AU770102B2 - Agent for occluding blood vessels - Google Patents

Agent for occluding blood vessels Download PDF

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Publication number
AU770102B2
AU770102B2 AU65613/00A AU6561300A AU770102B2 AU 770102 B2 AU770102 B2 AU 770102B2 AU 65613/00 A AU65613/00 A AU 65613/00A AU 6561300 A AU6561300 A AU 6561300A AU 770102 B2 AU770102 B2 AU 770102B2
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AU
Australia
Prior art keywords
preparation
agent
dye
thrombin
blood vessels
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AU6561300A (en
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Peter Sterk
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Oberschwabenklinik gGmbH
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Oberschwabenklinik gGmbH
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/717—Celluloses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • A61L24/108—Specific proteins or polypeptides not covered by groups A61L24/102 - A61L24/106
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/00491—Surgical glue applicators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12099—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder
    • A61B17/12109—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12131—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
    • A61B17/12181—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device formed by fluidized, gelatinous or cellular remodelable materials, e.g. embolic liquids, foams or extracellular matrices
    • A61B17/12186—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device formed by fluidized, gelatinous or cellular remodelable materials, e.g. embolic liquids, foams or extracellular matrices liquid materials adapted to be injected
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • A61L24/106—Fibrin; Fibrinogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/00491—Surgical glue applicators
    • A61B2017/00495—Surgical glue applicators for two-component glue

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Surgery (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Medical Informatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Vascular Medicine (AREA)
  • Reproductive Health (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Materials Engineering (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Materials For Medical Uses (AREA)
  • Adhesives Or Adhesive Processes (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • External Artificial Organs (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to an agent for occluding blood vessels. Said agent contains at least two components, namely an agent for bringing about a vascular occlusion and a physiologically acceptable dye.

