Injection device

Abstract

There is provided an injection device [1] for injecting a substance into a living body [20] using a syringe [14], comprising: a holding unit [2] adapted to hold the syringe [14]; an actuating unit [3] adapted to quantitatively inject an injection substance and detachably coupled to the holding unit [2] and capable of coupling with the syringe [14] when the holding unit [2] holds the syringe [14]; a needle guide (8) adapted to be removably coupleable with the injection needle (11) and for changing the injection position of the injection needle (11); and a connection structure [12] that connects the gripping 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 dosing an injection substance, a medical device equipped with such an injection device and a method for injecting an injection substance into biological tissue, in particular muscle tissue. Background Art

[0002] In recent years, several methods for treating incontinence have been developed, such as stress urinary incontinence (SUI), male stress urinary incontinence after prostatectomy, and fecal incontinence. SUI is characterized by involuntary urine outflow associated with effort, straining, or coughing / sneezing. In the treatment of female SUI, there are several non-surgical and surgical options. Urethral injection is a well-described minimally invasive technique and represents a common surgical procedure for SUI. There are several urethral fillers (UBA) available for injection, such as those summarized in Li and Westney, Urol Clin North Am 46 (2019), 1-15, and cell therapy methods have been further developed recently, such as those described in WO 2019 / 215090 A1.

[0003] Injections of fillers and cells are usually performed using an injection needle while visualizing the tissue, for example using an ultrasound probe or a cystoscope. For practical medical applications, precise positioning of the injection needle is essential in order to deposit the injectable substance exactly at the desired injection site and to minimize the risk of damage to surrounding tissue.

[0004] To position the injection needle, an injection device with a needle guide is usually used, which has a predetermined position and orientation relative to the ultrasound probe; see for example WO 02 / 45588 A1.

[0005] Although some injection devices are known in the art, there is a continuing need to provide devices that allow for precise injection of an injectable matrix. Summary of the invention

[0006] The present invention provides an injection device, which is configured to inject an injection substance into a living body using a syringe, and is particularly suitable for injection into the sphincter muscle, and a medical device, which includes the injection device, and a directional injection method, preferably a limited volume directional injection.

[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 a fluid outlet). Preferably, the syringe further comprises an injection needle (hollow syringe needle). The syringe needle can be straight or curved. The syringe body can have one or more chambers, preferably cylindrical. Each chamber is configured to receive a syringe plunger including a piston. Displacement of at least one syringe plunger in the syringe body can cause an injectable substance (e.g., a fluid) to be discharged from the syringe body through an outlet (i.e., a nozzle), preferably through a syringe needle connected to the outlet. For example, a syringe can include a syringe body having a single chamber, a syringe needle connected to the single chamber and a syringe plunger arranged in the single chamber, or a syringe body having two or more chambers, the syringe needle connected to the two or more chambers and each of the two or more chambers is provided with a syringe plunger.

[0008] The term "injectable substance" is generally used herein to refer to any injectable substance, that is, 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 includes a cell suspension (or dispersion), in particular a suspension of muscle-derived precursor cells. In particular, the cells are suspended in a suitable liquid, for example, a buffer, a cell culture medium and / or a carrier solution, such as collagen. Such cells are described, for example, in WO 2019 / 216090 A1, the contents of which are incorporated herein by reference.

[0009] Regarding the device, the present invention provides an injection device, which comprises at least a syringe holding unit (i.e., the syringe holding unit is designed to hold the syringe), an actuation unit and a needle guide, and optionally, a structure connecting at least the holding unit to the needle guide. The injection device of the present invention is designed to inject an injectable substance in a specific dose (preferably a constant dose), i.e., is designed to quantitatively inject an injectable substance, and more particularly, is designed to repeatedly quantitatively inject a specific dose (preferably a constant dose) at a plurality of different injection sites.

[0010] The quantitative injection is achieved by an actuating unit as part of the injection device of the present invention, the actuating unit comprising a joystick and a piston, and being detachably connected to the syringe in the holding unit. In particular, the actuating unit is connected to the plunger of the syringe. By operating the joystick, a specific / predetermined amount of injection substance, i.e. a specific dose, is ensured to be dispensed. Therefore, the actuating unit can also be referred to as a quantitative unit. The quantitative injection is ensured by the predetermined displacement distance of the actuating unit, the lever being translated to a predetermined distance by the piston of the actuating unit via the joystick connected to the syringe plunger, whereby the syringe plunger is moved into the syringe body, thereby injecting a specific amount of the injectable substance through the needle.

[0011] In more detail, the actuation unit of the injection device of the present invention is detachably coupled to the holding unit and is capable of being coupled to the syringe via the plunger of the syringe when the holding unit holds the syringe, wherein the actuation unit comprises a lever and a piston, wherein a displacement of the lever from a first position to a second position, preferably performed by pivoting the lever from the first position to the second position about a pivot axis, causes the piston to move along its longitudinal axis, wherein the actuation unit is adapted to transfer the movement at least partially to the plunger of the syringe when the syringe is coupled to the actuation unit. In particular, the displacement of the lever causes the piston to move forward along its longitudinal axis in a forward direction, i.e. towards the piston stop. The distance between the first and second positions of the lever is predetermined, thereby ensuring that the piston is advanced by a predetermined distance. Thus, when the distance between the first and second positions of the lever changes, it has an effect on the movement of the piston. In other words, the piston moves from a first position to a second position, wherein the distance is predetermined by the distance between the first and second positions of the lever.

[0012] Even more in detail, the actuation unit of the injection device of the present invention further comprises an actuator (clamp) through which the piston extends, and wherein a displacement of the lever from the first position to the second position causes the lever to engage the actuator, preferably via a pivot point, such that the actuator is frictionally connected to the piston, causing the actuator to advance along the longitudinal axis together with the piston in a first piston movement direction (forward direction), i.e., when the syringe is placed in the holding unit and the actuation device is coupled to the syringe, the piston of the actuation unit is moved towards the plunger of the syringe, such that the plunger of the syringe is advanced in the first plunger movement direction (forward direction), i.e., the plunger of the syringe is moved such that an injection substance is dispensed from the syringe body. The frictional connection between the actuator and the piston of the actuation unit can be caused by (slightly) pivoting the actuator relative to a vertical orientation of the actuator and the piston. Thus, when the joystick is displaced from the first position to the second position, the piston of the actuating unit is displaced a certain displacement distance along the longitudinal axis, that is, displaced from the first position to the second position in the direction (forward direction) of the piston stopper. In other words, tilting the actuator can cause the friction connection between the actuator and the piston rod, so that they are frictionally engaged with each other, and then cause the above-mentioned forward movement. The forward movement of the piston applies a force in the direction of the plunger of the syringe, causing the forward direction of the plunger, thereby obtaining the metering matrix delivery. When the actuator and / or the joystick arm are close to the stopper in the housing of the actuating unit, the piston of the actuating unit completes the displacement, that is, arrives the second position. The actuation of the actuator is performed by spring force. The forward direction is understood to be toward the connector of the syringe, wherein the position of the connector on the syringe is defined as in the front, and the movement of an object (e.g., an injectable substance or a plunger) through the syringe toward it is defined as movement in the forward direction, and the other open end of the syringe (through which the plunger is introduced into the syringe) is defined as the rear end of the syringe, and the movement of an object (e.g., an injectable substance or a plunger) through the syringe toward the rear end is defined as movement in the reverse or rearward direction.

[0013] When the joystick is displaced back to the first position, i.e., 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 so that the actuator is displaced from the second position to its first position relative to the piston rod.

[0014] Thus, when the lever of the injection device of the present invention is brought from the first position to the second position, a specific amount (i.e. a specific dose) of the injection substance is dispensed, in particular by dispensing through the connector of the syringe via a needle, and thus injecting (if applied to an animal or human body) without having to manually advance the plunger of the syringe in a forward direction along its longitudinal axis, the latter being less accurate in terms of the dispensed amount of the injection substance, since the distance to which the plunger of the syringe has to be advanced to ensure the dispensing of a certain amount of the injection substance has to be estimated by the operator (e.g. a physician) and is not predetermined by a predetermined displacement distance of the lever.

[0015] Ensuring that a specific dose is injected without major variations is particularly important for clinical studies and subsequent treatment methods. For example, during the clinical development of a new drug, a correct dose exploration study is essential. The ineffective dose must be defined as well as the average effective dose and the maximum effective dose. Then, taking into account tolerance, the optimal therapeutic dose range can be selected. Thus, when the injection device of the present invention is used in clinical studies and therapeutic applications, the precise amount of the injected substance can be ensured.

[0016] In one embodiment, injection device of the present invention, particularly the actuating unit of injection device of the present invention further comprises a retaining element, preferably, retaining bracket (clamping plate), wherein, retaining element frictionally engages the piston rod in the retaining position, so that the piston is retained in place and prevents the piston from retracting along its longitudinal axis, that is, when the joystick and actuator move from the second position to the first position respectively, move backward (direction opposite to the above-mentioned forward direction). This allows the actuating unit to actuate again, that is, the joystick (and actuator) moves from the first position to the second position again, thereby re-dosing the matrix delivery. By actuating the retaining bracket, it is released so that the piston rod is relaxed and can be reset. In order to make this principle work, the force transmission from the actuator to the piston must be greater than the force transmission from the retaining bracket to the piston.

[0017] This mechanism allows for repeated injections and thus multiple injections of a specific dose of an injectable substance without having to refill the syringe or replace the syringe with another one, thus saving time and reducing the risk of contamination.

[0018] The injection device of the present invention further comprises a needle guide adapted to allow guided injection at different injection sites. Preferably, the needle guide comprises a guide tube holder and a guide tube adapted to be detachably coupled to the injection needle.

[0019] In a preferred embodiment, Fig. 9As shown, the guide tube comprises two pieces or preferably consists of two pieces, which form a complete guide tube when assembled. In this case, the two corresponding parts are positively connected to each other. In particular, the guide tube is divided into two pieces along its longitudinal axis, and the two pieces when assembled form the guide tube. When the two pieces are connected to the guide tube, at least one channel is formed, through which the injection needle can be guided. The channel is preferably located outside the symmetry axis of the guide tube. In a preferred embodiment, two channels are formed when the two pieces of the guide tube are assembled into the guide tube, preferably, wherein a channel is formed, through which the injection needle can be guided, wherein the channel is preferably located outside the symmetry axis of the guide tube, and a channel is formed, through which the catheter can be guided, wherein the channel is preferably located within the symmetry axis of the guide tube. Thus, at least one piece or each piece includes one or more respective protrusions to form one or more channels when assembled with another piece. In a preferred embodiment, one piece of the guide type includes a protrusion that forms a catheter-channel when assembled with another piece to form a guide tube, and another piece includes a complementary protrusion to form a catheter-channel, and includes another protrusion that forms a needle-channel when connected to another piece to form a guide tube. Preferably, the catheter-channel has such a size that the catheter tube is just suitable for passing through, which ensures that the guide tube itself is narrow, that is, has a small diameter, and is therefore convenient for the patient. In a preferred embodiment, the diameter of the catheter-channel is about 1mm to 6mm, preferably about 2mm to 5mm, more preferably about 3mm to 4mm, and most preferably about 3.6mm. In addition or alternatively, the diameter of the guide tube at its widest point is about 4mm to 9mm, preferably about 5mm to 8mm, more preferably about 6mm to 7mm, and most preferably about 6.7mm. Therefore, in the most preferred embodiment, the diameter of the catheter-channel is 3.6mm, and the diameter of the guide tube at its widest point is 6.7mm. This narrow configuration allows a catheter tube to fit through the passage, but does not allow a balloon (transurethral bladder catheter) attached to the end of the catheter to pass through.

