WO2007003199A1 - An electrospinning apparatus and process - Google Patents
An electrospinning apparatus and process Download PDFInfo
- Publication number
- WO2007003199A1 WO2007003199A1 PCT/DK2006/000395 DK2006000395W WO2007003199A1 WO 2007003199 A1 WO2007003199 A1 WO 2007003199A1 DK 2006000395 W DK2006000395 W DK 2006000395W WO 2007003199 A1 WO2007003199 A1 WO 2007003199A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- electrode
- medical device
- stream
- electrical potential
- polymer
- Prior art date
Links
Classifications
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
- D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
- D01D5/0092—Electro-spinning characterised by the electro-spinning apparatus characterised by the electrical field, e.g. combined with a magnetic fields, using biased or alternating fields
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
- D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
- D01D5/0076—Electro-spinning characterised by the electro-spinning apparatus characterised by the collecting device, e.g. drum, wheel, endless belt, plate or grid
- D01D5/0084—Coating by electro-spinning, i.e. the electro-spun fibres are not removed from the collecting device but remain integral with it, e.g. coating of prostheses
Definitions
- US patent No. 6,713,011 B2 discloses an apparatus and a method for electrospinning polymer fibers and membranes.
- the method includes electrospinning polymer fibers from a conducting fluid in the presence of a first electric field established between a conducting fluid introduction device and a ground source and modifying the first electric field with a second electric field to form a jet stream of the conducting fluid.
- the method also includes electrically controlling the flow characteristics of the jet stream, forming a plurality of electrospinning jet streams and independently controlling the flow characteristics of at least one of the jet streams.
- the invention provides an apparatus for providing a coating to a medical device by electrospinning, the apparatus comprising:
- the apparatus being arranged to maintain a second electrical potential at the second electrode, so that an electrical field exists between the first and second electrode, the stream of dissolved polymer being conveyed away from the first electrode under the action of the electrical field.
- the apparatus is preferably configured to guide a stream of gas in a direction different from the direction from the first electrode to the second electrode.
- the invention provides a method for providing a polymer coating to a medical device by electrospinning, the method comprising the steps of: - dispersing, from a first electrode maintained at a first electrical potential, a stream of dissolved polymer toward the medical device;
- the method preferably includes the further step of conveying a stream of gas in a direction different to the direction from the first electrode to the second electrode during the step of dispersing.
- the action of the electrical field may thus at least partially cause that the dissolved polymer is coated onto the medical device.
- the electrical field is essentially solely responsible for conveying the dissolved polymer toward the medical device.
- the combined action of the electrical field and the gas stream may cause the dissolved polymer to be conveyed from the first electrode to the medical device.
- the apparatus and method of the present invention includes at least two electrodes.
- the first electrode is partly or fully surrounded by an airstream.
- the first or second electrode is adapted to emerge a stream of dissloved polymer.
- an electrical potential is established between the first and the second electrode. Due to the electrical potential at least some of the fibres formed near the emerging electrode will be attracted towards the second electrode.
- the formed fibres may also be affected by the stream of gas emerging from a gas outlet, which may, e.g., surround the first electrode.
- the viscous forces subjected by the flowing gas to the fibres preferably overcomes the attracting electrostatic forces and prevents thus the fibres from accumulating on one or both electrodes.
- a shield may optionally be provided to reduce exterior impact on the existing electrical field and on the stream of polymer, which may enhance control and reproducibility of the electrospinning process.
- Many therapeutic agents may be chosen, among these lubricants, human growth factors or analogies to these, antiseptic agents or agents suppressing inflammatory tissue response. These agents among others, or mixtures hereof, may be dissolved in the spinning solution, thus giving the spun surface drug releasing properties.
- the therapeutic material in itself dissolves into monomers or dimmers that can diffuse to the surrounding tissue.
- An alternative approach is to include materials that degenerate thus releasing therapeutic materials.
- One example of such a material is nitric oxide modified linear poly(ethylenimine) diazeniumdiolate as described in US patent No. 6,737,447. Upon subjection to neutral or acidic water this material will release NO.
- the polymer solution forming the conducting fluid may preferably have a polymer concentration in the range of about 1 to about 35 wt%, more preferably in the range of about 5 to about 20 wt%, or, alternatively in the range of about 0.1 to about 5 wt%.
- the coating may after electrospinning be subjected to therapeutic agents, which are absorbed by the coating. These therapeutic agents are to be released in the body upon implantation of the coating.
- therapeutic agents which are absorbed by the coating.
- linear poly(etihylenimine) may be applied to the medical device by electrospinning.
- nitric oxide may be applied to the outer surface of the medical device by exposing the outer surface of the device to nitric oxide in a chamber containing pressurized nitric oxide at a pressure of e.g. 1-5 bar, or 1.5-5 bar or 2-5 bar.
- the feed rate of the conducting fluid to the first electrode may preferably be in the range of about 0.1 to about 1000 microliters per min., more preferably in the range of about 1 to about 25 microliters per min.
- Electrospinning comprises a process of formation of fibers from a fluid exploiting the interactions between surface tension and the electrostatic forces exerted in the fluid surface by an applied electrostatic field.
- an electrostatic field is applied to e.g. a droplet of conducting fluid
- the fluid surface will experience forces both due to the surface tension as well as due to the applied electrostatic field.
- the surface tension of the fluid will dominate and the droplet will essentially remain spherical.
- the electrostatic field is increased the droplet will become increasingly deformed by electrostatic forces until the surface of the droplet becomes unstable and a tiny stream of liquid is ejected from the surface. The material in this stream eventually solidifies, thus forming a fiber.
- electrospinning comprises a process wherein particles (dissolved polymer) emerge from a source, a first electrode, kept at a certain, preferably constant, electric potential. By applying a second electrode kept at another certain, preferably constant, electrical potential, an electrical field exists. The dissolved polymer will under influence of this electrical field be directed toward the medical device.
- the electric field created in the electrospinning process may preferably be in the range of about 1 to about 100 kV, such as aoubt 5 to about 100 kV, such as in the range of about 5 to about 20 kV.
- the first electrode is a hollow conducting tube where the spinning droplet may be located at the end of the tube. According to this layout the droplet may continuously be replenished by a steady flow of liquid through the tube.
- the first electrode is grounded.
- the required electrical field is accomplished by applying an electrical potential to the second electrode.
- the electrical potential applied to the second electrode may be either positive, negative or alternating having a numerical peak value preferably in the range of 0.1 kV and 50 kV, more preferably in the range of 1 kV and 20 kV, such as in the range of 5 kV and 15 kV.
- the power supply may either output a DC current or an alternating current.
- the power supply used is a DC current having means for arch suppression. Arch suppression may be achieved either by using a power supply having high output impedance or by using a power supply with an active current limiter.
- a stent graft is a stent comprising a membrane which may cover the stent partly or fully.
- the purpose of the membrane may be to stop injury of a blood vessel or to stop e.g. the blood flow to an aneurysm.
- the purpose might also be to provide a membrane releasing desired amounts of a therapeutic substance.
- the second electrode (or mandrel) may be integrated in the support for supporting the medical device in order to simplify the process of directing the stream of polymers toward the medical device.
- the second electrode is positioned at a distance from the support for supporting the medical device, so that the direction from the first electrode to the second electrode is different from the direction from the first electrode to the medical device.
- the fibers will thereby initially be conveyed toward the second electrode.
- an additionally force may be applied, the additional force and the electrical field in combination being responsible for the transport of the fibers from the first electrode to the medical device.
- the auxiliary electrode may in excess of reducing exterior impact of the emerging stream of polymer also enhance the electrical field and reflect the fibers, thereby encouraging the deposition of the fibers at the medical device.
