Injection device

Abstract

Provided is an injection device [1] for injecting a substance into a living organism [20] using a syringe [14], the device comprising: a holding unit [2] adapted to hold a syringe [14]; an actuation unit [3] adapted for administering and injecting an injection substance, the actuation unit [3] being detachably connected to the holding unit [2] when the holding unit [2] holds the syringe [14] and being connectable with the syringe [14]; a needle guide [8] adapted to be detachably connectable with an injection needle [11] and adapted to change the injection position of the injection needle [11]; and a connecting structure [12] connecting the holding unit [2] and the needle guide [8].

Description

[Technical Field]

[0001] The present invention relates to an injection device arranged for positioning an injection needle and for administering and delivering an injectable substance, a medical device comprising such an injection device, and a method for injecting an injectable substance into living tissue, in particular muscle tissue. [Background technology]

[0002] In recent years, several therapeutic approaches have been developed for the treatment of incontinence, such as stress urinary incontinence (SUI), male stress urinary incontinence after prostatectomy, and fecal incontinence. SUI is characterized by involuntary urine loss associated with exertion, working, or coughing / sneezing. Several non-surgical and surgical options are available for the treatment of female SUI. Urethral injection is a well-described minimally invasive technique and represents a common surgical procedure for SUI. Several urethral bulking agents (UBA) are available for injection, as summarized in Li and Westney, Urol Clin North Am 46 (2019), 1–15, and cell therapy approaches have recently been further developed, as described in WO 2019 / 215090.

[0003] Injection of filler and cells is typically performed using a needle with simultaneous tissue visualization, for example, using an ultrasound probe or cystoscope. In practical medical applications, precise needle positioning is crucial to accurately place the injectable material at the desired injection site and minimize the risk of damage to surrounding tissue. To position the injection needle, an injection device is usually used that includes a needle guide that has a predetermined position and orientation relative to the ultrasound probe, see for example WO 02 / 45588. Although several injection devices are known in the art, there is a continuing need to provide a device that allows for precise injection of the injection substance. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2019 / 215090 [Patent Document 2] WO 02 / 45588 [Non-patent literature]

[0005] [Non-Patent Document 1] Li and Westney, Urol Clin North Am 46(2019),1-15 Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention provides an injection device for injecting an injection substance into a living organism by means of a syringe, and which is particularly suitable for injection into a sphincter, as well as a medical device comprising said injection device and a method for directed injection, preferably of a defined amount. [Means for solving the problem]

[0007] The term "injection syringe" or "syringe" is generally used herein to refer to any fluid delivery device having a fluid reservoir (a syringe body having at least one chamber) and at least one syringe plunger including a piston and an outlet for the fluid. Preferably, the injection syringe further includes an injection needle (a hollow syringe needle). The syringe needle may be straight or curved. The syringe body may have one or more chambers, preferably cylindrical in shape. Each of the chambers is adapted to receive a syringe plunger including a piston. Displacement of the at least one syringe plunger within the syringe body allows an injection substance, e.g., a fluid, to be expelled from the syringe body through an outlet, i.e., a nozzle, preferably through a syringe needle connected to the outlet. For example, the syringe may include a single chamber to which a syringe needle is connected and a syringe plunger disposed therein, or a syringe body having two or more chambers to which a syringe needle is connected and each chamber having a syringe plunger disposed therein.

[0008] The term "injectable substance" is used herein generally to refer to any injectable substance, ie, a substance that can be passed through a syringe under pressure. Preferably, the injectable substance is a liquid containing at least one pharmacologically or biologically active substance in dissolved or suspended form. According to a preferred application of the present invention, the injectable substance comprises a cell suspension (or dispersion), in particular a suspension of muscle-derived progenitor cells. In particular, the cells are suspended in a suitable liquid, for example, a buffer, cell culture medium and / or carrier solution such as collagen. Such cells are described, for example, in WO 2019 / 216090, the contents of which are incorporated herein by reference.

[0009] Regarding the device, the present invention provides an injection device comprising at least one holding unit for a syringe, i.e. designed to hold a syringe, an actuation unit, a needle guide and, optionally, a structure connecting at least the holding unit with the needle guide. The injection device of the present invention is designed for injection of a specific, preferably constant dose of an injectable substance, i.e., for the administration injection of an injectable substance, and more particularly for the repeated administration injection of specific, preferably constant doses at a number of different injection sites.

[0010] The dose injection is achieved by an actuation unit as part of the injection device of the present invention, which comprises a lever and a piston and is removably coupled to a syringe in a holding unit. In particular, the actuation unit is coupled to the plunger of the syringe. Operating a lever ensures that a specific / predefined amount of injection substance, i.e. a specific dose, is dispensed. The actuation unit can therefore also be called a dosing unit. The dosing injection is ensured by a predetermined displacement distance of the lever of the actuation unit, which is translated a predetermined distance via the piston of the actuation unit by connecting to the syringe plunger, thereby moving the syringe plunger into the syringe body, resulting in the injection of a specific amount of the injection substance through the needle.

[0011] More specifically, the actuation unit of the injection device of the present invention is detachably coupled to the holding unit and is connectable to the syringe via its plunger when the holding unit holds the syringe, the actuation unit comprising a lever and a piston, the displacement of the lever from a first position to a second position being effected preferably by pivoting the lever from the first position to the second position about a pivot axis, resulting in the piston moving along its longitudinal axis, and the actuation unit is adapted to at least partially transmit the movement to the plunger of the syringe when the syringe is coupled to the actuation unit. In particular, displacement of the lever results in the piston moving forward along its longitudinal axis, i.e., toward the piston stop, and the distance between the first and second positions of the lever is predetermined to ensure that the piston is advanced a predetermined distance. Therefore, a change in the distance between the first and second positions of the lever affects the movement of the piston. In other words, the piston moves from the first position to the second position, and the distance is predetermined by the distance between the first and second positions of the lever.

[0012] In even more detail, the actuation unit of the injection device of the present invention further comprises an actuator (clamp piece) through which the piston extends, and displacement of the lever from the first position to the second position engages the lever with the actuator, preferably via a pivot point, so that the actuator is frictionally connected to the piston, and advances the actuator together with the piston in a first direction of piston movement (forward) along the longitudinal axis, i.e. the piston of the actuation unit is moved towards the plunger of the syringe such that the plunger of the syringe advances in a first direction of plunger movement (forward), i.e. the plunger of the syringe moves and the injection substance is dispensed from the syringe body, when the syringe is placed in the holding unit and the actuation device is coupled to the syringe. The frictional connection between the actuator and the piston of the actuation unit can be achieved by (slightly) pivoting the actuator relative to the vertical orientation of the actuator and the piston. Thus, when the lever is displaced from the first position to the second position, the piston of the actuation unit is displaced along the longitudinal axis in the direction (forward) of the piston stopper by a certain displacement distance, i.e., from the first position to the second position. In other words, tilting the actuator creates a frictional connection between the actuator and the piston rod by frictionally engaging them, which then leads to the aforementioned forward movement. The forward movement of the piston exerts a force toward the syringe plunger, moving the plunger forward, resulting in the delivery of the metered amount of substance. When the actuator and / or lever arm abuts against a stop in the actuation unit housing, the displacement of the actuation unit's piston is completed, i.e., it reaches its second position. Actuation of the actuator is performed by a spring force. Forward is understood to be toward the syringe nozzle, and the position of the nozzle on the syringe is defined as forward. The movement of an object, such as an injection substance or a plunger, through the syringe toward the nozzle is defined as forward movement. The other open end of the syringe, through which the plunger is introduced, is defined as the rear end of the syringe. The movement of an object, such as an injection substance or a plunger, through the syringe toward the rear end is defined as reverse or backward movement. When the lever returns to the first position, i.e., is displaced from the second position to the first position, the connection between the actuator and the piston is released and the actuator can slide along the piston rod such that the actuator is displaced from the second position to its first position relative to the piston rod.

[0013] Thus, when the lever of the injection device of the present invention is moved from the first position to the second position, a specific amount of injection substance, i.e. a specific dose, is dispensed, in particular via the needle and through the nozzle of the syringe, and thus injected (when applied to the animal or human body) without the need to manually advance the syringe plunger forward along its longitudinal axis, which, in the case of manual advancement, is not very accurate as to the amount of injection substance dispensed, since the distance the syringe plunger must be advanced to ensure a specific amount of injection substance to be dispensed must be estimated by the operator, e.g. a physician, and is not predetermined by a predetermined displacement distance of the lever. Ensuring a specific dose without significant variation during injection is particularly important for clinical trials and subsequent treatment procedures. For example, accurate dose-finding studies are essential during the clinical development of new drugs. Dose-finding studies must define the ineffective dose, as well as the mean and maximum effective doses.

[0014] An optimal therapeutic dose range can then be selected, taking into account tolerability. Thus, when using the injection device of the present invention in clinical trials and therapeutic applications, administration of a precise amount of injection substance is assured. In one embodiment, the injection device of the present invention, in particular the actuation unit of the injection device of the present invention, further comprises a retaining element, preferably a retaining bracket (clamp plate), which frictionally engages the piston rod in a retaining position so that the piston is held in a fixed position and prevents the piston from moving backward along its longitudinal axis, i.e., backward (in the opposite direction to the forward direction mentioned above), when the lever and the actuator, respectively, move from the second position to the first position.

[0015] This allows re-actuation of the actuation unit, i.e., moving the lever (and actuator) again from the first position to the second position, resulting in renewed delivery of the metered substrate. By actuating the retaining bracket, the retaining bracket is released, allowing the piston rod to relax and reset. For this principle to work, the force transfer from the actuator to the piston must be greater than the force transfer from the retaining bracket to the piston. This mechanism allows for repeat injections, so that a particular dose of injection substance can be injected several times without the need to refill the syringe or exchange the syringe for another syringe, saving time and reducing the risk of contamination.

[0016] The injection device of the present invention further comprises a needle guide adapted to allow guided injections at different injection sites. Preferably, the needle guide comprises a guide tube holder and a guide tube adapted to be removably connectable with the injection needle. In a preferred embodiment, as shown in FIG. 9, the guide tube comprises, or preferably consists of, two pieces which when assembled form the complete guide tube.

[0017] In this regard, the two corresponding parts are connected to each other in a push-fit manner. In particular, the guide tube is divided into two parts along its longitudinal axis, which, when assembled, form the guide tube. When the two parts are connected to the guide tube, at least one channel is formed through which the injection needle can be guided. This channel is preferably located outside the axis of symmetry of the guide tube. In a preferred embodiment, when the two parts of the guide tube are assembled into the guide tube, two channels are formed, preferably one chancel capable of guiding an injection needle, which channel is preferably outside the axis of symmetry of the guide tube, and one channel capable of guiding a catheter, which channel is preferably within the axis of symmetry of the guide tube.

