Instrument, instrument head and application system
Patent Information
- Application Number
- BR102020005236
- Authority / Receiving Office
- BR · BR
- Patent Type
- Patents
- Current Assignee / Owner
- Publication Date
- 2026-09-15
Smart Images
Figure 00000035_0000 
Figure 00000035_0001 
Figure 00000035_0002
Abstract
Description
1 / 29 INSTRUMENT, INSTRUMENT HEAD AND APPLICATION SYSTEM
[0001] The present invention relates to an instrument, particularly an instrument for applying a substance to body tissue, an instrument head, an application system, and a method.
[0002] In methods for injecting a substance into tissue known from the prior art, an injection cannula paired with a disposable syringe may be used. The injection cannula (cannula) may, for example, have a diameter of up to 1.6 mm. There is an increased risk of insufficient positioning, as well as the danger of perforating the tissue in an undesirable location for the manual application and injection of a substance with an injection needle. In addition, comparable tissue trauma occurs at the penetration site due to the large diameter of the cannula (up to 1.6 mm). Furthermore, a large penetration channel or opening is characterized by the fact that a large amount of the introduced substance may escape from the tissue, and thus valuable material may be lost. Besides the loss, this can also lead to an increased accumulation of the substance in tissue areas outside the target area.Muscle damage due to penetration, which can lead to scarring of healthy muscle tissue (fibrosis), is an additional disadvantage, especially if, with a puncture needle, only a small volume of the substance can be produced in a rather limited spatial area. Thus, for example, a circumferential treatment of the sphincter requires several punctures. Besides the increased time required, this also reduces the effectiveness of the treatment because it creates an additional effect on the muscle that, in the worst case, increases the regenerative effect of the substance therapy. This aspect gains importance due to the diameter. Petition 870260077615, dated 04 / 08 / 2026, p. 5 / 82 2 / 29 relatively large cannula up to 1.6 mm.
[0003] Document EP 3 040 036 A1 proposes an approach for needle-free cell introduction using a water jet. The proposed instrument allows for spatial and point-source delivery of two substances, so that, for example, sequential application of cells and carrier medium is possible.
[0004] EP 3 040 101 A1 proposes a pump or distribution system that allows sequential application with different amounts of pressure levels.
[0005] Document EP 2 907 582 A1 describes a device for spraying medicinal fluids into overlapping spray cones.
[0006] During cell application, the shear forces applied to them can damage the cells. A concept would be advantageous for a needle-free injection of a substance, particularly active ingredients, into cells, in which the function of the active ingredients is primarily maintained, particularly the damage to the cells that need to be inserted is primarily avoided.
[0007] This object is solved with an instrument according to claim 1, an instrument head according to claim 13, an application system according to claim 14 and a method according to claim 16:
[0008] The inventive instrument comprises a first conduit for the outlet of a first fluid from a first opening of the first conduit in the axial direction into a reacceleration zone. Furthermore, the instrument comprises a second conduit for channeling a second fluid into the reacceleration zone in the axial direction such that at least portions of the second fluid, as a result of the flow of the first fluid into the reacceleration zone, are reaccelerated in the axial direction by the first fluid entering the reacceleration zone. The first Petition 870260077615, dated 04 / 08 / 2026, page 6 / 82 3 / 29 fluid can also be referred to as a working fluid. The second fluid can also be referred to as an active ingredient fluid and may comprise cells that are to be applied to body tissue via the instrument.
[0009] Upon entering the reacceleration zone, the second fluid, particularly the ingredients to be reaccelerated, already possesses a velocity component in the axial direction. The relative velocity in the axial direction between the first fluid to reaccelerate the ingredients of the second fluid and the ingredients of the second fluid is therefore lower than the velocity of the first fluid. Thus, the ingredients, for example, cells, are subject to lower velocities, pressures, velocity and pressure differences and, as a consequence, also to reduced shock and shear stresses, so that they can be transported remarkably more carefully into the tissue.
