Method of manufacturing a catheter

Abstract

Method of manufacturing a catheter, including: -at least a first dipping step including: dipping a catheter mandrel (8) in a catheter precursor bath; moving the mandrel (8) out of the bath for providing at least one first catheter layer on the mandrel (8), wherein the mandrel movement out of the bath is preferably performed at a varying speed; curing each first catheter layer; -wherein a reinforcement wire is wound onto the at least one catheter layer; -at least a second dipping step including dipping the catheter mandrel (8) in a catheter precursor bath; moving the mandrel out of the bath for providing at least one second catheter layer on the at least one first layer and the reinforcement wire, wherein the mandrel (8) movement out of the bath is preferably performed at a varying speed; curing each second catheter layer.

Description

[0001] Title: Method of manufacturing a catheter

[0002] The invention relates to a method of manufacturing a catheter.

[0003] Percutaneous Mechanical Circulatory Support (MCS) is increasingly recognized as an important adjunct in the management of challenging coronary anatomies in high risk patients among other conditions.

[0004] Heart teams may select patients for Percutaneous Coronary Intervention (PCI) over Coronary Artery Bypass Grafting (CABG) despite the presence of high-risk features like poor V function, high SYNTAX score and hemodynamic instability. Percutaneous MCS may also complement treatment of cardiogenic shock as a rescue or to limit the need for inotropes and vasopressors which are known to increase myocardial oxygen consumption and worsen prognosis.

[0005] There is international consensus on the use of percutaneous MCS in cardiovascular care with the purpose to reduce LV (left ventricle) stroke work and myocardial oxygen demand while maintaining systemic and coronary perfusion in the setting of cardiogenic shock or to provide hemodynamic support during complex cardiac procedures including HR-PCI and certain high-risk ablation procedures.

[0006] A pulsatile device like an Intra-aortic Balloon Pump (IABP) offers diastolic augmentation to increase myocardial perfusion and reduces afterload during systole to promote forward flow from the LV. However, the hemodynamic support is only very modest. A known prior art catheter system includes a iVAC 2L (http s : / / ww.pulsecath .eom / pro ducts / ivac--2I / ) which is a cardiac support catheter that is inserted across the aortic valve into the LV and that is driven by a genuine IABP console. It can generate a sufficient, pulsatile flow on top of the existing patient cardiac output. The iVAC system has shown favorable results. However, because of its diameter, only selected patients with a reasonably well condition and inner size of the artery at the insertion site, are suited to be treated with support of the 17 FriVAC 2L.

[0007] A known method for manufacturing a catheter involves extrusion of the catheter, having the advantage that relatively long catheters of small diameter can be obtained. Another method includes manufacturing long catheters from catheter sections that are glued together, wherein the individual sections have been provided via a dipping process (dip molding). Dip coating as such is commonly known, an example of the dipping process is described in US4874373.

[0008] An aspect of the invention aims to provide an improved, efficient method for manufacturing a catheter (or at least a catheter section that is to be used to form a catheter).

[0009] Another aspect of the present invention aims to further reduce the risk of vascular complications and achieve an even lower resistance in the LV outflow tract. In particular, the invention aims to provide a (e.g. pulsatile cardiac support) catheter having a relatively small diameter, preferably a diameter of only 17 Fr or even 16 Fr (i.e. 16 French scale), in an economical efficient manner. The resulting catheter can reduce the risk of vascular complications, when used in medical treatment of a patient.

[0010] Also, an aim of the invention is to provide a new catheter device that, in terms of Safety, Efficacy, Usability and Applicability, matches or exceeds the very good performance of the prior art catheter system.

[0011] According to an aspect of the invention, one or more of these goals can be achieved by the features of claim 1.

[0012] Advantageously, there is provided a method of manufacturing a catheter, including:

[0013] -at least a first dipping step including: dipping a catheter mandrel in a catheter precursor bath; moving the mandrel out of the bath for providing at least one first catheter layer on the mandrel, wherein the mandrel movement out of the bath is preferably performed at a varying speed; curing each first catheter layer;

[0014] -wherein a reinforcement wire is wound onto the at least one catheter layer;

[0015] -at least a second dipping step including dipping the catheter mandrel in a catheter precursor bath; moving the mandrel out of the bath for providing at least one second catheter layer on the at least one first layer and the reinforcement wire, wherein the mandrel movement out of the bath is preferably performed at a varying speed; curing each second catheter layer; and

[0016] -removing the catheter mandrel from the cured catheter layers and embedded reinforcement wire to provide a catheter section (of the catheter).

[0017] It has been found that in this way, a durable reliable catheter can be manufactured, in an efficient manner.

[0018] According to an embodiment, the formed catheter section as such can be long enough so that it can provide the catheter that is to be manufactured.

[0019] According to an embodiment, the method includes providing a plurality of catheter sections and gluing the sections together, preferably via intermediate catheter connector sections (to form the catheter).

[0020] A respective catheter section can be made relatively long, e.g. at least 40 or 50 cm, or even at least 100 cm, so that a relatively small number of catheter sections has to be prepared for providing a relatively long catheter.

[0021] Further, the method preferably includes providing a catheter valve section (which can also be called a section of the catheter that is to be formed) and gluing the valve section to two catheter sections, preferably via intermediate catheter connector sections. Catheter valve sections as such as known per se, as will be appreciated by the skilled person, see e.g. the iVAC 2L system.

[0022] In each case, it has been found that good gluing results can be achieved in case the gluing includes:

[0023] -applying a (thin) layer of curable glue to a contact surface of a first catheter section;

[0024] -curing the layer of curable glue to provide a cured glue layer;

[0025] -applying a further quantity of curable clue (e.g. a plurality of glue drops) onto the cured glue layer;

[0026] - joining a contact surface of a second catheter section to the contact surface of the first catheter section, such that the contact surfaces contact each other via the cured glue layer and further quantity of curable glue; and

[0027] -curing the further quantity of curable clue.

