Combined delivery catheter system

Abstract

A combined catheter (1) comprising a tubular guide catheter (10) and a therein arranged delivery catheter (20). The tubular guide catheter comprises a proximal main portion with a pair of opposed pull wires (17), and a distal cavity portion, the pair pull wires being anchored proximally of the distal portion. The main portion has a central lumen with a first diameter and the cavity portion has a cavity (14) with a second larger diameter. The delivery catheter comprises a proximal tubular main portion and a distal hollow helical needle (30). The hollow helical needle has an outer diameter smaller than the second diameter but larger than the first diameter. The delivery catheter main portion is arranged in the guide catheter and the hollow helical needle is arranged in the guide catheter distal cavity from which it can be extended axially in a distal direction.

Description

[0001] 240046W001

[0002] 1

[0003] COMBINED DELIVERY CATHETER SYSTEM

[0004] The present invention generally relates to catheter- based cell delivery systems and components therefor adapted for delivery of a cell formulation to a tissue site. In a specific embodiment the system is adapted for delivery of a cell formulation to a myocardial treatment site.

[0005] 5 Alternatively, the disclosed catheter system may be used for delivery of fluid drugs in general to a tissue site.

[0006] BACKGROUND OF THE INVENTION

[0007] In the disclosure of the present invention reference is mostly made to the treatment of the heart

[0008] 10 by ventricular delivery of a fluid substance, however, this is only an exemplary use of the present invention.

[0009] The present invention generally relates to medical methods and systems suitable for trans- endocardial intramyocardial delivery of cellular material in the form of a fluid cell or cell aggregate substance to the heart via a peripheral artery for the treatment of e.g. acute myocardial infarction, chronic myocardial ischemia, ischemic heart failure, and nonischemic heart failure.

[0010] WO 00 / 9185 and family member US 2009 / 0177152 disclose different designs for a combined catheter comprising an outer steerable shaft from which a hollow helical delivery needle can be axially advanced, either by rotation relative to the outer shaft or by retracting a tubular sheet covering the helical needle. The hollow helical needle is supplied with torque via a solid shaft and with fluid via a separate fluid delivery tube designed to provide and allow the relative movement between the helical needle and the outer shaft. Steering of the outer shaft is provided by a pair of opposed pull wires guided in tubular lumens in the outer shaft wall, the pull

[0011] 25 wires providing deflection in a plane of the distal-most part of the outer shaft in which the helical needle initially is located.

[0012] US 11 ,986,611 discloses a catheter with an axially deployable helical infusion needle. The catheter is optimized for radial artery introduction with a small outer diameter and is not steerable on its own for which reason it has to be advanced to its delivery location via a steerable guide sheath or a guide sheath in combination with a guide wire.

[0013] US 2015 / 0005740 discloses a catheter with an axially deployable helical infusion needle. It is contemplated that the catheter may be used in combination with an insertion device which may

[0014] 35 include a steering mechanism to help deflect distal portions of the insertion device to help 240046W001

[0015] 2 navigate into and through the subject’s body, e.g. in the form of longitudinally extending pull wires.

[0016] US 2006 / 0030833 discloses a catheter with an axially deployable helical infusion needle. The

[0017] 5 catheter is steerable comprising one or more axially extending pull wires terminating at the distal end of the outer catheter. It is contemplated that the needle may have a helical or cork- screw-like shape, however, no details are disclosed enabling such a modification.

[0018] Having regard to the above, it is an object of the present invention to provide a combined

[0019] 10 steerable delivery catheter comprising an inner delivery catheter with a distal helical infusion needle axially deployable from a steerable outer shaft having a small outer diameter. In a specific aspect of the invention, it is an object to provide such a catheter assembly adapted for intramyocardial delivery of cells or cell agglomerates in a fluid suspension.

[0020] It is a further object of the invention to provide such a combined catheter in which axial advancement and rotational control of the helical needle can be provided by handle control means allowing for safe and effective operation.

[0021] It is a yet further object of the invention to provide a combined catheter in which access to the annular space between the outer shaft and the inner catheter can be controlled in a reliable and cost-effective way.

[0022] It is a yet further object of the invention to provide a cell suspension transfer system which safely and effectively can transfer a liquid cell suspension to a delivery catheter.

[0023] 25

[0024] DISCLOSURE OF THE INVENTION

[0025] In the disclosure of the present invention, embodiments and aspects will be described which will address one or more of the above objects or which will address objects apparent from the below disclosure as well as from the description of exemplary embodiments.

