WO2016115228A1 - Revêtement de dispositifs médicaux avec des molécules biologiques, induit par décharge électrostatique - Google Patents

Revêtement de dispositifs médicaux avec des molécules biologiques, induit par décharge électrostatique Download PDF

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Publication number
WO2016115228A1
WO2016115228A1 PCT/US2016/013211 US2016013211W WO2016115228A1 WO 2016115228 A1 WO2016115228 A1 WO 2016115228A1 US 2016013211 W US2016013211 W US 2016013211W WO 2016115228 A1 WO2016115228 A1 WO 2016115228A1
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WIPO (PCT)
Prior art keywords
coating
medical device
poly
charge
coating material
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PCT/US2016/013211
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English (en)
Inventor
Garima BHARDWAJ
Thomas J. Webster
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Northeastern University
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Publication of WO2016115228A1 publication Critical patent/WO2016115228A1/fr

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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
    • 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
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D13/00—Electrophoretic coating characterised by the process
    • C25D13/12—Electrophoretic coating characterised by the process characterised by the article coated
    • C25D13/14—Tubes; Rings; Hollow bodies
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D13/00—Electrophoretic coating characterised by the process
    • C25D13/20—Pretreatment
    • 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
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D1/00—Processes for applying liquids or other fluent materials
    • B05D1/18—Processes for applying liquids or other fluent materials performed by dipping
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D3/00—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials
    • B05D3/14—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials by electrical means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D7/00—Processes, other than flocking, specially adapted for applying liquids or other fluent materials to particular surfaces or for applying particular liquids or other fluent materials
    • B05D7/02—Processes, other than flocking, specially adapted for applying liquids or other fluent materials to particular surfaces or for applying particular liquids or other fluent materials to macromolecular substances, e.g. rubber
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C18/00—Chemical coating by decomposition of either liquid compounds or solutions of the coating forming compounds, without leaving reaction products of surface material in the coating; Contact plating
    • C23C18/02—Chemical coating by decomposition of either liquid compounds or solutions of the coating forming compounds, without leaving reaction products of surface material in the coating; Contact plating by thermal decomposition
    • C23C18/04—Pretreatment of the material to be coated
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C18/00—Chemical coating by decomposition of either liquid compounds or solutions of the coating forming compounds, without leaving reaction products of surface material in the coating; Contact plating
    • C23C18/02—Chemical coating by decomposition of either liquid compounds or solutions of the coating forming compounds, without leaving reaction products of surface material in the coating; Contact plating by thermal decomposition
    • C23C18/12—Chemical coating by decomposition of either liquid compounds or solutions of the coating forming compounds, without leaving reaction products of surface material in the coating; Contact plating by thermal decomposition characterised by the deposition of inorganic material other than metallic material
    • C23C18/125—Process of deposition of the inorganic material
    • C23C18/1254—Sol or sol-gel processing

