MXPA99010357A - Self-expanding endoprosthesis - Google Patents

Abstract

A luminal endoprosthesis comprising a framework (1) made up of braided filaments. The framework (1) is self-expanding, that is to say that after it has been radially compressed for positioning of the endoprosthesis, it automatically recovers its nominal diameter. The metal of the framework has undergone a thermal treatment bringing about a state transition, at a temperature close to that of the organism, and this confers upon it a suitable rigidity after it has been positioned in an anatomical conduit.

Description

AUTO-EXPAND ENDOPROTESIS IBLE Description: The invention is related to a radially expanded luminal endoprosthesis and more particularly to a vascular endoprosthesis, and especially stents. From the work done by C. DIDCOTT about the dilation and the support of anatomical ducts, the concept of a dilatable stent has been very successful. One of the most important discoveries in this field is related in particular to cardiovascular surgery, especially the reduction of aneurysms and the opening of stenosis. One consequence of the general level of success of these methods has been the increased demand on the part of the practitioners, both in terms of the quality of the products in the market, and also their ease of use. The crucial criterion in this respect includes the high level between the diameter of the endoprosthesis in its contracted form and its nominal diameter (non-contracted state), but also the flexibility of this endoprosthesis, which must be capable, during the insertion, to follow sinuous paths without causing writhing. Furthermore, when in place, such a stent must demonstrate mechanical characteristics compatible with those of the vessels being treated, and must be able to withstand the stresses of understanding generated by the pressure of the environment and the presence of adjacent organs. The investigations initially focused in particular on blood vessels of a small and medium caliber, but much remains to be done in the field of very small diameter vessels and, in contrast, in large diameter anatomical canals. The treatment of thoracic and abdominal aneurysms in this way requires the use of a large diameter endoprosthesis: in the order of 35 to 45 mm for thoracic aneurysms, and in the order of 22 to 31 mm for abdominal aneurysms. None of the stents available in the market in this diameter range fully meet the expectations of practitioners today, essentially because they are able to fulfill their role in the long term, are not easy to use, or because the materials used They are not adequate. The endoprostheses used to repair the anatomical conduits comprise a rotating structure which is very often provided with a coating. Stents that consist only of one structure are called "stent". There are basically two types of structures (or stents) on the market, specifically structures that are dilated by inflatable balloons, and self-expanding structures which comprise braided or non-braided structures. Stents are known to be placed in place and then dilated to their nominal diameter by the introduction of an inflatable balloon. The particular disadvantages of this technique are the interruption in the blood flow and the dimensions of the structure. Balloon stents can only be used to treat lesions in small arteries (maximum 12 mm). The reason for this is simple: for a stent with, for example, an initial diameter of 3 mm that will be dilated to a diameter of 8, 10 or even 12 mm, it is necessary to use a pressure of 5 to 10 atmospheres (as indicated in US-4, 950, 227). The balloon must therefore be extremely strong, which causes problems in terms of diameter. In addition, it is not possible to treat long lesions using this technique. It should be noted that an intervention performed in an abdominal aneurysm can last from 6 to 8 hours when a femoral or iliac surgical approach is used (compared to the average duration of 2 hours for treatment through a direct surgical route). As for the self-expanding stents, they do not require balloons: they generally extend longitudinally and are introduced, in a form with a reduced diameter, inside the applicator consisting of a tubular catheter equipped with a plunger. The entire assembly is introduced, particularly by the femoral or iliac route, to the site of deployment, where the endoprosthesis is released. Although they have some advantages, known models of self-expanding stents also have a number of limitations, which for a long time have been unsurpassed. Its diameter does not generally exceed 25 mm. Braided stents with cobalt / nickel / chromium alloys (ELCILOY® or PHYNOX®), however, allow diameters ranging from 2mm to 45mm or even up to 50mm. When they are released, the endoprostheses, initially subjected to an elongation, with narrowing of their diameter, automatically recover their nominal diameter. The first braided stents of that type were made by C. DIDCOTT. FR-1,602,513 discloses stents provided by a rigid structure which is formed by intertwining metal filaments to form a braid. This document describes braids having a high angle of intersection a between 45 and 90 ° between the filaments of two different layers. It should be mentioned, strictly from the mechanical point of view, that a braid resists compression less effectively, while more braided filaments of which it is built there is a deviation of an almost annular structure, that is to say a spiral of a very small size, which corresponds at an angle as close as possible to 90 ° in relation to the angle of the braid angle (which means that the angle α between the filaments should be as close as possible to 180 ° C, ie currently around 120 ° C ) (as described in FR-2, 333, 487). The smaller this angle, the braid will less effectively resist the c omp r e s. US Pat. No. 5,061,275 describes a stent with a braided structure, in which the intersection angle a is obtuse. In this case, the elongation coefficient of the prosthesis is high, which causes problems when it is being placed in its place. (The elongation coefficient is defined as the level of axial extension of said prosthesis in its contracted form, therefore with its reduced diameter, and in its non-contracted form, in its nominal diameter). Therefore, the release of this type of endoprosthesis requires a long practice, since detection is difficult (the stent undergoes a considerable shortening at the time of its release). The endoprosthesis encompasses a substantial length in the introducer, which creates friction and reduces the ab ility.