[0026] Thus, in a first aspect of the invention a combined catheter comprising a tubular guide catheter and a therein arranged delivery catheter is provided. The tubular guide catheter comprises a proximal main portion, a distal cavity portion, and a pair of opposed pull wires. The main portion has a tubular wall forming a central lumen with a first diameter, the distal portion has a tubular

[0027] 35 wall forming a distal cavity with a second larger diameter, and the pair of opposed pull wires arranged in the main portion wall are anchored proximally of the distal portion. The delivery 240046W001

[0028] 3 catheter comprises a proximal tubular main portion with a distal end, and a distal hollow helical needle comprising one or more outlet openings. The proximal tubular main portion has a central delivery lumen, the hollow helical needle is attached to the main portion distal end in fluid communication with the central lumen, and the hollow helical needle has an outer diameter

[0029] 5 smaller than the second diameter but larger than the first diameter. The delivery catheter main portion is arranged in the guide catheter central lumen, and the helical needle is arranged in the guide catheter distal cavity from which it can be pushed axially in a distal direction.

[0030] By this axial arrangement of structures, a self-contained combined catheter is provided which

[0031] 10 is both steerable and provides a small outer diameter allowing for more effective introduction of the combined catheter through a patient’s vasculature to a desired treatment site.

[0032] The combined catheter may comprise a handle attached to the guide catheter main portion, the handle comprising guide control means for exerting a proximally directed pulling force to the pull wires.

[0033] In an exemplary embodiment the proximal portion of the guide catheter comprises a handle portion arranged within the handle, the handle portion comprising a pair of opposed exit openings through which the pull wires exit to engage the handle control means.

[0034] The guide catheter may be provided with a proximal fluid inlet end arranged within the housing and from which the delivery catheter proximal portion exits, the delivery catheter proximal portion exiting from the housing. A flush hub may be arranged in the housing, comprising a distal end attached to the guide catheter to sealingly surround the guide catheter proximal fluid inlet,

[0035] 25 and a proximal sealing valve from which the delivery catheter proximal portion exits, the sealing valve allowing axial and rotational movement of the delivery catheter relative to the flush hub and thus the guide catheter. A flush port may be in fluid communication with an interior of the flush hub, whereby the axially extending space between the delivery catheter and the guide catheter can be flushed with a fluid via the flush port.

[0036] In an exemplary embodiment the handle comprises user actuatable clutch means operatable between a locked state in which the delivery catheter is axially locked relative to the handle, and an un-locked state in which the delivery catheter can be moved axially relative to the handle to thereby move the helical needle out of the distal cavity. By axially locked is to be under¬

[0037] 35 stood a locked state in which the delivery catheter cannot be moved axially by the user by pulling or pushing. 240046W001

[0038] 4

[0039] The handle may be provided with threaded control means allowing the delivery catheter and thus the helical needle to be moved distally by rotational movement of the delivery catheter with a movement corresponding to a pitch of the helical needle. In such an embodiment the

[0040] 5 helical needle would have a constant pitch.

[0041] In an exemplary embodiment the handle comprises an actuation member adapted to actuate the clutch means between the locked and the un-locked state when moved axially, the actuation member also serving to rotate the delivery catheter relative to the threaded control means.

[0042] 10

[0043] In exemplary embodiments each pull wire along a portion of its length is surrounded by a compression coil embedded in the wall of the guide catheter main portion and anchored axially at its ends, the compression coils providing rigidity and controlled flexibility to the guide catheter.

[0044] A primary objective of the invention relates to catheter-based cell delivery systems and components therefor adapted for delivery of a cell formulation to a tissue site, however, the disclosed catheter system may alternatively be used for delivery of fluid drug. The term "drug" is meant to encompass any drug formulation capable of being passed through a delivery catheter and into the specified target site. The drug may be a single drug compound or a premixed or co-formulated multiple drug compounds drug agent from a single reservoir. Representative drugs include pharmaceuticals such as peptides, proteins, and hormones, biologically derived or active agents, hormonal and gene-based agents, nutritional formulas and other substances in both suspended and liquid form.