- the apparatus may further comprise at least one screen at the support for supporting the medical device thereby supporting the guidance of the stream of polymer toward the medical device during use of the apparatus.
- the apparatus may be arranged to maintain an electrical potential at the at least one screen.
- the at least one screen comprises a first and a second screen, which screens may be arranged at respective opposite ends of the medical device.
- the second electrode is an elongated conducting member partly or fully surrounded by a pipe made from a dielectric material.
- gas may be passed through the pipe thus forming a jet stream surrounding the second electrode.
- process parameters are readily controllable in a multitude of ways.
- fibers are formed at the first electrode well outside the jet stream, and they will be attracted toward the second electrode due to electrostatic forces. By varying the distance between the first and second electrode as well as the applied electrical field, the local field strength near the first electrode as well as the transition time before the fibers are subjected to the gas stream may be readily controlled.
- control of evaporation of solvents from the formed fibers may be improved.
- the rate of evaporation may furthermore be controlled by variation of the distance to be traveled by the fibers in the gas stream before arriving at the surface to be coated.
- the support for supporting the medical device may be arranged so as to keep the mandrel at a predetermined electrical potential. If the mandrel is kept at an electrical potential which is opposite to the first electrode the electrical field will be intensified and the coating process further improved.
- the apparatus may further comprise at least one electrically charged ring element arranged on an outer surface of the cylindrical wall.
- the apparatus may be arranged to keep one of the gas and the mandrel at a positive electrical potential and the other one at a negative electrical potential.
- the use of gas may enhance control of the stream of dissolved polymer, whereby the coating process may be improved.
- the apparatus is arranged in order to keep the mandrel at a positive electrical potential, is arranged to keep the stream of gas at a negative electrical potential, and is arranged to keep the first electrode at a negative electrical potential.
- the gas may e.g. be kept at a positive or negative electrical potential by ionizing the gas.
- the coating of the medical device may define a plurality of sections along the length of the device.
- the sections may have different properties, such as different hardness.
- Such different properties may be arrived at by employing different fiber-forming materials for different sections and/or by changing production parameters, such as voltage of the first and/or second electrode, distance between the electrodes, rotational speed of the device, electrical field intensity, corona discharge initiation voltage or corona discharge current.
- the properties of the coating are controlled by controlling the fluidity or formation of the fibers, for example by controlling the distance between the first and second electrode. It has been found, that a stronger electrical field and/or a thin solvent of polymer result in thinner fibers. Furthermore, it has been found that the longer the distance between the first electrode and the medical device, the thinner dimension of the fibers. Furthermore, is has been found that the more polarized the dissolved polymer is, the thinner the fibers are, and the control of the fibers can thereby be enhanced.
- the process may be controlled by exposing the coated medical device to UV/IR light and checking the absorption thereof.
- the diameter of the fibers may be checked by exposing the stream of dissolved polymer to white light. Using a camera, the wavelength of the light reflected may be analyzed, thereby receiving information of the thickness of fibers.
- Fig.l is a first illustration of an electrospinning apparatus applicable for performing a hybrid spinning process.
- Fig. 2 is an illustration of an embodiment of an electrospinning apparatus
- Fig. 3 is a second illustration of an electrospinning apparatus applicable for performing a hybrid spinning process.
- Fig. 1 shows an embodiment of an apparatus according to the present invention.
- the dissolved polymer is passed through a hollow, conducting spinning electrode, a first electrode 1, resulting in formation of a liquid droplet in the top of the first electrode Ia.
- the drop is subjected to a strong electrical field due to presence of the second electrode 2.
- the second electrode 2 is surrounded by a hollow tube 3.
- a stream of gas is passed over the second electrode 2 and the formed fibers are prevented from arriving at the second electrode 2 even though the fibers are attracted to the second electrode 2 by electrostatic forces.
- the effect of the strong electrical field between the first electrode 1 and the second electrode 2 is that fibers are formed at the first electrode 1 and attracted toward the second electrode 2. Before the formed fibers reach the second electrode 2 they are, however, cached in the stream of gas surrounding the second electrode 2. As the force exerted on the fibers by the gas stream exceeds the force exerted on the fibers by the electrostatic field, the fibers are forced to follow the stream of gas.
- a large charge is induced on the charged electrode.
- a grounded (and conducting) spinning nozzle is provided in relatively close proximity to the electrode. Because of the positive potential on the electrode, a negative potential will build up on the tip of the nozzle. This will create an electric field between the nozzle and the electrode. Polarity can also be reversed.
- the driving electric field is between the nozzle and the electrode (not between the nozzle and the target, i.e. medical device to be coated).
- a weaker field may exist between the nozzle and the target, however this is not utilized in the process.
- the spinning fibers will be charged, even though the nozzle is grounded
- Fig. 2 shows a syringe pump 10 from which a solution of dissolved polymer 11 is delivered to a nozzle 12 comprising a first electrode (not shown).
- a power supply 13 is arranged to maintain a first electrical potential at the first electrode.
- a second power supply 14 is arranged to maintain a second electrical potential at the support 15 for supporting the medical device 16.
- An electrical field exists between the first electrode 1 and the support 15 due to the presence of the electrical potentials maintained at the first electrode and at the support 15.
- a stream of dissolved polymer 17 is conveyed toward the medical device 16 under the action of the electrical field present.
- Spinning is carried out using a liquid comprising 7 wt% TecoflexTM polyurethane, 50 wt% tetrahydrofurane (THF) and 43 wt% methanol (MeOH).
- the first electrode 1 is a gauge 25 needle, which is fed by a syringe pump at a rate of 2.5 ml/h
- the second electrode 2 is a plain steel wire.
- a glass tube 3 having an inner diameter of 6 mm is surrounding the steel wire.
- dried air is passed through the glass tube 3 at a pressure of 0.1-10 bar, typically at a pressure of 1-3 bar.
- the required electrostatic field is established by connecting the first electrode 1 to ground potential and connecting the second electrode 2 to a high tension supply adjusted to an output voltage of +12 kV.
- the distance between the first electrode 1 and the second electrode 2 is 50 mm.
- Coating is carried out by placing the objects to be coated in a distance of approximately 10- 20 cm from the first electrode 1.
- Example 2 Production of non-releasing polyurethane fibers
- Spinning is carried out using a liquid comprising 3.5 wt% TecoflexTM polyurethane, 50 wt% tetrahydrofurane (THF) and 46.5 wt% methanol (MeOH).
- the first electrode 1 is a gauge 25 needle, which is fed by a syringe pump at a rate of 2.5 ml/h, and the second electrode 2 is a plain steel wire.
- a POM (Polyoxymethylene) tube 3 having an inner diameter of 8 mm is surrounding the steel wire.
- dried air is passed through the glass tube 3 at a pressure of 0.1-10 bar, typically at a pressure of 1-3 bar.
- Coating is carried out by placing the objects to be coated in a distance of approximately 10 cm from the first electrode 1.
- Spinning is carried out using a liquid comprising 3.5 wt% TecoflexTM polyurethane, 45 wt% tetrahydrofurane (THF) and 43 wt% methanol (MeOH).
- THF tetrahydrofurane
- MeOH methanol
- the mixture is mixed with 5 wt% H 2 O containing glocoseoxidase (GOD).
- GOD glocoseoxidase
- the required electrostatic field is established by connecting the first electrode 1 to ground potential and connecting the second electrode 2 to a high tension supply adjusted to an output voltage of -12 kV.
- the distance between the first electrode 1 and second electrode 2 is 40 mm.
- Coating is carried out by placing the objects to be coated in a distance of approximately 10 cm from the first electrode 1.
