US20080102034A1 - Preparation for the prophylaxis of restenosis - Google Patents

Preparation for the prophylaxis of restenosis Download PDF

Info

Publication number
US20080102034A1
US20080102034A1 US11763125 US76312507A US2008102034A1 US 20080102034 A1 US20080102034 A1 US 20080102034A1 US 11763125 US11763125 US 11763125 US 76312507 A US76312507 A US 76312507A US 2008102034 A1 US2008102034 A1 US 2008102034A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
agent
preparation
preparation according
solution
active agent
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
US11763125
Inventor
Ulrich Speck
Bruno Scheller
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Speck Ulrich
Original Assignee
Ulrich Speck
Bruno Scheller
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

Links

Images

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
    • A61L29/08Materials for coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/095Sulfur, selenium, or tellurium compounds, e.g. thiols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/04X-ray contrast preparations
    • A61K49/0433X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/04X-ray contrast preparations
    • A61K49/0433X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A61K49/0438Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/04X-ray contrast preparations
    • A61K49/0433X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A61K49/0447Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/04X-ray contrast preparations
    • A61K49/0433X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A61K49/0447Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
    • A61K49/0452Solutions, e.g. for injection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/06Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10Organic compounds
    • A61K49/101Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
    • A61K49/103Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being acyclic, e.g. DTPA
    • A61K49/105Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being acyclic, e.g. DTPA the metal complex being Gd-DTPA
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/06Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10Organic compounds
    • A61K49/101Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
    • A61K49/106Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/06Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/18Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5094Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
    • 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
    • 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
    • A61L29/18Materials at least partially X-ray or laser opaque
    • 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
    • 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

Abstract

The invention relates to a preparation for restenosis prevention. The preparations for restenosis prevention known as yet do not reach sufficient active agent concentrations in the affected sections of the vascular walls as higher doses cause undesirable side effects. The present invention is a preparation to which at least one antihyperplastic agent is added that has a distribution ratio between butanol and water .gtoreq.0.5. The lipophilic active agent is absorbed by the vascular wall fast and in sufficient quantity. The preparation may be a liquid that can pass through capillaries and may contain a contrast agent so that the active agent is transferred into the vascular wall without any additional effort while the usually required contrast radiograms are taken. The preparation may also be applied to a catheter.