[0045] 25 BRIEF DESCRIPTION OF THE DRAWINGS

[0046] In the following exemplary embodiments of the invention will be described with reference to the drawings, wherein: fig. 1 shows a perspective view of a catheter assembly comprising a combined catheter and a handle, the combined catheter comprising an outer guide catheter and an inner delivery catheter, fig. 2 shows a perspective detail view of the distal-most portion of the catheter of fig. 1 , fig. 3 shows an x-ray view of the guide catheter distal portion, fig. 4 shows a longitudinal cross-sectional view of the combined catheter distal end,

[0047] 35 fig. 5 shows a transversal cross-sectional view of the combined catheter, fig. 6 shows an exploded view of the handle, 240046W001

[0048] 5 fig. 7 shows the handle seen from below with a lower housing portion removed, fig. 8 shows a longitudinal cross-sectional view of the handle as shown in fig. 7, fig. 9 shows the components of a dose delivery device, fig. 10 shows a longitudinal cross-sectional of the dose delivery device of fig. 9 in an assembled

[0049] 5 state, and fig. 11 shows an alternative configuration of a dose delivery device to be used in combination with a syringe.

[0050] In the figures like structures are mainly identified by like reference numerals.

[0051] 10

[0052] DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0053] When in the following terms such as “upper” and “lower”, “right” and “left”, “horizontal” and “vertical” or similar relative expressions are used, these only refer to the appended figures and not necessarily to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only. When the term member or element is used for a given component, it generally indicates that in the described embodiment the component is a unitary component, however, the same member or element may alternatively comprise a number of sub-components just as two or more of the described components could be provided as unitary components, e.g. manufactured as a single injection moulded part. The terms “assembly” and “subassembly” do not imply that the described components necessarily can be assembled to provide a unitary or functional assembly or subassembly during a given assembly procedure but is merely used to describe components grouped together as being functionally more closely related.

[0054] 25

[0055] With reference to figs. 1-8 an exemplary embodiment of a catheter-based cell delivery system will be described, the system comprising a catheter assembly 1 comprising a steerable tubular guide catheter and a therein arranged fluid delivery catheter, as well as a dose control device adapted to supply a cell suspension to the fluid delivery catheter. For illustrative purposes, in the figures the catheters are shown having a reduced length. In an exemplary actual embodiment, the free length of the guide catheter is approximately 110 cm and the full length of the delivery catheter from the distal tip to the proximal injection port is approximately 150 cm.

[0056] As shown in fig. 1 the assembly comprises a main or outer shaft 10 in the form of a steerable

[0057] 35 tubular guide catheter attached to a handle 100, and an inner shaft 20 in the form of a fluid delivery catheter arranged rotationally and axially moveable within the guide catheter and 240046W001

[0058] 6 extending through the handle, the delivery catheter comprising a distal helical delivery needle 30. The handle comprises a deflection control member 200 for controlling deflection of the distal end of the guide catheter, a combined control member 300 for controlling axial and rotational movement of the fluid delivery catheter relative to the guide catheter, a proximal injection

[0059] 5 port 400 in fluid communication with the fluid delivery catheter, a flush port 500 in fluid communication with the tubular space between the guide and delivery catheter, and a wire connector 600 communicating with the helical needle 30.

[0060] Fig. 2 shows a detail view of the distal end 13 of the guide catheter 10 with the helical needle

[0061] 10 30 mounted on the delivery catheter 20 extending therefrom. As will be described in greater detail below, the helical needle can be moved axially between a retracted position in which the helical needle is housed inside the guide catheter distal end, and an extended position as shown.

[0062] The hollow helical needle 30 is in an exemplary embodiment manufactured from stainless steel 304 (SS304) and comprises an atraumatic distal tip 31 and one or more exit openings 32 in the distal part for delivery of a fluid suspension to a treatment site. In an exemplary embodiment the helical needle is formed from tubing with a 0.25 mm ID and a 0.50 mm OD (25G), the helix having a 1 .6 mm OD and comprising three coils with a 1 mm pitch and a proximal centred stem portion 35 attached in fluid communication to the distal end of the delivery catheter, e.g. by welding.

[0063] Referring to figs. 3-6 the guide catheter 10 comprises a dual deflection main portion adapted to navigate through vasculature and carry the needle housed in the distal tip portion 13 to the

[0064] 25 desired location.

