DE10230720A1 - Implant for use in human or animal, e.g. stent, has surface of e.g. glass, glass ceramic, cermet or metal alloy with low angle of contact with water and coating containing albumen - Google Patents

Abstract

Implant for use in humans or animals comprises a material (I) with surface having angle of contact with water less than 50 degrees and provided with substance containing albumen. (I) is selected from: (a) material containing e.g. boron, silicon, phosphorus, iron and/or chromium; (b) cermet containing sub-group 4, 5 and/or 6 metal(s);or (c) specified steel or cobalt or titanium alloy. Implant for use in humans or animals comprises a material (I), the surface of which has an angle of contact with water less than 50 degrees and is provided with a substance containing albumen. (I) is selected from: (a) a material containing boron (B), silicon (Si), phosphorus (P), iron (Fe), chromium (Cr), aluminum (Al), magnesium (Mg), tantalum (Ta), calcium (Ca), potassium (K), germanium (Ge), arsenic (As) and/or antimony (Sb); (b) a material with cermet structure, which contains sub-group 4, 5 and/or 6 metal(s) and also oxygen (O), nitrogen (N) and/or carbon (C); or (c) a steel containing Fe, Cr, cobalt (Co), molybdenum (Mo), tungsten (W), titanium (Ti) and/or nickel (Ni), a cobalt (Co) alloy containing Cr, Mo, Ni, Fe, Si, manganese (Mn), P, sulfur (S), W and/or Ti or a Ti alloy containing Al, vanadium (V) and/or Fe. Independent claims are also included for methods of producing the implant.

Description

The invention relates to an implant, such as a stent, a process for its manufacture and its use.

Modern biomedical science is characterized by the fact that natural organic liquids and tissue with artificial objects be brought into contact to imitate defined physiological processes or to influence. Examples include the use of implants, extracorporeally used medical devices or the in vitro breeding of certain Tent cultures in an artificial environment.

The principle applies, the higher the compatibility between the natural and the artificial substance the better the result. Relates to biocompatibility thus on the specific use of a technically defined Materials in a physiologically defined environment with the aim of support or replace specific physiological functions. For example, the ideal surface an orthopedic Design the prosthesis so that it grows in as quickly as possible possible in the bone is, but at the same time should be a low risk of infection consist. The biological compatibility of a stent for coronary arteries would be then optimal if he has little or no thrombogenicity and the function of the cells in the immediate vicinity, e.g. of the endothelial cells not at all or as little as possible is affected, in particular the proliferation of the cells the so-called intimal layer of the vessel wall can be avoided.

Another achievement in the modern medicine is the temporary substitution of organs or their Functions through medical devices e.g. Hemodialysis, cardiac bypass or extracorporeal membrane oxygenation (ECMO). There is also one here direct relationship between biocompatibility and the incidence of Part of life-threatening complications, such as hemolysis or hemorrhagic Complications from iatrogenic anticoagulation.

There have been in the past few years many approaches to solve the problems described, at least in part. So the group around Dunn et al. 1994 (Ciprofloxacin Attachment to Porous-Coated Titanium Surfaces, D.S. Dunn, S. Raghavan, R.G. Volz, Journal of Applied Biomaterials, Vol. 5, 325-331, 1994) a titanium surface Modify to deposit the antibiotic ciprofloxacin.

Narrowing of coronary arteries in particular is increasingly being treated today by the implantation of stents. These stents are made of medical grade stainless steel, tantalum, nitinol or titanium (see DE-A-195 33 682 . DE-A-196 53 708 , Characteristics of metals used in implants, I. Gotman, J. Endourol., 11 (6): 383-389; and US-A-5,356,433 ). When used, however, two serious complications can arise. On the one hand, the metal activates blood coagulation. This can lead to occlusion of the stent by thrombosis, especially within the first four days after implantation. The second problem with the use of coronary stents is restenosis due to intimal hyperplasia. The coronary artery is made up of the three layers of tissue, intima, media and adventitia. The intima consists of endothelial cells that line the vascular lumen and are in direct contact with the bloodstream. It is delimited by the so-called lamina fibrosa interna from the media, which consists of smooth muscle cells. The outer layer, adventitia, then forms the connection between the vessel and the surrounding tissue. Histological studies show that the insertion of stents leads to a lesion of the endothelial layer of the intima and in particular of the internal lamina fibrosa. The body reacts to this irritation with an overgrowth of intimal cells, the so-called intimal hyperplasia, which can be so strong that the vascular lumen within the stent is closed again.