[0028] It has been found that in this way, a very reliable, strong, catheter glue joint between two catheter sections can be achieved.

[0029] For example, said contact surfaces can be provided on respective catheter sections that have been manufactured in the above-described dipping process (i.e. via the above-mentioned dipping steps), on a said valve section and on said catheter connector sections (depending on the sections that are to be glued together).

[0030] According to a preferred embodiment, said mandrel has a low- friction outer surface, for example a poly tetr afluorethylene surface.

[0031] According to an embodiment, said reinforcement wire is made of a memory metal (e.g. nitinol).

[0032] According to a preferred embodiment, each dipping step involves using a thermoplastic polyurethane solution, for example, a tecothane<tm) solution, the solution for example including Tetrahydrofuran (THF) as a solvent.

[0033] According to a preferred embodiment, one of the curing steps (of curing a first or second catheter layer) includes a relatively short room temperature drying step, for example air drying for about 5 minutes, and an thermal treatment drying step, for example oven drying at about 60 °C for about 1 hour. Alternatively, one of the curing steps (of curing a first or second catheter layer) includes a relatively long room temperature drying step, for example air drying for several hours, without any subsequent thermal treatment drying step.

[0034] According to a preferred embodiment the first dipping step is repeated, for example at least once and preferably at least twice, to provide a plurality of first catheter layers.

[0035] According to a preferred embodiment, the second dipping step is repeated, for example at least once and preferably at least twice, to provide a plurality of second catheter layers.

[0036] According to a preferred embodiment each, catheter section is demolded from the mandrel by longitudinally tensioning the mandrel, applying alcohol, and longitudinally moving the mandrel and the catheter section with respect to each other.

[0037] Further, according to an aspect of the invention, there is provided a method of manufacturing a catheter (e.g. catheter preform or catheter section), the method including:

[0038] -dipping a catheter mandrel in a catheter precursor bath (containing catheter precursor material); and

[0039] -moving the mandrel out of the bath; wherein the mandrel movement out of the bath is performed at a varying speed.

[0040] It has been found that in this way, a relatively long catheter of small diameter can be formed, for example via a single dipping step (or by repeating the dipping steps to obtain the catheter via a stack of concentric dipping layers), so that joining separate catheter sections to form a desired long catheter can be avoided. In this way, efficient catheter manufacture can be achieved, wherein gluing together of a plurality of elongated catheter sections (to provide a long catheter) can be avoided. The resulting catheter can e.g. be used in sheathless patient treatment.

[0041] According to an embodiment, the speed of the mandrel (during mandrel withdrawal) is gradually reduced. For example, the mandrel can follow a predetermined speed profile during withdrawal. In this way, good results, with a desired substantially constant catheter diameter (viewed along the entire catheter’s longitudinal direction), can be achieved.

[0042] It is preferred that the mandrel is heated to a predetermined temperature, for example during a separate heating step temperature, before the mandrel enters the precursor bath. Mandrel heating can e.g. be halted (just) before the mandrel enters the precursor bath. Besides, a temperature of the mandrel can drop during a subsequent curing of catheter precursor (i.e. a coating) on the mandrel’s surface.

[0043] Preferably, the mandrel has an outer diameter that is smaller than 17 FR or 16 Fr.

[0044] Also, preferably, the mandrel can be coated with the precursor such that the outer diameter of the precursor coating is (at most) 17 Fr or at most 16 Fr after curing.

[0045] For example, the mandrel can be coated with the precursor such that a thickness of the coating is smaller than 0.5 mm, for example a thickness of 0.3 mm.

[0046] It should be noted that the method can be carried out using a single dipping step (and curing) step, or a number of dipping (and curing steps) to achieve a desired final catheter thickness. In particular, this can be combined with embedding a reinforcement wire in the catheter (or catheter section) as mentioned above. Further, an aspect of the invention provides a system for manufacturing a catheter, in particular for carrying out a method according to the invention. The system includes:

[0047] -a bath containing catheter precursor, preferably curable polyurethane ;

[0048] -a catheter mandrel, movable from a first position in the bath to a second position away from the bath;

[0049] -an actuator for moving the mandrel from the first to the second position;

[0050] -an actuator controller for controlling a speed of the movement of the mandrel, wherein the actuator controller is configured to apply a mandrel movement with a varying speed, in particular including a first speed at initial mandrel withdrawal and a subsequent second speed that is lower than the first speed.

[0051] In this way, the above-mentioned advantages can be achieved.

[0052] In particular, the invention can provide a relatively long catheter, of small outer diameter (preferably 17 Fr or 16 Fr). Such a catheter can be applied in high-risk I emergency patients where the catheter diameter size is too large to penetrate calcified femoral arteries.

[0053] Further extra advantageous embodiments of the invention are provided in the dependent claims.

