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Publication numberUS20030069632 A1
Publication typeApplication
Application numberUS 10/281,140
Publication dateApr 10, 2003
Filing dateOct 28, 2002
Priority dateJun 3, 1998
Also published asDE69913342D1, DE69913342T2, EP1083946A1, EP1083946B1, US6572651, WO1999062572A1
Publication number10281140, 281140, US 2003/0069632 A1, US 2003/069632 A1, US 20030069632 A1, US 20030069632A1, US 2003069632 A1, US 2003069632A1, US-A1-20030069632, US-A1-2003069632, US2003/0069632A1, US2003/069632A1, US20030069632 A1, US20030069632A1, US2003069632 A1, US2003069632A1
InventorsIvan De Scheerder, Eddy Demeyere, Dominique Neerinck, Wilfried Coppens
Original AssigneeN.V. Bekaert S.A.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Stents with a diamond like coating
US 20030069632 A1
Abstract
An intravascular metal stent having a tubular wall and a biocompatible coating on at least a major part of the wall surface which coating has a thickness of less than 4 μm and contains a diamond like amorphous material, preferably DLN.
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Claims(5)
1. An intravascular stent having a tubular wall and a biocompatible coating on at least a major part of the wall surface, said coating having a thickness of less than 4 μm and containing a diamond like nanocomposite (DLN) material, said nanocomposite material comprising two interpenetrating networks of a-C:H and a-Si:O.
2. A stent according to claim 1 wherein the stent wall is a radially expandable metal mesh or metal spring structure.
3. A stent according to claim 1 wherein the material comprises 30 to 70 at % of C, 20 to 40 at % of H, 5 to 15 at % of Si and 5 to 15% of O.
4. A stent according to claim 1 wherein the material closest to the wire surface is a nanocomposite DLN-material comprising interpenetrating networks of a-C:H and a-Si:O and wherein this material is covered with a transition layer comprising a mixture of said nanocomposite DLN and a diamond like carbon (DLC) layer and further with a DLC-layer.
5. A stent according to claim 2 wherein the metal structure is a polished stainless steel structure.
Description
    FIELD OF THE INVENTION
  • [0001]
    The present invention relates to an intravascular stent which is coated with a specific biocompatible composition.
  • BACKGROUND OF THE INVENTION
  • [0002]
    It is known that heparin, phosphorylcholine and certain polymer coatings may decrease the thrombogenicity of coronary stents. However they do not appear to reduce neointimal hyperplasia and in-stent restenosis. A large variety of vasoactive substances can easily be embedded in the polymer network without firm chemical bonds. Consequently they potentially can act as an intramural slow release formulation for vasoactive drugs.
  • [0003]
    Numerous tubular stent designs are now on the market. Many of them consist of a radially expandable metal network, either in the form of a fine wire mesh, of a corrugated ring structure or of a slotted metal tube wall wherein a recurring pattern of holes are cut (e.g. by laser cuting). The stent wall has a thickness of between 0.08 and 0.20 mm and the metal is preferably stainless steel, tantalum or NITINOL. Stents can also have an expandable tubular metal spring like structure (coil stent). Examples of stent structures are known from e.g. U.S. Pat. Nos. 4,739,762, 4,856,516, 5,133,732, 5,135,536, 5,161;547, 5.158,548, 5,183,085, 5,282,823, from WO 94/17754, from European patent applications Nos. 0282175, 0382014, 0540290, 0621017, 0615769, 0669114, 0662307, 0657147 and from European patent application 0791341 of applicant.
  • [0004]
    Diamond like amorphous material such as diamond like nano composition (DLN) are known from WO97/40207 and WO98/33948.
  • [0005]
    The use of DLN as biocompatible coating for medical devices is for example known from U.S. Pat. No. 5,352,493, WO 97/40207 and WO 96/39943. U.S. Pat. No. 5,352,493 and WO96/39943 disclose the application of DLN as biocompatible coating for medical devices such as orthopedic devices. WO 97/40207 describes the application of DLN for coating of hip prostheses.