Description

WO 01/02029 PCT/EP0O/06282 Agent for the Occlusion of Blood Vessels The object of the invention is an agent for the occlusion of blood vessels, which significantly improves the success of surgical procedures, especially of surgical procedures for the removal of carcinoma.
In a method for the embolization of blood vessels already known from European patent application 0 797 988, an antiangiogenic preparation is introduced into a blood vessel that feeds the tumor to treat carcinoma. The blood supply from the diseased tissue to the healthy tissue and viceversa is interrupted by the "embolization" of the blood vessel.
It has furthermore already been proposed in DE-OS 197 31 741 to use specific conjugates that comprise a compound capable of fluorescence and a carrier to distinguish between healthy and diseased tissue.
Fibrin glues have also proven useful as agents for the occlusion of vessels. However, the use of conventional fibrin glue in oncology surgery has the disadvantage that so far, it has been very difficult or impossible to distinguish between the diseased tissue to be removed and the healthy issue.
The present invention is therefore based on the problem to provide a suitable agent for the occlusion of blood vessels, which allows a safe distinction between healthy and diseased tissue and can therefore be used WO 01/02029 PCT/EPOO/06282 advantageously during the surgical removal of the diseased tissue.
The object of the invention is attained with an agent for the occlusion of blood vessels comprising at least two components, an agent to effect an occlusion of the vessel and a physiologically safe dye. Especially preferred is an agent that comprises a liquid fibrinogen solution to effect the occlusion of the vessel and can be used in cooperation with a liquid thrombin preparation.
The physiologically safe dye is added to one of the two preparations, generally to the thrombin preparation.
The use of the agent in accordance with the invention results in the advantage that it is possible not only to occlude the individual blood vessels, but to stain them as well and thus render the blood- or lymphatic supply visible. The agent can occlude and stain venous as well as arterial blood vessels, and it can also be used in lymphatic vessels.
With the agent in accordance with the invention, it is furthermore possible to visibly separate healthy tissue from diseased tissue. Because each tissue is supplied by a specific artery and vein and by a specific lymph tract, it may be cut off from the blood supply when the appropriate supplying or evacuating supply tract is embolized.
Doing this, it is irrelevant what tissue tract is embolized. It is only important that the blood supply to the diseased tissue is interrupted, which can be achieved with the embolization of the arterial as well as the venous WO 01/02029 PCT/EP00/06282 tissue tracts. Thus, during surgical procedures, the use of the agent in accordance with the invention leads to an occlusion of the vessels that supply the operating area.
For the surgeon, the surgical procedure is significantly simplified by the use of the agent in accordance with the invention because he can now readily distinguish between the diseased and the healthy tissue during the surgery, and can retain as much as possible of the healthy tissue when removing the diseased tissue.
Another advantage of the described agent is that it prevents a diffusion of pathogenic bacteria or body cells into the healthy body tissue because of the occlusion of the blood vessels that supply the operating area. Bacteria, viruses, and tumor cells in particular are therefore fixated in the diseased tissue. The same advantages are obtained when the diseased tissue is infested with parasites, in which case the connection between the healthy tissue and the diseased tissue is also interrupted.
The fibrin glue usable in accordance with the invention is preferably comprised of a stabilized, liquid fibrinogenand a liquid thrombin preparation. One or both of these preparations should contain a physiologically safe dye that clearly stains the embolized blood vessels. Examples of suitable dyes are methylene blue, quinoline yellow, patent blue, tolonium chloride, indocyanine green and foodstuffas well as fluorescence dyes.
In addition to this, the tissue glue can contain an added preparation containing the blood coagulation factor XIII, WO 01/02029 PCT/EP00/06282 and thus be used as a three-component-glue. It is also possible, however, to mix the blood coagulation factor XIII into the fibrinogen preparation from the beginning, thus making it a two-component glue. In the case of a threecomponent glue, the mixing ratio of the fibrinogen, Factor XIII and thrombin components can be appropriately chosen to obtain good mechanical properties of the glue. Suitable mixing ratios, for example, are 1:1:1 and approximately 2:1:1 to approximately 10:1:1.
The tissue glue used in accordance with the invention contains a chaotropic substance in the fibrinogen preparation. Primarily arginine, guanidine, citrulline, urea or its derivatives or mixtures thereof have been shown to be suitable chaotropic substances. They are generally added to the fibrinogen preparation in quantities of 0.1 to mol per liter, preferably in quantities of less than mol per liter.
The properties of the aforementioned new tissue glues are furthermore advantageously influenced by the addition of an antifibrinolytic. Aprotinine, e-amino caproic acid (EACA), p-amino methyl benzoic acid (PAMBA) or one of their physiologically safe salts or derivatives are primarily used as antifibrinolytic.
Furthermore, the fibrinogen preparation can comprise -an inorganic salt or WO 01/02029 5 PCT/EP00/06282 one or more physiologically safe salts of organic carboxylic acids, especially citric acid or lactic acid, or -one or more amino acids or a mono- or disaccharide or a sugar alcohol or one of the mixtures thereof as stabilizers.
The Factor VIII-preparation added to the tissue glue to be used in accordance with the invention must also be stabilized if it is not added to already stabilized fibrinogen. In that case, it is advantageous to add a physiologically safe salt of an organic di-, tri- or tetracarboxylic acid, especially citric acid, and, if necessary, other stabilizers and/or buffer substances for the Factor XIII. Other stabilizers may be a mono- or disaccharide or a sugar alcohol and/or an amino acid from the group of the glycine, glycylglycine, alanine, cysteine, histidine, glutamine or a physiologically safe salt of the glutamine- or aspartic acid and/or a reducing or anti-oxidation agent and/or a surface-active substance.
They are generally added to the Factor XIII-preparation in a quantity of up to 5 percent-by-weight. Tissue glues of this type are described in the German patent applications DE-A-198 53 033 and DE-A-198 61 158.
The invention is explained in more detail by means of the examples.