Researchers who have proposed the task of solving the problem associated with the use of self-expanding prostheses with mechanical action, have asked questions regarding the angle, thickness and composition of the filaments, without being able to obtain a prosthesis that in its entirety have all the criteria of quality: it has not been possible to obtain a prosthesis that combines a low angle of intersection and good resistance to compression. It should also be noted that for the same angle a = 85 °, a braid with 32 strands presents a resistance to radial pressure which is 50% higher than a braid with 24 strands of identical diameter, a fact which shows that such a structure responds to relatively common relations. EP-A-0 740 928 describes a braided stent made of an alloy with a cob base at 11 o / n or 1 / cr, in which, in order to increase the resistance to radial compression, a double strand has been used, which has a problem in the space occupied in the applicator. The use of such filaments to make medical braids should initially give good results. However, the limit of breaking strength of the cold forged filament is approximately 2000 N / mm2 and, after heat treatment, the filament reaches values of breaking strength of 2500 to 2700 N / mm2, which is it makes the filament rigid and brittle; they prove to be relatively difficult to enlist and braid due to their inherent elasticity. The frequent breaking of the filaments affects in particular the uses of the machines, which are subject to an accelerated deterioration. Furthermore, when used in the long term, especially for vascular conditions where stresses on the metal are very high (for example abdominal aneurysms), it has been found that stents made from these filaments age rapidly (fatigue effect). Fatigue tests have shown the same results after a simulated longitudinal compression for an equivalent period of five months. Other endoproses a u t o - e xpandi b 1 e s described for example in US 5,354,309 and US 5,540,713 are characterized by a portion of memory alloy having a cylindrical outer contour in the form of a sleeve. For example, nickel / titanium alloys such as Nitmol © can be used. Different shapes are known: truncated mcised cylinders, helical structures, network structures, rolled metal sheets and the like. When they reach body temperature, they tend to adopt a radially expanded form, which prior treatment has forced them to memop. If they are not placed quickly at the release site, they tend to jump back to their nominal diameter. Therefore generally, it is necessary to cool these stents and / or the applicator in which they are placed, as also described in US 5,037,427. In this document, the applicator of an improving alloy stent is cooled through the placement phase by physiological saline solution cooled with ice. When the desired portion is reached, the flow of cooling fluid stops and the stent, gradually heated by body heat, expands. According to this method, it would theoretically be possible to remove the stent by cooling it again, so that it could be freely returned to its reduced original diameter. Truncated incised cylinders and network structures generally lack flexibility, are rigid and twist excessively. Because of this, there is a high risk of damaging the walls of the vessels. In addition, they occupy a considerable space in the introducer. Helical structures (or spirals) when activated by the simple phase change do not open the arteries sufficiently and are not effective in the treatment of stenosis, since they do not cover the entire arterial wall. In addition, none of these types of stents can be used in large arteries. Nevertheless, it is necessary to anticipate the possibility that the voltage gates generated by the phase transition of the materials forming the structure is not sufficient to withstand the pressure due to the wall and friction. In this case, there is a high risk that the stent will not be able to deploy. The operator must anticipate the possibility of the subsequent introduction of an inflatable balloon to be able to regist the endoprosthesis to its nominal diameter. This "forced" spreading technique often leads, in the long term, to reactions by the organism (in particular tissue proliferation). The object of the invention is to develop an endoprosthesis which exhibits high flexibility during its introduction, but which m s i t u exhibits good compressive strength. Another object of the invention is that the stent exhibits good stability at the site of implantation. Another object of the invention is to develop an endoprosthesis that covers a wide range of diameter and which in particular can be implanted in large diameter anatomical canals. The subject matter of the invention is a lummal endoprosthesis comprising a braided structure with mu 11 f 11 ame ntosauto-e xp andi b 1 is, radially expandable to a given nominal diameter, made of braided metal filaments of a shape memory alloy , wherein the structure: can compress to a reduced diameter for introduction into the body conduit and that at the time of its release spontaneously adopts, regardless of the temperature surrounding it, such nominal diameter, which corresponds substantially to the diameter of an anatomical duct to be treated; the braided filaments form one another, when the braided structure has its nominal diameter an argon of between 30 and 95 °, and advantageously between 50 and 90 °; the metal of the filaments is chosen from a group consisting of nickel / titanium alloys and nickel / titanium / cobalt alloys, with a nickel content of between 52 and 56% by weight; the structure is treated with heat so that the metal of all the filaments undergoes a complete and stable transition phase taking it from a given rigidity to a greater rigidity at a temperature equal to or lower than the body temperature but higher than the ambient temperature. The shape memory alloy of the filaments is preferably up to 1 s t i c a. The angle a may vary along the length of the braid. The invention also relates to a method for manufacturing a