  • [0006]
    In contrast with the above mentioned applications, the coating of intravascular implants, such as stents must meet more severe requirements. The coating needs not only to meet the requirement to be biocompatible, but has to decrease or even to avoid thrombogenicity and histiolymphocytic inflammatory foreign body reaction. Neointimal hyperplasia has to be avoided since it can result in a narrowing or even in a closing of the blood vessel cavity. The narrowing of the blood vessel cavity after implantation of a stent is known as in-stent restenosis.
  • SUMMARY OF THE INVENTION
  • [0007]
    It is an object of the present invention to provide an intravascular stent coated with a biocompatible material in order to avoid thrombogenicity, histiolympocytic inflammatory foreign body reaction and neointimal hyperplasia. As a consequence the risk for in-stent restenosis is decreased or avoided.
  • [0008]
    The object of the invention is met by using a new class of biocompatible materials for coating at least a major part of the wall surface of the stent with a coating thickness of preferably less than 4 μm and most preferably between 0.05 and 3 μm. The material used according to the invention contains a diamond like amorphous material. Since the coating resists repeated deformation, it can be applied to a stent with a radially expandable metal mesh or metal coil structure.
  • [0009]
    The diamond like amorphous material in the coating is preferably a diamond like nano composition (DLN) comprising interpenetrating networks of a-C:H and a-Si:O. Such coatings and methods to apply them are known i.a. from WO 97/40207, PCT/EP97/01878 and WO98/33948. A representative coating of a-C:H and a-Si:O comprises 30 to 70 at % of C, 20 to 40 at % of H, 5 to 15 at % of Si and 5 to 15% of O. For applying these coatings to stents, the latter are preferably in their expanded state, not only radially but also they are longitudinally (axially) stretched to a certain extent if the mesh or spring structure so permits. This allows a substantially uniform deposition of the biocompatible diamond like material (DLN) using plasma-assisted CVD-processes. The plasma is created from a siloxane precursor. A Si-doped DLC can also be deposited; a silane precursor is then used.
  • DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION
  • [0010]
    The invention will now be illustrated by the description of two exemplary embodiments. The coronary stent of a coil-type design was used, as described in U.S. Pat. No 5,183,085. It consisted of a preconditioned, non ferromagnetic, highly polished stainless steel wire (AISI 316L) with a diameter of 0.18 mm. This design allows folding (radial compression) on any conventional balloon, resulting in a low profile 6F guiding catheter compatible stent delivery system. Percentage of axial shortening upon expanding the balloon is less than 5% and the stent is available in lengths from 12 mm up to 40 mm allowing customized stenting. These stents are available as bare stents or as mounted stents. In the present example stents of a length of 16 mm were used. Highly polished laser cut stainless steel mesh stents can be used as well.
  • [0011]
    The coil stent in its radially expanded form (as shown FIG. 1 of U.S. Pat. No. 5,183,085) was mounted as cathode in the vacuum reactor where the diamond like nanocomposition was deposited.
  • [0012]
    In a first embodiment, a single diamond like nanocomposition material (DLN) of the type described in claim 2 of WO 97/40207 was deposited with an average thickness of 2.5 μm. In a second embodiment a coating with the same thickness was deposited, using essential features of the process of WO 98/33948. This means that a first layer of the diamond like nanocomposite material was deposited with an average thickness of 0.5 μm. On top of that a layer of the same average thickness of diamond like carbon (DLC=a-C:H) was deposited with a transition layer interbetween having a thickness of 1.5 μm and comprising a mixture with a composition changing gradually from the first nanocomposition (DLN) to the DLC. The coating on the outer side of the coil was generally slightly thicker than on its inner side. The outer surface of the coated wire of the stent was extremely even and smooth.
