimulating a cellular growth around said mesh.

Description

Endoluminal vascular prosthesis for small vessels

The invention relates to an endoluminal vascular prosthesis, also called an endovascular prosthesis, or more generally a device intended to be introduced into a vessel presenting a stenosis or a narrowing of the arterial lumen of the vessel. The installation of such an endovascular prosthesis makes it possible to recover a satisfactory arterial lumen conducive to normal circulation within said vessel. The invention relates more particularly but not limited to a prosthesis for small veins, coronary arteries or vessels of the lower or upper limbs.

As described by way of example Figures la and lb, a stenosis generally stems from an accumulation of fat deposits on the inner wall or intima 3 of a vessel 1 thus forming one or more plates 2. These deposits can consist of cholesterol, calcium or other blood-borne substances. The formation of said plates may eventually close vessels, including small arteries such as coronary arteries, making them rigid and irregular. To treat this pathology, the interventional cardiologist may use a transluminal angioplasty to introduce a balloon, which when inflated, pushes out the plates formed against the intima. The balloon is subsequently removed and the arterial lumen 4 is restored. However, the effect can be short-lived. To prolong the latter, a therapeutic gesture may consist in placing an endovascular prosthesis or a stent in the form of a flexible metal cylinder whose mesh provides a radial force exerted against the inner wall of the vessel as a scaffolding. At the level of the lesion, the stent remains in the vessel. he thus keeps the vessel open enough for the blood to circulate normally.

There are different types of endovascular prosthesis. As indicated by way of example in US 6,010,530, a metal mesh (stent) such as a wire constrained to materialize zigzags may optionally include a polymer type coating. The stent (e.g. based on nitinol) may be self expandable ^¬ during its installation by means of a catheter and a retractable sheath. It can alternatively be deployed using a balloon. In the latter case, the stent is crimped onto said balloon as the interventional cardiologist inflates within the vessel to repel the plaques and restore the arterial lumen. The balloon is then deflated and removed. Once the plates are pushed against the inner wall of the vessel, the stent is a scaffolding supporting the wall of said vessel. The stent remains in the vessel to keep it open. The therapeutic effects of stent placement are relatively long-lasting thanks to the scaffolding provided by said stent.

However, it has been found that the body can react following the stent placement by rejecting this foreign body. The metallic structure of the stent seems to have a major role in this reaction, which can result in restenosis, ie a new formation of stent narrowing at the level of the stent limiting the arterial lumen of the vessel. This phenomenon can occur within one to two years depending on the patient, his lifestyle or diet, etc. To delay the occurrence of restenosis, US 6,010,530 teaches that the coating (if any) of the endovascular prosthesis may be impregnated with a stent. substance or a medicinal agent - for example heparin - which is gradually released into the body after placement of the stent within a vessel. This substance may have a particular effect or a plurality of effects, among which we may mention anti-inflammatory, antimicrobial, antibacterial, antithrombotic or endothelial cell-promoting effects. In particular, it makes it possible to limit the formation of thrombosis and the excessive proliferation of cells thus preventing early restenosis. As a variant, the metal mesh may be covered with a substance equivalent to that impregnated with the coating of the preceding stent or with a plurality of substances the combined effects of which slow down the occurrence of restenosis. Thus, restenosis can be delayed for several years compared to a bare stent. Such stents having an additional assimilable substance are commonly referred to as "drug eluting stents".

Although having a remarkable advance, such endovascular prostheses raise some disadvantages.

An endovascular prosthesis with a coated stent does not promote "uptake" of the stent by the treated vessel. Once the effect induced by the substance (s) fades, the coating contributes to the "rejection" effect of the endovascular prosthesis.

US 6,010,530 teaches that to limit this disadvantage, the coating may have holes or be made using a porous material. Thus, endothelial cells can infiltrate into said wall and constitute a new intima which, like a filter allows the blood to feed the vessel wall again.

Other known embodiments use a prosthesis devoid of coating. The mesh is thus directly applied against the inner wall of the treated vessel. In order for the prosthesis to prevent early restenosis, the substances making it possible to constitute a drug-eluting stent are deposited in successive layers on the metal mesh of the stent. Alternatively, the substance or substances may be deposited in a single layer by spraying or dipping. Thus, in addition to its scaffolding function, this metal mesh fulfills the role of "substance carrier". In order that a sufficient quantity of substances can be diluted within the treated vessel, it is necessary that the mesh of the stent is particularly dense to convey said substances. This high metal density comes at the expense of the flexibility of the whole (very useful depending on the configuration of the vessel treated), the cost of the endovascular prosthesis and the desired effect to prevent restenosis linked to an excessive presence of compounds metal. After the dilution of the substances, a high density of the mesh can thus reinforce a risk of restenosis requiring a new therapeutic intervention.

The invention makes it possible to meet all the disadvantages raised by the known solutions. The main object of the invention is to provide a prosthesis having a minimum but sufficient radial force to maintain a nominal arterial lumen while preventing the risk of thrombosis as a result of the prosthesis fitting and by improving the tolerance of the prosthesis. organism by the presence of bio-absorbable means carrying substances with virtues mainly anticoagulant and conducive to cellular development to form a new intima imprisoning the prosthesis.