[0018] Thus, at least one or each of the components has a respective protrusion(s) for forming a channel(s) when assembled with the other component. In a preferred embodiment, one guide-type component has a protrusion for forming a catheter channel when assembled with the other component to form a guide tube, and the other component has a complementary protrusion for forming the catheter channel and a further protrusion for forming a needle channel when connected to the other component to form the guide tube. Preferably, the catheter channel is sized to fit the catheter tube snugly, thereby ensuring that the guide tube itself is narrow, i.e., has a small diameter, and is therefore convenient for the patient. In a preferred embodiment, the catheter channel has a diameter of about 1 mm to 6 mm, preferably about 2 mm to 5 mm, more preferably about 3 mm to 4 mm, and most preferably about 3.6 mm. Additionally or alternatively, the guide tube has a diameter at its widest point of about 4 mm to 9 mm, preferably about 5 mm to 8 mm, more preferably about 6 mm to 7 mm, and most preferably about 6.7 mm. Thus, in the most preferred embodiment, the catheter channel has a diameter of 3.6 mm and the guide tube has a diameter of 6.7 mm at its widest point. This narrow configuration allows the catheter tube to pass through the channel but not the balloon attached to the tip of the catheter (transurethral bladder catheter).

[0019] Therefore, the two-part design / structure of the guide tube is advantageous because it allows the insertion of a catheter into the guide tube. In particular, the catheter, i.e., the catheter tube, is inserted into a protrusion on one part of the guide tube, and then the other part of the guide tube with a complementary protrusion is connected to the part of the guide tube that already holds the catheter. The part of the catheter with the balloon is outside the guide tube and protrudes from the guide tube toward the patient. If the guide tube were made from a single piece, the catheter balloon would have to be pushed through the channel of the guide tube, which would be impossible because the channel would be too narrow.

[0020] Furthermore, the design of the guide tube with two channels, one for the needle and one for the catheter, ensures that the needle and the catheter tube pass in parallel, thereby preventing accidental puncture of the catheter by the needle, which can occur when the injection device, and in particular the guide tube, does not include a means for inserting the catheter.

[0021] In one embodiment, the needle guide is movable to adjust and change the injection location and adjust and change the position of the injection needle, respectively. In particular, in one embodiment, the guide tube is rotatable about its longitudinal axis within the guide tube holder, and the guide tube and guide tube holder are toleranced relative to one another by a clearance fit. In one embodiment, the injection device of the present invention is preferably adapted to guide an injection needle to at least two injection positions that differ from one another, which is preferably achieved by a rotatable guide tube comprising a channel outside the axis of symmetry of the guide tube, the guide tube being adapted to guide the injection needle through said channel. Multiple injection sites, especially along a crescent-shaped tissue, require multiple injection steps in which new injection sites are alternately established and the injectable material is placed at the established injection sites, which is important to ensure even distribution of the injectable material along the tissue leading to successful tissue regeneration.

[0022] In one embodiment, a section of the guide tube is provided with circumferential teeth directed outward relative to the surface of the guide tube, which, together with a locking disc disposed on the guide tube holder, ensure that the teeth of the guide tube engage with the locking disc when the guide tube is rotated a certain distance. Thus, the guide tube can have different locking positions relative to the guide tube holder, and the distance between the two locking positions, in particular the two teeth of the guide tube, is preferably 15°. Thus, when the guide tube is moved, in particular rotated, the position of the needle is changed by a specific distance, preferably 15°. For ease of handling, the guide tube in one embodiment is operably coupled to a handle, i.e., a handle that can be used to move, in particular rotate, the guide tube is operably coupled to the guide tube.

[0023] This feature is advantageous because it allows for an even distribution of the injected substrate along the tissue into which the substrate is to be injected, and the correct position does not have to be adjusted by hand but is predetermined by the interaction between the teeth of the guide tube and the locking disc of the guide tube holder. Therefore, there is no undesirable variation in injection location. As mentioned above, in one embodiment the injection device of the present invention is further adapted to guide the catheter into the organ of interest, preferably into the bladder. This is in one embodiment achieved by a guide tube further comprising a channel in its axis of symmetry, the guide tube being adapted to guide the catheter through said channel. The catheter is used to empty the bladder, fill and secure the bladder, and fill the bladder with an isotonic liquid such as sodium chloride solution to facilitate targeted injection into the sphincter.

[0024] In one embodiment, the injection device of the present invention comprises a cooling device which is preferably inserted into and removable from the holding unit. In particular, the cooling device is adapted to hold a syringe. The presence of the cooling device has the advantageous effect of keeping the injection substance cold before administration to a subject, which can increase the shelf life of the injection substance, for example. For example, when the injection device is used to administer a cell suspension mixed with a collagen solution, which is a preferred use of the injection device of the present invention, the cooling device is most important, as without cooling, the collagen solution will form a gel, making the suspension no longer injectable or only resulting in a severe loss of cell viability. Furthermore, when the injectate contains cells, such as muscle progenitor cells, cooling the cells ensures high viability. When the injection device of the present invention is equipped with a removable cooling device, the cooling device can be used to transport the injectate and the syringe containing the injectate to the injection device, respectively.

[0025] In one embodiment, as shown in Figures 2 and 4, the cooling device of the injection device of the present invention has facets that surround the cooling device, preferably spaced about 15 degrees apart from each other. Thus, each facet corresponds to 15°. The cooling unit is clamped with a holding unit such that after rotating the cooling unit 15°, the cooling tool snaps back into place after every 15° rotation, allowing an operator, e.g., a physician, to release the device at any position without having to reposition the device.

[0026] In one embodiment, the injection device of the present invention includes the aforementioned cooling device, which can rotate, particularly around its longitudinal axis, to allow mixing of the injection substances contained in the syringe. This is particularly useful when the injection substances are not homogeneous solutions of each substance, but rather heterogeneous mixtures, such as suspensions composed of at least two immiscible substances, such as cells (as particles) and a surrounding (preferably fluid) medium, such as a carrier solution like a collagen solution. Rotation of the cooling unit prevents one phase, such as cells, from settling when both substances are fluids, or in the case of suspensions, for example, when the cells and medium are homogeneously distributed in the syringe, ensuring that both phases are homogeneously distributed.

[0027] As mentioned above, the injection device of the present invention in one embodiment comprises a connection structure operatively connecting at least the holding unit with the needle guide. The connection structure is preferably designed as an elongated column, in particular an elongated rod, to which the other components of the injection device of the present invention are attached directly or by means of further connection means. Preferably, the holding unit is attached directly to the connection structure (the actuation unit is attached to the holding unit) and the needle guide is attached to the connection structure via further connection means, i.e. a positioning structure as defined below. The connecting structure therefore extends along an axial reference plane of the injection device (see FIG. 1).

[0028] The connecting structure is preferably designed such that the needle guide is slidable along its rod and the holding unit (including the actuation unit) is slidable along its rod, the needle guide and the holding unit being able to slide independently of each other. The holding unit including the actuating unit is connected to a syringe disposed in the holding unit of the injection device and slides to advance the injection needle when guided by the needle guide. During the injection procedure, the actuating unit including the holding unit is advanced toward the organism, i.e., toward the injection site, until the tip of the needle penetrates sufficiently deep into the injection site, preferably human or animal tissue, more preferably into the sphincter, even more preferably into the external urethral sphincter, and particularly preferably into the human sphincter or the external urethral sphincter. The sliding of the actuating unit and the holding unit can each be performed manually or motor-driven, for example, controlled by artificial intelligence (AI) as further described below. The needle guide slide is advantageous for adjusting the distance between the guide tube / injection needle and the head of the ultrasound probe as it is guided through the guide tube, and the ultrasound probe can be connected to the injection device of the present invention as described below in order to adapt the injection device of the present invention to the anatomical structure of the subject to be treated.

[0029] The connecting structure is preferably further adapted to be removably connectable to an imaging device, preferably an ultrasound probe. The ultrasound probe is advantageous for observing the tissue into which the injection substance is to be administered, particularly to determine the optimal position of the injection needle and the injection depth. Ultrasound probe-guided injections are usually more accurate than cystoscopy-guided injections and are therefore advantageous. Therefore, in one embodiment, the connection structure further comprises attachment means for an imaging device, in particular an ultrasound probe. Thus, in one embodiment, the injection device of the present invention comprises an imaging device, preferably an ultrasound probe, which is removably coupled to the injection device of the present invention via a connecting structure, which in one embodiment thus comprises attachment means for the imaging device.

[0030] Injections are typically performed by trained physicians in a hospital setting, and the accuracy of the injection can be further improved via artificial intelligence (AI)-enabled ultrasound interpretation, which, for example, allows for targeted, preferably powered, needle insertion, preferably automatically confirming successful puncture of the respective tissue, e.g., the external urethral sphincter. This allows users to quickly and accurately locate the exact injection site, particularly the injection depth and / or angle, without the need for manual ultrasound interpretation, thereby reducing intersurgeon and intrasurgeon variability. The principles of AI-enabled ultrasound interpretation are described, for example, in Brattain et al., Biosensors 11 (2021), 522.

[0031] In one embodiment, the injection device of the present invention further comprises positioning structures for the needle guides, i.e., the needle guides are each removably and movably connected on the positioning structures, and the positioning structures preferably comprise rails connected to the connecting structures and extending perpendicular to the connecting structures, and more preferably further comprise slides removably and movably connectable to said rails.

[0032] The positioning structure allows the needle guide to move in different directions, thereby allowing the injection needle to move with the needle guide when inserted into the needle guide. Thus, in one embodiment, the guide tube holder of the injection device of the present invention is movable. In particular, in one embodiment, the needle guide, including the guide tube and the guide tube holder, is movable relative to the holding unit, preferably towards or away from the holding unit, i.e. the distance between the holding unit and the guide tube holder is adjustable, while the distance between the guide tube holder and the shaft of the imaging device, in particular the ultrasound probe, remains the same when connected to the connecting structure of the imaging device. In particular, the needle guide can be moved along the connecting structure, so that the distance between the needle guide and the shaft of the imaging device, in particular the ultrasound probe, remains the same. This allows for adjustment of the distance between the guide tube (and the injection needle when inserted) and the head of the ultrasound probe, in one embodiment this is achieved by a rail to which the guide tube holder containing the guide tube is connected, the rail being movable in the above directions.

[0033] In one embodiment, the needle guide including the guide tube holder and the guide tube is movable relative to the imaging device, in particular relative to the shaft of the ultrasound probe, preferably towards or away from the imaging device, i.e. the distance between the needle guide and the imaging device is adjustable, in one embodiment this is achieved by a slide connected to a rail, along which the slide to which the guide tube holder including the guide tube is connected can slide.

[0034] In one embodiment, the needle guide, including the guide tube and the guide tube holder, is pivotable about a pivot axis, which may be achieved by a slide connected to a rail via a pivot bearing. Due to differences in the anatomical structure of the organism to be treated, for example the anatomical structure of the vagina and bladder of female patients, and thus the position of the external urethral sphincter, it is important to be able to adjust the distance between the guide tube, and therefore the needle when inserted into the guide tube, and the ultrasound probe. For the same reason, it is advantageous to be able to adjust the distance between the guide tube, and therefore the needle when inserted into the guide tube, and the ultrasound probe head. Furthermore, the pivotable nature of the guide tube holder containing the guide tube is advantageous, as this allows for adaptation of the injection angle, which is the angle between the injection needle and the longitudinal direction of the tissue, in particular the muscle, e.g. the sphincter, into which the injection substance is to be introduced.

