WO2003045461A1 - Produit textile a surface modifiee et procede de modification de surface correspondant - Google Patents

Produit textile a surface modifiee et procede de modification de surface correspondant Download PDF

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Publication number
WO2003045461A1
WO2003045461A1 PCT/DE2002/004291 DE0204291W WO03045461A1 WO 2003045461 A1 WO2003045461 A1 WO 2003045461A1 DE 0204291 W DE0204291 W DE 0204291W WO 03045461 A1 WO03045461 A1 WO 03045461A1
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WO
WIPO (PCT)
Prior art keywords
textile product
product according
substrate
pvdf
spacer molecules
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/DE2002/004291
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German (de)
English (en)
Inventor
Boris Obolenski
Uwe Klinge
Bernd Klosterhalfen
Stefan Schneemelcher
Bernhard Hartwig HÖCKER
Doris Klee
Zahida Ademovic
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
FEG TEXTILTECHNIK FORSCHUNGS- und ENTWICKLUNGSGESELLSCHAFT MBH
Original Assignee
FEG TEXTILTECHNIK FORSCHUNGS- und ENTWICKLUNGSGESELLSCHAFT MBH
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Priority to AU2002358421A priority Critical patent/AU2002358421A1/en
Priority to DE10295443.7T priority patent/DE10295443B4/de
Publication of WO2003045461A1 publication Critical patent/WO2003045461A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • 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
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • 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
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • 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
    • A61L27/52—Hydrogels or hydrocolloids
    • 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
    • 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
    • A61L29/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L29/126—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • 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
    • A61L29/145—Hydrogels or hydrocolloids
    • 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
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • 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
    • A61L31/145—Hydrogels or hydrocolloids
    • 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
    • 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
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406—Antibiotics

Definitions

  • the invention relates to a textile product with surface modification and a corresponding method for surface modification.
  • EP-A-0 809 997 proposes to subject an implant to a surface modification in which a matrix is arranged on a polymer and in which biomolecules, in particular proteins and collagens, by covalent bonding in the outer region of the Matrix be immobilized. This is based on the idea that a high level of biomolecules on the surface should enable tissue cells to attach quickly and thereby prevent inflammation.
  • a method is also known from DE-C-196 04 173 in which medical objects to be used extracorporeally or intracorporeally are first provided with a polymer layer and then with a further layer of immobilized biomolecules.
  • the likelihood of complication-free integration of an implant to be used can be increased enormously, however, if an implant is effectively provided with medicinal substances as a preventive measure to combat any infections that may arise.
  • an accumulation of tissue cells as well as an accumulation of proteins on the surface of the matrix prevents any active substances that may be provided from reaching the inflamed area from the matrix.
  • the invention is based on the object of developing a textile product which, when used as an implant, has a hitherto unknown, very high biocompatibility
  • PVDF polyvinylidene fluoride
  • the textile properties of PVDF are stable within a temperature range of -20 ° C to +150 ° C.
  • the friction resistance of PVDF is on the level of the polyamides and thus considerably exceeds that of the polyester PVDF also shows a high resistance to many organic acids and mineral acids as well as towards ahphatic and aromatic hydrocarbons, alcohols and halogenated solvents.
  • the inflammatory foreign body reaction of human tissue is also significantly reduced
  • active ingredients can be directly integrated into the implant, which are continuously released after the implant is inserted with such a current that biochemical processes can be specifically prevented and / or required in the tissue area adjacent to the implant is that the implant or the active ingredient contained and delivered can not only exert its effect within the implant or on its surface, but rather the effect penetrates the surrounding tissue to a certain extent
  • the matrix arranged on the substrate has a free surface, in particular a surface that is free of bound proteins.
  • the release of active substances is much more effective with a free implant surface than with previously known surface-treated implants.
  • the drug-release matrix according to the invention has spacer molecules which are connected to the substrate, at least some of the spacer molecules being designed as a hydrogel layer.
  • Spacer molecules are understood in the context of this application to mean matrix-generating or voluminous molecular forms, in particular molecular chains.
  • the spacer molecules then form the matrix on the surface of the substrate.
  • the spacer molecules determine the spatial extent of the drug release matrix as well as its density and strength.