Shown are: Fig. 1 the representation of two ampoules with various content substances Fig. 2 the ampoules in accordance with Fig. 1, with the addition of further additives; Fig. 3 the application of the agent in a first embodiment; Fig. 4 the application of the agent in a second embodiment, and; Fig. 5 the explanation of the effect of the agent in the tissue.
Fig. 1 shows two ampoules 1 and 3 that can be designed in various forms.
The ampoule 1 can contain a thrombin solution 2, with a physiologically safe dye being dissolved in connection with thrombin in said bottle. The invention is not limited to this; the ampoule 1 may also contain only a dye solution. The thrombin is added only to improve blood coagulation, but is not absolutely necessary for the agent in accordance with the invention.
The ampoule 3 contains a solution of fibrinogen 4. The fibrinogen is present in a semi-fluid, highly viscous solution.
20 To prepare the agent in accordance with the invention, an additive 5, which is preferably comprised of a CaCI 2 solution for the later hardening of the agent in the tissue, is placed into the ampoule 1.
An aprotinine solution is placed into the second ampoule 3 as additive 6.
A mixing ratio of 1:1 of the aprotinine solution and the fibrinogen solution is preferred.
The additive 6 (aprotinine solution) for the fibrinogen is required to start the 9.o .9 S desired later coagulation chain.
At first, the content substances of the ampoules 1 and 3 do not react with each other.
30 A reaction takes place only after, according to Fig. 3, the contents of the two ampoules 1 and 3 are drawn into the C C
C.
C. U C CC )INbiS A11VNOI1N~1NI SI ~DVd SIHI WO 01/02029 PCTIEP00/06282 assigned syringes 1' and 3' and they are connected with one another by a Y-connector according to Fig. 3, as soon as the contents of the two syringes 1' and 3' is injected into the tissue through the Y-connector 7 and a cannula 8.
Fig. 4 shows as another embodiment a combination vessel 9, which contains the components of the two ampoules 1 and 3 in the embodiment according to Fig. 2.
In the upper part, it can contain the contents of the ampoule 3, while the content substances of the ampoule 1 are in the lower part of the combination vessel 9. The two components are separated by a center membrane A combination vessel of this type is used in a way that the center, separating membrane 10 is destroyed and the combination vessel is then shaken in such a way that all components are mixed. The agent prepared in this way can then be injected into the issue through the opening 19 and an appropriate cannula 8.
Instead of a horizontal membrane, it is also possible that several horizontal membranes or one or more vertical membranes may be present in the combination vessel 9.
Fig. 5 shows an example of the application of the agent on a rectum 11. However, the application of the agent is not limited to a rectum; it is also possible to treat living as well as dead tissues in human and animal bodies with the agent in accordance with the invention.
WO 01/02029 PCT/EP00/06282 Fig. 5 shows that at position 15, for example, far away of the diseased tissue, the agent from the cannula 8 is injected into a vein 14 under pressure so that it flows into the direction of the arrow 16 and against the direction of the blood flow in the vein 14.
This stains and simultaneously closes all venous tracts (venules 17) in the affected, diseased tissue 12 and creates the possibility to separate the tissue 12 from the adjacent tissue that is not being supplied by the vein 14.
Thus, the adjacent tissue is separated from the diseased tissue 12 by a tissue border 18 and is easily distinguishable. In this way, the diseased tissue 12 can be removed from the adjacent, healthy tissue by a simple, optical control during the surgery.
Another essential advantage of the agent in accordance with the invention is that the diseased tissue has, at least in the border area, closed vessels in which bacteria are immobilized and fixated and thus cannot enter into healthy, not yet diseased tissue.
However, the agent in accordance with the invention can also be injected into an artery 13, and can then also enter the arterial tracts of the tissue 12 in the direction of the arrow 16, where it closes the arterial tracts there permanently while simultaneously staining them.
It is therefore important for the present invention that the agent is comprised of at least two components, a substance that is suitable for effecting an embolization of 17-12-03:11:15 :WATERMARK PATENT :61 3 98196010 3/ 6 the tissue, and also a dye that is suitable to stain the appropriate occluded tissue during the occlusion.
Comprises/comprising and grammatical variations thereof when used in this specification are to be taken to specify the presence of stated features, integers, steps or components or groups thereof, but do not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof.
In particular, the invention is directed to an agent for the occlusion of blood vessels, characterized in that it contains a physiologically acceptable dye, a stabilised liquid fibrinogen preparation and an aprotinine preparation.
Further, the invention is directed to an agent for the occlusion of blood vessels, characterized in that it contains a physiologically acceptable dye, a stabilised liquid fibrinogen preparation and an aprotinine preparation and additionally a liquid thrombin preparation.
Furthermore, the invention is directed to an agent for the occlusion of blood vessels, characterized in that it contains a physiologically acceptable dye, a stabilised liquid fibrinogen preparation and an aprotinine preparation and may include any one or more of the following agents, liquid thrombin preparation, Factor XIII, preparation, antifibrinolytic agent, chaotropic agent and/or stabilizing agent.
The invention is also directed to a pharmaceutical preparation when used in the occlusion of blood vessels, characterized in that it comprises two solutions, the first solution containing a physiologically acceptable dye, and optionally a thrombin preparation wherein the said dye, may be dissolved in the thrombin S 25 preparation with or without a hardening agent, and the second solution containing a stabilised fibrinogen preparation admixed with an aprotinine preparation, wherein the first and second solutions are administered simultaneously.
The invention also relates to a kit of parts.
COMS ID No: SMBI-00539698 Received by IP Australia: Time 12:31 Date 2003-12-17 WO 01/02029 11 PCTIEP00/06282 List of reference symbols: 1 Ampoule 2 Filling (colorant solution with or without thrombin) 3 Ampoule 4 Filling (fibrinogen) Additive (CaCl2) 6 Additive (aprotinine solution) 7 Y-connector 8 Cannula 9 Combination vessel Membrane 11 Rectum 12 Tissue 13 Artery 14 Vein Position 16 Direction of arrow 17 Venules 18 Tissue border 19 Opening Lymph tract