[0065] The main portion has a tubular wall 11 forming a central lumen 12 through which the delivery catheter 20 extends thereby forming an axially extending circular space 12A. Along most of its length the tubular wall comprises an embedded helical braiding formed from stainless steel threads. The braiding may vary along the length of the guide catheter (e.g. material, dimensions, and pitch) to provide the desired amount of pushability, flexibility and torqueability. The wall may be made from reflowing Pebax ® (a block copolymer variation of PEBA) of different stiffness over the braid and an inner liner, e.g. made from polyimide (PI). The tubular wall comprises a pair of opposed tubular lumens 15 in which a pair of corresponding compression

[0066] 35 coils 16 are embedded, the coils terminating at a distance from an embedded distal pull ring 19. Extending through the compression coils a pair of axially moveable pull wires 17 are 240046W001

[0067] 7 arranged, the pull wires being connected to the deflection control member 200 at their proximal ends and to the pull ring 19 at their distal ends, this allowing the distal end of the guide catheter to be deflected in a plane. The compression coils reduce the guide catheter’s tendency to buckle when the pull wires are actuated. In an exemplary embodiment the diameter of the pull

[0068] 5 wire is 0.20 mm, the inner diameter of the compression coil is 0.23 mm, and the outer diameter of the compression coil is 0.38 mm.

[0069] In the following an exemplary way of manufacturing the guide catheter will be described. As a first step a Teflon line is stretched over the length of an inner lumen mandrel. All second lumens

[0070] 10 are then position over the main lumen Teflon liner. At this point, the second lumens are a combination of their desired material composition (Teflon or Polyimide) and small mandrels to control their shape and position. At this point, the assembly of components is being “locked in” by assembling the braid made from SS304. This is performed in equipment referred as a braider that braids a number of specified stainless-steel wires in an orderly manner, respecting the pitch of the different sections of the shaft. This is typically programmed into the equipment, so it is the same every time. Once braiding is completed, the PEBAX extrusion segments are fed on the braided assembly as specified by the design. Harder durometer is used to give the shaft stiffness and torqueability and softer durometer is used to create the deflection segments. Once all the extrusions are positioned, a long PET heat-shrink if positioned over the assembly. Once in place, both ends of the PET are shrinked in place using a heat gun to “lock” everything in place. The assembly is now ready to be reflowed using proprietary equipment. This equipment is normally a motorized hot air machine that very slowly run a circular die feeding hot air on along the length of the assembly. This can be performed horizontally or vertically but vertically better ensures that the shaft remains axially symmetrical. The hot air essentially melts

[0071] 25 the PEBAX briefly allowing it to both bite in the braid and ensure smooth transition between the different durometer extrusions. Once cooled the PET is cut out and the shaft is revealed. For a complex design, this last step is repeated a couple of times in phases to allow assembly of the pull wires and the compression coils which require the second lumens mandrel to be removed if present. At this point there is normally some finishing work performed on the PEBAX to ensure that there are no sharp edges on the ends, that the shaft, pull wires and compression coils are cut to length, etc. The main lumen mandrel is then pulled out and the assembled shaft is completed. The shaft is then annealed to ensure that it will maintain its shape and dimensions during aging as polymer may shrink with time and braid may relax during the same period so annealing reduces this phenomenon before the shaft can be used as part of the assembly.

[0072] 35 240046W001

[0073] 8

[0074] The tubular distal tip portion 13 has the same OD as the main portion but a lumen with a larger ID, the lumen forming a cavity 14 for housing the helical needle during advancement of the combined catheter. The distal tip portion is relatively soft and flexible comprising no braiding and being manufactured from a softer material than the neighbouring portion of the catheter.

[0075] 5 The tip portion comprises a distal embedded marker band 13A allowing the distal tip to be observed by e.g. X-ray during operation.

[0076] The proximal main portion of the delivery catheter to which the helical needle is attached comprises as the core component a stainless-steel tube 22 with a plurality of laser cut transversal

[0077] 10 slots along its length, the specific cut pattern providing the desired balance of flexibility, pushability and torque transmission. The laser cut tube (LCT) is embedded in inner and outer layers 23, 24 of e.g. Pebax ® 35D. The inner fluid transmission lumen 21 is provided with an inner liner 25 of e.g. PI. In fig. 4 the delivery catheter is shown without the helical needle.

[0078] Turning to fig. 6 an exploded view of the handle 100 is shown. The handle comprises an upper housing part 110 with a cylindrical proximal bore portion 111 having an inner thread 112 (see fig. 8), and a lower housing portion 120. In the housing three main subassemblies are housed: In the distal portion a deflection control assembly for the guide catheter is arranged, in the middle portion a flush assembly is arranged, and at the proximal end a combined control assembly for the delivery catheter is arranged.

[0079] The deflection control assembly comprises upper and lower control discs 210, 220 between which a pair of opposed disc dowel pins 230 are held in place. The interior discs are attached non-rotationally to the exterior deflection control member 200 by locking screw 240. A user¬

[0080] 25 operatable disc / cap 245 is attached to the locking screw allowing a user to lock the control member 200 in a desired rotational position. For easy operation the control member is provided with an opposed pair of downwardly oriented arms 201 . A pair of opposed housing dowel pins 130 are mounted in the housing just as the housing comprises a pair of anchor points 121 for the compression coils. Attachment of the pull wires to the deflection control assembly will be described below with reference to fig. 7.

