EP2049168A2 - Beschichtung künstlicher oberflächen von medizinischen hilfsmitteln und geräten sowie reinigung und/oder vorbehandlung von kathetern und anderen medizinischen hilfsmitteln und geräten - Google Patents
Beschichtung künstlicher oberflächen von medizinischen hilfsmitteln und geräten sowie reinigung und/oder vorbehandlung von kathetern und anderen medizinischen hilfsmitteln und gerätenInfo
- Publication number
- EP2049168A2 EP2049168A2 EP07786084A EP07786084A EP2049168A2 EP 2049168 A2 EP2049168 A2 EP 2049168A2 EP 07786084 A EP07786084 A EP 07786084A EP 07786084 A EP07786084 A EP 07786084A EP 2049168 A2 EP2049168 A2 EP 2049168A2
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- EP
- European Patent Office
- Prior art keywords
- formula
- devices
- compounds
- solvates
- salts
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- 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.)
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0005—Use of materials characterised by their function or physical properties
- A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
- A61L33/0041—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate characterised by the choice of an antithrombatic agent other than heparin
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- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
Definitions
- the present invention relates to the use of anticoagulant factor Xa (FXa) inhibitors for the antithrombotic coating and / or treatment of artificial surfaces of medical devices and / or devices for the prevention of fibrin deposits and / or blood clots and thrombi, and the use of FXa inhibitors in the cleaning and / or pretreatment of catheters and other medical devices and devices.
- FXa anticoagulant factor Xa
- the platelets are activated by adhesion to artificial surfaces. Activated platelets amplify the coagulation process.
- the function of the medical device or device may be impaired by the blood clot. In addition, it can lead to thrombus formation and thus to a vascular occlusion or thromboembolism, cause of various thromboembolic complications such as myocardial infarction, cerebral infarction, pulmonary embolism.
- Substances that inhibit the activity of FXa and thereby inhibit the formation of thrombin prevent blood clotting triggered by contact activation and thus fibrin deposition and thrombogenesis.
- FXa inhibitors to prevent fibrin deposition and thrombus formation on artificial surfaces is complicated by the need to administer the anticoagulant over a long period of time depending on the use of the artificial surface, and bleeding complications, both short-term and long-term Long-term use could come.
- the coating of artificial surfaces with an FXa inhibitor allows a permanent local drug treatment and therefore could offer significant benefits. So allows the connection of a medical device or Device with FXa inhibitors a high local concentration of active ingredient, without causing the undesirable systemic side effects (eg bleeding or stroke).
- a medical device and / or device can be coated with active substance-containing paint materials.
- the release of active ingredient takes place by diffusion from the paint or by degradation of the paint when using biodegradable paint systems.
- medicated medications and / or devices may be prepared by melt-embedding the active ingredient in a polymeric carrier, e.g. be produced by means of injection molding. The release of the active ingredient in these medical aids and / or devices usually by diffusion.
- Factor Xa inhibitors which are suitable for coating foreign medical surfaces are described in WO 01/047919.
- the substances described are potent, selective FXa inhibitors which inhibit the extrinsic and intrinsic blood clotting systems and thus can be used to prevent contact activation.
- oxazolidinones of the formula (I) are suitable for this type of treatment, which act in particular as anticoagulants and as selective inhibitors of the blood coagulation factor Xa and are described in detail in WO 01/47919.
