WO2002094332A1 - Dispositif medical - Google Patents

Dispositif medical Download PDF

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Publication number
WO2002094332A1
WO2002094332A1 PCT/DE2002/001856 DE0201856W WO02094332A1 WO 2002094332 A1 WO2002094332 A1 WO 2002094332A1 DE 0201856 W DE0201856 W DE 0201856W WO 02094332 A1 WO02094332 A1 WO 02094332A1
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WO
WIPO (PCT)
Prior art keywords
ions
substrate
medical device
foreign
stent
Prior art date
Application number
PCT/DE2002/001856
Other languages
German (de)
English (en)
Inventor
Manfred GÜLCHER
Martina Nissl
Andreas Mucha
Original Assignee
Qualimed Innovative Medizinprodukte Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Qualimed Innovative Medizinprodukte Gmbh filed Critical Qualimed Innovative Medizinprodukte Gmbh
Priority to KR1020037015178A priority Critical patent/KR100613951B1/ko
Priority to US10/478,342 priority patent/US20040176838A1/en
Priority to DE20220589U priority patent/DE20220589U1/de
Priority to EP02740372A priority patent/EP1389135A1/fr
Priority to DE10292142T priority patent/DE10292142D2/de
Publication of WO2002094332A1 publication Critical patent/WO2002094332A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0005—Use of materials characterised by their function or physical properties
    • A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A61F2/07—Stent-grafts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L29/123—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L31/121—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment

Definitions

  • the invention relates to a medical device for placement in a patient's body vessel according to the features in the preamble of patent claim 1.
  • the invention is related to vascular or cardiovascular stents.
  • vascular diseases are a major cause of disability and death.
  • arteriosclerosis which causes inadequate blood supply to organs.
  • Heart attack, stroke and kidney failure can result.
  • Atherosclerosis can result from a vascular injury in which the vascular smooth muscle cells of an arterial wall of a hyper undergo proliferation, penetrate into the inner vascular mucosa and spread. This can result in the vessels becoming completely blocked in the event of local blood clotting. This can lead to the death of the tissue supplied by this artery. If this is a coronary artery, this constipation can result in heart attack and death.
  • Coronary artery blockage can be treated with coronary artery bypass and / or angioplasty. Both procedures may initially be promising, but are practically useless if restenosis occurs after such treatment. It is suspected that hyperproliferation of vascular smooth muscle cells also occurs with restenosis. In a third of the patients treated by angioplasty, restenosis and closure occur within six months after treatment, whereby it has been proven that the restenosis rate is significantly increased in some patient groups (diabetics, smokers).
  • restenosis While the result of restenosis is the same (loss of intraluminal space), it is believed that the mechanism is different in the case of percutaneous transluminal coronary angioplasty (PTCA) and stenting.
  • PTCA percutaneous transluminal coronary angioplasty
  • a main cause of restenosis after PTCA is a stenotic occlusion due to elastic reshaping of the vessel wall, whereas a loss of lumen due to non-growth of the tissue cells in the intraluminal space (intimal hyperplasia) is less dominant.
  • intimal hyperplasia In the case of stented vessels, restenosis is dominant due to intimal hyperplasia.
  • the vessel After a balloon injury from angioplasty or stenting, the vessel is exposed - exposed from the endothelial layer. This leads to increased leukocyte proliferation, separated into neutrophils and mononucleocytes, in order to remove the cellular debris (scavenge). The activation of these cells leads to the release of various mediating factors (cytokines) which have been shown to induce smooth muscle cell proliferation. Lowering these factors stops proliferation. However, if the injury persists, there is no decrease, which leads to vascular hyperplasia and restenosis. The extent and type of inflammation therefore correlate directly with the extent and severity of restenosis due to cellular hyperplasia (smooth muscle cell proliferation).
  • cytokines mediating factors
  • PTCA does not induce chronic injury compared to stenting.
  • numerous foreign body reactions occurred in stented vessels.
  • High concentrations of macrophages and tissue granulation were found. This indicates that a foreign body reaction has occurred in addition to wound healing.
  • the cause may be the stent material.
  • Nitinol contains a high concentration of nickel.
  • Stainless steel contains nickel, chrome and molybdenum. Acute toxicity and cytotoxicity of ions of these metals have been demonstrated.
  • ICAM Improved Chemical Agent Monitor / intercellular adhesion molecules
  • Radioisotopes with high decay energy are used for this, so that the effect of the radiation is limited to the immediate vicinity of the stent.
  • the problem is known that the restenosis can be almost completely suppressed within the radioactive stent, but there is still a strong proliferation of tissue at the ends of the stent.
  • the negative behavior of the radioactive stents could be due to the radiation dose at the stent ends being too low due to the short range of the ⁇ radiation.
  • This problem can only be solved by increased activity at the stent ends.
  • a commonly used ball implantation catheter is approx. 2-3 mm longer on both ends than the stent, so that it is not lost when it is inserted into the stenosis. This can lead to injury to the artery wall at a relatively large distance from the stent.
  • Another approach to avoid restenosis is to introduce radioactivity before or after balloon distillation. It was shown that radiation of the vessel wall can significantly reduce cell growth after balloon distillation. The disadvantage of this is that a strong radioactive source has to be introduced into the patient's body in order to bring a correspondingly high radiation dose to the vessel wall in a short time. With this approach, the surgical team and patients are exposed to a higher radiation exposure than when using a radioactive stent with less activity.
  • Radioactive stents can be produced by the method of ion implantation, in which ions are shot into the material of the stent from a special ion source. The radioactivity is under the surface of the stent material. It is also known that stents passivate by applying layers. Certain metals, such as iron, chromium, nickel and possibly their alloys, react very slowly in the presence of a surface film that acts as a corrosion protection. Stainless steel, for example, is refined by the thin, protective chrome layer. The type of passive film depends primarily on the metal and the conditions under which the film is made.
  • an implanted medical device such as e.g. a stent placed in the patient's body, applied coatings, does not always have the desired adhesion to the substrate of the stent, so that the surface of the stent changes and metal alloys can be washed out with the substrate of the stent exposed, with those described above adverse consequences.