[0081] The flush assembly comprises a tubular flush hub 510 with a distal opening to which the guide catheter proximal end is fixedly attached. At the proximal end a flush manifold 520 provides fluid communication between the flush port 500 and the interior of the flush hub via flush tube

[0082] 35 530. The proximal end of the flush hub is sealed with a gasket member 511 comprising a 240046W001

[0083] 9 central opening allowing the delivery to pass through in sliding and sealing engagement. A couple of bracket members 540 position the flush hub inside the housing.

[0084] The combined control assembly comprises a generally tubular anchor member 310 with an

[0085] 5 axially extending bore and a distal thread 312 in engagement with the housing bore thread 112, the main proximal portion of the anchor member extending proximally from the housing bore. The generally tubular combined control member 300 is mounted in axially splined engagement with the anchor member and axially moveable thereon between a proximal and a distal position. The combined control member 300 comprises a distal circular opening rotation-

[0086] 10 ally and axially engaging the housing proximal portion 111. The anchor member 310 comprises a pair of opposed cut-outs 313 in the tubular wall in which a pair of clutch pins 320 are arranged, the clutch pins engaging a tubular elastomeric pinching clutch member 330 arranged in the anchor member bore to provide an actuatable clutch. The combined control member 300 further comprises a pair of opposed inner grooves 305 adapted to receive and actuate the clutch pins when the combined control member is moved between its proximal and a distal position as will be described in greater detail below.

[0087] The handle 100 is adapted to receive the delivery catheter and provide axial and rotational control thereof. To provide support to the delivery catheter it is enforced by sections of hypotube bonded to the exterior thereof. A first section 410 of hypotube is provided on the delivery catheter portion running through the flush hub (see fig. 7), and a second section 420 of hypotube is provided on the portion running through the anchor member. The second section hypotube terminates proximally in an axial control member 430 allowing a user to grip and axially move the delivery catheter. On the second section hypotube 420 a stopper member 440 is

[0088] 25 arranged, the stopper member engaging axial stops in the anchor member bore to thereby limit axial movement of the delivery catheter between a fully retracted and a fully extended position. As shown in fig. 7 a gap 411 is formed between the first and second sections of hypotube, this allowing the ECG wire to be connected to the conducting delivery catheter core member 22. A third section 450 of hypotube supports the delivery catheter between the axial control member 430 and the flush port 400. In an exemplary embodiment the first and second sections of hypotube are manufactured from SS304 and the third section is manufactured from a clear kink resistant polymer tube made of DEHP-Free PVC. Between the flush hub and the anchor member a support disc 340 for the delivery catheter is provided.

[0089] 35 In fig. 7 the handle 100 is shown seen from below without the lower housing portion 120 and the lower control disc 220 mounted, however, in contrast to fig. 6 the guide catheter 10 and 240046W001

[0090] 10 the delivery catheter 20 are shown. The guide catheter 10 enters the distal end of the handle and continues past the deflection control assembly to the flush hub 510 distal opening to which the guide catheter proximal end is fixedly attached. Corresponding to the distal end of the handle, the guide catheter comprises a pair of opposed exit openings 15A in communication

[0091] 5 with the corresponding tubular lumens 15 from which the compression coils and the therein arranged pull wires exit. In this way the integration of the guide catheter with the deflection control assembly respectively the flush hub is axially separated. The compression coils 16 proximal ends are attached to the anchor points 121 whereas the pull wires 17 are terminated as loops 17A using stainless crimp tubing 17B and continue in sliding engagement with the

[0092] 10 housing dowel pins 130 to the disc dowel pins 230 to which they are looped around. When the control discs are rotated via the deflection control member 200 a pulling respectively a pushing force are exerted on the distal pull ring 19 via the pull wires 17 causing the distal end of the guide catheter to deflect in a plane. For a desired degree of deflection, the deflection control member can be rotationally locked by tightening the locking screw 240.

[0093] In the middle portion of the handle the tubular flush hub 510 is mounted by brackets 540. The delivery catheter exits the guide catheter at the flush hub distal end, passes axially through the flush hub and exits through the gasket member 511. Corresponding to the flush hub and the gasket member, the guide catheter is embedded in the first section 410 of hypotube. By this arrangement the cylindrical space between the guide and delivery catheter can be flushed from the flush port 500 via the flush tube 530, the flush manifold 520 and the flush hub 510. Corresponding to the flush hub the ECG wire connects to the conducting metallic core of the delivery catheter.