[0035] In a further embodiment, the present invention relates to an injection device and an injection needle of the present invention, wherein at least a front part of the injection needle protruding from the guide tube towards the injection site is bent. In other words, the present invention relates to an injection device of the present invention further comprising an injection needle, wherein the injection needle protruding from the guide tube towards the injection site is bent. Preferably, the injection needle itself is not bent, but the bending of the needle is caused by grinding in the guide tube, so that the injection needle exits the guide tube in a curved shape.

[0036] In particular, the needle has a bend directed radially outward relative to the axial orientation of the ultrasound probe and the guide tube, respectively. In a preferred embodiment, the injection needle is bent by a maximum of 10°, preferably by less than 10°, more preferably by less than 7.5°. In a further preferred embodiment, the injection needle is bent by 3° to 10°, preferably by 3° to 9°, more preferably by 3° to 8°, more preferably by 3° to 7.5°, more preferably by 3° to 7°, more preferably by 3° to 6.5° or 4° to 6.5°, more preferably by 3° to 6° or 4° to 6.5°, more preferably by 3° to 5.5° or 4° to 5.5°, more preferably by 3° to 5°. Most preferably, the injection needle is bent by 5° to 7.5°, preferably by 5° or 7.5°. In a preferred embodiment, the front part of the needle itself, which protrudes through the guide tube, has a curvature of 3° to 6°, preferably 4° to 5°, most preferably 5°, and the guide tube can be positioned to adjust the curvature of the needle, preferably by a further 1° to 3°, preferably less than 2.5°, i.e. the guide tube can be adjusted upwards or downwards relative to its longitudinal axis.

[0037] The bending of the needle is advantageous to avoid the needle penetrating the tissue into which the injection substance is to be injected, but instead the injection angle of the needle is shifted by a certain curvature radially outward or inward relative to the center of the longitudinally extending tissue, so that the injection direction is shifted radially in the longitudinal direction of the tissue.

[0038] In a preferred embodiment, the injection needle is attached to a syringe, in particular to the nozzle of the syringe. The connection between the syringe nozzle and the needle is leak-tight. In one embodiment, the leak-tight connection is achieved by a Luer taper. In one embodiment, the needle is connected to the syringe nozzle via an intermittent tubing. In a preferred embodiment, the connection of the intermittent tubing to the nozzle at one end and to the needle at the other end of the tubing is achieved by a Luer taper.

[0039] In one embodiment, the injection device of the present invention is connected to a mount, such as a bed or floor mount, preferably via a base that is part of the connecting structure, to ensure a stable position of the injection device relative to the organism to be treated. In a further embodiment, the present invention relates to a medical device adapted for injecting an injection substance into a living organism. The medical device of the present invention comprises the injection device of the present invention, a syringe having a plunger including a syringe body and a piston, and an injection needle, the syringe being arranged in a holding unit of the injection device and / or the injection needle being arranged in a needle guide. The present invention further relates in one embodiment to the use of a syringe comprising an injection substance and an injection needle in the injection device of the present invention and the medical device of the present invention, respectively.

[0040] In one embodiment, the medical device further comprises an imaging device, preferably an ultrasound probe.

[0041] In one embodiment, the injection device of the present invention and the medical device of the present invention are adapted to be removably connectable to a bed or floor mount, such as a brachytherapy stepper arm.

[0042] The present invention further relates to a method for injecting an injection substance into a living organism, in which the injection device and medical device of the present invention are used, respectively, and which includes at least the step of administering and injecting the injection substance into the living organism by displacing the lever of the operating unit of the medical device from a first position to a second position, as described in detail above.

[0043] Furthermore, the present invention relates to a method for treating muscle dysfunction, such as smooth muscle or skeletal muscle dysfunction, preferably skeletal muscle dysfunction, in a subject. In a preferred embodiment, the skeletal muscle dysfunction may be, for example, a sphincter dysfunction. Sphincters are circular muscles that function as valves to open and close specific parts of the body. For example, there are six different sphincters in the digestive system: the upper esophageal sphincter, the lower esophageal sphincter, the pyloric sphincter, the sphincter of Oddi, the ileocecal sphincter, and the anal sphincter. The body also contains additional sphincters, such as the urethral sphincter. Sphincter action can occur involuntary via the autonomic nervous system or under some voluntary control via the somatic nervous system. If sphincters lose muscle tone or have excessive tone (spasm), symptoms and illnesses can ensue. This can include urinary retention, which is the inability of the bladder to empty completely. Sphincter problems can also lead to urinary and fecal incontinence, or bladder or bowel control disorders. Thus, the injection device / medical device of the present invention can be used in a method for the treatment of the above-mentioned sphincter-related diseases, preferably diseases associated with a deficiency or dysfunction of the urethral sphincter, more preferably the external urethral sphincter. Thus, in a further preferred embodiment, the skeletal muscle dysfunction is a deficiency of the sphincter, preferably the external urethral sphincter.Accordingly, the present invention in one embodiment relates to a method for the treatment of diseases associated with muscle dysfunction, preferably associated with the treatment of stress urinary incontinence, including but not limited to (female) urinary incontinence, e.g. male urinary incontinence after prostatectomy, and anal incontinence.

[0044] Urinary incontinence, the involuntary loss of urine, is a major medical problem affecting approximately half of the female population over the age of 45 and 17% of men over the age of 70. Continence and voiding involve a balance between urethral closure and detrusor activity. There are different types of urinary incontinence, such as stress incontinence and urge incontinence. Stress urinary incontinence (SUI) is the loss of small amounts of urine associated with coughing, laughing, sneezing, exercise, or other movements that increase intra-abdominal pressure and, therefore, pressure on the bladder. The external striated urethral sphincter, made of skeletal muscle and therefore under voluntary control of the somatic nervous system, is largely responsible for preventing SUI. Damage to the external urethral sphincter occurs primarily during childbirth, surgical procedures, or as a result of aging. SUI affects more than 200 million people worldwide, is twice as common in women as in men, and reduces patients' quality of life due to limitations in daily activities, discomfort, odor caused by wet diapers, and infections. It also carries significant healthcare costs. Treatment options for SUI primarily include non-surgical therapies (bladder training, dietary modifications), drug therapy, and surgical therapy. These therapies only provide short-term relief, and their overall success is often limited by complications (e.g., the invasive nature of surgery, damage to surrounding tissue, and increased rates of urinary tract infections) or side effects (e.g., tissue damage from drugs and non-degradable biomaterials). However, significant advances have been made in cell therapy approaches for treating urinary incontinence that can restore sphincter function in SUI patients (see, for example, International Publication No. WO 2019 / 215090). Generally, the injection device / medical device of the present invention can be used to inject any substance into tissue, but is preferably used to inject cells capable of regenerating tissue, such as sphincter tissue. In a preferred embodiment, the method of the present invention comprises injecting an injectate comprising at least muscle-derived progenitor cells and optionally further components, such as a carrier solution for the cells, such as a collagen solution, into the respective tissue, in particular into muscle tissue, preferably into a sphincter, preferably into muscle tissue of the (external) urethral sphincter or the (external) anal sphincter, using the medical device of the present invention.

[0045] In one embodiment, as outlined in more detail below, the method of the invention further comprises neuromuscular electromagnetic stimulation (NMES) of the patient's pelvic floor, as described in WO 2019 / 215090. The NMES treatment following injection of the cell suspension supports muscle and nerve regeneration by activating muscle-nerve crosstalk and induces maturation of the neuromuscular junction.

[0046] As mentioned above, muscle-derived progenitor cells are preferably used in the methods of the present invention as the injectable material, optionally mixed with a carrier solution, such as a collagen solution as described in WO 2019 / 215090. Further, respective treatment techniques are described in WO 2019 / 215090, U.S. Patent Application Publication No. 2009 / 0098094, WO 2004 / 096245, and WO 2008 / 104883, all of which are incorporated herein by reference. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used to practice or test the present invention, exemplary methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present application, including definitions, will control. The materials, methods, and examples are illustrative only and are not intended to be limiting. Other features and advantages of the invention will become apparent from the following detailed description and claims. To avoid any doubt, it is emphasized that expressions such as "in some embodiments," "in particular embodiments," "in particular cases," "optionally," "in a further embodiment," "in one embodiment," etc., should be read with the understanding that any of the embodiments described therein may be combined with each of the features of those embodiments, and that the present disclosure is used in such a way that combinations of features of those embodiments should be treated in the same manner as if they were recited in one embodiment. The same applies to any combination of embodiments and features in the appended claims, which are shown in the examples and which are also intended to be combined with features from the corresponding embodiments disclosed herein; while for consistency and brevity only, the embodiments are characterized by dependency relationships, in fact each embodiment and combination of features can be interpreted due to dependency relationship(s) and must be considered literally disclosed and not as a choice between different alternatives. [Brief explanation of the drawings]

[0047] [Figure 1] 1 is a schematic diagram of an injection device according to one embodiment of the present invention, including dimensions (in mm, indicated by arrows). [Figure 2] 1 is a perspective view of an injection device according to an embodiment of the present invention; FIG. [Figure 3] 1 is a schematic diagram of an injection device according to an embodiment of the invention including an imaging device, here an ultrasound probe, including dimensions (in mm, indicated by arrows). [Figure 4] 1 is a perspective view of an injection device according to an embodiment of the present invention including an imaging device, here an ultrasound probe. [Figure 5] 1A and 1B are enlarged detailed views of an embodiment of an actuation unit of an injection device of the present invention, showing the lever in a first position (A) and a second position (B). [Figure 6] FIG. 2 is an enlarged detail view of the syringe and needle of the injection device of the present invention when placed within the cooling fixture. [Figure 7]1A-1D are enlarged detailed views of one embodiment of a guide tube and the major part of said guide tube (comprising 3 / 4 of the guide tube) of an injection device of the present invention, including dimensions (in mm, indicated by arrows) and radius specifications (R in degrees). A) Complete guide tube, B) Major part of guide tube, C) Cross section of the major part of guide tube, D) Cross section of the disk with radially protruding teeth of the major part of guide tube. [Figure 8] 1A-1D are enlarged detailed views of a small section of one embodiment of a guide tube (comprising 1 / 4 of the guide tube) of an injection device of the present invention, including dimensions (in mm, indicated by arrows) and radius specifications (R in degrees). A) Guide tube small section, B) Cross section of guide tube small section, C) Cross section of a disk with radially protruding teeth of guide tube small section, D) Radial cross section of guide tube small section. [Figure 9] 1 is a schematic diagram of the assembly of the guide tube, i.e., the assembly of the major and minor components into the complete guide tube. [Figure 10] FIG. 1 is a schematic diagram of one embodiment of a locking disc of an injection device of the present invention, including dimensions (in mm, indicated by arrows) and radius specifications (R in degrees). [Figure 11] A schematic diagram of one embodiment of a positioning structure (with rails and slides) including a guide tube holder and a locking disk, as well as a cross-section of a guide tube within the guide tube holder of an injection device of the present invention, and corresponding enlarged views of the cross-sections of the locking disk and guide tube. [Figure 12] 1 is a schematic diagram of one embodiment of a rail for an injection device of the present invention, including dimensions (in mm, indicated by arrows) and radius specifications (R in degrees). A) Side view of the rail. B) Front view of the rail. [Figure 13] 1 is a schematic diagram of one embodiment of a slide of an injection device of the present invention, including dimensions (in mm, indicated by arrows) and radius specifications (R in degrees). DETAILED DESCRIPTION OF THE INVENTION

[0048] An embodiment of the injection device 1 of the invention is shown in Figures 1 and 2, the position of the syringe 14 within the injection device is shown in Figure 6 and details regarding different positions of the actuation unit 3, in particular the lever, are shown in Figure 5. The injection device 1 of the invention comprises at least one holding unit 2 for the syringe 14, i.e. designed to hold the syringe 14, the actuation unit 3, a needle guide 8 and a structure connecting at least the holding unit 2 with the needle guide 8, i.e. a connecting structure 12.