[0020] Therefore, a two-piece design / construction of the guide tube is advantageous because it allows the catheter to be inserted into the guide tube. In particular, the catheter, i.e. the catheter tube, is inserted into a protrusion of one piece of the guide tube, and then the other piece of the guide tube comprising a complementary protrusion is connected to the piece of the guide tube that already holds the catheter. The part of the catheter comprising the balloon is outside the guide tube and protrudes from the guide tube in the direction of the patient. If the guide tube is made of one piece, the catheter-balloon must be pushed through the passage of the guide tube, which is not possible because the passage is too narrow.

[0021] Furthermore, the guide tube is constructed to include two channels, one for the needle and one for the catheter, to ensure that the needle and catheter tube travel in parallel, thereby preventing accidental puncture of the catheter by the needle, which could occur if the injection device, and in particular the guide tube, did not include a device for inserting the catheter.

[0022] In one embodiment, the needle guide is movable for adjusting and changing the injection position and adjusting and changing the position of the injection needle, respectively.

[0023] In particular, in one embodiment, the guide tube is rotatable about its longitudinal axis within the guide tube holder, wherein the guide tube and the guide tube holder are toleranced to one another by means of a clearance fit.

[0024] In one embodiment, the injection device of the present invention is adapted to guide the injection needle to at least two injection positions, preferably, the orientations of the two injection positions are different from each other. Preferably, this is achieved by a rotatable guide tube, which comprises a channel located outside the symmetry axis of the guide tube, and wherein the guide tube is adapted to guide the injection needle through the channel.

[0025] Injection at multiple injection sites, in particular, along the crescent-shaped tissue requires multiple injection steps, in which new injection sites are set alternately and the injectable material is stored at the set injection sites. This is very important to ensure that the injected material is equally distributed along the tissue to achieve successful tissue regeneration.

[0026] In one embodiment, a section of the guide tube comprises circumferential teeth pointing outwardly relative to the guide tube surface, wherein the teeth together with a locking disk arranged on the guide tube holder ensure that the teeth of the guide tube engage with the locking disk when the guide tube is rotated a certain distance. Thus, the guide tube can have different locking positions relative to the guide tube holder, wherein the distance between two locking positions, in particular the distance between two teeth of the guide tube is preferably 15°. Thus, when moving, in particular rotating the guide tube, the position of the needle changes a certain distance, preferably 15°. For ease of manipulation, in one embodiment, the guide tube is operably connected to a handle, i.e., the handle is operably connected to the guide tube, which can be used to move, in particular rotate the guide tube.

[0027] This feature is advantageous because it allows the injection matrix to be evenly distributed along the tissue where the matrix is ​​to be injected, and the correct position does not need to be adjusted manually, but is predetermined by the interaction between the teeth of the guide tube and the locking disk of the guide tube holder. Therefore, unnecessary changes in the injection position do not occur.

[0028] As mentioned above, in one embodiment, the injection device of the present invention is further adapted to guide the catheter to the target organ, preferably to the bladder. This is achieved by a guide tube, which in one embodiment further comprises a channel located at the axis of symmetry of the guide tube, and wherein the guide tube is adapted to guide the catheter through the channel. The catheter is used to empty the bladder and fill the bladder with an isotonic fluid (such as sodium chloride solution), so that the bladder is filled and thus fixed, which facilitates targeted injection to the sphincter muscle.

[0029] In one embodiment, the injection device of the present invention comprises a cooling tool, which is preferably inserted into the holding unit and is detachable. In particular, the cooling tool is suitable for holding a syringe. The presence of the cooling tool has a favorable effect, that is, the injection material is kept cool before being administered to the subject, which increases, for example, the shelf life of the injection material. For example, if the injection tool is used to administer a cell suspension mixed with a collagen solution, which is a preferred use of the injection tool of the present invention, the cooling device is most important, because if there is no cooling, the collagen solution will form a gel, which will make the suspension no longer injectable, or, only seriously lose cell viability. In addition, if the injection material includes cells, for example, muscle precursor cells, cooling the cells ensures a high survival rate. If the injection device of the present invention includes a detachable cooling tool, the cooling tool can be used to transport the injection material and the syringe including the injection material to the injection device, respectively.

[0030] In one embodiment, Figure 2 and 4 As shown, the cooling tool of the injection device of the present invention has facets, wherein preferably, the facets are spaced about 15° from each other and distributed around the cooling tool. Thus, each facet corresponds to 15°. The cooling unit is clamped with a holding unit so that after the cooling unit is rotated 15°, the cooling tool snaps back into place every 15° rotation, which allows an operator (e.g., a physician) to release the device at any position without changing its position.

[0031] In one embodiment, the injection device of the present invention comprises the above-mentioned cooling means, which is rotatable, in particular, can be rotated about its longitudinal axis, so as to allow mixing of the injection substance contained in the syringe. This is particularly useful if the injection substance is not a solution of each homogeneous substance, but a heterogeneous mixture, for example, a suspension consisting of at least two immiscible substances, for example, cells (as particles) and a surrounding (preferably fluid) medium, for example, a carrier solution, such as a collagen solution. The rotation of the cooling unit prevents precipitation of one phase (e.g., cells) and ensures that in the case of both substances being fluid, or in the case of a suspension, for example, cells and medium, the two phases are homogeneously distributed in the syringe.

[0032] As described above, in one embodiment, the injection device of the present invention comprises a connection structure, which operatively connects at least the holding unit and the needle guide. Preferably, the connection structure is designed as an elongated support, in particular an elongated rod, on which the other parts of the injection device of the present invention are mounted directly or via further connection devices. Preferably, the holding unit is mounted directly on the connection structure (and the actuation unit is mounted on the holding unit), wherein the needle guide is mounted on the connection structure via further connection devices (i.e. positioning structures as defined below). Thus, the connection structure extends along an axial reference plane of the injection device (see Figure 1 ).

[0033] Preferably, the connection structure is designed such that the needle guide can slide along its rod and the holding unit (including the actuation unit) can slide along its rod.The needle guide and the holding unit are slidable independently of each other.

[0034] When the injection needle is connected to the syringe in the holding unit of the injection device and is guided through the needle guide, a sliding of the holding unit including the actuation unit is performed to advance the injection needle. During the injection procedure, the actuation unit including the holding unit is advanced in the direction of the biological body, i.e. in the direction of the injection site, until the tip of the needle is sufficiently penetrated into the injection site, preferably human or animal tissue, more preferably into the sphincter muscle, even more preferably into the external urethral sphincter muscle, particularly preferably into the human sphincter muscle or the external urethral sphincter muscle. The sliding of the actuation unit and the holding unit, respectively, can be performed manually or driven by a motor, e.g., artificial intelligence (AI) controlled, as further explained below.

[0035] The sliding of the needle guide facilitates adjustment of the distance between the guide tube / injection needle and the head of the ultrasound probe when it is guided through the guide tube, which can be connected to the injection device of the present invention as described below to adapt the injection device of the present invention to the anatomical structure of the subject to be treated.

[0036] Preferably, the connection structure is further adapted to be detachably coupled to an imaging device, preferably an ultrasound probe. The ultrasound probe is useful for observing the tissue to which the injection substance is to be administered, in particular for determining the optimal position of the injection needle and the injection depth. Injections guided by ultrasound probes are generally more accurate than injections guided by cystoscopy and therefore have advantages.

[0037] Therefore, in one embodiment, the connection structure further comprises an attachment device for an imaging apparatus, in particular for an ultrasound probe.

[0038] Thus, in one embodiment, the injection device of the invention comprises an imaging device, preferably an ultrasound probe, and the imaging device is detachably coupled to the injection device of the invention via a connecting structure. Thus, in one embodiment, the connecting structure has an attachment device for the imaging device.

[0039] Injections are typically performed by trained physicians in a hospital setting, and the accuracy of the injections can be further improved via artificial intelligence (AI)-supported ultrasound interpretation, which can, for example, perform targeted, particularly motorized needle insertions, and preferably automatically confirm successful puncture of the corresponding tissue, such as the external urethral sphincter. This enables the user to quickly and accurately locate the correct injection site, and in particular the injection depth and / or angle, without the need for manual ultrasound interpretation, and thus reduces inter- and intra-surgeon variability. The principles of AI-supported ultrasound interpretation are described, for example, in Brattain et al., Biosensors 11 (2021), 522.

[0040] In one embodiment, the injection device of the present invention further includes a positioning structure for the needle guide, that is, the needle guide is detachably and movably connected to the positioning structure, wherein the positioning structure preferably includes a track connected to the connecting structure and extending in a direction perpendicular to the connecting structure, and more preferably, further includes a sliding member detachably and movably connected to the track.

[0041] 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.

[0042] In particular, in one embodiment, the needle guide comprising the guide tube and the guide tube holder is movable relative to the holding unit, preferably towards and away from the holding unit, i.e. the distance between the holding unit and the guide tube holder is adjustable, wherein, when connected to a connection structure of the imaging device, the distance between the guide tube holder and the imaging device (in particular the shaft portion of the ultrasound probe) remains unchanged. In particular, the needle guide is movable along the connection structure and thus the distance between the needle guide and the imaging device (in particular the shaft portion of the ultrasound probe) remains unchanged. This allows adjusting 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 track to which the guide tube holder comprising the guide tube is connected, wherein the track is movable in the above-mentioned direction.

[0043] 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, and preferably, towards and 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 track, wherein the slide connected by the guide tube holder including the guide tube can slide along the track.

[0044] In one embodiment, the needle guide including the guide tube and the guide tube holder is pivotable about a pivot axis. This is also achieved by a slide connected to the track via a pivot bearing.

[0045] 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 therefore the position of the external urethral sphincter muscles, it is important that the distance between the guide tube and thus the needle when inserted into the guide tube and the ultrasound probe can be adjusted. For the same reason, it is advantageous that the distance between the guide tube and thus the needle when inserted into the guide tube and the head of the ultrasound probe can be adjusted.

[0046] Furthermore, the pivotable feature of the guide tube holder (including the guide tube) is advantageous because it allows the injection angle to be adapted. The injection angle (penetration angle, inclination angle) is the angle between the longitudinal direction of the tissue (particularly the muscle, e.g. the sphincter muscle, into which the injection substance is to be introduced) and the injection needle.