  • passivating layers to stents is particularly problematic because the stents are subjected to considerable mechanical stress when placed in the body lumen. Due to the different material properties of the coating and the substrate, it cannot be ruled out that cracks will appear in the coating or that the coating might even flake off.
  • the object of the invention is to provide a medical device for placement in the body of a patient which improves the passivation of the surface of its substrate and thus has more favorable biocompatible / hemocompatible properties.
  • the invention solves this problem by providing a medical device with the features of claim 1.
  • the essence of the invention is that foreign ions are embedded in the substrate of the medical device, which ions are diffusion-resistant for substrates. forming boundary layer between the surface and the interior of the substrate.
  • Ion implantation is a vacuum process in which the charged elementary particles (ions) are shot with high energy at solid surfaces.
  • the ions penetrate into the near-surface areas of the substrate in the form of metal ions, noble gas ions or as here in the form of reactive ions.
  • the plasma ion implantation no additional layer is "applied” to the substrate during ion implantation, but atomic building blocks are "introduced” under the substrate surface.
  • One advantage is the excellent dimensional accuracy of the coated surfaces. In particular, there are no problems with adhesive strength, as are known from other coating processes.
  • finish processing can, for example, be a smoothing of the surface by electrical or mechanical polishing.
  • Ion implantation is also an environmentally compatible process that is particularly harmless with regard to radiation problems, such as those that can occur with radioactive stents. Another advantage is the extremely low penetration depth of the introduced foreign ions into the substrate, so that the mechanical properties of the substrate remain largely unchanged.
  • foreign ions with relatively high energy are shot under vacuum and penetrate into the entire surface of the substrate. This means that the foreign ions either replace the free places in the lattice structure of the substrate or displace other atoms from the near-surface places of the substrate and replace these places. There is no significant enrichment of the foreign ion concentration, since only vacant and vacant lattice sites are replaced by foreign ions.
  • substrates in particular nickel ions
  • the diffusion-preventing boundary layer can therefore also be formed further away from the substrate surface inside the substrate.
  • the diffusion-preventing boundary layer is therefore not necessarily located directly on or below the surface.
  • a high energy dose is preferably selected so that substrates, in particular of the nickel element, are shifted into sufficiently deep layers.
  • the implantation energy By varying the implantation energy, it is also possible, in addition to the boundary layer formed in the interior of the substrate, to enrich the outer surface of the substrate with foreign ions such that the concentration of the foreign ions on the surface or in areas close to the surface is greater than 90%. The concentration can even be greater than 95%.
  • the biocompatibility of the substrate is decisively improved by the choice of suitable foreign ions.
  • the combination of a diffusion-preventing boundary layer in the deeper interior of the substrate with a biocompatible layer introduced directly below the surface is particularly advantageous.
  • the penetration depth of the carbon is between a few nanometers and up to approx. 20 micrometers, which is a very small penetration depth compared to the material thickness of a conventional stent that the substrate as a whole maintains its mechanical properties.
  • the device according to the invention can therefore also have a substrate with very specific physical properties, such as nitinol.
  • Foreign ions can be ions of a single element such as carbon, oxygen, nitrogen or tantalum, the latter at the same time improving the X-ray visibility. Ions of the elements mentioned have the positive property of displacing metal ions, in particular heavy metal ions.
  • the foreign ions can also be a mixture of ions of several elements, for example carbon and oxygen.
  • the decisive factor here is that this mixture of foreign ions enables the composition of the diffusion-preventing boundary layer to be specifically influenced. If foreign ions of a first element were first introduced into the medical device by ion implantation and then foreign ions of a second element, this would have the consequence that the foreign ions of the second element displace the foreign ions of the first element into deeper layers, so that the desired properties of the medical device Device may not be reached. It is therefore crucial that ions of the desired elements are implanted simultaneously and not in succession.
  • Carbon ions or carbon, analogs and / or derivatives thereof have been shown to be particularly advantageous as foreign ions, as well as oxygen ions which, because of their ability to displace heavy metal ions, can be referred to as metal ion displacers in the sense of the invention.
  • metal ion displacers in the sense of the invention.
  • foreign ions can be implanted to a depth of approximately 20 ⁇ m, but significantly smaller penetration depths can also suffice to form a sufficiently diffusion-preventing boundary layer between the surface and the interior of the substrate.
  • the surface is impermeable to ions of metals with a density higher than 4.5 g / cm 3 (heavy metals), regardless of the position of the boundary layer.
  • Metals with a density higher than 4.5 g / cm 3 e.g. iron, zinc, copper, manganese, tin, chromium, cadmium, lead, mercury, nickel
  • Suitable metals are medical stainless steels, nitinol, but also cobalt alloys with a high nickel content.