- the present invention relates to the use of one or more compounds of the formula (I)
- R 1 is optionally benzo-fused thiophene (thienyl), which may optionally be mono- or polysubstituted;
- R 2 is any organic radical
- R 3, R 4, R 5, R 6, R 7 and R 8 are identical or different and represent hydrogen or (C r C 6) alkyl
- R 1 is optionally benzo-fused thiophene (thienyl), which may optionally be mono- or polysubstituted by a radical from the group of halogen; cyano;
- R 2 is one of the following groups:
- radical "A” is (C 6 -C 4) -aryl, preferably (C 6 -C 0) aryl, in particular phenyl or naphthyl, very particularly preferably phenyl;
- the radical 3 ' is a 5- or 6-membered aromatic heterocycle containing up to 3 heteroatoms and / or hetero-chain members, in particular up to 2 heteroatoms and / or hetero-chain members, from the series S, N, NO ( N-oxide) and O;
- the radical, J) is a saturated or partially unsaturated, monocyclic or bicyclic, optionally benzo-fused 4- to 9-membered heterocycle containing up to three heteroatoms and / or hetero-chain members from the series S, SO, SO 2 , N, NO (N-oxide) and O;
- radical JA for -NH-, -CH 2 -, -CH 2 CH 2 -, -O-, -NH-CH 2 -, -CH 2 -NH-, -OCH 2 -, -CH 2 O- , -CONH-, -NHCO-, -COO-, -OOC-, -S-, -SO 2 - or is a covalent bond;
- the previously defined groups "A” > "B” and “JD” may each optionally be monosubstituted or polysubstituted by a radical from the group of halogen; trifluoromethyl; oxo; cyano; nitro; carbamoyl; pyridyl; (C r C 6 ) alkanoyl; (C 3 -C 7 ) cycloalkanoyl; (C 5 -C 10) -heteroarylcarbonyl; (C) -C 6 ) alkanoyloxymethyloxy;
- R 28 and R 29 are identical or different and are independently hydrogen, (C r C4) alkyl, (C 3 -C 7) cycloalkyl, (C, -C 4) alkanoyl, carbamoyl, trifluoromethyl, Phenyl or pyridyl,
- R 27 and R 28 or R 27 and R 29 together with the nitrogen atom to which they are attached, a saturated or partially unsaturated 5- to 7-membered heterocycle having up to three, preferably up to two identical or different hetero atoms from the group of N, O and S form, and
- R 30 and R 31 are identical or different and are independently hydrogen, (C, -C 4) alkyl, (C 3 -C 7) cycloalkyl, (C r C 4) alkylsulfonyl, (C r C4) - hydroxyalkyl,
- R 33 (C 1 -Ce) -alkoxy, (C 1 -C 4) alkoxy- (C, -C 4) alkyl, (C, -C 4) alkoxycarbonyl (C 1 -C 4) - alkyl , (QC ⁇ aminoalkyl, (C r C4) alkoxycarbonyl, (C 1 -C 4) alkanoyl (C 1 -C 4) - alkyl, (C 3 -C 7) cycloalkyl, (C 2 - C 6 ) -alkenyl, (C 1 -Cg) -AlkVl, which may optionally be substituted by phenyl or acetyl, (C 6 -C 4 ) -aryl, (C 5 -C 10 ) -
- R 3, R 4, R 5, R 6, R 7 and R 8 are identical or different and represent hydrogen or (C r C 6) alkyl
- R 1 is thiophene (thienyl), in particular 2-thiophene, which may optionally be mono- or polysubstituted by halogen, preferably chlorine or bromine, amino, aminomethyl or (C 1 -Cg) -alkyl, preferably methyl, wherein the (CrCg) -alkyl radical, if appropriate, may in turn be monosubstituted or polysubstituted by halogen, preferably fluorine,
- R 2 is one of the following groups: A-,
- the radical "B” is a 5- or 6-membered aromatic heterocycle containing up to 3 heteroatoms and / or hetero-chain members, in particular up to 2 heteroatoms and / or hetero-chain members, from the series S, N, NO (N-oxide) and O contains;
- v means either 0 or 1
- R 27 , R 28 and R 29 are identical or different and independently of one another are hydrogen, (C 1 -C 4 ) -alkyl or (C 3 -C 7 ) -cycloalkyl,
- R 27 and R 28 or R 27 and R 29 together with the nitrogen atom to which they are attached, a saturated or partially unsaturated 5- to 7-membered heterocycle having up to three, preferably up to two identical or different hetero atoms from the group of N, O and S form, and