  • An embodiment as a hydrogel layer with the absorption of body fluid can produce a very dense matrix. This prevents biomolecules from accessing the substrate surface. An adsorptive binding of the biomolecules is effectively and simply prevented, while the bulk properties of the PVDF substrate remain unchanged.
  • the spacer molecules are covalently bound to the substrate. Since a covalent bond has a very high strength, such a bond of the matrix to the substrate enables a high level of reliability and durability even under mechanical stress.
  • the spacer molecules can advantageously be polyethylene glycols, dialdehydes, diisocyanates and / or dicarboxylic acid chlorides.
  • glutardialdehyde can be used as the dialdehyde, hexamethyl diisocyanate as the diisocyanate and EDC or DDC as the dicarboxylic acid chloride;
  • methoxy-PEG-aldehydes, PEG-dialdehydes, polyethyleneimines, modified starch, modified dextrans and / or hydrogel-complex polyethyleneimines or polyethylene glycols (PEI / PEG) can be used to design a hydrogel layer.
  • polyethylene glycols Due to their toxicity and solubility in aqueous and organic solvents, polyethylene glycols have found a wide range of applications. PEG are characterized by extremely low interactions with proteins and show a high resistance to bacterial attack. The protein absorption on the substrate surface can be suppressed in this way. The graft density of the PEG at the interface is of immense importance. A very high PEG graft density can be achieved by functionalizing the surface with polyethyleneimine-poly (ethylene oxide) (PEI-PEO) hydrogen complexes the.
  • PEI-PEO polyethyleneimine-poly hydrogen complexes the.
  • the outer PEI-PEO coating offers additional advantages in terms of the biocompatibility of the implant.
  • the hydrogel layer allows slow and long-term release of an active ingredient from the matrix, which means that the implant remains resistant to infections over a longer period of time.
  • the spacer molecules are designed entirely as a hydrogel layer.
  • Such a structure of the drug release matrix can be produced very reliably, it being particularly advantageous if the hydrogel layer is covalently bound to the substrate.
  • the hydrogel layer contains vinyl monomers, in particular acrylic acid or polyacrylic acid. If these substances are present in the hydrogel layer, it is highly hydrophilic and thus contributes to preventing protein adsorption on the substrate.
  • the acrylic acid or polyacrylic acid has a concentration of 10 "8 to 5 * 10 " 7 , preferably 2 * 10 '8 to 4 * 10 "8 mol COOH / cm 2 .
  • the pH of the drug release matrix be higher than the pKa of the PVDF substrate. Specifically, a threshold of around 4 can be assumed here. This ratio facilitates the storage of active substances in the matrix.
  • the hydrogel layer can also contain macromonomers, in particular polyethylene glycol methacrylates (PEGMA), polyethylene glycols (PEGs), polyethyleneimines, modified starch, modified dextrans and / or hydrogel-complex polyethyleneimines / polyethylene glycols (PEI / PEG).
  • PEG polyethylene glycol methacrylates
  • PEGs polyethylene glycols
  • PEGs polyethyleneimines
  • modified starch modified dextrans and / or hydrogel-complex polyethyleneimines / polyethylene glycols
  • PEI / PEG hydrogel-complex polyethyleneimines / polyethylene glycols
  • vinyl monomers with a reactive residue such as glycidyl methacrylate (GMA)
  • GMA glycidyl methacrylate
  • a methacrylate with poly (oxyethylene) chain lengths of 4 to 100 can be present as the macromonomer.
  • the drug-release matrix or the matrix consisting of the hydrogel layer and the spacer molecules advantageously has a thickness of 0.1 to 1 ⁇ m, preferably 0.5 to 1 ⁇ m. Tests have shown that these values are very suitable.
  • the hydrogel layer is loaded directly with active ingredients. This ensures uniform release of the active ingredients over a long period of time. In addition, there are also practical reasons for this, especially if the hydrogel layer makes up a large part of the drug-release matrix. It is particularly preferred if the active substances are adsorptively deposited in the drug release matrix. In particular on PVDF substrates which are grafted with poly (acrylic acid) chains (PAAc-PVDF), it is advisable to realize the release of active substances by means of an adsorptive storage.
  • PAAc-PVDF poly (acrylic acid) chains
  • the active ingredients can include an antibiotic, preferably the cationically charged gentamycin.
  • active ingredients with cationic groups are highly suitable for use in the textile product according to the invention, since the cationic action facilitates adsorptive incorporation into the drug release matrix.