Technically, attempts have been made to reduce the tendency to thrombosis and / or intimal hyperplasia by means of various stent coatings. So revealed EP-A-0 836 839 a gold layer on a stent. In Antithrombogenic Coating of Stents Using a Biodegradable Drug Delivery Technology, R. Herrmann, G. Schmidmaier, B. Märkl, A. Resch, I. Hähnel, A. Stemberger, E. Alt; Thromb Haemost, 82, 51-57, 1999 discloses stents with steel or gold surfaces which are coated with biodegradable polylactic acid. The article Local drug delivery of argatroban from a polymeric-metallic composite stent reduces platelet deposition in a swine coronary model, KR Kruse, JJ Crowley, JF Tanguay, RM Santos, DS Millare, HR Phillips, JP Zidar, RS Stack, Catheter Cardiovasc Interv ., 46 (4), 503-7, 1999 relates to a polymer-metal stent which is provided with argatroban. In addition to the anticoagulant heparin ( DE-A-195 33 682 ) the anti-proliferative agent taxol and the anti-inflammatory substance dexamethasone were applied to stents, cf. Antiproliferative stent coatings: Taxol and related compounds, C. Herdeg, M. Oberhoff, KR Karsch, Semin Interv. Cadiol., 3, (3-4), 179-9, 1998; and anti-inflammatory stent coatings. Dexamethasone and Related Compounds, SH Park, AM Lincoff Semin. Interv. Cardiol., 3 (3-4): 191-5, 1998. A stent that has been coated with a layer of silicon carbide has also been studied in clinical trials the reduction of endothelial proliferation and platelet activation was examined, cf. Silicon carbide-coated stents: clinical experience in coronary lesions with increased thrombotic risk, B. Heublein, C. Ozbek, K. Pethig, J. Endovasc. Surg., 5 (1), 32-6, 1998; and Silicon-carbide coated coronary stents have low platelet and leukocyte adhesion during platelet activation, SH Monnink, AJ van Boven, HO Peels, I. Tigchelaar, PJ deKam, HJ Crijns, W. van Oeveren, J. Investig. Med., 47 (6), 304-10, 1999.

Coated stents are also described in Coated stents: local pharmacology, V.K. Raman, Edelman E.R., Semin. Interv. Cardol., 3 (3-4), 133-7, 1998; In vivo evaluation of a fluorine-acrylic-styrene-urethane-silicone antithrombogenic coating material copolymer for intravascular stents, T. Matsuhashi, H. Miyachi, T. Ishibashi, K. Sakamoto, A. Yamadera, Acad. Radiol., 3 (7), 581-8, 1996; and antithrombogenic coating of stents using a biodegradable drug delivery technology, R. Herrmann, G. Schmidmaier, B. Märkl, A. Resch, I. Hahnel, A. Stemberger, E. Alt, Thromb. Haemost., 82 (1), 51-7, 1999.

In addition to these approaches, attempts have also been made to use surfaces to coat covalently modified albumin, cf. The Potent Platelet Inhibitory Effects of S-Nitrosated Albumin Coating of Artificial Surfaces, N. Maalej, R. Albrecht, J. Loscalzo, J.D. Folts, J.A.C.C., 33 (5), 1408-1414, 1999; and adherence and Proliferation of Endothelial Cells on Surface-Immobilized Albumin-Heparin Conjugate, G.W. Bos, N.M. Scharenborg, A.A. Poot, G.H.M Engbers, J.G.A. Terlingen, T. Beugeling, W.G. Van Aken, J. Feijen, Tissue Engineering, 4 (3), 267-279, 1998. In Hydration and preferential molecular adsorption on titanium in vitro, K.E. Healy and P. Ducheyne, Biomaterials 1992, Vol. 13, No. 8, 553-561, was the behavior of titanium towards human serum by means of surface spectroscopy examined.

None of the methods developed so far in the market to a convincing Product led. While the occurrence of stent thrombosis by systemically administered Medications, so-called platelet aggregation inhibitors, are currently sufficient there is good treatment for restenosis due to intimal hyperplasia still no satisfactory therapy.

The invention was therefore the object based on the known implants and their manufacturing processes to further develop that implants are obtained at which the above-mentioned disadvantages not or only in a significantly reduced Scope occur.

To solve this problem, a Proposed implant that includes a defined material on the surface there is albumin. The albumin is in the form of an albumin-containing Substance on this surface applied. Before it is applied to the surface, it has a contact angle for water less than 50 °.