[0054] The invention will now be explained in more detail, with reference to the drawing. Therein shows:

[0055] Figure 1 schematically a manufacturing system, during a first manufacturing step, according to an embodiment of the invention;

[0056] Figure 2 the system of Figure 1, during a second manufacturing step;

[0057] Figure 3 the system of Figure 1, during a third manufacturing step;

[0058] Figure 4 the system of Figure 1, during a fourth manufacturing step; Figure 5A part of a mandrel of the system shown in Figure 1, in side view;

[0059] Figure 5B a cross-section over hne V-V of Fig. 5A

[0060] Figure 6 a side view of a catheter, having an additional catheter unit; and

[0061] Figure 7 A a detail Q of Fig. 6, in side view;

[0062] Figure 7B a cross-section over hne VII -VII of Fig. 7A;

[0063] Figure 8 a graph of mandrel withdrawal speed versus time;

[0064] Figure 9 depicts a mandrel carrying a first catheter layer, in side view;

[0065] Figure 10 is a cross-section over line X-X of Figure 9;

[0066] Figure 11 is similar to Figure 10, showing a stack of first catheter layers on the mandrel;’

[0067] Figure 12 is similar to Figure 9, showing the mandrel and stack of first catheter layers and reinforcement wire;

[0068] Figure 13 is a cross-section over line XIII -XIII of Figure 12;

[0069] Figure 14 is similar to Fig. 14, depicting a stack of second catheter layers on the first stack of catheter layers on the mandrel;

[0070] Figure 15 is similar to Fig. 6, showing a further example of the catheter;

[0071] Figure 16 depicts a side view of a catheter connector section of the catheter of Fig. 15;

[0072] Figure 17 depicts a side view of a catheter valve section of the catheter of Fig. 15;

[0073] Figure 18 depicts a side view of a catheter tip section of the catheter of Fig. 15;

[0074] Figure 19 depicts a first gluing step for joining catheter sections;

[0075] Figure 20 depicts a second gluing step for joining the catheter sections;

[0076] Figure 21 depicts a third step for joining the catheter sections Figure 22 schematically an alternative manufacturing system, during the first manufacturing step, according to an embodiment of the invention;

[0077] Figure 23 the system of Figure 22, during the second manufacturing step;

[0078] Figure 24 the system of Figure 22, during the third manufacturing step; and

[0079] Figure 25 the system of Figure 22, during the fourth manufacturing step.

[0080] In the present application, corresponding or similar features are denoted by corresponding or similar reference signs.

[0081] Figure 1 schematically shows a system 1 for manufacturing a catheter 20 (or catheter section). An example of a resulting catheter 20 is shown in Figures 6, 7. The catheter 20 to be formed can include a flexible tubular catheter wall 20a enclosing a single lumen 20b. According to an embodiment, the catheter 20 can be made of a single catheter section, or of a plurality of catheter sections that are joined (in particular glued) together.

[0082] The catheter 20 can include a distally open tip 20c and / or e.g. one or more side ports / openings (not shown). Also, at a proximal end the catheter can be configured to be connected to another device (that is not part of the catheter), e.g. a balloon or pump 50 or the like, e.g. via an integral connection, via a suitable connector 40 (see Figures 15-2 Inot shown) or the- like. The resulting catheter 20 can be used for patient treatment, e.g. for guiding blood through the lumen 20b from a proximal end to a distal end and / or to a said side port.

[0083] Referring to Figure 1, a catheter manufacturing system 1 (for manufacturing a respective catheter or catheter section) can include e.g.:

[0084] -at least one bath (e.g. provided by a reservoir) 4 containing (liquid) catheter precursor F; -at least one catheter mandrel 8, movable to a first position (see Figure 2) in the bath to a second position (see Figures 1, 3) away from the bath 4 (i.e. out of the precursor F);

[0085] -at least one actuator 2 for moving the mandrel from the first to the second position; and

[0086] -at least one actuator controller 3 for controlling a speed of the movement of the mandrel.

[0087] A reservoir 4 for providing the bath can be configured in various ways. For example, it can be dimensioned for receiving the entire mandrel 8, or for receiving the mandrel 8 over a desired length K of a catheter (or catheter section) 20 to be manufactured. Preferably, the precursor bath F provided by the reservoir is configured to receive a relatively large section K of the mandrel, preferably a section of at least 1 meter (so that a relatively long section of the mandrel can be wetted / coated by the precursor). In an example, the reservoir 4 can be configured to hold a precursor bath having a depth that is larger than said desired catheter (section) length K.

[0088] The bath reservoir 4 can include heating means (not shown) for heating bath contents (in particular catheter precursor F) to a predetermined temperature, for example a temperature for maintaining catheter precursor in a liquid precursor state. In the present example, the reservoir 4 holds liquid precursor such that the mandrel 8 can enter and leave the precursor via a top surface S, for example vertically (with the mandrel being held in a vertical state).

[0089] Part of the mandrel 8 is shown in more detail in Figures 5A, 5B. The mandrel can be an elongated (rigid) element, for example a long straight needle-shaped element, wire or rod, preferably having a constant circular cross-section over at least the mandrel section on which the catheter (or catheter section) is to be formed. It follows that a length L of the mandrel is the same as or larger than a desired catheter (section) length K (for example at least 40 cm or at least 1 meter). The mandrel can e.g. be made of metal, steel, stainless steel, or the-like.

[0090] According to a preferred embodiment, the mandrel 8 has a low- friction outer surface, for example a poly tetr afluorethylene surface. This can ease removal of a manufactured catheter section from the mandrel 8. For example, the mandrel 8 can be substantially made of poly tetr afluorethylene.

[0091] Preferably, the mandrel 8 has an outer diameter OM that is smaller than 17 Fr or 16 Fr, at least over a mandrel section that is to receive the coating to form the catheter (or catheter section), so that a small diameter catheter (or catheter section) can be manufactured.

[0092] The actuator 2 can e.g. include a driven, movable actuator arm (e.g. an articulated arm) or movable element or structure, that is configured to hold the mandrel 8. For example the actuator 2 can be (or be part of) a robot 2, configured to move the mandrel 8 into and out of the precursor F (e.g. in a suspended state). For example, the actuator can be a dipping robot. In the present example, a single mandrel 8 is dipped into the precursor bath F, by the actuator 2, alternatively, a plurality of spaced-apart mandrels 8 can be applied (and handled by the same actuator 2) for manufacturing a plurality of catheters (or catheter sections) at the same time.