[0049] In particular, the injection device 1 of the present invention comprises: a holding unit 2 adapted to hold a syringe 14; an actuation unit 3 detachably coupled to the holding unit 2 when the holding unit 2 holds the syringe 14, and connectable with the syringe 14, in particular with a plunger 28 of the syringe 14, the actuation unit 3 comprising a lever 4 and a piston 5, wherein displacement of the lever 4 from a first position 35 to a second position 36 results in a movement of the piston 5 along its longitudinal axis, in particular forward, in particular a forward movement, the actuation unit 3 being adapted to transmit the forward movement at least partially to the syringe 14, in particular to the plunger 28 of the syringe, when the syringe 14 is connected to the actuation unit 3; a needle guide 8 adapted to be detachably connectable with an injection needle 11 and adapted to change the injection position of the injection needle 11, the needle guide 8 preferably comprising a guide tube holder 9 and a guide tube 10, the guide tube 10 being movable relative to the guide tube holder 9, in particular rotatable within the guide tube holder 9, in order to change the injection position of the injection needle 11; a connecting structure 12 that connects the holding unit 2 and the needle guide 8; Equipped with.

[0050] In particular, the holding unit 2, the actuation unit 3 and the needle guide 8 are arranged in series such that they are operatively connected when the injection device is used, i.e. when the syringe 14 is inserted into the holding unit and when the injection needle 11 is attached to the nozzle 34 of the syringe 14 and guided through the guide tube 10, and the connecting structure 12 connects the different elements. In particular, the connecting structure 12 connects the holding unit 2 to the needle guide 8, and thus, since the actuation unit 3 is attached to the holding unit 2, the actuation unit 3 is also indirectly connected to both above-mentioned components of the injection device 1.

[0051] 1 and 2 show one embodiment of an injection device 1 of the present invention, with FIG. 1 further showing the orientation of the device relative to an organism, and in particular relative to an injection site 19 of an organism 20. More specifically, Figure 1 shows the orientation of the injection device 1 relative to the external urethral sphincter muscle (schematic, not drawn to scale). The external urethral sphincter muscle has a length of approximately 10 mm to 18 mm and a thickness of approximately 1.5 mm to 5 mm (Morgan et al., J Urol. 182 (2009), 203-209). Figure 6 shows the orientation of the syringe 14 within the injection device 1 of the present invention, and in particular within the holding unit 2 of the injection device 1 of the present invention.

[0052] The injection device 1 of the present invention comprises a holding unit 2 for a syringe 14, into which the syringe 14 can be inserted. The holding unit 2 can be made of any material that enables the function of the holding unit and is preferably suitable for medical purposes, can be designed to be disposable, and / or can be made of, for example, a plastic material or steel, preferably stainless steel. An example of a preferred plastic material is polyamide, preferably polyamide-12, most preferably fine polyamide PA 2200 for EOSINT P. The same applies to the other parts of the injection device 1 of the present invention, unless otherwise specified. Preferably, any plastic material can be used, as long as it is certified for medical use and can be cleaned and / or sterilized.

[0053] In principle, the holding unit 2 can have any design as long as it holds the syringe body 39 in a fixed position and the syringe plunger 28 is movable. In particular, the syringe plunger 28 can perform a forward movement along its longitudinal axis in the direction towards the outlet / tip of the syringe 14 and a backward movement along its longitudinal axis in the opposite direction, i.e. towards the actuation unit 3 of the injection device 1.

[0054] In particular, the injection device 1 of the present invention comprises a holding unit 2 which holds the syringe body 39 in place so that it does not change position within the holding unit 2 .

[0055] In one embodiment, the holding unit 2 and the syringe 14, particularly the syringe body 39, are push-fit connected to one another. In another embodiment, the syringe body 39 and the holding unit 2 are toleranced to one another by a clearance fit such that the syringe body 39 can rotate within the holding unit 2 along its longitudinal axis.

[0056] As mentioned above, the injection device 1 of the present invention is preferably designed for multiple injections of specific, predetermined amounts. In this regard, the holding unit 2 of the injection device 1 of the present invention is, in one embodiment, provided with a count marker that allows the operator to estimate how many injections have already been administered. In particular, this can be estimated based on the position of the syringe piston 29.

[0057] In one embodiment, the holding unit 2 of the injection device 1 of the present invention further holds a cooling device 13, preferably a cooling device for the syringe 14 and its contents within the syringe body 39, respectively.

[0058] In one embodiment, the cooling device 13 of the injection device 1 of the present invention is removable, ie it can be removed from the holding unit 2, for example for transport.

[0059] In one embodiment, the cooling device 13 is removably fixed to the holding unit 2 so that it does not change its position within the holding unit 2 after being inserted into the holding unit 2 and cannot be rotated, i.e., the holding unit 2 and the cooling device 13 are push-fit connected to each other.

[0060] In a preferred embodiment, the cooling device 13 is removably fixed to the holding unit 2 such that after being inserted into the holding unit 2, it does not change its position within the holding unit 2 but is rotatable along its longitudinal axis. In the latter case, the cooling device 13 and the holding unit 2 have a tolerance to one another by a clearance fit such that the cooling device 13 can rotate within the holding unit 2 along its longitudinal axis.

[0061] In a further preferred embodiment, the cooling device 13 has facets 60 as shown in Figures 2 and 4, which are preferably spaced apart and surround the cooling device 13. The facets are preferably uniformly distributed around the cooling device, i.e., have the same distance from each other. Preferably, the facets are spaced apart from each other by about 5° to 25°, more preferably about 10° to 20°, more preferably about 12° to 18°, more preferably about 14° to 16°, and most preferably about 15°. Thus, the cooling unit is clamped to the holding unit such that after rotating the cooling unit a prescribed number of degrees, preferably 15°, the cooling fixture snaps back into place after every 15° rotation.

[0062] In principle, the cooling device can have any design as long as the syringe 14 can be inserted, i.e., the cooling device 13 has an opening for inserting the syringe 14 and / or holds the syringe 14 in place.

[0063] In a preferred embodiment, the cooling device 13 is a hollow cylinder that surrounds the syringe, particularly preferably the syringe body 39 containing the contents to be cooled, on all sides. The cooling device 13 can be made of an iron-based alloy, such as aluminum or stainless steel, and is cooled on ice before use, i.e., before the cooling device 13, including the syringe 14 containing the substance to be injected, is connected to the holding unit 2 of the injection device 1 of the present invention. Preferably, the cooling device 13 is made of any material with optimal separation properties. In particular, in one embodiment, the cooling device 13 has a threading 51 that can be screwed onto the actuation unit 3 of the injection device 1 of the present invention, and the actuation unit 3, including the syringe 14 and the cooling device 13 containing the substance to be injected, is connected to the holding unit 2 of the injection device 1 of the present invention, for example, as shown in Figures 1 and 2.

[0064] As mentioned above, the cooling device 13 is designed to hold the syringe 14. In particular, the cooling device 13 holds the syringe body 39 in place while the syringe plunger 28 is movable. In particular, the syringe plunger 28 is capable of forward movement along its longitudinal axis in a direction toward the outlet / tip of the syringe 14 and of retraction movement along its longitudinal axis in the opposite direction. In particular, the injection device 1 of the present invention comprises a holding unit 2 for holding the cooling device 13 which holds the syringe body 39 in place so that it does not change its position within the cooling device 13 .

[0065] In one embodiment, the syringe body 39 and the cooling device 13 have a clearance fit to one another so that the syringe body 39 can rotate within the cooling device 13 along its longitudinal axis, and in another embodiment, the syringe body 39 and the cooling device 13 are push-fit connected to one another.

[0066] In a preferred embodiment, the syringe body 39 is fixed within the cooling fixture 13 such that it cannot change its position or rotate within the cooling fixture 13, i.e., the syringe body 39 and the cooling fixture 13 are push-fit connected to each other. Thus, in one embodiment, neither the cooling fixture 13 nor the syringe body 39 can change its position relative to the holding unit 2.

[0067] In a preferred embodiment, the cooling device 13 is rotatable as described above, and thus the syringe 14, particularly the syringe body 39, is removably fixed within the cooling device 13, so that the syringe 14, particularly the syringe body 39, is rotatable within the holding unit 2.

[0068] Syringe 14 can be of any size as long as it fits into holding unit 2 and cooling fixture 13, respectively.

[0069] In one embodiment, syringe 14 holds a volume of at least 10 μl, at least 400 μl, at least 600 μl or at least 800 μl, preferably at least 400 μl or 600 μl.

[0070] In preferred embodiments, the injection syringe 14 holds a volume of at least 1 ml, at least 4 ml, at least 6 ml, or at least 8 ml, preferably at least 4 ml (for 10 x 400 μl injections (low dose)) or 6 ml (for 15 x 400 μl injections (high dose)). Most preferably, a 10 ml syringe 14, such as a Braun Omnifix 10 ml Luer Lock syringe, is used in accordance with the present invention.

[0071] The injection device 1 of the present invention further comprises an actuation unit 3. One embodiment of the actuation unit 3 is shown in more detail in Figure 5. The actuation unit 3 can be made of any material that allows handling of the actuation unit and is preferably suitable for medical purposes, can be designed to be disposable and / or can be made, for example, of a plastic material or steel, preferably stainless steel. An example of a preferred plastic material is polyamide, preferably polyamide-12, most preferably fine polyamide PA 2200 for EOSINT P.

[0072] In one embodiment, the actuation unit 3 is mounted on the holding unit 2 of the injection device 1 of the present invention, i.e., slid onto the holding unit 2 when the injection device 1 of the present invention is assembled. In particular, the actuation unit 3 is removably coupled to the holding unit 2 and is connectable with the syringe 14 when the holding unit 2 holds the syringe 14.

[0073] In one embodiment, the actuation unit 3 is removably coupled to the holding unit 2, is removably coupled to the cooling unit 13, and is connectable with the syringe 14 when the holding unit 2 holds the syringe 14. In principle, the actuation unit 3 can have any design, as long as it allows for the administration of the injection substance. In particular, the actuation unit 3 can have any design, as long as it allows for the administration of the injection substance present in the syringe 14. In one embodiment, the actuation unit 3 is designed as shown in FIG. 5.

