Classifications

• • 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
  • A61L31/08—Materials for coatings
  • A61L31/10—Macromolecular materials
• • 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
  • A61L27/28—Materials for coating prostheses
  • A61L27/34—Macromolecular materials
• • 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
• • 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
  • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
  • A61L29/08—Materials for coatings
  • A61L29/085—Macromolecular materials
• • 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
  • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
  • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
• • 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
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G18/00—Polymeric products of isocyanates or isothiocyanates
  • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
  • C08G18/08—Processes
  • C08G18/10—Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
  • C08G18/12—Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step using two or more compounds having active hydrogen in the first polymerisation step
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G18/00—Polymeric products of isocyanates or isothiocyanates
  • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
  • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
  • C08G18/2805—Compounds having only one group containing active hydrogen
  • C08G18/2815—Monohydroxy compounds
  • C08G18/283—Compounds containing ether groups, e.g. oxyalkylated monohydroxy compounds
• • C—CHEMISTRY; METALLURGY
  • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
  • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
  • C09D175/00—Coating compositions based on polyureas or polyurethanes; Coating compositions based on derivatives of such polymers
  • C09D175/02—Polyureas

Definitions

• the present invention relates to a coating composition in the form of a polyurethane solution which can be used to prepare hydrophilic coatings.
• Another object of the present invention is a method for
• Equipment with hydrophilic surfaces can be greatly improved.
• the insertion and displacement of urine or blood vessel catheters is made easier by the fact that hydrophilic surfaces in contact with blood or urine adsorb a water film.
• the friction of the catheter surface is reduced compared to the vessel walls, so that the catheter is easier to use and move.
• a direct watering of the equipment before the intervention can be made to reduce the friction by the formation of a homogeneous water film. Affected patients have less pain and the risk of injury to the vessel walls is thereby reduced.
• the use of catheters always involves the risk of blood clots forming.
• Polyurethane coatings which are prepared starting from solutions or dispersions of corresponding polyurethanes, are generally suitable for the production of corresponding surfaces.
• US Pat. No. 5,589,563 describes the use of surface-modified end-group coatings for polymers used in the field of biomedicine, which can also be used for coating medical devices.
• the resulting coatings are prepared from solutions or dispersions and the polymeric coatings comprise various end groups selected from amines, fluorinated alkanols, polydimethylsiloxanes and amine-terminated polyethylene oxides.
• these polymers do not have satisfactory properties as a coating for medical devices, especially with regard to the required hydrophilicity.
• Polyurethane solutions per se are known from the prior art, but have not been used for coating medical devices, with the exception of the already mentioned polyurethane solutions according to US Pat. No. 5,589,563.
• DE 22 21 798 A describes a process for preparing stable and light-stable solutions of polyurethane ureas from prepolymers having terminal isocyanate groups and diamines in low-polar solvents, with prepolymers of
• substantially linear polyhydroxyl compounds having molecular weights of about 500 to 5,000
• DE 22 52 280 A describes a process for coating textile substrates by the reversal process with adhesive and topcoats from solutions of aliphatic, segmented polyurethane elastomers which are polycarbonate-containing.
• EP 0 125 466 A describes a process for the multi-line reverse coating of textile, preferably sheet-like, bases for the production of artificial leather from at least one top coat solution and at least one adhesion coat solution based on polyurethanes.
• the object of the present invention is thus to provide a composition which is suitable for the coating of medical devices with hydrophilic surfaces. Since these surfaces are often used in blood contact, the surfaces of these materials should also have good blood compatibility and in particular reduce the risk of the formation of blood clots. Furthermore, the resulting coatings should be smooth and have high stability.
• the subject of this invention are coating compositions in the form of specific polyurethane solutions.
• the polyurethane solutions of the invention comprise at least one polyurethaneurea terminated with a copolymer unit of polyethylene oxide and polypropylene oxide.
• compositions of these particular polyurethane ureas in solutions are outstandingly suitable for the production of
• Coatings on medical devices provide them with an excellent hydrophilic coating, form smooth surfaces, have a high stability and at the same time reduce the risk of blood clots during treatment with the medical device.