[0093] The actuator controller 3 can e.g. be part of the actuator 2 (e.g. robot), or it can be remotely located with respect to the actuator 2. In the latter case the controller 3 and actuator 2 can be communicatively connected, e.g. via a wired or wireless communication link, such that the controller 3 can transmit suitable actuator control signals to the actuator 2 for controlling actuator operation and resulting mandrel movement. The controller 3 can e.g. be a computer, microcontroller, hardware executing actuator control software and / or the like. Preferably, the controller 3 includes a digital memory, e.g. for storing actuator control information (and for example for storing actuator control software to be executed by the controller 3 for controlling actuator operation). Also, the system can include one or more sensors (not shown) for monitoring actuator operation, e.g. for detecting actuator movement, actuator speed and / or actuator position, or for detecting mandrel movement, mandrel speed and / or mandrel position. Such one or more sensors can be integrated in the actuator, or e.g. be external sensors (e.g. an optical sensor for optically detecting a mandrel position with respect to the reservoir and / or precursor F in the reservoir 4). Resulting sensor detection results can e.g. be communicated to the controller 3 (such as via suitable communication means) to assist actuator control, for example such that the controller can check if actual actuator or mandrel movement matches a set desired actuator or mandrel movement (such as a predetermined speed profile) and / or to adjust actuator operation to match a desired movement.

[0094] According to a preferred embodiment, the actuator controller 3 is configured to apply a mandrel movement with a varying speed, in particular including a first speed at initial mandrel withdrawal and a subsequent second speed that is lower than the first speed. In particular, the controller 3 can be configured to apply a varying mandrel speed during operation. Preferably, the system is configures such that the mandrel 8 can be immersed in the catheter precursor F over a length of at least 40 cm, and preferably at least 100 cm. Preferably, the actuator controller 3 is configured to control the actuator such that the speed of the mandrel 8 is gradually, e.g. linearly, reduced during mandrel withdrawal. For example, also, it is preferred that the control of the mandrel (applied by the controller 3) is such that the speed of the mandrel follows a predetermined speed profile. A non-limiting example of such a speed profile is depicted in figure 8. Therein, it is shown that at an initial mandrel withdrawing time, a relatively high withdrawal speed vl is applied, wherein the speed is gradually reduced to a second speed v2 of zero (i.e. a final speed), the second speed being when the mandrel has been entirely lifted out of the precursor bath F by the actuator 2. Alternatively, the actuator controller 3 can be configured to control the actuator such that the speed of the mandrel 8 stays substantially constant during mandrel withdrawal.

[0095] According to a highly preferred embodiment, the precursor F is or substantially contains (liquid) curable polyurethane. For example, the precursor curable polyurethane F can be a polyurethane resin that dries (cures) in ambient air (i.e. air external of the reservoir 4). Examples of suitable curable precursor polyurethane are known per-se.

[0096] Also, for example, the precursor bath F can be a solution of polyurethane resin in a solvent, the solvent for example being tetrahydrofuran (THF), dimethylacetamide, methylene chloride, toluene, or a combination of such or other solvents.

[0097] For example, the bath F can be a thermoplastic polyurethane solution, for example, a tecothane<tm) solution, the solution for example including Tetrahydrofuran (THF) as a solvent. In a non-limiting example, Tecothan TT-1095A is used.

[0098] For example, according to an embodiment, the mandrel 8 can be dipped in a 8 - 9 % (for example about 8.4%) Tecothane-THF solution. It has been found that this last mixture makes the PU layer dry relatively fast.

[0099] According to an embodiment, operation of the system can include dip molding, i.e. dipping the catheter mandrel 8 into the polyurethane catheter precursor bath F (from a mandrel position located outside the bath F, see Figure 1), by the actuator 2 (under the control of the respective controller 3). The bath entry movement is shown in Figure 2, and it can e.g. be carried out using a substantially constant mandrel speed (e.g. relatively swiftly). Dipping can e.g. involve vertically lowering the mandrel 8 into the precursor F, via a top surface F of the precursor. As is shown, the dipping can be such that the mandrel 8 is immersed in the catheter precursor F over a relatively long length K, e.g. a length K of at least 40 cm and preferably at least 100 cm. As is mentioned before, optionally, the precursor F can be heated to a desired, predetermined precursor temperature, in particular for maintaining the precursor in a desired liquid state (and respective viscosity) as will be appreciated by the skilled person.

[0100] Next, the mandrel 8 is moved out of the bath F (the withdrawal being shown in Figure 3), at a speed v(t). This movement is preferably performed at a controlled, in particular varying speed, or alternatively at a substantially constant speed (the speed being significantly smaller than a bath entry speed of the mandrel). The mandrel 8 can e.g. be entirely moved out of the bath, wherein a final mandrel position is shown in Figure 4. The final position can be above a top surface S of the bath F, or elsewhere (remotely) from the bath F.

[0101] For example, the withdrawal speed v(t) of the mandrel 8 can be gradually, e.g. linearly, reduced during mandrel withdrawal, and / or it can follow a predetermined speed profile (see Figure 8), from a first (high) speed vl to a second speed v2 (e.g. zero).

[0102] Due to the dipping, the mandrel 8 is coated with a layer of precursor from the bath. Curing that precursor (i.e. the coating on the mandrel 8) can start immediately once the coating has left the bath F and contacts ambient air (present outside or above the bath F). Optionally, a curing agent can be applied. It follows that the curing can mainly consist of air drying. In particular, the curing can e.g. involve drying of the precursor F, e.g. under evaporation of part of the precursor and / or due to a chemical curing process and / or via a thermal curing process.

