WO1999065537A1

WO1999065537A1 - Superficial implant and surface coating for stents and other implants

Info

Publication number: WO1999065537A1
Application number: PCT/EP1999/003919
Authority: WO
Inventors: Bernd Starck
Original assignee: Micro Science Medical Ag
Priority date: 1998-06-12
Filing date: 1999-06-08
Publication date: 1999-12-23
Also published as: AU4606199A; DE29810483U1

Abstract

A superficial implant or surface coating made of a material differing from that of the base material is provided for stents or other implants that are to be permanently or temporarily lodged in the human or animal body and that have a different basic body shape made of a base material owing to mechanical or geometric requirements. The invention makes it possible to combine the favorable mechanical properties of the base material with the biocompatible properties of tantalum or niobium due to the fact that the surface coating is made of tantalum or niobium.

Description

Surface implantation and surface coating for stents or other implants

description

Field of the Invention

The invention relates to a surface implantation or surface coating for stents and other implants according to the preamble of claim 1

State of the art

In current implantation technology, products such as stents, implants for healing bones (screws, plates, etc.), dental implants, cardio- and cardio-surgical implants (e.g. thoracic wires, defibrillators and pacemakers and their electrodes, coronary stents, etc.), endoprostheses, vena Cava filter, etc. used. The prior art and the exemplary embodiments are now explained using stents as examples. However, it goes without saying that such surfaces and coatings are also suitable for other implants.

Since more and more allergies are occurring in many people today, the materials used for this either cause such allergic reactions and / or exacerbate other symptoms of the implant wearer.

As Rabenseifner demonstrated in his book "Tantalum and Niobium as an Implant Material" on pages 46, 50 and 79 at the beginning of the 1980s, niobium and tantalum are the two elements that have been implanted in a living body and have produced no or the least defense reactions .

So far, (coronary) stents have been made from materials such as (full) tantalum, stainless steel, nitinol, etc. Since after a stent has been implanted in a previously narrowed coronary vessel, it will try to narrow again within 6 months with a probability of up to 45%, which is known as re-stenosis various manufacturers of such stents, by surface coating with gold, carbon, radioactive isotopes, etc., to achieve better results.

Gold and platinum are generally considered to be biocompatible. As a rule, stainless steel stents are electroplated with an approximately 5 μm thick gold layer. Modern PVD processes are an alternative to galvanic processes. In order to achieve good adhesion to the stent surface, these must first be chemically cleaned and pickled in order to be able to remove greases, dirt residues and, last but not least, the chromium oxide layer, which protects against corrosion. However, gold is noble compared to the stainless steel base material and builds up an electrical potential difference to it. As a result of this electrical potential difference (- = voltage), pore formation and crack formation in the layer can lead to pitting in the base material with the result of increased ion release into the blood, and, not least, this results in a mechanical weakening of the stent. Because e.g. If, on the other hand, a stent is expanded in the vessel at the target site, the pores and cracks, on which the pitting can attack, develop on their own.

Titanium nitride is also considered to be biocompatible. The coating is carried out using the PVD process. Titanium nitride is very hard (> 2500HV) and has a comparatively high elastic modulus. Similar to gold, similar problems occur or are exacerbated, because the low ductility of the layer compared to gold means that the layers tend to crack even more when the stent is expanded; In this respect, an increased risk of pitting in the base material must be taken into account.

Based on Rabenseifner's findings, attempts were made to overcome these problems with full tantalum stents. These full tantalum stents did not bring much better results either, since stents have to be made from full tantalum with relatively thick walls. The reason: Stents made of steel or tantalum are expanded to the vessel diameter there with the help of a balloon catheter after they have been introduced into the constriction site. Since the implanted stent is in the blood stream, the smaller the wall thickness of the stents and the more resistance that acts on the blood flowing through them, the better the results (lower re-stenosis rates). On the other hand, due to the more complex processing Possibility of full tantalum cannot achieve an extremely smooth surface, but this would be necessary for an optimized result in the implant carrier (patient). Studies have shown that the smoother the stent surface, the less blood cells can settle on it and the less the risk of restenosis.