  • a release of the active ingredient is achieved in a desired quantity. It has been found in medical experiments that it is sufficient if an active level of 0.5 ⁇ g / ml to 1000 ⁇ g / ml gentamycin is calibrated in the immediate vicinity of the implant. For economic reasons, it is proposed that an active level of 0.5 ⁇ g / ml to 100 ⁇ g / ml be achieved.
  • the textile product according to the invention can preferably be present as a knitted fabric, a knitted fabric, a woven fabric, a mesh, a scrim, a thread or, in particular, directly as at least part of an implant.
  • the biocompatible effect is largely independent of the specific constructive design of the implant that will ultimately be used. Rather, the advantages described are already achieved by surface modification of the materials mentioned or similar when used as an implant.
  • the task described also solves the method for surface modification of a textile polymer, in which a protein-free drug release matrix is generated on a PVDF substrate.
  • a PVDF substrate is plasma-activated, since the spacer molecules can thereby be bound particularly well to the PVDF substrate.
  • radicals can be generated on the PVDF substrate by inert gas, which radicals react after ventilation with atmospheric oxygen to form peroxy radicals and finally to hydroperoxides, which subsequently react with Thermal and / or photochemical cleavage form free radicals, via which monomers are graft-copolymerized.
  • the hydroperoxides formed after ventilation of the plasma system act as initiators of the radical graft copolymers due to their radicals. on.
  • the graft copolymerization is a method which is advantageous for the hydrophilization and functionalization of surfaces and the associated possibility of increasing the biocompatibility.
  • UV-induced cleavage can also be carried out using an excimer lamp for photochemical cleavage.
  • excimer lamps allow the emission of incoherent narrow-band UV radiation.
  • the textile product can preferably be washed extensively with water or an aqueous solution.
  • monomers produced in the gas phase as chemical spacers by means of chemical vapor deposition polymerization processes are polymerized by cooling at reduced temperature and these polymerized monomers in the form of a polymer matrix be bound to the PVDF substrate.
  • the temperatures or pressures required to prepare the monomers are between 500 and 1000 ° C. and less than 500 Pa.
  • the monomers are polymerized at temperatures below 120 ° C.
  • the monomers to be polymerized can advantageously 4-amino [2,2] -paracyclophane (amino-pcp), 4-hydroxymethyl- [2,2] -paracyclophane (hydroxymethyl-pcp), 4-carboxyl- [2,2] - Paracyclophane (car-boxyl-pcp) and / or [2,2] -paracyclophane-4,5,12,13-tetracarboxylic acid dianhydride (anhydride-pcp).
  • the good insulating properties and chemical resistance of poly-p-xylylenes to practically all solvents can also be used advantageously for numerous applications.
  • Objects coated with poly-2-chloro-p-xylylene have received FDA approval for various applications such as catheters or pacemakers. A toxic or carcinogenic effect of poly-p-xylylene is not known.
  • the monomers to be grafted vinyl monomers in particular acrylic acid (Aac), and / or macromonomers, in particular include special polyethylene glycol methacrylates (PEGMA) to form a highly hydrophilic hydrogel layer.
  • acrylic acid acrylic acid
  • PEGMA polyethylene glycol methacrylates
  • a multilayer textile product a band replacement, an esophagus replacement, an intestinal replacement, a catheter, a membrane or a vascular prosthesis will be produced.
  • a knitted fabric, a knitted fabric, a woven fabric, a braid, a scrim, a thread or in particular at least part of an implant can preferably be produced using the method according to the invention.
  • FIG. 1 shows schematically the molecular structure of a surface modified according to the invention
  • FIG. 2 shows the results of crystallinity studies in a diagram
  • FIG. 3 shows basic measurement values in a table
  • FIG. 4 shows measured values for the release of gentamycin as a function of the loading concentration and the incubation time
  • FIG. 5 shows, in a further diagram, results of an experiment for loading with gentamycin as a function of the loading concentration and the pre-swelling and
  • the modified surface shown in FIG. 1 represents the invention schematically.
  • a matrix of polyacrylic acid 2a, 2b, 2c is arranged on a PVDF substrate 1 and covalently bound to the substrate 1.
  • the cationic gentamycin G is adsorptively attached to the anionic COO " groups.