[0074] Thus, in a preferred embodiment, the administration injection is realized by an actuation unit 3 which, when actuated, for example by displacing the lever 4 of the actuation unit 3 from a first position 35 shown in FIG. 5A to a second position 36 shown in FIG. 5B, preferably by pivoting the lever 4 about a pivot axis from the first position 35 to the second position 36, ensures that the piston 5 of the actuation unit is displaced, i.e. advanced, by a certain displacement distance along its longitudinal axis in the direction of the piston stop (forward), i.e. from the first position to the second position, and when the piston 5 is advanced, exerts a force on the syringe plunger 28 such that the syringe plunger 28 is also advanced a certain distance along its longitudinal axis in the direction towards the outlet of the syringe 14, thereby expelling the injection substance present in said syringe, i.e. injecting it into the desired injection site 19.

[0075] In a preferred embodiment, the displacement distance of the lever 4 and the piston 5, respectively, is adapted so that 400 μl of injection substrate is dispensed from the syringe 14 via the nozzle 34 as described above per piston stroke, i.e. each triggering of the lever dispenses 400 μl of injection substrate from the syringe 14. The distance covered depends on the syringe dimensions, but if a 10 ml syringe is used, for example a Braun Omnifix 10 ml Luer Lock syringe with an internal diameter of 15.9, the displacement distance of the lever is preferably 20 mm and / or the displacement distance of the piston is preferably 2 mm.

[0076] In one embodiment, the actuation unit 3 of the injection device 1 of the present invention further comprises a lever shell 32. In one embodiment, the actuation unit 3 of the injection device 1 of the present invention further comprises a lever shell cover 44, which is preferably connected to the lever shell 32 via a knurled screw 52. The lever shell 32 and the lever shell cover 44 together form the lever housing 40. In particular, the lever 4 and at least a portion of the actuator 31 are arranged inside a housing 40, which has at least one recess for accessing, i.e., manipulating, the lever 4.

[0077] In one embodiment, the lever actuation point 45 , i.e. the handle 45 of the lever, is outside the housing 40 of the actuation unit 3 . The lever shell 32, including its cover 44, can be used as a handle to facilitate handling and operation of the injection device 1 of the present invention. The force transmission from the lever 4 to the piston 5 is preferably via an actuator 31 such as a clamp piece. Thus, the lever 4, the actuator 31, and the piston 5 are operatively connected. In particular, the lever 4 and the actuator 31 are operatively connected, for example, by one or more bolts 33. When the lever 4 is actuated from a first position 35 to a second position 36, the actuator 31 is tilted, i.e., moved from its first position 37 to its second position 38, thereby clamping the piston rod 6 as described above and advancing the piston 5 along its longitudinal axis. In other words, by displacing the lever 4 from the first position 35 to the second position 36, the lever 4 engages with the actuator 31 via the pivot point in such a way that the actuator 31 tilts and brings them into frictional engagement with one another, thereby providing a frictional connection between them, which then provides the aforementioned forward movement. The frictional connection between the actuator 31 and the piston 5 of the actuation unit 3 can be achieved by (slightly) tilting, in particular by pivoting the actuator 31 relative to the vertical orientation of the actuator 31 and the piston 5.

[0078] The displacement of the piston 5 of the actuation unit 3 is completed, i.e. the second position is reached, when the actuator 31 abuts against a stopper in the housing 40 of the actuation unit 3, in particular against a compression spring 30 arranged at the level of the actuator 31 on the inner wall of the housing 40, in particular on the inner wall of the part of the housing 40 that faces the syringe 14 when inserted into the injection device and the cooling instrument 13, respectively, and / or when the lever 4, i.e. the lever handle 45, abuts against a stopper 59 of the housing 40.

[0079] In one embodiment, the actuation unit 3 of the injection device 1 of the present invention further comprises a retaining element 16, preferably a retaining bracket, also referred to as a clamping plate, which surrounds the piston rod 6 of the actuation unit 3 at its distal end, i.e., the end opposite the piston stopper 7. The retaining element is held in a recessed outer portion of the housing 40 of the actuation unit 3 and is tensioned by a compression spring 17. The retaining element 16 frictionally engages the piston rod 6 in the retaining position so as to hold the piston 5 in place and prevent the piston 5 from moving backward along its longitudinal axis, i.e., backward (in the opposite direction to the forward direction mentioned above), when the lever 4 and the actuator 31, respectively, move from the second position 35 to the second position 36. This allows re-actuation of the actuation unit 3, i.e., re-movement of the lever 4 from the first position 35 to the second position 36, thereby renewing the delivery of the metered amount of substrate.

[0080] The injection device 1 according to the invention further comprises a needle guide 8, which comprises at least one guide tube 10 and a guide tube holder 9, and is adapted to be able to guide an injection needle 11 through its guide tube 10 when connected to the injection device 1 of the invention, in particular to a syringe 14 when inserted into the holding unit 2 of the injection device 1 of the invention.

[0081] In a preferred embodiment, the guide tube is adapted in particular to (i) guide an injection needle 11 through its guide tube 10 when connected to the injection device 1 of the present invention, in particular to a syringe 14 when inserted into the holding unit 2 of the injection device 1 of the present invention, and (ii) guide a catheter through its guide tube 10 when connected to the injection device 1 of the present invention, most preferably the needle and catheter pass in parallel when both are connected to the injection device 1 of the present invention and guided through the guide tube 10. Details of one embodiment of the needle guide 8 are shown in Figures 7, 8, 9 and 11. The needle guide 8 is preferably made of a metallic material, preferably steel, more preferably stainless steel, more preferably implant-grade steel, more preferably austenitic chromium-nickel-molybdenum steel, for example material 1.4044. The guide tube holder 9 has a recess through which the tubular guide tube 10 extends, and the guide tube 10 is fixed to the guide tube holder 9 so as not to change its position within the guide tube holder 9, but the guide tube 10 is rotatable along its longitudinal axis within the guide tube holder 9. In particular, the guide tube holder 9 and the guide tube 10 have a tolerance to one another by a clearance fit such that the guide tube 10 is rotatable.

[0082] Preferably, the guide tube 10 comprises a channel 43 outside the axis of symmetry of the guide tube 10, and the guide tube 10 is adapted to guide the injection needle through said channel, i.e. the injection needle is guided through said channel 43 when connected to the injection device 1 of the present invention, in particular to the injection syringe 14 when inserted into the holding unit 2 of the injection device 1 of the present invention.

[0083] In one embodiment, the guide tube is assembled as shown in Figures 7, 8, and 9. In particular, the guide tube 10 in one embodiment consists of two parts: a major part (major guide) 25 and a minor part (minor guide) 26. The two counterpart parts are press-fit connected to each other, and in particular, their sheath surfaces are polished together. Assembly of the large guide 25 and small guide 26 into the guide tube 10 can be accomplished by conventional techniques, for example, by stacking or sliding one on top of the other. When the large guide 25 and the small guide 26 are assembled to the guide tube 10, a channel 43 is formed through which the injection needle can be guided, as described above. This channel 43 is preferably outside the axis of symmetry of the guide tube 10, see for example Figure 11.

[0084] In one embodiment, the guide tube 10 further comprises a channel 41, preferably at the axis of symmetry of the guide tube 10, through which a catheter (not shown) can be guided. Thus, in one embodiment, when the large guide 25 and the small guide 26 are connected to the guide tube 10, two channels 43, 41 are formed through which an injection needle and a catheter, respectively, can be guided as described above. Thus, in one embodiment, at least the large guide 25 or the small guide 26, or the large guide 25 and the small guide 26, are provided with respective protrusions (one or more) for forming the channel 41 and / or the channel 43 when assembled with the other part.

[0085] In a preferred embodiment, the larger guide 25 includes a protrusion for forming a catheter channel 41 when assembled with the smaller guide 26 to form the guide tube 10, and the smaller guide 26 includes a complementary protrusion for forming the catheter channel 41. In a further preferred embodiment, the smaller guide 26 further includes an additional protrusion for forming a needle channel 43 when connected to the larger guide 25 to form the guide tube 10.

[0086] In one embodiment, one section of the guide tube 10 is provided with circumferential teeth 42 that are directed outward relative to the surface of the guide tube 10. In a preferred embodiment, the distance between two teeth is between 5° and 25°, preferably between 10° and 20°, and most preferably 15°.

[0087] In one embodiment, the guide tube 10 includes a handle 23 for rotating the guide tube 10 along its longitudinal axis. The handle 23 is preferably positioned perpendicular to the guide tube 10.

[0088] In one embodiment, the guide tube holder 9 of the injection device 1 of the present invention comprises a locking disc 24. One embodiment of the locking disc 24 is shown in FIG.

[0089] In particular, in one embodiment, the locking disc 24 is clamped onto the guide tube holder 9 from above, such that the guide tube 10 is axially fixed within the guide tube holder 9. More particularly, the locking disc 24 is clamped onto the guide tube holder 9 via its grid, i.e., clamping foot 54.

[0090] In one embodiment, the locking disc 24 further comprises notches 53 into which the teeth 42 of the guide tube 10 can engage, thereby enabling engagement of the teeth 42 of the guide tube 10 with the locking disc 24 when the guide tube 10 is rotated a certain distance. Thus, the guide tube 10 can have different locking positions relative to the guide tube holder 9, and the distance between the two locking positions, in particular between the two teeth 42 of the guide tube 10, is between 5° and 25°, preferably between 10° and 20°, and most preferably 15°.

[0091] In one embodiment, the locking disc 24 has laser markers that indicate different locking positions, for example, between 0° and 90°, preferably between 0° and 75°, in each direction. The locking disc 24 is preferably made from a plastic material, more preferably from polyoxymethylene (POM). Thus, moving, and in particular rotating, the guide tube 10 changes the position of the needle 11 by a particular distance, preferably 5° to 25°, preferably 10° to 20°, and most preferably 15°. For ease of handling, the guide tube 10 is in one embodiment operably coupled to a handle 23 that can be used to move, and in particular rotate, the guide tube. Thus, movement of the guide tube 10 results in a change in the injection location.

[0092] In a preferred embodiment, the injection locations are spaced apart from one another by 5° to 25°, preferably 10° to 20°, most preferably 15°, and preferably the injection locations extend along a crescent-shaped tissue within the organism.

[0093] In one embodiment, a spacing of, for example, 15° between at least two injection locations allows for targeting of radial sectors of the urethral sphincter as injection sites. Specifically, targetable sphincter sectors are 13 sectors of 15° each spanning a total angle of 195° around the urethral axis, and preferably 9-10 sectors of 15° each spanning a total angle of 150° around the urethral axis, centered symmetrically about the sagittal plane of the organism.

[0094] In one embodiment, the needle guide 8 is connected to a connecting structure 12 of the injection device 1 of the present invention. The connecting structure 12 operatively connects the above-mentioned parts of the injection device 1 of the present invention. In particular, the connecting structure 12 connects the holding unit 2 to the needle guide 8, and thus also indirectly connects the actuation unit 3 to both above-mentioned components of the injection device 1, since the actuation unit 3 is attached to the holding unit 2. The connecting structure can have any design, as long as it connects the above-mentioned parts of the injection device 1 of the present invention.

[0095] In one embodiment, the connecting structure 12 comprises proximal elongated struts, preferably rods, preferably four elongated guide rods, to which the positioning structures 15 of the holding unit 2 and needle guide 8 of the injection device 1 of the present invention can be attached, i.e., removably connected.