Description

  • The invention relates to a preparation for restenosis prevention and its application to an angiography catheter.
  • Stenoses of blood vessels are a major cause of morbidity and morality. Local stenoses or occlusions of larger vessels up to ca. 2 mm in diameter can be dilated back to their original lumen in many instances using inflatable balloon catheters. High pressures are applied when doing this, which may result in lacerations of the thickened vascular walls that are squeezed and displaced into the surrounding tissue. In some of these operations, tubular perforated metal supports (stents) are implanted to keep the vessels open. The vascular walls treated in this way frequently respond by increased growth in thickness that is similar to developing a scar within a few weeks and months. As a result and due to advancing arteriosclerosis, these vessels may relatively soon become stenosed again (restenosis). Restenosis is a severe medical problem that causes high costs.
  • A proven clinical method to prevent restenosis is irradiation of the affected vascular wall sections with a high dosage of X-rays (extracorporal sources or intraluminal radioisotopes) immediately after the surgery.
  • Major disadvantages of irradiation are the required precautions when handling preventive radiation dosages. Many other methods for preventing premature restenosis have been tested in labs and clinical practice but as yet without any major breakthrough [Bult H. Restenosis: A challenge for pharmacology. Tips 21 pp. 274-279, 2000]. Good results were only achieved using drug-releasing stents. For this method to be effective, stents have to be implanted so that restenosis cannot be prevented when the vessel is just dilated and no stent is implanted.
  • Inhibition of mitosis, reactive vascular wall thickening and restenosis has been described for a great number of drugs: Important principles of action are inhibition of platelet aggregation, enzyme inhibition, inhibition of mitosis, cytostatics, and corticoids. Favorable results were achieved in vitro and partly in animal experiments but have not been confirmed in clinical tests. A frequent explanation offered is that active agent concentrations in the affected sections of the vascular wall are insufficient. This is particularly true for oral and intravenous administration where side effects prevent higher doses. As an alternative, administration using specific catheters was attempted wherein these catheters either press the drug solution through the pores of a tight-sitting balloon directly into the vascular wall or block supply and discharge in a vessel section and expose the vessel wall to the drug solution for some time [Herdeg, C., M. Oberhoff, D. I. Siegel-Axel, A. Baumbach, A. Blattner, A. Kuttner, S. Schroder, K. R. Karsch: Paclitaxel: Ein Chemotherapeutikum zur Restenoseprophylaxe? Experimentelle Untersuchungen in vitro und in vivo. Z Kardiol 89 pp. 390-397, 2000]. Drug exposure of previously dilated vessel sections that was effective over a longer period of time was achieved by the slow release of active agents from coated stents. However, the problem of achieving sufficient active agent concentrations over a sufficient exposure time in the vessel sections requiring treatment remains the same with all these methods. Hydrophilic active agents are quickly washed out of tissues [Baumbach, A., C. Herdeg, M. Kluge, M. Oberhoff, M. Lerch, K. K. Haase, C. Wolter, S. Schroder, K. R. Karsch: Local drug delivery: Impact of pressure, substance characteristics, and stenting on drug transfer into the arterial wall. Cathet Cardiovasc Intervent 47 pp. 102-106, 1999]. Repeated administration is impossible because of the invasive access using catheters. Lipophilic active agents do not dissolve well enough in vessel-compatible aqueous media or are kept in solution as micelles or liposomes; these micelles or liposomes are only slowly absorbed by the tissue. Administration using special catheters that interrupt the blood flow for some time or press the active agent solution under high pressure into the vascular wall first of all causes additional tissue damage and intensifies reactive hyperplasia.
  • Coated, drug-releasing stents are difficult to produce in constant quality, they contain only very low active agent quantities due to their light weight and delicate design and are not suitable for proximal and distal treatment of the vascular sections at risk of restenosis a few millimeters around the stent. If a stent was implanted at an earlier time, and there is stenosis in its lumen, this can be removed by inflating a balloon catheter. This implantation of a second stent into the lumen of the first stent to prevent vessel wall hyperplasia as a consequence of dilatation is undesirable so that there is no effective method of restenosis prevention for this case. The same applies when there is no indication for implanting a stent after angioplasty or when hyperplastic vessel processes are taking place without clear stenosis of the lumen so that neither vessel dilatation nor stent implantation are required. Some of these vessel wall changes may cause sudden, mostly thrombotic occlusions. In this case, too, a method independent of stent implantation for inhibiting pathological vessel wall changes is desirable.
  • Active agents that were tested with some success in laboratory settings are heparin and hirudin derivatives, prostacyclins, corticoids, rapamycin, colchicine, and paclitaxel.
  • In most cases, the active agents were applied to stents; whenever solutions were used, these were aqueous solutions or, for the poorly water-soluble paclitaxel (4,10-β-diacetoxy-13-α-((2R,3S)-3-ben-zamido-2-hydroxy-3-phenylpropionyloxy)-2α-benzoyloxy-5-β, 20-epoxy-1, 7-β-dihydroxy-11-taxene-9-one), aqueous solutions with an ethanol or cremophor additive. Micelles are formed when using cremophor [poly(oxyethylene)-35-castor oil] that can largely be avoided when using ethanol.
  • Suspensions or emulsions with relatively large-sized particles in aqueous cytostatic solutions with or without an added contrast agent have been described for direct injection into tumor-feeding blood vessels. These preparations are used to close tumor vessels and for simultaneous cytostatic treatment. Closing the vessels is directly opposed to the purpose of this invention.
  • It is the problem of this invention to provide agents for the local treatment of potentially hyperproliferative tissue that can be handled easily and do not harm the patient.
  • Based on the state of the art, this problem is solved according to the invention by a preparation containing at least one antihyperplastic agent with a distribution ratio between butanol and water of ≧0.5, and by inserting said preparation in an agent for enhancing the imaging of arteries and veins or by applying it to a catheter.
  • The concept of the invention is based on the observation that active agents from adequately concentrated solutions, gels or other matrices are absorbed fast and in sufficient quantities by a vessel wall unless they are enclosed in outwardly hydrophilic micelles by solubility promoters. When the active agents are lipophilic (butanol to aqueous buffer solution (pH 7) distribution ratio ≧0.5, preferably ≧1 and ≧5 particularly preferred, or octanol to aqueous buffer solution (pH 7) distribution ratio ≧1, preferably ≧10, and ≧50 particularly preferred), and/or reversibly (>10%, preferably >50%, >80% particularly preferred) and/or irreversibly bind to cell components (such as paclitaxel, probucol (4,4′-(isopropylidenebisthio)bis(2,6-di-tert-butylphenol), porphyrin derivatives), the retention time in the blood vessel when administered during vessel dilatation and optional stent implantation is sufficient for the treatment effect. Prevention of reduction of initial reactive hyperplasia as a consequence of vascular injury prevents the vessel wall from growing too thick over many months. Surprisingly, the preparations according to the invention did not require longer exposure of the tissue to be treated or indirect infiltration and additional injury of the vessel wall.
  • Contrast agents were selectively injected into the affected vessels several times during angioplasty and stent implantation to determine positioning, degree and form of the stenosis, to specify the exact position of the dilatation catheter, evaluate dilatation success, and, optionally, to implant a stent of appropriate thickness and length. By adding the active agents or their preparations that are suited for the purpose to the contrast agents used for diagnostic purposes, the active agent is transferred into the vascular wall with each injection of contrast agent, without additional effort or damage to the vessels. The entire vessel section imaged for diagnostic purposes is treated including the area in front of the stenosis and the area away from its center. This has the major benefit that critical zones upstream and downstream from the dilated stenosis and optional stent implantation are not excluded from treatment.
  • If the injection of contrast media is not required or undesirable, solutions of lipophilic active agents in other aqueous carriers can be used without adding micelle-forming substances. One requirement is that these solutions contain a higher active agent concentration than the saturation concentration in the aqueous medium. This can be achieved by adding organic solvents that form few or no micelles such as ethanol or DMSO and/or by dissolving the active agents under conditions that are not beneficial for storage and administration (e.g. heating, mixing with concentrated active agent solutions in organic solvents) to form sufficiently stable oversaturated solutions.
  • In some cases, solubility of the lipophilic active agents in the contrast agent solutions or the stability of oversaturated solutions are surprisingly improved. Another surprising effect due to the contrast agents is enhanced adhesion and absorption of active agents by vessel walls and good local tolerance of some substances of extreme systemic toxicity in sensitive vessel sections.
  • When active agent and contrast medium are incompatible or when the active agent does not dissolve properly in the contrast medium, the active agent solution can also be directly infused or injected through the diagnostic catheter into the respective vessel. It is preferred to use similar volumes as they are common for vessel imaging using contrast media through catheters [Elke M: Kontrastmittel in der radiologischen Diagnostik, pp. 113-119, 3rd edition, Georg Thieme Verlag Stuttgart New York, 1992].
  • Contrast agents are solutions, suspensions or emulsions well tolerated by vessels that can be used to enhance the representation of blood vessels or the bloodstream in radiograms, sonograms, optical imaging or magnet resonance imaging.
  • These contrast agents include Visipaque 320 (iodixanol), Ultravist 370 (iopromide), Omnipaque 350 (iohexol) or Solutrast 370 (iopamidol) or Magnevist (gadolinium-DPTA) or Gadovist 1M (Gd-DO3A-butrol).
  • Active agents can be all substances suitable for inhibiting cell growth, cell multiplication and hyperplastic proliferation provided they meet the criteria defined above regarding lipophilia and/or binding to tissue components. Inasmuch as some active agents are not sufficiently lipophilic or capable of binding, their pharmacologically active derivatives or precursors of pharmacologically active substances may be used that release the actual active agent when in the tissue only. Preferred are cytostatics from the taxoid group such as paclitaxel and docetaxel ((2R,3S)-N-(tert-butoxycarbonyl)-2-hydroxy-3-phenyl-β-alan-ine-(4-acetoxy-2-α-benzoyloxy-5-β, 20-epoxy-1, 7-β, 10-β-trihydroxy-9-oxo-11-taxene-13-α-yl-ester)), or epothilones as examples of lipophilic substances. These are so lipophilic and insoluble in water that even more hydrophilic derivatives as described by Nicollaou K C, Riemer C, Kerr M A, Rideout D, Wrasidlo W. Design, Synthesis and biological activity of protaxols. Nature, 1993; 364: pp. 464-466 or in U.S. Pat. No. 457,674, Novel Taxoids, are preferred as long as their molecular weight does not exceed ca. 10 kD.
  • Other useful active agents are selected from the groups of corticoids, mitosis inhibitors such as colchicine, antibiotics such as azithromycin or roxithromycin (Gupta et al. 1998) or antioxidants such as probucol, as well as heparin and hirudin derivatives or prostacyclins. Furthermore, immunosuppressants such as rapamycin are among the active agents that can be used.
  • Examples of lipophilic derivatives of otherwise hydrophilic cytostatics can be found in Brunner H, Schellerer K-M, Treittinger B. Synthesis and in vitro testing of hematoporphyrin type ligands in platinum(II) complexes as potent cytostatic and phototoxic antitumor agents. Inorganica Chimica Acta, 1997; 264: pp. 67-79 in the form of conjugates of platinum complexes with porphyrins.
  • The preparations according to the invention that contain a cytostatic as an active ingredient are also suitable for treating tumor diseases. It is advantageous in this case that the treatment is local, which minimizes the strain the patient is put under.
  • Besides lipophilic substances, other active agents or substrate-bound active agents with a specific affinity to vessel walls, particularly to vessel walls showing pathological change, are suitable. Substances have a specific affinity to vessel walls when they are not washed away by the bloodstream within a few minutes. It is known that small concentrations of magnetites are deposited after intravenous administration in vessel walls that show arteriosclerotic change (Schmitz S A et al. Superparamagnetic iron oxide—enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits. Invest Radiol, 2000; 35: 460-471). However it is surprising that these magnetites reach concentrations sufficient for treatment after a short-time flow through the vessels that are dilated using a balloon. To make these magnetites usable for treatment, they must be coated with drugs as described, for example, by Lubbe A S, Bergemann C, Huhnt W. Fricke T, Riess H, Brock J W, Huhn D. Preclinical experiences with magnetic drug targeting: Tolerance and efficacy. Cancer Research, 1996, 56: 4694-4701).
  • The active agents are dissolved as much as possible in the undiluted contrast agents. They can also be prepared as a separate solution that is diluted with contrast agents prior to use. The mixing ratio of active agent solution and contrast agent solution should not be greater than 2:1, preferably <1:1, <0.2:1 being particularly preferred. The active agent should be dissolved in a well-tolerable aqueous medium or a medium that can be mixed with water. Also admissible are organic solvents that are well tolerated (at least after being diluted with the contrast agent solution or another aqueous medium) such as ethanol, DMSO, DMF, etc. The prepared injection solution will mostly contain as great a portion of water as possible (>90 volume percent, preferred >95 volume percent, >99 volume percent particularly preferred).
  • The concentration range of each active agent is dependent on their solubility in physiologically tolerable solvents without having to resort to micelle-forming agents such as cremophor and on the efficacy and tolerability of the active agents. The upper limit of the concentration is always determined by the volume to be administered (e.g. 100 to 200 ml for repeated injection into the coronary arteries) and the maximum systemically tolerable dose (e.g. ca. 100 mg per sqm body surface for paclitaxel). Preferred and sufficiently effective due to local administration and action are dosages of 1/10th or less of the maximum systemically tolerable dose.
  • Other effective substances such as coagulation inhibitors, platelet aggregation inhibitors, enzyme inhibitors, complex-forming agents for calcium ions, etc. may be added to the preparations. These do not have to meet the criteria for lipophilia, binding to tissue components or molecular weight as the effect can also be acute and intravascular; what has been said in the paragraph regarding concentration and dosage above applies here because the focus is on the local effect in the vessel section through which the preparation flows.
  • Another way of administering antiproliferative agents is provided by a catheter used for vessel dilatation that has an inflatable balloon which itself causes the vascular dilatation. The balloon can be coated with the active agent. When the vessel is dilated, the balloon is pressed against the vessel wall. This provides an opportunity for the active agent to transfer into the vessel wall. If the balloon is used to dilate a stent, even the active agent between the balloon and the stent can be released because the metal struts of the stent are displaced relative to the balloon surface. These variations of active agent administration do not constitute an additional step for the physician as compared to the original process of vessel dilatation or stent implantation.
  • The following methods can be used if the active agents are to be applied to the part of the catheter that is used for vessel dilatation: Dissolution of the active agent(s) in a solvent that does not corrode the catheter, immersion of the respective catheter part in the solution, removal of the catheter from the solution, and drying. Optionally, matrix or gel-forming adjuvants can be added to the active agent solution in the vessel, e.g. lipides or polymers used in pharmacology. Coating can be performed in several steps, while agent-containing and agent-free layers may alternate. The solvents for the respective layers should be selected in such a way that the subsequent coating does not strip off the previous one.
  • The examples below shall explain the invention:
  • EXAMPLES Example 1a Solution for Direct Administration into the Arteries
  • 80 mg of 7-(2″,3″-dihydroxypropyl oxycarbonyl)-paclitaxel are dissolved in 5 ml of dimethyl sulfoxide and diluted with 5 ml of a 5% glucose solution. The solution or a part thereof is slowly infused into the previously dilated arteries.
  • Example 1b X-ray Contrast Medium with an Additive for Inhibiting Intimal Hyperplasia
  • 99 parts of a portion of the solution described in 1a are added to the Visipaque 320, a commercial X-ray contrast medium, and immediately mixed well. The solution can be used as is common for angiography prior to or after vessel dilatation.
  • Example 2a Solution as an Additive to Contrast Agents
  • 200 mg of 7-(2″,3″-dihydroxypropyl oxycarbonyl)-paclitaxel are dissolved in 10 ml of absolute ethanol (=solution A); 0.35 ml of this solution can be added to 100 ml of contrast agent.
  • Example 2b X-ray Contrast Medium for Restenosis Prevention
  • 100 ml of Ultravist 370 (Schering AG, Berlin; active ingredient iopromide equivalent to 370 mg of iodine/ml) containing 0.35 volume percent of ethanol and 7 mg of 7-(2″,3″-dihydroxypropyl oxycarbonyl)-paclitaxel. The solution is produced by dissolving the 7-(2″,3″-dihydroxypropyl oxycarbonyl)-paclitaxel in ethanol and adding it under constant stirring to the contrast agent.
  • Example 2c X-ray Contrast Medium for Restenosis Prevention
  • The preparation according to Example 2b with an addition of 10 I.U. of low-molecular heparin
  • Example 2d Restenosis-inhibiting Perfusion Solution
  • 3.5 ml of the solution A described in Example 2a are mixed with 46.5 ml of ethanol and added under fast shaking to 1000 ml of warm (˜50.degree. C.) 5% glucose solution or isotonic electrolyte solution. This solution is infused via a catheter into the vessels to be treated just like a contrast medium; however, the infusion rate can be reduced as compared to that of contrast agents.
  • Example 3a X-ray Contrast Medium for Inhibiting Intimal Hyperplasia
  • 100 ml of Ultravist 370 (see Example 2b) mixed with 0.4 volume percent of ethanol and 14.4 mg of 7-(2″,3″-dihydroxypropyl oxycarbonyl)-paclitaxel. The preparation is produced as described in Example 2b.
  • Example 4a X-ray Contrast Medium for Inhibiting Cell Growth
  • 100 ml of Solutrast 370 (Byk-Gulden, Konstanz; active ingredient iopamidol equivalent to 370 mg of iodine/ml) containing 1.0 volume percent of ethanol and 8.2 mg of paclitaxel/ml. The preparation is produced by first dissolving the paclitaxel in absolute ethanol while heating it slightly, then adding the contrast agent quickly and under strong stirring.
  • Example 4b X-ray Contrast Medium for Inhibiting Intimal Hyperplasia
  • Preparation according to Example 4a plus adding 5 I.U. of heparin and 5 mmol/l of citrate buffer (pH 7.0).
  • Example 5a Solution as an Additive to Contrast Agents or Infusion Solutions
  • 20 mg of (±)-trans-1,2-diaminocyclohexane{7,12-bis[1-(1,4,7,10,1-3,16-hexaoxaheptadecyl)-ethyl]-3,8,13,17-tetramethylporphyrin-2,18-dipropionato}platinum(II) are dissolved in 10 ml of dimethyl sulfoxide (=solution B)
  • Example 5b X-ray Contrast Medium with an Additive for Inhibiting Cell Growth
  • 1 ml of solution B is added under fast stirring to 100 ml of Ultravist 370 (see Example 2b). The solution is suitable for infusion into arteries or injection into living or dead tissues or body cavities. It allows excellent control of its initial distribution and causes a long-lasting cytostatic effect.
  • Example 5c Contrast Medium for Magnetic Resonance Tomography with an Additive for Inhibiting Cell Growth
  • 1 ml of solution B is added to 10 ml of 50 mmolar gadolinium DTPA (=gadopentetate) solution. A 50 mmolar gadolinium-DTPA solution is prepared from Magnevist, a commercial preparation (Schering AG, Berlin), by diluting the product ten times. The solution can be infiltrated, for example, in vital tumors or in tumors after they were destroyed by ethanol, heat or cold treatment. The distribution of the solution is well visible in magnetic resonance tomograms. The solution itself supports the total destruction of the tumor in the immediately infiltrated area and its vicinity.
  • Example 6 In-Vivo Efficacy of the Preparation as Described in Example 2b
  • 2 coronary arteries each in a total of 8 pigs were dilated under anesthesia, and stents (fine, heavily perforated metal tubes) were implanted. The arteries respond by wall thickening, which results in narrowing the original lumen of the arteries. 4 pigs were administered a regular X-ray contrast agent (Ultravist 370) for imaging the arteries and checking the stent implantation, 4 pigs were administered the preparation according to Example 2b. The vessels of both test groups practically had the same widths (inside diameters 3.4±0.2 mm and 3.5±0.2 mm) immediately after treatment. 4 weeks after treatment, the inside arterial diameter in animals that only received the regular contrast agent had stenosed by 1.9±0.8 mm, whereas the arterial diameter in the animals that were treated with the solution according to Example 2b was only reduced by 0.9±0.6 mm. This difference is statistically significant (p=0.01). The undiluted solution according to Example 2b was tolerated without side effects despite the addition of a high concentration of a relatively toxic cytostatic after injection in the coronary arteries and simultaneous ECG and blood pressure measurements.
  • Example 7a Coating a Catheter
  • The distal area carrying the balloon of a balloon catheter designed for vessel dilatation is immersed under sterile conditions in the ethanolic solutions from Example 2a (=solution A), kept in the solution for ca. 5 minutes, then removed and dried for 2 hours at room temperature. The balloon catheter can then be used in the common way for dilating vessels.
  • Alternatively, a stent is placed on the balloon after drying.
  • Example 7b
  • The procedure is like in Example 7a, but 100 mg of pharmaceutical castor oil are now added to solution A.
  • Example 8a Solubility in the Contrast Agent or Physiological NaCl Solution
  • 7.6 mg of paclitaxel are dissolved in 0.5 mg of ethanol and added at room temperature to 50 ml Ultravist-370 (contains 768 mg of iopromide/ml, specific weight ca. 1.4 g/ml). A clear solution without any turbidity is obtained after mixing that remains stable for several days. No particles can be identified in the solution under a microscope.
  • 4.2 mg of paclitaxel are dissolved in 0.5 ml of ethanol and added at room temperature to 50 ml of a 0.9% NaCl solution. The preparation becomes turbid immediately after mixing; most particles are found on the surface of the solution after 2 hours. Large aggregations of fine particles are found using a microscope.
  • Evaluation: The solubility of paclitaxel in the contrast agent is highly surprising. The contrast agent solution contains 0.7 ml of water/ml of solution mixture, i.e. Less solvent is available to paclitaxel in the contrast agent solution than in the NaCl solution. In spite of that, paclitaxel dissolves better in the contrast agent solution than in the NaCl solution.
  • Example 8b Magnetite as the Carrier of the Antihyperplastic Agent
  • 75 mg of paclitaxel are dissolved in 5 ml of ethanol. The paclitaxel solution is added to 50 ml of an aqueous preparation of a colloidal magnetite coated with degraded dextrane (concentration refers to Fe2+/3+ 0.5 molar, e.g. SH U 555C, test preparation by Schering AG, Berlin) and quickly intermixed. The magnetite particles adsorb paclitaxel and carry it after intravenous or intra-arterial injection, inter alia, into arterial walls showing arteriosclerotic change and brain tumors. Dosage depends on the use of the magnetite and is ca. 50 μmol referred to Fe/kg of body weight.