stent as described above, which comprises the following operations: selecting a memory alloy in an elastic form from the group consisting of alloys of 1 / titanium and nickel alloys. where 1 / titanium / c to 11 o and comprising between 52 and 56% by weight of nickel, - produce filaments of this alloy, braid these filaments around a mandrel in such a way that a braid of a nominal diameter can be obtained which corresponds substantially to the diameter of an anatomical canal to be treated, the filaments form an angle a between 30 ° and 95 ° to each other, subjecting sections of this braid, in this nominal diameter, to a thermal treatment that establishes a transition phase Complete and stable that causes the metal of this to change from a given stiffness to a higher stiffness, at a temperature equal to or less than the temperature of the ganism, - place an optional lining on the structure, cut the braid sections into segments of appropriate length. Advantageously, the braiding is carried out using strands of 1 / titanium cold-formed from a die, and the heat treatment comprises at least one heating operation in an area between 400 ° and 600 ° C, preferably at 500 ° C. for 10 minutes and with air cooling. The braiding is preferably carried out in such a way that the angle α varies along the length of the braid. Several advantages of the invention are that the stent allows a large reduced coefficient of elongation, which is very flexible in its contracted form, is not prone to twisting and completely resists understanding after it has been placed in place. Another advantage is that below its transition temperature, the stent is very easy to manipulate, so that it can easily be placed in the proper (nominal) dimension, can be brought to its reduced diameter and can be inserted into a Applicator without fear of damaging it. Other features and advantages of the invention will be apparent from the description of the particular embodiments, with reference to the attached figures, of which: Figures 1 and 2 are two-stage diagrammatic representations for placing an endoprosthesis according to the invention in an anatomical conduit. Figure 3 is a graph showing the relationship between a (angle of intersection between two strands of a stent) and the radial force (corresponding to the resistance of the stent to the radial pressure of this), established for a braided stent according to with the current state of technology and for a stent according to the invention. Figure 1 shows the general appearance of a device used to place a stent according to the invention. For the sake of clarity of the drawings, only the structure 1 of the stent is shown here. Of course, what appears here as a simple stent may include an internal and / or external reflex. The structure 1 is made of a braid of interlaced metal filaments. The particular feature of the endoprosthesis according to the invention is found in the design of its structure, which involves the effects of a naturally elastic braided structure, and the particular physical properties of the filaments of which it is made, combined with an effect of transition phase. The filaments forming the braided structure are made of a specific structure (in this case a Ni / Ti alloy) which, by virtue of an adequate treatment, which will be described later, suffers, at a certain temperature, close to that of the hot-blooded organisms, a reversible transition of their crystal structure, causing a radical change in their mechanical characteristics. The metal of structure 1 in its initial state (ie below its transition phase temperature) looks perfectly ductile. Under these conditions, the operator can easily manipulate the stent without fear of damaging it, breaking the structure or interrupting the arrangement of the filaments. In particular, it is possible to adjust the stent to the appropriate dimension by cutting it and compressing it radially (the effect of which is to bring the filaments close to one another, their angle of intersection tending at this time towards an insignificant value close to zero). With the stent in this state, the operator can easily pass it over the hollow rod 3 of an applicator, between a non-traumatic tip 1 and a plunger 5, and slide thereon an outer sleeve 2 which holds the stent in place by subjecting it to a radial tension, which in this state is virtually ignifying. Figure 1 shows the distal end of the applicator after the latter has been introduced for a short time into an anatomical duct 6, in such a way that it brings the endoprosthesis to the place to be treated 7. In the instant when the operator releases the stent by sliding the sleeve 2 backwards, the radial tension ceases when applied, and, by virtue of the inherent elasticity of the braided structure, the structure 1 expands to its nominal diameter, which corresponds to the anchor Also, the transition of the crystal structure mentioned above occurs when the temperature of structure 1 reaches that of the organism. This change exerts its effect at the moment when structure 1 is deployed, this corresponds to an increase in the value of the intersection angle between the filaments. The filaments thus participate in two ways in the opening of the braided structure: there is an important synergistic effect between the displacement of the braided structure of the structure and the stiffening of the filaments due to their transition state. The endoprosthesis that, until the moment of its release, exhibited a great flexibility, perfectly adapted for its insertion into the sinuosities of the anatomical ducts, in this way it stiffens and, almost instantaneously, is perfectly capable not only of exerting a pressure suitable in the internal wall of the anatomical duct 6, but also to withstand the external stresses which this anatomical duct 6 will necessarily suffer. The two combined effects (mechanical expansion coupled with thermal stiffening) reinforce each other and allow a complete expansion of the endoprosthesis without trauma, a fact that in the long term is beneficial for the patient.