Claims (1)

17-12-03:11:15 :WATERMARK PATENT :61 3 98196010 4/ 6 12 THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS: 1. An agent for the occlusion of blood vessels, characterized in that it contains a physiologically acceptable dye, a stabilised liquid fibrinogen preparation and an aprotinine preparation. 2. The agent as claimed in claim 1, characterized in that it contains additionally a liquid thrombin preparation. 3. The agent as claimed in claims 1 or 2, characterized in that it contains additionally a Factor XIII preparation. 4. The agent as claimed in any one of claims 1 to 3, characterized in that it 10 contains additionally an antifibrinolytic agent. 5. The agent as claimed in any one of claims 1 to 4, characterized in that it contains additionally a stabilising agent. 6. The agent as claimed in any one of claims 1 to 5, characterized in that it contains additionally.a chaotropic agent. 7. A pharmaceutical preparation when used in the occlusion of blood vessels, characterized in that it comprises two solutions, the first solution containing a physiologically acceptable dye, and optionally a thrombin preparation wherein said dye may be dissolved in the thrombin preparation, and the second solution containing a stabilised fibrinogen preparation admixed with an aprotinine preparation, wherein the first and second solutions are administered simultaneously. 8. A pharmaceutical preparation when used in the occlusion of blood vessels, characterized in that it comprises two solutions, the first solution containing a physiologically acceptable dye, and optionally a thrombin preparation wherein said dye may be dissolved in the thrombin preparation, together with a hardening agent, preferably CaCI 2 solution, and the second solution containing a stabilised COMS ID No: SMBI-00539698 Received by IP Australia: Time 12:31 Date 2003-12-17 13 fibrinogen preparation admixed with an aprotinine preparation, wherein the first and second solutions are administered simultaneously. 9. A kit when used in the occlusion of blood vessels characterised in that it comprises two ampoules, the first ampoule containing a physiologically acceptable dye, and optionally a thrombin preparation wherein said dye may be dissolved in the thrombin preparation, and the second ampoule containing a stabilised fibrinogen preparation admixed with an aprotinine preparation, wherein the first and second ampoules are mixed for use. A kit when used in the occlusion of blood vessels characterised in that it comprises a single ampoule, the ampoule comprising a first and second portion separated by a membrane, the first portion containing a physiologically acceptable dye, and optionally a thrombin preparation wherein said dye may be dissolved in the thrombin preparation, and the second portion containing a stabilised fibrinogen preparation admixed with an aprotinine preparation, wherein the contents of the first and second portion are mixed for use following removal of the separating membrane. DATED this 3 rd day of December 2003 OBERSCHWABENKLINIK GMBH WATERMARK PATENT TRADE MARK ATTORNEYS 290 BURWOOD ROAD HAWTHORN VICTORIA 3122 AUSTRALIA KJS/ALJ/MEH P20804AU00 *oooo *oo ooo* *•*oo
AU65613/00A 1999-07-06 2000-07-05 Agent for occluding blood vessels Ceased AU770102B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE29911689U DE29911689U1 (en) 1999-07-06 1999-07-06 Agents for occluding organic tissue
DE29911689 1999-07-06
PCT/EP2000/006282 WO2001002029A1 (en) 1999-07-06 2000-07-05 Agent for occluding blood vessels

