# Patent

## Title
Medical-surgical devices

## Abstract

An embryo replacement catheter has a flexible extruded shaft of a transparent polyurethane with a bore extending along its length. Gas bubbles of a diameter in the range 5.0 mu. to 10.0 mu. are incorporated into the thickness of the wall of the shaft by adding gas during extrusion. The bubbles are selected to increase the visibility of the catheter under ultrasound imaging whilst still enabling material flowing along the catheter to be seen. The inventive catheter is not confined to embryo replacement catheters.

## Background
BACKGROUND OF THE INVENTION
This invention relates to medico-surgical devices.
The invention is more particularly concerned with medico-surgical devices, such as catheters, that are visible under ultrasound observation.
Ultrasound imaging equipment is increasingly being used during surgical procedures to monitor the location of a device within the body. The visibility of a device under ultrasound depends on various factors including the difference between the acoustic impedance of the material of the device and that of the surrounding medium, such as the patient tissue or body fluid within which the device is located. This difference is relatively low with plastic devices such as catheters and may make conventional catheters difficult to locate. Even devices of metal, such as needles, present problems of visibility under ultrasound observation because of the directional nature of the reflections. In some orientations a metal needle may be clearly visible but in other orientations it may be considerably less visible.
Attempts have been made to increase the visibility of medico-surgical devices under ultrasound observation in various ways. The surface of the device may be modified, such as by forming grooves or indentations in its surface. A reflective coating may be applied to the device, such as incorporating bubbles, as described in WO98/19713 and EP0624342. Alternatively, a metal marker may be secured to a plastics catheter.
BRIEF SUMMARY OF THE INVENTION
It is an object of the present invention to provide an alternative medico-surgical device.
According to one aspect of the present invention there is provided a medico-surgical device of a plastics material, the material including gas bubbles through the major part of the thickness of the material in at least a part of the device such as to increase the visibility of the device under ultrasound imaging.
The device is preferably tubular and the gas bubbles may be provided around the entire circumference of the device or may be provided in a region of the device occupying only a part of the circumference of the device, such as a strip extending along the length of the device. The outer surface of the device may be smooth and uninterrupted by gas bubbles, and the device may have an inner surface that is smooth and uninterrupted by gas bubbles. The bubbles may have a diameter in the range 1.mu. to 50.mu. and preferably have a diameter in the range 5.mu. to 10.mu. The bubbles may be substantially spherical. The device may be extruded, the gas bubbles being formed by addition of gas during extrusion of the device. Alternatively, the gas bubbles may be formed by a chemical foaming agent or by the incorporation of hollow microspheres into the plastics material. The plastics material is preferably substantially transparent, the size and density of the bubbles being selected such as to enable material flowing along the device to be viewed by the eye. The plastics material may be polyurethane.
According to another aspect of the present invention there is provided an embryo replacement catheter comprising a flexible, hollow, extruded shaft of a substantially transparent plastics material, the shaft including gas bubbles through the thickness of its wall, the density and size of the bubbles being selected to increase visibility of the catheter under ultrasound imaging whilst enabling an embryo within the catheter to be viewed by the eye, and the bore of the catheter being smooth and uninterrupted by the gas bubbles.
According to a further aspect of the present invention there is provided a method of making a medico-surgical device comprising the steps of extruding a plastics material while incorporating a gas into the wall of the device such as to form gas bubbles through the major part of the thickness of the wall of the device sufficient to increase the visibility of the device under ultrasound observation.
According to a fourth aspect of the present invention there is provided a method of making a medico-surgical device comprising forming a wall of a plastics material containing a chemical foaming agent such as to form gas bubbles through the major part of the thickness of the wall of the device sufficient to increase the visibility of the device under ultrasound observation.
According to a fifth aspect of the present invention there is provided a method of making a medico-surgical device comprising forming a wall of a plastics material containing hollow microspheres such as to form gas bubbles through the major part of the thickness of the wall of the device sufficient to increase the visibility of the device under ultrasound observation.
According to a sixth aspect of the present invention there is provided a device made by a method according to the above further aspect of the present invention.
According to a seventh aspect of the present invention, there is provided a nerve blocker catheter to administer a local anesthetic to a patient.
The different embodiments of catheters, including an embryo-transfer catheter and a nerve block catheter and their method of manufacture, according to the present invention, will now be described, by way of example, with reference to the accompanying drawings.



BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a side elevation view of the catheter;
FIG. 2 is a sectional side elevation view of a part of the catheter of FIG. 1 to a larger scale;
FIG. 3 illustrates schematically manufacture of the catheter;
FIG. 4 is a sectional transverse view through an alternative catheter;
FIG. 5 is yet another alternative embodiment catheter;
FIG. 6 shows an embodiment of the catheter of FIG. 5 having an open forward end;
FIG. 7 shows an embodiment of the catheter of FIG. 5 having a closed end with lateral eyes or aperture openings;
FIG. 8 is a cross sectional view of the FIG. 7 catheter at section VIII-VIII; and
FIG. 9 is an enlarged cut away view of one of the openings of the catheter shown in FIGS. 7 and 8.



DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
With reference first to FIGS. 1 and 2, the catheter comprises a flexible shaft 1 and a hub 2 joined at the rear end of the shaft. The shaft 1 has a circular section and a bore 10 extending along its length. The shaft 1 opens at its forward, right-hand, patient end 11, which is atraumatically rounded. The shaft 1 is extruded from a clear, transparent polyurethane material and incorporates small, gas-filled bubbles 12 the size and distribution of which are selected to increase the visibility of the catheter under ultrasound observation. Typically, the gas bubbles have a diameter in the range of about 0.1.mu. to 300.mu., preferably being between 1.mu. and 50.mu. with the most preferred range being 5.mu. to 10.mu. The bubbles 12 extend through the entire thickness of the wall of the shaft 1 and may be spherical or of any other regular or irregular shape. The outer and inner surfaces 13 and 14 of the shaft may be smooth and uninterrupted by gas bubbles or the bubbles may break the surface.
The hub 2 serves to make connection with the shaft 1 and is moulded from a rigid, transparent plastics material, being subsequently bonded with the rear end of the shaft.
The shaft 1 is extruded in the manner shown in FIG. 3 using an extrusion machine 20. Polyurethane material 21 is heated and supplied to the extrusion head 22 in the usual way but a gas such as nitrogen of carbon dioxide is also injected through the inlet 23 under pressure into the melt. As the plastics emerges from the extrusion head 22 the gas expands to form the bubbles 12. The relatively gas-permeable nature of the plastics means that after manufacture the bubble-forming gas will quickly escape and be replaced With air.
The shaft 1 can be extruded continuously at low cost, without the need for any subsequent operations apart from attaching the hub 2 and end forming the patient end tip 11.
The catheter shaft could be formed by other melt processes, such as injection moulding or blow moulding.
The bubbles could be formed in ways other than by injection of gas into the melt. For example, chemical foaming agents could be added to the plastics material, such as: azocarbonomides, dinitrosopentmethelyene-tetramine, benzenephonohydrazine, 4,4 oxybis(benzenephonohydrazine), NN.sup.1dimethyl-NN.sup.1 dinitrosoterephthalamide, azoisobutyronitrile, sodium bicarbonate, terephthalazide or trihydrazinatrazine. Another way of forming the gas bubbles would be by incorporating a liquid into the plastics melt which volatises during the melt process. Alternatively, solid powdered dry ice (carbon dioxide) could be incorporated into the melt so that the particles of dry ice become gas bubbles during the forming process. It might be possible to use other solids which undergo sublimation in this way. The bubbles could be formed directly as a result of chemical reaction during polymerisation and or alternatively during cross-linking. The bubbles could be formed mechanically by whipping the plastics in a liquid form, such as in the manner used to form latex foam. The bubbles could be formed by the incorporation of hollow microspheres of resin or glass. Alternatively, small particles of a soluble material could be added to the plastics melt and subsequently dissolved away.
A shaft of this kind can have good visibility under ultrasound imaging without producing multiple echoes and can produce a good image regardless of the orientation of the shaft. The shaft can be made sufficiently transparent to ultrasound energy to enable material flowing along the bore of the catheter to be observed on the ultrasound image.
Because the catheter does not require any coating or separate marker there is no need for subsequent assembly operations and there is no risk of detachment. The catheter can be made of conventional medically-approved materials so does not present any new risk to the patient. Because the surface of the catheter can be smooth, the catheter can be inserted or slid through an outer tube with low friction. The smooth bore of the catheter ensures free flow along the bore, which can be important where the catheter is used to transfer embryos. The smooth surfaces also reduce the accumulation of biofilm on the catheter. The catheter can be made without the need for metal components, which can be an advantage where the catheter is used while the patient is being viewed by magnetic imaging techniques. The catheter can be completely transparent to x-rays or the plastics from which it is formed could incorporate an x-ray opaque filler, such as barium sulphate.
The bubble size and density can be selected so that the optical transparency of the plastics forming the shaft remains sufficient to enable material flowing along the shaft to be viewed by the eye.