- the formed coating contains ⁇ -crystals of GOD 7 which releases H 2 O 2 upon exposure to glucose.
- Spinning is carried out using a liquid comprising 10 wt% TecoflexTM polyurethane, 47 wt% tetrahydrofurane (THF). Immediately prior to spinning the mixture is mixed with 2 wt% linear poly(etihylenimine) diazeniumdiolate dissolved in 41 wt% methanol (MeOH).
- the required electrostatic field is established by connecting the first electrode 1 to ground potential and connecting the second electrode 2 to a high tension supply adjusted to an output voltage of +9 kV.
- the distance between the first electrode 1 and second electrode 2 is 50-100 mm.
Landscapes
- Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Textile Engineering (AREA)
- Spinning Methods And Devices For Manufacturing Artificial Fibers (AREA)
Abstract
An apparatus for providing a coating to a medical device by electrospinning comprises a first electrode adapted to emerge a stream of dissolved polymer, a support for supporting the medical device at a distance from the first electrode, and a second electrode. The apparatus is arranged to maintain a first electrical potential at the first electrode, and arranged to maintain a second electrical potential at the second electrode, so that an electrical field exists between the first and second electrode. The stream of dissolved polymer is conveyed toward the medical device under the action of the electrical field, the stream of polymer being influenced by a gas flow. The apparatus may comprise a shield which is arranged to reduce exterior impacts to the stream of polymer and the electrical field.
Description
AN ELECTROSPINNING APPARATUS AND PROCESS
Technical field
The present invention relates to an apparatus for providing a coating to a medical device by electrospinning and a method for providing this coating.
Background of the invention
Medical devices, such as angioplasty balloons are widely used in various diagnostic procedures and medical treatments. For example, balloons are employed to expand stents for implantation in the lumen of a body duct for the treatment of blood vessels exhibiting stenosis. It is generally desired that medical devices for insertion in the vascular system of a living being meet certain physical requirements. For example, the surface of stents should be hydrophilic and have a low surface friction in order to facilitate introduction. The stent surface may be coated with a pharmaceutical agent, such as a nitric oxide releasing compound.
In the prior art, various medical devices, including stents and catheters, as well as methods for their manufacture have been proposed. US patent No. 6,030,371 discloses a method for non-extrusion manufacturing of catheters that can be used to produce catheters having a simple or complex configuration. A polymer material in a particulate preform is applied in a layer over an outer surface of a core member. By applying the layer in a particulate preform, a composition of the polymer material can be varied continuously as it is being applied to provide a variable hardness over the length of the catheter. A fibrous reinforcement can be used having a constant or variable pitch, and a constant or variable number of fibers and fiber types may be employed.
International patent application WO 2004/006976 suggests a single layer of lipophilic bioactive material posited or applied to a balloon base material for direct application to a vessel wall after the previous introduction of a stent. The layer of bioactive material can be posited on the balloon by dipping, soaking or spraying.
Various nitric oxide donor components, pharmaceutical compositions containing such nitric oxide donor components and polymeric compositions capable of releasing nitric oxide have also been proposed in the prior art. For example, US patent No. 6,737,447 Bl discloses a medical device comprising at least one nanofiber of a linear poly(etihylenimine) diazeniumdiolate forming a coating layer on the device. US 6,737,447 mentions the possibility of depositing the polymer by an electrospinning process.
US patent No. 4,323,525 discloses a process for electrostatically spinning a fiber forming material. The process of electrostatic spinning involves the introduction of a liquid into an electric field whereby the liquid is caused to produce fibers. The spun fiber is collected on a removable sheath on a rotating mandrel. The sheath is electroconductive. The tubular spun fiber product is subsequently separated from the sheath prior to use.
US patent No. 4,689,186 discloses a process for production of products having a tubular portion, the process comprising electrostatically spinning a fiberizable liquid, the electrostatic field being distorted by the presence of an auxiliary electrode, preferably so as to encourage the deposition of circumferential fibers.
US patent No. 6,713,011 B2 discloses an apparatus and a method for electrospinning polymer fibers and membranes. The method includes electrospinning polymer fibers from a conducting fluid in the presence of a first electric field established between a conducting fluid introduction device and a ground source and modifying the first electric field with a second electric field to form a jet stream of the conducting fluid. The method also includes electrically controlling the flow characteristics of the jet stream, forming a plurality of electrospinning jet streams and independently controlling the flow characteristics of at least one of the jet streams. The apparatus for electrospinning includes a conducting fluid introduction device containing a plurality of electrospinning spinnerets, a ground member positioned adjacent to the spinnerets, a support member disposed between the spinnerets and the ground member and movable to receive fibers formed from the conducting fluid, and a component for controlling the flow characteristics of conducting fluid from at least one spinneret independently from another spinneret.
None of the above mentioned references address, however, the problem of even deposition on objects of different forms made partly or fully from a dielectric material. The present inventors have found that one problem associated with conventional electrospinning is that the dielectric parts of the objects will charge in a non-controllable and irreproducible way, thus deflecting the charged fibers in an uncontrollable manner due to erratic electrostatic fields. The resulting coatings will consequently be uneven and irreproducible and therefore not applicable for medical applications, where reproducibility and end result of the coating are highly important.
Summary of the invention
It is an object of embodiments of the present invention to provide an apparatus for improved coating of a medical device by electrospinning.
In a first aspect, the invention provides an apparatus for providing a coating to a medical device by electrospinning, the apparatus comprising:
- a first electrode adapted to emerge a stream of dissolved polymer, the apparatus being arranged to maintain a first electrical potential at the first electrode; - a support for supporting the medical device at a distance from the first electrode, so as to define a space between the first electrode and the medical device;
- a second electrode, the apparatus being arranged to maintain a second electrical potential at the second electrode, so that an electrical field exists between the first and second electrode, the stream of dissolved polymer being conveyed away from the first electrode under the action of the electrical field.
The apparatus is preferably configured to guide a stream of gas in a direction different from the direction from the first electrode to the second electrode.
In a second aspect, the invention provides a method for providing a polymer coating to a medical device by electrospinning, the method comprising the steps of: - dispersing, from a first electrode maintained at a first electrical potential, a stream of dissolved polymer toward the medical device;
- supporting the medical device at a distance from the first electrode;
- maintaining a second electrical potential at a second electrode, so that an electrical field exists in between the first electrode and the second electrode, so as to convey a stream of polymer away from the first electrode under the action of the electrical field, so as to form said polymer coating on the medical device.
The method preferably includes the further step of conveying a stream of gas in a direction different to the direction from the first electrode to the second electrode during the step of dispersing.
In the first and second aspects of the invention, the action of the electrical field may thus at least partially cause that the dissolved polymer is coated onto the medical device. In embodiments including no gas stream, the electrical field is essentially solely responsible for conveying the dissolved polymer toward the medical device. In embodiments including the gas stream, the combined action of the electrical field and the gas stream may cause the dissolved polymer to be conveyed from the first electrode to the medical device.
It will hence be appreciated that the apparatus and method of the present invention includes at least two electrodes. Preferably the first electrode is partly or fully surrounded by an airstream. The first or second electrode is adapted to emerge a stream of dissloved polymer. During operation of the device an electrical potential is established between the first and the
second electrode. Due to the electrical potential at least some of the fibres formed near the emerging electrode will be attracted towards the second electrode. However, the formed fibres may also be affected by the stream of gas emerging from a gas outlet, which may, e.g., surround the first electrode. The viscous forces subjected by the flowing gas to the fibres preferably overcomes the attracting electrostatic forces and prevents thus the fibres from accumulating on one or both electrodes.