For equivalent performances, the number of filaments forming structure 1 of the endoprosthesis can be reduced, or, optionally, it is possible to use smaller diameter filaments than in the braided endoprosthesis according to the prior art, the fact of which leads to a reduction substantial in the diameter of the stent in the compressed state, and thus in the applicator, and flexibility increases. This design also provides apart from this other appreciable advantages, particularly for placement in large-diameter anatomical canals. If it is desired to treat lesions which are highly eteromatose, then, with stents that use conventional self-expanding structures, it is only possible at the expense of the technology which can be described as onerous: these structures then have to be provided with reinforcement elements. which occupy a lot of space (relatively thick metal, a large number of filaments and / or large diameter filaments). Even in their radially contracted form, said stents have a large diameter and length.

By using the stents according to the invention, not only the structure is light (due to the reduction of the diameter in the splicer), but also the risk that the stent does not suffer a radial displacement is considerably reduced. Figure 2 shows the final angle α formed between the braided filaments when the structure is deployed radially. The endoprosthesis, in practice, provides excellent results, regardless of the value of the chosen angle. Tests have shown an excellent adaptation of the stent according to the invention, especially for values of a between 30 and 95 °, and, optimally, in a range of 50 to 90 °. In this range of angles, the difference in length between the compressed endoprosthesis (see Figure 1) and the released stent (see Figure 2) is small in size. It should be noted that the diameter of the stent (represented here as almost cylindrical) may vary along its length, and that as a consequence of the angle a may also vary depending on the particular section of the endoprosthesis.

A low value of a makes it possible in particular to reduce the phenomenon of friction to the increase of the release and that the stent is better adapted to the biomechanical characteristics of the anatomical conduits. As indicated above, the phenomenon of friction, which is a feature of endoprosthesis that has a high elongation coefficient, has in fact limited the possibilities of treating lesions of small axial extensions up to now. In addition, placement operations are made easier due to the improved flexibility, positioning accuracy and freedom of movement of the release. Even in the case of a small angle of intersection between the filaments, the clinical tests reveal what is at first sight a paradoxical effect: the endoprosthesis does not tend to migrate along the axis, as the practitioner might expect. The fabrication of the endoprosthetic structure according to the invention involves a limited number of operations, which has favorable repercussions on the cost of production.