There are various ways in which the catheter could be modified. For example, it could be preferable for the bubbles to have a non-spherical shape and be oriented in a particular direction, such as longitudinally. This could be achieved by means of an obstruction in the extrusion die that constricts and elongates the bubbles as they flow through. Such an arrangement may give an increase in ultrasound visibility whilst reducing the opacity of the shaft to the eye.
It is not essential for the bubbles to be provided around the entire circumference of the shaft. As shown in FIG. 4, the bubbles 12′ could be formed only in one or more stripes extending along the shaft 1′, such as in the stripe 40. This arrangement can be used where the shaft needs to have increased clarity so that material within the catheter can be seen by the eye. The bubble region need not be continuous along the length of the catheter. Instead, discrete separate regions with bubbles could be separated from one another along the length of the catheter by regions without bubbles. A shaft for such a catheter could be made by interrupting gas flow to the extruder. Where the bubbles are contained within a stripe, this could be interrupted to make it discontinuous by extruding the stripe using two auxiliary extruders, one having material with a blowing agent and the other having material without the blowing agent. Alternate extruders are switched on and off so that the stripe can have sections containing bubbles separated from one another by sections without bubbles. A catheter with an interrupted bubble region may give a clearer ultrasound indication of movement of the catheter along its length and may also enable clearer observation of material flowing along the catheter both by ultrasound and by the eye.
The present invention is not confined to use with embryo replacement catheters but could be used in various medico-surgical devices. An alternative exemplar device is shown in FIGS. 5 to 9 which takes the form of a peripheral nerve block (PNB) catheter, or simply nerve block catheter, that is, a catheter used to administer a local anesthetic intermittently to peripheral nerves in order to control operative, postoperative, acute or chronic pain. Without limitations to the sample dimensions disclosed herein, the exemplar catheter 100 shown in FIGS. 5-9 may be about 944 mm long with an outer diameter of about 0.83 mm and an internal diameter of about 0.41 mm. The forward end of the catheter 100 may be open 101, as illustrated in the enlarged patient end 112 of the catheter shown in FIG. 6, or it may be closed 102, as shown in the enlarged patient end 112 of FIG. 7, which also shows three lateral aperture openings or eyes 103 to 105. Per shown in the cross sectional view at VIII-VIII of FIG. 8, eyes 103, 104 and 105 are formed at 120° spacings around the catheter and spaced from the forward end by, for example, about 7 mm, 11 mm and 15 mm respectively. Each eye 103 to 105 may have a diameter of about 0.25 mm. The rear end 110 of the catheter 100 is cut square and is open without any permanently attached hub or coupling. The local anesthetic may be output at the opened end 101 of the catheter embodiment shown in FIG. 6, if the catheter is an open end catheter. Alternatively, the local anesthetic is output from the aperture openings or eyes 103-105 were the catheter the closed end catheter shown in FIG. 7. FIG. 9 shows an enlarged cut away view of a portion of the catheter of FIG. 7 showing in particular eye 103 formed through the wall of shaft 1 of the catheter. As shown in FIGS. 6 and 7, the tips of the catheter, at 101 and 102, respectively, are marked so as to enable the clinician to visually observe the tip of the catheter.
The catheter 100 is made from tubing that may be extruded from a plastics material, for example a plastic base polymer such as nylon (PA) or a nylon based polyether block amide (PEBA) that may be purchased from a number of companies including for example EMS-Grivory, Degussa and Sabic (for PA), and Arkema and Evonik (for PEBA). A foaming agent such as Safoam RIC (from Reedy International Corp) is added to the PEBA (or PA). The foaming agent, which may be in the form of a powder, is mixed with pre-dried base material together with a small amount of paraffin oil, or other suitable oil, to help the foaming agent powder adhere to the PEBA (or PA) to ensure a consistent mixture. The tubing is formed from this material mixture using a conventional screw extruder and the tubing is cooled in a water bath, then cut to form shafts of the desired length. The extrusion conditions are carefully controlled, such as the temperature, screw speed, process pressure and haul off speed in order to control the concentration of bubbles and the tube size. The concentration of bubbles in the tubing is controlled by periodically checking lengths of tubing with an ultrasound scanner. Alternatively, the lengths of tube could be cut and examined with a microscope to determine the size and number of bubbles. Appropriate adjustments to the extrusion process are made as necessary to keep the bubbles within the desired parameters. After the extruded tubing is cut to the appropriate length, the catheter 100 is finished by printing appropriate tip and distance markings 112 onto the extruded shaft lengths. Where the catheter is to have lateral eyes, the tip 102 is closed by pressing into a heated cavity and the eyes 103 to 105 are formed by any conventional technique, such as using a heated mandrel, a drill, laser or the like. There are alternative ways of producing the bubbles in the tubing instead of by the use of an added foaming agent, such as by direct gas injection to the extruder or by the inclusion of microspheres. Catheters could be formed with a thin inner and/or outer layer without bubbles.