In the present context, the terms"electrical potential" is used synonymously with "electrical charge".
To reduce exterior impact on the electrospinning process a shield may optionally be provided to reduce exterior impact on the existing electrical field and on the stream of polymer, which may enhance control and reproducibility of the electrospinning process.
The polymer may be prepared from various polymer-based materials and composite matrixes thereof, including polymer solutions and polymer melts. Applicable polymers are, e.g. polyamides including nylon, polyurethanes, fluoropolymers, polyolefins, polyimides, polyimines, (meth)acrylic polymers, and polyesters, as well as suitable co-polymers.
The solvent for the polymer may be any solvent capable of dissolving the polymer and providing a conducting fluid capable of being electrospun. Typical solvents include a solvent selected from N,N-Dimethyl formamide (DMF)7 tetrahydrofuran (THF), methylene chloride, dioxane, methanol, ethanol, higher alcohols, chloroform, water and mixtures hereof. The conducting fluid may optionally comprise a therapeutic material, i.e. a material releasing therapeutic agents when subjected to bodily fluids.
Many therapeutic agents may be chosen, among these lubricants, human growth factors or analogies to these, antiseptic agents or agents suppressing inflammatory tissue response. These agents among others, or mixtures hereof, may be dissolved in the spinning solution, thus giving the spun surface drug releasing properties.
Basically two types of therapeutic agents exist. In one case the therapeutic material in itself dissolves into monomers or dimmers that can diffuse to the surrounding tissue. An alternative approach is to include materials that degenerate thus releasing therapeutic materials. One example of such a material is nitric oxide modified linear poly(ethylenimine) diazeniumdiolate as described in US patent No. 6,737,447. Upon subjection to neutral or acidic water this material will release NO.
The polymer solution forming the conducting fluid may preferably have a polymer concentration in the range of about 1 to about 35 wt%, more preferably in the range of about 5 to about 20 wt%, or, alternatively in the range of about 0.1 to about 5 wt%. The polymer concentration may be chosen based on the molecule weight of the polymers. This may result in a relatively higher molar polymer concentration for polymers having a low molecule weight and a relatively lower molar polymer concentration for polymers having a higher molecule weight.
In one embodiment the liquid used for the electrospinning process comprises at least 0.25% polyurethane as well as a therapeutic agent which may exist either as diluted or as suspended particles. The therapeutic agent may e.g .comprise nitric oxide modified linear poly(ethylenimine) diazeniumdiolate as described in US patent No. 6,737,447 for achieving aterial relaxation.
In another embodiment the coating may after electrospinning be subjected to therapeutic agents, which are absorbed by the coating. These therapeutic agents are to be released in the body upon implantation of the coating. As an example, linear poly(etihylenimine) may be applied to the medical device by electrospinning. Subsequently, nitric oxide may be applied to the outer surface of the medical device by exposing the outer surface of the device to nitric oxide in a chamber containing pressurized nitric oxide at a pressure of e.g. 1-5 bar, or 1.5-5 bar or 2-5 bar.
The feed rate of the conducting fluid to the first electrode may preferably be in the range of about 0.1 to about 1000 microliters per min., more preferably in the range of about 1 to about 25 microliters per min.
Electrospinning comprises a process of formation of fibers from a fluid exploiting the interactions between surface tension and the electrostatic forces exerted in the fluid surface by an applied electrostatic field. When an electrostatic field is applied to e.g. a droplet of conducting fluid, the fluid surface will experience forces both due to the surface tension as well as due to the applied electrostatic field. At comparably low electrostatic fields the surface tension of the fluid will dominate and the droplet will essentially remain spherical. When the electrostatic field is increased the droplet will become increasingly deformed by electrostatic forces until the surface of the droplet becomes unstable and a tiny stream of liquid is ejected from the surface. The material in this stream eventually solidifies, thus forming a fiber.
It should be understood that the term electrospinning comprises a process wherein particles (dissolved polymer) emerge from a source, a first electrode, kept at a certain, preferably constant, electric potential. By applying a second electrode kept at another certain,
preferably constant, electrical potential, an electrical field exists. The dissolved polymer will under influence of this electrical field be directed toward the medical device. The electric field created in the electrospinning process may preferably be in the range of about 1 to about 100 kV, such as aoubt 5 to about 100 kV, such as in the range of about 5 to about 20 kV.
In one embodiment of the invention, the first electrode is a hollow conducting tube where the spinning droplet may be located at the end of the tube. According to this layout the droplet may continuously be replenished by a steady flow of liquid through the tube.
In another embodiment of the invention, the first electrode is grounded. Thus, the required electrical field is accomplished by applying an electrical potential to the second electrode. The electrical potential applied to the second electrode may be either positive, negative or alternating having a numerical peak value preferably in the range of 0.1 kV and 50 kV, more preferably in the range of 1 kV and 20 kV, such as in the range of 5 kV and 15 kV.
Due to the high electrical potentials needed for electrospinning, the apparatus may be designed such that arching and short circuits do not influence the attached supporting device. For some embodiments it has been found that the most robust spinning process may be achieved when the first electrode is coupled to ground, and the needed electrostatic field is achieved by coupling the required high voltage supply to the second electrode. A coupling scheme where the first electrode is grounded is furthermore beneficial if spinning is carried out using a conducting spinning fluid. This is due to the fact that destructive stray currents may run along the liquid supply line if an electrical potential is coupled to the first electrode.
Many types of high voltage supplies may be employed for spinning according to the present invention. The power supply may either output a DC current or an alternating current. In one embodiment, the power supply used is a DC current having means for arch suppression. Arch suppression may be achieved either by using a power supply having high output impedance or by using a power supply with an active current limiter.
The medical device may be a balloon for use in angioplasty, a stent for implantation in the lumen of a body duct for the treatment of blood vessels exhibiting stenosis, a catheter, vascular prostheses, a flexible tube, a stent graft, etc.
The flexible tube may be coated separately and subsequent it may be slipped over a medical device. An example hereof is a stent which is not flexible if coated. If coating a flexible tube and subsequently slipping the tube over a stent of this type, the stent may be expanded without weakening the coated stent. The flexible tube may have a diameter smaller than the diameter of the stent to be slipped over, thereby attaching the coated tube to the stent by an
inward gripping action. To ensure the fastening even further, the coated tube may be secured to the stent using adhesives, e.g. "glued" to the stent.
A stent graft is a stent comprising a membrane which may cover the stent partly or fully. In some cases the purpose of the membrane may be to stop injury of a blood vessel or to stop e.g. the blood flow to an aneurysm. However, the purpose might also be to provide a membrane releasing desired amounts of a therapeutic substance.
The apparatus comprises a support for supporting the medical device in order to position the medical device at a certain distance from the first electrode. The support may e.g. be in the form of an elongated element around which the medical device is positioned. Alternatively, the medical device may be supported by a gripping device at one or at both ends or supported by e.g. an air cushion.
The second electrode (or mandrel) may be integrated in the support for supporting the medical device in order to simplify the process of directing the stream of polymers toward the medical device.
In other embodiments of the present invention, the second electrode is positioned at a distance from the support for supporting the medical device, so that the direction from the first electrode to the second electrode is different from the direction from the first electrode to the medical device. The fibers will thereby initially be conveyed toward the second electrode. In order to prevent the fibers from reaching the second electrode, an additionally force may be applied, the additional force and the electrical field in combination being responsible for the transport of the fibers from the first electrode to the medical device.
