WO2009136239A2 - Medical device and method for the manufacture thereof - Google Patents

Medical device and method for the manufacture thereof Download PDF

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Publication number
WO2009136239A2
WO2009136239A2 PCT/IB2009/000545 IB2009000545W WO2009136239A2 WO 2009136239 A2 WO2009136239 A2 WO 2009136239A2 IB 2009000545 W IB2009000545 W IB 2009000545W WO 2009136239 A2 WO2009136239 A2 WO 2009136239A2
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WO
WIPO (PCT)
Prior art keywords
medical device
kininogen
characterized
device according
domain
Prior art date
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PCT/IB2009/000545
Other languages
German (de)
French (fr)
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WO2009136239A3 (en
Inventor
Lothar Sellin
Original Assignee
Lothar Sellin
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
Family has litigation
Priority to DE200820006190 priority Critical patent/DE202008006190U1/en
Priority to DE202008006190.3 priority
Priority to DE102008063889.7 priority
Priority to DE200810063889 priority patent/DE102008063889A1/en
Application filed by Lothar Sellin filed Critical Lothar Sellin
Publication of WO2009136239A2 publication Critical patent/WO2009136239A2/en
Publication of WO2009136239A3 publication Critical patent/WO2009136239A3/en
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=39628665&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2009136239(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0043Catheters; Hollow probes characterised by structural features
    • A61M25/0045Catheters; Hollow probes characterised by structural features multi-layered, e.g. coated
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/1027Making of balloon catheters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/104Balloon catheters used for angioplasty
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0043Catheters; Hollow probes characterised by structural features
    • A61M2025/0057Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/1027Making of balloon catheters
    • A61M25/1029Production methods of the balloon members, e.g. blow-moulding, extruding, deposition or by wrapping a plurality of layers of balloon material around a mandril
    • A61M2025/1031Surface processing of balloon members, e.g. coating or deposition; Mounting additional parts onto the balloon member's surface
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/1027Making of balloon catheters
    • A61M25/1029Production methods of the balloon members, e.g. blow-moulding, extruding, deposition or by wrapping a plurality of layers of balloon material around a mandril

Abstract

A medical device with a base body and a coating, wherein the device comprises a kininogen or the domain 5 of a kininogen. These exhibit a specific bonding affinity for CD-34 positive cells, thereby preventing or reducing restenosis. In the process, the coating is applied directly or indirectly to the vessel wall. The invention further relates to a method for manufacturing such a device, and a device and a method for directly applying a kininogen or a domain 5 of a kininogen onto the vessel wall.

Description

Medical device and process for their preparation

[Ol] The present invention relates to a medical device and a method for their preparation.

[02] Medical devices in the form of implants or catheters are known from the prior art numerous. Implants in the form of stents and catheters for percutaneous transluminal coronary angioplasty (PTCA catheter) can be used by means of endovascular techniques in blood vessels to eliminate bottlenecks. In any case, they should make the vessel in which they are used consistently.

[03] A frequent complication of stent placement or balloon dilatation is the so called restenosis, that is the re-occlusion of the vessel after dilatation of a vessel and / or insertion of a stent. Restenosis is due to the proliferation of cells, especially smooth muscle cells, which settle on the inner wall of the vessel and cause the free lumen of the vessel narrows again. In case of excessive cell attachment this can lead to life-threatening situations, particularly in the coronary.

[04] One reason for the restenosis is common after balloon angioplasty and / or stenting injury Endotheli- killed with corresponding inflammatory reaction and release of growth factors that promote cell proliferation. Therefore, especially, the injury of the vessel wall to stir the balloon or stent in the conventional Ballondilatationstechniken or with conventional implantation techniques with considerable pressures on and pressed into the vessel wall to dilate the vessel in this manner conducive to a lumen. This balloon pressure-induced vascular wall injury and the inflammatory symptoms associated lead to an increased release of growth factors, resulting in increased proliferation of the smooth muscle cells result. So that there is already in the short term to a renewed occlusion of the vessel because of uncontrolled growth.

[05] Currently, it is assumed that the restenosis is primarily determined by the circumstances in the first few weeks after dilation / implantation. With the healing of the wounds caused by implantation in the vessel wall, the inflammatory symptoms and the release of growth factors subside. Cell proliferation stops. However, the cell layers at this time already formed continue to be a starting point for new waste and deposits that can lead to a long-term restenosis process.