The catheter 100 may be used intermittently for peripheral nerve block procedures to supply a liquid local anesthetic to a region of the body to control operative, postoperative, acute or chronic pain. In addition to peripheral nerve block procedures, the inventive catheter may also be used for other procedures that require the catheter to act as a conduit to convey a medicament to a region of the body of a patient. Typically, the duration of use does not exceed 72 hours. However, there are some PNB catheters sold outside the United States that have been approved with duration of use up to 30 days. The catheter 100 is usually inserted through the bore of a needle, which can then be removed over the rear end 110 of the catheter after the catheter has been properly positioned inside the patient. The catheter may or may not be used with a stylet, depending on the preference of the clinician to add rigidity to the catheter or not when he manipulates the catheter. If the clinician desires to manipulate a more rigid catheter, the stylet is threaded along the catheter. In most instances, the tip of the stylet is not extended beyond the distal end of the catheter to prevent the tip of the stylet from contacting any organ parts of the patient. The stylet is removed when the catheter is in the desired location, i.e., the distal end of the catheter where the medicament is to be output to the patient is correctly positioned. The rear end 110 of the catheter 100 is then connected to a catheter connector, such as similar to the Epifuse or Perifuse connectors available from Smiths Medical ASD, Inc, which clamp about the end of the catheter and provide a connection, possibly via Luer and non-Luer connectors, to which a syringe or the like can be connected to establish a fluid path between the catheter and the syringe or the like. The anesthetic or medication in the syringe or the like is output to the desired location of the patient via the catheter either by way of its open end, if the catheter is an open ended catheter, or by way of the lateral eyes, if the catheter is a closed end catheter, as discussed above.
It will be appreciated that very similar catheters according to the present invention can be provided for related anesthesia procedures, such as epidural, spinal or regional anesthesia procedures. Furthermore, not to be limited to regional anesthesia procedures, other catheters similar to that disclosed above may be used for intravenous (IV) therapy, cardiac therapy and other therapies where a medicament fluid has to be directed to a specific organ or location internal to a patient.
Catheters can be inserted to a patient under ultrasound guidance. The typical practice is to detect the needle placement with ultrasound and then predict or deduce the end location of the catheter tip. As the needle is inserted into the patient, ultrasound observation of the needle is possible since the metal needle (and the stylet that may be used in these procedures) may provide ultrasound reflection. However, after the needle has been removed from the catheter, it can be difficult to check the location of a prior non-inventive catheter to make sure that the catheter has not been displaced. Alternatively, previous catheters can be placed using a nerve stimulation technique but this requires special equipment, can be painful to the patient and does not give any indication that the catheter may be close to a blood vessel. Some previous catheters have been made visible under ultrasound by incorporating a metal element, such as a helical wire, within the wall of the catheter. Such elements, however, do not usually extend right to the patient end of the catheter in order to avoid the risk that the metal element be exposed. Also, such metal elements may not be compatible with MRI scanners so would have to be removed if a patient required an emergency MRI scan.
Catheters according to the present invention can be made highly visible under ultrasound scanning as gas bubbles may be provided throughout the length of the catheters so that they can be accurately placed without the need for nerve stimulation, with the tips of the catheters being able to be observed under ultrasound, for example after the needle has been removed from a catheter and/or the tip of the catheter needs to be repositioned. Ultrasound scanning also enables the catheter to be manipulated to avoid any blood vessels or other anatomical features. The catheters can be made echogenic right to the patient end tip, thereby increasing the likelihood that the catheter will be placed accurately in the targeted area and avoid hitting a nerve (paraesthesia) or blood vessels The bubbles in the wall of the catheter make it visible even at relatively steep angles of more than 45°. The catheter can be seen clearly on an ultrasound scanner even when placed relatively deep below the skin at depths of 3 cm or 4 cm. Correct placement can be confirmed at any time during use of the catheter using a conventional ultrasound scanner so that the clinician can have early warning if the catheter has migrated away from the desired site. The catheter can be provided without any metal component so that it is safe to use in an MRI environment, unlike many previous catheters having wire elements for ultrasound or X-ray use.