[0094] 25 Proximally of the flush hub the delivery catheter passes through the anchor member 310 of the combined control assembly and exits the handle at the proximal end at which point it passes through the axial control member 430 to subsequently terminate at the injection port 400. The functionality of the combined control assembly will be described in greater detail with reference to fig. 8.

[0095] As also described above with reference to fig. 6 the combined control assembly comprises a generally tubular anchor member 310 in threaded engagement with the housing. The anchor member comprises a pair of clutch pins 320 received in corresponding handle actuation grooves 305 serving to actuate the clutch by moving the clutch pins inwards by axial movement

[0096] 35 of the combined control member to thereby compress the clutch member 330. As the delivery catheter 20 passes through the tubular clutch member compression thereof will pinch the 240046W001

[0097] 11 delivery catheter and thus hold it axially and rotationally in place relative to the anchor member. Correspondingly, the combined control member can be moved axially to release pressure on the clutch pins and thereby also the clutch member 330, this releasing the holding grip on the delivery catheter allowing it to move axially and rotationally relative to the anchor member. In

[0098] 5 the shown embodiment axial movement of the combined control member is limited by the length of the groove 305 traveling over the clutch pins 320. During assembly the combined control member is mounted on the housing by axially forcing the combined control member distally over the clutch pins and the elastomeric clutch member 330.

[0099] 10 In the shown embodiment the combined control member has a first axial position in which the fluid delivery catheter is axially and rotationally locked relative to the anchor member (and thus the housing and the guide catheter) and in which rotational movement of the control member causes rotational movement of the fluid delivery catheter, and a second axial position in which the fluid delivery catheter is axially and rotationally free relative to the housing and thus the guide catheter, this allowing the delivery catheter to be moved axially (and rotationally) by means of the axial control member 430, the amount of axial movement being limited by the distal and proximal stop surfaces engaging the stopper member 440 inside the anchor member. In the shown embodiment the first axial position is a distal-most position of the combined control member relative to the housing and the second axial position is a proximal-most position of the combined control member relative to the housing.

[0100] As follows from the treaded engagement 112, 312 between the anchor member and the housing, when the combined control member is in the first axial position, the clutch is actuated and the fluid delivery catheter is coupled axially and rotationally locked to the anchor member,

[0101] 25 whereby rotational movement of the combined control member causes axial movement of the “axially locked” fluid delivery device corresponding to the threaded engagement between the anchor member and the housing. In an exemplary embodiment the threaded engagement between the anchor member and the housing has the same pitch as the helical needle whereby rotation of the combined control member is transferred 1 :1 to the helical needle. Correspondingly, the length of the thread may correspond to the length of the helical needle.

[0102] In a situation of use the catheter assembly is prepared before operation by moving the combined control member to its second axial position to unlock the clutch, this allowing the helical needle to be moved axially to its fully retracted position inside the distal cavity of the guide

[0103] 35 catheter, and the anchor member to be rotated to its proximal-most position. When this is assured the combined control member is moved to its first axial position to lock the clutch. 240046W001

[0104] 12

[0105] Fluid may be introduced through the flush port and the injection port to purge air from the catheter assembly. As the fluid contained in the delivery catheter represents a dead space for the treatment fluid or fluid suspension to be introduced into the target tissue via the helical needle, the guide catheter may be loaded with the treatment fluid at this point. Alternatively,

[0106] 5 the dead space may be purged just prior to the helical needle being advanced into the target tissue. In an aspect of the invention a suspension transfer device is provided which will be described below.

[0107] The catheter is now ready for introduction into the vasculature of a patient. Using the flexibility,

[0108] 10 pushability, torqueability and the ability to control and lock deflection of the distal tip of the guide catheter, the skilled surgeon will manoeuvre the distal end of the guide catheter into the vicinity of the treatment site, e.g. at a desired location in the heart for subsequent injection of cardiomyocytes into the myocardium. At this point, the operator will release the clutch and move / push the helical needle axially out of the guide catheter and into contact with a desired myocardial surface area of the moving heart. To help position the helical needle precisely, the operator may be guided by ECG signals picked up by the catheter distal tip. After re-engaging the clutch, the combined control member can be used to rotate the delivery catheter and thus the helical needle into the myocardium, the rotational and axial movement of the helical needle being determined by the pitch and length of the threaded engagement between the anchor member and the handle housing.