• Polyurethane ureas in the context of the present invention are polymeric compounds which
• compositions in the form of a solution to be used according to the invention are based on polyurethane adhesives which are essentially nonionic
• polyurethaneureas to be used according to the invention essentially have no ionic groups, in particular no sulfonate, carboxylate, phosphate and phosphonate groups have.
• Polyurethaneurea ionic groups in a proportion of generally not more than 2.50 wt .-%, in particular at most 2.00 wt .-%, preferably at most 1.50 wt .-%, particularly preferably at most 1.00 wt .-%, especially at most 0.50 wt .-%, more particularly no ionic groups.
• the polyurethaneurea has no ionic groups, since high concentration of ions in organic solution cause the polymer is no longer sufficiently soluble and thus no stable solutions can be obtained.
• the polyurethane used according to the invention has ionic groups, these are preferably carboxylates.
• the coating composition according to the invention in the form of a solution comprises polyurethanes, which are preferably substantially linear molecules but may also be branched, but this is less preferred.
• substantially linear molecules are understood as meaning slightly crosslinked systems which contain a polyol component having an average hydroxyl functionality of preferably from 1.7 to
• the number-average molecular weight of the polyurethane ureas preferably used according to the invention is preferably from 1000 to 200,000, more preferably from 5,000 to 100,000.
• the polyurethane-containing coating compositions according to the invention in the form of a solution are prepared by reacting building components comprising at least one polycarbonate polyol component, at least one polyisoyanate component, at least one polyoxyalkylene ether component, at least one diamine and / or aminoalcohol component and optionally one further polyol component.
• the coating composition based on polyurethaneurea in the form of a solution according to the invention has units which are based on at least one hydroxyl-containing polycarbonate.
• polyhydroxy compounds having an average hydroxyl functionality of 1.7 to 2.3, preferably from 1.8 to 2.2, particularly preferably from 1.9 to 2.1.
• hydroxyl-containing polycarbonates are polycarbonates of specific molecular weight by OH number of preferably 400 to 6000 g / mol, more preferably 500 to 5000 g / mol, in particular from 600 to 3000 g / mol in question, for example by reaction of carbonic acid derivatives, such as Diphenyl carbonate, dimethyl carbonate or phosgene, with polyols, preferably diols, are available.
• carbonic acid derivatives such as Diphenyl carbonate, dimethyl carbonate or phosgene
• diols examples include ethylene glycol, 1,2- and 1,3-propanediol, 1,3- and 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, neopentyl glycol, 1,4-bishydroxymethylcyclohexane, 2 Methyl-1, 3-propanediol, 2,2,4-trimethylpentane-1, 3-diol, di-, tri- or tetraethylene glycol, dipropylene glycol, polypropylene glycols, dibutylene glycol, polybutylene glycols, bisphenol A, tetrabromobhenol A but also lactone-modified Diols in question.
• the diol component contains from 40 to 100% by weight of hexanediol, preferably 1,6-hexanediol and / or hexanediol derivatives, preferably those which, in addition to terminal OH groups, contain ether or ester groups, e.g. Products obtained by implementation of 1
• Mol hexanediol with at least 1 mole, preferably 1 to 2 moles of caprolactone or by etherification of hexanediol with itself to di- or trihexylenglycol were obtained.
• Polyether-polycarbonate diols can also be used.
• the hydroxyl polycarbonates should be substantially linear. However, they may optionally be easily branched by the incorporation of polyfunctional components, especially low molecular weight polyols.
• glycerol trimethylolpropane, hexanetriol-1, 2,6, butanetriol-1, 2,4, trimethylolpropane, pentaerythritol, quinitol, mannitol, sorbitol, methyl glycoside or 1,3,4,6-dianhydrohexitols are suitable for this purpose.
• butane-1,4-diol or ⁇ -caprolactone Further preferred polycarbonate diols are those based on mixtures of hexanediol-1, 6 and butanediol-1, 4.
• the polycarbonate is preferably substantially linear and has only a slight three-dimensional cross-linking, so that polyurethanes are formed which have the aforementioned specification.
• the polyurethaneurea-based coating composition according to the invention has units which are based on at least one polyisocyanate as the synthesis component.
• polyisocyanates (b) all known to the expert aromatic, araliphatic, aliphatic and cycloaliphatic isocyanates of an average NCO functionality> 1, preferably> 2 individually or in any mixtures with each other are used, and it is irrelevant whether these are phosgene or phosgene -free process were made. These may also have iminooxadiazinedione, isocyanurate, uretdione, urethane, allophanate, biuret, urea, oxadiazinetrione, oxazolidinone, acylurea and / or carbodiimide structures.
• the polyisocyanates can be used individually or in any mixtures with one another.
• Isocyanates from the series of aliphatic or cycloaliphatic representatives are preferably used, these having a carbon skeleton (without the NCO groups contained) of 3 to 30, preferably 4 to 20 carbon atoms.