## Claims

1. A catheter for use in supplying a local anesthetic to a region of the body having a shaft consisting of a plastic material including gas bubbles in said plastic material through the major part of the thickness of the shaft in at least a part of the shaft, wherein said gas bubbles are selected to increase the visibility of the catheter under ultrasound imaging substantially solely by reflection of ultrasound energy at interface with the gas in the bubbles, such that the patient end of the catheter can be placed in the region under ultrasound imaging.

2. A catheter according to claim 1, wherein the patient end tip of the catheter is open.

3. A catheter according to claim 1, wherein the patient end tip of the catheter is closed and the catheter has at least one lateral eye close to the patient end through which the local anaesthetic flows from the catheter.

4. A catheter according to claim 1, wherein the gas bubbles extend along the entire length of the catheter.

5. A catheter according to claim 1, wherein said gas bubbles are formed by a chemical foaming agent.

6. A method of performing local anesthesia using a catheter according to claim 1 and including the steps of inserting the patient end tip of the catheter close to a nerve while observing the patient end tip using an ultrasound scanner from outside the body, supplying an anaesthetic along the catheter to the region of the nerve, and subsequently observing the patient end tip of the catheter using an ultrasound scanner from outside the body to check that the patient end tip of the catheter has not migrated away from the region of the nerve.

7. A catheter for use in supplying a local anesthetic to a region of a body having a shaft defined by a wall consisting of a plastic material that has gas bubbles incorporated in at least one portion of the wall along at least one part of the shaft, wherein the shaft is visible under ultrasound imaging due to the bubbles in the wall of the shaft.

8. The catheter of claim 7, wherein the bubbles are incorporated along the length and throughout the wall of the shaft.

9. The catheter of claim 7, wherein the catheter has an open patient end tip.

10. The catheter of claim 7, wherein the catheter has a closed patient end tip and at leaser one lateral eye close to the patient end tip.

11. A catheter for use in supplying a local anesthetic to a region of the body having a shaft consisting of a plastic material having solely gas bubbles in said plastic material through the major part of the thickness of the shaft in at least a part of the shaft, wherein said gas bubbles are selected to increase the visibility of the catheter under ultrasound imaging, such that the patient end of the catheter can be placed in the region under ultrasound imaging.

12. A catheter according to claim 11, wherein the patient end tip of the catheter is open.

13. A catheter according to claim 11, wherein the patient end tip of the catheter is closed and the catheter has at least one lateral eye close to the patient end through which the local anaesthetic flows from the catheter.

14. A catheter according to claim 11, wherein the gas bubbles extend along the entire length of the catheter.

15. A catheter according to claim 11, wherein said gas bubbles are formed by a chemical foaming agent.