  • [0013]
    Both embodiments were subjected to cyclic fatigue bending tests to determine their adhesion behaviour and adhesion retention to the wire after a number of bending cycles. No significant separation of the coating from the steel surface was discovered, especially for the stent with the single DLN-coating since indeed the critical load in a scratch test had indicated before a value of 33 to 36 N. The scratch tests were performed at about 50% relative humidity at 22 C. with a Revetest device (CSEM). The scratch stylus used is a diamond Rockwell C tip (120 C. on with a 200 μm tip radius). The loading rate is 100 N/mm, whereas the displacement rate of the stylus on the coating is 10 mm per minute. The critical load is determined with optical microscopy and corresponds to the load where delamination of the coating starts at the edges of the scratch track. It is thus confirmed here that DLN offers an excellent adhesion and adhesion retention after repeated bending. The inert diamond like material presents at the same time a suitable protective layer against possible corrosive attack of the steel surface (release of Cr, Ni and/or Fe) by the blood and vascular tissue in contact with the stent surface.
  • [0014]
    The stents were then radially compressed on a balloon catheter (diameter 3 to 3.5 mm) to the configuration shown in FIG. 3 of U.S. Pat. No. 5,183,085 and randomly implanted in a series of coronary arteries of 20 domestic cross bred pigs of both sexes weighing 25 to 30 kg. Thirteen specimen of each of three types of stents, viz. coated stents according to the first and to the second embodiment described above and (as third type) non coated, highly polished stainless steel spring stents were implanted for comparison. All stent deployments and implantations were successful and resulted in properly stented vessel segments. The pigs were fed throughout the study period with a standard natural grain diet without lipid or cholesterol supplementation. All animals were treated and cared for in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals. Six weeks after implantation, control angiography of the stented vessels was performed and subsequently pigs were sacrificed. At that time their average weight was about 70 kg and the vessels had thus grown considerably, compared to their size at the time of implantation.
  • [0015]
    Angiographic analysis (quantitative coronary angiography) of stented vessel segments was performed before stenting, immediately after stenting, and at follow-up using the POLYTRON 1000-system as described by De Scheerder et al. in the Journal of Invasive Cardiology 1996; 8: 215-222. The lumen diameters of the vessel segments were measured before stent implantation (=pre-stenting artery diameter values), immediately thereafter (=post-stenting values) and at follow-up (=diameters after 6 weeks). The degree of oversizing (%) was expressed as measured maximum balloon size minus selected artery diameter divided by the selected artery diameter. Recoil (%) was expressed as measured maximum balloon size minus mimimal stent lumen diameter (measured 15 minutes after stent implantation) and divided by measured maximum balloon size. The late loss value is an indication of hyperplasia and is the difference between the post-stenting value and the diameter at follow-up. The results of the angiographic measurements for each of the three types of stents is summarized in table 1.
    TABLE 1
    Mean Artery Coating Coating
    diameter (mm) Non-coated DLN DLN/DLC
    Pre-stenting (mm) 2.52 0.18 2.57 0.22 2.41 0.18
    Balloon size (mm) 2.93 0.16 2.96 0.10 2.91 0.15
    Post-stenting (mm) 2.68 0.16 2.71 0.20 2.64 0.14
    Oversizing (%) 16 6  16 8  21 7 
    Recoil (%) 8 4 8 4 9 6
    6 weeks FU (mm) 2.52 0.29 2.65 0.27 2.54 0.37
    Late loss 0.16 0.28 0.06 0.27 0.10 0.34
  • [0016]
    Baseline selected arteries, measured balloon diameter and post stenting diameter were similar for the three types. Oversizing and recoil were also similar. At six week follow-up a somewhat larger minimal luminal stent diameter and a somewhat decreased late loss was found for the DLN-coated stent embodiment.
  • [0017]
    After the pigs were sacrificed coronary segments were carefully dissected together with 10 mm minimum vessel segment both proximal and distal to the stent. Histopathology, as evaluated by light microscopic examination, was performed on very thin cross-section slices of the stented artery sections. Injury of the arterial wall, due to stent deployment, was evaluated as a first factor and graded according to the method of Schwartz et al. (J. Am. Coll. Cardiol 1992; 19: 267-274). Likewise, inflammatory reaction at every stent filament site was examined (second factor) by searching for inflammatory cells and graded as well. Appearance of thrombus was evaluated as a third factor and graded. The mean value of every factor for the 12 samples of each of the three stent types was calculated.