  • Gentamycin G is found within the entire matrix 2a, 2b, 2c.
  • the outer openings 3a, 3b, which lie between the polyacrylic acid 2a, 2b, 2c, are free of proteins.
  • FIG. 2 shows DSC thermograms of PVDF filament blue (curve profile 10) and PVDF filament green (curve 11).
  • the heat flow in W / g is plotted on an axis 12 above the temperature in ° C, as it resulted from the crystallinity tests on PVDF filaments.
  • Line 20 contains data for curve 10 (blue) and line 21 data for curve 11 (green).
  • the lines Hl denote values for a first heating up and the line H2 measurement values for a second heating up.
  • Column 22 shows the values for the melting peak, while column 23 contains measurements for the crystallization peak.
  • the value in column 24 indicates the degree of crystallinity with the associated melting temperature T m and mass-related energy difference ⁇ H m , while T 0 and ⁇ H 0 represent the respective values during crystallization.
  • FIG. 4 The diagram shows the influence of the gentamycin concentration in the loading solution on the subsequent release of the active substance from the matrix examined.
  • the abscissa 30 shows the incubation time in serum at 37 ° C. in minutes, while the ordinate shows the release of gentamycin normalized to 25 mg of the matrix in micrograms per milliliter.
  • the measuring points on the curves 31, 32, 33, 34 represent measured values which resulted after a loading concentration of 10 mg, 1 mg, 0.25 mg or 0.5 mg / ml.
  • a loading concentration of 0.5 mg / ml gentamycin was used for the measured values marked with triangles on curves 42 and 45, the measured values represented by solid triangles on curve 45 on a loading solution of 0.5 mg / ml gentamycin in PBS (unswollen ) are based, while the measured values on curve 42 were caused by twelve hours of swelling in Aqua bidest.
  • the parameters on which the measured values shown by the filled-in IC circles on curve 46 are based differ from those that led to curve 45 only in the loading concentration, because curve 46 contains a loading solution with a concentration of 0.25 mg / ml gentamycin in PBS (not swollen).
  • Diagram 50 in FIG. 6 shows measurement results for the release of gentamycin, the amount of gentamycin being normalized to 25 mg of the matrix, given in micrograms per milliliter, on which ordinate 51 is plotted.
  • the abscissa 52 represents the incubation time in serum at 37 ° C. in minutes.
  • the measured values on the curve 53 result from a loading concentration of 0.5 mg / ml, the measured values on the curve 54 from a concentration of 0.25 mg / ml. It should be noted here that the curves 53, 54 were each placed along the lowest measured values (numbered 55a, b for example), while significantly higher measured values (numbered 56a, b for example) have resulted. Medical examinations have shown that a release of 20 ⁇ g / ml is definitely therapeutically sufficient.
  • the tests show that the technically and economically optimal loading concentration of the PVDF networks with gentamycin is 0.25 mg / ml.
  • the PVDF networks grafted with polyacrylic acid should be loaded from PBS buffer in the non-pre-swollen state. In this way, release amounts are achieved which ensure a therapeutically sufficient amount.
  • a magnetic stirrer with heating plate for acrylic acid distillation, a magnetic stirrer with heating plate, a heating hood with temperature control device, a round bottom flask, a Vigreux column, a Claisen still with a Liebig cooler and vacuum connection, a thermometer, a Schlenk flask with nitrogen connection and a vacuum system with HV pump with cold trap and nitrogen connection are used.
  • the chemicals used are acrylic acid with stabilizer (2-hydroxyethyl metacrelate, 99%), 4-methoxyphenol (hydroquinone monomethyl ether) with 1 g / 1 acrylic acid, ultra-pure nitrogen 5.0 and liquid nitrogen to cool the cold trap.
  • the cold trap is first cooled with the liquid nitrogen. After connecting the cooling water system, 800 ml of acrylic acid and 800 mg of hydroclünone are added to the template and the stirring magnet is added. After setting a vacuum of at least 6 * 10 "2 mbar in the system, the system is purged with nitrogen so that it can be distilled under an inert gas atmosphere.
  • the template is slowly heated to 80 ° C.