• (a) einem Bor-, Silizium-, Phosphor-, Eisen-, Chrom-, Aluminium-, Magnesium-, Tantal-, Kalzium-, Kalium-, Germanium-, Arsen- und/oder Antimon-haltigen Material,
• (b) einem Material mit einer Cermet-Struktur, das wenigstens eines der Metalle der 4., 5. und 6. Nebengruppe des Periodensystems und zudem Sauerstoff, Stickstoff und/oder Kohlenstoff enthält, und
• (c) einem Eisen-, Chrom-, Kobalt-, Molybdän-, Wolfram-, Titan- und/oder Nikkel-haltigen Stahl, einer Chrom, Molybdän, Nickel, Eisen, Silizium, Mangan, Phosphor, Schwefel, Wolfram und/oder Titan enthaltenden Kobaltlegierung oder einer Aluminium, Vanadium und/oder Eisen enthaltenden Titanlegierung.

The invention thus relates to an implant for use in the human or animal body, which is characterized in that it comprises a material whose surface has a contact angle for water of less than 50 ° and on whose surface there is an albumin-containing substance, the material is selected from

• (a) a material containing boron, silicon, phosphorus, iron, chromium, aluminum, magnesium, tantalum, calcium, potassium, germanium, arsenic and / or antimony,
• (b) a material with a cermet structure, which contains at least one of the metals of the 4th, 5th and 6th subgroup of the periodic table and also contains oxygen, nitrogen and / or carbon, and
• (c) a steel containing iron, chromium, cobalt, molybdenum, tungsten, titanium and / or nickel, a chromium, molybdenum, nickel, iron, silicon, manganese, phosphorus, sulfur, tungsten and / or Titanium-containing cobalt alloy or an aluminum, vanadium and / or iron-containing titanium alloy.

The invention also relates to a method for producing an implant, in which at least partially at least one layer containing boron, silicon, phosphorus, iron, chromium, aluminum, magnesium, tantalum, Contains glasses containing calcium, potassium, germanium, arsenic and / or antimony or glass ceramics or a cermet which contains at least one of the metals of the 4th, 5th and 6th subgroup of the periodic table and also contains oxygen, nitrogen and / or carbon , or also several layers of different materials from the above-mentioned material groups, is applied to produce a contact angle for water of less than 50 °, and then an albumin-containing substance is at least partially applied to the coated substrate. Furthermore, the invention relates to a method for producing an implant, in which at least partially at least one layer, the boron, silicon, phosphorus, iron, chromium, aluminum, magnesium, is applied to a substrate by means of a sol-gel method - Contains, tantalum, calcium, potassium, germanium, arsenic and / or antimony-containing glasses or glass ceramics, is applied to produce a contact angle for water of less than 50 ° and then at least partially an albumin-containing substance on the coated substrate is applied. In addition, the invention relates to a method for producing an implant, in which a material selected from iron, chromium, cobalt, molybdenum, tungsten, titanium and / or Nickel-containing steels, cobalt alloys that contain chromium, molybdenum, nickel, iron, silicon, manganese, phosphorus, sulfur, tungsten and / or titanium, or titanium alloys that contain aluminum, vanadium and / or iron to create a contact angle for water is roughened from less than 50 ° and an albumin-containing substance is at least partially applied to the roughened surface.

The invention also relates on the use of the item for implantation, insertion or Attachment in or on the animal or human body. preferred Embodiments of the Invention are in the following description of the figure Examples and the subclaims are described.

The figure shows the determination schematically of the contact angle.

As an implant in the sense of the invention every device should or any device understood in human or animal body implanted or longer- or introduced at short notice or can be attached to the human or animal body. Examples include: catheters, probes, sensors, stents, artificial Heart valves, endotracheal tubes or pacemakers.

In the present case, the contact angle, which is also referred to as the wetting angle or wetting angle, is determined in accordance with the equation (Young's equation) given in the figure. Here θ denotes the contact angle, σ _S and σ _L the surface tension of the solid or liquid, in the present case of water, and σ _SL the solid / liquid interfacial tension. The contact angle is determined here under normal conditions, ie room temperature (25 ° C) and normal pressure (1.013 bar). To determine the contact angle, all common devices commercially available for this purpose, for example the contact angle measuring device G10 or the drop contour analysis system DSA10, each from the company KRÜSS, Hamburg, can be used.

According to the invention, the contact angle is for water less than 50 °, preferably 30 ° or smaller, more preferred less than 20 °, in particular less than 10 °, each based on the surface of the material before applying the albumin-containing substance.