[0047] In a further embodiment, the present invention relates to the injection device and injection needle of the present invention, wherein at least the front part of the injection needle protruding from the guide tube to the injection site is curved. In other words, the present invention relates to the injection device of the present invention, which further comprises an injection needle, wherein the injection needle protruding from the guide tube to the injection site is curved. Preferably, the injection needle itself is not curved, but the curvature of the needle is caused by a grind in the guide tube, which causes the injection needle to leave the catheter in a curved shape.

[0048] In particular, the needle has a bending angle 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 at most 10°, preferably less than 10°, and more preferably less than 7.5°. In another preferred embodiment, the injection needle is bent, that is, its bending angle is 3° to 10°, preferably 3° to 9°, more preferably 3° to 8°, more preferably 3° to 7.5°, more preferably 3° to 7°, more preferably 3° to 6.5° or 4° to 6.5°, more preferably 3° to 6° or 4° to 6.5°, more preferably 3° to 5.5°, or 4° to 5.5°, more preferably 3° to 5°. Most preferably, the injection needle is bent, that is, its bending angle is between 5° and 7.5°, preferably 5° or 7.5°. In a preferred embodiment, the bend angle of the needle itself protruding from the front of the guide tube is 3° to 6° bend angle, preferably 4° to 5°, and most preferably 5°, and the guide tube can be arranged to adjust the bend angle of the needle, preferably an additional 1° to 3°, preferably less than 2.5°, that is, the guide tube can be adjusted upward or downward relative to its longitudinal axis.

[0049] The bending angle of the needle helps to avoid the needle piercing through the tissue to be injected with the injectable substance, but instead offsets the injection angle of the needle radially outward or inward at a certain bending angle relative to the center of the longitudinally extending tissue, so that the injection direction is radially offset in the longitudinal direction of the tissue.

[0050] In a preferred embodiment, the injection needle is attached to a syringe, in particular to a connector of the syringe. The connection between the connector of the syringe and the needle is leak-free. In one embodiment, the leak-free connection is achieved by a Luer connector. In one embodiment, the needle is connected to the connector of the syringe via an intermittent tube. In a preferred embodiment, the connection of one end of the intermittent tube to the connector and the connection of the other end of the tube to the needle are achieved by a Luer connector.

[0051] In one embodiment, the injection device of the invention is connected to a mount, such as a bed or floor mount, preferably via a base as part of the connection structure to ensure a stable position of the injection device relative to the organism to be treated.

[0052] In a further embodiment, the present invention relates to a medical device, which is suitable for injecting an injection substance into a living body. The medical device of the present invention comprises the injection device of the present invention and a syringe having a syringe body and a plunger comprising a piston and an injection needle, wherein the syringe is arranged in a holding unit of the injection device, and / or, wherein the injection needle is arranged in the needle guide. In one embodiment, the present invention further relates to a syringe comprising an injectable substance and an injection needle, the use of which in the injection device of the present invention and the medical device of the present invention, respectively.

[0053] In one embodiment, the medical device further comprises an imaging device, preferably an ultrasound probe.

[0054] In one embodiment, the injection device of the present invention and the medical device of the present invention are adapted to be removably coupled to a bed or floor mount (eg, a brachytherapy stepper arm).

[0055] The present invention further relates to a method for injecting an injection substance into a living body, wherein the injection device and the medical device of the present invention are used, respectively, comprising at least the following steps: the injection substance is quantitatively injected into the living body by displacing the operating lever of the actuation unit of the medical device from a first position to a second position, as detailed above.

[0056] In addition, the present invention relates to a method for treating a muscle dysfunction in a subject, for example, a smooth muscle or skeletal muscle dysfunction, preferably a skeletal muscle dysfunction. In a preferred embodiment, the skeletal muscle dysfunction can be, for example, a sphincter dysfunction. A sphincter is a circular muscle that is used as a valve to open and close certain parts of the body. For example, there are six different sphincters in the digestive system, namely the upper esophageal sphincter, the lower esophageal sphincter, the pyloric sphincter, the sphincter of Oddi, the ileocecal sphincter and the anal sphincter. Other sphincters are also present in the body, such as the urethral sphincter. The activity of the sphincter may occur involuntarily through the autonomic nervous system, or may also occur under certain voluntary control through the somatic nervous system. If the sphincter loses muscle tone or has too much tone (spasticity), symptoms and illnesses may occur. This may include urinary retention, in which the bladder cannot be completely emptied. Sphincter problems can also cause bladder and fecal incontinence, or inability to control the bladder or bowels.

[0057] Thus, the injection device / medical device of the present invention can be used in a method for treating a disease associated with the above-mentioned sphincter muscles, preferably a disease associated with a defect or dysfunction of the urethral sphincter, more preferably a disease associated with a defect or dysfunction of the external urethral sphincter muscles.

[0058] Thus, in a further preferred embodiment, the skeletal muscle dysfunction is a sphincter defect, preferably an external urethral sphincter muscle defect. Thus, in one embodiment, the present invention relates to a method for treating a disease associated with muscle dysfunction, including but not limited to (female) urinary incontinence, male urinary incontinence (e.g. after prostatectomy) and anal incontinence, but preferably treating stress urinary incontinence.

[0059] Urinary incontinence, the involuntary loss of urine, is a major medical problem, affecting approximately half of women over 45 and 17% of men over 70. Continence and urination involve a balance between urethral closure and detrusor activity. There are several types of urinary incontinence, such as stress urinary incontinence and urge urinary incontinence. Stress urinary incontinence (SUI) refers to the loss of small amounts of urine associated with increased intra-abdominal pressure and, in turn, bladder pressure during coughing, laughing, sneezing, exercise or other movements. The striated external urethral sphincter, which is composed of skeletal muscle and is therefore under the voluntary control of the somatic nervous system, is largely responsible for preventing SUI. Injury to the external urethral sphincter occurs primarily during childbirth, surgical treatment or aging. SUI is a disease that affects more than 200 million people worldwide, and the incidence in women is twice that in men, with a reduced quality of life for patients due to restrictions on daily activities, discomfort, odor, and infections caused by wet diapers. The resulting medical costs are enormous.

[0060] Treatment options for SUI mainly include non-surgical treatment (bladder training, dietary adjustment), drug therapy and surgical therapy. These therapies can only provide short-term relief, and their overall success rate is usually limited by complications (invasiveness of surgery, damage to surrounding tissues, increased rates of urinary tract infections) or side effects (tissue damage caused by drugs, non-degradable biomaterials, etc.). However, cell therapy methods for the treatment of urinary incontinence have made great progress and can restore sphincter function in SUI patients; see, for example, WO 2019 / 215090 A1. In general, the injection device / medical device of the present invention can be used to inject any substance into a tissue, but it is preferably used to inject cells that can regenerate tissue, such as sphincter muscle tissue.

[0061] In a preferred embodiment, the method of the present invention comprises injecting an injection substance into the corresponding tissue, in particular into the muscle tissue, and preferably into the muscle tissue of the sphincter, preferably the urethral (external) sphincter muscle or the anal (external) sphincter muscle, using the medical device of the present invention, wherein the injection substance comprises at least muscle-derived precursor cells and optional additional components, for example, a carrier solution for the cells, for example, a collagen solution.

[0062] In one embodiment, the method of the present invention (outlined in more detail below) further comprises performing neuromuscular electromagnetic stimulation (NMES) on the patient's pelvic floor, as described in WO 2019 / 215090 A1. NMES treatment after injection of the cell suspension supports muscle and nerve regeneration by activating muscle-nerve crosstalk and inducing maturation of neuromuscular junctions.

[0063] As described above, in the method of the present invention, muscle-derived precursor cells are preferably used as injectable substances, which are optionally mixed with a carrier solution, for example, a collagen solution as described in WO 2019 / 215090 A1. In addition, corresponding treatment methods are described in WO 2019 / 215090 A1, US 2009 / 0098094 A1, WO 2004 / 096245 A2 and WO 2008 / 104883 A1, all of which are incorporated herein by reference.

[0064] Unless otherwise defined, all technical terms and scientific terms used herein have the same meanings as those of ordinary skill in the art to which the present invention belongs. Although methods and materials similar to or equivalent to methods and materials described herein can be used for the practice or testing of the present invention, exemplary methods and materials will be described below. All publications, patent applications, patents and other references mentioned herein are incorporated herein by reference in their entirety. In the event of a conflict, the present application (including definitions) shall prevail. Materials, methods and examples are illustrative only and are not intended to be limiting.

[0065] Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.

[0066] For the avoidance of any doubt, it is emphasized that the use and meaning of expressions such as "in some embodiments", "in certain embodiments", "in some cases", "in some cases", "in further embodiments", "in one embodiment", etc. is that any embodiment described therein should be read with consideration of each and every feature in combination with these embodiments, and the disclosure must be treated in the same manner as the combination of features of these embodiments is set forth in one embodiment. The same is true for any embodiment and combination of features shown in the accompanying claims and examples, which are also intended to be combined with the features of the corresponding embodiments disclosed in the specification, wherein only for consistency and simplicity, the embodiments are characterized by dependencies, and in fact, each embodiment and combination of features that may be interpreted due to (multiple) dependencies must be regarded as literally disclosed and cannot be regarded as a choice between different options. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] Figure 1 : Schematic diagram of a device for injection according to one embodiment of the present invention, including dimensions (in mm and indicated by arrows).

[0068] Figure 2 : A perspective view of a device for injection according to one embodiment of the present invention.

[0069] Figure 3: Schematic diagram of an injection device according to one embodiment of the present invention, including an imaging device, here an ultrasound probe, including dimensions (in mm and indicated by arrows).

[0070] Figure 4 : A perspective view of a device for injection according to an embodiment of the present invention, including an imaging device, here an ultrasound probe.

[0071] Figure 5 : An enlarged detailed view 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).

[0072] Figure 6 : An enlarged detailed view of the syringe and injection needle when placed in the cooling tool of the injection device of the present invention.

[0073] Figure 7 : Enlarged detailed views of one embodiment of a guide tube and a large piece of said guide tube (comprising three quarters of the guide tube), respectively, of an injection device of the present invention, including dimensions (in mm and indicated by arrows) and radius specifications (R, in °). A) Complete guide tube; B) Large piece of guide tube; C) Section of the large piece of guide tube; D) Section of the disk of the large piece of guide tube with radially protruding teeth.

[0074] Figure 8 : Enlarged detailed view of a small piece (comprising a quarter of the guide tube) of one embodiment of a guide tube of an injection device of the present invention, including dimensions (in mm and indicated by arrows) and radius specifications (R, in °). A) Small piece of guide tube; B) Section of small piece of guide tube; C) Section of a disk of a small piece of guide tube with radially protruding teeth; D) Radial section of small piece of guide tube.