Definitions

  • Coatings offer many improved features for implanted medical devices, including resistance to infection and the formation of biofilms, integration with tissue, promotion of healing, treatment or prevention of disease and harmful medical conditions, and the ability for long-term release of medications. Nevertheless, adding coatings to the surfaces of medical devices presents many challenges, such as lack of adhesion to certain materials, degradation or delamination of coating material, and the need to specially adapt coating chemistry to the substrate, to chemically modify the substrate, or to deposit multiple layers, often with considerable waste of expensive materials. Thus, there remains a need to develop simple, efficient, cost effective, and robust coatings and coating methods for medical devices.
  • the invention provides methods, systems, and kits for coating medical devices and devices prepared thereby.
  • the methods are based on electrostatic attraction between a non-conductive material surface on the medical device and a coating material including a charged biopolymer or pharmaceutical agent. Surface charge is induced or enhanced in the non-conductive material using a physical method, and does not require chemical derivatization or pre-coating with a charged material.
  • the methods are simple and applicable to a wide variety of non-conductive substrate materials and coatings containing any of a wide variety of biological
  • the methods of the invention are unlike conventional coating methods that require chemical derivatization or pre-coating of non-conductive materials, or that require specifically tailored substrates or substrate treatments for each different type of coating material.
  • One aspect of the invention is a method of coating a medical device or a portion thereof.
  • the method includes the steps of: (a) physically inducing or enhancing a surface charge on a non-conductive material at a surface of the medical device; and (b) depositing a coating material onto the surface, wherein the coating material has a charge which is opposite to the surface charge resulting from step (a).
  • the method further includes step (c) of depositing one or more additional layers of coating material onto the coating resulting from step (b).
  • Preferred methods of physically inducing surface charge in step (a) include plasma treatment, laser treatment, ion bombardment, physical deposition, charging by friction, and charging by induction.
  • step (a) Excluded from step (a) are chemical functionalization or derivatization of the non-conductive material with a charged molecular species or coating with a charged molecular species, as well as applying an electrical potential to the medical device, so as to provide a surface charge.
  • Preferred methods of depositing the coating material in step (b) are dip coating, electrophoretic deposition, spray coating, electrophoretic spray coating, spin coating, spin dipping, and sol-gel coating; more preferred are dip coating and electrophoretic deposition.
  • Another aspect of the invention is a system for coating a medical device according to the method described above.
  • the system includes: (a) a medical device having an uncoated non-conductive material surface; (b) a device for physically inducing or enhancing a surface charge in the non-conductive material at the surface; and (c) a coating composition.
  • Yet another aspect of the invention is a coated medical device produced by the method or the system described above.
  • kits containing a medical device that includes a non-conductive material disposed at its surface.
  • the kit further contains a charged coating material and instructions for inducing or enhancing a surface charge at the surface using a physical surface charge induction method and coating the charged non-conductive material surface of the device with the charged coating material.
  • the charged coating material is a non-conductive material that has been electrostatically charged using a physical method that does not apply or leave any chemical residue on the surface and does not chemically derivatize the surface.
  • the invention can be further summarized in following list of items.
  • the non-conductive material comprises one or more materials selected from the group consisting of polyurethane, polyester, polyethylene, polyethylene terephthalate, polypropylene, polyamide, nylon, polycarbonate, polystyrene, poly(tetrafluoroethylene), poly(lactic-co-glycolic acid), poly(lactic-co-caprolactone), poly(lactide-co-glycolide), ceramic, glass, silicone, latex, rubber, and combinations thereof.
  • the coating material comprises a biomolecule selected from the group consisting of peptides, oligopeptides, polypeptides, proteins, glycoproteins, antibodies, enzymes, nucleic acids,
  • nucleotides nucleotides, oligonucleotides, polynucleotides, oligosaccharides, polysaccharides, lipids, glycosaminoglycans, proteoglycans, hormones, growth factors, cytokines, and combinations thereof.
  • the pharmaceutical agent is selected from the group consisting of antimicrobial agents, antibiotics, anticoagulants, antiinflammatory agents, nitric oxide releasing agents, heparin, anti-tumor agents, and combinations thereof.
  • step (a) comprises a method selected from the group consisting of plasma treatment, laser treatment, ion bombardment, physical deposition, charging by friction, charging by induction, and combinations thereof.
  • step (a) does not include chemical functionalization or coating with a charged molecular species.
  • step (a) does not include applying an electrical potential to the medical device.
  • step (b) comprises a method selected from the group consisting of dip coating, electrophoretic deposition, spray coating, electrophoretic spray coating, spin coating, spin dipping, and sol-gel coating.
  • step (b) comprises dip coating or
  • step (c) depositing one or more additional layers of coating material onto the coating resulting from step (b).
  • said surface comprises a surface material selected from the group consisting of polyurethane, polyester, polyethylene, polyethylene terephthalate, polypropylene, polyamide, nylon, polycarbonate, polystyrene, poly(tetrafluoroethylene), poly(lactic-co-glycolic acid), poly(lactic-co- caprolactone), poly(lactide-co-glycolide), ceramic, glass, silicone, latex, rubber, and combinations thereof.
  • the coating composition comprises a pharmaceutical agent.
  • the device for inducing or enhancing an electrostatic charge is capable of performing a method selected from the group consisting of plasma treatment, laser treatment, ion bombardment, physical deposition, charging by friction, charging by induction, and combinations thereof.
  • a coated medical device produced by the method of any of items 1 -15 or the system of any of items 16-20.
  • a kit comprising a medical device, the device comprising a non-conductive material disposed at a surface of the device, a charged coating material, and instructions for inducing or enhancing a surface charge at the surface using a physical surface charge induction method and coating the surface with the charged coating material.