[0103] According to a preferred embodiment, leading to good results, at least one of the curing steps includes an room temperature drying step, for example air drying for about 5 minutes, and an thermal treatment drying step, for example oven drying at about (or over) 60 °C for about 1 hour. Also, a drying step can be carried out without using oven drying, e.g. in case air drying for several hours is applied. This e.g. holds for a finished base layer (consisting of all first layers) or a finished outer layer (consisting of all second layers).

[0104] The system can include e.g. an air treatment system or device, for example, a fan or the-like, for directing an air flow towards and / or away from the withdrawn mandrel 8, for example for assisting drying of the coating and / or for removing evaporated coating (such as solvent) content (if any).

[0105] According to an embodiment, after the curing of the coating has been finished, the thus formed cured precursor can be removed from the mandrel 8, to cure and to provide the catheter 20 (or catheter section) that is to be manufactured.

[0106] Preferably above bath dipping (and removing) steps can be repeated one or more times to achieve a coating consisting of several subsequent layers. This will be explained in more detail below.

[0107] In any case, a resulting cured catheter (or catheter section) 20 preferably has a thin wall 20a, e.g. the cured coating having a total thickness W that is smaller than 0.5 mm, for example a thickness of 0.3 mm (see Figure 7B). Also, it is preferred that the mandrel 8 is coated with the precursor such that the outer diameter OP of the precursor coating is (at most) 17 Fr or 16 Fr after curing.

[0108] It has been found that by removing the mandrel 8 at the above- mentioned controlled (varying) withdrawing speed, a small diameter catheter (or catheter section) can be obtained having a long length K and a constant diameter OP. Thus, a resulting long catheter 20, preferably made of polyurethane, can be made efficiently and swiftly, using relatively little processing steps.

[0109] A time period for moving the mandrel 8 from an initial position (out of the bath, see Figure 1) to a wetting position in the bath (see Figure 2) can be significantly faster than the total time required for removing the mandrel 8 from the bath again. Next, after the curing of the coating(s) has (have) been finished, the thus formed cured precursor can be removed from the mandrel 8, to cure and to provide the catheter 20 (or catheter preform) that is to be manufactured.

[0110] The removing of the cured precursor (i.e. catheter or catheter preform) 20 from the mandrel 8 can be achieved in various ways, for example using a stripping method (see below) and suitable stripping tool, (not shown).

[0111] For example, it has been found that good results are achieved in case the catheter section is demolded from the mandrel 8 by longitudinally tensioning the mandrel, applying alcohol, and longitudinally moving the mandrel 8 and the catheter section with respect to each other.

[0112] The resulting catheter (or catheter section) 20 can be subjected to with one or more subsequent treatment steps, such as manufacturing a suitable catheter tip 20c and / or one or more catheter side ports, and / or providing a catheter connector or device 40 at a proximal end. Also, optionally, the catheter (or catheter section) 20 can be provided with a valve (see valve 30 in the example of Figures 15-21) for regulating flow through a respective lumen 20b.

[0113] According to an especially advantageous aspect of the invention, the manufacturing method includes the following steps:

[0114] -at least a first dipping step including: dipping a catheter mandrel 8 in a catheter precursor bath F; moving the mandrel 8 out of the bath F for providing at least one first catheter layer on the mandrel 8, wherein the mandrel movement out of the bath is preferably performed at a varying speed, or alternatively at a substantially constant speed (as is described above), curing each first catheter layer.

[0115] In particular, Figure 9 depicts the mandrel 8, carrying a first catheter layer 21 (see Figure 10), resulting from the first dipping step. The first dipping step is preferably repeated at least once and more preferably at least twice, leading to a mandrel 8 carrying to and preferably at least three catheter layers 21, as is shown in the cross-section of Figure 11. It is then preferred that a first catheter layer 21 is not yet cured, or only partially cured, before a subsequent first catheter layer 21 is applied thereon. In particular, no dedicated thermal treatment (e.g. such as oven drying) is applied during the repeating of a first layer dipping step. Optionally, immediately after a first layer 21 has been applied, a curing agent is applied to that layer for promoting the extraction of the PU solvents (to avoid that the PU forms blisters / bubbles on the surface). Also, preferably after a first layer has been applied, it is cured via above-mentioned air drying and optional thermal treatment (e.g. oven drying). For example, the curing of a stack of first layers 21 can includes a room temperature drying step, for example air drying for about 5 minutes, and a thermal treatment drying step, for example oven drying at about 60 °C (or a higher temperature) for about 1 hour.

[0116] Good results can also be achieved in case a finished base layer, consisting of all first layers 21 is dried in the air for a relatively long time period, e.g. several hours, without any dedicated thermal treatment step (such as oven drying).

[0117] Then, after the forming of the one or more cured first catheter layers, a reinforcement wire is wound onto that at least one catheter layer.

[0118] According to an extra-advantageous embodiment, the reinforcement wire 23 is made of a memory metal (known per se).

[0119] Figures 12 and 13 depict the mandrel 8 and stack of first layers 21, on which the reinforcement wire 23 has been wound (in particular along a helical path).

[0120] Next, the reinforcement wire 23 can be embedded in a number of subsequent second first catheter layers 22. To that aim, the method includes: -at least a second dipping step including dipping the catheter mandrel in a catheter precursor bath; moving the mandrel out of the bath for providing at least one second catheter layer 22 on the at least one first layer 21 and the reinforcement wire 23, wherein the mandrel movement out of the bath is preferably performed at a varying speed (as is described above), or alternatively at a substantially constant speed; curing each second catheter layer 22.

[0121] Optionally a second catheter layer 22 is not yet cured, or only partially cured, before a subsequent second catheter layer 22 is applied thereon. In that case, no dedicated thermal treatment (e.g. such as oven drying) is applied during the repeating of a second layer dipping step.