[0075] Fig. 9 : Schematic diagram of guide tube assembly, that is, the large and small parts of the guide tube are assembled into a complete guide tube.

[0076] Fig.10 : Schematic diagram of an embodiment of the locking disk of the injection device of the present invention, including dimensions (in mm and indicated by arrows) and radius specifications (R, in °).

[0077] Fig.11 : A schematic diagram of an embodiment of a positioning structure (including a track and a sliding member) including a guide tube holder and a locking disk, and a cross-section of the guide tube within the guide tube holder of the injection device of the present invention and a corresponding enlarged view of the locking disk and the guide tube cross-section.

[0078] Fig.12: Schematic diagram of an embodiment of the track of the injection device of the present invention, including dimensions (in mm and indicated by arrows) and radius specifications (R, in °). A) Side view of the track; B) Front view of the track.

[0079] Fig.13 : Schematic diagram of an embodiment of a slide of an injection device of the present invention, including dimensions (in mm and indicated by arrows) and radius specifications (R, in °).

[0080] Figure 1 and Figure 2 An embodiment of the injection device 1 of the present invention is shown, wherein Figure 6 The position of the syringe 14 in the injection device is shown, Figure 5 Details about the actuation unit 3, in particular different positions of the joystick, are shown. The injection device 1 of the present invention comprises at least a syringe 14 holding unit 2, i.e., it is designed to hold the syringe 14, the actuation unit 3, the needle guide 8, and at least a structure connecting the holding unit 2 to the needle guide 8, i.e., the connecting structure 12.

[0081] In particular, the injection device 1 of the present invention comprises

[0082] - a holding unit 2, which is suitable for holding a syringe 14;

[0083] an actuation unit 3 which is detachably coupled to the holding unit 2 and which is capable of being coupled to the syringe 14, in particular to the plunger 28 of the syringe 14, when the holding unit 2 holds the syringe 14, wherein the actuation unit 3 comprises a lever 4 and a piston 5, wherein a displacement of the lever 4 from a first position 35 to a second position 36 causes a movement of the piston 5, in particular an advancement movement along its longitudinal axis, in particular in a forward direction, wherein the actuation unit 3 is adapted to transfer the advancement movement at least partially to the syringe 14, in particular to the plunger 28 of the syringe, when the syringe 14 is coupled to the actuation unit 3;

[0084] a needle guide 8 adapted to be detachably coupled to the injection needle 11 and adapted to change the injection position of the injection needle 11, wherein the needle guide 8 preferably comprises a guide tube holder 9 and a guide tube 10, wherein the guide tube 10 is movable relative to the guide tube holder 9, in particular rotatable within the guide tube holder 9, for changing the injection position of the injection needle 11; and

[0085] A connecting structure 12 which connects the holding unit 2 and the needle guide 8 .

[0086] In particular, the holding unit 2, the actuating unit 3 and the needle guide 8 are arranged in series so that they are operably 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), wherein the connecting structure 12 connects the different elements. In particular, the connecting structure 12 connects the holding unit 2 with the needle guide 8, and since the actuating unit 3 is mounted on the holding unit 2, it also indirectly connects the actuating unit 3 with the two said components of the injection device 1.

[0087] Figure 1 and Figure 2 An embodiment of the injection device 1 of the present invention is shown, and Figure 1 Also shown is the orientation of the device relative to the biological body, in particular the orientation of the injection site 19 relative to the biological body 20. More particularly, Figure 1 The orientation of the injection device 1 relative to the external urethral sphincter muscle is shown (schematic diagram, not drawn to scale). The external urethral sphincter muscle is between about 10 mm and 18 mm in length and between about 1.5 mm and 5 mm in thickness (Morgan et al., J Urol. 182 (2009), 203-209). Figure 6 The orientation of the syringe 14 within the injection device 1 of the invention, in particular within the holding unit 2 of the injection device 1 of the invention, is shown.

[0088] The injection device 1 of the present invention comprises a holding unit 2 for a syringe 14, and thus, the syringe 14 can be inserted into the holding unit 2. The holding unit 2 can be made of any material that allows the holding unit to function and is preferably suitable for medical purposes, and 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, and most preferably, fine polyamide PA 2200 for EOSINT P. Unless otherwise specified, the same applies to other parts of the injection device 1 of the present invention. Preferably, any plastic material can be used as long as it is certified for medical use and can be cleaned and / or sterilized.

[0089] In principle, the holding unit 2 can be of any design as long as it holds the syringe body 39 in place, wherein the plunger of the syringe 28 is movable. In particular, the plunger of the syringe 28 can be moved forward along its longitudinal axis in the direction towards the outlet / tip of the syringe 14 and can be moved backward along its longitudinal axis in the opposite direction (i.e. in the direction towards the actuation unit 3 of the injection device 1).

[0090] 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 its position within the holding unit 2. In one embodiment, the holding unit 2 and the syringe 14, in particular the syringe body 39, are positively connected to each other. In another embodiment, the syringe body 39 and the holding unit 2 are set to tolerances with each other by means of a clearance fit, so that the syringe body 39 can be rotated within the holding unit 2 along its longitudinal axis.

[0091] As described above, the injection device 1 of the present invention is preferably designed to perform repeated dosing injections in a specific predetermined amount. In this case, in one embodiment, the holding unit 2 of the injection device 1 of the present invention includes a digital mark based on which the operator can estimate how many injections have been performed. In particular, this can be estimated based on the position of the piston 29 of the syringe.

[0092] In one embodiment, the holding unit 2 of the injection device 1 of the present invention additionally holds a cooling tool 13, which is preferably a cooling tool for the syringe 14 and the contents inside its syringe body 39, respectively. In one embodiment, the cooling tool 13 of the injection device 1 of the present invention is detachable, i.e. it can be removed from the holding unit 2, for example for transport. In one embodiment, the cooling tool 13 is detachably fixed to the holding unit 2, so that it does not change its position inside the holding unit 2 after being inserted into the holding unit 2, and it is also not rotatable, i.e. the holding unit 2 and the cooling tool 13 are positively connected to each other.

[0093] In a preferred embodiment, the cooling tool 13 is detachably fixed to the holding unit 2, so that it does not change its position in the holding unit 2 after being inserted into the holding unit 2, but it can be rotated along its longitudinal axis. In the latter case, the cooling tool 13 and the holding unit 2 are set to tolerances with each other by means of a clearance fit, so that the cooling tool 13 can be rotated along its longitudinal axis in the holding unit 2. In a further preferred embodiment, the cooling tool 13 has a Figure 2 and 4 The facets 60 shown, wherein the facets 60 are preferably spaced apart from each other and distributed around the cooling tool 13. Preferably, the facets are evenly distributed around the cooling tool, 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 by about 10° to 20°, more preferably by about 12° to 18°, more preferably by about 14° to 16°, and most preferably by about 15°. Therefore, the cooling unit is clamped by the holding unit so that after the cooling unit is rotated by the above angle (preferably 15°), the cooling tool snaps back into place every 15° of rotation.

[0094] In principle, the cooling tool can have any design as long as the syringe 14 can be inserted, i.e. the cooling tool 13 has an opening for inserting the syringe 14 and / or as long as the cooling tool 13 holds the syringe 14 in place. In a preferred embodiment, the cooling tool is a hollow cylinder which surrounds the syringe from all sides, in particular surrounds the syringe body 39, which preferably contains the content to be cooled. The cooling tool 13 can be made of aluminum or an iron alloy (such as stainless steel) and is cooled on ice before use, i.e. before connecting the cooling tool 13 comprising the syringe 14 containing the substance to be injected to the holding unit 2 of the injection device 1 of the present invention. Preferably, the cooling tool 13 is made of any material with optimal insulating properties. In particular, in one embodiment, the cooling tool 13 comprises a thread 51, with which the cooling tool can be screwed onto the actuating unit 3 of the injection device 1 of the present invention, wherein the actuating unit 3 comprising the cooling tool 13 (containing the syringe 14 and the substance to be injected) is connected to the holding unit 2 of the injection device 1 of the present invention, for example, as Figure 1 and Figure 2 shown.

[0095] As mentioned above, the cooling tool 13 is designed to hold the syringe 14. In particular, it holds the syringe body 39 in place, wherein the plunger of the syringe 28 is movable. In particular, the plunger of the syringe 28 can be moved forward along its longitudinal axis in the direction towards the outlet / tip of the syringe 14, and can be moved backward along its longitudinal axis in the opposite direction.

[0096] In particular, the injection device 1 of the invention comprises a holding unit 2 which holds a cooling tool 13 which holds a syringe body 39 in place, so that the syringe body does not change its position within the cooling tool 13. In one embodiment, the syringe body 39 and the cooling tool 13 are set to tolerances with each other by means of a clearance fit, so that the syringe body 39 can be rotated within the cooling tool 13 along its longitudinal axis, and in another embodiment, the syringe body 39 and the cooling tool 13 are positively connected to each other.

[0097] In a preferred embodiment, the syringe body 39 is fixed in the cooling tool 13 so that it does not change its position in the cooling tool and so that it is also not rotatable, i.e., the syringe body 39 and the cooling tool 13 are positively connected to each other. Therefore, in one embodiment, neither the cooling tool 13 nor the syringe body 39 can change its position relative to the holding unit 2. In a preferred embodiment, the cooling tool 13 is rotatable as described above, and therefore, the syringe 14, in particular, the syringe body 39 can be rotated in the holding unit 2 because the syringe 14, in particular, the syringe body 39 is detachably fixed in the cooling tool 13.

[0098] The syringe 14 can have any size as long as it fits the holding unit 2 and the cooling means 13, respectively. In one embodiment, the syringe 14 accommodates 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. In a preferred embodiment, the syringe 14 accommodates 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 doses) or 6 ml for 15 x 400 μl injections (high doses). Most preferably, a 10 ml syringe 14 is used according to the present invention, for example a Braun Omnifix 10 ml Luer lock syringe.

[0099] The injection device 1 of the invention further comprises an actuation unit 3 . Figure 5 An embodiment of the actuation unit 3 is shown in more detail. The actuation unit 3 can be made of any material that allows the actuation unit to be manipulated and is preferably suitable for medical purposes and 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, and most preferably, fine polyamide PA2200 for EOSINT P.

[0100] In one embodiment, the actuation unit 3 is mounted on the holding unit 2 of the injection device 1 of the present invention, that is, when the injection device 1 of the present invention is assembled, the actuation unit is slid onto the holding unit 2. In particular, the actuation unit 3 is detachably coupled to the holding unit 2, and when the holding unit 2 holds the syringe 14, the actuation unit can be coupled with the syringe 14. In one embodiment, the actuation unit 3 is detachably coupled to the holding unit 2, detachably coupled to the cooling unit 13, and when the holding unit 2 holds the syringe 14, the actuation unit can be coupled with the syringe 14.