The shield may comprise a first wall section upstream of the stream of polymer primarily in order to reduce longitudinal exterior impact on the emerging stream of polymer and the electrical field. Furthermore, the shield may comprise a second wall section extending essentially perpendicularly to the first wall at a distance from the first electrode primarily in order to reduce transversal exterior impact. One example of a shield according to the present invention is a shield in the form of an essentially cylindrical element closed at at least one of its ends, so that an end wall of the cylindrical element defines the first wall section, and the cylindrical wall of the cylindrical element defines the second wall section. Also e.g. a rectangular form of the shield may be used. Furthermore, a shield in the form of an auxiliary electrode may be used. The auxiliary electrode may in excess of reducing exterior impact of the emerging stream of polymer also enhance the electrical field and reflect the fibers, thereby encouraging the deposition of the fibers at the medical device.
In order to improve control of the coating process, the apparatus may further comprise at least one screen at the support for supporting the medical device thereby supporting the guidance of the stream of polymer toward the medical device during use of the apparatus. To further improve the control, the apparatus may be arranged to maintain an electrical potential at the at least one screen. In one embodiment of the present invention, the at least one screen comprises a first and a second screen, which screens may be arranged at respective opposite ends of the medical device.
If the apparatus is arranged to keep at least one screen at a negative electrical potential, this screen will, if the first electrode is also kept at a negative electrical potential, improve the coating of the medical device due to the fact that the fibers are repelled from the at least one screen, thereby increasing the electrical forces influencing the fibers.
As discussed above, the apparatus is preferably configured to guide a stream of gas in a direction which is different from the direction from the first electrode to the second electrode. Furthermore, it may be configured in order to facilitate that the electrical field and the stream of gas guide the dissolved polymer toward the medical device, thereby creating a spinning process, which in the following will be referred to as a hybrid spinning process.
For some embodiments it has been found that polymeric fibers may advantageously be produced by a hybrid spinning process, wherein the second electrode may be surrounded by a stream of gas, and wherein the forces, which are exerted on the fibers by the gas stream near the second electrode, may exceed the electrostatic forces near the second electrode. Upon spinning, the fibers emerge from the first electrode and, they are conveyed toward the second electrode by the influence of the electrical field. However, as the force on the formed fibers exerted by the gas stream exceeds the electrostatic forces, the formed fibers are prevented from reaching the second electrode. Instead the fibers are caught in the gas stream and transported away from the electrostatic field. For some embodiments, this layout of the apparatus improves control of the deposition of fibrous electrospun coating at medical devices.
In one embodiment of the invention the second electrode is an elongated conducting member partly or fully surrounded by a pipe made from a dielectric material. According to this embodiment, gas may be passed through the pipe thus forming a jet stream surrounding the second electrode. One of the advantages of this particular embodiment is that process parameters are readily controllable in a multitude of ways. According to this embodiment, fibers are formed at the first electrode well outside the jet stream, and they will be attracted toward the second electrode due to electrostatic forces. By varying the distance between the first and second electrode as well as the applied electrical field, the local field strength near
the first electrode as well as the transition time before the fibers are subjected to the gas stream may be readily controlled. By controlling the force and temperature of the gas stream, control of evaporation of solvents from the formed fibers may be improved. The rate of evaporation may furthermore be controlled by variation of the distance to be traveled by the fibers in the gas stream before arriving at the surface to be coated.
Different types of gas may be passed over the second electrode, among other gasses air, dried air, and nitrogen. However, many other gasses may be used instead. One example may be a gas partly or fully saturated with a solvent. By using a solvent containing gas to cover the second electrode, evaporation from the formed fibers may be reduced, which may be advantageous for certain applications. Another example may be to mix the used gas with small amounts of sulfurhexaflouride (SF6). If arching occurs between the first electrode and the second electrode, SF6 disintegrates and thus releases fluorine gas which will quench the arch.
In another embodiment of the invention, the apparatus may be configured to guide the stream of gas in a direction which is opposite to the direction from the first electrode to the second electrode. In this case the electrical field directs the stream of dissolved polymer from the first electrode to the second electrode, whereas the stream of gas may help controlling this process. If the first electrode is kept at a negative potential and if the stream of gas is ionized air kept at a positive potential, this may enhance the transport of the fibers toward the medical device, thereby improving the coating process. The size of the stream of gas may be in the range of 1-100 l/min.
The support for supporting the medical device may comprise a mandrel, and the apparatus may further comprise a motor for continuously rotating the mandrel, whereby even deposition of the dissolved polymer may be improved and control and reproducibility of the process may be enhanced. The mandrel may be rotated at a rotational speed in the range of 1-500 rpm, such as 20-500 rpm.
The support for supporting the medical device may be arranged so as to keep the mandrel at a predetermined electrical potential. If the mandrel is kept at an electrical potential which is opposite to the first electrode the electrical field will be intensified and the coating process further improved.
In case of a shield in the form of an essentially cylindrical element, the apparatus may further comprise at least one electrically charged ring element arranged on an outer surface of the cylindrical wall. By applying an external field of the same polarity as the first electrode it has shown possible to control or eliminate the bending instability inherent in conventional
electrospinning processes. On start-up of the electrospinning process there is often some jet instability near the initiating electrode (the first electrode) because of the edge effects. As the jet proceeds toward the target (the medical device), the instability is dampened under the influence of the covering electric field lines. Since the jet is continuous, the dampening of the instability and acceleration of the jet downstream act to stabilize the part of the jet near the initiating electrode.
The apparatus may be arranged to keep one of the gas and the mandrel at a positive electrical potential and the other one at a negative electrical potential. By keeping the gas and the mandrel at opposite electrical potentials the use of gas may enhance control of the stream of dissolved polymer, whereby the coating process may be improved. One example is that the apparatus is arranged in order to keep the mandrel at a positive electrical potential, is arranged to keep the stream of gas at a negative electrical potential, and is arranged to keep the first electrode at a negative electrical potential. The gas may e.g. be kept at a positive or negative electrical potential by ionizing the gas.
The coating of the medical device may define a plurality of sections along the length of the device. For example, the sections may have different properties, such as different hardness. Such different properties may be arrived at by employing different fiber-forming materials for different sections and/or by changing production parameters, such as voltage of the first and/or second electrode, distance between the electrodes, rotational speed of the device, electrical field intensity, corona discharge initiation voltage or corona discharge current.
In one embodiment of the present invention, the properties of the coating are controlled by controlling the fluidity or formation of the fibers, for example by controlling the distance between the first and second electrode. It has been found, that a stronger electrical field and/or a thin solvent of polymer result in thinner fibers. Furthermore, it has been found that the longer the distance between the first electrode and the medical device, the thinner dimension of the fibers. Furthermore, is has been found that the more polarized the dissolved polymer is, the thinner the fibers are, and the control of the fibers can thereby be enhanced.
The coating process may be controlled optically by checking the color of the coated medical device. Alternatively and/or supplementary, the coating process may be controlled by measuring the diameter of the coated medical device by the use of a laser curtain.
Furthermore, the process may be controlled by exposing the coated medical device to UV/IR light and checking the absorption thereof.
During the coating process, the diameter of the fibers may be checked by exposing the stream of dissolved polymer to white light. Using a camera, the wavelength of the light reflected may be analyzed, thereby receiving information of the thickness of fibers.
Brief description of the drawings
Embodiments of the invention will now be further described with reference to the drawings, in which:
Fig.l is a first illustration of an electrospinning apparatus applicable for performing a hybrid spinning process.
Fig. 2 is an illustration of an embodiment of an electrospinning apparatus;
Fig. 3 is a second illustration of an electrospinning apparatus applicable for performing a hybrid spinning process.