It is preferably the material either by at least one material selected from boron, Silicon, phosphorus, iron, chromium, aluminum, magnesium, tantalum, Glasses containing calcium, potassium, germanium, arsenic and antimony or Glass ceramics, or selected from cermets from metals of the 4th, 5th and / or 6th subgroup of the Periodic table that contains oxygen, nitrogen and / or carbon included, or a material selected from iron, chromium, cobalt, Molybdenum-, Tungsten, titanium and / or nickel-containing steels, cobalt alloys, the Cobalt, chrome, molybdenum, Nickel, iron, silicon, manganese, phosphorus, sulfur, tungsten and / or Contain titanium, or titanium alloys, the titanium, aluminum, vanadium and / or Iron and optionally carbon, oxygen and / or nitrogen contain.

In particular come as a material Boron, silicon, phosphorus, iron, chromium, aluminum, magnesium, Contains tantalum, calcium, potassium, germanium, arsenic and / or antimony glasses or glass ceramics in question.

All glasses are suitable as glasses at least one of the elements selected from boron, silicon, phosphorus, Iron, chrome, aluminum, magnesium, tantalum, calcium, potassium, germanium, Contain arsenic and antimony. Technical glasses are preferably used, for example borosilicate or aluminosilicate glasses.

Bioactive are also suitable glasses, such as B. 45S5, 45S5-F, 45S5-B5, 52S4.6 or Ceravital.

A glass is defined by the fact that there are very small ordered areas - so-called crystallites - in the glass, which are interconnected via disordered areas. These crystallites can be of very different types and, depending on the particular composition of the glass, can consist of silicates and the crystalline modifications of SiO ₂ (or another glass former) or corresponding mixed crystallites. I.e. that glasses, like liquids, only have short-range orders within the smallest structural units (the crystallites). Long-range orders, as they have crystals, are completely absent.

A glass is built from the so-called "Network builder" and "network converters".

• 1. Die Koordinationszahlen gegenüber dem Sauerstoff betragen 3 oder 4.
• 2. Die Polyeder aus 3 oder 4 Sauerstoffatomen, die um ein Zentralatom angeordnet sind, dürfen nur über die Ecken, nicht über die Flächen oder Kanten miteinander verknüpft sein. Mindestens drei Ecken eines Polyeders müssen mit anderen Polyedern gemeinsam sein.
• 3. Jedes Sauerstoffatom kann im Netzwerk nur an zwei Kationen gebunden sein.

The network builders are able to form a glass structure on their own. The best known network builder is SiO ₂ . In addition, z. B. B ₂ O ₃ , Al ₂ O ₃ , P ₂ O ₃ , BeF, LiF, KNO ₃ and Ca (NO ₃ ) ₂ network formers. Connections that meet the following conditions are referred to as network formers:

• 1. The coordination numbers with respect to oxygen are 3 or 4.
• 2. The polyhedra consisting of 3 or 4 oxygen atoms, which are arranged around a central atom, may only be linked to one another via the corners, not via the faces or edges. At least three corners of a polyhedron must be common to other polyhedra.
• 3. Each oxygen atom in the network can only be bound to two cations.

As network converters are mostly other metal oxides are used, which are themselves unable to To form glass structure, but which are built into the glass network can.

The best-known network converter is Na ₂ O. When installed, the Si-O bridges are weakened, so that the melting point drops.

Set the most common types of glass composed of mixtures of network builders and network converters. Sometimes different network formers are mixed.

Glass ceramics are controlled by Crystallization of glasses manufactured. They are characterized by a structure in which larger crystallites grew from the small crystallites of the glass phase are that are still surrounded by a glassy residual phase.

Common is z. B. the glass ceramic Bioverit (SiO2 40–50%, Al2O3 25-30%, MgO 10-15%, K2O, Na2O, F each about 5%).

Cermets are ceramics in which finely divided metallic clusters are embedded.

It is preferably the used metal alloys around iron, chromium, cobalt, molybdenum, tungsten, Steels containing titanium and / or nickel. Cobalt alloys can also Chrome, molybdenum, Nickel, iron, silicon, manganese, phosphorus, sulfur, tungsten and / or Contain titanium, used as material. Titanium alloys, the aluminum, vanadium and / or iron and additionally carbon, oxygen and / or contain nitrogen can be used. It also exists the possibility, the surface using one of these materials through an ion implantation procedure to enrich one or more of these elements.

Also suitable as a material to manufacture the implant all of the above-mentioned metal alloys, the on a smooth surface a contact angle for Have water less than 90 °. If this condition is met is, lets the surface Modify these materials by roughening so that the contact angle for water reduced below a value of 50 ° can be. The prerequisite is that the roughness by a statistical Distribution of deviations from the middle level marked and the standard deviation of this distribution is in the range of 0.5 to 50,000 nm, preferably from 10 to 1200 nm.