Even after the thermal treatment that determines the temperature at which the transition state is to be carried out, the current shape memory filament remains flexible and does not exhibit the rigidity of a memory filament in a trilateral fashion. : obtains a breaking strength of just 1500 N / mm2. The fabrication of the structure of an endoprosthesis according to the invention generally comprises the following operations: - producing filaments made of an alloy of not less than 1/11 anio cold-forged, braiding these metal filaments around a mandrel before annealing them in the exit portion of the die, - cutting the braid into sections, subjecting the sections of the braid, in its nominal diameter, to a thermal treatment by establishing a transition phase of the metal at a temperature equal to or lower than the body temperature. The origin of the shape memory is the existence of a reversible crystal change which is carried out during the cycles of c a 1 e n t am i n t o / e n f r i am i n t o the specimen. In the case of metals, the high temperature phase called austenitic is characterized by a high symmetry cell unit (occupies a larger volume without a mass transfer). The low temperature phase, called ma r t e n s i t i ca, has a lower symmetry cell and occupies a minimum volume. This phase can appear in different variants. In order to obtain the change from one to another of these two states in a perfectly reproducible way, it is necessary to force the martensitic into one of several equivalent variants, in such a way that the appropriate rigidity of the metal contributing to the physical structure can be obtained of the braid that forms the structure. The composition of the alloy (in which nickel is present in a proportion ranging between 52 and 562 by weight) plays an important role in determining the optimum parameters. It has been found that a small variation in the composition is sufficient to change the temperature of the treatment necessary to obtain a given martensitic transformation by several degrees. For example, a variation of 0.1% by weight of nickel causes a variation of 15 ° C in the temperature of the heat treatment. Therefore it is necessary to look for the composition as well as the treatments when it is sought to obtain a precise martensitic transformation temperature and stable effects. The braided structure is prepared by fixing it on a metal bar with a diameter in relation to the nominal diameter of the stent, or by inserting it into a hollow mold. The total undergoes a thermal treatment of between 400 and 600 ° C during an appropriate amount of time (generally in the order of 10 minutes), whose operation is followed by cooling by air. The martensitic transformation temperature is then between 30 and 40 ° C. By way of example, for an alloy with 55.7% nickel, cold forged at 40%, a treatment time of 10 minutes at 500 ° C can be applied, and maximum hardening is obtained around 37 ° C. As a function of the diameter of the filaments used, the heat treatment may, if appropriate, be repeated in order to remove the residual martensite. In comparison, the heat treatment of the ELGILOY® alloys used for the classic braided stents should be carried out in vacuum at 550 ° C and lasts for more than 4 hours. As mentioned above, the present stent is also capable of withstanding very high radial requirements. Table 1 below allows the comparison of the radial pressure resistance of various structures of e ndopr o t e s i s. The best and best known method is carried out with the help of a TNSTRON® extensometer apparatus. The specimens are raised to a temperature of 37 ° C, either using thermostatic bath or air. A very thin filament, approximately 0.10 mm in diameter, is woven around each structure. One end of this filament is fixed to the base of the apparatus and the other is fixed to the upper part of the apparatus that is removable. This upper part consists of a probe that simultaneously measures the force exerted on the specimens and the corresponding displacement. The resulting value is determined (in Newton) using a computer program.

The table clearly shows that the stents according to the invention remain close to their nominal diameters under a sufficient radial constraint to cause the stents according to the current state of the technology to almost collapse. It should be noted that the filaments of 1 / titanium used are covered, after the present heat treatment, with a layer of titanium oxide which ensures the stabilization of the metal (by way of comparison, the metal surface of the structures). of cobalt alloy should be stabilized by a subsequent treatment with phosphoric or nitric acid). The ends of conventional alloy structures are sharp and aggressive due to the stiffness of the filaments. Cases of arterial perforation or applicator cuff are common. By way of comparison, the stents provided with a structure according to the invention do not traumatize and are simple to cut, which makes it easy to adjust the length from one case to another, if necessary in the current place of an intervention, starting from from segments of a standard length, which facilitate the packing of the structure elements and the endografts themselves.