[0109] Turning to figs. 9 and 10 an exemplary embodiment of a suspension transfer device, or “dose control kit” will be scribed.

[0110] 25 The suspension transfer device 700 comprises a syringe barrel 710 comprising a proximal main portion 711 with a cylindrical inner surface defining a variable volume main chamber 718, a distal transfer opening 715, and a distal transfer portion 712 with an inner surface which smoothly and positively tapers towards the distal transfer opening. In the present context the reduced cross-sectional area in the direction from the cylindrical portion towards the transfer opening defines a positive taper, no taper being 0 degrees. In exemplary embodiments the positive taper is less than 20 degrees, less than 10 degrees or less than 5 degrees from the centre axis of the syringe, i.e. a total taper for the transfer portion of less than 40 degrees, less than 20 degrees or less than 10 degrees. The taper may be straight in case of the transfer portion having a conical shape. Alternatively, if the taper is curved (as in the embodiment

[0111] 35 shown in fig. 11) the taper may refer to the average taper. In the shown embodiment the 240046W001

[0112] 13 transfer portion is conical with a taper of 5 degrees from the centre axis of the syringe and thus a total taper for the transfer portion of 10 degrees.

[0113] The syringe barrel comprises at the distal end a coupling portion 716 (here a male Luer cou¬

[0114] 5 pling) allowing the transfer device to be initially connected to a fluid / cell source and subsequently to a fluid receiving device, e.g. the injection port 400 of the above-described catheter assembly 1. The cylindrical main portion comprises a proximal opening 717 adapted to receive a piston. The suspension transfer device further comprises a piston 720 arranged in sliding and sealing engagement with the cylindrical inner surface to define a variable volume main

[0115] 10 chamber, and a piston rod 730 having a distal end to which the piston is attached and a proximal end with a handle disc 731. The syringe barrel is provided with a pair of proximally extending flanges 716 cooperating with the handle disc 731 to limit distal movement of the piston. In the shown embodiment the main portion and the transfer portion are formed as an integral component with a smooth transition between the respective inner surfaces. The barrel main portion may be provided with indices (not shown) to help identify the exact position of the piston during loading and expelling of fluid suspensions. The taper of the distal transfer portion and the smooth transition between the two portions ensure that when a suspension of e.g. cells or cell agglomerates have been transferred to the syringe barrel, e.g. through suction via the transfer opening, and collected in the transfer portion, e.g. through vertical sedimentation, then the cells or cell agglomerates can be purged into (in the present context) the delivery catheter with only a minimal loss of cells or cell agglomerates, this in contrast to a traditional syringe set-up in which a larger portion of the cells or cell agglomerates would be trapped in corners and at edges.

[0116] 25 Fig. 11 shows an alternative embodiment of a transfer system in which the transfer portion is provided as a separate transfer member 800 comprising an intermediate portion 813 arranged between the proximal main portion (e.g. in the form of a separate syringe, not shown) and the distal transfer 812 portion, wherein the inner surface of the intermediate portion smoothly and negatively tapers towards the distal transfer portion inner surface, the intermediate and distal portions thereby forming a bulbous combined transfer portion 814. To enlarge the volume of the suspension transfer device without increasing the outer diameter the bulbous transfer portion may comprise a non-tapered, e.g. cylindrical, portion between the tapered distal and intermediate portions.

[0117] 35 The transfer member 800 comprises a distal transfer opening 815 with a threaded connector 816 (here a male threaded luer lock connector), and a proximal opening 811 with a threaded 240046W001

[0118] 14 connector 819 (here a female threaded luer lock connector) adapted to be connected to a proximal main portion in the form of a traditional syringe comprising a mating connector. As appears from fig. 11 the transfer portion has a non-straight taper.

[0119] During initial preparation for delivery of e.g. a cell suspension to a treatment site using the

[0120] 5 above-described catheter assembly 1 , an amount of a cell suspension comprising a known volume of cells or cell agglomerates is transferred to the transfer device 700, 800 by withdrawing the piston rod to fill the transfer portion and the main portion with cell suspension. Positioning the transfer device vertically will allow the cells or cell agglomerates to fully or partly sediment in the transfer portion. In an exemplary use of the transfer device the volume of cells or cell agglomerates is smaller than the volume of the transfer portion.