Claims (15)

  1. 1. A preparation containing at least one antihyperplastic agent with a distribution ratio between butanol and water of ≧0.5 in liquid form suitable for passing through capillaries together with an agent for enhancing artery/vein imaging.
  2. 2. A preparation containing at least one antihyperplastic agent with a distribution ratio between butanol and water of ≧0.5 that is applied to a catheter.
  3. 3. A preparation in aqueous solution that may optionally contain additives as well as at least one antihyperplastic agent with a distribution ratio between butanol and water of ≧0.5 at a concentration that exceeds the saturation concentration in the purely aqueous medium wherein the active agent is not enclosed in micelles.
  4. 4. The preparation according to claims 1 through 3 wherein the antihyperplastic agent is a cytostatic, a corticoid, a prostacyclin, an antioxidant, an antibiotic, an agent inhibiting cell proliferation or an immunosuppressant.
  5. 5. The preparation according to claims 1 through 4 wherein the antihyperplastic agent is a taxoid.
  6. 6. The preparation according to claims 1 through 5 wherein the antihyperplastic agent is paclitaxel, docetaxel, probucol, a porphyrin derivative, colchicine or epithilone.
  7. 7. The preparation according to claims 1 through 6 wherein the agent for enhancing artery/vein imaging consists of solutions, suspensions or emulsions that the vessels can tolerate and that are used in X-raying, sonography, optical imaging, or magnetic resonance imaging for improved representation of the blood vessels or the bloodstream.
  8. 8. The preparation according to claims 1 through 7 wherein the agent for enhancing artery/vein imaging is an X-ray contrast medium.
  9. 9. The preparation according to claims 1 through 8 wherein the agent for enhancing artery/vein imaging is iodixanol (Visipaque), gadolinium-DTPA (Magnevist), Gd-DO3A-butrol (Gadovist), iopromide (Ultravist), iohexol (Omnipaque), or iopamidol (Solutrast).
  10. 10. The preparation according to claims 1 through 9, characterized in that the preparation additionally contains coagulation inhibitors and/or platelet aggregation inhibitors and/or enzyme inhibitors and/or calcium chelators.
  11. 11. The preparation according to claims 1 through 10 wherein the active agent irreversibly or reversibly binds to tissue at a minimum percentage of 10%.
  12. 12. The preparation according to claims 1 through 11 wherein the active agent or the component carrying the active agent comprises a specific affinity to vascular walls.
  13. 13. The preparation according to claims 1 through 12 wherein the preparation contains a solubility promoter that does not form micelles.
  14. 14. Use of the preparation according to claims 1 through 13 for restenosis prevention.
  15. 15. Use of the preparation according to claims 1 through 13 for treating tumor diseases.
US11763125 2001-03-26 2007-06-14 Preparation for the prophylaxis of restenosis Abandoned US20080102034A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE10115740.1 2001-03-26
DE2001115740 DE10115740A1 (en) 2001-03-26 2001-03-26 Preparation for the prophylaxis of restenosis
US10472844 US7750041B2 (en) 2001-03-26 2001-12-20 Preparation for the prophylaxis of restenosis
US11763125 US20080102034A1 (en) 2001-03-26 2007-06-14 Preparation for the prophylaxis of restenosis

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US11763125 US20080102034A1 (en) 2001-03-26 2007-06-14 Preparation for the prophylaxis of restenosis
US12835420 US8389043B2 (en) 2001-03-26 2010-07-13 Preparation for restenosis prevention
US12835414 US9066990B2 (en) 2001-03-26 2010-07-13 Preparation for restenosis prevention
US14255316 US20140227192A1 (en) 2001-03-26 2014-04-17 Preparation for Restenosis Prevention
US14255392 US20140227194A1 (en) 2001-03-26 2014-04-17 Preparation for Restenosis Prevention
US14255359 US20140227193A1 (en) 2001-03-26 2014-04-17 Preparation for Restenosis Prevention

Related Parent Applications (4)

Application Number Title Priority Date Filing Date
US10472844 Division
US10472844 Division 2001-12-20
US10472844 Division US7750041B2 (en) 2001-03-26 2001-12-20 Preparation for the prophylaxis of restenosis
PCT/DE2001/004782 Division WO2002076509A3 (en) 2001-03-26 2001-12-20 Preparation for the prophylaxis of restenosis

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12835420 Division US8389043B2 (en) 2001-03-26 2010-07-13 Preparation for restenosis prevention
US12835414 Division US9066990B2 (en) 2001-03-26 2010-07-13 Preparation for restenosis prevention

Publications (1)

Publication Number Publication Date
US20080102034A1 true true US20080102034A1 (en) 2008-05-01

Family

ID=7679661

Family Applications (8)

Application Number Title Priority Date Filing Date
US10472844 Active 2023-12-05 US7750041B2 (en) 2001-03-26 2001-12-20 Preparation for the prophylaxis of restenosis
US11763116 Abandoned US20080102033A1 (en) 2001-03-26 2007-06-14 Preparation for the prophylaxis of restenosis
US11763125 Abandoned US20080102034A1 (en) 2001-03-26 2007-06-14 Preparation for the prophylaxis of restenosis
US12835420 Active US8389043B2 (en) 2001-03-26 2010-07-13 Preparation for restenosis prevention
US12835414 Active US9066990B2 (en) 2001-03-26 2010-07-13 Preparation for restenosis prevention
US14255316 Abandoned US20140227192A1 (en) 2001-03-26 2014-04-17 Preparation for Restenosis Prevention
US14255392 Pending US20140227194A1 (en) 2001-03-26 2014-04-17 Preparation for Restenosis Prevention
US14255359 Abandoned US20140227193A1 (en) 2001-03-26 2014-04-17 Preparation for Restenosis Prevention

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US10472844 Active 2023-12-05 US7750041B2 (en) 2001-03-26 2001-12-20 Preparation for the prophylaxis of restenosis
US11763116 Abandoned US20080102033A1 (en) 2001-03-26 2007-06-14 Preparation for the prophylaxis of restenosis

Family Applications After (5)

Application Number Title Priority Date Filing Date
US12835420 Active US8389043B2 (en) 2001-03-26 2010-07-13 Preparation for restenosis prevention
US12835414 Active US9066990B2 (en) 2001-03-26 2010-07-13 Preparation for restenosis prevention
US14255316 Abandoned US20140227192A1 (en) 2001-03-26 2014-04-17 Preparation for Restenosis Prevention
US14255392 Pending US20140227194A1 (en) 2001-03-26 2014-04-17 Preparation for Restenosis Prevention
US14255359 Abandoned US20140227193A1 (en) 2001-03-26 2014-04-17 Preparation for Restenosis Prevention

Country Status (10)

Country Link
US (8) US7750041B2 (en)
EP (4) EP1666071B1 (en)
JP (1) JP4484432B2 (en)
KR (1) KR100874308B1 (en)
CN (5) CN1935277B (en)
CA (1) CA2442080C (en)
DE (8) DE10115740A1 (en)
DK (4) DK1666071T3 (en)
ES (4) ES2289721T3 (en)
WO (1) WO2002076509A3 (en)

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050101522A1 (en) * 2001-03-26 2005-05-12 Ulrich Speck Preparation for the prophylaxis of restenosis
US20080304101A1 (en) * 2007-06-08 2008-12-11 Naoko Sasase Server and printer introducing method under thin client environment
US20100068170A1 (en) * 2008-09-15 2010-03-18 Michal Eugene T Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US20100228228A1 (en) * 2002-09-20 2010-09-09 Ulrich Speck Medical device for dispersing medicaments
US20110046723A1 (en) * 1995-06-07 2011-02-24 Bates Brian L Coated implantable medical device
US8114429B2 (en) 2008-09-15 2012-02-14 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8128951B2 (en) 2008-09-15 2012-03-06 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8257722B2 (en) 2008-09-15 2012-09-04 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8366662B2 (en) 2006-11-20 2013-02-05 Lutonix, Inc. Drug releasing coatings for medical devices
US8366660B2 (en) 2006-11-20 2013-02-05 Lutonix, Inc. Drug releasing coatings for medical devices
US8414526B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids
US8414910B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US8425459B2 (en) 2006-11-20 2013-04-23 Lutonix, Inc. Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent
US8430055B2 (en) 2008-08-29 2013-04-30 Lutonix, Inc. Methods and apparatuses for coating balloon catheters
US8597720B2 (en) 2007-01-21 2013-12-03 Hemoteq Ag Medical product for treating stenosis of body passages and for preventing threatening restenosis
US8669360B2 (en) 2011-08-05 2014-03-11 Boston Scientific Scimed, Inc. Methods of converting amorphous drug substance into crystalline form
US8889211B2 (en) 2010-09-02 2014-11-18 Boston Scientific Scimed, Inc. Coating process for drug delivery balloons using heat-induced rewrap memory
US8998846B2 (en) 2006-11-20 2015-04-07 Lutonix, Inc. Drug releasing coatings for balloon catheters
US9056152B2 (en) 2011-08-25 2015-06-16 Boston Scientific Scimed, Inc. Medical device with crystalline drug coating
US9192697B2 (en) 2007-07-03 2015-11-24 Hemoteq Ag Balloon catheter for treating stenosis of body passages and for preventing threatening restenosis
US9402935B2 (en) 2006-11-20 2016-08-02 Lutonix, Inc. Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs
US9700704B2 (en) 2006-11-20 2017-07-11 Lutonix, Inc. Drug releasing coatings for balloon catheters
US9737640B2 (en) 2006-11-20 2017-08-22 Lutonix, Inc. Drug releasing coatings for medical devices
US9956385B2 (en) 2012-06-28 2018-05-01 The Spectranetics Corporation Post-processing of a medical device to control morphology and mechanical properties
US10080821B2 (en) 2009-07-17 2018-09-25 Boston Scientific Scimed, Inc. Nucleation of drug delivery balloons to provide improved crystal size and density

Families Citing this family (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6955661B1 (en) 1999-01-25 2005-10-18 Atrium Medical Corporation Expandable fluoropolymer device for delivery of therapeutic agents and method of making
US7947015B2 (en) 1999-01-25 2011-05-24 Atrium Medical Corporation Application of a therapeutic substance to a tissue location using an expandable medical device
WO2005027996A3 (en) 2003-09-15 2006-06-08 Atrium Medical Corp Application of a therapeutic substance to a tissue location using an expandable medical device
US20050113687A1 (en) * 2003-09-15 2005-05-26 Atrium Medical Corporation Application of a therapeutic substance to a tissue location using a porous medical device
US8021331B2 (en) 2003-09-15 2011-09-20 Atrium Medical Corporation Method of coating a folded medical device
US9278015B2 (en) * 2003-10-16 2016-03-08 Minvasys Catheter system for stenting and drug treatment of bifurcated vessels
US8431145B2 (en) 2004-03-19 2013-04-30 Abbott Laboratories Multiple drug delivery from a balloon and a prosthesis
US20070027523A1 (en) * 2004-03-19 2007-02-01 Toner John L Method of treating vascular disease at a bifurcated vessel using coated balloon
US7989490B2 (en) * 2004-06-02 2011-08-02 Cordis Corporation Injectable formulations of taxanes for cad treatment
US10076641B2 (en) 2005-05-11 2018-09-18 The Spectranetics Corporation Methods and systems for delivering substances into luminal walls
US20080243068A1 (en) * 2005-12-29 2008-10-02 Kamal Ramzipoor Methods and apparatus for treatment of venous insufficiency
US7919108B2 (en) * 2006-03-10 2011-04-05 Cook Incorporated Taxane coatings for implantable medical devices
DE102006028232A1 (en) * 2006-06-20 2007-12-27 Bayer Technology Services Gmbh Device and method for calculating and delivering a dose of medicament
US20080140002A1 (en) * 2006-12-06 2008-06-12 Kamal Ramzipoor System for delivery of biologically active substances with actuating three dimensional surface
DE102007036685A1 (en) 2007-08-03 2009-02-05 Innora Gmbh Improved drug coated medical their preparation and use
DE102007040868A1 (en) 2007-08-29 2009-04-16 Innora Gmbh Balloon catheter with protection against unfolding
WO2009041691A1 (en) 2007-09-28 2009-04-02 Terumo Kabushiki Kaisha In-vivo indwelling matter
US8613721B2 (en) * 2007-11-14 2013-12-24 Medrad, Inc. Delivery and administration of compositions using interventional catheters
DE102008008926A1 (en) * 2008-02-13 2009-08-20 Biotronik Vi Patent Ag A system for introducing an intraluminal endoprosthesis and method for fabricating such a system
DE102008008925A1 (en) * 2008-02-13 2009-08-20 Biotronik Vi Patent Ag Catheter system for introducing an intraluminal endoprosthesis, as well as methods for making same
WO2009135125A8 (en) 2008-05-01 2010-03-18 Bayer Schering Pharma Ag Catheter balloon drug adherence techniques and methods
DE112009001065A5 (en) 2008-05-31 2011-04-14 Lothar Sellin Medical device and process for their preparation
US8049061B2 (en) 2008-09-25 2011-11-01 Abbott Cardiovascular Systems, Inc. Expandable member formed of a fibrous matrix having hydrogel polymer for intraluminal drug delivery
US8226603B2 (en) 2008-09-25 2012-07-24 Abbott Cardiovascular Systems Inc. Expandable member having a covering formed of a fibrous matrix for intraluminal drug delivery
US8500687B2 (en) 2008-09-25 2013-08-06 Abbott Cardiovascular Systems Inc. Stent delivery system having a fibrous matrix covering with improved stent retention
US8076529B2 (en) 2008-09-26 2011-12-13 Abbott Cardiovascular Systems, Inc. Expandable member formed of a fibrous matrix for intraluminal drug delivery
WO2010080575A3 (en) 2008-12-18 2010-10-14 Michal Konstantino Method and apparatus for transport of substances into body tissue
US20100261662A1 (en) * 2009-04-09 2010-10-14 Endologix, Inc. Utilization of mural thrombus for local drug delivery into vascular tissue
WO2010120620A1 (en) 2009-04-13 2010-10-21 Cook Incorporated Coated balloon catheter
CN102802816A (en) 2009-06-17 2012-11-28 Dot有限公司 Method and device for coating catheters or balloon catheters
WO2011024614A1 (en) 2009-08-27 2011-03-03 テルモ株式会社 Medical device for delivery of drug
US8951595B2 (en) 2009-12-11 2015-02-10 Abbott Cardiovascular Systems Inc. Coatings with tunable molecular architecture for drug-coated balloon
US8480620B2 (en) 2009-12-11 2013-07-09 Abbott Cardiovascular Systems Inc. Coatings with tunable solubility profile for drug-coated balloon
EP2380604A1 (en) 2010-04-19 2011-10-26 InnoRa Gmbh Improved coating formulations for scoring or cutting balloon catheters
EP2380605A1 (en) 2010-04-19 2011-10-26 InnoRa Gmbh Improved formulations for drug-coated medical devices
DE102010023105A1 (en) * 2010-06-04 2011-12-08 Bayer Schering Pharma Aktiengesellschaft Gadobutrolherstellung one-pot process using DMF-acetal and N-methylimidazole
DE102011000340A1 (en) 2010-12-04 2012-06-06 Alexander Rübben Coating for balloon of balloon catheter, has active substance and medium for modifying drug delivery at vessel that surrounds balloon
DK2646066T3 (en) 2010-12-04 2018-06-25 Aachen Scient International Pte Ltd The coatings and coating method for balloon on a balloon catheter and balloon catheter coated balloon
WO2012084024A1 (en) 2010-12-21 2012-06-28 Invatec Technology Center Gmbh Drug eluting balloon for the treatment of stenosis and method for manufacturing the balloon
WO2013079476A1 (en) 2011-11-30 2013-06-06 Bayer Materialscience Ag Drug-coated medical device and method for the production thereof
WO2013091722A1 (en) 2011-12-23 2013-06-27 Innora Gmbh Drug-coated medical devices
CN105797218A (en) 2012-03-27 2016-07-27 泰尔茂株式会社 Coating composition and medical device
EP2801379B1 (en) 2012-03-27 2017-03-08 Terumo Kabushiki Kaisha Coating composition and medical device
CA2869102A1 (en) 2012-06-08 2013-12-12 Biotronik Ag Rapamycin 40-o-cyclic hydrocarbon esters, compositions and methods
US10064981B2 (en) 2012-07-10 2018-09-04 Bayer Pharma Aktiengesellschaft Catheter with drug coating
DE102013104029A1 (en) 2013-04-22 2014-10-23 Innora Gmbh balloon catheter
US20150190618A1 (en) 2014-01-09 2015-07-09 Medtronic Vascular, Inc. Balloon Catheter With Elastomeric Sheath and Methods
US9655998B2 (en) 2014-08-07 2017-05-23 Cook Medical Technologies Llc Encapsulated drug compositions and methods of use thereof
US9180226B1 (en) 2014-08-07 2015-11-10 Cook Medical Technologies Llc Compositions and devices incorporating water-insoluble therapeutic agents and methods of the use thereof
US9675734B2 (en) 2014-08-29 2017-06-13 Invatec S.P.A. Medical balloon coated with therapeutic agent, carboxylic acid, and salt thereof