[0096] In one embodiment, the connecting structure 12 is made of a metallic material, preferably steel, more preferably stainless steel, more preferably implant grade steel, more preferably austenitic chromium-nickel-molybdenum steel, for example material 1.4044.

[0097] In one embodiment, the connecting structure 12 further comprises attachment means for an imaging device, in particular an ultrasound probe 27. The attachment means and the connecting structure 12 are designed such that the imaging device 27 is removably coupleable with the connecting structure 12. One particular example of such a connecting structure is that of BK Medical, catalog number UD0238.

[0098] Therefore, in one embodiment, the injection device 1 of the present invention further comprises an imaging device, preferably an ultrasonic probe 27, attached to the injection device 1 via the above-mentioned connecting structure 12. One embodiment of the injection device 1 of the present invention comprising said imaging device 27 is shown in Figures 3 and 4. In particular, in one embodiment, the imaging device 27 extends in the longitudinal direction and is arranged parallel to the connecting structure 12 and the guide tube 10 when the guide tube 10 is perpendicular to the positioning structure 15 and below the guide tube 10, respectively, as shown in Figures 3 and 4, with the head 46 of the ultrasonic probe 27 facing towards the injection site 19 (rather than towards the actuation unit 3 of the injection device 1 of the present invention). The ultrasound probe 27 is preferably a rod ultrasound probe, such as a vaginal or rectal ultrasound probe, preferably a vaginal ultrasound probe. In one embodiment, the ultrasound probe shaft 47 has a diameter of about 10 mm to 20 mm, preferably about 15 mm to 17 mm, and most preferably 16 mm.

[0099] In one embodiment, the ultrasound probe is of BK Medical type 8838 (Endocavity 3D 8838). The ultrasound probe is preferably adapted to generate radial and lateral-frontal cross-sectional patterns.

[0100] In one embodiment, the ultrasonic probe 27 can be moved axially within the connecting structure 12, for example, by losing and reconnecting a clamping ring 48 that secures the ultrasonic probe 27 within the connecting structure 12. In a manner known per se, the ultrasonic probe 27 is connected to an ultrasound device (not shown) that can be used to acquire and display images of tissue.

[0101] In one embodiment, the injection device 1 of the present invention further comprises a positioning structure 15 to which the needle guide 8, which comprises a guide tube holder 9 and a guide tube 10, is connected. Details of one embodiment of the positioning structure are shown in Figures 11, 12 and 13.

[0102] In one embodiment, the positioning structure 15 comprises at least one rail 21, which is movably connected to the connecting structure 12 of the injection device 1 of the present invention, preferably by means of a knurled screw 55. In particular, the rail 21 extends perpendicular to the connecting structure 12, and the guide tube holder 9 is connected to the rail 21 such that the guide tube 10 extends in its functional orientation parallel to the connecting structure 12, with the needle exit opening 49 of the guide tube 10 pointing towards the injection site 19. The rail in one embodiment is shown in Figure 12.

[0103] Thus, in one embodiment, the positioning structure 15 including the rail 21, as well as the needle guide 8 including the guide tube 10 and the guide tube holder 9, are slidable along the connecting structure 12 parallel to the imaging device, in particular parallel to the shaft 47 of the longitudinal ultrasonic probe 27, to adjust the distance of the guide tube 10 relative to the head 46 of the ultrasonic probe 27.

[0104] In a preferred embodiment, the positioning structure 15 further comprises a slide 22, via which the needle guide 8 including the guide tube holder 9 and the guide tube 10 is connected to the above-mentioned rail 21, and the slide 22 is adapted to slide in the above-mentioned direction along the rail 21 in one embodiment. Alternatively, or preferably additionally, the slide 22 pivots the needle guide 8 including the guide tube 10 and the guide tube holder 9 about its pivot axis. In particular, the slide 22 can be pivoted towards or away from the imaging device 27, in particular towards or away from the shaft 47 of the longitudinal ultrasound probe 27, which is achieved by a pivot bearing and a knurled screw 55 of the slide 22.

[0105] In one embodiment, the slide 22 can rotate 360° about its pivot axis. A detailed view of the slide in one embodiment is shown in Figure 13, and one embodiment of the positioning structure 15 including the rail 21 and the slide 22 is shown in Figure 11. The positioning structure 15 including the rail 21 and the slide 22 is in one embodiment made of a metallic material, preferably steel, more preferably stainless steel, more preferably implant grade steel, more preferably austenitic chromium-nickel-molybdenum steel, for example material 1.4044.

[0106] The pivoting of the needle guide 8, and thus of the guide tube 10 and therefore of the injection needle 11 when inserted into the injection device 1 of the invention, makes it possible to adjust the injection angle. The guide tube 10 performs different functions: on the one hand, it provides a guide for the injection needle 11, and on the other hand, it sets the injection angle (the inclination angle of the injection syringe 11 relative to the axial reference direction). From the axial reference direction, the injection angle forms an angle in the range of 3° to 10°, preferably 4° to 9°, more preferably 5° or 7.5°, and most preferably 7.5°.

[0107] In one embodiment, the injection needle 11 is bent by 3° to 10°, preferably 4° to 9°, more preferably 5° or 7.5°, and most preferably 7.5°, i.e., its curvature is 3° to 10°, preferably 4° to 9°, more preferably 5° or 7.5°, and most preferably 7.5°.

[0108] In a preferred embodiment, the front of the needle itself, which projects through the guide tube 10, has a 5° curvature, and the guide tube 10 can be positioned to adjust the curvature of the needle, preferably by a further 2.5°, i.e., the guide tube 10 can be adjusted upward or downward relative to its longitudinal axis. To safely guide the injection needle 11, the length of the tapered section 58 of the guide tube, i.e., the section that is provided with the needle exit opening 49 and faces the injection site 19, is generally not limited and is selected, inter alia, to ensure a certain maximum penetration depth of the injection needle 11 and / or to reach the respective tissue to be injected. For example, the female urethra is approximately 4.8-5.1 cm long, and the male urethra is approximately 20-25 cm long.

[0109] Thus, in one embodiment, the tapered section 58 has a length in the range of 2 cm to 50 cm, preferably at least 4 cm, preferably in the range of 4 cm to 40 cm, preferably in the range of 4 cm to 20 cm or 4 cm to 15 cm, but most preferably about 4 cm. The insertion depth of the injection needle 11 is selected depending on the desired use of the injection device 1 of the present invention. Generally, the tissue into which the injectable substance is to be injected, such as a sphincter, in particular the external urethral sphincter, is observed by the imaging device 27, and when injecting the substance, the user of the injection device ensures that the injection needle 11 does not penetrate the tissue.

[0110] As described above, in one embodiment, the injection device 1 of the present invention comprises an injection needle 11 that is detachably connected to the injection syringe 14 when inserted into the injection device 1, and the injection needle 11 protrudes in a bent form from the needle exit opening 49 of the guide tube 10, the bend of the needle 11 being caused by grinding 50 in the guide tube 10. In particular, the needle 11 has a bend that faces radially outward relative to the axial orientation of the ultrasonic probe 27 and the guide tube 10, respectively.

[0111] In one embodiment, the injection needle 11 has a length of 10 cm to 30 cm, preferably 15 cm to 25 cm, and most preferably 20 cm. In one embodiment, the size of the injection needle 11 ranges from 18 gauge to 23 gauge (G). In one embodiment, an injection needle 11 with a length of 20 cm and specifications of 17 to 18 G is used.

[0112] In one embodiment, the injection device 1 of the present invention is connected to a mount, such as a bed or floor mount, preferably via a base 18 which is part of the connecting structure 12 . As mentioned above, the present invention further relates to a method for injecting an injectate into a living organism, preferably into the external urethral sphincter 20 (schematically, not drawn to scale), in which an injection device 1 and a medical device of the present invention are used, respectively, and which includes at least one step of administering and injecting the injectate by displacing the lever 4 of the actuation unit 3 of the injection device 1 from a first position 35 to a second position 36, as described in detail above. More particularly, in a preferred embodiment, the method of the present invention comprises: a) positioning the injection device 1 of the present invention so that it has a predetermined position relative to an injection site 19 in a living organism 20; b) advancing the injection needle 11 until it reaches the injection site 19, i.e., until the injection needle 11 penetrates the desired tissue 20; c) injecting the injection substance by displacing the lever 4 of the actuation unit 3 of the injection device 1 from the first position 35 to the second position 36; d) optionally retracting the needle 11; e) changing the injection position by moving the guide tube 10 from the first locking position to the second locking position, preferably by moving the guide tube 10 clockwise by 15°; wherein steps b) through e) can be repeated at different injection sites and / or until the entire injection substance has been injected, or only one injection or multiple injections at one injection site are performed (repeating steps a) through d) and steps b) through d), respectively).

[0113] In a preferred embodiment, steps b) to e) are repeated at least 2 times, preferably 2 to 13 or 2 to 18 times, more preferably 2 to 10 or 2 to 15 times, and most preferably 9 or 10 or 15 times, and the injections are preferably performed at at least 2 different injection sites, preferably 2 to 13 different injection sites, more preferably 2 to 10 different injection sites, and most preferably 9 or 10 different injection sites.

[0114] In one embodiment, 10 injections of 400 μl are given at 10 different injection sites (low dose). In one embodiment, 9 injections of 400 μl are given at 9 different injection sites (low dose). In another embodiment, 15 injections of 400 μl are given at 9 or 10, preferably 10, different injection sites (high dose), meaning that some injection locations receive two injections. The injection(s) can be placed along the course of the urethra, for example, mid-urethral, ​​circumferential and / or proximal urethral injection(s).

[0115] In one embodiment, 9 to 10 injections of 400 μl are performed, with one or two injections in the central part of the external urethral sphincter (-30° to +30° calculated from the center of the longitudinally extending muscle) and four injections of 400 μl each further radially outward, preferably at -45° to -90° and +45° to +90°.

[0116] In another embodiment, 15 injections of 400 μl are made, with one or two injections made in the muscle belly portion of the external urethral sphincter (-30° to +30° calculated from the longitudinally extending muscle belly), four injections of 400 μl each made further radially outward, preferably at -45° to -90° and +45° to +90°, and five more injections made in the central region mentioned above (-30° to +30°, particularly at 0°, -15°, -30°, +15°, and +30°). The injection volume can also be varied. For example, it can be adjusted taking into account the amount of active ingredient in the injection material, for example, the density of muscle-derived progenitor cells to be injected for the treatment of the above-mentioned diseases. In particular, a lower or higher injection volume can be selected. When cells are used as the injection material, the injection volume should preferably not exceed 500 μl, more preferably not exceed 400 μl, to ensure sufficient oxygen supply and eliminate necrosis. However, as long as the supply of oxygen to the cells is ensured, even higher injection volumes are feasible.

[0117] Therefore, in one embodiment, any injection volume can be selected as long as the supply of oxygen to the cells is ensured. For example, if the injectable substance spreads over a large area at the injection site, i.e., the surface area to volume ratio of the injection depot is large, so that oxygen can easily diffuse to the cells, a higher injection volume, for example up to the ml range, can be selected.