[0010] Additional advantageous features of the inventive instrument, the head of the inventive instrument, the inventive application system and the inventive method are derived from the following description.
[0011] Preferably, the second conduit comprises a reacceleration zone upstream of the reacceleration zone. The instrument is preferably configured to pre-accelerate the second fluid in the reacceleration zone in the axial direction. The first opening is arranged in the reacceleration zone so that the outlet of the first fluid from the first opening re-accelerates the pre-accelerated second fluid in the axial direction. Through the pre-acceleration zone, the second fluid can be brought to a high velocity only briefly before the reacceleration zone in order to reduce the relative velocity between the first and second fluids at the beginning of the reacceleration zone. A pre-acceleration zone upstream of the reacceleration zone adjacent to the distal end of the instrument has the advantage that the second fluid can be supplied up to the pre-acceleration zone. Petition 870260077615, dated 04 / 08 / 2026, page 7 / 82 4 / 29 adjacent to the distal end of the instrument with low velocity and the second fluid is only pre-accelerated adjacent to the distal end of the instrument, for example, in an instrument head.
[0012] The pre-acceleration zone is preferably formed by a nozzle section of the second conduit, in which the cross-sectional area of the second conduit tapers in the direction of flow (axial direction). The ratio of velocity in a cross-section to velocity in a conical section is known proportionally to the ratio between the area of the conical section and the area of the cross-section.
[0013] A pressure pulsation of the second fluid in and / or after the nozzle section is mainly avoided if the cross-sectional area decreases continuously in at least one subsection of the nozzle section.
[0014] Preferably, the second conduit surrounds the first conduit at the first opening in a concentric manner, in order to form a ring-shaped jet of the second fluid around the fluid exiting the first opening. This improves the uniform loading of the jet surface of the first fluid with ingredients of the second fluid.
[0015] Preferably, the second fluid is configured to guide the jet from the casing radially close to the first conduit, so that the working jet, which is produced from the first opening, draws the ingredients from the casing jet into the working jet. This effect can be traced to the Bernoulli effect, due to the initially higher velocity of the operating jet compared to the jet from the casing.
[0016] Preferably, the outer wall of the second conduit is elastic in a section around the first opening. This leads to autonomous centering of the second conduit around the first opening, for example, in order to balance comparably larger tolerances where the second conduit concentrically surrounds the first conduit at the first opening.
[0017] The section can be formed by an elastic element that Petition 870260077615, dated 04 / 08 / 2026, page 8 / 82 5 / 29 also forms the nozzle section completely or partially. An autonomous centering can therefore be performed on the nozzle section.
[0018] Preferably, the elastic element is fluidically connected upstream with a section of the second conduit's tubing. A centering device may be radially effective between the tubing section and the first conduit. The tubing section is rigid and / or inflexible, at least for the pressures and forces that generally occur during normal operation. This ultimately improves the formation of a ring-shaped jet of the second fluid around the carrier jet of the first fluid.
[0019] The section of the second conduit that is radially inflexible preferably surrounds a section of the first conduit that is radially inflexible, wherein the centering device may be disposed between the section of the second conduit and the section of the first conduit in order to concentrically align the section of the first conduit and the section of the second conduit.
[0020] Preferably, the re-acceleration zone, in which the introduction of ingredients of the second fluid into the carrier jet still occurs, is formed within the instrument. The instrument preferably comprises a. The carrier jet with ingredients of the second fluid exits through the distal opening of the instrument downstream of the re-acceleration zone.
[0021] For example, the distal opening of the instrument can be placed in the tissue. An injection channel can be introduced into the tissue through the instrument in a needle-free manner with a pilot jet of the first fluid.