Citations (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4101984A (en) * 1975-05-09 1978-07-25 Macgregor David C Cardiovascular prosthetic devices and implants with porous systems
US4502158A (en) * 1981-11-11 1985-03-05 Masami Mouri Slip down-free socks with a garter
US4573476A (en) * 1983-11-14 1986-03-04 Ruiz Oscar F Angiographic catheter
US4677143A (en) * 1984-10-01 1987-06-30 Baxter Travenol Laboratories, Inc. Antimicrobial compositions
US4909799A (en) * 1987-09-18 1990-03-20 Olav Thulesius Methods for preventing thrombosis; and surgical implant having reduced platelet deposition characteristics
US4917686A (en) * 1985-12-16 1990-04-17 Colorado Biomedical, Inc. Antimicrobial device and method
US4925668A (en) * 1989-01-18 1990-05-15 Becton, Dickinson And Company Anti-infective and lubricious medical articles and method for their preparation
US4994047A (en) * 1988-05-06 1991-02-19 Menlo Care, Inc. Multi-layer cannula structure
US5004461A (en) * 1989-03-23 1991-04-02 Wilson Joseph E Methods for rendering plastics thromboresistant and product
US5019393A (en) * 1988-08-03 1991-05-28 New England Deaconess Hospital Corporation Biocompatible substance with thromboresistance
US5019601A (en) * 1987-12-29 1991-05-28 Cuno, Incorporated Elastomeric composition containing therapeutic agents and articles manufactured therefrom
US5019096A (en) * 1988-02-11 1991-05-28 Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
US5098977A (en) * 1987-09-23 1992-03-24 Board Of Regents, The University Of Texas System Methods and compositions for providing articles having improved biocompatability characteristics
US5102402A (en) * 1991-01-04 1992-04-07 Medtronic, Inc. Releasable coatings on balloon catheters
US5108424A (en) * 1984-01-30 1992-04-28 Meadox Medicals, Inc. Collagen-impregnated dacron graft
US5112457A (en) * 1990-07-23 1992-05-12 Case Western Reserve University Process for producing hydroxylated plasma-polymerized films and the use of the films for enhancing the compatiblity of biomedical implants
US5182317A (en) * 1988-06-08 1993-01-26 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coatings and methods of manufacture
US5197977A (en) * 1984-01-30 1993-03-30 Meadox Medicals, Inc. Drug delivery collagen-impregnated synthetic vascular graft
US5217493A (en) * 1992-03-11 1993-06-08 Board Of Regents, The University Of Texas System Antibacterial coated medical implants
US5222971A (en) * 1990-10-09 1993-06-29 Scimed Life Systems, Inc. Temporary stent and methods for use and manufacture
US5229172A (en) * 1993-01-19 1993-07-20 Medtronic, Inc. Modification of polymeric surface by graft polymerization
US5282823A (en) * 1992-03-19 1994-02-01 Medtronic, Inc. Intravascular radially expandable stent
US5288711A (en) * 1992-04-28 1994-02-22 American Home Products Corporation Method of treating hyperproliferative vascular disease
US5298255A (en) * 1988-10-28 1994-03-29 Terumo Kabushiki Kaisha Antithrombic medical material, artificial internal organ, and method for production of antithrombic medical material
US5304121A (en) * 1990-12-28 1994-04-19 Boston Scientific Corporation Drug delivery system making use of a hydrogel polymer coating
US5314688A (en) * 1991-11-21 1994-05-24 Eli Lilly And Company Local delivery of dipyridamole for the treatment of proliferative diseases
US5320634A (en) * 1990-07-03 1994-06-14 Interventional Technologies, Inc. Balloon catheter with seated cutting edges
US5380299A (en) * 1993-08-30 1995-01-10 Med Institute, Inc. Thrombolytic treated intravascular medical device
US5383927A (en) * 1992-05-07 1995-01-24 Intervascular Inc. Non-thromogenic vascular prosthesis
US5383928A (en) * 1992-06-10 1995-01-24 Emory University Stent sheath for local drug delivery
US5419760A (en) * 1993-01-08 1995-05-30 Pdt Systems, Inc. Medicament dispensing stent for prevention of restenosis of a blood vessel
US5500013A (en) * 1991-10-04 1996-03-19 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5504102A (en) * 1993-09-29 1996-04-02 Bristol-Myers Squibb Company Stabilized pharmaceutical composition and stabilizing solvent
US5510330A (en) * 1994-03-25 1996-04-23 Boehringer Mannheim Gmbh Combinations of thrombolytically active proteins and non-heparin anticoagulants, and uses thereof.
US5531716A (en) * 1993-09-29 1996-07-02 Hercules Incorporated Medical devices subject to triggered disintegration
US5605896A (en) * 1992-02-25 1997-02-25 Recordati S.A., Chemical And Pharmaceutical Company Bicyclic heterocyclic derivatives having α1 adrenergic and 5HT1A activities
US5607463A (en) * 1993-03-30 1997-03-04 Medtronic, Inc. Intravascular medical device
US5607475A (en) * 1995-08-22 1997-03-04 Medtronic, Inc. Biocompatible medical article and method
US5609629A (en) * 1995-06-07 1997-03-11 Med Institute, Inc. Coated implantable medical device
US5624411A (en) * 1993-04-26 1997-04-29 Medtronic, Inc. Intravascular stent and method
US5626562A (en) * 1994-11-28 1997-05-06 Devices For Vascular Intervention Drug delivery catheter
US5629008A (en) * 1992-06-02 1997-05-13 C.R. Bard, Inc. Method and device for long-term delivery of drugs
US5716981A (en) * 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
US5733327A (en) * 1994-10-17 1998-03-31 Igaki; Keiji Stent for liberating drug
US5762638A (en) * 1991-02-27 1998-06-09 Shikani; Alain H. Anti-infective and anti-inflammatory releasing systems for medical devices
US5766158A (en) * 1995-02-06 1998-06-16 Surface Solutions Laboratories, Inc. Medical apparatus with scratch-resistant coating and method of making same
US5770198A (en) * 1988-05-18 1998-06-23 The Research Foundation Of The State Of New York Platelet-specific chimeric 7E3 immunoglobulin
US5772640A (en) * 1996-01-05 1998-06-30 The Trustees Of Columbia University Of The City Of New York Triclosan-containing medical devices
US5863745A (en) * 1986-09-24 1999-01-26 The United States Of America As Represented By The Department Of Health And Human Services Recombinant antibody-toxin fusion protein
US5873904A (en) * 1995-06-07 1999-02-23 Cook Incorporated Silver implantable medical device
US5902283A (en) * 1995-04-24 1999-05-11 Baylor College Of Medicine Board Of Regents Antimicrobial impregnated catheters and other medical implants
US5916596A (en) * 1993-02-22 1999-06-29 Vivorx Pharmaceuticals, Inc. Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof
US6017948A (en) * 1998-10-30 2000-01-25 Supergen, Inc. Water-miscible pharmaceutical compositions
US6039721A (en) * 1996-07-24 2000-03-21 Cordis Corporation Method and catheter system for delivering medication with an everting balloon catheter
US6064624A (en) * 1997-09-16 2000-05-16 Micron Technology, Inc. Circuit and method for eliminating idle cycles in a memory device
US6171232B1 (en) * 1997-06-26 2001-01-09 Cordis Corporation Method for targeting in vivo nitric oxide release
US6177061B1 (en) * 1997-04-23 2001-01-23 Nycomed Imaging As Contrast agents comprising an azeotropic mixture of two gases for ultrasound investigations
US6191619B1 (en) * 1999-08-24 2001-02-20 Analog Devices, Inc. Translators and methods for converting differential signals to single-ended signals
US6203487B1 (en) * 1997-12-31 2001-03-20 Thomas Jefferson University Use of magnetic particles in the focal delivery of cells
US6207133B1 (en) * 1997-06-06 2001-03-27 Max-Delbrück-Centrum für Molekulare Medizin Anti-tumoral therapy agent containing a contrast agent
US6214333B1 (en) * 1997-07-08 2001-04-10 Texas Heart Institute Vasoprotective recombinant adenovirus vector containing a human TFPI gene
US6221467B1 (en) * 1997-06-03 2001-04-24 Scimed Life Systems, Inc. Coating gradient for lubricious coatings on balloon catheters
US6231615B1 (en) * 1997-10-14 2001-05-15 Parallax Medical, Inc. Enhanced visibility materials for implantation in hard tissue
US6240616B1 (en) * 1997-04-15 2001-06-05 Advanced Cardiovascular Systems, Inc. Method of manufacturing a medicated porous metal prosthesis
US6248100B1 (en) * 1997-08-14 2001-06-19 Scimed Life Systems, Inc. Drainage catheter delivery system
US6335029B1 (en) * 1998-08-28 2002-01-01 Scimed Life Systems, Inc. Polymeric coatings for controlled delivery of active agents
US6355058B1 (en) * 1999-12-30 2002-03-12 Advanced Cardiovascular Systems, Inc. Stent with radiopaque coating consisting of particles in a binder
US20020032414A1 (en) * 1998-08-20 2002-03-14 Ragheb Anthony O. Coated implantable medical device
US6364856B1 (en) * 1998-04-14 2002-04-02 Boston Scientific Corporation Medical device with sponge coating for controlled drug release
US6369039B1 (en) * 1998-06-30 2002-04-09 Scimed Life Sytems, Inc. High efficiency local drug delivery
US6375931B2 (en) * 1996-10-21 2002-04-23 Nycomed Imaging As Contrast agents
US6503954B1 (en) * 2000-03-31 2003-01-07 Advanced Cardiovascular Systems, Inc. Biocompatible carrier containing actinomycin D and a method of forming the same
US6515016B2 (en) * 1996-12-02 2003-02-04 Angiotech Pharmaceuticals, Inc. Composition and methods of paclitaxel for treating psoriasis
US20030028244A1 (en) * 1995-06-07 2003-02-06 Cook Incorporated Coated implantable medical device
US20030028243A1 (en) * 1995-06-07 2003-02-06 Cook Incorporated Coated implantable medical device
US20030036794A1 (en) * 1995-06-07 2003-02-20 Cook Incorporated Coated implantable medical device
US20030059454A1 (en) * 2001-09-24 2003-03-27 Barry James J. Optimized dosing for drug coated stents
US6544544B2 (en) * 1993-07-19 2003-04-08 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions and methods of use
US6544223B1 (en) * 2001-01-05 2003-04-08 Advanced Cardiovascular Systems, Inc. Balloon catheter for delivering therapeutic agents
US20030100600A1 (en) * 1993-07-29 2003-05-29 The Gov't Of The U.S.A. As Represented By The Secretary Of The Dept. Of Health And Human Service Method for treating atherosclerosis or restenosis using microtubule stabilizing agent
US6682546B2 (en) * 1994-07-08 2004-01-27 Aga Medical Corporation Intravascular occlusion devices
US6682545B1 (en) * 1999-10-06 2004-01-27 The Penn State Research Foundation System and device for preventing restenosis in body vessels
US6695811B2 (en) * 1998-08-06 2004-02-24 Cardeon Corporation Aortic catheter with porous aortic arch balloon
US6706892B1 (en) * 1999-09-07 2004-03-16 Conjuchem, Inc. Pulmonary delivery for bioconjugation
US20040068241A1 (en) * 1996-06-04 2004-04-08 Fischer Frank J. Implantable medical device
US20040073284A1 (en) * 2002-07-12 2004-04-15 Cook Incorporated Coated medical device
US20050010522A1 (en) * 2003-07-10 2005-01-13 Finalabo Co., Ltd. Management system for open position with indication for loss cut and held stock management system with indication for loss cut
US20050042295A1 (en) * 1993-07-19 2005-02-24 Hunter William L. Anti-angiogenic compositions and methods of use
US6867190B2 (en) * 2000-07-12 2005-03-15 The Board Of Regents, The University Of Texas System Methods of therapy with thrombin derived peptides
US20060020243A1 (en) * 2002-09-20 2006-01-26 Ulrich Speck Medical device for dispensing medicaments
US7060051B2 (en) * 2002-09-24 2006-06-13 Scimed Life Systems, Inc. Multi-balloon catheter with hydrogel coating
US20070128118A1 (en) * 2005-12-05 2007-06-07 Nitto Denko Corporation Polyglutamate-amino acid conjugates and methods
US20080102033A1 (en) * 2001-03-26 2008-05-01 Ulrich Speck Preparation for the prophylaxis of restenosis