  • kit of item 22 wherein the coating material comprises a biomolecule and/or a pharmaceutical agent.
  • Figure 1 shows a schematic representation of a device in use for electrophoretic deposition of a coating on a non-conductive surface of a medical device.
  • Figures 2A - 2C show scanning electron micrographs of the surface of a CA- 13 coating deposited on a polyurethane endotracheal tube.
  • the figures show increasing magnification from Fig. 2A (scale increments of 20 Mm) to 2B (scale increments of 5 pm) to Fig. 2C (scale increments of 2 pm).
  • the present invention provides methods, systems, and kits for creating bioactive, uniform, and strongly-adherent coatings on medical devices to improve their performance.
  • the invention utilizes induction or enhancement of electrostatic charge on the surface of a medical device, specifically on a surface of a non- conductive material of the medical device, by a physical method.
  • the use of physical surface charge induction enables materials to be coated that are otherwise difficult or impossible to coat without complex and individualized chemical functionalization methods, and enables a variety of coating materials to be used with minimal or no individual adaptation. Uniform and thick coatings can be achieved on inside and outside surfaces, and without altering the inherent mechanical properties of the device. Biological activity of coating materials can be retained by employing gentle coating processes such as dip coating or electrophoretic deposition, without the need to chemically alter the coating material.
  • the invention is useful in commercial applications where, for example, it can prevent bacterial adhesion and proliferation, thereby reducing infection caused by implanted medical devices.
  • the coating methods of the invention also can be used to promote bioactivity, reduce infection, and limit inflammation of medical devices such as hip implants and other joint replacements, cornea implants, pacemaker leads, and skin grafts.
  • the methods of the invention provide ease of coating due to their simplicity and wide applicability, and are cost efficient.
  • the invention also can be used to transform existing FDA-approved materials into materials that improve implant performance.
  • any medical device that is implanted, in whole or in part, into a subject's body can be used in the invention.
  • suitable medical devices include, but are not limited to, catheters (e.g., vascular or balloon catheters), stents (e.g.
  • biliary, coronary vascular, peripheral vascular, cerebral, esophageal, gastrointestinal, tracheal, urethral, or ureteral stents cochlear implants
  • corneal implants defibrillators
  • dental implants endotracheal tubes
  • filters guide wires, grafts
  • artificial hearts heart valves, joint prostheses, leads, orthopedic screws, pins, and plates, ports, plugs, patches, pacemakers, pumps, surgical clips, staples, sutures, and meshes, tissue scaffolds, and vascular valves.
  • a subject can be any human or non-human animal subject, such as a mammalian subject, that is the recipient of a coated medical device provided by the invention.
  • the non-conductive material whose surface is coated can contain, for example, one or more materials selected from the group consisting of polyurethane, polyester, polyethylene, polyethylene terephthalate, polypropylene, polyamide, nylon, polycarbonate, polystyrene, poly(tetrafluoroethylene), poly(lactic-co-glycolic acid), poly(lactic-co- caprolactone), poly(lactide-co-glycolide), ceramic, glass, silicone, latex, rubber, and combinations thereof.
  • polyurethane polyester, polyethylene, polyethylene terephthalate, polypropylene, polyamide, nylon, polycarbonate, polystyrene, poly(tetrafluoroethylene), poly(lactic-co-glycolic acid), poly(lactic-co- caprolactone), poly(lactide-co-glycolide), ceramic, glass, silicone, latex, rubber, and combinations thereof.
  • small amounts of conductive materials such as metals or conductive polymers also can be included in the non-conductive material; inclusions of such materials may aid in inducing or sustaining a surface charge prior to coating.
  • the non-conductive material can be biodegradable or nonbiodegradable.
  • the coating material can contain, for example, a biomolecule selected from the group consisting of peptides, oligopeptides, polypeptides, proteins, glycoproteins, antibodies, enzymes, nucleic acids, nucleotides, oligonucleotides, polynucleotides, oligosaccharides, polysaccharides, lipids, glycosaminoglycans, proteoglycans, hormones, growth factors, and cytokines.
  • a biomolecule selected from the group consisting of peptides, oligopeptides, polypeptides, proteins, glycoproteins, antibodies, enzymes, nucleic acids, nucleotides, oligonucleotides, polynucleotides, oligosaccharides, polysaccharides, lipids, glycosaminoglycans, proteoglycans, hormones, growth factors, and cytokines.
  • the coating material can contain, for example, a pharmaceutical agent selected from the group consisting of antimicrobial agents, antibiotics, anticoagulants, anti-inflammatory agents, nitric oxide releasing agents, heparin, anti-tumor agents, and combinations thereof.
  • a pharmaceutical agent selected from the group consisting of antimicrobial agents, antibiotics, anticoagulants, anti-inflammatory agents, nitric oxide releasing agents, heparin, anti-tumor agents, and combinations thereof.
  • the coating material can further include one or more components to aid in adhesion of the coating to the medical device or to cells or extracellular matrix components within the body of the subject, stability of the biomolecule, release of the biomolecule, function of the biomolecule, stability or degradation of the coating, lubricity, opacity to X-rays, and the like.
  • the coating material can include pharmaceutical formulation components, such as excipients, diluents, carriers, buffers, delayed release agents, dispersants, surfactants, emulsifiers, or antioxidants.
  • polymers either organic or inorganic. Such polymers can be used either as non-conductive components of a medical device, or forming an entire medical device, or as components of a coating composition, or as pharmaceutical formulation ingredients. Polymers can be linear, branched, cyclic, or can have a comb or dendritic configuration. Polymers also can be homopolymers or copolymers, such as block copolymers.
  • the medical device includes at least a portion or component having a non-conductive material at its surface.
  • a non-conductive material Unlike metals or other conductive materials, it is difficult or impossible to establish a surface potential on a non-conductive material by simply using the material as an electrode in an electrophoretic or dip-coating deposition process, i.e., by applying an electrical potential between the material and a solution containing charged molecules of a coating material.