This means that the requirements for a stent are extraordinarily high, particularly in their combination, both mechanically, biologically and hemodynamically.

Mechanically, stents require good elasticity with very good support strength. The mechanical parameters that characterize this are expressed in the elongation at break of the material and in its modulus of elasticity. The higher the modulus of elasticity, the more delicate the structure of the stent can be "designed". Among the medically relevant materials, for example, austenitic stainless steel 316 L with subgroups etc. (DIN 1.4435) has a maximum elongation at break of almost 80% and a modulus of elasticity of 210 GPa. The most favorable conditions. Other materials such as titanium or tantalum are much less favorable in this regard. With titanium, similar to tantalum, a maximum elongation at break of 30% can be set, but on average only between 10-15% Overexpansions (eg expansion through the balloon catheter) quickly lead to crack formation. The modulus of elasticity for titanium is 110-120 GPa and for tantalum 160-170 GPa. Mechanically, the classic material "stainless steel" therefore has clear advantages for this application compared to the "new materials".

Biologically and chemically, however, it is clearly inferior to them, not least because of its high nickel content of 12% (nickel allergies) and its chromium content (chromium allergies). Stainless steel stents lead to the strong formation of neointimal hyperplasia, are thrombogenic and have a thermodynamic residual risk of ion release into the surrounding biological environment.

Various stent designs have already been subjected to corrosion tests with regard to the base material used and the coatings. The so-called Machu solution, which is composed of 5% NaCl and 1% H ² O ² and is adjusted to pH 6 with acetic acid, was used as the corrosion medium. The solution represents a sharper salt spray test and may be considered to be physiologically very approximate in that the oxygen potential in the blood is taken into account by the addition of H ² 0 ² . Due to the very harsh conditions, the stents were examined by scanning electron microscopy after 30 minutes, 1 hour, 3 hours and finally 5 hours. The pitting frequency and / or surface corrosion attacks were evaluated as evaluation criteria.

As a result, it was found that the corrosion behavior of stents is related to the release of ions into the biological environment. In principle, this should be completely prevented. The biological environment reacts with a spontaneous connective tissue encapsulation of the foreign body - in this case the stent - which leads to the formation of a neointima and thus to a narrowing of the blood vessels.

Stents e.g. austenitic steel 316 L or the like have a comparatively high corrosion sensitivity. The causes are, on the one hand, the relatively inhomogeneous structure and, on the other hand, the residues of "delta" ferrite in the austenite. None of the stents customary in the market was completely "delta" ferrite.

Coatings should remedy this. A 5 μm thick gold surface is offered as a coating on the market. Gold builds up a very high pitting sensitivity to the base material, so that increased corrosion occurs especially over pores and on the rough cut surfaces. This is even stronger than with uncoated stents.

Summary of the invention

Starting from this prior art, the present invention is based on the object of combining favorable mechanical properties of the base material with the biocompatible properties of tantalum or niobium.

This object is achieved by a surface or surface coating with the features of claim 1, surface also being understood to mean a surface treated as by ion implantation. In fact, numerous studies with tantalum-based coatings have shown very good biological and chemical corrosion-protecting properties. The latest in vivo tests also confirm favorable antithrombogenic properties of these surfaces.

But especially with regard to the use of coatings for stents, several requirements are essential.

The layers should be electrochemically compatible with the base material and must not build up any pitting potential. This happens primarily with noble and electrically conductive layers such as gold or platinum. Due to the expansion of the stent, cracking and pore formation in the layer can never be completely avoided. This can lead to increased corrosion and thus ion release of the base material via the "pitting" potential.

These risks can be avoided by means of a multi-layer structure with a spontaneous self-passivating ability of the coating and last but not least by a "self-sealing" effect. The introduction of reintantal intermediate layers favors the "self-sealing" of layers in the event of cracking and pore formation and their electrically insulating self-passivation.