Family Cites Families (202)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US554181A (en) * 1896-02-04 Robert frederick hall
US2624642A (en) * 1950-05-24 1953-01-06 Symington Gould Corp Journal box lid
US4247352A (en) * 1976-11-29 1981-01-27 North American Philips Corporation Method of bonding crystal layers to insulating substrates
DE2721752C2 (en) 1977-05-13 1983-12-29 Siemens Ag, 1000 Berlin Und 8000 Muenchen, De
DE2909439A1 (en) * 1979-03-08 1980-09-18 Schering Ag New nonionic roentgenkontrastmittel
US4479795A (en) 1979-06-29 1984-10-30 The Procter & Gamble Company Antimicrobial polymer compositions
US4343788A (en) 1979-06-29 1982-08-10 The Procter & Gamble Company Antimicrobial polymer compositions
US4305926A (en) 1979-09-13 1981-12-15 Johannes Everse Immobilization of Streptokinase
US4476590A (en) 1980-03-27 1984-10-16 National Research Development Corporation Antimicrobial surgical implants
US4502159A (en) 1982-08-12 1985-03-05 Shiley Incorporated Tubular prostheses prepared from pericardial tissue
US4769013A (en) 1982-09-13 1988-09-06 Hydromer, Inc. Bio-effecting medical material and device
FR2540128B1 (en) 1983-01-27 1986-02-21 Rhone Poulenc Spec Chim organopolysiloxane compositions containing polyacyloxysilanes and curing very quickly elastomers in the presence of the accelerator metal hydroxide type
US5456663A (en) 1984-05-25 1995-10-10 Lemelson; Jerome H. Drugs and methods for treating diseases
US4879135A (en) 1984-07-23 1989-11-07 University Of Medicine And Dentistry Of New Jersey Drug bonded prosthesis and process for producing same
GB8422876D0 (en) 1984-09-11 1984-10-17 Secr Defence Silicon implant devices
US4677413A (en) * 1984-11-20 1987-06-30 Vishay Intertechnology, Inc. Precision power resistor with very low temperature coefficient of resistance
WO1986007541A1 (en) 1985-06-19 1986-12-31 Yasushi Zyo Composition which can impart antithrombotic ability and medical apparatus to be in contact with blood
JPH0663145B2 (en) 1985-09-11 1994-08-17 豊和工業株式会社 Sliver for a spinning machine - feeding method and device
US4733665C2 (en) 1985-11-07 2002-01-29 Expandable Grafts Partnership Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft
US5059211A (en) * 1987-06-25 1991-10-22 Duke University Absorbable vascular stent
US4886062A (en) 1987-10-19 1989-12-12 Medtronic, Inc. Intravascular radially expandable stent and method of implant
JP2561853B2 (en) 1988-01-28 1996-12-11 株式会社ジェイ・エム・エス Compacts and methods of use thereof with a shape memory
US5157049A (en) 1988-03-07 1992-10-20 The United States Of America As Represented By The Department Of Health & Human Services Method of treating cancers sensitive to treatment with water soluble derivatives of taxol
US4950256A (en) 1988-04-07 1990-08-21 Luther Medical Products, Inc. Non-thrombogenic intravascular time release catheter
JP3682974B2 (en) 1991-11-27 2005-08-17 株式会社ファノスディベロップメント Compound to bind bio active substance to the bio-particle surface layer, composition, and methods
US5019090A (en) 1988-09-01 1991-05-28 Corvita Corporation Radially expandable endoprosthesis and the like
US5053048A (en) 1988-09-22 1991-10-01 Cordis Corporation Thromboresistant coating
US5165952A (en) 1989-01-18 1992-11-24 Becton, Dickinson And Company Anti-infective and antithrombogenic medical articles and method for their preparation
US6146358A (en) 1989-03-14 2000-11-14 Cordis Corporation Method and apparatus for delivery of therapeutic agent
EP0429585A4 (en) 1989-04-28 1992-03-25 Syracuse University Cytochalasin compositions and therapeutic methods
US5051257A (en) 1989-05-09 1991-09-24 Pietronigro Dennis D Antineoplastic solution and method for treating neoplasms
WO1990013332A1 (en) 1989-05-11 1990-11-15 Cedars-Sinai Medical Center Stent with sustained drug delivery
US4997643A (en) * 1989-07-12 1991-03-05 Union Carbide Chemicals And Plastics Company Inc. Polymeric salt delivery systems
US5455040A (en) 1990-07-26 1995-10-03 Case Western Reserve University Anticoagulant plasma polymer-modified substrate
US5232685A (en) * 1989-11-03 1993-08-03 Schering Aktiengesellschaft Nonionic x-ray contrast medium with high iodine content
US5067491A (en) 1989-12-08 1991-11-26 Becton, Dickinson And Company Barrier coating on blood contacting devices
US5059166A (en) 1989-12-11 1991-10-22 Medical Innovative Technologies R & D Limited Partnership Intra-arterial stent with the capability to inhibit intimal hyperplasia
US5135516A (en) 1989-12-15 1992-08-04 Boston Scientific Corporation Lubricious antithrombogenic catheters, guidewires and coatings
DE69108423T2 (en) 1990-02-08 1995-07-27 Howmedica Inflatable dilator.
WO1991012779A1 (en) 1990-02-28 1991-09-05 Medtronic, Inc. Intralumenal drug eluting prosthesis
US5166143A (en) * 1990-05-31 1992-11-24 E. R. Squibb & Sons, Inc. Method for preventing onset of restenosis after angioplasty employing an ace inhibitor
US5407683A (en) 1990-06-01 1995-04-18 Research Corporation Technologies, Inc. Pharmaceutical solutions and emulsions containing taxol
US5163952A (en) 1990-09-14 1992-11-17 Michael Froix Expandable polymeric stent with memory and delivery apparatus and method
US5244654A (en) 1990-11-08 1993-09-14 Cordis Corporation Radiofrequency plasma biocompatibility treatment of inside surfaces of medical tubing and the like
US5674192A (en) 1990-12-28 1997-10-07 Boston Scientific Corporation Drug delivery
US6524274B1 (en) 1990-12-28 2003-02-25 Scimed Life Systems, Inc. Triggered release hydrogel drug delivery system
EP0565604B1 (en) 1990-12-28 1999-07-28 Boston Scientific Corporation Catheter for drug delivery system
US5893840A (en) * 1991-01-04 1999-04-13 Medtronic, Inc. Releasable microcapsules on balloon catheters
US5324261A (en) 1991-01-04 1994-06-28 Medtronic, Inc. Drug delivery balloon catheter with line of weakness
US5344411A (en) 1991-02-27 1994-09-06 Leonard Bloom Method and device for inhibiting HIV, hepatitis B and other viruses and germs when using a catheter in a medical environment
US5171217A (en) 1991-02-28 1992-12-15 Indiana University Foundation Method for delivery of smooth muscle cell inhibitors
DE4115950A1 (en) 1991-05-16 1992-11-19 Herberts Gmbh Liquid mixtures of photo initiators, methods for their preparation and their use
NL9101159A (en) 1991-07-03 1993-02-01 Industrial Res Bv Shape-retaining to make expandable ring, cylinder or sleeve.
US5356433A (en) 1991-08-13 1994-10-18 Cordis Corporation Biocompatible metal surfaces
US6491938B2 (en) 1993-05-13 2002-12-10 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6515009B1 (en) 1991-09-27 2003-02-04 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5981568A (en) 1993-01-28 1999-11-09 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
WO1993006792A1 (en) 1991-10-04 1993-04-15 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5464450A (en) 1991-10-04 1995-11-07 Scimed Lifesystems Inc. Biodegradable drug delivery vascular stent
DE4135193C1 (en) 1991-10-22 1993-03-11 Schering Ag Berlin Und Bergkamen, 1000 Berlin, De
JP3093375B2 (en) 1991-11-01 2000-10-03 株式会社東海メディカルプロダクツ Method for immobilizing antithrombotic agent
US5264220A (en) 1991-11-12 1993-11-23 Long David M Jr Method of extending the vascular dwell-time of particulate therapeutic and particulate diagnostic agents
US5302397A (en) 1991-11-19 1994-04-12 Amsden Brian G Polymer-based drug delivery system
WO1993011668A1 (en) 1991-12-10 1993-06-24 Rush-Presbyterian-St. Luke's Medical Center Methods and compositions for reducing multi-drug resistance
CA2086642C (en) 1992-01-09 2004-06-15 Randall E. Morris Method of treating hyperproliferative vascular disease
US5176626A (en) * 1992-01-15 1993-01-05 Wilson-Cook Medical, Inc. Indwelling stent
US5571166A (en) * 1992-03-19 1996-11-05 Medtronic, Inc. Method of making an intraluminal stent
US5599352A (en) 1992-03-19 1997-02-04 Medtronic, Inc. Method of making a drug eluting stent
DE4222380A1 (en) 1992-07-08 1994-01-13 Ernst Peter Prof Dr M Strecker In the body of a patient percutaneously implantable endoprosthesis
DE4225553C1 (en) 1992-08-03 1994-05-11 Michael Dr Rudolf Balloon catheter with inner and outer balloons for cardiology - allowing application of both dilatation and active agents
EP1512398A1 (en) 1997-03-31 2005-03-09 Boston Scientific Limited Intravascular stent with cytoskeletal inhibitors for the prevention of restenosis
CA2145093C (en) 1992-09-25 2007-04-10 Lawrence Leroy Kunz Therapeutic inhibitor of vascular smooth muscle cells
US5336178A (en) 1992-11-02 1994-08-09 Localmed, Inc. Intravascular catheter with infusion array
US5449382A (en) 1992-11-04 1995-09-12 Dayton; Michael P. Minimally invasive bioactivated endoprosthesis for vessel repair
US5578075B1 (en) 1992-11-04 2000-02-08 Daynke Res Inc Minimally invasive bioactivated endoprosthesis for vessel repair
US5342348A (en) 1992-12-04 1994-08-30 Kaplan Aaron V Method and device for treating and enlarging body lumens
EP0604022A1 (en) 1992-12-22 1994-06-29 Advanced Cardiovascular Systems, Inc. Multilayered biodegradable stent and method for its manufacture
US5443458A (en) 1992-12-22 1995-08-22 Advanced Cardiovascular Systems, Inc. Multilayered biodegradable stent and method of manufacture
EP1447098A3 (en) 1993-01-28 2005-06-29 Boston Scientific Limited Therapeutic inhibitor of vascular smooth muscle cells
US5976534A (en) * 1993-02-25 1999-11-02 Zymogenetics, Inc. Inhibition of intimal hyperplasia using antibodies to PDGF receptors and heparin
US5534288A (en) * 1993-03-23 1996-07-09 United States Surgical Corporation Infection-resistant surgical devices and methods of making them
WO1994023787A1 (en) 1993-04-22 1994-10-27 Rammler David H Sampling balloon catheter
US5531715A (en) 1993-05-12 1996-07-02 Target Therapeutics, Inc. Lubricious catheters
EP1510220B1 (en) 1993-05-13 2008-07-23 Poniard Pharmaceuticals, Inc. Therapeutic inhibitor of vascular smooth muscle cells
US5567495A (en) 1993-08-06 1996-10-22 The Trustees Of Columbia University In The City Of New York Infection resistant medical devices
US5746745A (en) * 1993-08-23 1998-05-05 Boston Scientific Corporation Balloon catheter
WO1995005860A1 (en) 1993-08-23 1995-03-02 Boston Scientific Corporation Improved balloon catheter
DE4334272C2 (en) 1993-10-07 1996-07-18 Stemberger Axel Dr Coating for biomaterial and its use
US5457113A (en) 1993-10-15 1995-10-10 Eli Lilly And Company Methods for inhibiting vascular smooth muscle cell proliferation and restinosis
US5454886A (en) 1993-11-18 1995-10-03 Westaim Technologies Inc. Process of activating anti-microbial materials
DE4341478C2 (en) 1993-12-02 1998-10-08 Max Delbrueck Centrum Means for anti-tumor therapy
US5397307A (en) 1993-12-07 1995-03-14 Schneider (Usa) Inc. Drug delivery PTCA catheter and method for drug delivery
DE4408768C1 (en) * 1994-03-15 1995-05-04 Siemens Ag Method for filtering a series of digital values with an improved signal-to-noise behaviour (noise performance), and circuit arrangement for carrying out the method
DE4412055C1 (en) 1994-04-07 1995-05-18 Siemens Ag MOS terminal resistance circuit for transmission line
US5554181A (en) 1994-05-04 1996-09-10 Regents Of The University Of Minnesota Stent
JP3631777B2 (en) 1994-06-03 2005-03-23 テルモ株式会社 Drug delivery catheter
US5824644A (en) * 1994-07-07 1998-10-20 G. D. Searle & Co. Method of attenuating arterial stenosis
US5649977A (en) * 1994-09-22 1997-07-22 Advanced Cardiovascular Systems, Inc. Metal reinforced polymer stent
US5643580A (en) * 1994-10-17 1997-07-01 Surface Genesis, Inc. Biocompatible coating, medical device using the same and methods
GB9423419D0 (en) * 1994-11-19 1995-01-11 Andaris Ltd Preparation of hollow microcapsules
DE4446694A1 (en) 1994-12-09 1996-06-13 Schering Ag Use of additives to contrast agents for improving imaging
CA2163837C (en) 1994-12-13 1999-07-20 Robert K. Perrone Crystalline paclitaxel hydrates
DE19505155A1 (en) 1995-02-16 1996-08-22 Magna Zippex Autotechnik Gmbh A method for manufacturing a lining part made of plastic and produced especially for this procedure lining part
US6558798B2 (en) * 1995-02-22 2003-05-06 Scimed Life Systems, Inc. Hydrophilic coating and substrates coated therewith having enhanced durability and lubricity
US5681846A (en) 1995-03-17 1997-10-28 Board Of Regents, The University Of Texas System Extended stability formulations for paclitaxel
US5605696A (en) 1995-03-30 1997-02-25 Advanced Cardiovascular Systems, Inc. Drug loaded polymeric material and method of manufacture
DE19514104C2 (en) 1995-04-13 1997-05-28 Behringwerke Ag Coating for can be introduced into the bloodstream or into the tissue of the human body biomaterial
US5820607A (en) 1995-06-05 1998-10-13 Board Of Regents, University Of Texas Systems Multipurpose anti-microbial silastic sheath system for the prevention of device-related infections
DK0804151T3 (en) 1995-06-29 2003-01-20 Macrochem Corp Lipophilic and amphiphilic film-forming polymer compositions and their use in topical agent delivery systems, and process for the delivery of the agents to the skin
DE69611378D1 (en) 1995-11-08 2001-02-01 Scimed Life Systems Inc necking process for balloon manufacture by cold drawing /
US5792158A (en) 1995-11-15 1998-08-11 Lary; Banning Gray University dilator with expandable incisor
ES2208884T3 (en) 1996-01-25 2004-06-16 Schering Aktiengesellschaft Solutions improved contrast agents for intravascular administration.
US6264642B1 (en) 1996-02-29 2001-07-24 Kimberly-Clark Worldwide, Inc. Elasticized laminate, liquid impermeable backsheet for a disposable absorbent article
EP1683520B1 (en) * 1996-03-12 2013-11-20 PG-TXL Company, L.P. Water-soluble prodrugs
US6441025B2 (en) * 1996-03-12 2002-08-27 Pg-Txl Company, L.P. Water soluble paclitaxel derivatives
US6071285A (en) 1996-03-25 2000-06-06 Lashinski; Robert D. Rapid exchange folded balloon catheter and stent delivery system
WO1997046268A1 (en) 1996-06-04 1997-12-11 Cook Incorporated Implantable medical device
US5797887A (en) * 1996-08-27 1998-08-25 Novovasc Llc Medical device with a surface adapted for exposure to a blood stream which is coated with a polymer containing a nitrosyl-containing organo-metallic compound which releases nitric oxide from the coating to mediate platelet aggregation
CA2209366C (en) 1996-09-13 2004-11-02 Interventional Technologies, Inc. Incisor-dilator with tapered balloon
US5954740A (en) 1996-09-23 1999-09-21 Boston Scientific Corporation Catheter balloon having raised radial segments
US5978698A (en) * 1996-10-08 1999-11-02 Merck & Co., Inc. Angioplasty procedure using nonionic contrast media
US5893867A (en) 1996-11-06 1999-04-13 Percusurge, Inc. Stent positioning apparatus and method
US6495579B1 (en) 1996-12-02 2002-12-17 Angiotech Pharmaceuticals, Inc. Method for treating multiple sclerosis
US6071616A (en) 1996-12-05 2000-06-06 Texas Instruments Incorporated Opaque low reflecting coating aperture on glass
US5980972A (en) 1996-12-20 1999-11-09 Schneider (Usa) Inc Method of applying drug-release coatings
US5871692A (en) 1997-01-14 1999-02-16 Steris Corporation Method and apparatus for cleaning, decontaminating, and sterilizing catheters
US5868719A (en) 1997-01-15 1999-02-09 Boston Scientific Corporation Drug delivery balloon catheter device
US6491619B1 (en) 1997-01-31 2002-12-10 Endologix, Inc Radiation delivery catheters and dosimetry methods
US6273913B1 (en) 1997-04-18 2001-08-14 Cordis Corporation Modified stent useful for delivery of drugs along stent strut
DE19718339A1 (en) * 1997-04-30 1998-11-12 Schering Ag Polymer coated stents, methods for their preparation and their use for the prophylaxis of restenosis
JPH1112160A (en) 1997-06-19 1999-01-19 Nippon Schering Kk Water-soluble anti-tumor medicine-containing emulsion type preparation and kit
US6306166B1 (en) * 1997-08-13 2001-10-23 Scimed Life Systems, Inc. Loading and release of water-insoluble drugs
US5921952A (en) * 1997-08-14 1999-07-13 Boston Scientific Corporation Drainage catheter delivery system
EP1004195A1 (en) 1997-08-20 2000-05-31 Maxon Systems Inc. (London) Ltd. Communication apparatus and method for locating stored entries in an electronic telephone directory
US6284333B1 (en) 1997-09-10 2001-09-04 Scimed Life Systems, Inc. Medical devices made from polymer blends containing low melting temperature liquid crystal polymers
WO1999013916A3 (en) 1997-09-18 2001-12-20 Nycomed Imaging As Methods and compositions for medical imaging
US6890546B2 (en) 1998-09-24 2005-05-10 Abbott Laboratories Medical devices containing rapamycin analogs
DE69810951T2 (en) * 1997-10-15 2004-01-29 Sherwood Serv Ag Lubricant coating for medical devices
US6273908B1 (en) 1997-10-24 2001-08-14 Robert Ndondo-Lay Stents
US6485514B1 (en) 1997-12-12 2002-11-26 Supergen, Inc. Local delivery of therapeutic agents
US6123923A (en) * 1997-12-18 2000-09-26 Imarx Pharmaceutical Corp. Optoacoustic contrast agents and methods for their use
CN1224622A (en) 1998-01-24 1999-08-04 张尚权 Tumor target direction contrast agent
US6221425B1 (en) 1998-01-30 2001-04-24 Advanced Cardiovascular Systems, Inc. Lubricious hydrophilic coating for an intracorporeal medical device
GB9802745D0 (en) * 1998-02-09 1998-04-08 Pharmacia & Upjohn Spa Benzyloxy prodigiosine compounds
US6623521B2 (en) * 1998-02-17 2003-09-23 Md3, Inc. Expandable stent with sliding and locking radial elements
US5997162A (en) 1998-03-13 1999-12-07 Osram Sylvania Inc. Horizontal HID vehicle headlamp with magnetic deflection
US6306151B1 (en) 1998-03-31 2001-10-23 Interventional Technologies Inc. Balloon with reciprocating stent incisor
DE69942348D1 (en) 1998-04-27 2010-06-17 Surmodics Inc Bioactive agents releasing coatings
US6296655B1 (en) 1998-04-27 2001-10-02 Advanced Cardiovascular Systems, Inc. Catheter balloon with biased multiple wings
WO1999059556A1 (en) 1998-05-15 1999-11-25 Nasa/Johnson Space Center Externally triggered microcapsules
WO2000000238A9 (en) 1998-06-26 2000-05-11 Quanam Medical Corp Topoisomerase inhibitors for prevention of restenosis
US6203812B1 (en) 1998-06-29 2001-03-20 Hydromer, Inc. Hydrophilic polymer blends used to prevent cow skin infections
US6013092A (en) * 1998-08-18 2000-01-11 Baxter International Inc. Folding of catheter-mounted balloons to facilitate non-rotational radial expansion of intraluminal devices
WO2000010552A3 (en) 1998-08-24 2000-11-23 Global Vascular Concepts Inc Use of anti-angiogenic agents for inhibiting vessel wall injury
CA2497640C (en) 2002-09-06 2012-02-07 Abbott Laboratories Medical device having hydration inhibitor
US5922754A (en) * 1998-10-02 1999-07-13 Abbott Laboratories Pharmaceutical compositions containing paclitaxel
JP2002529778A (en) * 1998-10-30 2002-09-10 サートコ インコーポレイテッド Integration into shared randomness of distributed encryption
US6120533A (en) 1998-11-13 2000-09-19 Isostent, Inc. Stent delivery system for a radioisotope stent
EP1135165A1 (en) * 1998-12-03 2001-09-26 Boston Scientific Limited Stent having drug crystals thereon
US6040330A (en) * 1999-01-08 2000-03-21 Bionumerik Pharmaceuticals, Inc. Pharmaceutical formulations of taxanes
US7780628B1 (en) 1999-01-11 2010-08-24 Angiodynamics, Inc. Apparatus and methods for treating congestive heart disease
CA2368196A1 (en) 1999-01-28 2000-08-03 You-Ling Fan Lubricious medical devices
US6419692B1 (en) 1999-02-03 2002-07-16 Scimed Life Systems, Inc. Surface protection method for stents and balloon catheters for drug delivery
WO2000047197A3 (en) 1999-02-12 2001-04-05 Quanam Medical Corp Alkylating agents for treatment of cellular proliferation
US6790228B2 (en) * 1999-12-23 2004-09-14 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
US6203551B1 (en) * 1999-10-04 2001-03-20 Advanced Cardiovascular Systems, Inc. Chamber for applying therapeutic substances to an implant device
WO2001024866A1 (en) 1999-10-06 2001-04-12 The Penn State Research Foundation System and device for preventing restenosis in body vessels
JP4613406B2 (en) 1999-11-05 2011-01-19 株式会社デンソー Light-receiving element, the distance measuring device and the distance-vision measuring instrument
US6616591B1 (en) * 1999-12-08 2003-09-09 Scimed Life Systems, Inc. Radioactive compositions and methods of use thereof
US6254921B1 (en) 1999-12-08 2001-07-03 Surmodics, Inc. Coating process and apparatus
US6719774B1 (en) 1999-12-23 2004-04-13 Advanced Cardiovascular Systems, Inc. Method for forming low profile balloon and low profile balloon for use with a catheter
US6899731B2 (en) 1999-12-30 2005-05-31 Boston Scientific Scimed, Inc. Controlled delivery of therapeutic agents by insertable medical devices
EP1250166B1 (en) 2000-01-25 2010-03-17 Edwards Lifesciences Corporation Delivery systems for treatment of restenosis and anastomotic intimal hyperplasia
US6575888B2 (en) * 2000-01-25 2003-06-10 Biosurface Engineering Technologies, Inc. Bioabsorbable brachytherapy device
JP4626005B2 (en) * 2000-01-27 2011-02-02 東洋紡績株式会社 Hemocompatibility composition and coated medical devices it
US6599448B1 (en) * 2000-05-10 2003-07-29 Hydromer, Inc. Radio-opaque polymeric compositions
US6585765B1 (en) 2000-06-29 2003-07-01 Advanced Cardiovascular Systems, Inc. Implantable device having substances impregnated therein and a method of impregnating the same
KR20030045847A (en) 2000-10-31 2003-06-11 쿡 인코포레이티드 Coated implantable medical device
US6635082B1 (en) * 2000-12-29 2003-10-21 Advanced Cardiovascular Systems Inc. Radiopaque stent
US7179251B2 (en) * 2001-01-17 2007-02-20 Boston Scientific Scimed, Inc. Therapeutic delivery balloon
US20020119178A1 (en) 2001-02-23 2002-08-29 Luc Levesque Drug eluting device for treating vascular diseases
FR2823118B1 (en) * 2001-04-04 2004-03-19 Lavipharm Lab Inc New film forming composition for topical use and its use for the issuance of active agents
JP4294470B2 (en) 2001-06-14 2009-07-15 クック インコーポレイテッド Intravascular filter
WO2003022264A1 (en) * 2001-09-13 2003-03-20 Korea Institute Of Science And Technology Paclitaxel mixed composition and water-in-oil type emulsion formulation for chemoembolization and preparation method thereof
US20030143189A1 (en) 2001-11-14 2003-07-31 Askill Ian N Therapy for topical diseases
DE60237915D1 (en) 2001-12-03 2010-11-18 Universitaetsklinikum Charite Podophyllotoxine als antiproliferative mittel
CA2444781A1 (en) 2002-10-17 2004-04-17 Rolf C. Hagen Inc. Topical gel matrix
US7491234B2 (en) * 2002-12-03 2009-02-17 Boston Scientific Scimed, Inc. Medical devices for delivery of therapeutic agents
US20040224003A1 (en) 2003-02-07 2004-11-11 Schultz Robert K. Drug formulations for coating medical devices
US7445792B2 (en) 2003-03-10 2008-11-04 Abbott Laboratories Medical device having a hydration inhibitor
US20050063926A1 (en) * 2003-09-23 2005-03-24 Bathina Harinath B. Film-forming compositions for protecting animal skin
EP1765429A2 (en) 2004-05-12 2007-03-28 Medtronic Vascular, Inc. Drug-polymer coated stent
US20060029720A1 (en) 2004-08-03 2006-02-09 Anastasia Panos Methods and apparatus for injection coating a medical device
US7919108B2 (en) * 2006-03-10 2011-04-05 Cook Incorporated Taxane coatings for implantable medical devices
JP4892289B2 (en) * 2006-07-07 2012-03-07 株式会社日立製作所 Storage system including a plurality of storage devices
US20080012034A1 (en) 2006-07-17 2008-01-17 3M Innovative Properties Company Led package with converging extractor
US8414526B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids
US8425459B2 (en) 2006-11-20 2013-04-23 Lutonix, Inc. Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent
US8414525B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
EP2092941A3 (en) 2006-11-20 2009-11-18 Lutonix, Inc. Drug releasing coatings for medical devices
US8414909B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
DE102007003184A1 (en) * 2007-01-22 2008-07-24 Orlowski, Michael, Dr. A method for loading of structured surfaces