[0101] In principle, the actuation unit 3 can have any design as long as it allows for a metered injection of the injectable substance. In particular, the actuation unit 3 can have any design as long as it allows for a metered injection of the injectable substance present in the syringe 14. In one embodiment, the actuation unit 3 is designed as follows: Figure 5 shown.

[0102] Thus, in a preferred embodiment, the metered injection is achieved by the actuation unit 3, which, when actuated, for example, moves the lever 4 of the actuation unit 3 from Figure 5 The first position 35 shown in A is shifted to Figure 5B, preferably, pivoting the lever 4 from the first position 35 about the pivot axis to the second position 36 ensures that the piston 5 of the actuation unit is displaced, i.e. advanced along the longitudinal axis by a certain displacement distance, i.e. in the direction of the piston stop, from the first position to the second position (forward direction), wherein the piston 5 exerts a force on the plunger of the syringe 28 during advancement, so that it also advances along its longitudinal axis by a certain distance in the direction of the outlet of the syringe 14, thereby releasing the injection substance present in the syringe, i.e., injecting it into the desired injection site 19. In a preferred embodiment, the displacement distances of the lever 4 and the piston 5 are respectively adapted so that each piston step dispenses 400 μl of injection matrix from the syringe 14 via the joint 34 as described above, i.e., each triggering of the lever results in dispensing 400 μl of injection matrix from the syringe 14. The distance covered depends on the size of the syringe, but when using a 10 ml syringe, for example a Braun Omnifix 10 ml Luer lock syringe with an inner 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.

[0103] In one embodiment, the actuation unit 3 of the injection device 1 of the present invention further comprises a joystick housing 32. In one embodiment, the actuation unit 3 of the injection device 1 of the present invention further comprises a joystick housing cover 44, which is preferably connected to the joystick housing 32 via a knurled screw 52. The joystick housing 32 and the joystick housing cover 44 together form a joystick housing 40. In particular, at least a part of the joystick 4 and the actuator 31 are placed inside the housing 40, and wherein the housing 40 has at least one recess to store the joystick 4, i.e. the operating joystick 4. In one embodiment, the joystick actuation point 45, i.e. the handle 45 of the joystick, is outside the housing 40 of the actuation unit 3.

[0104] The joystick housing 32 including its cover 44 may be used as a handle, which facilitates the handling and operation of the injection device 1 of the present invention.

[0105] The force is transmitted from the lever 4 to the piston 5, preferably, via the actuator 31 (e.g., a clamp). 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. As previously described, when the lever 4 is actuated from the first position 35 to the second position 36, the actuator 31 tilts, i.e., moves from the first position 37 of the actuator to the second position 38 of the actuator, such that the actuator clamps the piston rod 6 and advances the piston 5 along its longitudinal axis. In other words, the displacement of the lever 4 from the first position 35 to the second position 36 causes the lever 4 to engage the actuator 31 via the pivot point, such that the actuator 31 tilts, which results in a friction connection between the actuator 31 and the piston rod 6 by frictionally engaging them with each other, which then results in the above-mentioned forward movement. The friction connection between the actuator 31 and the piston 5 of the actuation unit 3 can be brought about by (slightly) tilting, in particular pivoting, the actuator 31 relative to a vertical orientation of the actuator 31 and the piston 5 .

[0106] That is, when the actuator 31 is pressed against a stopper in the housing 40 of the actuating unit 3, in particular, against the compression spring 30, the piston 5 of the actuating unit 3 completes the displacement, i.e., reaches the second position, wherein the compression spring is in a horizontal position of the actuator 31 at the inner wall of the housing 40, in particular, when the injection device and the cooling tool 13 are inserted respectively, the inner wall of the part of the housing 40 facing the syringe 14 and / or the joystick 4, i.e., the joystick handle 45 is pressed against the stopper 59 of the housing 40.

[0107] 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 called a clamping plate, which surrounds the piston rod 6 of the actuation unit 3 at its distal end (i.e., the end opposite to the piston stop 7). The retaining element is retained in a recess outside the housing 40 of the actuation unit 3 and is tensioned by means of a compression spring 17. The retaining element 16 frictionally engages the piston rod 6 in the retaining position so that the piston 5 is retained in place and prevents the piston 5 from retracting along its longitudinal axis, i.e., moving backwards (in the direction opposite to the forward direction described above) when the operating lever 4 and the brake 31 are moved from the second position to the first position, respectively. This allows the actuation unit 3 to be actuated again, i.e., the operating lever 4 is moved again from the first position 35 to the second position 36, so that the metered matrix delivery is resumed.

[0108] The injection device 1 according to the present invention further comprises a needle guide 8, wherein the needle guide 8 comprises at least a guide tube 10 and a guide tube holder 9, and in particular, the needle guide is adapted so that when the injection needle 11 is coupled to the injection device 1 of the present invention, and in particular, when the injection needle is coupled to a syringe 14 when inserted into the holding unit 2 of the injection device 1 of the present invention, the injection needle can be guided through its guide tube 10. In a preferred embodiment, the guide tube is particularly adapted so that (i) the injection needle 11, when the injection needle is coupled to the injection device 1 of the present invention, and in particular, when the injection needle is coupled to the syringe 14 when inserted into the holding unit 2 of the injection device 1 of the present invention, the injection needle can be guided through its guide tube 10, and (ii) the catheter, when the catheter is coupled to the injection device 1 of the present invention, can be guided through its guide tube (10), wherein, most preferably, when both the needle and the catheter are coupled to the injection device 1 of the present invention and are guided, the needle and the catheter pass through the guide tube 10 in parallel. Figure 7 , 8 , 9 and 11 show details of one embodiment of the needle guide 8. The needle guide 8 is preferably made of a metallic material, preferably of steel, more preferably of stainless steel, more preferably of implant grade steel, and more preferably of austenitic chromium-nickel-molybdenum steel, for example material 1.4044. The guide tube holder 9 has a recess through which a tubular guide tube 10 extends, and the guide tube 10 is fixed to the guide tube holder 9 so that it does not change its position within the guide tube holder 9, but the guide tube 10 can be rotated within the guide tube holder 9 along its longitudinal axis. In particular, the guide tube holder 9 and the guide tube 10 are set to tolerance with each other by means of a clearance fit so that the guide tube 10 is rotatable.

[0109] Preferably, the guide tube 10 comprises a channel 43 outside the axis of symmetry of the guide tube 10, and wherein the guide tube 10 is adapted to guide the injection needle through the channel, i.e., the injection needle is guided through the channel 43 when the injection needle is connected to the injection device 1 of the present invention, and in particular, when the injection needle is connected to the syringe 14 when inserted into the holding unit 2 of the injection device 1 of the present invention.

[0110] In one embodiment, a guide tube such as Figure 7 , 8 9. In particular, in one embodiment, the guide tube 10 is composed of two pieces, a large piece (large guide tube) 25 and a small piece (small guide tube) 26. The two corresponding parts are positively connected to each other, and in particular, their sheath surfaces are polished together.

[0111] Assembly of the large guide 25 and the small guide 26 with the guide tube 10 may be performed by conventional techniques, for example, by stacking or sliding one guide onto another.

[0112] When the large guide 25 and the small guide 26 are assembled into the guide tube 10, a channel 43 is formed, through which the injection needle can be guided, as described above. The channel 43 is preferably located outside the symmetry axis of the guide tube 10; see for example Fig.11 .

[0113] In one embodiment, the guide tube 10 further comprises a channel 41, which is preferably located on the symmetry axis 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 female guide 26 are connected to the guide tube 10, two channels 43 and 41 are formed, through which an injection needle and a catheter can be guided, respectively, as described above.

[0114] Thus, in one embodiment, the large guide 25 or the small guide 26, or the large guide 25 and the small guide 26 at least include respective protrusions to form the channels 41 and / or 43 when assembled with the other part. In a preferred embodiment, the large guide 25 includes protrusions to form the catheter-channel 41 when assembled with the small guide 26 to form the guide tube 10, and the small guide 26 includes complementary protrusions to form the catheter-channel 41. In another preferred embodiment, the small guide 26 additionally includes additional protrusions to form the needle-channel 43 when connected to the large guide 25 to form the guide tube 10.

[0115] In one embodiment, a section of the guide tube 10 comprises circumferential teeth 42 pointing outwardly relative to the surface of the guide tube 10. In a preferred embodiment, the spacing angle between two teeth is between 5° and 25°, preferably between 10° and 20°, and most preferably 15°.

[0116] In one embodiment, the guide tube 10 includes a handle 23 to rotate the guide tube 10 along its longitudinal axis. Preferably, the handle 23 is positioned perpendicular to the guide tube 10.

[0117] In one embodiment, the guide tube holder 9 of the injection device 1 of the present invention comprises a locking disk 24 . Fig.10An embodiment of a locking disk 24 is shown. In particular, in one embodiment, the locking disk 24 is clamped onto the guide tube holder 9 from above so that the guide tube 10 is axially fixed in the guide tube holder 9. More particularly, the locking disk 24 is clamped onto the guide tube holder 9 via its grid, i.e. the clamping feet 54. In one embodiment, the locking disk 24 further comprises a recess 53 into which the teeth 42 of the guide tube 10 can engage. This allows the teeth 42 of the guide tube 10 to engage with the locking disk 24 when the catheter 10 is rotated a certain distance. Thus, the guide tube 10 can have different locking positions relative to the guide tube holder 9, wherein the distance between two locking positions, in particular the distance between two teeth 42 of the guide tube 10, is between 5° and 25°, preferably between 10° and 20°, and most preferably 15°.

[0118] In one embodiment, the locking disk 24 has laser markings showing different locking positions, for example, from 0° to 90° in each direction, preferably from 0° to 75°.

[0119] Preferably, the locking disk 24 is made of a plastic material, more preferably, of polyoxymethylene (POM).

[0120] Thus, when moving, in particular rotating, the guide tube 10, the position of the needle 11 changes by a distance, preferably between 5° and 25°, preferably between 10° and 20°, and most preferably 15°. To facilitate manipulation, in one embodiment, the guide tube 10 is operably coupled to a handle 23, which can be used to move, in particular rotate, the guide tube.

[0121] Thus, movement of the guide tube 10 results in a change in the injection location. In a preferred embodiment, the injection locations are spaced between 5° and 25°, preferably between 10° and 20°, and most preferably 15° from each other, preferably, wherein the injection locations extend along a crescent-shaped tissue within the organism. In one embodiment, the spacing between at least two injection locations, for example 15°, allows radial sectors of the urethral sphincter muscle to be targeted as injection sites. In particular, the sphincter sectors that can be targeted are the upper 13 sectors, each 15°, spanning a total angle of 195° around the urethral axis, and preferably 9-10 sectors, each 15°, spanning a total angle of 150° around the urethral axis, and symmetrical about the sagittal center of the organism.