Among the many advantages provided by the invention, we can mention that the invention allows:

to slow down or even prevent restenosis after placement of an endovascular prosthesis and thus to reduce the occurrences of therapeutic gestures to maintain a satisfactory and perennial arterial lumen in a treated vessel;

to facilitate tolerance by organizing prostheses by the optimized and minimal presence of metallic material;

- To improve the homogeneity of the intima recreated after placement of the prosthesis by a homogeneous intake of substances preventing the formation of thrombosis clots and promoting controlled cell growth.

To this end, an endovascular prosthesis is provided first comprising a substantially tubular main member consisting of a wire mesh. To prevent early restenosis, such an endovascular prosthesis comprises bioabsorbable means cooperating with said wire mesh, said bioabsorbable means comprising a drug agent and a biocompatible monomer stimulating cell growth around said mesh. To prevent excessive and undirected cell growth around the wire mesh, the wire mesh is consisting of a continuous wire and bent in the form of scissors. According to a preferred embodiment, the wire of the lattice is advantageously based on cobalt chromium or nitinol.

In order to allow the introduction of the prosthesis via a catheter and then the expansion of its main limb, said expansion being able to be automatic or assisted by a balloon, the internal radius of curvature of the plications of the wire may be of the order of one to ten times the diameter of the wire.

According to a preferred embodiment, the bioabsorbable means consist of a polymer.

More specifically, said bioabsorbable means may consist of polymer fibers interwoven with the wire mesh to homogeneously distribute said bioabsorbable means along the main member.

To prevent thrombosis during the application of the endovascular prosthesis, the medicinal agent is advantageously an anticoagulant.

To facilitate the therapeutic gesture and control the positioning of an endovascular prosthesis according to the invention in the vessel, said prosthesis may comprise radiopaque means located at the ends of the main member of the endovascular prosthesis.

In a preferred configuration, an endovascular prosthesis may comprise a quantity of bioabsorbable means substantially equivalent to that of the wire mesh constituting the main member of said endovascular prosthesis.

Other features and advantages will appear more clearly on reading the description which follows. and examining the figures that accompany it, among which:

FIGS. 1a and 1b (already described) show a partial view of the vascular system of a patient with arterial stenosis;

- Figure 2 describes a prosthesis according to one invention;

FIGS. 3a and 3b describe a partial view of the vascular system of a patient presenting with an arterial stenosis after the application of a prosthesis according to the invention;

- Figures 3c and 3d describe a partial view of the vascular system of a patient with arterial stenosis several weeks or months after an intervention of applying a prosthesis according to the invention.

Figure 2 shows a preferred embodiment of an endovascular prosthesis 10 according to the invention when it is deployed.

This comprises a main member or substantially tubular stent consisting of a continuous wire 11 and folded into a configuration allowing the contraction (or crimping of the member if the deployment of this denier is assisted by balloon) and the expansion of the prosthesis. Such a wire is preferably made based on cobalt chromium or nitinol. As shown in Figure 2, the wire has a zigzag or scissor configuration. This configuration is particularly advantageous because, when the prosthesis is deployed, the scissors materialized by the wire prevent excessive cell growth in regions in contact with said wire. To constitute such a stent, a wire may advantageously be folded successively in the form of scissors, the internal radius of curvature at the level of the plicatures remaining small compared to the diameter of the wire (of the order of one to ten times said diameter ). According to such a configuration, the folded wire forms as many tips as plications, each of said plicatures being preceded and followed by a substantially linear portion of the wire. The length of a substantially linear portion of wire may be greater or less depending on the total length of the desired stent and the number of crowns thus formed. This scissors construction allows an ideal contraction of the stent by decreasing the angle between two successive linear portions of the wire but also an expansion adapted by increasing said angle. Combined with a small proportion of metal, a scissor shape of such a stent whose expansion is particularly optimized provides an optimal artery support and prevents excessive and non-oriented extracellular proliferation around the wire mesh by reducing contact between said stent and an arterial wall. A risk of restenosis is thus greatly reduced.

The invention would however be limited to this preferred configuration.

The invention provides that the stent can be self expanding ^¬ when released from the catheter carrying the or alternatively be expanded using a balloon. According to the embodiment chosen, the mesh is designed according to well-known techniques to ensure such automatic deployment or assisted by a balloon. The density of the mesh is further determined to deliver after deployment a radial force sufficient to maintain an open vessel. The function of the wire is reduced to a scaffolding role to sufficiently support the inner wall of the treated vessel.