[0022] The second conduit preferably terminates downstream of the first opening. In other words, the second conduit preferably encloses at least one section of the zone of Petition 870260077615, dated 04 / 08 / 2026, page 9 / 82 6 / 29 reacceleration. As a result, the flow of the second fluid in the reacceleration zone remains in a predefined shape and does not diverge excessively outwards. The second conduit is preferably cylindrical in the section protruding beyond the first opening. This improves the transfer of ingredients from the second fluid into the carrier flow or carrier jet.
[0023] The second conduit preferably terminates upstream of the instrument's distal opening. Therefore, if the instrument's end section that is preferably rigid under compression is placed with the distal opening in the tissue, the tissue will not reach the distal end of the second conduit and therefore will not press against the second conduit. By doing so, the second conduit is not unintentionally deformed, especially if it includes an elastic conduit element at the distal end.
[0024] The instrument is preferably configured to channel the first fluid and the second fluid adjacent to each other towards the vicinity of the distal end of the instrument in conduit sections that are arranged adjacent to each other, preferably parallel to each other. The instrument is preferably further configured to subsequently channel the first fluid and the second fluid still in the direction towards the distal end in coaxial conduit sections.
[0025] Preferably, the pre-acceleration zone and / or the acceleration zone are located in the head of the instrument. By doing so, the second fluid flows only along a short distance between the pre-acceleration zone and / or the re-acceleration zone and the distal end of the instrument. Damage to the cells due to transport over longer distances and at higher speeds is avoided.
[0026] The instrument head is preferably replaceable.
[0027] According to the invention, there is also a head of the instrument. Petition 870260077615, dated 04 / 08 / 2026, page 10 / 82 7 / 29 for an instrument is provided. It preferably comprises the pre-acceleration zone and / or the re-acceleration zone. The instrument head is preferably fixable to the proximal conduit sections of the first and second conduits in a replaceable form.
[0028] In addition, an application system with any of the embodiments of the inventive instrument is provided. Furthermore, the application system comprises a supply device that is fluidically connectable to the first conduit and the second conduit and that is configured to supply the first fluid and the second fluid in a sequence of supply intervals.
[0029] Preferably, the supply device comprises a control that controls the application system so that within an application time interval during a first working fluid supply interval, the first fluid is supplied so as to comprise a first velocity at the first opening to form a channel in the tissue. Furthermore, the control controls the application system so that during a second working fluid supply interval, the first fluid is supplied so as to comprise a reduced first velocity at the first opening that is lower than the first velocity. Furthermore, the control controls the application system so that at least in the phases during the second working fluid supply interval, the second fluid is supplied so that the second fluid comprises a second velocity at the first opening that is lower than the reduced first velocity.
[0030] The inventive method for applying an active ingredient, particularly cells, into body tissue comprises a needle-free opening step of a channel in the tissue by means of a working jet of the first fluid emitted from a first conduit of a first opening of an instrument. The instrument is preferably, Petition 870260077615, dated 04 / 08 / 2026, page 11 / 82 8 / 29 an inventive instrument as described in this document, particularly according to any of the embodiments described above. In a second step, a jet of a second fluid is emitted from a second instrument conduit parallel or coaxially to the working jet. The second fluid comprises ingredients, particularly active ingredients such as cells that are accommodated from the working jet and carried to the channel. The ingredients are preferably accommodated by suction of the second fluid from the second fluid jet into the working jet. Between the first and second steps, the output or creation of the working jet may be interrupted. Preferably, the working jet is weakened only for the second step and may be emitted at a lower velocity compared to the velocity for opening the channel in the tissue. Furthermore, the working jet may be produced without interruption during the first and second steps.By doing this, it can be ensured that the channel created by the work jet is kept open by the work jet.