All steels are suitable as steels at least one of the elements selected from iron, chromium, cobalt, Molybdenum, Contain tungsten, titanium and / or nickel. High alloys are preferred steels used, for example 316LVM ASTM F55-82, 316L ASTM F138-86 or X2CrNiMoN25.7.4. The composition of these steels is listed in Tab. 1.

Tab. 1: Composition of high-alloy steels in% by weight

Cobalt alloys are also suitable, such as Endocast (ASTM F75-82), Vitallium FHs (ASTM F90-82), Syntacoben (ASTM F563-83) or Protasul 10 (ASTM F562-78).

Tab. 2: Composition of cobalt alloys in% by weight

Titanium alloys are also suitable, such as cp-titanium (ASTM F67-83), TiAl6V4 (ASTM F136-79), TiAl5Fe2.5 or TiAl6Nb 7 (IMI 367).

Tab. 3: Composition of titanium alloys in% by weight

In a preferred embodiment According to the invention, the implant comprises a substrate that is at least partially, preferably complete, covered with at least one layer that contains the material. The thickness of the layer is preferably in the range between 0 and 5 μm, further preferably from 50 to 3000 nm, very preferably from 100 to 1000 nm. Such a layer thickness ensures that bends of the respective implant without damage can be tolerated.

The layer is a thin layer on a substrate. Suitable substrates are made of a metal such as molybdenum, silver, gold, copper, aluminum, tungsten, nickel, chromium, zirconium, titanium, hafnium, tantalum, niobium, vanadium, iron or their mixtures or alloys, in particular stainless steel, cobalt alloys, titanium alloys or Nitinol, or from a polymer such as polyester, polyamide, polyurethane (PU), polyethylene (PE), polytetrafluoroethylene (PTFE) or DACRON ^® . The substrate preferably consists of stainless steel, in particular medical stainless steel, tantalum, nitinol, titanium, gold or a polymer. The layer is preferably applied to a rough substrate surface, the roughness of which is characterized by a statistical distribution of the deviations from the mean level and the standard deviation of this distribution lung is in the range of 0.5-50000 nm, preferably 10-1200 nm.

In a preferred embodiment an intermediate layer is provided between the substrate and the layer, the one higher Adhesion causes. This intermediate layer consists of a Metal, preferably a metal of the 4th, 5th, 6th, 10th or 11th Subgroup of the periodic table or alloys of these metals or a semiconductor, e.g. Silicon. To increase the adhesive strength is a graded layer is also possible as an intermediate layer, in the oxygen, nitrogen or / and from the substrate to the layer Carbon with increasing concentration during the coating (application of the intermediate layer) built into the metals of the intermediate layer become. It is also conceivable that the composition of an alloy of several metals, preferably of 2 metals from the substrate to the shift changes continuously.

Suitable substances containing albumin are albumin alone or albumin along with other organic ones Substances, for example fibrinogen; heparins; collages; Blood proteins, e.g. alpha-2-globulin; Immunoglobulins such as IgG, IgM, IgE, IgA as well Complement system proteins, cytokines, interleukins and interferons; Glycoproteins such as ferritin and lactoferrin; Saliva proteins like Lysozyme, IgA2, mucin and glandulin; and / or alpha-1 proteinase inhibitors. Most preferred is albumin alone. Albumin is a water-soluble, highly hydrated, difficult to salt out protein body of elliptical shape with a molecular weight of about 660,000, with a proportion of sulfur-containing amino acids, an isoelectric point of 4.6 and ampholytic behavior. Particularly suitable albumins are human albumin, bovine albumin, pig albumin, Chicken albumin, Dog albumin, albumin from cat, monkey, guinea pig, mouse, turkey, Hamster, rhesus monkey, or sheep. Most preferred is human albumin.

The layer is at least partially preferably complete, covered with the substance containing albumin.

The object of the invention reduces the Foreign body reaction and allows a variety of desired properties to be created. So will for example by the modification of the surface of a Medical stainless steel stents for restenosis and hyperplasia towards the intima not modified according to the invention Stents made from the same substrate material significantly (up to 50%) reduced. The proliferation of the endothelial cells is also evident reduced. The inventive modification of the surface of a The implant can also increase the adhesion of bacteria and thus the development of inflammation be significantly reduced.