To limit the risk of occurrence of restenosis, the invention provides that the metal mesh is reduced to its simplest expression - simply sufficient to allow it to exert a radial force after deployment to sustainably maintain the vessel. In addition, to prevent the formation of thrombotic clots during the fitting of a prosthesis according to the invention, bioabsorbable means 12 cooperate with said wire 11. These means can be preferably made in the form of a or multiple polymers having one or more agents. Thus, as indicated by way of example in FIG. 2, one or more bioabsorbable fibers 12 is (are) interlaced with the metallic wire 11. The fibers 12 appear in fine lines in FIG. wire 11 shown in thick lines. The carriers are - non-exhaustively - an anticoagulant to limit clot formation or a monomer whose role is to catalyze or promote cell growth of tissues in contact with the prosthesis. The tissues can thus interfere within the mesh to constitute after a few weeks or months a new intima imprisoning the mesh metal. The latter - in addition to its role of scaffolding provides a role of trellis. The function of the agents is temporary. The means carrying the agents are therefore intended to be bioabsorbable. A few weeks or a few months after the insertion of the endovascular prosthesis, said means 12 are completely resorbed. Only the mesh remains metal 11 which continues its role of scaffolding and trellis. The density of foreign body remaining present can thus be reduced in view of the prior art. Different configurations of bioabsorbable means are possible. For example, fibers 12 may be interwoven cooperating with the wire 11 to diffuse the agents along the tubular member homogeneously and equitably distributed. Said medicinal agents and / or biocompatible monomer (s) can thus be regularly distributed along the wire mesh 11 (mainly on one of the inner or outer parts of the mesh or equitably on said parts). For a metal stent calibrated to exert a determined radial force, the density of bioabsorbable means can be adjusted to determine the amount and dynamics of elution of the carriers regardless of the density of metal compounds. The invention thus reduces the risk of restenosis and promotes the assimilation of the prosthesis by organizing the patient.

According to a preferred embodiment, a prosthesis according to the invention is substantially composed (before its application within a vessel) of 50% metal elements 11 and 50% bioabsorbable means 12. Other proportions could be envisaged according to the wish to strengthen or reduce the radial force exerted by the mesh 11 or the degree and distribution of the medicinal agents carried by the bioabsorbable means 12.

To facilitate the therapeutic gesture, the invention provides that radio-opaque markers can be positioned on the main member of the prosthesis. By way of example, markers 13 and 14 may be positioned at the extremities of the limb. The practitioner can thus control his gesture by positioning perfectly - using a catheter conveying the prosthesis - the latter prior to its automatic or assisted expansion. Figures 3a and 3b depict a vessel 1 as illustrated in connection with Figures 1a or 1b. This has a stenosis in the form of a plate 2. After having dilated the vessel and pushed out the plate 2, a prosthesis 10 according to the invention has been applied. Whether its expansion is automatic or assisted by the inflation of a balloon, the metal mesh 11 rests against the intimal 3 of the vessel and exerts a radial force against said intimal. This force is sufficient to keep the vessel open so that the arterial lumen 4 of the latter is satisfactory. Bioabsorbable means 12 cooperating with the mesh 11 appear in fine lines with respect to the wire 11 shown in thick lines. The presence of anticoagulants carried by said means 12 or other medicinal substances prevent the risk of thrombosis or infection.

Figures 3b and 3c describe the same vessel, a few weeks after the application of the prosthesis 10. The bioabsorbable means are resorbed. The presence of a monomer carried by the bioabsorbable means 12 (present in FIGS. 3a and 3b), a monomer promoting cell growth of the tissues in contact with the tubular member of the prosthesis, has favored the creation of a new intimal 3 imprisoning the mesh 11 represented by transparency in FIG. 3c in dotted lines. This one continues its function of scaffolding but the new intima 3 'perfectly irrigated and having a smooth surface facilitates the circulation blood. The arterial lumen 4 is thus durably preserved.

The invention has been described in a preferred manner in connection with an endovascular prosthesis for small vessels such as coronary arteries or arteries of the lower limbs (femoral, tibial, popliteal arteries) or upper limbs. The invention applies naturally to any other endovascular prosthesis having a persistent metallic mesh cooperating with bioabsorbable means.

Claims

An endovascular prosthesis (10) comprising a substantially tubular main member consisting of a wire mesh (11), bioabsorbable means (12) cooperating with said wire mesh, said bioabsorbable means comprising a drug agent and a biocompatible monomer stimulating a cellular growth around said mesh, said prosthesis being characterized in that the mesh consists of a continuous wire and bent in the form of scissors.

Prosthesis according to the preceding claim, wherein the wire is based on cobalt chromium or nitinol.

Prosthesis according to the preceding claim, wherein the internal radius of curvature of the plications of the wire (11) is the order of one to ten times the diameter of the wire allowing a contraction or a crimping on a balloon and an expansion of the main member of the prosthesis.

The prosthesis of any one of the preceding claims, wherein the bioabsorbable means (12) is a polymer.

Prosthesis according to any one of the preceding claims, wherein the bioabsorbable means (12) consist of polymer fibers interwoven with the wire mesh (11) ·

The prosthesis of any one of the preceding claims, wherein the drug agent is an anticoagulant.

7. Prosthesis according to any one of the preceding claims, comprising radiopaque means (13, 14) located at the ends of the main member of the endovascular prosthesis.

8. Prosthesis according to any one of the preceding claims, comprising a quantity of bioabsorbable means (12) substantially equivalent to that of the wire mesh (11) constituting the main member of said endovascular prosthesis.