[06] There are a number of approaches to solve the problem of restenosis by a stent is in addition to the balloon set. Here, too, however, restenosis occur. [07] On a purely mechanical side of the stent is smoothed on all sides with a very sorgfaltigen polishing, to prevent the accumulation of cell material and the injury of the endothelium by roughness or burrs. This method brings some success, but some restenosis rate in the range of about 15% can be previously difficult below.

[08] It was tried vainly to solve the problem of thrombosis-related restenosis by equipping the stents with heparin, see J. Whöne et al, European Heart Journal 2001, 11, 1808 -. 1816. heparin ad- ested anticoagulant only the thrombosis-related restenosis and can be fully effective only in solution beyond. Here, a drug treatment has prevailed.

to prevent [09] Initial attempts neointimal proliferation by coating the stents, mostly remain without resounding success. Neither the coating with gold or a silicon carbide or Carbonbe- coating gave clear results so far.

[10] It has also tried to equip stents and PTCA catheter with proliferation-onshemmenden drugs to counteract cell proliferation. Known means for this are paclitaxel and rapamycin. Thus equipped stents and PTCA catheters currently have a more favorable rate of restenosis as polished stent or uncoated PTCA catheter.

[11] The US-A-5,891,108 discloses a hollow molded stent, which contains pharmaceutical active agents in its interior, which are released through a plurality of openings in the stent. EP-AI 127 582 describes another variant of a stent which is adapted to receive an active ingredient. Drug containing stent coatings are known for example from WO 95/03036 A, which corresponds in particular paclitaxel holding coatings are described. DE-10244847 Al discloses a PTCA catheter has been coated with paclitaxel.

[12] Such stents are equipped by design drug reservoirs that release the pharmaceutical agent selectively in a high concentration and over a relatively long period of time. Coated PTCA catheters deliver the paclitaxel or other drugs directly to the vascular wall construction-related coatings.

[13] While not proliferation-retardant stents covered within a few months with a protective layer of cells acting anti-proliferative drugs, such as rapamycin and Pac litaxel, this healing mechanism contrary. This causes the smooth muscle cells or are no longer very delayed capable of enclosing the stent. Therefore, the stent is much longer exposed to the blood, what leads again to increased vessel occlusions by thromboses, see F. Liestro, A. Colombo, "Late acute thrombosis after Paclitaxel Elluting stent implantation," Heart 2001.86, 262-264. The resulting artificially prolonged healing time represents a more or less open wound in the vessel wall, which can easily lead to clots and thrombosis. So thrombosis are still a year after the successful and uncomplicated use of drug-eluting stents has been observed E. McFadden et al, Lancet 2004, 364, 1519- 1521. In addition, appear to significantly increase the risk of heart attacks, according to recent findings coated with antiproliferative drugs implants. In the field of coated PTCA B allonkatheter with paclitaxel or Rapa- no long-term studies are mycin yet been published.

[14] There is also a tendency for uneven delivery of the agent, which prevents a controlled healing of the stent or healing of the vessel wall with drug eluting stents or PTCA balloon catheters.

[15] Under the prevailing physiological conditions there is often an episodic or sustained release. The delayed release is disadvantageous for the desired purpose, as it arrives in particular in the first few days after implantation to a uniform release of the active ingredient. The batches release is un- desirable because it is used in the drugs are highly effective systems, which can cause damage in higher concentrations.

[16] WO 2004/05513 A describes the use of aptamers for coating surfaces to promote adhesion of biological material is known. The coated articles may be around implants, including those intended for the vascular system. When the biological material can be, stem cells, epithelial cells and the like, and Vorläuferzel- len, for example. The aptamers are bound to the implant surface. The surface, ie, the implant can be made of a plastic material. The connection is made in a photochemical way.

have become [17] Also known special micro-proteins with up to 40 amino acids that are able to take conformationally stable three-dimensional structures, which makes them versatile binding molecules. Examples of such proteins are micro-cystine knot proteins (Krause et al., FEBS 2007, 274, 86-95).

[18] The object of the present invention herein is to provide improved to provide medical American facilities.

[19] This object is achieved with a medical device with a base body and a coating, wherein the means comprises a coating having a kininogen or a domain of a 5 Kinino- gene.

[20] This has the advantage that a reliable and controlled Einhei- is ensured development and proliferation inhibition, in particular the establishment of epithelial cells is enhanced on the damaged vascular surface.

