Classifications

• • 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
  • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
  • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
  • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheets or tubes, e.g. perforated by laser cuts or etched holes
• • 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
  • A61L31/08—Materials for coatings
  • A61L31/082—Inorganic materials
  • A61L31/088—Other specific inorganic materials not covered by A61L31/084 or A61L31/086
• • 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
  • A61L31/148—Materials at least partially resorbable by the body

Definitions

• the invention relates to stents for use in the interventional treatment of vascular diseases and vascular surgery
• Implantable stents are used in cardiology for the treatment of coronary vascular occlusions and in the interventional treatment of vascular diseases and vascular surgery, among other things for the treatment of peripheral stenoses, aneurysms, aortic dissections or accident-related vascular lesions. This could z. B. in the case of coronary stents, mortality due to acute myocardial infarctions can be significantly reduced. After implantation, the mechanical integrity of a stent must be guaranteed until the vessel is remodelled. This duration depends on the application, the type and severity of the lesion and the patient's condition.
• stent disappears from the vessel again in order to avoid late-occurring complications such as restenosis or thrombosis.
• This is not possible with stents made of classic materials such as steel.
• Bioresorbable stents based on magnesium or polymers e.g. poly-L-lactide
• a material is referred to as bioresorbable if it is degradable in the body and the degradation products are either excreted directly from the body or in the course of regular metabolic processes used or converted into forms usable by the body.
• An implant or a part of an implant formed from a bioresorbable material loses its original shape over time after implantation. During degradation, levels of the elements contained in the material may exceed normal levels in the body. After complete degradation of the material at the site of implantation, these concentrations return to normal.
• the solution according to the invention consists in a stent which is formed with two bioresorbable metallic materials.
• the stent according to the invention is formed with a tubular support structure which is formed from interconnected struts which are formed from a first bioresorbable metallic material.
• a coating formed with a second metallic bioresorbable material is formed on the surface of the struts.
• the second metallic material has a lower dissolution rate during bioresorption under physiological conditions in the implanted state and a more positive electrode potential than the first metallic material. If a first and a second metallic material have a negative electrode potential compared to a common reference electrode (e.g. standard hydrogen or calomel electrode), the absolute value of the electrode potential of the second metallic material is therefore smaller than the absolute value of the electrode potential of the first metallic material. Under physiological conditions, the electrode potential of the second metallic material should preferably be +150 mV higher than the electrode potential of the first metallic material in order to achieve the greatest possible galvanic effect.
• the sum of the volume of the second metallic material is less than the volume of the first metallic material with which the stent struts are formed.
• the first metallic material can advantageously be tungsten, molybdenum or a base alloy of one of these two metals.
• At least one metal contained in a molybdenum-based alloy can be selected from W, Re, Nb, Ta and Mn or at least one can be contained in a tungsten-based alloy.
• holding metal can be selected from Mo, Re, Nb, Ta and Mn.
• a molybdenum-based alloy consists of at least 50 at% Mo and a tungsten-based alloy consists of at least 50 at% tungsten.
• These metallic materials have a very high strength and rigidity, which allows the formation of thin stent struts.
• the materials are also characterized by constant wear across the entire surface due to corrosion or bioresorption. Since the alloying elements W, Ta and Nb can be mixed with Mo in any ratio, one or more of these elements can be part of a molybdenum-based alloy in any proportion greater than 0 at% and less than 50 at%. The same applies to the alloying elements Mo, Ta and Nb in a tungsten-based alloy.
• a Mo-based alloy can contain rhenium with more than 0 at % and at most 42 at % and manganese with more than 0 at % and at most 36 at %.
• a W-based alloy can contain rhenium with more than 0 at% and a maximum of 37 at% and manganese with more than 0 at% and a maximum of 20 at%.
• a second metallic material can be pure rhenium.