[0121] When the cells or cell agglomerates have collected in the transfer portion, the transfer portion is connected to the injection port 400 (see fig. 1) and the known volume of collected cells or cell agglomerates can be transferred to the delivery catheter. As the inner diameter and the

[0122] 15 length of the delivery catheter lumen is known it can be calculated at which position the distal- most portion of the cells or cell agglomerates are positioned in the inner fluid transmission lumen 21 , this allowing the cells or cell agglomerates to be moved distally into the vicinity of the helical needle by injecting a metered amount of fluid from the transfer device main portion.

[0123] In the above description of exemplary embodiments, the different structures and means providing the described functionality for the different components have been described to a degree to which the concept of the present invention will be apparent to the skilled reader. The detailed construction and specification for the different components are considered the object of a normal design procedure performed by the skilled person along the lines set out in the present

[0124] 25 specification.

[0125] *****

Claims

240046W00115CLAIMS1. A combined catheter (1) comprising a tubular guide catheter (10) and a therein arranged delivery catheter (20),5 the tubular guide catheter (10) comprising: a proximal main portion, a distal cavity portion (13), and a pair of opposed pull wires (17),10 wherein: the main portion has a tubular wall (11) forming a central lumen (12) with a first diameter, the distal portion (13) having a tubular wall forming a distal cavity (14) with a second larger diameter, and the pair of opposed pull wires (17) arranged in the main portion wall are anchored (19) proximally of the distal portion, the delivery catheter (20) comprising: a proximal tubular main portion with a distal end, and a distal hollow helical needle (30) comprising one or more outlet openings (32), wherein:25 the proximal tubular main portion has a central delivery lumen (21), the hollow helical needle (30) is attached to the main portion distal end in fluid communication with the central lumen, the hollow helical needle has an outer diameter smaller than the second diameter but larger than the first diameter, and the delivery catheter main portion is arranged in the guide catheter central lumen (12) and the helical needle (30) is arranged in the guide catheter distal cavity (14) from which it can be pushed axially in a distal direction.

2. A combined catheter as in claim 1 , further comprising:35240046W00116 a handle (100) attached to the guide catheter main portion, the handle comprising guide control means (200) for exerting a proximally directed pulling force to the pull wires.

3. A combined catheter as in claim 2, wherein:5 the proximal portion of the guide catheter comprises a handle portion arranged within the handle, the handle portion comprising a pair of opposed exit openings (15A) through which the pull wires (17) exit to engage the handle control means (200, 230).10 4. A combined catheter as in claim 3, wherein: the handle comprises a housing (110, 120), the guide catheter (10) has a proximal fluid inlet end arranged within the housing and from which the delivery catheter (20) proximal portion exits, and the delivery catheter proximal portion exits from the housing, the combined catheter further comprising a flush hub (510) arranged in the housing, comprising: a distal end attached to the guide catheter (10) and sealingly surrounding the guide catheter proximal fluid inlet, a proximal sealing valve (511) from which the delivery catheter proximal portion exits, the sealing valve allowing axial and rotational movement of the delivery catheter relative to the flush hub (510) and thus the guide catheter, and a flush port (500) in fluid communication (520, 530) with an interior of the flush hub,25 whereby the axially extending space (12A) between the delivery catheter (20) and the guide catheter (10) can be flushed with a fluid via the flush port (500).

5. A catheter assembly as in claim 4, wherein the guide catheter proximal fluid inlet end is arranged in the housing proximally of the control means.

6. A combined catheter as in any of claims 1-5, wherein: the handle (100) comprises user actuatable clutch means (300, 330) operatable be¬35 tween a locked state in which the delivery catheter (20) is axially locked relative to the handle,240046W00117 and an un-locked state in which the delivery catheter can be moved axially relative to the handle to thereby move the helical needle (30) out of the distal cavity (14).

7. A combined catheter as in claim 6, wherein:5 the handle (100) comprises threaded control means (112, 312) allowing the delivery catheter (20) and thus the helical needle (30) to be moved distally by rotational movement of the delivery catheter with a movement corresponding to the pitch of the helical needle.10 8. A combined catheter as in claim 7, wherein: the handle (100) comprises an actuation member (300) adapted to actuate the clutch means (330) between the locked and the un-locked state when moved axially, the actuation member also serving to rotate the delivery catheter relative to the threaded control means.

9. A combined catheter as in any of claims 1-8, wherein: each pull wire (17) along a portion of its length is surrounded by a compression coil (16) embedded in the wall (11) of the guide catheter main portion and anchored (19) axially at20 its ends, the compression coils providing rigidity and controlled flexibility to the guide catheter.*****

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