[21] A high molecular weight kininogen (HK) is an endogenous, consisting of 626 amino acids, a single strand plasma glycoprotein having a glycosylation dependent on the molecular weight 88-120 kDa. The molecule consists of six domains having different properties and functions are taking. HK is also known as alpha2-thiol proteinase inhibitor and belongs to the superfamily of cystatins, which are cysteine ​​proteinase inhibitors. It was first identified as a precursor molecule of the bioactive peptide bradykinin and has an average plasma concentration of 0.67 uM.

[22] HK is also known as William Fitzgerald Flaujeac factor or simply Fitzgerald factor of the intrinsic pathway of blood coagulation and acts as an activating, non-enzymatic cofactor for factor XII (Hegemann factor) and XI. This activating function has HK for prekallikrein in kinin kallikrein system. Thus, it plays an important role in many pathophysiological processes such as fibrinolysis, thrombosis formation and in inflammatory processes.

[23] A lack of kininogen is associated not only with a prolonged aPTT clotting time, but should, according to recent studies favor and make internal organs for fatty degeneration also susceptible to the formation of abdominal aortic aneurysms in Brown Norway rat-th. By proteolytic cleavage of high molecular weight kininogen by kallikrein ensteht by dissolving out the short-lived bradykinin, which contains large parts of the domain 4, the activated so-called kininogen (TCA). When bradykinin is a potent vasodilator with influence on blood pressure, the permeability of small blood vessels and pain perception. In addition, it still promotes angiogenesis.

[24] In HKa is a conformational Resulting by double-stranded molecule consisting of a heavy chain with the domains 1, 2 and 3 and a light chain that contains the domains 5 and 6. FIG. Both chains are linked together via a single disulfide bridges. In HKa a larger area of ​​the domain 5 is exposed compared to HK on the surface.

[25] The medical device may in particular a PTA or PT CA-catheter or stent, particularly for use in the vascular system to be. However, other implants can benefit from improved Einheileigenschaften.

[26] layer or coating according to the invention is any type of coating which is applied topically to the balloon catheter or stent. In particular, coatings for the purposes of the invention are an amino-functionalized or carboxyl-functionalized coatings, which are applied to the balloon catheter or stent by amination and to which the kininogen is covalently bound or photochemically.

[27] To produce such layers, the surfaces can be modified in different ways.

[28] The kininogen or the domain 5 of kininogen may be chemically modified. This can further improve the properties to a Einheilei- result of the inhibition of proliferation and the Ansieldung of epithelial cells. [29] It is particularly advantageous if the coating has a molecule with a specific binding affinity for CD-34-positive cells. In particular, the CD-34-positive cells may be endothelial progenitor cells. Also chemically modified cells with the same characteristics can be used. This endothelialization is accelerated and thus counteracts restenosis.

The kininogen or the domain 5 of kininogen may be physically or chemically bonded. Thereby, the strength of the bond to the base body can be varied. If it is in the medical input device is a catheter, a weaker bond is advantageous because the kininogen or domain 5 of kininogen via the removal of the catheter should remain at the application site. In an implant, however, a stronger bond can be selected, as this remains in the body.

[30] Advantageously, the medical device comprises at least a hemocompatible layer. This may in particular donned as a base or base layer directly on the balloon.

[31] The medical device may optionally include one or more additional layers, including at least one additional layer, to which the above-described kininogen, in particular the domain 5 of kininogen is bound.

[32] As hemocompatible layers are also particularly applied on the surface oxide layers in question. The medical Einrich- processing can also be modified by hydroxylation or amination so that it can according to the invention bind Kininogens or their domain. 5

[33] The hemocompatible coating provides a further improvement of the blood compatibility, while the Kininogens or their domain 5 promote rapid docking of endothelial cells and the prevention of proliferation and rapid healing of the affected vessel.

[34] It is of advantage if the medical device has a biokompa- tible base layer. This may be an oxide layer, a surface obtained by amination or a plastic layer.

[35] The kininogen or domain 5 of the kininogen may be bonded to the hemocompatible layer or biocompatible base.

[36] The medical device may have an amino-functionalized layer.

[37] Depending on the application, a carboxyl-functionalized layer can be advantageous. Both layers lead to stable binding of kininogen or domain 5 of kininogen to the base body.

[38] Next is of advantage if the medical device has a pharmaceutical. This can then be continuously released into the environment. [39] It is also advantageous if the medical device having a bio-soluble overcoat layer. This protects the medical establishment, but dissolves after implantation.