The layers must have exceptionally good adhesion to stainless steel. The smallest layer flaking in vivo carries the risk of embolism. The production of the layers should therefore include thermal and thermodynamic redundant safety factors. These are achieved using the PVD (Physical Vapor Depositation) process. This also minimizes the internal stresses of the layer and the base material.

Like niobium, tantalum is considered the most body-friendly metal among materials. In the following, for the sake of simplicity, reference is made to the results and findings that are available on the use of tantalum. However, it goes without saying that these results can also be applied to niobium. Accelerated wound healing has been observed in studies on tantalum implants. Besides the precious metals gold and silver, tantalum is the most chemically resistant metal, in some respects it is even more stable than the precious metals. As a layer, tantalum has the advantage over precious metals that it tends to spontaneously self-passivate while building up an electrically insulating layer. As a result, the formation of pitting potentials can be completely ruled out. Furthermore, the reactions of the metal tantalum (Ta) to its oxide or hydroxy oxide can partially or completely increase pores and cracks, depending on the size; this process is known as soap sealing. Corrosion tests confirm the exceptional protection that tantalum layers on stainless steel stents can offer.

Although pure tantalum layers have a very good biocompatibility, blood wetting tests and adsorption studies indicate a preferred adsorption of fibrinogen. Bipolar surfaces are formed by chemical bonding with nitrogen and oxygen to form tantalum oxynitrides, which leads to preferential adsorption of albumin from the blood. This creates the prerequisites for setting a surface that is both biocompatible and improved in terms of thrombogenicity.

In practice, tantalum also shows moderate x-ray contrast on stents, i.e. the stent is easily visible on the screen or image, but you can still look into the stent. This makes it easier to diagnose even stenoses in the stent than e.g. is the case with pure stainless steel stents.

In an embodiment according to claim 3, despite the previous concerns, the advantages and favorable properties of a stainless steel can now be used as the base material.

Description of a preferred embodiment

A tantalum / tantalum ceramic layer composite is applied in several layers to the base material in layer thicknesses of up to 5 micrometers or more, so that largely continuous pores to the substrate can be avoided. But even if continuous pores occur, one can speak of chemically and electrochemically dense layers: firstly due to the above-discussed soap sealing effects of the layer and secondly due to the formation of electrically insulating passive layers. The corrosion results confirm this impressively.

The disadvantages already proven by L. Rabenseifner in his publication (book "Tantalum and niobium as implant material," pages 8, 46, 49, 50 and 78) in the early 1980s that stainless steel such as 316 L is subject to corrosion in the body, which Element nickel is particularly problematic, and this leads to uncontrollable, harmful reactions, are thus eliminated. The advantages, also described in this book (page 46, 50 and 79), as well as the connections (page 46) referring to the studies by Harms and Mäusle 1980 referring to the fact that when conventional materials are implanted in the human body, they are present in all If an enclosing connective tissue membrane had formed after only 2 weeks, but no connective tissue membrane was detectable with tantalum and niobium, our invention comes into its own (the formation of a connective tissue membrane in the stent can be equated with a reduction in the flow lumen and thus possibly a restenosis).

The results of this basic research were the basis for the development of the tantalum implant surface. Since the surface hermetically encloses the 316 L base body of the stent and thus only the applied elements tantalum or niobium come into contact with body cells, at least lower body reactions can be expected with stents that have been treated in this way.

Claims

Expectations

1. Surface implantation or surface coating for stents or other implants that are permanent or temporary in human or animal

Bodies remain, with a basic body formed from mechanical or geometrical requirements from a different basic material than the surface implantation or surface coating, characterized in that the surface or surface coating is made of tantalum or niobium.

2. Surface impiantation or surface coating according to claim 1, characterized in that the base material is another metal or a metal alloy.

3. Surface impiantation or surface coating according to claim 2, characterized in that the base material is stainless steel.

4. Surface implantation or surface coating according to claim 3, characterized in that the base material is stainless steel 316 L or a

Steel from its sub-groups.

5. surface implantation or surface coating according to claim 1, characterized in that the tantalum in the tantalum ceramic layer composite is applied in several layers to the base material in layer thicknesses of several micrometers.