The graph in Figure 3 shows two curves obtained when measuring on an extensometer the values (expressed in Newton) of the radial force F (resistance to radial pressure) of the braided stents at different degrees (30 ° < a < 130 °) respectively of a classic cobalt alloy cable (curve A) and a nitinol cable (curve B) as in the present invention other parameters remain constant (stent diameter = 8mm, cable diameter = 0.07mm, number of wires = 24). As it becomes directly apparent from the graph, curve A shows a virtually linear relationship between the angle and the radial force F. As discussed above, the higher the value of a, the higher the elongation coefficient of the stent As a consequence, the practitioner has to make a commitment when he chooses a given value of a. Curve B, on the other hand, exhibits a virtually constant value of F between 60 ° and 90 ° (flat segment of the curve), significantly above the values in curve A, then a slightly increased value between 90 ° and 104 °.

Above 105 °, the mechanical effect of the geometry of the braided structure becomes predominant with respect to the thermal effect. The practitioner thus has a stent at his disposal which simultaneously exhibits a resistance to radial pressure and a low length decrease when it is released in place. On the other hand clinical studies in the present stent showed particularly advantageous properties of it: its cycle of hysterisis is surprisingly similar to that of one of the vessels, allowing it to comply with the variations in diameter of the vessels according to the pulsations of the heart, accompanying them in their cycle of traction - di 1 ataci ón. The present stent thus copies an active component of the circulatory system. As a consequence, the chances of rejection and other side effects are minimized. Another proven advantage is that the stent still remains close to its nominal diameter after a long time while conventional stents are known to have a tendency to dilate the walls of the vessels, causing as counter-reaction a widening of the adjacent sections of the vessel. The arteries.

Claims (8)

1. A luminal endoprosthesis comprising a braided structure with self-expanding multifilaments, radially expandable to a given nominal diameter, made of braided metal filaments of a shape memory alloy, characterized in that the structure can be compressed to a reduced diameter for its introduction into a body duct and at the time of its release spontaneously adopts, regardless of the temperature that surrounds it, the same nominal diameter, which corresponds to the diameter of an anatomical duct that is going to be treated the filaments The braided structures form one another, when the braided structure has its nominal diameter an angle a of between 30 and 95 ° - the metal of the filaments is chosen from a rupe consisting of nickel / titanium alloys and nickel / titanium / cobalt alloys , with a proportion of nickel of between 52 and 56% by weight, the structure is treated with heat so that the metal of all the fil catkins undergoes a complete and stable transition phase taking it from a given rigidity to a greater rigidity at a temperature equal to or lower than the body temperature but higher than the ambient temperature.

2. The endoprosthesis according to the indication 1, characterized in that the angle a is between 50 and 90 °.

3. The endoprosthesis according to one of the rei indications 1 to 2, characterized in that the shape memory alloy of the filaments is uperelastic.

4. The stent according to one of the preceding claims, characterized in that the angle α varies along the length of the braid.

5. A method for manufacturing an endoprosthesis according to one of the claims is precedent, comprising the following operations: selecting a memory alloy of elastic form from the group consisting of alloys of not less than 1/111 anion and alloys of n / a / 1 / tita ni o / coba 11 oy comprising between 52 and 56% by weight of nickel, - produce filaments of this alloy, braid these filaments around a mandrel in such a way that a braid of a nominal diameter is obtained that corresponds substantially to the diameter of an anatomical duct to be treated, the filaments form an angle a between 30 ° and 95 ° to each other, subjecting the sections of this braid, in this nominal diameter, to a thermal treatment that establishes a complete and stable transition phase that causes the metal of the latter to change from a given rigidity to a higher rigidity, to a temperature equal to or lower than the body temperature, to place a re optionally in the structure, cut the braid sections into segments of appropriate length.

6. The method according to claim 5, characterized in that the braiding is carried out using nickel / titanium filaments cold-forged from a die, and in which part of the heat treatment comprises at least one heating operation in an area between 400 ° and 600 ° C, and cooled by air.

7. The method according to claim 5, characterized in that the heat treatment is carried out at 500 ° C for 10 minutes.

8. The method according to one of claims 5 to 7, characterized in that the braiding is carried out in such a way that the angle ex varies along the length of the braid.