Detailed description of the drawings
Fig. 1 shows an embodiment of an apparatus according to the present invention. The dissolved polymer is passed through a hollow, conducting spinning electrode, a first electrode 1, resulting in formation of a liquid droplet in the top of the first electrode Ia. The drop is subjected to a strong electrical field due to presence of the second electrode 2. The second electrode 2 is surrounded by a hollow tube 3. By ejecting gas through the surrounding hollow tube 3 a stream of gas is passed over the second electrode 2 and the formed fibers are prevented from arriving at the second electrode 2 even though the fibers are attracted to the second electrode 2 by electrostatic forces.
The effect of the strong electrical field between the first electrode 1 and the second electrode 2 is that fibers are formed at the first electrode 1 and attracted toward the second electrode 2. Before the formed fibers reach the second electrode 2 they are, however, cached in the stream of gas surrounding the second electrode 2. As the force exerted on the fibers by the gas stream exceeds the force exerted on the fibers by the electrostatic field, the fibers are forced to follow the stream of gas.
As shown in Fig. 3, a large charge is induced on the charged electrode. In relatively close proximity to the electrode a grounded (and conducting) spinning nozzle is provided. Because
of the positive potential on the electrode, a negative potential will build up on the tip of the nozzle. This will create an electric field between the nozzle and the electrode. Polarity can also be reversed.
It will hence be appreciated that the driving electric field is between the nozzle and the electrode (not between the nozzle and the target, i.e. medical device to be coated). A weaker field may exist between the nozzle and the target, however this is not utilized in the process. The spinning fibers will be charged, even though the nozzle is grounded
Fig. 2 shows a syringe pump 10 from which a solution of dissolved polymer 11 is delivered to a nozzle 12 comprising a first electrode (not shown). A power supply 13 is arranged to maintain a first electrical potential at the first electrode. A second power supply 14 is arranged to maintain a second electrical potential at the support 15 for supporting the medical device 16. An electrical field exists between the first electrode 1 and the support 15 due to the presence of the electrical potentials maintained at the first electrode and at the support 15. A stream of dissolved polymer 17 is conveyed toward the medical device 16 under the action of the electrical field present.
The following four examples all relate to Figs. 1 and 3.
Example 1 - Production of non-releasing polyurethane fibers
Spinning is carried out using a liquid comprising 7 wt% Tecoflex™ polyurethane, 50 wt% tetrahydrofurane (THF) and 43 wt% methanol (MeOH).
The first electrode 1 is a gauge 25 needle, which is fed by a syringe pump at a rate of 2.5 ml/h, and the second electrode 2 is a plain steel wire. A glass tube 3 having an inner diameter of 6 mm is surrounding the steel wire. To protect the second electrode 2, dried air is passed through the glass tube 3 at a pressure of 0.1-10 bar, typically at a pressure of 1-3 bar.
The required electrostatic field is established by connecting the first electrode 1 to ground potential and connecting the second electrode 2 to a high tension supply adjusted to an output voltage of +12 kV. The distance between the first electrode 1 and the second electrode 2 is 50 mm.
Coating is carried out by placing the objects to be coated in a distance of approximately 10- 20 cm from the first electrode 1.
Example 2 - Production of non-releasing polyurethane fibers
Spinning is carried out using a liquid comprising 3.5 wt% Tecoflex™ polyurethane, 50 wt% tetrahydrofurane (THF) and 46.5 wt% methanol (MeOH).
The first electrode 1 is a gauge 25 needle, which is fed by a syringe pump at a rate of 2.5 ml/h, and the second electrode 2 is a plain steel wire. A POM (Polyoxymethylene) tube 3 having an inner diameter of 8 mm is surrounding the steel wire. To protect the second electrode 2, dried air is passed through the glass tube 3 at a pressure of 0.1-10 bar, typically at a pressure of 1-3 bar.
The required electrostatic field is established by connecting the first electrode 1 to ground potential and connecting the second electrode 2 to a high tension supply adjusted to an output voltage of -12 kV. The distance between the first electrode 1 and the second electrode 2 is 40 mm.
Coating is carried out by placing the objects to be coated in a distance of approximately 10 cm from the first electrode 1.
Example 3 - Production of active fibers
Spinning is carried out using a liquid comprising 3.5 wt% Tecoflex™ polyurethane, 45 wt% tetrahydrofurane (THF) and 43 wt% methanol (MeOH). Immediately prior to spinning, the mixture is mixed with 5 wt% H2O containing glocoseoxidase (GOD). When the GOD containing H2O is mixed with the Tecoflex solution, the H2O is dissolved in the THF/MeOH resulting in formation of GOD μ-crystals.
The first electrode 1 is a gauge 25 needle, which is fed by a syringe pump at a rate of 2.5 ml/h, and the second electrode 2 is a wire made from carbon fiber/epoxy. A POM tube 3 having an inner diameter of 8 mm is surrounding the carbon fiber/epoxy wire. To protect the second electrode 2, dried air is passed through the glass tube 3 at a pressure of 0.1-10 bar, typically at a pressure of 1-3 bar.
The required electrostatic field is established by connecting the first electrode 1 to ground potential and connecting the second electrode 2 to a high tension supply adjusted to an output voltage of -12 kV. The distance between the first electrode 1 and second electrode 2 is 40 mm.
Coating is carried out by placing the objects to be coated in a distance of approximately 10 cm from the first electrode 1. The formed coating contains μ-crystals of GOD7 which releases H2O2 upon exposure to glucose.
Example 4 - Production of active fibers
Spinning is carried out using a liquid comprising 10 wt% Tecoflex™ polyurethane, 47 wt% tetrahydrofurane (THF). Immediately prior to spinning the mixture is mixed with 2 wt% linear poly(etihylenimine) diazeniumdiolate dissolved in 41 wt% methanol (MeOH).
The first electrode 1 is a gauge 25 needle, which is fed by a syringe pump at a rate of 2.5 ml/h, and the second electrode 2 is a wire made from carbon fiber/epoxy. A POM tube 3 having an inner diameter of 8 mm is surrounding the carbon fiber/epoxy wire. To protect the second electrode 2, dried air is passed through the glass tube 3 at a pressure of 0.1-10 bar, typically at a pressure of 1-3 bar.
The required electrostatic field is established by connecting the first electrode 1 to ground potential and connecting the second electrode 2 to a high tension supply adjusted to an output voltage of +9 kV. The distance between the first electrode 1 and second electrode 2 is 50-100 mm.
Coating is carried out by placing the objects to be coated at a distance of approximately 3-40 cm, typically at a distance of 5-20 cm from the second electrode 2.The resulting fibers are special in that they release nitric oxide (NO) upon exposure to a humid acidic environment.
Claims
1. An apparatus for providing a coating to a medical device by electrospinning, the apparatus comprising:
- a first electrode adapted to emerge a stream of dissolved polymer, the apparatus being arranged to maintain a first electrical potential at the first electrode;
- a support for supporting the medical device at a distance from the first electrode, so as to define a space between the first electrode and the medical device;
- a second electrode, the apparatus being arranged to maintain a second electrical potential at the second electrode, so that an electrical field exists between the first and second electrode, the stream of dissolved polymer being conveyed away from the first electrode under the action of the electrical field.
2. The apparatus of claim 1, the apparatus being configured to guide a stream of gas in a direction different from the direction from the first electrode to the second electrode.
3. The apparatus of claim 1 or 2, further comprising a shield arranged to reduce exterior impacts to the stream of polymer and the electrical field.
4. The apparatus of any of the preceding claims, wherein the support for the medical device comprises the second electrode.
5. The apparatus of any of the preceding claims, wherein the direction from the first electrode to the second electrode is different from the direction from the first electrode to the medical device.