- R 30 and R 31 are the same or different and are independently hydrogen
- Ci 4 ) -Arylcarbonyl, (C 5 -Cio) -Heteroarylcarbonyl, (Ci-C 4 ) -Alkylaminocarbonyl or
- R 3, R 4, R 5, R 6, R 7 and R 8 are identical or different and represent hydrogen or (C r C 6) alkyl
- R 1 is thiophene (thienyl), in particular 2-thiophene, which may optionally be mono- or polysubstituted by halogen, preferably chlorine or bromine, or
- (C 1 -C 6) -alkyl preferably methyl, where the (C 1 -C 6) -alkyl radical may optionally itself be monosubstituted or polysubstituted by halogen, preferably fluorine,
- R 2 is one of the following groups:
- radical "A” is phenyl or naphthyl, in particular phenyl;
- radical 3 is a 5- or 6-membered aromatic heterocycle which is up to
- radical "D” is a saturated or partially unsaturated 5- or 6-membered heterocycle containing up to two heteroatoms and / or hetero-chain members from the series S, SO, SO 2 , N, NO (N-oxide) and O contains;
- the previously defined groups "A", “B” and “JD” can each optionally be monosubstituted or polysubstituted by a radical from the group of halogen; trifluoromethyl; oxo; cyano; pyridyl; (C r C 3 ) alkanoyl (C 6 -C 0) aryl-carbonyl, (C 5 -C 6) -
- (C 1 -C 4 ) -alkyl and cyclopropyl, cyclopentyl or cyclohexyl may in turn be optionally substituted by a radical from the group of cyano; -OH;
- v is either 0 or 1, preferably 0, and
- R 27, R 28 and R 29 are identical or different and are independently hydrogen, (Ci-C 4) -alkyl or cyclopropyl, cyclopentyl or cyclohexyl
- R 27 and R 28 or R 27 and R 29 together with the nitrogen atom to which they are bonded, a saturated or partially unsaturated 5- to 7-membered heterocycle having up to two identical or different heteroatoms from the group of N, O. and S can form, and
- R 30 and R 31 are identical or different and are independently hydrogen, (Ci-C 4) alkyl, cyclopropyl, cyclopentyl, cyclohexyl, (C r C4) alkylsulfonyl,
- R 3, R 4, R 5, R 6, R 7 and R 8 are identical or different and represent hydrogen or (C r C 6) alkyl
- R 1 is 2-thiophene, which may optionally be substituted in the 5-position by a radical from the group consisting of chlorine, bromine, methyl or trifluoromethyl,
- R 2 is one of the following groups:
- radical "A” is phenyl or naphthyl, in particular phenyl;
- radical 3 is a 5- or 6-membered aromatic heterocycle which is up to
- radical "D” is a saturated or partially unsaturated 5- or 6-membered heterocycle having one nitrogen atom and optionally one further heteroatom and / or hetero-chain member from the series S, SO, SO 2 and O; contains two heteroatoms and / or hetero-chain members from the series S, SO, SO 2 and O;
- oxo cyano; pyridyl; (C, -C 3 ) alkanoyl; (C 6 -C, 0) aryl-carbonyl; (C 5 -C 6 ) heteroarylcarbonyl; (C 1 -C 3 ) alkanoyloxymethyloxy; -CONR 28 R 29 ; -SO 2 NR 28 R 29 ; -OH; -NR 30 R 31 ; (C 1 -C 4 ) -alkyl; and cyclopropyl, cyclopentyl or cyclohexyl,
- (C 1 -C 4 ) -alkyl and cyclopropyl, cyclopentyl or cyclohexyl may in turn optionally be substituted by a radical from the group of cyano; -OH;
- v is either O or 1, preferably O, and
- R 27 , R 28 and R 29 are identical or different and independently of one another are hydrogen, (C 1 -C 4 ) -alkyl or else cyclopropyl, cyclopentyl or cyclohexyl
- R 27 and R 28 and R 27 and R 29 together with the nitrogen atom to which they are attached, a saturated or partially unsaturated 5- to 7-membered heterocycle with can form up to two identical or different heteroatoms from the group of N, O and S, and
- R 30 and R 31 are identical or different and are independently hydrogen, (C r C4) alkyl, cyclopropyl, cyclopentyl, cyclohexyl, (C r C 4) alkylsulfonyl, (C r C 4) hydroxyalkyl, (Ci- C 4) aminoalkyl, di- (Ci-C 4) -alkylainino- (C r C4) alkyl,