[0031] Other preferred features and optional embodiments may be derived from the following description as well as from the drawings. The drawings show:
[0032] Figure 1a is a highly schematic embodiment illustrating the inventive instrument in a partially longitudinal section,
[0033] Figure 1b is a cross-sectional view of the embodiment according to Figure 1a to illustrate an autonomous centering effect,
[0034] Figure 2 is a further embodiment of the inventive instrument in a longitudinal section,
[0035] Figure 3a is an enlarged view of a section drawn in Figure 2 of the instrument according to the embodiment of Figure 2, Petition 870260077615, dated 04 / 08 / 2026, page 12 / 82 9 / 29
[0036] Figure 3b is a cross-sectional view of an area of a transverse plane through Figure 3a,
[0037] Figure 3c is a cross-section of the instrument along the BB cutting line illustrated in Figure 3,
[0038] Figure 4 is a detailed view of a section that is illustrated in Figure 2,
[0039] Figure 5a is a highly schematic view of an embodiment of the inventive application system,
[0040] Figure 5b is a section of Figure 5a,
[0041] Figure 6 shows diagrams illustrating a time sequence of an application system control according to Figure 6a.
[0042] Figure 1a schematically illustrates an inventive instrument 10 with a first conduit 11 having a first opening 12 on the face 13 of the first conduit 11. The first conduit 11 is disposed in a second conduit 14. In this embodiment, the first conduit 11 forms an inner wall 27 of the second conduit 14. The first conduit 11 and the second conduit 14 are arranged coaxially. The first opening 12 is disposed upstream of an opening (second opening 15) of the second conduit 14. Through the first conduit 11 a first fluid 16 and through the second conduit 14 a second fluid 17 can flow in the axial direction A. As illustrated, the inner cross-section of the second conduit 14 provided for the second fluid 17 tapers in the axial direction A towards the second opening 15.By doing this, the second fluid 17 channeled within the second conduit 14 can be pre-accelerated before passing through the first opening 12 in the axial direction A and comes into contact with the first fluid 16 emitted from the first opening 12 in the axial direction A. The section with the conical internal cross-section forms a pre-acceleration zone 18. The area downstream of the first opening 12 can be... Petition 870260077615, dated 04 / 08 / 2026, page 13 / 82 10 / 29 referred to as acceleration zone 19, because in this zone the ingredients of the second fluid 17 are received in the carrier flow 20 of the first fluid 16, in order to be introduced by the carrier flow 20 into the tissue of a patient. Due to the coaxial configuration, the fluid flow of the second fluid 17 forms an envelope flow 21 around the carrier flow 20. This improves the transfer of ingredients from the second fluid 17 to the first fluid 16 at all circumferential locations. For this, the normal vector of the opening surface of the first opening 12 that is surrounded by the opening surface of the first conduit 11 is preferentially oriented parallel to the axial direction A. This configuration also preferentially applies to the modalities explained with reference to figures 2 to 4.If the first opening on the face side 12 in the first conduit 11 is oriented in the axial direction, this supports uniform loading of the work jet or work jet 20 with ingredients, particularly cells, substantially directly after exiting the first conduit 11.
[0043] Preferably, a section of the outer wall 22 of the second conduit 14, at least in the area of the first opening 12, is flexible, preferably elastically flexible. This leads to an autonomous centering effect of the flexible section 22 around the first opening 12. This is particularly and schematically illustrated in Figure 1b. Here a cross-sectional view of the instrument 10 according to Figure 1a is illustrated (cross-sectional area B is shown in Figure 1a). As is evident, the flexible (preferably elastic) section 22 is not concentrically arranged around a nozzle tube 23 that forms the distal end of the first conduit 11. This can occur due to large tolerances. It should be noted that Figures 1a and 1b are not true to scale. If the second conduit 14 is pressurized with the second fluid 17, the flexible axial section of the outer wall 22 that is Petition 870260077615, dated 04 / 08 / 2026, page 14 / 82 11 / 29, represented by the ring-shaped outer cross-sectional area, is moved and centered by the second fluid in the radial direction, as schematically illustrated by arrows P in Figure 1b (right-hand illustration). The first conduit 11 thus remains in its initial position. This is crucial because, in a first step, a channel can be opened in the tissue via the first conduit 11 and a fluid pulse from the first conduit 11 in a needle-free manner. In a second step, ingredients can be introduced into this tissue channel via the carrier flow 20. If the fluid flow of the second fluid 17 is interrupted, the ring-shaped outer wall section 22, being elastic, will automatically return to its initial position (Figure 1b left-hand illustration).There may also be embodiments in which an outer wall section in the form of an elastic ring of the second conduit comprising a self-contained centering feature may be omitted.