Several methods are suitable for producing the implant. If the material is a boron, silicon, phosphorus, iron, chromium, aluminum, magnesium, tantalum, calcium, potassium, germanium, arsenic and / or antimony-containing glass or glass ceramic or a Cermet of the 4th, 5th and / or 6th subgroup of the periodic table used, this can be applied to the substrate by means of a coating process. Appropriately, the coating method used is PVD (physical vapor deposition), CVD (chemical vapor deposition), PECVD (plasma enhanced chemical vapor deposition), ion plating, a plasma spraying method or an electrochemical method, in particular a PVD method such as reactive vapor deposition, sputtering, ARC- Evaporation or reactive plasma processes performed. The in DE-A-195 06 188 or DE-A-199 50 386 described method. The following method is particularly suitable for applying the layer to the substrate: The substrate is positioned in a vacuum chamber and heated to 20 to 500 ° C., preferably to 100 to 400 ° C., particularly preferably 200 to 350 ° C. For the coating is in the chamber by means of evaporation, preferably electron beam evaporation, under a vacuum of 10 ^- mbar ^2, preferably from 10 ^-4 to 10 ^{- - 6} to 10 ² mbar, particularly preferably from 10 ^{- 4} to 5 × 10 ^{- 3} × mbar or, preferably, from 10 ^-6 to 10 ^-4 mbar, particularly preferably from 10 ^{- from 6} to ^10-5 mbar, the glass or glass-ceramic as defined above is evaporated. The generation of the desired contact angle lies in the technical skill. For example, it can be adjusted by the pressure or the reactive gases introduced during the coating.

The applied to the substrate Layers can shortly after application and removal from the vacuum chamber be chemically unstable and undergo an aging process. So can the surface reoxidize the layer by reaction with atmospheric oxygen. This can change the contact angle over a certain period of time. The Albuminous substance is therefore at a defined time applied, in which the desired Contact angle is reached.

Alternatively, a boron, silicon, Phosphorus, iron, chromium, aluminum, magnesium, tantalum, calcium, Glass containing potassium, germanium, arsenic and / or antimony or Glass ceramics can also be applied by a sol-gel process, as described, for example, in C. J. Brinker and G. W. Scherer, Sol-Gel Science: The Physics and Chemistry of Sol-Gel Processing (Academic Press, Inc .: New York, 1990); C. J. Brinker and G. W. Scherer, J. Non-crystalline solids. 1985, 70, 301-322; and M. Prassas and L. L. Hench, in: Ultrastructure Processing of Ceramics, Glasses, and Composites; eds. L. L. Hench and D. R. Ulrich, (John Wiley & Sons: New York, 1984) pp. 100-125. Through suitable process control can the contact angle for Water should be set so that it is less than 50 °.

If a cermet is used as the material, the metals of the 4th, 5th and / or 6th subgroup of the periodic table used, this can, for. B. applied by sputtering, ARC evaporation or plasma spraying the.

As the direct to the albumin substance adjacent, using one of the coating processes defined above or the layer applied by the sol-gel method should be in the sense of Invention can also be understood as a layer after its application by means of the coating process by breaking the vacuum or after application using a natural sol-gel process Aging process, preferably in air or bearings under normal conditions, has been subjected, whereby the contact angle changes or can change.

If the material is an iron, chromium, cobalt, molybdenum, tungsten, titanium and / or nickel-containing steel, a chromium, molybdenum, nickel, iron, silicon, manganese, phosphorus, sulfur, tungsten and / or Titanium-containing cobalt alloy or an aluminum, vanadium and / or iron-containing titanium alloy, it is preferably roughened. The desired contact angle can be set by a person skilled in the art by generating a defined roughness. The roughening can be carried out by sandblasting, chemical or electrochemical etching with a solution containing HF, HCl, H ₂ O ₂ , HNO ₃ , CrO ₃ , NaOH and / or H ₂ O, or plasma etching or a combination of these methods. In a preferred embodiment, the roughened surface is treated with a solution containing hydrofluoric acid (HF), HCl, H ₂ O ₂ , HNO ₃ , CrO ₃ , NaOH and / or H ₂ O before applying the albumin-containing substance.

On the coated with the material Then substrate or the roughened surface of the material at least partially applied the albumin-containing substance. By The contact angle can change over an aging process of the material change certain period. The substance containing albumin is therefore at a defined point in time applied, in which the desired Contact angle is reached. According to the invention at the time of application the albuminous substance the contact angle for water on the surface of the Material less than 50 °.