  • the mixture is constantly stirred so that the distillation takes place evenly and can be monitored optically. Since the distillation requires a temperature of 80 ⁇ 5 ° C, it is first heated to 65 ° C and then heated further in steps of 2 ° C. From the start of the distillation, the temperature reached is kept constant, a temperature window of ⁇ 5 ° C being permitted.
  • the first 10 ml of the distillate is discarded in order to rule out any expected deviations during the start of the process.
  • the usable distillate obtained is stored under nitrogen at a maximum of 4 ° C in the refrigerator.
  • a heating element for thermal graft copolymerization, a heating element, a round bottom flask, teflon stones, a Soxhlet, a reflux condenser, a tripod plate, a tripod rod, solid clamps and a circulating air drying cabinet are used on devices. M-Hexane and ethanol are used as solvents. To extract the nets, they are placed in the Soxhlet so that they are free on all sides. The solvent is then added to the round bottom flask with a hexane to ethanol ratio of 79 to 21 w / w. After an extraction period of approx. 48 hours, the nets are dried in the drying cabinet at approx. 30 ° C for twelve hours.
  • the distilled acrylic acid is thawed and a 20% acrylic acid solution with H 2 0 is prepared. Then a quartz glass tube or another suitable container with a screw cap is attached to the stand with a clamp and the acrylic acid solution is added to the container. After careful degassing with nitrogen, the sample rack with the nets is added. The vessel is now tightly closed and hung in a water bath, which is then heated to 90 ° C and stirred. This process is continued until the solution becomes viscous.
  • the mesh films are then washed briefly once and five times within four hours with distilled H 2 O. It is then washed several times with distilled H 2 O over a period of one day. Finally, the foils are dried for about three hours at 30 ° C and then stored dry.
  • a PVDF substrate is applied to a pulsed microwave plasma (pulse duration 1600 ⁇ s, period duration 2000 ⁇ s) of 1.5 to 2 kW power with argon (flow rate 5 1 / h) as plasma gas under pressure of 10 exposed to 15 Pa and varying the treatment time from 15 to 300 seconds.
  • the PVDF substrate is further processed after an air exposure of 20 to 150 minutes.
  • the graft copolymerization of the argon plasma-treated PVDF substrate is carried out in each case under a nitrogen atmosphere. Since the OO binding energy in hydroperoxides is low at 150 kJ / mol, it is possible to split hydroperoxides by adding appropriate amounts of energy. Temperatures of 50 to 100 ° C are sufficient to achieve such a split.
  • Graft copolymerization is initiated by thermal hydroperoxide cleavage at 90 ° C.
  • a UN-induced cleavage can also be carried out.
  • excimer lamps enable the emission of incoherent narrow-band UN radiation.
  • a xenon chloride emitter with an emission maximum of 308 is used. The energy of these photons is around 400 kJ / mol.
  • PVDF-PAAc radical-induced graft copolymerization of acrylic acid
  • Acrylic acid (AAc) provides a hydrophilic, carboxyl group-containing surface on PVDF substrate.
  • the thermal plasma-induced graft copolymerization of acrylic acid is carried out using a monomer concentration of 5 to 50%, preferably approx. 25%, in deionized water (v / v), preferably 20 to 30% (v / v), and a polymerization time of 15 to 90, preferably 30 to 60. minutes at 90 ° C thermally or by a 2.5 to 5 minute irradiation with UV light.
  • homopolymer that is not covalently bound to the PVDF substrate is removed by extensive washing with water or an aqueous solution.
  • the modified surface obtained in this way is highly hydrophilic and has a high concentration of carboxyl groups. Now it can be used in particular for loading with antibiotics.
  • the surface-bound carboxyl groups are treated for 20 minutes with an aqueous EDC / NHS solution (0.2 M / 0.1 M) for activation.
  • the surfaces are then rinsed briefly with deionized water and incubated for several hours in a solution of 1 mg / ml GRGDS peptide in 0.1 M sodium hydrogen carbonate buffer (pH 8.4).
  • the unbound peptide is removed by repeated intensive rinsing with deionized water.
  • Example 5 A PVDF substrate is coated by means of plasma activation. The graft copolymerization of acrylic acid and the subsequent activation take place as described above.
  • a hydrogel complex is immobilized.
  • the activated PVDF-PAAc substrate is immersed in a PEI solution (1 mg / ml) for 1 hour at room temperature.