• Particularly preferred compounds of component (b) correspond to the abovementioned type with aliphatically and / or cycloaliphatically bonded NCO groups, for example bis (isocyanatoalkyl) ethers, bis- and tris- (isocyanatoalkyl) benzenes, -toluenes, and -xylols, propane diisocyanates , Butane diisocyanates, pentane diisocyanates, hexane diisocyanates (eg hexamethylene diisocyanate, HDI), heptane diisocyanates, octane diisocyanates, nonane diisocyanates (eg trimethyl-HDI (TMDI) usually as a mixture of the 2,4,4- and 2,2,4-isomers), nonane triisocyanates (eg 4-isocyanatomethyl-1,8-octane diisocyanate), decane di
• component (b) Very particularly preferred compounds of component (b) are hexamethylene diisocyanate (HDI), trimethyl-HDI (TMDI), 2-methylpentane-1, 5-diisocyanate (MPDI), isophorone diisocyanate (IPDI), 1, 3 and 1, 4-bis (isocyanatomethyl) cyclohexane
• HDI hexamethylene diisocyanate
• TMDI trimethyl-HDI
• MPDI 2-methylpentane-1
• MPDI 5-diisocyanate
• IPDI isophorone diisocyanate
• H 6 XDI bis (isocyanatomethyl) norbornane
• NBDI bis (isocyanatomethyl) norbornane
• IMCI isocyanatomethyl-1-methylcyclohexyl isocyanate
• H 12 MDI 4,4'-bis (isocyanatocyclohexyl) methane
• uretdione isocyanurate, urethane, allophanate, biuret, iminooxadiazinedione and / or oxadiazinetrione structure having more than two NCO groups.
• the amount of component (b) in the coating composition to be used according to the invention is preferably from 1.0 to 3.5 mol, particularly preferably from 1.0 to 3.3 mol, in particular from 1.0 to 3.0 mol, in each case based on the constituent (a) the coating composition to be used in the present invention.
• the polyurethaneurea used in the present invention has units derived from a copolymer of polyethylene oxide and polypropylene oxide as the constituent component. These copolymer units are present as end groups in the polyurethaneurea and cause a hydrophilization of the coating composition according to the invention.
• Nonionically hydrophilicizing compounds (c) are, for example, monovalent polyalkylene oxide polyether alcohols containing on average from 5 to 70, preferably 7 to 55, ethylene oxide units per molecule, as are obtainable in a conventional manner by alkoxylation of suitable starter molecules (eg in Ullmanns Enzyklopadie der ischen Chemie, 4 Edition, Volume 19, Verlag Chemie, Weinheim pp. 31-38).
• Suitable starter molecules are, for example, saturated monoalcohols, such as methanol,
• alkylene oxides ethylene oxide and propylene oxide can be used in any order or even as a mixture in the alkoxylation reaction.
• the polyalkylene oxide polyether alcohols are mixed
• Preferred nonionic compounds are monofunctional mixed polyalkylene oxide polyethers having at least 40 mole percent ethylene oxide and at most 60 mole percent propylene oxide units.
• the average molecular weight of the polyoxyalkylene ether is preferably 500 g / mol to 5000 g / mol, particularly preferably 1000 g / mol to 4000 g / mol, in particular 1000 to 3000 g / mol.
• the amount of component (c) in the coating composition to be used in the present invention is preferably 0.01 to 0.5 mol, more preferably 0.02 to 0.4 mol, more preferably 0.04 to 0.3 mol, in each case based on the
• Component (a) of the coating composition to be used according to the invention is Component (a) of the coating composition to be used according to the invention.
• the polyurethaneureas with end groups based on mixed polyoxyalkylene ethers of polyethylene oxide and polypropylene oxide are particularly suitable for coatings with a high degree of hardness
• the coatings according to the invention have a markedly low contact angle and are therefore more hydrophilic.
• the polyurethaneurea solution according to the invention has units which are based on at least one diamine or an amino alcohol component as a building component and serve as so-called chain extenders (d).
• Such chain extenders include di- or polyamines and hydrazides, for example hydrazine, ethylenediamine, 1, 2- and 1, 3-diaminopropane, 1, 4-diaminobutane, 1, 6-diaminohexane, isophoronediamine, isomer mixture of 2,2,4- and 2,4,4-trimethylhexamethylenediamine, 2-methylpentamethylenediamine, diethylenetriamine, 1, 3- and 1, 4-xylylenediamine, ⁇ , ⁇ , ⁇ ' , ⁇ ' -
• diamines or amino alcohols are generally low molecular weight diamines or
• Amino alcohols containing active hydrogen with respect to NCO groups of different reactivity such as compounds which in addition to a primary amino group and secondary amino groups or in addition to an amino group (primary or secondary) also have OH groups.
• primary and secondary amines such as 3-amino-1-methylaminopropane, 3-amino-1-ethylaminopropane, 3-amino-1-cyclohexylaminopropane, 3-amino-1-methylaminobutane, furthermore amino alcohols, such as N-aminoethylethanolamine, ethanolamine , 3-aminopropanol, neopentanolamine and more preferably diethanolamine.
• Coating composition can be used in their preparation as a chain extender.
• the amount of component (d) in the solution according to the invention of the coating composition is preferably 0.1 to 1.5 mol, particularly preferably 0.2 to 1.3 mol, in particular 0.3 to 1.2 mol, in each case based on the constituent (a) the coating composition to be used in the present invention.
• the coating composition of the invention formed as a solution comprises additional units which are based on at least one further polyol as the synthesis component.
• the other low molecular weight polyols (e) used to build up the polyurethane ureas generally cause stiffening and / or branching of the polymer chain.
• the molecular weight is preferably 62 to 500 g / mol, particularly preferably 62 to 400 g / mol, in particular 62 to 200 g / mol.