6. The apparatus of any of the preceding claims, wherein the shield comprises a first wall section upstream of the stream of polymer and a second wall section extending essentially perpendicular to said first wall at a distance from the first electrode.
7. The apparatus of claim 6, wherein the shield is in the form of an essentially cylindrical element closed at at least one of its ends, so that an end wall of the cylindrical element defines said first wall section, and a cylindrical wall of the cylindrical element defines said second wall section.
8. The apparatus of any of the preceding claims, further comprising at least one screen at said support for the medical device for guiding the stream of polymer toward the medical device during use of the apparatus.
9. The apparatus of claim 8, wherein the apparatus is arranged to maintain an electrical potential at the at least one screen.
10. The apparatus of claim 8 or 9, wherein the at least one screen comprises a first and a second screen arranged at respective opposite ends of the medical device.
11. The apparatus of any of the preceding claims, wherein the first electrode is partly or fully surruonded by said stream of gas.
12. The apparatus of any of the preceding claims, wherein the apparatus is configured to guide said stream of gas in a direction opposite to the direction from the first electrode to the second electrode.
13. The apparatus of any of the preceding claims, wherein the electrical field and the stream of gas guide the dissolved polymer toward the medical device.
14. The apparatus of any of the preceding claims, wherein said support comprises a mandrel, the apparatus further comprising a motor for continuously rotating the mandrel.
15. The apparatus of any of the preceding claims, wherein said support is arranged to keep the mandrel at a predetermined electrical potential.
16. The apparatus of claim 7, further comprising at least one electrically charged ring element arranged on an outer surface of the cylindrical wall.
17. The apparatus of claims 2 and 15, the apparatus being arranged to keep one of the gas and the mandrel at a positive electrical potential and the other one at a negative electrical potential.
18. The apparatus of claim 17, wherein the apparatus is arranged to keep the mandrel at a positive electrical potential and to keep the stream of gas at a negative electrical potential, and to keep the first electrode at a negative electrical potential.
19. The apparatus of claim 9, wherein the apparatus is arranged to keep said at least one screen at a negative electrical potential.
20. The apparatus of any of the preceding claims, wherein the electrical field is in the range of 0.1 to 100 kV.
21. The apparatus of any of the preceding claims, wherein the distance between the first electrode and the second electrode is in the range of 10 to 150 mm.
22. The apparatus of any of the preceding claims, wherein the distance between the first electrode and the medical device is in the range of 20 to 250 mm.
23. A method for providing a polymer coating to a medical device by electrospinning, the method comprising the steps of:
- dispersing, from a first electrode maintained at a first electrical potential, a stream of dissolved polymer toward the medical device;
- supporting the medical device at a distance from the first electrode; - maintaining a second electrical potential at a second electrode, so that an electrical field exists in between the first electrode and the second electrode, so as to convey a stream of polymer away from the first electrode under the action of the electrical field.
24. The method of claim 23, further comprising the step of conveying a stream of gas in a direction different to the direction from the first electrode to the second electrode during the step of dispersing.
25. The method of claim 23 or 24, further comprising providing, prior to the above steps, a shield for reducing exterior impacts to the stream of polymer and the electrical field.
26. The method of any of claims 21-25, wherein the support for the medical device comprises the second electrode.
27. The method of any of claims 21-26, wherein the direction from the first electrode to the second electrode is different from the direction from the first electrode to the medical device.
28. The method of any of claims 21-27, further comprising, prior to the step of dispersing, providing at least one screen at said support for the medical device for guiding the stream of polymer toward the medical device, the method comprising the further step of controlling an electrical potential at the at least one screen.
29. The method of claim 28, wherein the at least one screen comprises a first and a second screen arranged at respective opposite ends of the medical device, and wherein said step of controlling comprising controlling respective potentials at the first and second screens.
30. The method of claim 29, wherein the potentials at the first and second screens are negative.
31. The method of claim 30, wherein said stream of gas defines a direction which is opposite to the direction from the first electrode to the second electrode.
32. The method of claim 24, wherein the electrical field and the stream of gas guide the dissolved polymer toward the medical device.
33. The method of any of claims 21-32, wherein said support comprises a mandrel, the method further comprising the step of continuously rotating the mandrel during the step of dispersing.
34. The method of claim 33, comprising the step of maintaining the mandrel at a predetermined electrical potential.
35. The method of any of claims 21-34, wherein the shield comprises a first wall section upstream of the stream of polymer and an essentially cylindrical element extending essentially perpendicular to said first wall section at a distance from the first electrode, the method comprising the step of controlling the electrical field by means of at least one electrically charged ring element arranged on an outer surface of the cylindrical element.
36. The method of claims 24 and 34, the method comprising maintaining one of the gas and the mandrel at a positive electrical potential and the other one at a negative electrical potential.
37. The method of claim 36, comprising the steps of maintaining the mandrel at a positive electrical potential and to maintaining the stream of gas at a negative electrical potential, and wherein said predetermined electrical potential is negative.
38. The method of any of claims 21-37 wherein the electrical field is in the range of 0.1 to 100 kV.
39 The method of any of claims 21-38, wherein the distance between the first electrode and the second electrode is in the range of 10 to 150 mm.
40. The method of any of claims 21-39, wherein the distance between the first electrode and the medical device is in the range of 20 to 250 mm.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US69587605P | 2005-07-05 | 2005-07-05 | |
EP05388056.3 | 2005-07-05 | ||
US60/695,876 | 2005-07-05 | ||
EP05388056 | 2005-07-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2007003199A1 true WO2007003199A1 (en) | 2007-01-11 |
Family
ID=36918527
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DK2006/000395 WO2007003199A1 (en) | 2005-07-05 | 2006-07-05 | An electrospinning apparatus and process |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2007003199A1 (en) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102433595A (en) * | 2011-12-02 | 2012-05-02 | 上海纳米技术及应用国家工程研究中心有限公司 | Method for preparing degradable polymer sacculus |
CN102965743A (en) * | 2012-12-17 | 2013-03-13 | 厦门大学 | Nanofiber low-voltage electro-spinning device with auxiliary electrodes |
WO2013123147A1 (en) * | 2012-02-14 | 2013-08-22 | Neograft Technologies, Inc. | Kink resistant graft devices and related systems and methods |
CN103484953A (en) * | 2013-09-11 | 2014-01-01 | 天津工业大学 | Disc-type needle-free electrostatic spinning device |