[0122] 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 with the needle guide 8 and, since the actuating unit 3 is mounted on the holding unit 2, also indirectly connects the actuating unit 3 with the two said parts of the injection device 1. The connecting structure may be of any design as long as it connects the above-mentioned parts of the injection device 1 of the present invention. In one embodiment, the connecting structure 12 comprises a proximal elongated support, preferably a rod, preferably four elongated guide rods, to which the holding unit 2 and the positioning structure 15 of the needle guide 8 of the injection device 1 of the present invention can be attached (i.e., detachably connected).

[0123] In one embodiment, the connection structure 12 is made of a metallic material, preferably steel, more preferably stainless steel, more preferably implant grade steel, and more preferably austenitic chromium-nickel-molybdenum steel, such as material 1.4044.

[0124] In one embodiment, the connection structure 12 further comprises an attachment device for an imaging device, in particular, an attachment device for an ultrasound probe 27. The attachment device and the connection structure 12 are designed so that the imaging device 27 can be detachably coupled to the connection structure 12. A specific example of such a connection structure is the structure of BK Medical, catalog number UD0238.

[0125] Therefore, in one embodiment, the injection device 1 of the present invention further comprises an imaging device, preferably an ultrasound probe 27 , which is attached to the injection device 1 via the above-mentioned connection structure 12 . Figure 3 and Figure 4 An embodiment of the injection device 1 of the present invention comprising the imaging device 27 is described. 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, respectively, when the guide tube 10 is perpendicular to the positioning structure 15, and as Figure 3 and Figure 4 It is shown below the guide tube 10, with the head 46 of the ultrasound probe 27 facing in the direction of the injection site 19 (and not in the direction of the actuation unit 3 of the injection device 1 of the present invention).

[0126] Preferably, the ultrasound probe 27 is a rod-shaped ultrasound probe, for example, a vaginal or rectal ultrasound probe, preferably a vaginal ultrasound probe. In one embodiment, the diameter of the shaft portion of the ultrasound probe 47 is about 10 mm to 20 mm, preferably about 15 mm to 17 mm, most preferably 16 mm. In one embodiment, the ultrasound probe is BK Medical's 8838 model (Endocavity3D 8838). Preferably, the ultrasound probe is suitable for generating radial and side-front cross-sections. In one embodiment, the ultrasound probe 27 can be axially moved in the connecting structure 12, for example, by loosening and reconnecting the clamping ring 48 that fixes the ultrasound probe 27 in the connecting structure 12. In a manner known per se, the ultrasound probe 27 is connected to an ultrasound device (not shown) that can be used to acquire and display tissue images.

[0127] In one embodiment, the injection device 1 of the present invention further comprises a positioning structure 15, which connects the needle guide 8 including the guide tube holder 9 and the guide tube 10. The details of one embodiment of the positioning structure are as follows Fig.11 , 12 and 13. In one embodiment, the positioning structure 15 comprises at least a track 21, wherein the track 21 is movably connected to the connection structure 12 of the injection device 1 of the present invention, preferably, by a knurled screw 55. In particular, the track 21 extends in a direction perpendicular to the connection structure 12, and the guide tube holder 9 is connected to the track 21, so that the guide tube 10 extends parallel to the connection structure 12 in its functional orientation, wherein the needle outlet opening 49 of the guide tube 10 faces the injection site 19. The track in one embodiment is as shown in Fig.12 shown.

[0128] Therefore, in one embodiment, the positioning structure 15 including the track 21 and the needle guide 8 including the guide tube 10 and the guide tube retainer 9 are capable of sliding along the connecting structure 12 and parallel to the imaging device, in particular, parallel to the axis 47 of the longitudinal ultrasound probe 27, so as to adjust the distance between the guide tube 10 and the head 46 of the ultrasound probe 27.

[0129] In a preferred embodiment, the positioning structure 15 further comprises a slide 22, wherein the needle guide 8 comprising the guide tube holder 9 and the guide tube 10 is connected to the above-mentioned track 21 via the slide 22, wherein the slide 22 is adapted in one embodiment to slide along the track 21 in the above-mentioned direction. Alternatively, or preferably in addition, the slide 22 allows the needle guide 8 comprising the guide tube 10 and the guide tube holder 9 to pivot about its pivot axis. In particular, the slide 22 can pivot towards and away from the imaging device 27, in particular, towards and away from the axis 47 of the longitudinal ultrasound probe 27, which is achieved by the pivot bearing of the slide 22 and the knurled screw 55. In one embodiment, the slide 22 can pivot 360° about its pivot axis. Fig.13 A detailed view of a slide in one embodiment is given, and Fig.11 An embodiment of a positioning structure 15 including a rail 21 and a slide 22 is shown.

[0130] In one embodiment, the positioning structure 15 including the rail 21 and the slide 22 is made of a metal material, preferably steel, more preferably stainless steel, more preferably implant grade steel, and more preferably austenitic chromium-nickel-molybdenum steel, such as material 1.4044.

[0131] When the injection needle 11 is inserted into the injection device 1 of the present invention, the guide 8 is pivoted, and thus the guide tube 10 is pivoted, and thus the injection needle is pivoted, which allows the injection angle to be adjusted.

[0132] The guide tube 10 fulfills different functions. On the one hand, it provides guidance for the injection needle 11, and on the other hand, it sets the injection angle (the inclination angle of the syringe 11 relative to 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°, as seen from the axial reference direction.

[0133] 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 bending angle is 3° to 10°, preferably 4° to 9°, more preferably 5° or 7.5°, and most preferably 7.5°. In a preferred embodiment, the bending angle of the needle itself protruding from the front of the guide tube 10 is 5°, and the guide tube 10 can be arranged to adjust the bending angle of the needle, preferably by an additional 2.5°, i.e., the guide tube 10 can be adjusted upward or downward relative to its longitudinal axis.

[0134] In order to safely guide the injection needle 11, the length of the guide tube tapered portion 58 (i.e., the portion including the needle exit opening 49 and facing the injection site 19) is generally not limited, and is selected in particular to ensure a certain maximum penetration depth of the injection needle 11 and / or to reach the corresponding tissue to be injected. For example, the length of the female urethra is about 4.8 to 5.1 cm, and the length of the male urethra is about 20 to 25 cm. Therefore, in one embodiment, the length of the tapered portion 58 is 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 4 cm to 20 cm or 4 cm to 15 cm, but most preferably about 4 cm.

[0135] The insertion depth of the injection needle 11 is selected depending on the desired application of the injection device 1 of the present invention. Typically, the tissue into which the injectable substance is to be injected, such as the sphincter muscle, and in particular the external urethral sphincter muscle, is observed with 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.

[0136] As described above, the injection device 1 of the present invention includes, in one embodiment, an injection needle 11, which is detachably connected to the syringe 14 when inserted into the injection device 1, wherein the injection needle 11 protrudes from the needle outlet opening 49 of the guide tube 10 in a curved shape, wherein the bending angle of the needle 11 is caused by the grinding portion 50 in the guide tube 10. In particular, the needle 11 has a bending angle directed radially outward relative to the axial orientation of the ultrasound probe 27 and the guide tube 10, respectively.

[0137] In one embodiment, the length of the injection needle 11 is between 10 cm and 30 cm, preferably between 15 cm and 25 cm, and most preferably 20 cm. In one embodiment, the size of the injection needle 11 ranges from 18 to 23 gauge (G). In one embodiment, a needle 11 with a length of 20 cm and between 17 and 18 G is used.

[0138] 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 that is part of the connection structure 12 .

[0139] As mentioned above, the present invention further relates to a method for injecting an injection substance into a living body, preferably into the external urethral sphincter muscle 20 (schematic diagram, not drawn to scale), wherein the injection device 1 and the medical device of the present invention are used, respectively, comprising at least the following steps: the injection substance is quantitatively injected by displacing the operating lever 4 of the actuation unit 3 of the injection device 1 from the first position 35 to the second position 36, as detailed above.

[0140] In more detail and in a preferred embodiment, the method of the present invention comprises the following steps:

[0141] a) positioning the injection device 1 of the present invention so that it has a predetermined position relative to the injection site 19 in the biological body 20;

[0142] b) advancing the injection needle 11 until the injection site 19 is reached, i.e. until the injection needle 11 penetrates the desired tissue 20;

[0143] 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;

[0144] d) retracting the needle 11; optionally,

[0145] 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 15° clockwise;

[0146] Wherein, steps b) to e) can be repeated at different injection sites and / or until all the injection substance is injected, or wherein only one injection is performed, or multiple injections are performed at one injection site (respectively steps a) to d), and steps b) to d are repeated, respectively). In a preferred embodiment, steps b) to e) are repeated at least twice, preferably 2 to 13 times or 2 to 18 times, more preferably 2 to 10 times or 2 to 15 times, and most preferably 9 or 10 times or 15 times, and wherein the injection is preferably performed at: at least two different injection sites, preferably at 2 to 13 different injection sites, more preferably at 2 to 10 different injection sites, and most preferably at 9 or 10 different injection sites. In one embodiment, 10 injections are performed at 10 different injection sites, each of 400 μl (low dose). In one embodiment, 9 injections are performed at 9 different injection sites, each of 400 μl (low dose). In another embodiment, 15 injections of 400 μl each (high dose) are performed at 9 or 10, preferably 10 different injection sites, which means that two injections are performed at some injection locations.

[0147] One or more injections may be positioned along the course of the urethra, for example, one or more injections may be performed in the mid-urethra, peri-urethra, and / or proximal urethra.

[0148] In one embodiment, 9 to 10 injections of 400 μl are performed, wherein one or two injections are performed in the central part of the external urethral sphincter muscle (-30° to +30° calculated from the center of the longitudinally extending muscle), and each of four injections of 400 μl are performed radially outward (preferably -45° to -90° and +45° to +90°). In another embodiment, 15 injections of 400 μl are performed, wherein one or two injections are performed in the ventral part of the external urethral sphincter muscle (-30° to +30° calculated from the ventral side of the longitudinally extending muscle), and each of four injections of 400 μl are performed radially outward (preferably -45° to -90° and +45° to +90°), and in addition, five more injections are performed in the above-mentioned central area (-30° to +30°, in particular at 0°, -15°, -30°, +15°, +30°).

[0149] The injection volume can also vary. For example, it can be adjusted according to the amount of active ingredient in the injectable substance, for example, according to the amount of density of the muscle-derived precursor cells to be injected for the treatment of the above-mentioned diseases. In particular, a lower or higher injection volume can be selected. In the case of using cells as injectable substances, the injection volume should preferably not exceed 500 μl, and more preferably should not exceed 400 μl, in order to ensure sufficient oxygen supply and avoid necrosis. However, even higher injection volumes are feasible as long as the supply of oxygen to the cells is ensured.