• Suitable polyols may contain aliphatic, alicyclic or aromatic groups. Mentioned here are, for example, the low molecular weight polyols having up to about 20 carbon atoms per molecule, such as. Ethylene glycol, diethylene glycol, triethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,4-butanediol, 1,3-butylene glycol, cyclohexanediol, 1,4-cyclohexanedimethanol, 1,6-hexanediol, neopentylglycol, Hydroquinone dihydroxyethyl ether, bisphenol A (2,2-bis (4-hydroxyphenyl) propane), hydrogenated bisphenol A (2,2-bis (4-hydroxycyclohexyl) propane), and trimethylolpropane, glycerol or pentaerythritol and mixtures thereof and optionally also further low molecular weight polyol
• Adipic acid ( ⁇ -hydroxyethyl) ester or terephthalic acid bis ( ⁇ -hydroxyethyl) ester may be used.
• the amount of the component (s) in the coating composition to be used in the present invention is preferably 0.05 to 1.0 mol, especially preferably from 0.05 to 0.5 mol, in particular from 0.1 to 0.5 mol, in each case based on the constituent (a) of the coating composition to be used according to the invention.
• the reaction of the isocyanate-containing component (b) with the hydroxy- or amine-functional compounds (a), (c), (d) and optionally (e) is usually carried out while maintaining a slight excess of NCO over the reactive hydroxy or amine compounds.
• a target viscosity remains of active isocyanate remain.
• residues must be blocked to avoid reaction with large polymer chains.
• Such a reaction leads to three-dimensional crosslinking and gelling of the approach.
• the processing of such a coating solution is no longer possible.
• the approaches contain high levels of alcohols. These alcohols block the remainder within several hours of standing or stirring the batch at room temperature
• the polyurethaneurea coating compositions provided according to the invention in the form of a solution can also contain monomers (f) as structural components, which are located at the chain ends and close them.
• These structural components are derived, on the one hand, from monofunctional compounds reactive with NCO groups, such as monoamines, in particular mono-secondary amines or monoalcohols.
• monoamines such as monoamines, in particular mono-secondary amines or monoalcohols.
• monoamines such as monoamines, in particular mono-secondary amines or monoalcohols.
• examples of these are ethanol, n-butanol, ethylene glycol monobutyl ether, 2-ethylhexanol, 1-octanol, 1-dodecanol, 1-hexadecanol, methylamine, ethylamine, propylamine, butylamine, octylamine, laurylamine, stearylamine, isononyloxypropylamine, dimethylamine, diethylamine, Dipropylamine, dibutylamine, N-methylaminopropylamine, diethyl (methyl) amino
• the building blocks (f) are essentially used in the coating composition of the invention in the form of a solution to destroy the NCO excess, the amount required depends essentially on the amount of NCO excess and can not be generally specified.
• solutions of the polyurethaneurea coating composition provided according to the invention may also contain further constituents and additives customary for the intended purpose.
• An example of this are pharmacologically active substances,
• Pharmacological agents or drugs which can be used in the coatings according to the invention on the medical devices and thus can be contained in the solutions according to the invention are, for example, thromboresistant
• antibiotic agents antibiotic agents, antitumor agents, growth hormones, antiviral agents, antiangiogenic agents
• Agents angiogenic agents, antimitotic agents, antiinflammatory agents, cell cycle regulating agents, genetic agents, hormones, and their homologs, derivatives, fragments, pharmaceutical salts, and combinations thereof.
• pharmacological agents thus include, but are not limited to, thromboresistant (non-thrombogenic) agents or other agents for the suppression of acute thrombosis, stenosis, or late re-stenosis of the arteries, such as heparin, streptokinase, urokinase, tissue plasminogen activator, anti- Thromboxane B 2 -
• a growth factor may also be used as a drug In order to suppress subintimal fibromuscular hyperplasia at the arterial stenosis, or it may be any other inhibitor of cell growth at the
• Stenosestelle be used.
• the pharmacological agent or drug may also consist of a vasodilator to counteract vasospasm, for example an antispasmodic agent such as papaverine.
• the drug may be a vasoactive agent per se, such as
• the therapeutic agent may be a biological adhesive such as medical grade cyanoacrylate or fibrin used, for example, for adhering a tissue valve to the wall of a coronary artery.
• the therapeutic agent may also be an antineoplastic agent such as 5-fluorouracil, preferably with a controlling releasing carrier for the agent (eg for the application of a sustained controlled releasing antineoplastic agent at a tumor site).
• the therapeutic agent may be an antibiotic, preferably in combination with a controlling releasing carrier for sustained release from the coating of a medical device to a localized source of infection within the body.
• the therapeutic agent may contain steroids for the purpose of suppressing inflammation in localized tissue or for other reasons.
• Suitable drugs include:
• antibiotic agents such as penicillins, cephalosprins, vacomycins, aminoglycosides, quinolones, polymxins, erythromycins; Tertracyclines, chloramphenicols, clindamycins, lincomycins, sulfonamides, their homologues, analogues, derivatives, pharmaceutical salts and mixtures thereof;
• paclitaxel paclitaxel