  • therapeutic agents can be used.
  • the cytostatic paclitaxel is known to be particularly effective in inhibiting some types of cancer and in effectively combating restenosis if necessary.
  • Systematic administration of paclitaxel can cause undesirable side effects. This makes local application the preferred treatment.
  • Local paclitaxel treatment can be more effective if administered over a long period of time. This period is preferably at least as long as the normal response time of the body after angioplasty.
  • Trials have shown that topical administration of paclitaxel over a period of days or even months can most effectively prevent restenosis. Such a long period of time can be replaced by a timed release from the stent.
  • a stent is in contact with the bloodstream for an extended period of time, this can cause thrombus formation, which can also narrow the inner vessel diameter.
  • a substrate surface that releases a therapeutic agent such as paclitaxel can therefore prevent restenosis, but not prevent thrombus formation. It is therefore desirable to have a stent with restenosis-inhibiting properties that can remain in the body for a longer period of time without a thrombus forming at this point.
  • a restenosis-inhibiting substance By impregnating a restenosis-inhibiting substance into a stent, in contrast to a coating applied to the stent, i.e. If it is placed under the surface, the problems of breakage, peeling and poor adhesion of the coating and thus loss of the substance that inhibits restenosis are avoided.
  • a binding agent can be provided on the substrate which inhibits the binding of anticoagulants, e.g. Heparin, to the binding agent and thus to the substrate.
  • This combination of restenosis-inhibiting substances and anticoagulants assigned to the substrate via a binding agent makes it possible to effectively prevent both restenosis and thrombus formation. It is of course also possible within the scope of the invention to assign other therapeutic agents to the substrate via a binding agent, such as cytostatics such as paclitaxel, if this makes sense from a therapeutic point of view.
  • the binding agent can also be releasably assigned to the substrate. It is therefore possible within the scope of the invention that the bond detaches itself from the substrate either after the release of the therapeutic agent or simultaneously with the release of the therapeutic agent. After detachment of the binding agent, for example after a body reaction to a z. B. caused by stenting local injury, it is primarily important to avoid allergic reactions of the body to the substrate, especially restenosis.
  • the device according to the invention fulfills this function solely through the implanted diffusion-preventing boundary layer.
  • a binding agent such as a polymeric coating, has fulfilled its intended task with the complete release of the therapeutic agent.
  • the process of detaching or dissolving is not limited to a certain period of time, but can also be long-term.
  • a preferred area for using a medical device that is provided with a restenosis-inhibiting substance is stents for coronary arteries, made of a metallic material such as, for example, nitinol or stainless steel.
  • the substrate 1 or the stent is carbonized by the previously described method of ion implantation.
  • the method described above creates an inert surface 2 by firmly integrating the foreign ions 3, which prevents diffusion of substrates 4, in particular heavy metal ions. This provides protection against allergies and inflammatory reactions and helps to avoid restenosis.
  • FIG. 2 shows the relative concentration K of implanted foreign ions 3 (C ions) and the relative concentration of Fe ions and Ni ions as a function of the depth T.
  • the depth T is measured starting from the surface 2 of the substrate 1.
  • the concentration K of the foreign ions 3 at a short distance from the surface 2 initially increases to a maximum and decreases in the further course. It is striking that the concentration of Ni ions in areas near the surface tends to zero. The concentration of Ni ions tends towards zero even at a distance from the surface, so that apart from a narrow overlap zone between C ions and Ni ions, a boundary layer 5 formed by the increased C ion concentration represents a diffusion barrier for Ni ions , Ni ions can penetrate into the boundary layer up to a certain limit value of the concentration of foreign ions 3, but cannot penetrate it, so that at least some of the substrates, namely the Ni ions, which are representative of all heavy metal ions, cannot be penetrated by the Diffuse green layer through to the surface 2 of the substrate 1.
  • the process parameters for the ion implantation are chosen in each case in such a way that a diffusion of certain substrates is avoided. Sufficient enrichment of the interface with foreign ions and a certain minimum thickness of the interface are essential. Immediately on the surface 2 in this example there are only Fe ions and C ions in approximately the same distribution. The Fe-ion concentration then increases with increasing depth and, following the boundary layer, the concentration of the Ni-ions also increases to the concentration ratios prevailing in the interior 6 of the substrate 1.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Vascular Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Transplantation (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Biomedical Technology (AREA)
  • Surgery (AREA)
  • Dermatology (AREA)
  • Materials Engineering (AREA)
  • Composite Materials (AREA)
  • Inorganic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Cardiology (AREA)
  • Pulmonology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Hematology (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