In a preferred embodiment the substance becomes the same or soon after the layer rises or the generation of the roughened surface. Preferably this takes place from 1 minute to 1 week, particularly preferably 1 minute up to 5 hours after applying the layer or removing the coated substrate from the vacuum chamber or roughening.

Appropriate methods of application the substance in solution are immersion and spraying. The substance is convenient by introducing the coated substrate or the roughened surface applied in a solution containing the albumin-containing substance. suitable solutions contain 1 to 70 wt .-%, preferably 1 to 40 wt .-%, in particular 1 to 35% by weight of the substance, based on 100% by weight of solution. Prefers will be a solution with 1 to 30% by weight of human albumin, in particular 1 to 15% by weight of human albumin, based on 100 wt .-% solution, used. In addition to the substance described above, the solution contains water, optionally other proteins or organic substances and optionally salts, Electrolytes and / or buffers. In addition to a solution to the Application also available as a powder, e.g. by heat shock or (salt) crystallization was generated. In this case it will Powder spread over the layer or the roughened surface and then stored the implant in a humid chamber. It exists also the possibility that parts of the substance are denatured (i.e. that the chemical Structure of the albumin or other organic substances contained changed has) are what extends the range of applications. It also exists the possibility, that the albumin-containing substance has depot substances, e.g. anticoagulant Substances or antibiotics are added, which are then continuous released into the body when implanted. By insert of antibiotic or pharmacologically active agents that can Implant to the chemophysical conditions at the implantation site adjusted in the body become.

When applying the substance through Immerse yourself in a solution the implant is there for a few seconds to several days at temperatures from –12 up to + 20 ° C, preferably from 1 to + 7 ° C, kept. The item can be stored in the solution in stores come. In this form it is stable for at least 1 month.

In a preferred embodiment According to the invention, the implant is designed as a stent.

The object according to the invention can be used for implantation, introduction or used in or on the human or animal body become.

The invention will be more apparent from the following Examples, the preferred embodiments represent the invention, closer explains without restricting its scope.

example 1

A medical steel stent is placed in a vacuum chamber, such as in the DE-A-195 06 188 or DE-A-199 50 386 disclosed. Window glass (together settlement: 70-75% SiO ₂ , 0.5-3.1% Al ₂ O ₃ , 5-14% CaO, 0-12% MgO, 12-17% Na ₂ O or Ka ₂ O) at a rate of 5–10 Å / sec evaporated, creating an approximately 2 μm thick layer on the stent. Evaporation typically takes place at a pressure between 10 ^-6 and 10 ^-5 mbar. The contact angle of this layer for water is initially less than 5 ° and increases to 40 ° within 40 days when stored dry at 20 ° C (without having previously treated it with the albumin-containing substance). The stent was incubated with 1% human albumin solution (in% by weight) at room temperature for a few hours, preferably a few minutes after removal from the vacuum, and then dried. The contact angle immediately before incubation was less than 5 °. After incubation with albumin solution, the sample was rinsed with phosphate buffer (PBS) and excess, unbound albumin was rinsed off.

Example 2

The procedure was as in Example 1, but silicon dioxide SiO _{2 was} evaporated instead of window glass. The contact angle for water was initially 9 ° and rose much more slowly than in Example 1, since the aging process takes place much more slowly here.

Example 3

The procedure was as in Example 1 or 2, but during the coating, oxygen is still fed into the vacuum chamber in order to additionally incorporate oxygen into the layer. It is preferred to work at an oxygen partial pressure between 10 ^-4 and 5 · 10 ^-3 mbar.

This allowed the speed of the aging process can be reduced again.

Example 4

Standard stainless steel stents (e.g. B. from Transluminia GmbH. This is made of medical grade stainless steel 316LVM. This is a high-alloy steel with 17-20% chromium, 12-14% nickel and 2-4% molybdenum content) were made with fine grain Blasting material (sand, corundum, glass beads) with an average particle size of 10-5000μm with a usual Sandblaster sandblasted. After that, the stents were for the time specified below in hydrofluoric acid (HF) submerged.