• docetaxel immunosuppressants such as sirolimus or everolimus, alkylating agents including mechlorethamine, chlorambucil, cyclophosphamide, melphalan and ifosfamide;
• Antimetabolites including methotrexate, 6
• Mercaptopurine, 5-fluorouracil and cytarabine Plant alcohols including vinblastine; Vincristine and etoposide; Antibiotics including doxorubicin, daunomycin, bleomycin and mitomycin; Nitrosurea including carmustine and lomustine; inorganic ions including cisplatin; biological reaction modifiers including interferon; angiostatic agents and endostatin agents; Enzymes including asparaginase; and hormones including tamoxifen and flutamide, their homologues, analogs, fragments, derivatives, pharmaceutical salts and mixtures thereof;
• antiviral agents such as amantadine, rimantadine, rabavirin, idoxuridine, vidarabine,
• Trifluridine Trifluridine, acyclovir, ganciclocir, zidovudine, phosphonoformates, interferons, their homologues, analogs, fragments, derivatives, pharmaceutical salts and mixtures thereof;
• anti-inflammatory agents such as ibuprofen, dexamethasone or
• the coating composition according to the invention in the form of a solution comprises a polyurethaneurea, which is at least built up a) at least one polycarbonate polyol;
• the coating composition according to the invention in the form of a solution comprises a polyurethaneurea which is at least built up
• the coating composition according to the invention in the form of a solution comprises a polyurethane urethane which is at least built up
• the coating compositions according to the invention in the form of a solution preferably comprises polyurethane ureas which are at least built up a) at least one polycarbonate polyol having an average molecular weight between 400 g / mol and 6000 g / mol and a hydroxyl functionality of 1.7 to 2.3 or mixtures of such polycarbonate polyols;
• Polyethers having an average molecular weight between 500 g / mol and 5000 g / mol in an amount per mole of the polycarbonate polyol of 0.01 to 0.5 mol;
• At least one polycarbonate polyol having an average molecular weight between 500 g / mol and 5000 g / mol and a hydroxyl functionality of 1.8 to 2.2 or mixtures of such polycarbonate polyols;
• polyurethane ureas are used in the coating solution, which are at least built up
• Polyethylene oxide and polypropylene oxide are particularly preferred.
• the coating composition of the invention in the form of a solution can be used to form a coating on a medical device.
• medical device is to be broadly understood within the scope of the present invention
• suitable, non-limiting examples of medical devices include: contact lenses; cannulas; catheters, such as urological catheters such as bladder catheters or ureteral catheters, central venous catheters, venous catheters, or Inlet and outlet catheters; dilation balloons; catheters for angioplasty and biopsy; catheters used for introducing a stent, a graft or a kavafilter; balloon catheters or other expandable medical devices; endoscopes; larnygoscopes; tracheal devices such as endotracheal tubes , Breathing apparatus and other tracheal suction devices; bronchoalveolar
• Flushing catheters Flushing catheters; Catheters used in coronary angioplasty; Management staff, importers and the like; Gefäßpfropfen; Pacemaker components; Cochlear implants; Dental implant tubes for feeding, drainage hoses; and guide wires.
• the coating solutions according to the invention can be used for the production of protective coatings, for example for gloves, stents and other implants; extracorporeal (out-of-body) blood tubes (blood guide tubes); Membrane, for example for dialysis; Blood filter; Apparatus for circulatory support; Dressings for wound care; Hambags and ostomy pouches are used. Included are also
• Implants containing a medically effective agent such as medically acting stents or for balloon surfaces or for contraceptives.
• the medical device will include catheters, endoscopes, laryngoscopes, endotracheal tubes, feeding tubes, guide rods, stents, and others
• Coating of medical devices used aqueous, nonionic stabilized polyurethane dispersions of the type described above.
• the ones described above Coating compositions are preferably obtained as an organic solution and applied to the surface of medical devices.
• coating solutions consist of a mixture of polycarbonate polyols and a monofunctional polypropylene oxide-polyethylene oxide
• Coatings of medical devices are prepared starting from solutions of the coating composition described in more detail above.
• Coating composition is prepared from a dispersion or a solution.
• Coating compositions can be obtained.
• the medical devices according to the invention can be coated by means of various methods with the hydrophilic polyurethane solutions. Suitable coating techniques are, for example, doctoring, printing, transfer coating, spraying, spin coating or dipping.
• the organic polyurethane solutions can be prepared by any method.
• the reaction is carried out at a temperature of preferably between 60 and 110 0 C, more preferably 75 to 110 ° C, in particular 90 to 110 0 C, wherein temperatures to
• 110 0 C is preferred because of the speed of implementation. Higher temperatures can also be used, but there is a risk in individual cases and depending on the individual components used that decomposition processes and discoloration occur in the resulting polymer.
• the reaction in melt is preferred, but there is a risk that it comes to high viscosities of the reacted mixtures. In these cases, it is also advisable to add solvents. However, it should preferably not contain more than about 50 wt .-% of solvent, otherwise the dilution significantly slows down the reaction rate.