[0118] In a preferred embodiment, the injection volume is 500 μl or less, preferably 400 μl or less, more preferably 10 μl to 400 μl, more preferably 50 μl to 400 μl, more preferably 100 μl to 400 μl, more preferably 150 μl to 400 μl, more preferably 200 μl to 400 μl, more preferably 250 μl to 400 μl, more preferably 300 μl to 400 μl, more preferably 350 μl to 400 μl, and most preferably 400 μl. Thus, the described injection volumes can be administered one or more times as described above. In one embodiment, the total volume to be administered is 10 μl to 10 ml, preferably 1 ml to 10 ml, more preferably 3 ml to 8 ml, more preferably 4 ml to 6 ml, and most preferably 4 ml or 6 ml.

[0119] The positioning step a) comprises, in a preferred embodiment, assembling the injection device 1 of the present invention and attaching the device 1 to a mount, such as a bed or floor mount, more particularly a brachytherapy stepper arm, preferably positioned in front of the subject to be treated.

[0120] In a preferred embodiment, the injection device 1 is also coupled via the attachment means of the connecting structure 12 to an imaging device, preferably an ultrasound probe 27, which is preferably inserted into the vagina to visualize the bladder, urethra and external sphincter. The assembly steps include, inter alia, in a preferred embodiment, inserting the injection syringe 14 containing the injection substance into the injection device 1, in particular the holding unit 2 of the injection device 1, preferably together with the cooling unit 13; placing the injection needle 11 on the syringe nozzle 34 so that the needle tip should be aligned with the 0° mark of the locking disc 24 when viewed from the distal side; and guiding the injection needle 11 through a small channel 43 outside the axis of symmetry of the guide tube 10, with the handle 23 of the guide tube 10 preferably facing vertically upwards.

[0121] In a preferred embodiment, the assembling step further includes guiding a catheter through the central channel 41 of the guide tube 10, preferably inserting the catheter into the bladder via the urethra and filling the bladder with an isotonic sodium chloride solution. While any catheter that performs the functions described above may be used, in a preferred embodiment, the catheter has a length of 30-50 cm, preferably 35-45 cm, more preferably about 40 cm, and especially 41 cm. One specific example of a catheter that can be used in accordance with the present invention is the SupraCath Single Catheter, 3 ml, Ch. 8, 41 cm long.

[0122] In a preferred embodiment, the positioning step a) further comprises filling the needle 11 with the injection substance by pulling the lever 4 (once or several times) until the first droplet of injection substance appears at the tip of the needle 11. The injection needle 11 is preferably advanced until the needle tip just emerges from the guide tube 10, preferably as seen in the ultrasound image, which is preferably done by advancing the holding unit 2 including the actuation unit 3 along the connecting structure 12. Step b), i.e., the step of advancing the injection needle 11, is preferably carried out by advancing the actuation unit 3 including the holding unit 2 of the injection device 1 of the present invention in the direction of the injection site 19 along the connecting structure 12 until the injection needle 11 reaches the injection site 19, the operator, e.g., a physician, preferably being guided by ultrasound images. The injecting step c) results in the administration of preferably 400 μl of the injection substance via the mechanism as described above, in particular by triggering the lever 4 of the actuation unit 3, which is triggered once or twice depending on the dose to be injected. The retracting step d) preferably comprises completely retracting the needle 11 into the guide tube 10. The retracting step (step d)) of the syringe is preferably performed simultaneously with actuating the lever, and preferably also manually by an operator by retracting the actuation unit including the holding unit along the connecting structure, the operator also preferably being guided by ultrasound imaging. Step e) preferably further comprises rotating the image plane of the ultrasound probe 27 by at least one increment.

[0123] In the following, a preferred use of the present invention is described in the treatment of muscle dysfunction, preferably sphincter dysfunction, preferably dysfunction of the external urethral sphincter, and thus preferably in the treatment of urinary incontinence, preferably female stress urinary incontinence (SUI). The injection device 1 according to the present invention is preferably used for the treatment of said symptoms with muscle progenitor cells. By injecting cultured muscle progenitor cells into the corresponding muscle, muscle function is restored. In particular, by injecting the cells into the urethral sphincter, contractile force is increased, thereby restoring continence. When the treatment is particularly preferably carried out with autologous cells, a) obtaining a tissue sample by skeletal muscle biopsy of the subject to be treated; b) isolating muscle progenitor cells, preferably by surgically removing adipose tissue and / or tendon tissue and / or connective tissue from a tissue sample, and disrupting and enzymatically digesting the tissue sample to reduce the number of fibroblasts, thereby obtaining a population of muscle progenitor cells; c) expanding muscle progenitor cells; d) preferably forming an injectate by mixing the cells with a carrier solution, such as a collagen solution, preferably having a collagen concentration of 1-4 mg / ml, more preferably about 2 mg / ml; e) injecting the injectate into a corresponding muscle, preferably a sphincter, preferably the external urethral sphincter; is provided.

[0124] The muscle progenitor cells are preferably provided as described in WO 2019 / 215090, the contents of which are incorporated herein by reference. After formation of the injectate and prior to injection, the injectate is loaded into a syringe 14 . Alternatively, the injection material can be formed using a syringe with two syringe chambers, one containing muscle progenitor cells and the other containing a carrier solution, such as the collagen solution described above. During simultaneous injection from both syringe chambers, the carrier mixes with the cells, thereby forming the injection material. A syringe 14 filled with the injection substance is inserted into the injection device 1 of the present invention and the injection is performed as described above. One detailed example of how to assemble and use the injection device and medical device of the present invention for the treatment of female urinary incontinence is provided below.

[0125] 1) The chilled device 13 containing the cell suspension in the syringe 14 is removed from the shipping container and placed on sterile ice until use. 2) The needle guide 8, including the guide tube 10 and guide tube holder 9, and the positioning structure 15 are placed on sterile ice. Preparation of connecting structure 12: 3) Unpack the needle 11, remove the protective cover, blunt guide needle, and inner mandrel. Place the needle on sterile ice. 4) Position the floor / bed mount (brachystepper) in front of the patient 20. 5) The connecting structure 12 is connected to the base 18 on the Brachystepper and positioned. 6) Place the sterile cover around the base 18 on the Brachystepper. 7) The ultrasonic probe 27 is lubricated, protected and lubricated again, then inserted into the holder on the connecting structure 12 (observe the pins and notches) and fixed with two clamping rings 48. 8) Press the holding unit 2 onto the four proximal guide rods of the connecting structure 12 until the rear foot is flush with the ends of the guides, and if necessary, temporarily secure the holding unit 2 with the two clamping screws 57. 9) The positioning structure 15 (including the guide tube holder 9) containing the swivel bearings is pressed onto the two distal guide rods of the connecting structure 12 until it is approximately in the center position and temporarily fixed with the clamping screws 55. Adjusting the ultrasound probe and needle guide: 10) General anesthesia with intubation. 11) Antibiotic prophylaxis with intravenous Zinacef 1.5g (in case of intolerance, an alternative antibiotic will be determined before surgery). 12) Lithotomy Storage 13) Disinfection and covering of the external genitalia and urethral meatus. 14) By moving the brachystepper, the ultrasound probe 27 is inserted transvaginally to visualize the bladder with the bladder neck, striated sphincter and urethra in three-dimensional mode, after which the position of the brachystepper is fixed again. 15) Remove the Charlie 8 Balloon indwelling catheter from its packaging and thread it through the needle guide 8, particularly the central channel 41. 16) A catheter is inserted into the bladder via the urethra and occluded with 3 ml of sugar block or NaCl solution. The bladder is emptied. 17) Using a bladder syringe, fill the bladder with 100 ml of NaCl, attach a Kocher clamp to the end of the catheter, and temporarily position the clamped external part of the catheter on the holding unit 2. 18) Insert the distal section of the indwelling catheter (behind the needle guide 8) into the central channel of the large part 25, 10 of the guide tube (3 / 4 guide). 19) Press the small portion 26, 10 of the guide tube (1 / 4 guide) onto the large portion (3 / 4 guide) 25, 10 from the front so that the guide tube 10 surrounds the catheter; see also FIG. 20) Insert the guide tube 10 distally into the guide tube holder 9. 21) Clamp the plastic spring, i.e. the locking disc 24, onto the guide tube holder 9 from above so that the guide tube 10 is axially fixed in the guide tube holder 9. It is important to ensure that the clamping foot 54 is oriented straight = not bent and there will be a clicking noise. 22) Check for correct clamping by rotating the guide tube 10 using the guide tube handle 23, whereby the guide tube 10 should engage at the provided 15° increments 42. Then return the guide tube 10 to the 0° position (handle of the guide tube 23 pointing upwards). The angles are printed on the plastic code of the locking disc 24. 23) Loosen the two clamp screws 55 of the needle guide positioning structure 15 so that the guide tube 10 can be inserted into the urethra along with the balloon catheter. 24) Tighten the clamp screw 55 of the needle guide 10 according to the correct position and alignment, paying particular attention to the attenuating abdominal space of the guide tube 10, the distance to the bladder neck (DK balloon), and full visibility of the striated sphincter (hypoechoic periurethral structures). Preparation of actuation unit (dosing tool) 3: 25) Screw the lever shell cover 44 onto the lever shell 32. 26) The locking spring (retaining element 16) is held down so that the piston rod 6 can be pushed back completely. 27) Then check the operation and full return of the trigger (lever 4). For this purpose, operate the lever 4 five times, after which the piston rod 6 should move forward. 28) Remove the chilled device 13 containing the cell suspension from the sterile ice and swirl to mix. 29) The cooling device 13 including the syringe 14 is screwed onto the actuation unit 3. 30) Remove the luer lock closure on the syringe 14. 31) Thread the needle 11 onto the luer lock nozzle 34 of the syringe 14 so that the needle tip is aligned at the 0° mark (12 o'clock) when viewed distally. 32) Insert the actuation unit 3 a short distance into the holding unit 2 with the lever handle 45 pointing upwards. 33) Check again that the needle tip is aligned at the 0° mark (12 o'clock) when viewed from the distal side. The orientation of the needle 11 notch can be adjusted by slightly loosening the screw 51 on the cooling unit and turning the syringe 14, then tightening the actuation unit 3 again and inserting it into the holding unit 2. 34) Fill the needle 11 with liquid (prime) by squeezing the trigger 4 (possibly several times) only until the first droplet appears at the tip of the needle 11. 35) Advance the actuation unit 3 within the holding unit 2 until the distance to the forward limit within the holding unit 2 is at least as long as the expected puncture distance. 36) Loosen the clamp screw 57 of the holding unit 2, then carefully push the holding unit 2 together with the actuation unit 3 forward on the guide rod of the connecting structure 12 and manually insert the tip of the needle 11 into the upper lumen 43 in the guide tube 10. 37) Carefully push the holding unit 3 including the actuation unit 3 further forward until the tip of the needle 11 emerges from the guide tube 10 and is visible in the ultrasound image; tighten the clamping screw 57. Injection of cell (muscle-derived progenitor cell) suspension: 38) Select the starting position from a distal perspective of 0° (12 o'clock), with the handle 23 of the guide tube and the handle 45 of the lever of the actuation unit 3 pointing vertically upwards. 39) While observing the ultrasound image, manually advance the working unit 3 until the tip of the needle 11 penetrates sufficiently deep into the striated sphincter muscle 20. 40) The treatment product is injected by actuating trigger 4 with the index finger. Depending on the dosage, trigger 4 is actuated once or twice. One actuation of trigger 4 corresponds to a volume of 0.4 ml. The volume present in syringe 14 can be checked using the scale printed on holding unit 2. 41) When the needle 11 is fully retracted into the guide tube 10, rotate the guide tube 10 clockwise by one click (15°) and tilt the actuation unit 3 (15°) to set the next injection level. 42) Each time the guide tube 10 is clicked, the image plane of the ultrasound probe 27 is also rotated by at least one increment (+ / - keys). 43) Perform further radial injections in a clockwise direction (e.g., +15°, +30°, +45°, +60°), repeating steps 39 through 42 each time. 44) Once the needle 11 is fully retracted into the guide tube 10, realign the guide tube 10 and actuation unit 3 to 12 o'clock (0°) when viewed distally and place the remaining injections using a similar counterclockwise sequence (e.g., position -15°, position -30°, position -45°, position -60°). 45) To achieve the most complete coverage of the striated sphincter, perform the following in its entirety: A low dose of 4 ml = 9-10 injections of 0.4 ml each (1-2x central, 4x right and left). A high dose of 6 ml = 15 injections of 0.4 ml each, followed by a second injection in the central position (-30° to +30° range) with the same procedure. The dorsal periurethral area is omitted. 46) After the last injection, completely withdraw the actuation unit 3 including the needle 11 and set it aside. 47) Unblock the catheter. 48) Loosen the clamp screw 55 on the needle guide positioning structure 15 so that the guide tube 10 can be retracted. 49) Remove the Charr 8 catheter from the body. If the catheter cannot then be withdrawn through the needle guide lumen 41, the guide tube holder 9 must be withdrawn by removing the locking disc 24 and disassembled to expose the catheter. 50) Retract the Brachystepper arm (floor / bed mount) with the connecting structure 12 and ultrasound probe 27 so that the probe 27 is no longer inside the body. 51) Insert a new balloon catheter Charr.12 and occlude with 10 ml of Glycoblock or NaCl. 52) End of procedure 53) Disassembly of injection device 1.