  • other physical methods are used to impart an electrostatic charge, i.e., surface potential or surface charge, on an exposed surface of a non-conductive material of a medical device.
  • Preferred methods of physically inducing surface charge in a non-conductive material include plasma treatment, laser treatment, ion bombardment, physical deposition methods, charging by friction, and charging by induction. These are well known methods that are capable of inducing an electrical charge at the surface of a material. Furthermore, it is well understood how to practice such methods so as to induce a net positive or a net negative charge.
  • Exposure of non-conductive materials to a plasma can induce a surface charge or enhance a pre-existing surface charge.
  • Plasma treatment such as plasma etching involves exposing the material to atoms of a plasma typically formed as a high-speed stream of atoms of a gas or mixture of gases directed onto the material.
  • the plasma source can deliver charged atoms or radicals onto the surface of the material.
  • the plasma atoms can embed in the material and/or form reactive moieties in the material, which alter the surface charge, and optionally also the polarity of the surface, rendering hydrophobic surfaces more hydrophilic and more wettable.
  • Physical deposition methods such as sputtering, also can be used to introduce atoms onto the surface of a non-conductive material so as to increase the surface charge, as can bombardment with an ion beam or exposure to a laser.
  • Charging by friction and charging by induction are also suitable methods for surface charge induction.
  • Charging by friction uses the triboelectric effect, or contact electrification. In charging by friction, a charge-inducing material having greater or lesser electron affinity in comparison to the non-conductive material is rubbed across the surface of the non-conductive material. If the charge inducing material has greater electron affinity, then in will render the surface of the non-conductive material positive. If the charge inducing material has lesser electron affinity, then it will render the surface of the non-conductive material negative.
  • the relative electron affinities of different materials is known and can be found in the literature as triboelectric series, or can be measured, to aid in selecting a suitable material for charging any given non-conductive material either positively or negatively.
  • surface charge induction or enhancement may vary depending on the method used. Any amount of surface charge induced, or increased over preexisting levels, is considered within the invention provided that it results in a measurable increase in coating thickness, completeness of coverage, robustness, durability in use, or biological or pharmacological activity compared to a coating that results without the surface charge induction or enhancement.
  • Surface charge can be measured as an electrical potential difference between an outer surface of a non- conductive material of a medical device and the interior of the non-conductive material.
  • the surface charge can be affected by the ionic environment of the material; it is therefore preferable to determine the surface charge under conditions used to deposit the coating material, i.e., in a solution used for dip-coating or electrophoretic deposition.
  • Surface charge can also be represented by the surface charge density, which is the amount of electrical charge per unit of surface area.
  • any method can be used to deposit the coating material on that surface, or region of a surface.
  • the employed method should preserve the desired biological activity or pharmacological activity provided by the coating. Therefore, preferred coating methods include dip coating, electrophoretic deposition, spray coating, electrophoretic spray coating, spin coating, spin dipping, and sol-gel coating, because these methods can apply the coating material in the form of a solution containing and preserving the activity of the biological or pharmaceutical agent.
  • Apparatus 10 includes cathode 20 and anode 30 which are immersed in an electrolyte solution containing molecules of coating material 50.
  • the electrodes are set at a potential controlled by voltage source 40, which can be a DC or AC power supply or a battery.
  • voltage source 40 which can be a DC or AC power supply or a battery.
  • tube 60 such as an endotracheal tube, surrounds the cathode with a loose fit, so that electrolyte solution contacts both inner and outer surfaces of the tube, and a coating can be deposited on all surfaces of the device.
  • tube 60 has been provided with a negative surface charge, so that cationic coating molecules are attracted to it to form coating 70.
  • Example 1 Application by Dip Coating of an Antimicrobial Coating After Surface Charge Induction.
  • Polyurethane endotracheal tubes were coated with a compound known to have bactericidal activity (CSA-13).
  • CSA-13 bactericidal activity
  • a positive electrostatic charge was first induced on both the inside and outside surfaces of the tubes by rubbing them with wool for 5 minutes each.
  • the tubes were coated with CSA-13 by dip coating.
  • dip coating the charged tubes were dipped in a CSA-13 solution three times, each time for one minute. The result was a thick and uniform coating, if the surface of the tube previously had been charged, and no coating if the surface of the tube had not been charged.
  • Example 2 Application by Electrophoretic Deposition of an Antimicrobial Coating After Surface Charge Induction.
  • Polyurethane endotracheal tubes were coated with CSA-13 using electrophoretic deposition.
  • a positive electrostatic charge was first induced on both the inside and outside surfaces of the tubes by rubbing them with wool for 5 minutes each, which was followed by electrophoretic deposition using an apparatus similar to that depicted in Fig. 1 .
  • Titanium foil purchased from Alfa Aesar (catalog number 10385) was used as both the counter and working electrodes, and the CSA-13 solution was used as the electrolyte.
  • the polyurethane tube was placed around the titanium foil that functioned as the negative electrode, and this allowed the compound to coat the tube surface both inside and out. The voltage used was 20 V for a time period of 10 minutes.
  • Tubes whose surface had previously been charged became coated with CSA-13, but no coating was observed if no charge was induced prior to the coating procedure.
  • the tubes were removed from the apparatus and then allowed to dry at room temperature.
  • the coated tubes were visualized using scanning electron microscopy (SEM) to reveal the morphology of the surface coating. A uniform coating was observed (see Figs. 2A-2C) having a smooth surface, with occasional cracks.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Electrochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Metallurgy (AREA)
  • Materials Engineering (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)
  • Application Of Or Painting With Fluid Materials (AREA)