• the order of addition or conversion of the individual constituents may differ from the sequence indicated above. This may be particularly advantageous if the mechanical properties of the resulting coatings to be changed. If, for example, all hydroxyl-containing components are reacted simultaneously, a mixture of hard and soft segments is formed. For example, by adding the low molecular weight polyol to the polycarbonate polyol component, one obtains defined blocks, which may entail other properties of the resulting coatings.
• the present invention is thus not limited to any
• the further addition of the solvent is preferably carried out stepwise, so as not to slow down the reaction unnecessarily, which would happen if the amount of solvent were completely added, for example at the beginning of the reaction. Furthermore, it is bound at a high content of solvent at the beginning of the reaction at a relatively low temperature, which is at least co-determined by the nature of the solvent. This also leads to a slowing of the reaction.
• the remaining residues of NCO can be blocked by a monofunctional aliphatic amine.
• the remaining isocyanate groups are preferably blocked by reaction with the alcohols contained in the solvent mixture.
• Suitable solvents for the preparation and use of the polyurethaneurea solutions according to the invention are all conceivable solvents and solvent mixtures such as dimethylformamide, N-methylacetamide, tetramethylurea, N-methylpyrrolidone, aromatic solvents such as toluene, linear and cyclic esters, ethers,
• esters and ketones are, for example, ethyl acetate, butyl acetate, acetone, ⁇ -butyrolactone, methyl ethyl ketone and methyl isobutyl ketone.
• examples of the alcohols which are used together with the toluene are ethanol, n-propanol, iso-propanol and 1-
• the solids content of the polyurethane solutions is generally between 5 to 60 wt .-%, preferably 10 to 40 wt .-%.
• the polyurethane solutions can be diluted as desired with toluene / alcohol mixtures in order to be able to variably adjust the thickness of the coating. All concentrations of 1 to 60 wt .-% are possible, preferred are concentrations in the range 1 to 40 wt .-%.
• any layer thicknesses can be achieved, for example, some 100 nm up to a few 100 microns, and in the context of the present invention also higher and lower thicknesses are possible.
• Other additives such as antioxidants or pigments may also be used.
• further additives such as handle auxiliaries, dyes, matting agents, UV stabilizers, light stabilizers, water repellents and / or leveling agents may be used.
• Medical stainless steel and nickel-titanium alloys Many polymer materials are conceivable from which the medical device can be constructed, for example polyamide;
• polystyrene polycarbonate; polyether; Polyester; polyvinyl acetate; natural and synthetic rubbers; Block copolymers of styrene and unsaturated compounds such as ethylene,
• Butylene and isoprene Polyethylene or copolymers of polyethylene and polypropylene;
• Polyurethanes on the medical device can be applied as a substrate before applying these hydrophilic coating materials, other suitable coatings.
• the medical devices can be coated by various methods with the hydrophilic polyurethane dispersions. Suitable coating techniques are doctoring, printing, transfer coating, spraying, spin coating or dipping.
• the coating compositions provided according to the invention are also distinguished by high blood compatibility. As a result, working with these coatings is particularly advantageous in blood contact.
• the materials show reduced coagulation tendency in blood contact compared to prior art polymers.
• the NCO content of the resins described in the Examples and Comparative Examples was determined by titration in accordance with DIN EN ISO 11909.
• the solids contents were determined in accordance with DIN-EN ISO 3251. 1 g of polyurethane dispersion was dried at 115 ° C. to constant weight (15-20 min) using an infrared drier.
• Viscosity measurements were carried out with the Physics MCR 51 Rheometer from Anton Paar GmbH, Ostfildern, Germany.
• Desmophen C2200 polycarbonate polyol, OH number 56 mg KOH / g, number average molecular weight 2000 g / mol (Bayer MaterialScience AG, Leverkusen, DE)
• Desmophen C1200 polycarbonate polyol, OH number 56 mg KOH / g, number average molecular weight 2000 g / mol (Bayer MaterialScience AG, Leverkusen, DE)
• Desmophen XP 2613 polycarbonate polyol OH number 56 mg KOH / g, number average molecular weight 2000 g / mol (Bayer MaterialScience AG, Leverkusen, DE)
• PolyTHF ® 2000 Polytetramethylenglykolpolyol, OH number 56 mg KOH / g, number average
• This example describes the preparation of a polyurethane urea solution according to the invention.
• Methoxypropanol-2 added. After completion of the molecular weight and reaching the desired viscosity range (check by measuring the viscosity of a pulled sample with the above-cited rheometer) was stirred for another 4 hours to block the residual isocyanate content with iso-propanol. 927 g of a 30.4% strength polyurethane urea solution in toluene / isopropanol / 1-methoxy-2-propanol having a viscosity of 19600 mPas at 22 ° C. were obtained.
• This example describes the preparation of a polyurethane urea solution according to the invention.
• This example describes the preparation of a polyurethane urea solution according to the invention.