- R 3, R 4, R 5, R 6, R 7 and R 8 are identical or different and represent hydrogen or (C r C 4) alkyl
- R 1 is 2-thiophene which is substituted in the 5-position by a radical from the group consisting of chlorine, bromine, methyl or trifluoromethyl,
- a ring carbon member may be replaced by a heteroatom of the series S, N and O;
- Oxazolidinone may optionally be monosubstituted or disubstituted by a radical from the group of fluorine, chlorine, nitro, amino, trifluoromethyl, methyl or cyano, R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are hydrogen,
- the present invention describes the use of one or more compounds of the formula (I), optionally in combination with one or more other active substances, for
- the present invention describes the use of compounds of formula (I) for coating and / or treating artificial surfaces of medical devices and / or devices for preventing fibrin deposition and / or thrombus formation on their surfaces.
- the present invention describes the use of medical aids and / or devices for preventing fibrin coated with compounds of the formula (I) deposition and / or thrombus formation on their surfaces.
- the present invention also describes a method of preventing fibrin deposition and / or thrombus formation on artificial surfaces using one or more compounds of formula (I).
- the compounds of the formula (I) can be used either systemically or preferably in the form of a medical aid and / or device coated with compounds of the formula (I).
- a systemic and / or local administration of further suitable for the treatment and / or prophylaxis of thrombosis agents such as exemplified and preferably abciximab, eptifibatide, tirofiban, acetylsalicylic acid, ticlopidine, clopidogrel or prazabular.
- thrombosis agents such as exemplified and preferably abciximab, eptifibatide, tirofiban, acetylsalicylic acid, ticlopidine, clopidogrel or prazabular.
- the present invention also describes a method for the treatment and / or prophylaxis of fibrin deposition and / or thrombus formation on artificial surfaces by application of medical aids and / or devices which are coated with compounds of formula (I).
- the present invention also describes a method for the treatment and / or prophylaxis of fibrin deposition and / or thrombus formation on artificial surfaces by application of medical aids and / or devices which are coated with compounds of the formula (I) in combination with local and / or systemic administration of other agents suitable for the treatment and / or prophylaxis of fibrin deposition and / or thrombus formation on artificial surfaces.
- the present invention also describes a method for the treatment and / or prophylaxis of fibrin deposition and / or thrombus formation on artificial surfaces by application of medical aids and / or devices coated with compounds of formula (I) in combination with systemic administration of compounds of the formula (I).
- customary medical aids and devices are used, the medical device or device made of either glass, metal, metal alloys or non-degradable plastics such as by way of example and preferably polyethylene, polypropylene, polycarbonate, polyurethane and / or polytetrafluoroethylene (PTFE).
- the medical device or device made of either glass, metal, metal alloys or non-degradable plastics such as by way of example and preferably polyethylene, polypropylene, polycarbonate, polyurethane and / or polytetrafluoroethylene (PTFE).
- PTFE polytetrafluoroethylene
- the medical devices and / or devices are coated with the compounds of formula (I).
- compounds of formula (I) may be incorporated in non-metallic medical devices and / or devices directly into the material used to make the medical devices and / or devices.
- carrier materials are mixed with the compounds of the formula (I).