Abstract

La présente invention concerne des procédés, des systèmes, et des trousses fournissant des revêtements robustes et biologiquement actifs pour dispositifs médicaux implantés. Les procédés sont basés sur l'attraction électrostatique entre une surface de matériau non conducteur sur le dispositif médical et un matériau de revêtement comprenant un biopolymère ou un agent pharmaceutique chargé. La charge de surface est induite ou renforcée au niveau du matériau non conducteur en utilisant un procédé physique. Les procédés s'appliquent à une large variété de matériaux et de revêtements de substrat non conducteurs contenant un/une quelconque d'une large variété de molécules biologiques et d'agents pharmaceutiques.
PCT/US2016/013211 2015-01-13 2016-01-13 Revêtement de dispositifs médicaux avec des molécules biologiques, induit par décharge électrostatique WO2016115228A1 (fr)

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US201562102914P 2015-01-13 2015-01-13
US62/102,914 2015-01-13

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100079570A1 (en) * 2006-09-15 2010-04-01 Mcshane Robert J Apparatus for electrostatic coating
US20100196492A1 (en) * 2007-03-08 2010-08-05 Green Jordan J Electrostatic coating of particles for drug delivery
US20130022651A1 (en) * 2011-07-20 2013-01-24 Savage Paul B Hydrogel materials incorporating eluting ceragenin compound
US20140112994A1 (en) * 2002-12-19 2014-04-24 Novartis Ag Method for Making Medical Devices Having Antimicrobial Coatings Thereon

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140112994A1 (en) * 2002-12-19 2014-04-24 Novartis Ag Method for Making Medical Devices Having Antimicrobial Coatings Thereon
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