Publications (2)

Publication Number Publication Date
AU6561300A AU6561300A (en) 2001-01-22
AU770102B2 true AU770102B2 (en) 2004-02-12

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AU65613/00A Ceased AU770102B2 (en) 1999-07-06 2000-07-05 Agent for occluding blood vessels

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EP (1) EP1200137B1 (en)
JP (1) JP2003503466A (en)
KR (1) KR100699715B1 (en)
AT (1) ATE389422T1 (en)
AU (1) AU770102B2 (en)
CA (1) CA2378606A1 (en)
DE (2) DE29911689U1 (en)
WO (1) WO2001002029A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109069825A (en) * 2016-03-14 2018-12-21 通用电气公司 The assemble in situ of two-way neural interface

Citations (2)

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Publication number Priority date Publication date Assignee Title
US5648100A (en) * 1991-05-29 1997-07-15 Assistance Publique Hopitaux De Paris Microspheres useful for therapeutic vascular occlusions and injectable solutions containing the same
WO1999005521A2 (en) * 1997-07-23 1999-02-04 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Conjugate for differentiating between healthy and unhealthy tissue

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Publication number Priority date Publication date Assignee Title
CA1225585A (en) * 1983-06-30 1987-08-18 Maria T. Litvinova Composition for embolization of blood vessels
WO1987000062A1 (en) * 1985-07-02 1987-01-15 Target Therapeutics Vaso-occlusive collagen composition and method
US5219328A (en) * 1990-01-03 1993-06-15 Cryolife, Inc. Fibrin sealant delivery method
JP3534780B2 (en) * 1992-01-31 2004-06-07 テルモ株式会社 Vascular embolic agent
DE69435141D1 (en) * 1993-07-19 2008-10-30 Angiotech Pharm Inc Anti-angiogenic agents and methods of use
US5583114A (en) * 1994-07-27 1996-12-10 Minnesota Mining And Manufacturing Company Adhesive sealant composition
DE29518932U1 (en) * 1995-11-29 1996-06-20 Reul, Jürgen, Dr.med., 52146 Würselen Controlled detachable embolization ball spiral
DE19853033A1 (en) * 1998-11-18 2000-05-25 Centeon Pharma Gmbh Stabilized factor XIII and fibrinogen preparations useful as tissue adhesive components

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5648100A (en) * 1991-05-29 1997-07-15 Assistance Publique Hopitaux De Paris Microspheres useful for therapeutic vascular occlusions and injectable solutions containing the same
WO1999005521A2 (en) * 1997-07-23 1999-02-04 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Conjugate for differentiating between healthy and unhealthy tissue

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KR100699715B1 (en) 2007-03-27
KR20020068493A (en) 2002-08-27
EP1200137B1 (en) 2008-03-19
WO2001002029A1 (en) 2001-01-11
EP1200137A1 (en) 2002-05-02
CA2378606A1 (en) 2001-01-11
DE50015051D1 (en) 2008-04-30
ATE389422T1 (en) 2008-04-15
JP2003503466A (en) 2003-01-28
DE29911689U1 (en) 2000-04-06
AU6561300A (en) 2001-01-22

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