Patent Citations (98)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4101984A (en) * 1975-05-09 1978-07-25 Macgregor David C Cardiovascular prosthetic devices and implants with porous systems
US4502158A (en) * 1981-11-11 1985-03-05 Masami Mouri Slip down-free socks with a garter
US4573476A (en) * 1983-11-14 1986-03-04 Ruiz Oscar F Angiographic catheter
US5108424A (en) * 1984-01-30 1992-04-28 Meadox Medicals, Inc. Collagen-impregnated dacron graft
US5197977A (en) * 1984-01-30 1993-03-30 Meadox Medicals, Inc. Drug delivery collagen-impregnated synthetic vascular graft
US4677143A (en) * 1984-10-01 1987-06-30 Baxter Travenol Laboratories, Inc. Antimicrobial compositions
US4917686A (en) * 1985-12-16 1990-04-17 Colorado Biomedical, Inc. Antimicrobial device and method
US5863745A (en) * 1986-09-24 1999-01-26 The United States Of America As Represented By The Department Of Health And Human Services Recombinant antibody-toxin fusion protein
US4909799A (en) * 1987-09-18 1990-03-20 Olav Thulesius Methods for preventing thrombosis; and surgical implant having reduced platelet deposition characteristics
US5098977A (en) * 1987-09-23 1992-03-24 Board Of Regents, The University Of Texas System Methods and compositions for providing articles having improved biocompatability characteristics
US5019601A (en) * 1987-12-29 1991-05-28 Cuno, Incorporated Elastomeric composition containing therapeutic agents and articles manufactured therefrom
US5019096A (en) * 1988-02-11 1991-05-28 Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
US4994047A (en) * 1988-05-06 1991-02-19 Menlo Care, Inc. Multi-layer cannula structure
US5770198A (en) * 1988-05-18 1998-06-23 The Research Foundation Of The State Of New York Platelet-specific chimeric 7E3 immunoglobulin
US5182317A (en) * 1988-06-08 1993-01-26 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coatings and methods of manufacture
US5019393A (en) * 1988-08-03 1991-05-28 New England Deaconess Hospital Corporation Biocompatible substance with thromboresistance
US5298255A (en) * 1988-10-28 1994-03-29 Terumo Kabushiki Kaisha Antithrombic medical material, artificial internal organ, and method for production of antithrombic medical material
US4925668A (en) * 1989-01-18 1990-05-15 Becton, Dickinson And Company Anti-infective and lubricious medical articles and method for their preparation
US5004461A (en) * 1989-03-23 1991-04-02 Wilson Joseph E Methods for rendering plastics thromboresistant and product
US5320634A (en) * 1990-07-03 1994-06-14 Interventional Technologies, Inc. Balloon catheter with seated cutting edges
US5112457A (en) * 1990-07-23 1992-05-12 Case Western Reserve University Process for producing hydroxylated plasma-polymerized films and the use of the films for enhancing the compatiblity of biomedical implants
US5222971A (en) * 1990-10-09 1993-06-29 Scimed Life Systems, Inc. Temporary stent and methods for use and manufacture
US5304121A (en) * 1990-12-28 1994-04-19 Boston Scientific Corporation Drug delivery system making use of a hydrogel polymer coating
US5102402A (en) * 1991-01-04 1992-04-07 Medtronic, Inc. Releasable coatings on balloon catheters
US5762638A (en) * 1991-02-27 1998-06-09 Shikani; Alain H. Anti-infective and anti-inflammatory releasing systems for medical devices
US5500013A (en) * 1991-10-04 1996-03-19 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5314688A (en) * 1991-11-21 1994-05-24 Eli Lilly And Company Local delivery of dipyridamole for the treatment of proliferative diseases
US5605896A (en) * 1992-02-25 1997-02-25 Recordati S.A., Chemical And Pharmaceutical Company Bicyclic heterocyclic derivatives having α1 adrenergic and 5HT1A activities
US5217493A (en) * 1992-03-11 1993-06-08 Board Of Regents, The University Of Texas System Antibacterial coated medical implants
US5282823A (en) * 1992-03-19 1994-02-01 Medtronic, Inc. Intravascular radially expandable stent
US5288711A (en) * 1992-04-28 1994-02-22 American Home Products Corporation Method of treating hyperproliferative vascular disease
US5383927A (en) * 1992-05-07 1995-01-24 Intervascular Inc. Non-thromogenic vascular prosthesis
US5629008A (en) * 1992-06-02 1997-05-13 C.R. Bard, Inc. Method and device for long-term delivery of drugs
US5383928A (en) * 1992-06-10 1995-01-24 Emory University Stent sheath for local drug delivery
US5419760A (en) * 1993-01-08 1995-05-30 Pdt Systems, Inc. Medicament dispensing stent for prevention of restenosis of a blood vessel
US5229172A (en) * 1993-01-19 1993-07-20 Medtronic, Inc. Modification of polymeric surface by graft polymerization
US5916596A (en) * 1993-02-22 1999-06-29 Vivorx Pharmaceuticals, Inc. Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof
US5607463A (en) * 1993-03-30 1997-03-04 Medtronic, Inc. Intravascular medical device
US5624411A (en) * 1993-04-26 1997-04-29 Medtronic, Inc. Intravascular stent and method
US5886026A (en) * 1993-07-19 1999-03-23 Angiotech Pharmaceuticals Inc. Anti-angiogenic compositions and methods of use
US20050042295A1 (en) * 1993-07-19 2005-02-24 Hunter William L. Anti-angiogenic compositions and methods of use
US5716981A (en) * 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
US6544544B2 (en) * 1993-07-19 2003-04-08 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions and methods of use
US20050123605A1 (en) * 1993-07-19 2005-06-09 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions and methods of use
US20030100600A1 (en) * 1993-07-29 2003-05-29 The Gov't Of The U.S.A. As Represented By The Secretary Of The Dept. Of Health And Human Service Method for treating atherosclerosis or restenosis using microtubule stabilizing agent
US5380299A (en) * 1993-08-30 1995-01-10 Med Institute, Inc. Thrombolytic treated intravascular medical device
US5504102A (en) * 1993-09-29 1996-04-02 Bristol-Myers Squibb Company Stabilized pharmaceutical composition and stabilizing solvent
US5531716A (en) * 1993-09-29 1996-07-02 Hercules Incorporated Medical devices subject to triggered disintegration
US5510330A (en) * 1994-03-25 1996-04-23 Boehringer Mannheim Gmbh Combinations of thrombolytically active proteins and non-heparin anticoagulants, and uses thereof.
US6682546B2 (en) * 1994-07-08 2004-01-27 Aga Medical Corporation Intravascular occlusion devices
US5733327A (en) * 1994-10-17 1998-03-31 Igaki; Keiji Stent for liberating drug
US5626562A (en) * 1994-11-28 1997-05-06 Devices For Vascular Intervention Drug delivery catheter
US5766158A (en) * 1995-02-06 1998-06-16 Surface Solutions Laboratories, Inc. Medical apparatus with scratch-resistant coating and method of making same
US5902283A (en) * 1995-04-24 1999-05-11 Baylor College Of Medicine Board Of Regents Antimicrobial impregnated catheters and other medical implants
US20030028243A1 (en) * 1995-06-07 2003-02-06 Cook Incorporated Coated implantable medical device
US20030028244A1 (en) * 1995-06-07 2003-02-06 Cook Incorporated Coated implantable medical device
US5609629A (en) * 1995-06-07 1997-03-11 Med Institute, Inc. Coated implantable medical device
US5873904A (en) * 1995-06-07 1999-02-23 Cook Incorporated Silver implantable medical device
US20030036794A1 (en) * 1995-06-07 2003-02-20 Cook Incorporated Coated implantable medical device
US5607475A (en) * 1995-08-22 1997-03-04 Medtronic, Inc. Biocompatible medical article and method
US5772640A (en) * 1996-01-05 1998-06-30 The Trustees Of Columbia University Of The City Of New York Triclosan-containing medical devices
US20040068241A1 (en) * 1996-06-04 2004-04-08 Fischer Frank J. Implantable medical device
US6039721A (en) * 1996-07-24 2000-03-21 Cordis Corporation Method and catheter system for delivering medication with an everting balloon catheter
US6375931B2 (en) * 1996-10-21 2002-04-23 Nycomed Imaging As Contrast agents
US6515016B2 (en) * 1996-12-02 2003-02-04 Angiotech Pharmaceuticals, Inc. Composition and methods of paclitaxel for treating psoriasis
US6240616B1 (en) * 1997-04-15 2001-06-05 Advanced Cardiovascular Systems, Inc. Method of manufacturing a medicated porous metal prosthesis
US6177061B1 (en) * 1997-04-23 2001-01-23 Nycomed Imaging As Contrast agents comprising an azeotropic mixture of two gases for ultrasound investigations
US6221467B1 (en) * 1997-06-03 2001-04-24 Scimed Life Systems, Inc. Coating gradient for lubricious coatings on balloon catheters
US6207133B1 (en) * 1997-06-06 2001-03-27 Max-Delbrück-Centrum für Molekulare Medizin Anti-tumoral therapy agent containing a contrast agent
US6171232B1 (en) * 1997-06-26 2001-01-09 Cordis Corporation Method for targeting in vivo nitric oxide release
US6214333B1 (en) * 1997-07-08 2001-04-10 Texas Heart Institute Vasoprotective recombinant adenovirus vector containing a human TFPI gene
US6248100B1 (en) * 1997-08-14 2001-06-19 Scimed Life Systems, Inc. Drainage catheter delivery system
US6562024B2 (en) * 1997-08-14 2003-05-13 Scimed Life Systems, Inc. Drainage catheter delivery system
US6064624A (en) * 1997-09-16 2000-05-16 Micron Technology, Inc. Circuit and method for eliminating idle cycles in a memory device
US6231615B1 (en) * 1997-10-14 2001-05-15 Parallax Medical, Inc. Enhanced visibility materials for implantation in hard tissue
US6203487B1 (en) * 1997-12-31 2001-03-20 Thomas Jefferson University Use of magnetic particles in the focal delivery of cells
US6364856B1 (en) * 1998-04-14 2002-04-02 Boston Scientific Corporation Medical device with sponge coating for controlled drug release
US6369039B1 (en) * 1998-06-30 2002-04-09 Scimed Life Sytems, Inc. High efficiency local drug delivery
US6695811B2 (en) * 1998-08-06 2004-02-24 Cardeon Corporation Aortic catheter with porous aortic arch balloon
US6730064B2 (en) * 1998-08-20 2004-05-04 Cook Incorporated Coated implantable medical device
US20020032414A1 (en) * 1998-08-20 2002-03-14 Ragheb Anthony O. Coated implantable medical device
US6335029B1 (en) * 1998-08-28 2002-01-01 Scimed Life Systems, Inc. Polymeric coatings for controlled delivery of active agents
US6017948A (en) * 1998-10-30 2000-01-25 Supergen, Inc. Water-miscible pharmaceutical compositions
US6191619B1 (en) * 1999-08-24 2001-02-20 Analog Devices, Inc. Translators and methods for converting differential signals to single-ended signals
US6706892B1 (en) * 1999-09-07 2004-03-16 Conjuchem, Inc. Pulmonary delivery for bioconjugation
US6682545B1 (en) * 1999-10-06 2004-01-27 The Penn State Research Foundation System and device for preventing restenosis in body vessels
US6355058B1 (en) * 1999-12-30 2002-03-12 Advanced Cardiovascular Systems, Inc. Stent with radiopaque coating consisting of particles in a binder
US6503954B1 (en) * 2000-03-31 2003-01-07 Advanced Cardiovascular Systems, Inc. Biocompatible carrier containing actinomycin D and a method of forming the same
US6867190B2 (en) * 2000-07-12 2005-03-15 The Board Of Regents, The University Of Texas System Methods of therapy with thrombin derived peptides
US6544223B1 (en) * 2001-01-05 2003-04-08 Advanced Cardiovascular Systems, Inc. Balloon catheter for delivering therapeutic agents
US20080102033A1 (en) * 2001-03-26 2008-05-01 Ulrich Speck Preparation for the prophylaxis of restenosis
US20030059454A1 (en) * 2001-09-24 2003-03-27 Barry James J. Optimized dosing for drug coated stents
US20060020331A1 (en) * 2002-07-12 2006-01-26 Cook Incorporated Coated medical device
US20040073284A1 (en) * 2002-07-12 2004-04-15 Cook Incorporated Coated medical device
US20060020243A1 (en) * 2002-09-20 2006-01-26 Ulrich Speck Medical device for dispensing medicaments
US7060051B2 (en) * 2002-09-24 2006-06-13 Scimed Life Systems, Inc. Multi-balloon catheter with hydrogel coating
US20050010522A1 (en) * 2003-07-10 2005-01-13 Finalabo Co., Ltd. Management system for open position with indication for loss cut and held stock management system with indication for loss cut
US20070128118A1 (en) * 2005-12-05 2007-06-07 Nitto Denko Corporation Polyglutamate-amino acid conjugates and methods