  • the PVDF substrate in a buffer solution (NaHPO4 / Na0H pH 6.4) at 11% K 2 S0 ", 1 mg ml PEG- (aldehyde) 2 (MW 3400), 3 mg / ml NaCNBEL, as Incubating agent incubated for 8-12 h at 30 to 60 ° C (best results: 8h, 60 ° C) and then washed with water.
  • the sample is mixed with an RGD peptide solution (1 mg / ml in phosphate buffer, reducing agent NaCNBH4) at room temperature for 2 hours.
  • the plasma-induced graft copolymerization of a methacrylate by means of plasma activation can be carried out using a monomer concentration of 5 to 50% (v / v), preferably 20 to 30% (v / v) in a water / methanol mixture and a polymerization time of 1 to 4 hours , preferably 2 to 3 hours, at 90 ° C thermally or by 10 minutes to 30 minutes of exposure to UV light.
  • the free carboxyl or hydroxyl groups of the material surface generated by means of plasma graft polymerization are activated.
  • activating agents for the carboxyl groups e.g.
  • EDC [1- (3-dimethylaminopropyl) -3-20 ethyl carbodiimide hydrochloride] or DDC [1,2-dicyclohexyl carbodiimide] and for the hydroxyl groups e.g. Diisocyanate such as hexamethyl diisocyanate or 2,2,2-trifluoroethanesulfon chloride (tresyl chloride) can be used.
  • a PVDF surface modified with glycidyl methacrylate can be used without prior activation.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Dermatology (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Surgery (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Materials Engineering (AREA)
  • Composite Materials (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Materials For Medical Uses (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention vise, en technique médicale, à réaliser un produit textile servant à façonner des implants et devant présenter une haute biocompatibilité, et à prévenir simultanément des inflammations potentielles sur et autour de l'implant. A cet effet, le produit textile faisant l'objet de l'invention comporte une matrice de libération de médicaments exempte de protéines, disposée sur un substrat PVDF. La présente invention porte également sur un procédé de fabrication d'un tel produit.
PCT/DE2002/004291 2001-11-23 2002-11-22 Produit textile a surface modifiee et procede de modification de surface correspondant Ceased WO2003045461A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2002358421A AU2002358421A1 (en) 2001-11-23 2002-11-22 Surface-modified textile product and a corresponding method for surface modification
DE10295443.7T DE10295443B4 (de) 2001-11-23 2002-11-22 Textiles Implantat mit Oberflächenmodifikation, und entsprechendes Verfahren zur Oberflächenmodifikation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10157307.3 2001-11-23
DE10157307 2001-11-23

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10353930A1 (de) * 2003-07-18 2005-02-03 Feg Textiltechnik Textiles Intraperitoneal-Mesh
WO2005053838A1 (fr) * 2003-12-02 2005-06-16 BLüCHER GMBH Surfaces textiles traitees au plasma pour materiaux filtrants adsorbants
DE102009005792A1 (de) * 2009-01-22 2010-07-29 Feg Textiltechnik Forschungs- Und Entwicklungsgesellschaft Mbh Medizinisches Implantat mit Oberflächenbeschichtung
DE102009011991A1 (de) * 2009-03-05 2010-09-09 Peter Hildebrandt Chirurgisches Implantat mit einem Träger in flächiger Form
CN102276866A (zh) * 2011-07-18 2011-12-14 海狸（广州）生物科技有限公司 一种在细胞培养表面接枝羧基的等离子体-光化学方法
WO2019192116A1 (fr) * 2018-04-03 2019-10-10 北京大学口腔医学院 Membrane composite chargée ayant des caractéristiques de topologie électrique de matrice extracellulaire et son procédé de préparation
GB2579369B (en) * 2018-11-29 2023-08-30 Cook Medical Technologies Llc Bioactive agent coated medical device and method of coating such a device

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WO1992000047A1 (fr) * 1990-06-22 1992-01-09 Case Western Reserve University Procede de regulation de la croissance cellulaire sur des surfaces