• An alloy of rhenium with molybdenum can also be used as the second metallic material, which contains more than 0 at% and a maximum of 14 at% molybdenum, or an alloy of rhenium with tungsten that contains more than 0 at% and a maximum of 20 contains at-% tungsten. It is also possible to use an alloy of molybdenum and rhenium as the second metallic material, which contains more than 0 at% and a maximum of 42 at% rhenium, or an alloy of tungsten and rhenium, this alloy containing more than 0 at% and contains a maximum of 37 at % rhenium.
• the second metallic material contains a larger proportion of rhenium and has a more positive electrode potential than the first metallic material. If the first metallic material is tungsten or a tungsten-based alloy without rhenium, the second metallic material can also be pure molybdenum.
• the second metallic material can be applied to the first metallic material by means of various coating methods.
• methods of chemical vapor deposition such as. B. the atomic layer deposition (atomic layer de- position), or physical vapor deposition (CVD), such as e.g. B. magnetron sputtering or ion beam sputtering.
• the first metallic material should be covered completely and over the entire surface by the second metallic material in order to prevent rapid corrosion of the first metallic material during the functional period and to ensure the mechanical integrity of the stent.
• the thickness of the coating formed with the second metallic material should be in the range of 1 nm to 1000 nm, preferably 1 nm - 50 nm.
• the coating with the second metallic material preferably takes place in such a way that the layer thickness is uneven over the stent surface.
• the thickness of the coating should be designed considering the rate of dissolution of the metallic materials due to bioresorption and electrochemical corrosion and the time required for the vessel wall to be restored. A part of the coating can already have degraded by the time the respective vessel wall has reached a sufficiently healthy state, as long as the mechanical integrity of the stent is not endangered as a result. For example, the state of health and the age of a patient before the operation, the type of vessel receiving the implanted stent and the type and severity of the lesion can be taken into account for the required thickness of the coating with the second material.
• the coating can be applied either to the electropolished surface of the first metallic material or, after a separate surface structure has been embossed, to the respective surface areas of the first metallic material. This primarily concerns the surface areas of the struts of the stent, which are arranged or aligned in the direction of the vessel wall. These can be provided with a surface structure that is formed with elevations and depressions.
• the surface of the struts can be enlarged by a factor of 1.1 to 10 with the surface structuring compared to an electropolished surface of the struts.
• the surface structuring can advantageously have been formed periodically and/or with grooves, depressions, valleys as depressions and/or elevations with rings and/or peaks.
• the surface structuring can be achieved by a locally defined removal of material, preferably in the area of the surface of the struts of the stents that face the vessel wall, using laser radiation or photolithographic techniques. It can also be defined by an all-round etching of a stent structure or a tube used as a semi-finished product made of the first metallic material, e.g. B. with hydrogen peroxide, are formed.
• the stent By constructing the stent from two bioresorbable metallic materials, a resorption behavior favorable for interventional cardiology or vascular surgery under physiological conditions and the time until the metallic materials are completely dissolved can be adjusted.
• the dissolution of the implanted stent according to the invention in the vessel is characterized by three time segments with different dissolution rates.
• the duration of the time periods can be regulated in particular via the thickness of the coating, so that the dissolution behavior of the stent can be easily adapted to the respective application.
• the rate of dissolution is low because only the slowly degradable second metallic material is exposed and resorbed.
• the mechanical properties of the stent are therefore constant, since they are primarily determined by the first metallic material, which is protected from degradation during this period.
• the second period of time begins when the first metallic material has been partially exposed as a result of the degradation of the second metallic material.
• the partial exposure can be caused by an uneven thickness of the coating on the surface of the struts with the second metallic material. be promoted. If both metallic materials are exposed at the same time, galvanic corrosion occurs during this period due to the different electrode potentials, and the first metallic material is locally accelerated in the surface areas exposed by the second metallic material, while the second metallic material is locally protected from further corrosion.
• the degradation of the first metallic material is accelerated by the surface roughness/structuring, taking into account the particularly uniform degradation of molybdenum and tungsten over the entire exposed area.
• the rate of dissolution is lower than in the second period, since the influence of galvanic corrosion weakens due to advanced dissolution or fragmentation of the coating of the second metallic material.
• the surface roughness/structure still has a positive effect on the dissolution rate.