[40] Advantageously, distributed uniformly gens on the surface of the medical device, the kininogen or domain 5 of the Kinino-. The uniform distribution of the kininogens or their domain 5 over the entire surface of the PTCA catheter or stent causes the uniform and controlled delivery to the cells in addition to endothelial cells and on smooth muscle cells. Thus, there takes place a rapid colonization of the vessel with cells, simultaneously proliferation is counteracted, resulting in a prevention of restenosis with and greatly reduces the risk of thrombosis, in particular after a short healing time. In fact, the docking of the endothelial cells takes place within a few hours, as tests have shown. Versu che have also shown that kininogen and domain 5 of kininogen also counteracts a proliferation of the damaged vessel.

[41] Alternatively, the may be distributed of the domain 5 of kininogen facing only one of the blood side of the medical device, whereby the healing process will be accelerated.

[42] In addition, may be distributed on a side facing the vessel wall side of the medical device is a antiproliferatorischer active ingredient. This counteracts proliferation. [43] The kininogen or domain 5 of kininogen may be incorporated in a matrix. Thus, the kininogen is slowly released into the surrounding tissue (drug eluting).

[44] It is of advantage if the medical device molecularly imprinted polymers having overall. That is, the medical device comprises a layer comprising a specific binding affinity for CD-34-positve

includes cells containing and molecularly imprinted polymers. These polymers can be in the form of a coating, but nopartikeln in the form of Na, the advertising alone additionally applied to the implants or.

[45] With the technology of molecular imprinting synthetic materials for molecular recognition can be generated that are comparable in their affinity with biological systems. Molecular imprinting (molecular imprinting) is a template polymerization, the artificial mo--molecular recognition sites created. For this purpose, the target molecules are mixed with functional monomers and crosslinking agents and then subjected to free radical polymerization, forming a highly crosslinked polymer. The target molecules act as template - polymerization takes place around them. If the template molecules removed by extraction tion, remain in the polymer network voids which represent the spatial arrangement of functional groups. Through this freezing of the structure-specific recognition sites created in the polymer material. serve as target molecules each target of interest structures, in the present case, the goal structures of the CD-34-positive cells or endothelial progenitor cells. Their so improved annealing leads to a Poliferationshemmung.

[46] Another aspect of the invention comprises a method for the production of medical devices, wherein the coating is applied by dipping, plasma, 3d droplet or spray or CVD method on the implant.

[47] Another aspect relates to a PTCA catheter for the direct application of kininogen or domain 5 of kininogen to a vessel wall, wherein the catheter comprises a microporous balloon, with a solution containing the kininogen or domain 5 of kininogen is filled.

[48] ​​A final aspect of the invention relates to a method in which the kininogen or domain 5 of kininogen be administered directly to a vessel wall.

[49] The following describes a preparation, wherein the preparation is not limited to the herein described formulation.

[50] The 2-chain high molecular weight kininogen (TCA) is purified by the person skilled in known manner.

[51] The purified HKa shows so then a band of 110 kDa in non-reduced sodium dodecyl sulphate (SDS) gels, and two bands of 62 and 46 kDa in reduced SDS gels. The Gulthatione-S-transferase (GST) fusion peptides of the domain 5 of kininogen is prepared by the N-terminal GST is fused to the sequences of K420 to S513. The mutants are purified via a glutathione column to a purity of> 95%.

[52] The refolding to the corresponding tertiary structure of peptides cysteinhalti- gene is carried out by oxidation for 3 days at 4 0 C with continuous agitation.

[53] The buffer for this purpose is 50 mM amonium bicarbonate, pH 8.5 at a final concentration of 100 mg / ml. Subsequently, Pep tide freeze-dried.

[54] The heat-sensitive gel has to be prepared because it is supplied in powder form.

[55] It is dissolved in an Eppendorf tube in PBS at 0 0 C and kept in an ice-water-filled container.

[56] The liquid gel is mixes with three 500 micromol / 1 activated kininogen or domain 5 of kininogen.

[57] At room temperature, the gel is fixed and can be processed. Now, the coating of the PTCA catheter or stent is.