[0122] Optionally, a curing agent can be applied to a second catheter layer 22 immediately after the mandrel has left the bath. Also, it is preferred that each second catheter layer 22 cured before a subsequent second catheter layer 22 is applied thereon. In that case, a dedicated thermal treatment (e.g. such as oven drying, as described above) is applied before or during the repeating of a second layer dipping step.

[0123] According to an embodiment, it is preferred that after all second layers 22 have been applied, a curing step is applied for curing the second layer(s), which curing step can include e.g. above-mentioned air drying (e.g. air drying for at most 10 minutes) and thermal treatment (e.g. oven drying for more than 10 minutes). For example, a stack of second layers 22 curing step can include a room temperature drying step, for example air drying for about 5 minutes, and an thermal treatment drying step, for example oven drying at about 60 °C for about 1 hour.

[0124] The process of applying subsequent second layers 22 is preferably repeated until the cumulative stack of second layers has a predetermined outer diameter. Good results can be achieved in case a finished outer layer (including the one or more second layers 22) is dried in the air for a relatively long time period, e.g. several hours, without any dedicated thermal treatment step (such as oven drying), in particular before a subsequent processing step -such as demolding- is applied.

[0125] Optionally, the mandrel is immersed in a solvent bath (e.g. a mixture of THF and Toluene) before the mandrel is immersed in a said catheter precursor bath for forming one or more of said catheter layers or layer stacks (e.g. one or more of the second catheter layers 22 or respective layer stacks).

[0126] Figure 14 schematically depicts the result of the second dipping step, wherein one or more (in this example three) second catheter layers 22 have been applied onto the first catheter layer(s) 21, and cured, thereby embedding the reinforcement wire 23. As follows from the above, preferably, more than three second layers 22 are applied, for example several stacks of second layers 22, each stack containing thee such layers 22, depending e.g. on a desired outer diameter of the catheter.

[0127] Herein, each of the dipping steps, for forming each first layer 21 and second layer 22, can be carried out e.g. by the above-described dipping system (depicted in Figures 1-4). The winding of the reinforcement wire 23 onto the first layer(s) 21 can be carried out by a suitable winding machine (known per se), which can be configured for holding the mandrel 8 (carrying the one or more first catheter layers 21) and for winding the reinforcement wire onto and along the outer surface of the one or more first catheter layers 21 (i.e. to provide a helically wound reinforcement wire). The reinforcement wire 23 is preferably would along substantially the entire length of the one or more (cured) first catheter layers, viewed along a longitudinal direction of the mandrel 8. According to a non-limiting example, the winding of the wire can involve fastening a wire spool in a holder of a winding machine, and fix the mandrel (carrying the one or more first layers) in a chuck of the winding machine. Subsequently, the winding machine can be activated to wrap the wire around the mandrel and base catheter layer(s), preferably with a constant tension. After the winding, the mandrel, carrying the base catheter layer(s) and wire, can be removed from the chuck of the winding machine, to be dipped to achieve the one or more second catheter layers.

[0128] After the application (and curing) of the one or more second layers 22 (which can serve to cover both the first layer(s) 21 and the reinforcement wire 23), in particular after the second catheter layers 22 have air dried for a relatively long time period, the catheter mandrel 8 can be removed from the cured catheter layers 21, 22 (and embedded reinforcement wire 23) to provide a resulting catheter or catheter section 20.

[0129] It has been found that efficient and reliable removing of the catheter or catheter section 20 can be achieved (i.e. demolded the section from the mandrel 8) by longitudinally tensioning the mandrel 8, applying alcohol (to the mandrel and cured catheter section), and subsequently longitudinally moving the mandrel 8 and the catheter section 20 with respect to each other. The removing can e.g. be carried out manually, and / or by a tensioning device. Optionally, the removing can be carried out using the dipping system (e.g. the robot 2) to provide the longitudinally moving of the mandrel 8, in which case e.g. a clamping device (not shown) or manual interaction can be applied for engaging an outer surface of the cured catheter or catheter section 20, to achieve demolding thereof

[0130] According to a further embodiment, the method includes providing a plurality of catheter sections and gluing the sections together, preferably via intermediate catheter connector sections (to form a catheter 120).

[0131] According to a further embodiment, including providing a catheter valve section and gluing the valve section to two catheter sections, preferably via intermediate catheter connector sections.

[0132] According to a further embodiment, the gluing includes: -applying a layer of curable glue to a contact surface of a first catheter section;

[0133] -curing the layer of curable glue to provide a cured glue layer;

[0134] -applying a further quantity of curable clue onto the cured glue layer;

[0135] - joining a contact surface of a second catheter section to the contact surface of the first catheter section, such that the contact surfaces contact each other via the cured glue layer and further quantity of curable glue; and

[0136] -curing the further quantity of curable clue.

[0137] Figures 15 depicts a side view of a catheter 120, manufactured by an afore-described method according to the present invention. In this case, the catheter 120 is made of a number of catheter sections 20 and catheter valve section 30 and intermediate connector sections 40, that have been joined by above-described gluing steps Also, the catheter 120 can include a catheter tip section 35, providing a catheter tip 120c, that can be glued to an adjoining catheter section. (preferably via the above-described gluing steps).

[0138] A catheter connector section 40 is shown in more detail in Figure 16. It can include a hollow cylindrical element (e.g. a bushing), having opposite external ring-shaped contact surfaces CS (shown in dashed lines) for receiving butt ends (inner contact surface) of catheter elements to be glued thereto. In a preferred embodiment, the catheter connector section 40 is made of metal, an alloy, nickel-titanium, or steel.