[0150] Therefore, in one embodiment, any injection volume can be selected as long as oxygen is supplied to the cells. For example, when the injectable material is spread over a large area at the injection site, that is, when the surface area of ​​the injection reservoir is very large to the volume ratio, and therefore oxygen can be easily diffused into the cells, a higher injection volume can be selected, such as up to the ml range. In a preferred embodiment, the injection volume is less than or equal to 500 μl, preferably less than or equal to 400 μl, more preferably between 10 μl and 400 μl, more preferably between 50 μl and 400 μl, more preferably between 100 μl and 400 μl, more preferably between 150 μl and 400 μl, more preferably between 200 μl and 400 μl, more preferably between 250 μl and 400 μl, more preferably between 300 μl and 400 μl, more preferably between 350 μl and 400 μl, and most preferably 400 μl.

[0151] Thus, the injection volumes mentioned may be administered in one or more doses, as described above. In one embodiment, the total dose to be administered is between 10 μl and 10 ml, preferably between 1 ml and 10 ml, more preferably between 3 ml and 8 ml, more preferably between 4 ml and 6 ml, most preferably 4 ml or 6 ml.

[0152] In a preferred embodiment, the positioning step a) comprises assembling the injection device 1 of the invention and mounting the device 1 on a mount, such as a bed or floor mount, more particularly a brachytherapy stepper arm, which is preferably positioned in front of the subject to be treated. In a preferred embodiment, the injection device 1 is also coupled to an imaging device, preferably to an ultrasound probe 27, via the attachment means of the connection structure 12, wherein the ultrasound probe 27 is preferably inserted into the vagina to visualize the bladder, urethra and external sphincter muscles.

[0153] In particular, in a preferred embodiment, the assembly step comprises inserting a syringe 14 comprising an injectable substance, preferably together with a cooling unit 13, into the injection device 1, in particular into the holding unit 2 of the injection device 1, placing the injection needle 11 on the syringe connector 34, wherein the needle tip should be aligned with the 0° mark of the locking disk 24 when viewed from the distal side, and guiding the injection needle 11 through a small channel 43 located outside the axis of symmetry of the guide tube 10, wherein the handle 23 of the guide tube 10 should preferably point vertically upwards. In a preferred embodiment, the assembly step further comprises guiding a catheter through the central channel 41 of the guide tube 10, preferably wherein the catheter is inserted into the bladder via the urethra and the bladder is filled with an isotonic sodium chloride solution. In principle, any catheter that meets the above functions can be used, but in a preferred embodiment, the length of the catheter is 30 to 50 cm, preferably 35 to 45 cm, more preferably about 40 cm, in particular 41 cm. A specific example of a catheter that can be used according to the present invention is a SupraCath single catheter, 3 ml, Ch.8, 41 cm long.

[0154] 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 multiple times) until a first drop of the injection substance appears at the tip of the needle 11 .

[0155] Preferably, the injection needle 11 is advanced until the needle tip just emerges from the guide tube 10 and is preferably visible in the ultrasound image, which is preferably performed by advancing the holding unit 2 including the actuation unit 3 along the connecting structure 12 .

[0156] Step b), i.e., advancing the injection needle 11, is preferably performed by advancing the actuating unit 3 of the holding unit 2 of the injection device 1 of the present invention along the connecting structure 12 in the direction of the injection site 19 until the injection needle 11 reaches the injection site 19, wherein an operator, such as a physician, is preferably guided by an ultrasound image.

[0157] Injection step c) achieves a metered injection of preferably 400 μl of injection substance via a mechanism as described above. In particular, the lever 4 of the actuation unit 3 is triggered and, depending on the dose to be injected, the lever 4 is triggered once or twice.

[0158] The retraction step d) preferably comprises retracting the needle 11 completely into the guide tube 10. The step of retracting the syringe (step d)) is preferably performed simultaneously with the actuation of the joystick and is preferably also performed manually by an operator by retracting the actuation unit including the holding unit along the connecting structure, wherein the operator is again preferably guided by an ultrasound image.

[0159] Step e) preferably further comprises rotating the image plane of the ultrasound probe 27 by at least one increment.

[0160] The preferred use of the invention in the treatment of muscle dysfunctions, preferably sphincter dysfunctions, preferably external urethral sphincter dysfunctions, and therefore preferably for the treatment of urinary incontinence, preferably female stress urinary incontinence (SUI) is described below. The injection device 1 according to the invention is preferably used to treat the indicated condition with muscle precursor cells. By injecting the cultured muscle precursor cells into the corresponding muscle, muscle function is restored. In particular, by injecting the cells into the urethral sphincter muscle, the contractile force is increased and continence is thus restored. When the treatment is particularly preferably performed with autologous cells, the following steps are provided:

[0161] a) obtaining a tissue sample by performing a skeletal muscle biopsy on the subject to be treated;

[0162] b) isolating muscle precursor cells, preferably by surgically removing fat and / or tendon and / or connective tissue from a tissue sample; mincing and enzymatically digesting the tissue sample; reducing the number of fibroblasts, thereby generating a population of muscle precursor cells;

[0163] c) expansion of muscle precursor cells;

[0164] d) forming an injectable material, preferably by mixing the cells with a carrier solution (such as a collagen solution), preferably wherein the concentration of collagen is 1-4 mg / ml, more preferably about 2 mg / ml; and

[0165] e) injecting the injection substance into the corresponding muscle, preferably the sphincter muscle, preferably the external urethral sphincter muscle.

[0166] Preferably, muscle precursor cells are provided as described in WO 2019 / 215090 A1, the contents of which are incorporated herein by reference.

[0167] After the injection substance is formed and before injection, the injection substance is filled into the syringe 14 .

[0168] Alternatively, the formation of the injection material can be performed by a syringe having two syringe chambers, wherein one chamber comprises muscle precursor cells and the other chamber comprises a carrier solution, such as the collagen solution described above. During simultaneous injection from the two syringe chambers, the carrier mixes with the cells and thus forms the injection material.

[0169] The 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.

[0170] The following provides a detailed example of how to assemble and use the injection device and medical device of the present invention for treating female urinary incontinence:

[0171] 1) The cooling tool 13 including the cell suspension in the syringe 14 is removed from the transport container and placed on sterile ice until use.

[0172] 2) Place the needle guide 8 including the guide tube 10, the guide tube holder 9, and the positioning structure 15 on sterile ice.

[0173] Preparation of the connection structure 12:

[0174] 3) Unpack the injection needle 11 and remove the protective cap, blunt guide needle and inner mandrel. Place the injection needle on sterile ice.

[0175] 4) Position the floor / bed mount (brachystepper) in front of the patient 20 .

[0176] 5) Connect the connecting structure 12 and the base 18 to the close-range stepper and position them.

[0177] 6) Place the sterile cover around the base 18 on the proximal stepper.

[0178] 7) Treat the ultrasonic probe 27 with lubricant, provide protection, and treat it with lubricant again. Then, insert the ultrasonic probe 27 into the holder on the connecting structure 12 (observe the pin and the notch) and fix it with two clamping rings 48.

[0179] 8) Push the holding unit 2 onto the four proximal guide rods of the connecting structure 12 until the rear foot is flush with the end of the guide; if necessary, temporarily fix the holding unit 2 with two clamping screws 57.

[0180] 9) Push the positioning structure 15 including the pivot bearing (including the guide tube holder 9 ) onto the two distal guide rods of the connecting structure 12 until it is approximately in the center position and temporarily secure it with the clamping screws 55 .

[0181] Adjust the ultrasound probe and needle guide:

[0182] 10) General anesthesia via intubation.

[0183] 11) Antibiotic prophylaxis was performed by intravenous injection of 1.5 g Zinacef (if intolerance occurred, an alternative antibiotic was determined before surgery).

[0184] 12) Lithotomy storage

[0185] 13) Disinfection and covering of the external genitalia and urethral opening.

[0186] 14) Insert the ultrasound probe 27 into the vagina to visualize the bladder with bladder neck, striated sphincter and urethra in 3D mode by moving the proximal stepper, and then fix the position of the proximal stepper again.

[0187] 15) Remove the Charriere 8 Balloon indwelling catheter from its packaging and pass it through the needle guide 8, in particular, through the central channel 41.

[0188] 16) A catheter is inserted into the bladder through the urethra and blocked with 3 ml of glyco-block or NaCl solution. The bladder is emptied.

[0189] 17) Fill the urethral bladder with 100 ml NaCl using a bladder syringe; attach a Kocher clamp to the end of the catheter. The now clamped extracorporeal portion of the catheter is temporarily positioned on the holding unit 2.

[0190] 18) Insert the distal section of the indwelling catheter (behind the needle guide 8) into the central channel of the large piece (3 / 4 guide) 25,10 of the guide tube.

[0191] 19) Push the small piece (1 / 4 guide piece) 26, 10 of the guide tube from the front onto the large piece (3 / 4 guide piece) 25, 10 so that the guide tube 10 surrounds the catheter; see also Fig. 9 .

[0192] 20) Insert the guide tube 10 distally into the guide tube holder 9.

[0193] 21) Clamp the plastic spring, ie the locking disk 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 - with a click.

[0194] 22) Check that the clamping is correct by rotating the guide tube 10 with the guide tube handle 23, where the guide tube 10 should engage in set 15° increments 42. Then return the guide tube 10 to the 0° position (guide tube handle 23 pointing upwards). The locking disc 24 has the angle printed on the plastic line.

[0195] 23) Loosen the two clamping screws 55 of the needle guide positioning structure 15 so that the guide tube 10 can be inserted into the urethra along the balloon catheter.

[0196] 24) Tighten the clamping screw 55 of the needle guide 10 with proper position and alignment; paying special attention to the anechoic peritoneal cavity of the guide tube 10, the distance to the bladder neck (DK balloon) and the perfect view of the striated muscle sphincter (hypoechoic, periurethral structures).

[0197] Preparation execution unit (dosage tool) 3:

[0198] 25) Screw the joystick housing cover 44 onto the joystick housing 32.

[0199] 26) The locking spring (holding element 16) is compressed so that the piston rod 6 can be pushed back completely.

[0200] 27) Then check the actuation and full return of the trigger (operating lever 4). To do this, operate the operating lever 4 five times, after which the piston rod 6 should move forward.

[0201] 28) Remove the cooling means 13 containing the cell suspension from the sterile ice and invert to mix.

[0202] 29) Screw the cooling tool 13 including the syringe 14 onto the actuating unit 3 .

[0203] 30) Remove the Luer lock closure of syringe 14.

[0204] 31) Screw the needle 11 onto the Luer lock 34 of the syringe 14, wherein the needle tip must be aligned with the 0° mark (12 o'clock) when viewed from the distal side.

[0205] 32) With the handle 45 of the joystick facing upwards, insert the actuating unit 3 into the holding unit 2 a short distance.

[0206] 33) Check again that the needle tip is aligned with the 0° mark (12 o'clock) when viewed from the distal side. The orientation of the bevel (cut) of the needle 11 can be adjusted by slightly loosening the cooling unit thread 51 and turning the syringe 14; then tighten the actuation unit 3 again and insert it into the holding unit 2.

[0207] 34) Fill the needle 11 with liquid (filler) by pulling the trigger 4 (possibly multiple times) until the first drop appears at the tip of the needle 11.