• Desmophen C 1200, 23.0 g LB 25 and 47.8 g of 4,4'-bis (isocyanatocyclohexyl) methane (H 12 MDI) were at 110 0 C up to a constant NCO content of 2.4 % was reacted .. It was allowed to cool and diluted with 350.0 g of toluene and 200 g of iso-propanol. At room temperature, a solution of 13.2 g of isophoronediamine in 100.0 g of 1-methoxy-2-propanol was added.
• This example describes the preparation of a polyurethane urea solution according to the invention.
• This example describes the preparation of a polyurethane urea solution as a comparative product to Example 1 according to the invention.
• the Desmophen C2200 is replaced by the polyTHF 2000.
• Methoxypropanol-2 added. After completion of the molecular weight and reaching the desired viscosity range was stirred for another 4 hours to block the residual isocyanate content with iso-propanol. 916 g of a 30.2% was obtained solution of polyurethaneurea in toluene / iso-propanol / 1-methoxy-2 having a viscosity of 15200 mPas at 22 0 C.
• This example describes the preparation of a polyurethane urea solution as comparison product to Example 2 according to the invention.
• the Desmophen C2200 is replaced by the polyTHF 2000.
• the static contact angle measurements were made on 25x75 mm glass slides using a spincoater (RC5 Gyrset 5, Karl Suess, Garching, Germany). A slide was clamped on the sample plate of the spin coater and homogenously covered with about 2.5-3 g of organic 15% strength polyurethane solution. All organic polyurethane solutions were mixed with a solvent mixture of 65% by weight of toluene and 35% by weight of isopropanol to a polymer content of 15% by weight diluted. By rotation of the sample tray for 20 sec at 1300 revolutions per minute, a homogeneous coating was obtained which was dried at 100 ° C. for 1 h and then at 50 ° C. for 24 h. The resulting coated slides were subjected directly to a contact angle measurement.
• Example 9 As shown in Table 1, the polycarbonate-containing coatings of Examples 1-5 give highly hydrophilic coatings with static contact angles ⁇ 40 °. In contrast, the polyurithin F-containing coatings 7-9 are substantially more nonpolar, although the composition of these coatings are otherwise identical to those of Examples 1 and 2.
• Example 9 Example 9:
• This comparative example describes the synthesis of a polyurethane urea polymer which contains, instead of the mixed monofunctional polyethylene-polypropylene oxide alcohol LB 25, the same molar proportion of a pure monofunctional polyethylene oxide alcohol.
• the polymer is identical to that of Example 1 except that it contains a different terminal group.
• the synthesis in toluene and alcohols as described in Examples 1-7 does not work when using this alcohol. Therefore, the synthesis is carried out in pure dimethylformamide (DMF).
• DMF dimethylformamide
• This example describes the synthesis of a polyurethane urea polymer according to the invention in DMF as solvent.
• the polymer is identical to that of Example 1, but was therefore made in DMF to compare its physical properties with the polymer of Example 9.
• Viscosity range (check by measuring the viscosity of a drawn sample with the above-cited rheometer) was added to 0.5 g of n-butylamine to block the low residual isocyanate content. 930 g of a 30.6% were obtained
• Example 8 As described in Example 8, the polyurethane solutions of Examples 9 and 10 were used to produce films on glass and to measure static contact angles.
• Example 10 made with the blended (polyethylene oxide / polypropylene oxide) monofunctional polyether alcohol shows at 36 ° a significantly lower static contact angle than the film of Example 9 (55 °) containing pure polyethylene oxide units.
• This example describes the synthesis of a polyurethane according to the invention in organic solution. This product was compared with the appropriately aqueous-prepared polyurethane of Example 13 (see Example 14).
• Example 12 This example describes the synthesis of the polyurethane of Example 12 in aqueous dispersion. It consists of the same polymer as described in Example 12.
• Polymers are compared in Example 14 with each other.
• 277.2 g of Desmophen C 2200, 33.1 g of polyether LB 25 and 6.7 g of neopentyl glycol were initially introduced at 65 ° C. and homogenized by stirring for 5 minutes, at which 71 ° C. was first added at 65 ° C. within 1 minute g 4,4'-bis (isocyanatocyclohexyl) methane (Hi 2 MDI) followed by 11.9 g of isophorone diisocyanate, heated to 110 ° C. until a constant NCO value of 2.4% was reached.
• the finished prepolymer was dissolved at 50 0 C in 711 g of acetone and then added at 40 0 C, a solution of 4.8 g of ethylenediamine in 16 g of water within 10 min. The stirring time was 5 min. The mixture was then dispersed within 15 minutes by adding 590 g of water. This was followed by removal of the solvent by distillation in vacuo. A storage-stable polyurethane dispersion with a solids content of 40.7% and an average particle size of 136 nm was obtained. The pH of this dispersion was 6.7.
• Example 12 The two coatings of Examples 12 and 13 were applied to release paper with a 200 ⁇ m doctor blade.
• the coating of Example 12 was applied in undiluted form, the aqueous dispersion was mixed with 2% by weight of a thickener prior to film production (Borchi Gel A LA, Borchers, Langenfeld, Germany) and homogenized by stirring for 30 min at RT.
• the wet films were dried at 100 ° C for 15 minutes.
• the organic solution film of Example 12 has higher elasticity (700% elongation at break as compared to 550% for the aqueous dispersion polymer).