Claims

claims:
1. A medical device having a base body with a coating loading, characterized in that the medical device comprises a kininogen or a domain 5 of a kininogen.
2. Medical device according to claim 1, characterized in that it is an implant.
3. Medical device according to claim 1 or 2, characterized in that it is a catheter.
4. Medical device according to one of claims 1 to 3, by DA in that the kininogen or domain 5 of the
kininogen are chemically modified.
5. Medical device, in particular according to one of the preceding claims, characterized in that the coating has a molecule with a specific binding affinity for CD 34- positive cells.
6. Medical device according to one of the preceding claims, characterized in that the kininogen or domain 5 of kininogen is physically or chemically bonded.
7. Medical device according to one of the preceding Ansprü- surface, characterized in that it comprises a hemocompatible layer.
8. Medical device according to one of the preceding claims, characterized in that it comprises a biocompatible layer.
9. Medical device according to one of claims 7 or 8, data carried in that the kininogen or domain 5 of the
is kininogen bound to the hemocompatible or biocompatible base layer.
10. Medical device according to one of the preceding claims, characterized in that it comprises an amino-functionalized layer.
11. Medical device according to one of the preceding claims, characterized in that it has a carboxyl functionalized layer.
12. Medical device according to one of the preceding Ansprü- surface, characterized in that it comprises a pharmaceutical.
13. Medical device according to one of the preceding claims, characterized in that it comprises a bio-soluble overcoat layer.
14. Medical device according to one of the preceding claims, characterized in that the kininogen or domain 5 of kininogen is evenly distributed on the surface of the medical device.
15. Medical device according to one of the preceding claims, characterized in that the kininogen or domain 5 of kininogen on one of the blood-facing side is distributed to the medical facility.
16. Medical device according to one of the preceding claims, characterized in that on a side facing the vessel wall side of the medical device is a distributed antiproliferatori- shear active ingredient.
17. Medical device according to one of the preceding claims, characterized in that the kininogen or domain 5 of kininogen is bound in a matrix.
18. Medical device according to one of the preceding Ansprü- surface, characterized in that it comprises molecularly imprinted polymers.
19. A method for producing a medical device according to one of claims 1 to 18, characterized in that the coating-is applied by dipping, plasma, 3d droplet or spray or CVD method on the medical device.
20. Medical device, in particular a catheter for the direct application of kininogen or domain 5 of kininogen to a vessel wall, characterized in that the catheter has a microporous balloon with a solution containing the gene of the Kinino- or domain 5 of kininogen contains, is filled.
PCT/IB2009/000545 2008-05-06 2009-03-17 Medical device and method for the manufacture thereof WO2009136239A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE200820006190 DE202008006190U1 (en) 2008-05-06 2008-05-06 restenosis prophylaxis
DE202008006190.3 2008-05-06
DE102008063889.7 2008-12-19
DE200810063889 DE102008063889A1 (en) 2008-05-06 2008-12-19 Medical device and process for their preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE200911001050 DE112009001050A5 (en) 2008-05-06 2009-03-17 Medical device and process for their preparation

Publications (2)

Publication Number Publication Date
WO2009136239A2 true WO2009136239A2 (en) 2009-11-12
WO2009136239A3 WO2009136239A3 (en) 2010-07-29

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DE (3) DE202008006190U1 (en)
WO (1) WO2009136239A2 (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0372088A1 (en) * 1988-06-06 1990-06-13 Sumitomo Electric Industries, Ltd. Balloon for catheter
WO1991018992A2 (en) * 1990-06-08 1991-12-12 Wisconsin Alumni Research Foundation Methods to make and use proteinaceous material present in kinin-free high molecular weight kininogen

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0797988B1 (en) 1993-07-19 2009-01-14 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions and methods of use
US5891108A (en) 1994-09-12 1999-04-06 Cordis Corporation Drug delivery stent
AU780539B2 (en) 2000-02-25 2005-03-24 Cordis Corporation Use of cladribine on a stent to prevent restenosis
US20040072770A1 (en) 2002-07-03 2004-04-15 Besterman Jeffrey M. Methods for specifically inhibiting histone deacetylase-7 and 8
DE10244847A1 (en) 2002-09-20 2004-04-01 Ulrich Prof. Dr. Speck A medical device for drug delivery
DE10258924A1 (en) 2002-12-17 2004-07-08 Eberhard-Karls-Universität Tübingen Universitätsklinikum With the adhesion-promoting substances of biological material coated device

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0372088A1 (en) * 1988-06-06 1990-06-13 Sumitomo Electric Industries, Ltd. Balloon for catheter
WO1991018992A2 (en) * 1990-06-08 1991-12-12 Wisconsin Alumni Research Foundation Methods to make and use proteinaceous material present in kinin-free high molecular weight kininogen

Also Published As

Publication number Publication date
DE112009001050A5 (en) 2011-06-01
DE102008063889A1 (en) 2009-11-26
WO2009136239A3 (en) 2010-07-29
DE202008006190U1 (en) 2008-07-17

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