Cited By (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8469943B2 (en) 1995-06-07 2013-06-25 Cook Medical Technologies Llc Coated implantable medical device
US20110046723A1 (en) * 1995-06-07 2011-02-24 Bates Brian L Coated implantable medical device
US20050250672A9 (en) * 2001-03-26 2005-11-10 Ulrich Speck Preparation for the prophylaxis of restenosis
US9066990B2 (en) 2001-03-26 2015-06-30 Bayer Intellectual Property Gmbh Preparation for restenosis prevention
US20050101522A1 (en) * 2001-03-26 2005-05-12 Ulrich Speck Preparation for the prophylaxis of restenosis
US7750041B2 (en) 2001-03-26 2010-07-06 Bayer Schering Pharma Aktiengesellschaft Preparation for the prophylaxis of restenosis
US8389043B2 (en) 2001-03-26 2013-03-05 Bayer Pharma Aktiengesellschaft Preparation for restenosis prevention
US20100278997A1 (en) * 2001-03-26 2010-11-04 Ulrich Speck Preparation for restenosis prevention
US20080102033A1 (en) * 2001-03-26 2008-05-01 Ulrich Speck Preparation for the prophylaxis of restenosis
US20100228228A1 (en) * 2002-09-20 2010-09-09 Ulrich Speck Medical device for dispersing medicaments
US9649476B2 (en) 2002-09-20 2017-05-16 Bayer Intellectual Property Gmbh Medical device for dispersing medicaments
US8257305B2 (en) 2002-09-20 2012-09-04 Bayer Pharma Aktiengesellschaft Medical device for dispensing medicaments
US8439868B2 (en) 2002-09-20 2013-05-14 Bayer Pharma AG Medical device for dispersing medicaments
US9248220B2 (en) 2006-11-20 2016-02-02 Lutonix, Inc. Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent
US8366660B2 (en) 2006-11-20 2013-02-05 Lutonix, Inc. Drug releasing coatings for medical devices
US8366662B2 (en) 2006-11-20 2013-02-05 Lutonix, Inc. Drug releasing coatings for medical devices
US8403910B2 (en) 2006-11-20 2013-03-26 Lutonix, Inc. Drug releasing coatings for medical devices
US8404300B2 (en) 2006-11-20 2013-03-26 Lutonix, Inc. Drug releasing coatings for medical devices
US8414909B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US8414526B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids
US8414910B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US8414525B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US8425459B2 (en) 2006-11-20 2013-04-23 Lutonix, Inc. Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent
US9737640B2 (en) 2006-11-20 2017-08-22 Lutonix, Inc. Drug releasing coatings for medical devices
US9737691B2 (en) 2006-11-20 2017-08-22 Lutonix, Inc. Drug releasing coatings for balloon catheters
US9757351B2 (en) 2006-11-20 2017-09-12 Lutonix, Inc. Medical device rapid drug releasing coatings comprising oils, fatty acids and/or lipids
US8998846B2 (en) 2006-11-20 2015-04-07 Lutonix, Inc. Drug releasing coatings for balloon catheters
US9700704B2 (en) 2006-11-20 2017-07-11 Lutonix, Inc. Drug releasing coatings for balloon catheters
US9694111B2 (en) 2006-11-20 2017-07-04 Lutonix, Inc. Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent
US9757544B2 (en) 2006-11-20 2017-09-12 Lutonix, Inc. Drug releasing coatings for medical devices
US9402935B2 (en) 2006-11-20 2016-08-02 Lutonix, Inc. Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs
US9314598B2 (en) 2006-11-20 2016-04-19 Lutonix, Inc. Drug releasing coatings for balloon catheters
US9289537B2 (en) 2006-11-20 2016-03-22 Lutonix, Inc. Medical device rapid drug releasing coatings comprising oils, fatty acids and/or lipids
US8932561B2 (en) 2006-11-20 2015-01-13 Lutonix, Inc. Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent
US9764065B2 (en) 2006-11-20 2017-09-19 Lutonix, Inc. Drug releasing coatings for medical devices
US8998847B2 (en) 2006-11-20 2015-04-07 Lutonix, Inc. Drug releasing coatings for medical devices
US9937159B2 (en) 2006-11-20 2018-04-10 Lutonix, Inc. Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs
US9023371B2 (en) 2006-11-20 2015-05-05 Lutonix, Inc. Drug releasing coatings for medical devices
US9033919B2 (en) 2006-11-20 2015-05-19 Lutonix, Inc. Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids
US9289539B2 (en) 2006-11-20 2016-03-22 Lutonix, Inc. Drug releasing coatings for medical devices
US9283358B2 (en) 2006-11-20 2016-03-15 Lutonix, Inc. Drug releasing coatings for medical devices
US9005161B2 (en) 2006-11-20 2015-04-14 Lutonix, Inc. Drug releasing coatings for medical devices
US9314552B2 (en) 2006-11-20 2016-04-19 Lutonix, Inc. Drug releasing coatings for medical devices
US8597720B2 (en) 2007-01-21 2013-12-03 Hemoteq Ag Medical product for treating stenosis of body passages and for preventing threatening restenosis
US20080304101A1 (en) * 2007-06-08 2008-12-11 Naoko Sasase Server and printer introducing method under thin client environment
US9192697B2 (en) 2007-07-03 2015-11-24 Hemoteq Ag Balloon catheter for treating stenosis of body passages and for preventing threatening restenosis
US9770576B2 (en) 2008-08-29 2017-09-26 Lutonix, Inc. Methods and apparatuses for coating balloon catheters
US8430055B2 (en) 2008-08-29 2013-04-30 Lutonix, Inc. Methods and apparatuses for coating balloon catheters
US9180485B2 (en) 2008-08-29 2015-11-10 Lutonix, Inc. Methods and apparatuses for coating balloon catheters
US9132211B2 (en) 2008-09-15 2015-09-15 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8734825B2 (en) 2008-09-15 2014-05-27 Covidien Lp Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US10117970B2 (en) 2008-09-15 2018-11-06 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8673332B2 (en) 2008-09-15 2014-03-18 Covidien Lp Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US9603973B2 (en) 2008-09-15 2017-03-28 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US10046093B2 (en) 2008-09-15 2018-08-14 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US9034362B2 (en) 2008-09-15 2015-05-19 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8563023B2 (en) 2008-09-15 2013-10-22 Covidien Lp Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US9198968B2 (en) 2008-09-15 2015-12-01 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8257722B2 (en) 2008-09-15 2012-09-04 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8128951B2 (en) 2008-09-15 2012-03-06 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8114429B2 (en) 2008-09-15 2012-02-14 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US20100068170A1 (en) * 2008-09-15 2010-03-18 Michal Eugene T Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8491925B2 (en) 2008-09-15 2013-07-23 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US10080821B2 (en) 2009-07-17 2018-09-25 Boston Scientific Scimed, Inc. Nucleation of drug delivery balloons to provide improved crystal size and density
US8889211B2 (en) 2010-09-02 2014-11-18 Boston Scientific Scimed, Inc. Coating process for drug delivery balloons using heat-induced rewrap memory
US8669360B2 (en) 2011-08-05 2014-03-11 Boston Scientific Scimed, Inc. Methods of converting amorphous drug substance into crystalline form
US9056152B2 (en) 2011-08-25 2015-06-16 Boston Scientific Scimed, Inc. Medical device with crystalline drug coating
US9956385B2 (en) 2012-06-28 2018-05-01 The Spectranetics Corporation Post-processing of a medical device to control morphology and mechanical properties