- the carrier materials used are preferably polymeric carriers, in particular biocompatible, non-biodegradable polymers or polymer blends, such as, by way of example and by way of preference, polyacrylates and their copolymers such as, by way of example and by way of example, poly (hydroxyethyl) methyl methacrylates; polyvinylpyrrolidones; Cellulose esters and ethers; fluorinated polymers such as by way of example and preferably PTFE; Polyvinyl acetates and their copolymers; crosslinked and uncrosslinked polyurethanes, polyethers or polyesters; polycarbonates; Polydimethylsiloxanes.
- biocompatible, biodegradable polymers or polymer blends such as by way of example and preferably polymers or copolymers of lactide and glycolide, or of caprolactone and glycolide; other polyesters; polyorthoesters; polyanhydrides; polyaminoacids; polysaccharides; Polyimino carbonates; Polyphosphazenes and poly (ether-ester) copolymers used as polymeric carriers.
- Suitable polymeric carriers are mixtures of biodegradable and / or non-biodegradable polymers. Through these mixtures, the release rate of the drug is optimally adjusted.
- the mixtures of compounds of formula (I) and carriers are dissolved. These solutions are then processed by various techniques, e.g. Spraying, dipping or brushing applied to the medical device and / or device. After subsequent or simultaneous removal of the solvent, the medicated adjuvant and / or device is formed.
- mixtures of compounds of formula (I) and carrier can be melted and applied by the same application methods.
- the medical aids and / or devices are pretreated to effect an enlargement of the outer and / or inner surface of the medical device and / or device.
- the loading potential is increased and larger paint (drug / - polymer) amounts can be applied.
- various etching techniques for example, various etching techniques but also treatments with ionized radiation are used.
- micropores or cavities may be generated by various techniques in medical devices and / or equipment.
- the active substance contents of the medical aids and / or devices coated with compounds of the formula (I) are generally from 0.001% by weight to 50% by weight, preferably from 0.01% by weight to 30% by weight, particularly preferably 0.1% by weight to 15% by weight.
- the compounds of the formula (I) can also be incorporated directly, for example as a melt embedding, in the medical aids and / or devices.
- active-ingredient-containing polymeric carrier compositions are processed by customary processes, for example by injection molding, to give the final active ingredient-containing form. The release of the active ingredient is usually carried out by diffusion.
- the active substance contents of medical aids and / or devices with embedded compounds of the formula (I) are generally from 0.001% by weight to 70% by weight, preferably from 0.01% by weight to 50% by weight, particularly preferably 0.1% by weight to 30% by weight.
- the medical devices and / or devices coated with compounds of the formula (I) are optionally additionally coated with a membrane.
- This membrane serves, by way of example and preferably, for controlling the release of medicament and / or for protecting the active ingredient-containing medical aids and / or devices against external influences.
- FXa inhibitors may also be used for purification and / or pretreatment, e.g. of catheters and other medical devices and devices mentioned above by addition to the rinsing fluids or suitable pretreatment agents to inhibit contact activation by blood or blood products.
- the present invention further describes the use of one or more compounds of the formula (I), optionally in combination with one or more other active substances, in the purification and / or pretreatment of catheters and other medical aids and devices.
- washing liquids are commercially available washing liquids that are suitable for cleaning the medical instruments.
- the present invention further describes the use of compounds of formula (I) in the purification and / or pretreatment of catheters and other medical devices and devices for preventing fibrin deposition and / or thrombus formation on their surfaces.
- Medical aids and devices are used for all medical articles and apparatuses with surfaces which come into contact with human blood or animal blood and blood products, by way of example and preferably for hypodermic needles, cannulas, tubes, tube connections (connectors for tube connections) Syringes, catheters such as application catheters, indwelling catheter, indwelling central venous lines, percutaneous intravascular catheter recanalization devices such as balloons, ablation laser catheters, intravascular laser devises, rotary catheters, Atherectomy catheters, guide wires, port-systems for intravenous drug delivery, and surgical sutures and drug-depleting systems.