  • [0018]
    Thrombus formation was decreased in both coated stent types, i.e. with coatings DLN, resp. DLN/DLC. However, histopathology revealed for the non-coated stents and for the DLN/DLC-coated stents an increased inflammatory reaction when compared to the stent type with the single DLN-coating. It is believed that the inert DLN-coating is particularly useful to retard the attraction and sticking of proteins to the stent surface.
  • [0019]
    Finally, a morphometric study was carried out on the stented vessel segments at the time of follow-up after six weeks of implantation. The study was made using a computerized morphometry program (Leitz CBA 8000). Measurements of lumen area, lumen inside the internal elastic lamina area (=IEL area) and lumen inside the external elastic lamina area (=EEL area) were performed on the arterial sites, all in mm2. Neointimal hyperplasia (=IEL area minus Lumen area) and area stenosis in % as the ratio of hyperplasia to IEL area were derived therefrom. The results are shown in table 2.
    TABLE 2
    Mean Cross Coating Coating
    Section Area (mm2) Non-coated DLN DLN/DLC
    Lumen area (mm2) 1.71 0.66 2.31 0.89 1.93 0.73
    IEL area (mm2) 3.87 1.39 3.84 0.67 3.59 0.54
    EEL area (mm2) 5.74 2.06 5.15 0.89 4.95 0.66
    Hyperplasia (mm2) 2.16 1.48 1.53 0.54 1.66 0.38
    Area stenosis (%) 54 15 41 17 48 16
  • [0020]
    Again the DLN-coated stents offered the best results, i.e. the largest lumen area after 6 weeks, caused by a decreased neointimal hyperplasia. Covering the DLN/DLC- or DLN-coated stents with a heparin or phosphorycholine layer may further decrease neointimal hyperplasia. Although the invention has been described for blood vessels, similar results can be obtained for stents with diamond like coatings in other vessels in animal and human bodies, such as life stream conducts.
Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US5649951 *Jun 6, 1995Jul 22, 1997Smith & Nephew Richards, Inc.Zirconium oxide and zirconium nitride coated stents
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US7650976Jan 26, 2010Nissan Motor Co., Ltd.Low-friction sliding member in transmission, and transmission oil therefor
US7771821Aug 5, 2004Aug 10, 2010Nissan Motor Co., Ltd.Low-friction sliding member and low-friction sliding mechanism using same
US7931934 *Jan 15, 2007Apr 26, 2011Toyo Advanced Technologies Co., Ltd.Medical device having diamond-like thin film and method for manufacturing thereof
US8001922Aug 23, 2011Atrium Medical CorporationApplication of a coating on a medical device
US8096205Jan 17, 2012Nissan Motor Co., Ltd.Gear
US8124127Oct 16, 2006Feb 28, 2012Atrium Medical CorporationHydrophobic cross-linked gels for bioabsorbable drug carrier coatings
US8128688 *Jun 19, 2007Mar 6, 2012Abbott Cardiovascular Systems Inc.Carbon coating on an implantable device
US8152377Jul 13, 2010Apr 10, 2012Nissan Motor Co., Ltd.Low-friction sliding mechanism
US8206035Aug 6, 2004Jun 26, 2012Nissan Motor Co., Ltd.Low-friction sliding mechanism, low-friction agent composition and method of friction reduction
US8263102Sep 28, 2005Sep 11, 2012Atrium Medical CorporationDrug delivery coating for use with a stent
US8312836Nov 20, 2012Atrium Medical CorporationMethod and apparatus for application of a fresh coating on a medical device
US8367099Feb 5, 2013Atrium Medical CorporationPerforated fatty acid films
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US8574618Nov 21, 2012Nov 5, 2013Atrium Medical CorporationPerforated bioabsorbable oil film and methods for making the same
US8574627Oct 30, 2007Nov 5, 2013Atrium Medical CorporationCoated surgical mesh
US8575076Oct 22, 2008Nov 5, 2013Nissan Motor Co., Ltd.Sliding member and production process thereof