Also Published As

Publication number Publication date Type
US20050101522A1 (en) 2005-05-12 application
US20100278744A1 (en) 2010-11-04 application
DE20122582U1 (en) 2006-07-13 grant
US20140227194A1 (en) 2014-08-14 application
US8389043B2 (en) 2013-03-05 grant
CA2442080A1 (en) 2002-10-03 application
ES2289721T3 (en) 2008-02-01 grant
DE20122736U1 (en) 2007-08-09 grant
JP4484432B2 (en) 2010-06-16 grant
DE10115740A1 (en) 2002-10-02 application
KR100874308B1 (en) 2008-12-18 grant
CN1935277B (en) 2010-05-26 grant
ES2340407T3 (en) 2010-06-02 grant
US20080102033A1 (en) 2008-05-01 application
DK1666071T3 (en) 2008-01-07 grant
DE20122735U1 (en) 2007-08-02 grant
WO2002076509A3 (en) 2003-04-24 application
ES2289720T3 (en) 2008-02-01 grant
DK1669092T3 (en) 2010-07-12 grant
US20140227192A1 (en) 2014-08-14 application
WO2002076509A2 (en) 2002-10-03 application
EP1669092B1 (en) 2010-03-31 grant
EP1372737B1 (en) 2006-08-02 grant
EP1669092A1 (en) 2006-06-14 application
CN1899615B (en) 2011-02-02 grant
EP1372737A2 (en) 2004-01-02 application
US20050250672A9 (en) 2005-11-10 application
CN1935277A (en) 2007-03-28 application
JP2004524346A (en) 2004-08-12 application
KR20030097809A (en) 2003-12-31 application
DE50112886D1 (en) 2007-09-27 grant
CN1494435A (en) 2004-05-05 application
CN1899614A (en) 2007-01-24 application
US9066990B2 (en) 2015-06-30 grant
CA2442080C (en) 2014-05-27 grant
DK1372737T3 (en) 2006-11-27 grant
CN1824311A (en) 2006-08-30 application
US20140227193A1 (en) 2014-08-14 application
EP1372737B8 (en) 2006-12-13 grant
US7750041B2 (en) 2010-07-06 grant
CN1899614B (en) 2011-05-11 grant
EP1666070B1 (en) 2007-09-05 grant
EP1666071B1 (en) 2007-08-15 grant
DE50112978D1 (en) 2007-10-18 grant
ES2269500T3 (en) 2007-04-01 grant
EP1666071A1 (en) 2006-06-07 application
CN1261165C (en) 2006-06-28 grant
DK1666070T3 (en) 2008-01-14 grant
CN100379456C (en) 2008-04-09 grant
CN1899615A (en) 2007-01-24 application
DE50110649D1 (en) 2006-09-14 grant
US20100278997A1 (en) 2010-11-04 application
EP1666070A1 (en) 2006-06-07 application
DE50115417D1 (en) 2010-05-12 grant

Similar Documents

Publication Publication Date Title
Hao et al. MRI contrast agents: basic chemistry and safety
Jordan et al. Effects of magnetic fluid hyperthermia (MFH) on C3H mammary carcinoma in vivo
Geschwind et al. Chemoembolization of liver tumor in a rabbit model: assessment of tumor cell death with diffusion-weighted MR imaging and histologic analysis
Fatouros et al. In vitro and in vivo imaging studies of a new endohedral metallofullerene nanoparticle
US20030064965A1 (en) Method of delivering drugs to a tissue using drug-coated medical devices
US20050196343A1 (en) Degradable nanoparticles
US20080051335A1 (en) Methods, compositions and devices for treating lesioned sites using bioabsorbable carriers
Cole et al. Magnetic brain tumor targeting and biodistribution of long-circulating PEG-modified, cross-linked starch-coated iron oxide nanoparticles
US5514379A (en) Hydrogel compositions and methods of use
Kubo et al. Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamycin for osteosarcoma in hamsters.
Schleich et al. Dual anticancer drug/superparamagnetic iron oxide-loaded PLGA-based nanoparticles for cancer therapy and magnetic resonance imaging
Mou et al. Applications of magnetic nanoparticles in targeted drug delivery system
US5268165A (en) Polymer-deferoxamine-ferric iron adducts for use in magnetic resonance imaging
US20020133225A1 (en) Methods and apparatuses for delivering a medical agent to a medical implant
Konno Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium
US5508021A (en) Non-fluorinated polymeric shells for medical imaging
US6574497B1 (en) MRI medical device markers utilizing fluorine-19
Cremers et al. Comparison of two different paclitaxel-coated balloon catheters in the porcine coronary restenosis model
US5635207A (en) Methods for the preparation of blood substitutes for in vivo delivery
US5236410A (en) Tumor treatment method
Bellin et al. Extracellular gadolinium-based contrast media: an overview
US20080188830A1 (en) Selectively reinforced medical devices
Neuwelt et al. Ultrasmall superparamagnetic iron oxides (USPIOs): a future alternative magnetic resonance (MR) contrast agent for patients at risk for nephrogenic systemic fibrosis (NSF)?
Schleich et al. Comparison of active, passive and magnetic targeting to tumors of multifunctional paclitaxel/SPIO-loaded nanoparticles for tumor imaging and therapy
Alexiou et al. Magnetic mitoxantrone nanoparticle detection by histology, X-ray and MRI after magnetic tumor targeting