- medical aids and devices for apparatus for extracorporeal use such as oxygenators, blood pumps, blood sensors, detectors, blood tubes, kidney dialysis machines, dialysis membranes, detoxification cartridges and cardiac devices. Lungs machines.
- medical devices and devices for implanted prostheses such as vascular grafts, bypass grafts, pacemaker leads, prosthetic heart valves, venous valves, and other implants.
- medical aids and devices also for such aids and apparatus, which are installed in vessels or hearts, e.g. for recording data such as intra-ultrasound probes and ECG electrodes, and for repair procedures, e.g. Pumps to support cardiac assist devices and artificial organs, such as artificial hearts.
- medical aids and devices also include those aids and apparatus required in the processing and provision of blood and blood products, such as plasma separation aids, e.g. Centrifuges, membrane filters, cell separators, e.g. used in plasmapheresis, bags and preserves for blood and blood products.
- plasma separation aids e.g. Centrifuges, membrane filters, cell separators, e.g. used in plasmapheresis, bags and preserves for blood and blood products.
- Contact activation can be measured by means of a global plasma coagulation test, the activated partial thromboplastin time (aPTT), which measures the influence on factors of the intrinsic blood coagulation system.
- aPTT activated partial thromboplastin time
- the PTT reagent is a mixture of kaolin suspension, which are "silicates” that mimic the negatively charged foreign surface, and cephalin, which are phospholipids, which are needed as the surface for the conversion of factor XII into factor XIIa.
- Factor XII becomes factor XIIa in the presence of a foreign surface, phospholipid and Ca2 +.
- This PTT reagent is added to specially prepared plasma (see examples).
- the coagulation is triggered when the necessary calcium 2+ ions are present, ie by adding a calcium dichloride solution.
- the time between calcium 2+ addition and coagulation entry is then measured and the concentration of inhibitor [in ⁇ M] is shown, which causes a twofold prolongation of the aPTT.
- the test principle is as follows: The plasma sample is mixed with a mixture of the partial thromboplastin cephalin (phospholipid from rabbit brain) and the surface activator kaolin. This initiates contact activation of the intrinsic coagulation system until fibrin formation.
- the citrate (3.8%) is - whole blood at 2500 g for 10 min at 4 ° C centrifugation and stored at -20 0 C.
- aliquots of the platelet-poor plasma (0.1 ml) are incubated with ascending concentrations of test substance or the corresponding solvent for 10 min at 37.degree.
- the clotting time is determined according to the instructions of the manufacturer (PTT-reagent ® , Roche Diagnostics). The procedure is as follows: 0.1 ml of PTT reagent is pipetted into the plasma and the sample is incubated for three minutes at 37.degree. Coagulation is then carried out by adding 0.1 ml of calcium chloride Solution triggered in a coagulometer and measured the time to coagulation. In this way, the 2-fold extension of the aPTT is determined for selected compounds.