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Epidemiology (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Medicinal Chemistry (AREA)
• Organic Chemistry (AREA)
• Dermatology (AREA)
• Polymers & Plastics (AREA)
• Transplantation (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Vascular Medicine (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Surgery (AREA)
• Heart & Thoracic Surgery (AREA)
• Engineering & Computer Science (AREA)
• Wood Science & Technology (AREA)
• Materials Engineering (AREA)
• Polyurethanes Or Polyureas (AREA)
• Paints Or Removers (AREA)
• Coating Of Shaped Articles Made Of Macromolecular Substances (AREA)

Priority Applications (8)

Applications Claiming Priority (2)

Publications (1)

Family

ID=39590728

Family Applications (1)

Country Status (12)

Cited By (2)

Families Citing this family (7)

Citations (2)

Family Cites Families (12)

• 2008
  • 2008-03-20 EP EP08153055A patent/EP2103638A1/de not_active Ceased
• 2009
  • 2009-03-16 CN CN200980109968.5A patent/CN101977956B/zh not_active Expired - Fee Related
  • 2009-03-16 KR KR1020107020854A patent/KR20100134607A/ko not_active Withdrawn
  • 2009-03-16 JP JP2011500096A patent/JP2011514425A/ja not_active Withdrawn
  • 2009-03-16 US US12/933,473 patent/US20110021657A1/en not_active Abandoned
  • 2009-03-16 WO PCT/EP2009/001899 patent/WO2009115264A1/de not_active Ceased
  • 2009-03-16 ES ES09721595.8T patent/ES2548448T3/es active Active
  • 2009-03-16 EP EP09721595.8A patent/EP2257581B1/de not_active Not-in-force
  • 2009-03-16 AU AU2009226706A patent/AU2009226706A1/en not_active Abandoned
  • 2009-03-16 CA CA2718839A patent/CA2718839A1/en not_active Abandoned
  • 2009-03-16 RU RU2010142598/05A patent/RU2010142598A/ru not_active Application Discontinuation
  • 2009-03-16 BR BRPI0908998-5A patent/BRPI0908998A2/pt not_active IP Right Cessation
  • 2009-03-19 TW TW098108844A patent/TW201000578A/zh unknown

Patent Citations (2)

Also Published As

Similar Documents

Legal Events