EP0574352A1 (fr) * 1992-06-09 1993-12-15 Ciba-Geigy Ag Procédé de polymérisation par greffage sur les surfaces de substrats préformés afin de modifier leurs propriétés de surface
WO1994017904A1 (fr) * 1993-02-10 1994-08-18 Akzo Nobel N.V. Membrane modifiee pour utilisations medicales
US5576072A (en) * 1995-02-01 1996-11-19 Schneider (Usa), Inc. Process for producing slippery, tenaciously adhering hydrogel coatings containing a polyurethane-urea polymer hydrogel commingled with at least one other, dissimilar polymer hydrogel
EP0809997A2 (fr) * 1996-05-31 1997-12-03 Medtronic, Inc. Article médical ayant une matrice greffée sur la surface revêtue de biomolécules
WO2002013871A2 (fr) * 2000-08-15 2002-02-21 Surmodics, Inc. Matrice renfermant un medicament

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EP0920843B1 (fr) * 1990-12-28 2005-02-09 Boston Scientific Corporation Système d'administration de médicament
US5344455A (en) * 1992-10-30 1994-09-06 Medtronic, Inc. Graft polymer articles having bioactive surfaces
DE10106546A1 (de) * 2001-02-13 2002-08-22 Ethicon Gmbh Verfahren zum Herstellen eines medizinischen Implantats

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Publication number Priority date Publication date Assignee Title
DE8911028U1 (de) * 1989-09-14 1989-11-02 Krahmer, Gerhard M., 5064 Rösrath Nichtresorbierbares chirurgisches Nahtmaterial aus Monofilen aus Polyvinylidenfluorid
WO1992000047A1 (fr) * 1990-06-22 1992-01-09 Case Western Reserve University Procede de regulation de la croissance cellulaire sur des surfaces
EP0574352A1 (fr) * 1992-06-09 1993-12-15 Ciba-Geigy Ag Procédé de polymérisation par greffage sur les surfaces de substrats préformés afin de modifier leurs propriétés de surface
WO1994017904A1 (fr) * 1993-02-10 1994-08-18 Akzo Nobel N.V. Membrane modifiee pour utilisations medicales
US5576072A (en) * 1995-02-01 1996-11-19 Schneider (Usa), Inc. Process for producing slippery, tenaciously adhering hydrogel coatings containing a polyurethane-urea polymer hydrogel commingled with at least one other, dissimilar polymer hydrogel
EP0809997A2 (fr) * 1996-05-31 1997-12-03 Medtronic, Inc. Article médical ayant une matrice greffée sur la surface revêtue de biomolécules
WO2002013871A2 (fr) * 2000-08-15 2002-02-21 Surmodics, Inc. Matrice renfermant un medicament

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10353930A1 (de) * 2003-07-18 2005-02-03 Feg Textiltechnik Textiles Intraperitoneal-Mesh
WO2005053838A1 (fr) * 2003-12-02 2005-06-16 BLüCHER GMBH Surfaces textiles traitees au plasma pour materiaux filtrants adsorbants
US7572322B2 (en) 2003-12-02 2009-08-11 Blucher Gmbh Plasma-treated textile surfaces for adsorption filter materials
US8016926B2 (en) 2003-12-02 2011-09-13 Blucher Gmbh Plasma-treated textile surfaces for adsorption filter materials
DE102009005792A1 (de) * 2009-01-22 2010-07-29 Feg Textiltechnik Forschungs- Und Entwicklungsgesellschaft Mbh Medizinisches Implantat mit Oberflächenbeschichtung
DE102009005792B4 (de) * 2009-01-22 2019-06-19 Feg Textiltechnik Forschungs- Und Entwicklungsgesellschaft Mbh Medizinisches Implantat mit Oberflächenbeschichtung
DE102009011991A1 (de) * 2009-03-05 2010-09-09 Peter Hildebrandt Chirurgisches Implantat mit einem Träger in flächiger Form
CN102276866A (zh) * 2011-07-18 2011-12-14 海狸（广州）生物科技有限公司 一种在细胞培养表面接枝羧基的等离子体-光化学方法
WO2019192116A1 (fr) * 2018-04-03 2019-10-10 北京大学口腔医学院 Membrane composite chargée ayant des caractéristiques de topologie électrique de matrice extracellulaire et son procédé de préparation
US11141506B2 (en) 2018-04-03 2021-10-12 Peking University School And Hospital Of Stomatology Electrified composite membrane with extracellular matrix electrical topology characteristics, and preparation method thereof
GB2579369B (en) * 2018-11-29 2023-08-30 Cook Medical Technologies Llc Bioactive agent coated medical device and method of coating such a device

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