[0139] A catheter valve section 30 is shown in more detail in Figure 17. It can include a hollow cylindrical element (e.g. made of metal, an alloy, nickel-titanium, or steel) including a valve structure (known per se), and having opposite external ring-shaped contact surfaces 30S for receiving butt ends (inner contact surface) of catheter elements to be glued thereto.

[0140] A catheter tip section 35 is shown in more detail in Figure 18. It can include a hollow tip element including one or more fluid ports (known per se), and an external ring-shaped contact surface 35S for receiving butt ends (inner contact surface) of catheter elements to be glued thereto.

[0141] Figure 19 depicts a first gluing step, for joining catheter sections 20, 40 to each other. A connector section 40 is depicted, that is to be glued to two elongated catheter sections 20 that have been manufactured by the above-described dipping method. These gluing steps can also be applied for joining other catheter components to each other, such as for fixing the catheter valve section 30 to two elongated catheter sections 20 and for fixing the tip section 35 to an elongated catheter sections 20.

[0142] As follows from Figure 19, first, a layer of curable glue GL is applied onto each outer contact surface 40s of a the catheter connector section 40. Preferably, each contact surface is entirely wetted by the glue GL. Also, preferably, the glue layer is relatively thin. It is preferred that the glue GL is a so-called speed-glue or super-glue, for example glue that contains cyanoacrylate. It is preferred that each contact surface 40s is cleansed by at least one cleaning step, before the glue layer is applied thereon.

[0143] Next, after glue layer application, each glue layer is cured. For example, the curing can involve air drying (e.g. drying for at least about 30 minutes).

[0144] Figure 20 depicts a subsequent step, wherein a number of drops of (curable) glue DG (i.e. a further quantity or amount of glue) are applied onto the cured glue layer CGL.

[0145] After application of the glue drops DG, (open) butt ends of respective elongated catheter sections 20 can be joined onto the intermediate connector section 40 (indicated by arrows R). The butt end of each of the elongated catheter sections provides an inner contact surface, contacting (and snuggingly fitting onto) an outer contact surface (and respective glue layer CGL) of the connector section 40. It follows that the contact surfaces of the joined catheter sections contact each other via the cured glue layer and further quantity of curable glue. The result is shown in Figure 21.

[0146] It is preferred that each pair of joined catheter sections 20, 40 are mutually rotated (along respective center lines) as a next step, before the curable glue (of the applied glue drops GD) cures. It has been found that such mutual rotation, as indicated by arrows Y in Fig. 21, leads to improved, reliable, joining results.

[0147] In a next step, the further quantity of curable clue (of the applied glue drops GD) is being cured, thereby fixing two adjoining catheter sections 20, 40 to each other.

[0148] While this disclosure includes specific example embodiments, it will be apparent to one of ordinary skill in the art that various changes in form and details may be made in these example embodiments without departing from the scope of the claims. The example embodiments described herein are to be considered in a descriptive sense only, and not for purposes of limitation.

[0149] Herein, 16 Fr is a diameter of 16 / 3=5.3 mm (outer diameter), following Zen.wikipedia.org / wiki / French_catheter_scale.

[0150] Also, the catheter 20 can optionally be defined as an elongated tubular (flexible) medical device that is to be used for Percutaneous Coronary Intervention, for example in cooperation with a pulsatile device 10. like the Intra- aortic Balloon Pump (IABP). The catheter 20 in particular consists of a circle-cylindrical wall 20a, concentrically enclosing a single fluid channel 20b (e.g. a single lumen for guiding blood or another fluid). It will be appreciated that the ‘bare’ catheter 20 can be provided with additional catheter elements, e.g. a closed distal tip, one or more side ports (openings), integrated valve-means, a proximal connector structure (e.g. for connecting a medical device to the catheter), and / or the-like, in particular after that catheter 20 has been manufactured via the method and / or system according to the invention. While this disclosure includes specific example embodiments, it will be apparent to one of ordinary skill in the art that various changes in form and details may be made in these example embodiments without departing from the scope of the claims. The example embodiments described herein are to be considered in a descriptive sense only, and not for purposes of limitation.

[0151] Herein, 16 Fr is a diameter of 16 / 3=5.3 mm (outer diameter), following Zen.wikipedia.org / wiki / French_catheter_scale.

[0152] Also, the catheter 20 can optionally be defined as an elongated tubular (flexible) medical device that is to be used for Percutaneous Coronary Intervention, for example in cooperation with a pulsatile device 10. like the Intra- aortic Balloon Pump (IABP). The catheter 20 in particular consists of a circle-cylindrical wall 20a, concentrically enclosing a single fluid channel 20b (e.g. a single lumen for guiding blood or another fluid). It will be appreciated that the ‘bare’ catheter 20 can be provided with additional catheter elements, e.g. a closed distal tip, one or more side ports (openings), integrated valve-means, a proximal connector structure (e.g. for connecting a medical device to the catheter), and / or the-like, in particular after that catheter 20 has been manufactured via the method and / or system according to the invention.

[0153] It is further preferred that the manufacturing is mainly carried out in a Clean Room, under well controlled hygienical circumstances, as will be clear to the skilled person. Also, during the manufacturing process, preferably, several review steps are performed to check if manufactured catheter sections meet predetermined requirements (e.g. layer thickness, external diameter, et cetera).

[0154] Cleaning a catheter section, for example in preparation of a subsequent gluing step, can include e.g. a pretreatment step such as a sand blasting step. Further, according to an embodiment, an outer surface of the mandrel 8 is preferably cleansed before being dipped for the first time into the precursor bath 4. Such cleaning can e.g. include using a isopropanol I distilled water mixture or the-like, air blowing, et cetera, as will be clear to the skilled person.