The following results were measured:

Claims (20)

Implant for use in the human or animal body, characterized in that it comprises a material whose surface has a contact angle for water of less than 50 ° and an albumin containing substance is on the surface thereof, wherein the material is selected from (a) a Boron, silicon, phosphorus, iron, chromium, aluminum, magnesium, tantalum, calcium, potassium, germanium, arsenic and / or antimony-containing material, (b) a material with a Cermet structure, which contains at least one of the metals of the 4th, 5th and 6th subgroup of the periodic table and also oxygen, nitrogen and / or carbon, and (c) an iron, chromium, cobalt, molybdenum, tungsten -, Titanium and / or nickel-containing steel, a chromium, molybdenum, nickel, iron, silicon, manganese, phosphorus, sulfur, tungsten and / or titanium-containing cobalt alloy or an aluminum, vanadium and / or iron-containing titanium alloy. Implant according to claim 1, characterized in that the contact angle for water is 20 ° or small ner is. Implant according to claim 1 or 2, characterized in that the material from boron, silicon, phosphorus, iron, chrome, aluminum, Magnesium um, tantalum, calcium, potassium, germanium, arsenic and / or containing antimony glass or glass ceramics selected is. Implant according to one of claims 1 to 3, characterized in that that it comprises a substrate that is at least partially at least covered with a layer is that contains the material and on which the albumin-containing substance is located. Implant according to claim 4, characterized in that the Material (a) or (b) onto the substrate of the implant by Coating process selected from PVD (physical vapor deposition), CVD (chemical vapor deposition), PECVD (plasma enhanced chemical vapor deposition), a plasma spraying process or has been deposited using an electrochemical process. Implant according to one of claims 1 to 4, characterized in that that the material (a) was applied by a sol-gel process is. Implant according to one of the preceding claims, characterized characterized that the material was roughened. Implant according to claim 7, characterized in that the roughening by sandblasting, chemical or electrochemical etching with a solution containing HF, HCl, H ₂ O ₂ , HNO ₃ , CrO ₃ , NaOH and / or H ₂ O, or plasma etching or a combination of these procedures has been performed. Implant according to one of the preceding claims, characterized characterized that the albumin-containing substance in addition to the albumin contains other organic substances. Implant according to one of the preceding claims, characterized characterized that it is designed as a stent. Method for producing an implant according to one of claims 1 to 5, 9 or 10, characterized in that on a substrate by means of of a coating process at least partially at least one Layer containing boron, silicon, phosphorus, iron, chromium, aluminum, Magnesium, tantalum, calcium, potassium, germanium, arsenic and / or Glasses containing antimony or contains glass ceramics or a cermet containing at least one of the metals of the 4th, 5th and 6. Subgroup and also oxygen, nitrogen and / or carbon contains applied to produce a contact angle for water of less than 50 ° and then on the coated substrate at least partially containing albumin Substance is applied. Method for producing an implant according to one of claims 1 to 4, 6, 9 or 10, characterized in that on a substrate by means of a sol-gel process at least partially at least one layer, the boron, silicon, phosphorus, iron, chromium, aluminum, magnesium, Contains tantalum, calcium, potassium, germanium, arsenic and / or antimony glasses or contains glass ceramics, applied to produce a contact angle for water of less than 50 ° and then on the coated substrate at least partially containing albumin Substance is applied. A method according to claim 11, characterized in that as Coating process PVD (physical vapor deposition), CVD (chemical vapor deposition), PECVD (plasma enhanced chemical vapor deposition), a plasma spraying process or an electrochemical process is used becomes. The method of claim 13, characterized in that the substrate of the implant at a pressure of 10 ^{- From 6} to ^10-2 mbar is coated with the material. Method for producing an implant according to one of claims 1, 2, 7, 8, 9 or 10, characterized in that a material selected from Iron, chromium, cobalt, molybdenum, Containing tungsten, titanium and / or nickel steels, Cobalt alloys, the chromium, molybdenum, nickel, iron, silicon, Contain manganese, phosphorus, sulfur, tungsten and / or titanium, or Titanium alloys containing aluminum, vanadium and / or iron, roughened to produce a contact angle for water of less than 50 ° and at least partially on the roughened surface Albuminous substance is applied. A method according to claim 15, characterized in that the roughening by sandblasting, chemical or electrochemical etching with a solution containing hydrofluoric acid (HF), HCl, H ₂ O ₂ , HNO ₃ , CrO ₃ , NaOH and / or H ₂ O, or plasma etching or a combination of these methods. A method according to claim 15 or 16, characterized in that the roughened surface before the application of the albumin-containing substance with a solution, the hydrofluoric acid (HF), HCl, H ₂ O ₂ , HNO ₃ , CrO ₃ , NaOH and / or H ₂ O contains, is treated. Method according to one of claims 11 to 17, characterized in that that the albumin-containing substance by introducing it into an albumin containing solution is applied. A method according to claim 18, characterized in that the solution Contains 0.5 to 40 wt .-% albumin, based on 100 wt .-% solution. Use of an implant according to one of claims 1 to 10 for implantation, introduction or attachment in or on the human or animal body.