L'invention concerne un dispositif médical de placement dans le corps, en particulier dans un vaisseau chez un patient. Ce dispositif comporte un substrat (1) conçu pour un placement longue durée et dont les caractéristiques de biocompatibilité ont été modifiées par bombardement de sa surface (2) au moyen d'ions étrangers (3). Ainsi, ces ions étrangers sont stockés dans le substrat (1) et constituent une couche barrière (5) empêchant la diffusion des ions (4) du substrat, entre la surface et l'intérieur du substrat (1).
PCT/DE2002/001856 2001-05-21 2002-05-21 Dispositif medical WO2002094332A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
KR1020037015178A KR100613951B1 (ko) 2001-05-21 2002-05-21 의료장치
US10/478,342 US20040176838A1 (en) 2001-05-21 2002-05-21 Medical device
DE20220589U DE20220589U1 (de) 2001-05-21 2002-05-21 Medizinische Vorrichtung
EP02740372A EP1389135A1 (fr) 2001-05-21 2002-05-21 Dispositif medical
DE10292142T DE10292142D2 (de) 2001-05-21 2002-05-21 Medizinische Vorrichtung

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US29243401P 2001-05-21 2001-05-21
US60/292,434 2001-05-21
US34542601P 2001-10-19 2001-10-19
US60/345,426 2001-10-19

Publications (1)

Publication Number Publication Date
WO2002094332A1 true WO2002094332A1 (fr) 2002-11-28

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2002/001856 WO2002094332A1 (fr) 2001-05-21 2002-05-21 Dispositif medical

Country Status (4)

Country Link
EP (1) EP1389135A1 (fr)
KR (1) KR100613951B1 (fr)
DE (2) DE10292142D2 (fr)
WO (1) WO2002094332A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102009018013A1 (de) 2009-04-18 2010-10-21 Qualimed Innovative Medizin-Produkte Gmbh Beschichteter Stent

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US4743308A (en) * 1987-01-20 1988-05-10 Spire Corporation Corrosion inhibition of metal alloys
US5152783A (en) * 1989-09-28 1992-10-06 Sony Corporation Antithrombogenic material
EP0640353A2 (fr) 1993-08-26 1995-03-01 SMITH & NEPHEW RICHARDS, INC. Implants médicaux durcis en surface et du voisinage de la surface
US5492763A (en) 1992-06-08 1996-02-20 Spire Corporation Infection resistant medical devices and process
EP0875217A2 (fr) * 1997-04-15 1998-11-04 Advanced Cardiovascular Systems, Inc. Procédé de fabrication de prothèses métalliques poreuses renfermant des substances actives
DE19855786A1 (de) 1998-12-03 2000-06-08 Lothar Sellin Radioaktiver Carbon Stent
WO2000045892A1 (fr) * 1999-02-08 2000-08-10 Advanced Cardiovascular Systems, Inc. Procede de radiotherapie intravasculaire
US6159142A (en) * 1996-12-10 2000-12-12 Inflow Dynamics, Inc. Stent with radioactive coating for treating blood vessels to prevent restenosis
WO2001017577A1 (fr) * 1999-09-03 2001-03-15 Advanced Cardiovascular Systems, Inc. Prothese poreuse et procede de depot de substances dans les pores
US6217615B1 (en) * 1995-01-20 2001-04-17 Spire Corporation Arthroplasty process for securely anchoring prostheses to bone, and arthroplasty products therefor

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4743308A (en) * 1987-01-20 1988-05-10 Spire Corporation Corrosion inhibition of metal alloys
US5152783A (en) * 1989-09-28 1992-10-06 Sony Corporation Antithrombogenic material
US5492763A (en) 1992-06-08 1996-02-20 Spire Corporation Infection resistant medical devices and process
EP0640353A2 (fr) 1993-08-26 1995-03-01 SMITH & NEPHEW RICHARDS, INC. Implants médicaux durcis en surface et du voisinage de la surface
US6217615B1 (en) * 1995-01-20 2001-04-17 Spire Corporation Arthroplasty process for securely anchoring prostheses to bone, and arthroplasty products therefor
US6159142A (en) * 1996-12-10 2000-12-12 Inflow Dynamics, Inc. Stent with radioactive coating for treating blood vessels to prevent restenosis
EP0875217A2 (fr) * 1997-04-15 1998-11-04 Advanced Cardiovascular Systems, Inc. Procédé de fabrication de prothèses métalliques poreuses renfermant des substances actives
DE19855786A1 (de) 1998-12-03 2000-06-08 Lothar Sellin Radioaktiver Carbon Stent
WO2000045892A1 (fr) * 1999-02-08 2000-08-10 Advanced Cardiovascular Systems, Inc. Procede de radiotherapie intravasculaire
WO2001017577A1 (fr) * 1999-09-03 2001-03-15 Advanced Cardiovascular Systems, Inc. Prothese poreuse et procede de depot de substances dans les pores

Non-Patent Citations (1)

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Title
See also references of EP1389135A1 *

Also Published As

Publication number Publication date
KR100613951B1 (ko) 2006-08-18
DE20220589U1 (de) 2003-11-27
DE10292142D2 (de) 2004-04-29
EP1389135A1 (fr) 2004-02-18
KR20040011506A (ko) 2004-02-05

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