US8903506B2 (en) | 2011-08-12 | 2014-12-02 | Cardiac Pacemakers | Method for coating devices using electrospinning and melt blowing |
US9295541B2 (en) | 2009-12-31 | 2016-03-29 | Neograft Technologies, Inc. | Graft devices and methods of fabrication |
US9445874B2 (en) | 2010-07-19 | 2016-09-20 | Neograft Technologies, Inc. | Graft devices and methods of use |
US9855415B2 (en) | 2015-07-25 | 2018-01-02 | Cardiac Pacemakers, Inc. | Medical electrical lead with biostable PVDF-based materials |
US10465318B2 (en) | 2016-12-27 | 2019-11-05 | Boston Scientific Scimed Inc | Degradable scaffolding for electrospinning |
CN113293449A (en) * | 2021-07-27 | 2021-08-24 | 兴晔新材料(南通)有限公司 | Preparation method of high-temperature-resistant artificial fiber |
US11155933B2 (en) | 2013-07-22 | 2021-10-26 | Cardiac Pacemakers, Inc. | Lubricious, biocompatible hydrophilic thermoset coating using interpenetrating hydrogel networks |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030168756A1 (en) * | 2002-03-08 | 2003-09-11 | Balkus Kenneth J. | Electrospinning of polymer and mesoporous composite fibers |
WO2003080905A1 (en) * | 2002-03-26 | 2003-10-02 | Nano Technics Co., Ltd. | A manufacturing device and the method of preparing for the nanofibers via electro-blown spinning process |
WO2004016839A1 (en) * | 2002-08-16 | 2004-02-26 | Samshin Creation Co., Ltd. | Apparatus for producing nanofiber utilizing electrospinning and nozzle pack for the apparatus |
US20040137225A1 (en) * | 2002-06-21 | 2004-07-15 | Balkus Kenneth J. | Electrospun mesoporous molecular sieve fibers |
WO2005033381A2 (en) * | 2003-10-01 | 2005-04-14 | Stonybrook Technology And Applied Research | Electro-blowing technology for fabrication of fibrous articles and its applications of hyaluronan |
-
2006
- 2006-07-05 WO PCT/DK2006/000395 patent/WO2007003199A1/en active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030168756A1 (en) * | 2002-03-08 | 2003-09-11 | Balkus Kenneth J. | Electrospinning of polymer and mesoporous composite fibers |
WO2003080905A1 (en) * | 2002-03-26 | 2003-10-02 | Nano Technics Co., Ltd. | A manufacturing device and the method of preparing for the nanofibers via electro-blown spinning process |
US20040137225A1 (en) * | 2002-06-21 | 2004-07-15 | Balkus Kenneth J. | Electrospun mesoporous molecular sieve fibers |
WO2004016839A1 (en) * | 2002-08-16 | 2004-02-26 | Samshin Creation Co., Ltd. | Apparatus for producing nanofiber utilizing electrospinning and nozzle pack for the apparatus |
WO2005033381A2 (en) * | 2003-10-01 | 2005-04-14 | Stonybrook Technology And Applied Research | Electro-blowing technology for fabrication of fibrous articles and its applications of hyaluronan |
Non-Patent Citations (2)
Title |
---|
BOLAND E D ET AL: "Electrospinning polydioxanone for biomedical applications", ACTA BIOMATERIALIA, ELSEVIER, AMSTERDAM, NL, vol. 1, no. 1, January 2005 (2005-01-01), pages 115 - 123, XP004666954, ISSN: 1742-7061 * |
WANG X ET AL: "Formation of water-resistant hyaluronic acid nanofibers by blowing-assisted electro-spinning and non-toxic post treatments", POLYMER, ELSEVIER SCIENCE PUBLISHERS B.V, GB, vol. 46, no. 13, 17 June 2005 (2005-06-17), pages 4853 - 4867, XP004904232, ISSN: 0032-3861 * |
Cited By (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10149750B2 (en) | 2009-12-31 | 2018-12-11 | Neograft Technologies, Inc. | Graft devices and methods of fabrication |
US9295541B2 (en) | 2009-12-31 | 2016-03-29 | Neograft Technologies, Inc. | Graft devices and methods of fabrication |
US9445874B2 (en) | 2010-07-19 | 2016-09-20 | Neograft Technologies, Inc. | Graft devices and methods of use |
US10239071B2 (en) | 2010-07-19 | 2019-03-26 | Neograft Technologies, Inc. | Graft devices and methods of use |
US8965531B2 (en) | 2011-08-12 | 2015-02-24 | Cardiac Pacemakers, Inc. | Method for coating devices using electrospinning and melt blowing |
US9132269B2 (en) | 2011-08-12 | 2015-09-15 | Cardiac Pacemakers, Inc. | Method for coating devices using electrospinning |
US9415206B2 (en) | 2011-08-12 | 2016-08-16 | Cardiac Pacemakers, Inc. | Method for coating devices using electrospinning |
US8903506B2 (en) | 2011-08-12 | 2014-12-02 | Cardiac Pacemakers | Method for coating devices using electrospinning and melt blowing |
CN102433595A (en) * | 2011-12-02 | 2012-05-02 | 上海纳米技术及应用国家工程研究中心有限公司 | Method for preparing degradable polymer sacculus |
WO2013123147A1 (en) * | 2012-02-14 | 2013-08-22 | Neograft Technologies, Inc. | Kink resistant graft devices and related systems and methods |
EP2814425A4 (en) * | 2012-02-14 | 2015-10-07 | Neograft Technologies Inc | Kink resistant graft devices and related systems and methods |
CN102965743A (en) * | 2012-12-17 | 2013-03-13 | 厦门大学 | Nanofiber low-voltage electro-spinning device with auxiliary electrodes |
US11155933B2 (en) | 2013-07-22 | 2021-10-26 | Cardiac Pacemakers, Inc. | Lubricious, biocompatible hydrophilic thermoset coating using interpenetrating hydrogel networks |
CN103484953A (en) * | 2013-09-11 | 2014-01-01 | 天津工业大学 | Disc-type needle-free electrostatic spinning device |
US9855415B2 (en) | 2015-07-25 | 2018-01-02 | Cardiac Pacemakers, Inc. | Medical electrical lead with biostable PVDF-based materials |
US10465318B2 (en) | 2016-12-27 | 2019-11-05 | Boston Scientific Scimed Inc | Degradable scaffolding for electrospinning |
CN113293449A (en) * | 2021-07-27 | 2021-08-24 | 兴晔新材料(南通)有限公司 | Preparation method of high-temperature-resistant artificial fiber |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2007003199A1 (en) | An electrospinning apparatus and process | |
US8226603B2 (en) | Expandable member having a covering formed of a fibrous matrix for intraluminal drug delivery | |
US8076529B2 (en) | Expandable member formed of a fibrous matrix for intraluminal drug delivery | |
US7276271B2 (en) | Polymer fiber tubular structure having kinking resistance | |
EP1377420B1 (en) | Portable electrospinning device | |
US7507433B2 (en) | Method of coating a medical device using an electrowetting process | |
US8049061B2 (en) | Expandable member formed of a fibrous matrix having hydrogel polymer for intraluminal drug delivery | |
Bera | Literature review on electrospinning process (a fascinating fiber fabrication technique) | |
Garg et al. | Electrospinning jets and nanofibrous structures | |
US8637109B2 (en) | Manufacturing methods for covering endoluminal prostheses | |
US20070255206A1 (en) | Balloon for Use in Angioplasty | |
US8992817B2 (en) | Process of making a medical balloon | |
US9987478B2 (en) | Method for making a tubular medical device | |
US20070254091A1 (en) | System and method for electrostatic-assisted spray coating of a medical device | |
US20080286440A1 (en) | Process for coating a substrate | |
US20070232996A1 (en) | Balloon for Use in Angioplasty with an Outer Layer of Nanofibers | |
WO2005039664A9 (en) | Medical device with electrospun nanofibers | |
EP3862468A1 (en) | Coating production device | |
WO2008045475A1 (en) | Spraying device with improved tip and method of utilization thereof | |
WO2014118584A1 (en) | Delivering electrically charged liquids | |
Vijayakumar et al. | Electrospinning—material, techniques and biomedical applications | |
WO2014100811A1 (en) | Adhesive attachment discs | |
DE102010025302A1 (en) | Producing fiber coating or sleeve-like fleece body from electrospun fibers, comprises removing fiber from spinneret impinged with electric high voltage relative to collector and placing fiber on coaxially rotating spindle relative to nozzle | |
EP1741463A1 (en) | A guiding and an embolization catheter | |
Kim et al. | Optimum parameters for production of nanofibres based on poly (2-acrylamido-2-methyl-1-propane sulfonic acid) by electro-spinning |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWW | Wipo information: withdrawn in national office |
Country of ref document: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 06753332 Country of ref document: EP Kind code of ref document: A1 |