[0155] It will be appreciated that the system can include various means for controlled dipping of one or more catheter mandrels 8 in a catheter precursor bath. For example, the system can include a dipping machine (known per se), and / or a dipping structure that is very similar to the structure of a 3D -printer, wherein the dipping machine only provides movement in one dimension (in particular vertically, down-and-up). An example is shown in Figures 22-25, which generally correspond to Figures 1- 4 regarding dipping functionality. For example, as follows from Figures 22- 25, such a dipping structure 1’ can include an actuator 2’, e.g. a (stepper) motor, that drives a threaded shaft 90 or belt, which causes a movable element 91 (e.g. a horizontal bar) to move up and down. The movable element 91 can e.g. be guided vertically by respective guiding structures 95. Attached to this element 91 can be a chuck 92, which is configured to releasably hold the one or more mandrels 8, to be dipped into a respective bath 4’. It will be appreciated that an array / row of multiple chucks can be implemented in the dipping machine. The system has a controller 3’ for controlling operation of the dipping structure 1’. Respective dipping steps are shown in Figures 23, 24, 25, which correspond to the dipping steps shown in Figures 2, 3 and 4, respectively (as described above).

Claims

Claims1. Method of manufacturing a catheter, including:-at least a first dipping step including: dipping a catheter mandrel (8) in a catheter precursor bath (4); moving the mandrel (8) out of the bath (4) for providing at least one first catheter layer on the mandrel (8), wherein the mandrel movement out of the bath is preferably performed at a varying speed; curing each first catheter layer;-wherein a reinforcement wire is wound onto the at least one catheter layer; -at least a second dipping step including dipping the catheter mandrel (8) in a catheter precursor bath (4); moving the mandrel out of the bath (4) for providing at least one second catheter layer on the at least one first layer and the reinforcement wire, wherein the mandrel (8) movement out of the bath is preferably performed at a varying speed; curing each second catheter layer; and-removing the catheter mandrel (8) from cured catheter layers and embedded reinforcement wire to provide a catheter section.

2. The method according to claim 1, including providing a plurality of catheter sections and gluing the sections together, preferably via intermediate catheter connector sections.

3. The method according to any of the preceding claims, including providing a catheter valve section and gluing the valve section to two catheter sections, preferably via intermediate catheter connector sections.

4. The method according to claim 2 or 3, wherein the gluing includes:--applying a layer of curable glue to a contact surface of a first catheter section;-curing the layer of curable glue to provide a cured glue layer;-applying a further quantity of curable clue onto the cured glue layer;- joining a contact surface of a second catheter section to the contact surface of the first catheter section, such that the contact surfaces contact each other via the cured glue layer and further quantity of curable glue; and -curing the further quantity of curable clue.

5. The method according to any of the preceding claims, wherein the mandrel (8) has a low-friction outer surface, for example a poly tetr afluorethylene surface.

6. The method according to any of the preceding claims, wherein the reinforcement wire is made of a memory metal, e.g. nitinol.

7. The method according to any of the preceding claims, wherein each dipping step involves using a thermoplastic polyurethane solution, for example, a tecothane<tm) solution, the solution for example including Tetrahydrofuran as a solvent.

8. The method according to any of the preceding claims, wherein at least one of the curing steps includes- a room temperature drying step, for example air drying for about 5 minutes, and optionally an thermal treatment drying step, for example oven drying at about 60 °C for about 1 hour.

9. The method according to any of the preceding claims, wherein the first dipping step is repeated, for example at least once and preferably at least twice, to provide a plurality of first catheter layers.

10. The method according to any of the preceding claims, wherein the second dipping step is repeated, for example at least once and preferably at least twice, to provide a plurality of second catheter layers.

11. The method according to any of the preceding claims, wherein each catheter section is demolded from the mandrel (8) by longitudinallytensioning the mandrel, applying alcohol, and longitudinally moving the mandrel and the catheter section with respect to each other.

12. Method of manufacturing a catheter, for example a method according to any of the preceding claims, the method including: -dipping a catheter mandrel (8) in a catheter precursor bath (4); and -moving the mandrel (8) out of the bath; wherein the mandrel movement out of the bath is performed at a varying speed.

13. Method according to any of the preceding claims wherein the mandrel is immersed in the catheter precursor (4) over a length of at least 100 cm.

14. Method according to any of the preceding claims, wherein the speed of the mandrel (8) is gradually, e.g. linearly, reduced during mandrel withdrawal.

15. Method according to any of the preceding claims, wherein the speed of the mandrel (8) follows a predetermined speed profile.

16. Method according to any of the preceding claims, wherein the precursor is or substantially contains a curable polyurethane.

17. Method according to any of the preceding claims, including curing the precursor and removing the cured precursor from the mandrel.

18. Method according to any of the preceding claims, wherein the mandrel (8) has an outer diameter that is smaller than 17 Fr or 16 Fr.

19. Method according to any of the preceding claims, wherein the mandrel is coated with the precursor such that the outer diameter of the precursor coating is 17 Fr or 16 Fr.

20. Method according to any of the preceding claims, wherein the mandrel is coated with the precursor such that a thickness of the coating is smaller than 0.5 mm, for example a thickness of 0.3 mm.

21. System for manufacturing a catheter, in particular for carrying out a method according to any of the preceding claims, wherein the system includes:-a bath (4) containing catheter precursor; -a catheter mandrel (8), movable from a first position in the bath to a second position away from the bath;-an actuator (2) for moving the mandrel from the first to the second position; -an actuator controller (3) for controlling a speed of the movement of the mandrel, wherein the actuator controller is configured to apply a mandrel movement with a varying speed, in particular including a first speed at initial mandrel withdrawal and a subsequent second speed that is lower than the first speed.

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