[0126] Several documents are cited throughout the text of this specification. The contents of all cited references (including references cited throughout this application, issued patents, published patent applications, including background sections and manufacturer's specifications, instructions, etc.) are expressly incorporated herein by reference without any admission that the cited documents are in fact prior art with respect to this invention. The features of the invention disclosed in the specification, the drawings and the claims may be important individually or in any combination for realizing the invention in its various embodiments. [Explanation of symbols]

[0127] 1 Injection device 2 holding units 3. Operating unit 4 Lever (Trigger) 5 pistons 6 Piston rod 7 Piston stopper 8 Needle guide 9 Guide tube holder 10 Guide tube (consisting of two parts) 11 Syringe needle 12 Connection structure 13 Cooling equipment 14 syringes 15 Positioning structure 16 Retaining element (clamp plate) 17 First compression spring 18 Pedestal 19 Injection site 20 Living organisms, especially living organisms' sphincters 21 Rail 22 slides 23 Guide Tube 10 Handle 24 Rock Disc 25 Guide tube 10 major parts 26 Guide tube 10 small parts 27 Imaging devices, especially ultrasound probes 28 Syringe 14 plunger 29 Syringe 14 piston 30 Second compression spring 31 Actuator (clamp piece) 32 Lever Shell 33 Bolt connecting the actuator 31 (clamp piece) and the lever 4 (trigger) 34 Nozzle of syringe 14 35 Lever 4, first position 36 Lever 4 second position 37 Actuator 3 (clamp piece) first position 38 Actuator 3 (clamp piece) second position 39 Syringe body 40 Lever 4 housing 41 Catheter Channel 42 radial teeth 43 needle channels 44 Lever shell 32 cover 45 Lever 4 Handle 46 Head of ultrasound probe 27 47 Shaft of ultrasonic probe 27 48 Clamp ring 49 Needle exit opening 50 Grinding 51 Thread cutting 52 Knurled screw of actuation unit 3 53 Notches into which the teeth 42 of the guide tube 10 can engage 54 Grid for attachment to guide tube holder 9, i.e. clamp foot 55 Knurled screw of positioning structure 15 56 Opening for knurled screw 52 57 Clamp screw 58 Tapered portion of guide tube 59 Housing stopper 60 Cooling Device Facets

Claims

1. An injection device [1] provided for injecting an injectable substance into a living being by means of a syringe [14], comprising: a holding unit [2] adapted to hold the syringe [14]; an actuation unit [3] adapted for administering an injection of the injection substance, detachably coupled to the holding unit [2] when the holding unit [2] holds the syringe [14], and capable of coupling with a plunger [28] of the syringe [14], preferably the actuation unit [3] comprising a lever [4] and a piston [5], wherein displacement of the lever [4] from a first position [35] to a second position [36] results in movement of the piston [5] along its longitudinal axis, and the actuation unit [3] is adapted to at least partially transmit the movement to the plunger [28] of the syringe [14] when the syringe [14] is coupled with the actuation unit [3]; a needle guide [8] adapted to be removably connectable with an injection needle [11] and adapted to change the injection position of said injection needle [11]; a connecting structure [12] that connects the holding unit [2] and the needle guide [8]; Injection device [1].

2. The needle guide [8] is adapted to be removably connectable to a catheter, preferably a transurethral bladder catheter. An injection device [1] according to claim 1.

3. The needle guide [8] comprises a guide tube [10] and a guide tube holder [9], and the guide tube [10] is rotatable along its longitudinal axis within the guide tube holder [9]. An injection device [1] according to claim 1 or 2.

4. The guide tube [10] is composed of two parts, a major part (major guide, [25]) and a minor part (minor guide, [26]), which, when assembled, form the guide tube [10]. An injection device [1] according to claim 3.

5. When the major part (major guide, [25]) and the minor part (minor guide, [26]) of the guide tube [10] are assembled to form the guide tube [10], at least one channel is formed, preferably two channels [41], [43] are formed, preferably one channel [43] is outside the axis of symmetry of the guide tube [10] and is used to guide the injection needle [11] through, and the other channel [41] is inside the axis of symmetry of the guide tube [10] and is used to guide the catheter through. An injection device [1] according to claim 4.

6. The needle guide [8] is adapted so that the injection needle [11] and the catheter pass parallel to each other through the guide tube [10] and the channels [41, 43], respectively, when both are connected to the needle guide [8]. An injection device [1] according to claim 5.

7. The injection device [1] further comprises a cooling device [13] held by the holding unit [2], and preferably the cooling device [13] is removable and / or the cooling device [13] is rotatable about its longitudinal axis. An injection device [1] according to any one of claims 1 to 6.

8. The cooling devices [13] are spaced apart from each other by 10°-20°C, preferably 15°, and preferably comprise facets [60] surrounding the cooling devices [13]. An injection device [1] according to claim 7.

9. The actuation unit [3] further comprises a retaining element [16], preferably a retaining bracket, which frictionally engages the piston rod [6] in a retaining position so that the piston [5] is held in a fixed position and prevented from being retracted along its longitudinal axis when the lever [4] is moved from the second position [36] to the first position [35]. An injection device [1] according to any one of the preceding claims.

10. the displacement distance of the lever [4] between the first position [35] and the second position [36] is between 17 mm and 23 mm, preferably between 19 mm and 21 mm, most preferably 20 mm; An injection device [1] according to any one of the preceding claims.

11. The injection device [1] is adapted to guide the injection needle [11] to at least two injection positions different from each other by rotating the guide tube [10], the guide tube [10] having a channel [43] outside the axis of symmetry of the guide tube [10], and the guide tube [10] is adapted to guide the injection needle [11] through the channel [43]. An injection device [1] according to any one of the preceding claims.

12. The guide tube [10] has circumferential teeth [42] directed outward relative to the surface of the guide tube [10], and when the guide tube [10] is rotated in the guide tube holder [9], the teeth [42] engage with a locking disc [24] arranged on the guide tube holder [9], and preferably, the distance between the two teeth [42] of the guide tube [10] is 15°. An injection device [1] according to any one of the preceding claims.

13. the injection locations are spaced apart by 10° to 20°, preferably 15°, and preferably the injection locations span a total angle of 195°, preferably 150°, about the urethral axis and are symmetrically centered about the sagittal plane; An injection device [1] according to any one of the preceding claims.

14. The guide tube [10] comprises a channel [41] inside the axis of symmetry of the guide tube [10], and the guide tube [10] is adapted to guide the catheter through the channel [41]. An injection device [1] according to any one of the preceding claims.

15. The connecting structure [12] is adapted to be removably connectable to an imaging device, preferably an ultrasound probe [27]. An injection device [1] according to any one of the preceding claims.

16. further comprising an imaging device, preferably a longitudinal ultrasound probe [27], detachably coupled to the injection device [1] via the connection unit [12]; An injection device [1] according to any one of the preceding claims.

17. The needle guide [8] is movable and preferably (i) the needle guide [8] is movable relative to the imaging device [27], and preferably the distance from the needle guide [8] to the shaft [47] of the imaging device [27] is adjustable; (ii) the needle guide [8] is movable relative to the holding unit [2], preferably the distance from the needle guide [8] to the holding unit [2] is adjustable, while the distance from the needle guide [8] to the shaft [47] of the imaging device remains the same; and / or (iii) the needle guide [8] is pivotable; An injection device [1] according to any one of the preceding claims.

18. An injection device [1] and an injection needle [11], The injection device [1] is as described in any one of the preceding claims, At least the front part of the injection needle [11] protruding from the guide tube [10] toward the injection site [19] has a bend directed radially outward relative to the axial directions of the ultrasonic probe [27] and the guide tube [10], and preferably, the injection needle [11] has a curvature of 3° to 10°, preferably 5° to 7.5°, and more preferably less than 5° to 7.5°. An injection device [1] and an injection needle [11].

19. An injection device [1], an injection needle [11] and a catheter, The injection device [1] and the needle [11] are as described in any one of the preceding claims, The catheter is preferably a transurethral bladder catheter. An injection device [1], an injection needle [11] and a catheter.

20. The injection device [1] shown in Figures 1 to 13, as well as their equivalents.

21. A medical device adapted for injecting an injectable substance into a living being, comprising an injection device [1] according to any one of the preceding claims, a syringe [14] having a syringe body [39] and a piston [28], and an injection needle [11], the syringe [14] is arranged in a holding unit [2] of the injection device [1] and / or the injection needle [11] is arranged in a needle guide [8], preferably the medical device further comprises an imaging device [27], preferably an ultrasound probe, preferably the medical device further comprises a cooling instrument [13] according to claim 8 or 9, preferably the medical device further comprises a catheter arranged in the needle guide [8], Medical devices.

22. Use of a syringe [14] containing an injection substance in an injection device [1] according to any one of claims 1 to 20 or in a medical device according to claim 21.

Images