[0208] 35) The actuating unit 3 is advanced in the holding unit 2 only so far that its distance from the front limit in the holding unit 2 is at least as great as the desired puncture distance.

[0209] 36) Loosen the clamping screw 57 of the holding unit 2; then carefully push the holding unit 2 together with the actuating unit 3 forward on the guide rod of the connecting structure 12, while manually inserting the tip of the needle 11 into the upper lumen 43 in the guide tube 10.

[0210] 37) Carefully push the holding unit 3 including the actuating unit 3 further forward until the tip of the needle 11 just emerges from the guide tube 10 and is visible in the ultrasound image; tighten the clamping screw 57.

[0211] Injection of cell (muscle-derived precursor cell) suspension:

[0212] 38) The starting position is selected at 0° (12 o'clock) viewed from the distal side; the handle 23 of the guide tube and the handle 45 of the joystick of the actuation unit 3 point vertically upwards.

[0213] 39) Manually advance the actuator unit 3 and observe the ultrasound image until the tip of the needle 11 sufficiently penetrates into the striated sphincter 20.

[0214] 40) The therapeutic product can be injected by actuating the trigger 4 with the index finger. Depending on the dose, the trigger 4 can be actuated once or twice. One actuation of the trigger 4 corresponds to a volume of 0.4 ml. The volume present in the syringe 14 can be checked using the scale printed on the holding unit 2.

[0215] 41) When the needle 11 is fully retracted into the guide tube 10, turn the guide tube 10 clockwise by 1 step (15°) and tilt the actuation unit 3 (15°) to set the next injection level.

[0216] 42) Each time the guide tube 10 is rotated one grid, the image plane of the ultrasound probe 27 will also rotate at least one increment (+ / - key).

[0217] 43) Radially, perform further injections in clockwise direction (eg +15°, +30°, +45°, +60°), repeating steps 39-42 in each case.

[0218] 44) When the needle 11 is fully retracted into the guide tube 10, realign the guide tube 10 and the actuator unit 3 to the 12 o'clock position (0°) when viewed distally, and use a similar counterclockwise procedure to deploy the remaining injections (e.g., positions -15°, -30°, -45°, -60°).

[0219] 45) To achieve the most complete rhabdomyosphincteric coverage, a total of:

[0220] - Low dose 4 ml = perform 9-10 injections of 0.4 ml each (1-2x center, 4x right and 4x left).

[0221] - High dose 6 ml = 15 injections of 0.4 ml each. The same procedure is followed by a second injection in the central position (ranging from -30° to +30°).

[0222] The dorsal area around the urethra was omitted.

[0223] 46) After the last injection, the actuation unit 3 including the needle 11 is completely pulled out and set aside.

[0224] 47) The catheter is unobstructed.

[0225] 48) Loosen the clamping screw 55 on the needle guide retaining structure 15 so that the guide tube 10 can be retracted.

[0226] 49) The Charr 8 catheter is removed from the body. If the catheter cannot then be pulled out through the lumen 41 in the needle guide, the guide tube holder 9 must be pulled out by removing the locking disk 24 and disassembled to expose the catheter.

[0227] 50) The proximal stepper arm (floor / bed mount) with the connection structure 12 and ultrasound probe 27 is retracted so that the probe 27 is no longer within the body.

[0228] 51) Insert a new balloon catheter Charr.12 and block it with 10ml Glycoblock or NaCl.

[0229] 52) End of program

[0230] 53) Disassemble the injection device 1.

[0231] This specification has been cited throughout the text of multiple documents. The contents of all references cited in this application (including references cited throughout the application, granted patents, published patent applications, including background sections and manufacturer's specifications, instructions, etc.) are hereby incorporated herein by reference; however, it is not admitted that any of the cited documents are indeed prior art of the present invention.

[0232] The features of the invention disclosed in the description, the drawings and the claims are, either alone or in combination, significant for the implementation of the invention in its various embodiments.

[0233] Reference numerals:

[0234] 1Injection device

[0235] 2 Holding unit

[0236] 3 Actuation unit

[0237] 4 Joystick (trigger)

[0238] 5 Piston

[0239] 6 Piston rod

[0240] 7 Piston stop

[0241] 8-pin guide

[0242] 9 Guide tube holder

[0243] 10 Guide tube (consists of two parts)

[0244] 11 Injection needle

[0245] 12 Connection structure

[0246] 13 Cooling tools

[0247] 14 Syringes

[0248] 15 Positioning structure

[0249] 16 Holding element (clamping plate)

[0250] 17 First compression spring

[0251] 18 Base

[0252] 19 Injection Sites

[0253] 20 Organisms, especially the sphincter muscles of organisms

[0254] 21 tracks

[0255] 22 Slide

[0256] 23 Handle of guide tube 10

[0257] 24 Locking plate

[0258] 25 guide tube 10 large pieces

[0259] 26 small pieces of guide tube 10

[0260] 27 Imaging devices, especially ultrasound probes

[0261] 28 Plunger of syringe 14

[0262] 29 Piston of syringe 14

[0263] 30 Second compression spring

[0264] 31 Actuator (clamping piece)

[0265] 32 Joystick Shell

[0266] 33 bolts connect the actuator 31 (clamping member) and the operating lever 4 (trigger member)

[0267] 34 Connector for syringe 14

[0268] 35 First position of joystick 4

[0269] 36 Second position of joystick 4

[0270] 37 First position of actuator 3 (clamping member)

[0271] 38 Second position of actuator 3 (clamping member)

[0272] 39 Syringe body

[0273] 40 housing of joystick 4

[0274] 41 catheter channel

[0275] 42 radial teeth

[0276] 43 Injection needle channel

[0277] 44 cover of joystick housing 32

[0278] 45 Joystick 4 handle

[0279] 46 Head of ultrasonic probe 27

[0280] 47 Shaft of ultrasonic probe 27

[0281] 48 clamping ring

[0282] 49-pin outlet opening

[0283] 50 Grinding Department

[0284] 51 thread

[0285] 52 Knurled screw of actuator unit 3

[0286] 53 is a notch into which the teeth 42 of the guide tube 10 can engage

[0287] 54 Grid for attaching the guide tube holder 9, i.e. clamping foot

[0288] 55 Knurled screw for positioning structure 15

[0289] 56 Opening of knurled screw 52

[0290] 57 Clamping screw

[0291] 58 Conical section of guide tube

[0292] 59 Housing stopper

[0293] 60 Facets of cooling tool.

Claims

1. An injection device [1], the injection device being configured to inject an injectable substance into a living body using a syringe [14], the injection device comprising: - a holding unit [2], the holding unit being suitable for holding the syringe [14]; - an actuation unit [3], the actuation unit being adapted to dose the injectable substance, the actuation unit being detachably coupled to the holding unit [2] and being capable of coupling with the plunger [28] of the syringe [14] when the holding unit [2] is holding the syringe [14], preferably wherein the actuation unit [3] comprises a lever [4] and a piston [5], wherein displacement of the lever [4] from a first position [35] to a second position [36] causes the piston [5] to move along its longitudinal axis, wherein when the syringe [14] is coupled to the actuation unit [3], the actuation unit [3] is adapted to at least partially transfer the movement to the plunger [28] of the syringe [14]; - a needle guide [8] adapted to be detachably coupled to the injection needle [11] and adapted to change the injection position of the injection needle [11]; and - A connecting structure [12], which connects the holding unit [2] and the needle guide [8].

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

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

4. The injection device [1] according to claim 3, wherein: The guide tube [10] is composed of two pieces, a large piece (large guide piece, [25]) and a small piece (small guide piece, [26]), which, when assembled, form the guide tube [10].

5. The injection device [1] according to claim 4, wherein: When the large piece (large guide piece, [25]) and the small piece (small guide piece, [26]) of the guide tube [10] are assembled into the guide tube [10] When at least one channel is formed, preferably, two channels [41] and [43] are formed, preferably, one channel [43] is located 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 located inside the axis of symmetry of the guide tube [10] and is used to guide the catheter through.

6. The injection device [1] according to claim 5, wherein: The needle guide [8] is adapted to allow both the injection needle [11] and the catheter to pass through the guide tube [10] and the passageway [41, 43] respectively in parallel when both are coupled to the needle guide [8].

7. The injection device [1] according to any one of claims 11 to 6, wherein: The injection device [1] further comprises a cooling tool [13], which is held by the holding unit [2], preferably, wherein the cooling tool [13] is detachable and / or wherein the cooling tool [13] is rotatable about its longitudinal axis.

8. The injection device [1] according to claim 7, wherein: The cooling tool [13] comprises facets [60] which are spaced 10° to 20° apart from each other, preferably 15° apart, and which are preferably distributed around the cooling tool [13].

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

10. An injection device [1] according to any one of the preceding claims, wherein: The displacement distance of the joystick [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, and most preferably 20 mm.

11. An injection device [1] according to any one of the preceding claims, wherein: The injection device [1] is suitable for guiding the injection needle [11] to at least two injection positions whose positions are different from each other by rotating the guide tube [10], wherein the guide tube [10] includes a channel [43] located outside the symmetry axis of the guide tube [10], and wherein the guide tube [10] is suitable for guiding the injection needle [11] through the channel [43].

12. An injection device [1] according to any one of the preceding claims, wherein: The guide tube [10] comprises circumferential teeth [42] pointing outwardly relative to the surface of the guide tube [10], wherein when the guide tube [10] rotates within the guide tube holder [9], the teeth [42] engage with a locking disk [24] arranged on the guide tube holder [9], preferably, wherein the spacing angle between two teeth [42] of the guide tube [10] is 15°.

13. An injection device [1] according to any one of the preceding claims, wherein: The injection sites are spaced 10° to 20°, preferably 15° apart from each other, preferably wherein the injection sites span a total angle of 195°, preferably 150° around the urethral axis and are symmetrical about the sagittal center.

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

15. An injection device [1] according to any one of the preceding claims, wherein: The connection structure [12] is adapted to be detachably coupled to an imaging device, preferably an ultrasound probe [27].

16. The injection device [1] according to any of the preceding claims, further comprising an imaging device, preferably a longitudinal ultrasound probe [27], which is detachably connected to the injection device [1] via the connection unit [12].

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

18. An injection device [1] and an injection needle [11], wherein: The injection device [1] is defined by one of the preceding claims, and wherein the front portion of the injection needle [11] protruding from the guide tube [10] toward the injection site [19] has at least a radially outwardly directed bending angle relative to the axial orientation of the ultrasound probe [27] and the guide tube [10], respectively, preferably wherein the injection needle [11] comprises a bending angle of 3° to 10°, preferably 5° to 7.5°, and more preferably 5° to less than 7.5°.

19. An injection device [1], an injection needle [11] and a catheter, wherein: The injection device [1] and the injection needle [11] are defined by one of the preceding claims and wherein, preferably, the catheter is a transurethral bladder catheter.

20. The injection device [1] according to Figures 1 to 13 and its equivalents.

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

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

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