• the dissolution rate is much higher than in the first period because the dissolution rate of the first metallic material is generally higher than that of the second metallic material.
• FIG. 1 shows a sectional plan view of an example of a stent according to the invention with an enlarged partial illustration.
• FIG. 1 shows a sectional plan view in a plane which is aligned perpendicularly to the central longitudinal axis of the stent 1.
• the stent 1 is formed with struts 2 which are connected to one another at points (not shown). Free spaces are present between the struts 2 , as is also the case with conventional stents 1 .
• the surface area of the struts 2 which faces the vessel wall has been provided with a surface structure 3 which has been formed with grooves as depressions and rings as elevations.
• the grooves and rings have been formed periodically in this example.
• a coating 5.1 which is formed with the second metallic material 5, is formed.
• the dimensioning of all elements of the stent 1 can be selected according to the information in the general part of the description.
• FIG. 1 shows a schematic sectional view of an example of a stent 1 consisting of a plurality of struts 2 which are connected to one another at points in a manner not shown, the connection points being arranged in planes which differ from the plane of the shown section have a distance.
• the first metallic material 4 from which the struts 2 are made is pure molybdenum.
• This structure is produced by using standard drawing processes to obtain a molybdenum tube with a diameter of 3 mm and a wall thickness of 50 ⁇ m. The wall thickness results in the strut thickness (radial expansion) of the later stent structure.
• a stent structure with a length of 30 mm is then produced from this tube by means of a laser cutting process, the strut width (tangential extension) of the struts 2 being connected to one another at points being 50 ⁇ m.
• the structure formed with the struts 2 is then cleaned and deburred using electropolishing methods.
• a surface structure 3 with grooves as depressions along the length of the struts 2 with an average structure height of 5 ⁇ m is produced on the surface of the struts 2, which faces the vessel wall, with the aid of an ultra-short pulse laser, thus increasing the total surface area by a factor of 2.5 .
• a defect-free coating 5.1 made of pure rhenium as the second metallic material 5 with an average layer thickness of 20 nm is then applied using the atomic layer deposition method.
• the coating 5.1 encloses the Core of the struts 2, which consist of the first metallic material 4, completely. Rhenium has a dissolution rate of 50 nm per year.
• the thickness of the coating 5.1 is selected in such a way that it ensures the mechanical integrity of the stent 1 for the necessary service life of 4 months by protecting the molybdenum from corrosion.
• the thickness of the coating 5.1 varies slightly, particularly in the surface-structured area 3 of the struts 2.
• the rhenium has dissolved locally at several points of the struts 2 so that the molybdenum underneath is exposed. This preferably takes place in the surface-structured area 3, since areas of the coating 5.1 of different thickness were formed here.
• the formation of local galvanic cells accelerates the corrosion of the exposed molybdenum while protecting the surrounding rhenium from further corrosion. Due to the locally limited effect of the galvanic elements, further galvanic local elements form over the entire surface of the stent structure over time.
• the increased surface area in the structured area 3 ensures an additional acceleration of the dissolution and resorption of the stent 1.
• the local corrosion also weakens the integrity of the stent 1. This ultimately leads to a fracture of the stent structure, which in turn leads to an increase in the surface area and thus a increased dissolution of the molybdenum. Without the influence of galvanic corrosion, the dissolution rate of molybdenum is 25 pm per year. The duration of the complete degradation of this stent 1 is approximately one year.
• the exemplary embodiment describes a peripheral stent for leg arteries.
• a tube made of a molybdenum alloy with 25 at. The wall thickness results in the strut thickness (radial expansion) of the later stent structure.
• a stent structure with a length is then made from this tube using a laser cutting process of 50 mm, the strut width (tangential extension) of the struts connected to one another at points being 2 60 pm.
• the surface of the struts 2 is then cleaned and deburred using an electropolishing process. The total surface is then increased by a factor of 1.5 by roughening by etching with hydrogen peroxide.
• a defect-free coating 5.1 made of pure rhenium 5 with an average layer thickness of 5 nm is then applied using the atomic layer deposition method.