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102006034916A DE102006034916A1 (de) | 2006-07-28 | 2006-07-28 | Beschichtung künstlicher Oberflächen von medizinischen Hilfsmitteln und Geräten sowie Reinigung und/oder Vorbehandlung von Kathetern und anderen medizinischen Hilfsmitteln und Geräten |
PCT/EP2007/006282 WO2008012002A2 (de) | 2006-07-28 | 2007-07-16 | Beschichtung künstlicher oberflächen von medizinischen hilfsmitteln und geräten sowie reinigung und/oder vorbehandlung von kathetern und anderen medizinischen hilfsmitteln und geräten |
Publications (1)
Publication Number | Publication Date |
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EP2049168A2 true EP2049168A2 (de) | 2009-04-22 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP07786084A Withdrawn EP2049168A2 (de) | 2006-07-28 | 2007-07-16 | Beschichtung künstlicher oberflächen von medizinischen hilfsmitteln und geräten sowie reinigung und/oder vorbehandlung von kathetern und anderen medizinischen hilfsmitteln und geräten |
Country Status (13)
Country | Link |
---|---|
US (1) | US20100003542A1 (de) |
EP (1) | EP2049168A2 (de) |
JP (1) | JP2009544440A (de) |
KR (1) | KR20090035622A (de) |
CN (1) | CN101522229A (de) |
AU (1) | AU2007278508A1 (de) |
BR (1) | BRPI0714979A2 (de) |
CA (1) | CA2658901A1 (de) |
DE (1) | DE102006034916A1 (de) |
IL (1) | IL196528A0 (de) |
MX (1) | MX2009000818A (de) |
RU (1) | RU2009106953A (de) |
WO (1) | WO2008012002A2 (de) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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DE10355461A1 (de) | 2003-11-27 | 2005-06-23 | Bayer Healthcare Ag | Verfahren zur Herstellung einer festen, oral applizierbaren pharmazeutischen Zusammensetzung |
EP1685841A1 (de) | 2005-01-31 | 2006-08-02 | Bayer Health Care Aktiengesellschaft | Prophylaxe und Behandlung von thrombolischen Erkrankungen |
US11654036B2 (en) | 2020-05-26 | 2023-05-23 | Elixir Medical Corporation | Anticoagulant compounds and methods and devices for their use |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
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DE19962924A1 (de) * | 1999-12-24 | 2001-07-05 | Bayer Ag | Substituierte Oxazolidinone und ihre Verwendung |
DE10152460A1 (de) * | 2001-10-24 | 2003-05-08 | Bayer Ag | Stents |
-
2006
- 2006-07-28 DE DE102006034916A patent/DE102006034916A1/de not_active Withdrawn
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2007
- 2007-07-16 CA CA002658901A patent/CA2658901A1/en not_active Abandoned
- 2007-07-16 WO PCT/EP2007/006282 patent/WO2008012002A2/de active Application Filing
- 2007-07-16 CN CNA2007800364631A patent/CN101522229A/zh active Pending
- 2007-07-16 KR KR1020097004141A patent/KR20090035622A/ko not_active Application Discontinuation
- 2007-07-16 US US12/375,016 patent/US20100003542A1/en not_active Abandoned
- 2007-07-16 BR BRPI0714979-4A patent/BRPI0714979A2/pt not_active Application Discontinuation
- 2007-07-16 AU AU2007278508A patent/AU2007278508A1/en not_active Abandoned
- 2007-07-16 EP EP07786084A patent/EP2049168A2/de not_active Withdrawn
- 2007-07-16 MX MX2009000818A patent/MX2009000818A/es unknown
- 2007-07-16 JP JP2009522130A patent/JP2009544440A/ja active Pending
- 2007-07-16 RU RU2009106953/15A patent/RU2009106953A/ru not_active Application Discontinuation
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2009
- 2009-01-15 IL IL196528A patent/IL196528A0/en unknown
Non-Patent Citations (1)
Title |
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See references of WO2008012002A2 * |
Also Published As
Publication number | Publication date |
---|---|
CN101522229A (zh) | 2009-09-02 |
BRPI0714979A2 (pt) | 2013-03-19 |
CA2658901A1 (en) | 2008-01-31 |
WO2008012002A2 (de) | 2008-01-31 |
JP2009544440A (ja) | 2009-12-17 |
MX2009000818A (es) | 2009-04-28 |
KR20090035622A (ko) | 2009-04-09 |
AU2007278508A1 (en) | 2008-01-31 |
IL196528A0 (en) | 2009-11-18 |
RU2009106953A (ru) | 2010-09-10 |
WO2008012002A3 (de) | 2009-03-12 |
US20100003542A1 (en) | 2010-01-07 |
DE102006034916A1 (de) | 2008-01-31 |
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