US8722077Aug 24, 2012May 13, 2014Atrium Medical CorporationDrug delivery coating for use with a stent
US8722132Jul 18, 2011May 13, 2014Atrium Medical CorporationApplication of a coating on a medical device
US8795703Sep 28, 2005Aug 5, 2014Atrium Medical CorporationStand-alone film and methods for making the same
US8858978Sep 28, 2005Oct 14, 2014Atrium Medical CorporationHeat cured gel and method of making
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US9000040Feb 3, 2009Apr 7, 2015Atrium Medical CorporationCross-linked fatty acid-based biomaterials
US9012506Dec 1, 2008Apr 21, 2015Atrium Medical CorporationCross-linked fatty acid-based biomaterials
US9220820Jul 16, 2013Dec 29, 2015Atrium Medical CorporationHydrophobic cross-linked gels for bioabsorbable drug carrier coatings
US9278161Oct 19, 2009Mar 8, 2016Atrium Medical CorporationTissue-separating fatty acid adhesion barrier
US20030039677 *Sep 30, 2002Feb 27, 2003Estrogen Vascular Technology, Llc.Apparatus and method for delivering compounds to a living organism
US20040241448 *May 26, 2004Dec 2, 2004Nissan Motor Co., Ltd.Rolling element
US20050056241 *Aug 6, 2004Mar 17, 2005Nissan Motor Co., Ltd.Valve train for internal combustion engine
US20050158361 *Nov 8, 2002Jul 21, 2005Atrium Medical CorporationIntraluminal device with a coating containing a therapeutic agent
US20050213854 *May 6, 2005Sep 29, 2005Nissan Motor Co., Ltd.Low-friction sliding mechanism
US20060067975 *Sep 28, 2005Mar 30, 2006Atrium Medical CorporationUV cured gel and method of making
US20060067977 *Sep 28, 2005Mar 30, 2006Atrium Medical CorporationPre-dried drug delivery coating for use with a stent
US20060078586 *Sep 28, 2005Apr 13, 2006Atrium Medical CorporationBarrier layer
US20060079863 *Oct 8, 2004Apr 13, 2006Scimed Life Systems, Inc.Medical devices coated with diamond-like carbon
US20060083768 *Sep 28, 2005Apr 20, 2006Atrium Medical CorporationMethod of thickening a coating using a drug
US20060110457 *Sep 28, 2005May 25, 2006Atrium Medical CorporationHeat cured gel and method of making
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US20060178737 *Jan 12, 2006Aug 10, 2006Furcht Leo TCoated medical apparatus
US20070071798 *Sep 22, 2006Mar 29, 2007Atrium Medical CorporationPerforated bioabsorbable oil film and methods for making the same
US20070191923 *Feb 16, 2006Aug 16, 2007Jan WeberMedical balloons and methods of making the same
US20070202149 *Oct 16, 2006Aug 30, 2007Atrium Medical CorporationHydrophobic cross-linked gels for bioabsorbable drug carrier coatings
US20080109017 *Feb 2, 2007May 8, 2008Atrium Medical CorporationBarrier layer with underlying medical device and one or more reinforcing support structures
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US20080206305 *Mar 10, 2008Aug 28, 2008Atrium Medical CorporationImplantable barrier device
US20080236984 *Nov 28, 2007Oct 2, 2008Nissan Motor Co., Ltd.Low-friction sliding member in transmission, and transmission oil therefor
US20090011116 *Jul 30, 2008Jan 8, 2009Atrium Medical CorporationReducing template with coating receptacle containing a medical device to be coated
US20090181937 *Jul 16, 2009Atrium Medical CorporationCross-linked fatty acid-based biomaterials
US20090208552 *Feb 3, 2009Aug 20, 2009Atrium Medical CorporationCross-linked fatty acid-based biomaterials
US20090209942 *Jan 15, 2007Aug 20, 2009Tatsuyuki NakataniMedical device having diamond-like thin film and method for manufacturing thereof
US20100233232 *Sep 16, 2010Swanick Thomas MFatty-acid based particles
Classifications
U.S. Classification623/1.15, 623/1.46, 427/2.25
International ClassificationA61L33/00, A61L31/00, A61L29/00, A61L31/08
Cooperative ClassificationA61L31/082
European ClassificationA61L31/08B