• the coating 5.1 encloses the core of the struts 2 completely.
• Rhenium as the second metallic material 5 has an annual dissolution rate of 50 nm.
• the thickness of the coating 5.1 is chosen so that the mechanical integrity of the stent is guaranteed for a period of at least one month by the coating 5.1 the molybdenum-tungsten alloy as first metallic material 4 protects against corrosion.
• FIG. 1 shows a schematic sectional illustration of an example of a stent 1 consisting of several struts 2 which are connected to one another at points in a manner not shown, the connection points being arranged in planes which are at a distance from the plane of the section shown.
• the first metallic material 4 from where the struts 2 are made is pure tungsten.
• This structure is produced by using standard drawing processes to obtain a tungsten tube with a diameter of 3 mm and a wall thickness of 50 ⁇ m. The wall thickness results in the strut thickness (radial expansion) of the later stent structure.
• a stent structure with a length of 30 mm is then produced from this tube by means of a laser cutting process, the strut width (tangential extension) of the struts 2 being connected to one another at points is 50 ⁇ m.
• the structure formed with the struts 2 is then cleaned and deburred using electropolishing methods.
• a surface structure 3 with defined periodic indentations along the length of the struts 2 with an average structure height of 2 ⁇ m is produced on the surface of the struts 2, which faces the vessel wall, using a photolithographic process in conjunction with hydrogen peroxide etching, and thus the total surface around one Factor increased by 1.5.
• a coating 5.1 made of a second metallic material 5, a rhenium alloy with 15 at % tungsten, with an average layer thickness of 600 nm is then applied using the method of magnetron sputtering with a rotating substrate.
• the coating 5.1 completely encloses the core of the struts 2, which consist of the first metallic material 4.
• the rhenium-tungsten alloy has a dissolution rate of 3000 nm per year.
• the thickness of the coating 5.1 is selected in such a way that it ensures the mechanical integrity of the stent 1 for the necessary functional period of 2 months by protecting the tungsten from corrosion.
• the thickness of the coating 5.1 varies, in particular due to the production using magnetron sputtering and in the surface-structured area 3 of the struts 2.
• the rhenium-tungsten alloy has dissolved locally at several points of the struts 2 so that the tungsten underneath is exposed. This preferably takes place in the surface-structured area 3, since areas of the coating 5.1 of different thickness were formed here. Corrosion of the exposed tungsten is accelerated by the formation of local galvanic cells, while the surrounding rhenium-tungsten alloy is protected from further corrosion. Due to the locally limited effect of the galvanic elements, however, further galvanic local elements form over the entire surface of the stent structure over time. The increased surface in the structured area 3 provides an additional

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• Health & Medical Sciences (AREA)
• Public Health (AREA)
• Heart & Thoracic Surgery (AREA)
• Vascular Medicine (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Veterinary Medicine (AREA)
• Surgery (AREA)
• Epidemiology (AREA)
• Chemical & Material Sciences (AREA)
• Inorganic Chemistry (AREA)
• Engineering & Computer Science (AREA)
• Biomedical Technology (AREA)
• Physics & Mathematics (AREA)
• Optics & Photonics (AREA)
• Cardiology (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Transplantation (AREA)
• Materials For Medical Uses (AREA)
• Media Introduction/Drainage Providing Device (AREA)
• Prostheses (AREA)

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• 2020
  • 2020-12-17 DE DE102020216158.5A patent/DE102020216158B4/de active Active
• 2021
  • 2021-12-14 KR KR1020237024456A patent/KR20230121874A/ko active Pending
  • 2021-12-14 EP EP21839106.8A patent/EP4262904B1/de active Active
  • 2021-12-14 CN CN202180092358.XA patent/CN116761643A/zh active Pending
  • 2021-12-14 JP JP2023536870A patent/JP2023553698A/ja active Pending
  • 2021-12-14 US US18/267,810 patent/US20240050247A1/en active Pending
  • 2021-12-14 WO PCT/EP2021/085591 patent/WO2022128979A1/de not_active Ceased

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