[0044] Figure 2 shows a longitudinal cross-sectional view of portions of a further embodiment of an inventive instrument 10. The instrument 10 can be usable for an open endoscopic or laparoscopic intervention. In particular, the instrument 10 can be a catheter instrument 10, which can be inserted into the urethra in order to perform a bladder sphincter treatment by introducing cells into it. Thus, by means of the same instrument 10, a channel can be created through the outer layers of the sphincter into the muscle tissue in a needle-free manner and the cells comprising fluid can be injected in a needle-free manner.
[0045] Instrument 10 comprises a longitudinally extended head 24 at the distal end 25 of instrument 10. The head 24 is inflexible and / or rigid. A section of the conduit pair defined by the sections of conduits 11, 14 up to the head 24 is flexible. At the head 24, the first conduit 11 is arranged concentrically Petition 870260077615, dated 04 / 08 / 2026, page 15 / 82 12 / 29 in a second conduit 14. As is particularly evident in Figure 3, the first conduit 11 comprises a configuration of several conduit sections forming stages of internal cross-section. The internal cross-section is reduced towards the distal end or in the axial direction in a gradual manner. The end of the first conduit 11 is formed by a nozzle tube 23. Also from the proximal section of the conduit 26 to the nozzle tube 23, the internal cross-section of the first conduit 11 decreases so that the first fluid is subjected to acceleration during passage through the first conduit 11. The reduction of the internal cross-section and therefore preferably also of the external cross-section of the first conduit 11 in this region, however, does not primarily serve to accelerate the first fluid. Embodiments can also be carried out without reducing the cross-section of the conduit 11 at the distal end.Furthermore, due to the reduction of the internal and external cross-section, high stability of the nozzle tube 23 can be achieved in the distal region, as well as a smaller reduction in the internal cross-section of the second conduit 14. A diameter reduction is particularly advantageous when it comprises continuous and / or uniform diameter transitions (different from the illustration according to Figures 2 or 3). A nozzle tube 23 with continuous reduction of the internal cross-section in the axial direction to the first conduit 11 can, for example, be manufactured as an integral part, for example, by forging or stamping a cylindrical tube, particularly a rotary stamped tube. By doing so, the nozzle opening (first opening 12) can also be created in the nozzle tube 23.
[0046] In head 24, the second conduit 14 comprises an outer wall formed by at least two elements. The inner wall is formed by the outer wall 27 of the first conduit 11, such that a cross-section of the ring-shaped conduit (section Petition 870260077615, dated 04 / 08 / 2026, page 16 / 82 13 / 29 internal transverse) of the second conduit 14 is obtained at the head 24 of the instrument 10. A rigid shaft, the tube section 28 of the second conduit 14 of uniform diameter, is connected at its distal end with an outer wall elastic element 29 that forms a nozzle 30 of the second conduit 14. The outer wall elastic element 29 is displaced at the distal end of the shaft tube 28. The outer wall elastic element 29 comprises a cylindrical section 29a, an adjacent conical section 29b, as well as an additional cylindrical section 29c. The other cylindrical section 29c may alternatively be a section that tapers in the axial direction A, for example, conical.
[0047] The nozzle tube 23 opens with a first opening 12 in the additional cylindrical section 29c of the outer wall elastic element 29 which is circumferentially closed. A coaxial arrangement of the first nozzle tube 23 and the outer nozzle 30 formed with the outer wall elastic element 29 is created. The outer nozzle 30 for cell suspension comprises a conduit cross-section in the form of a ring gap 31 and is arranged concentrically with the nozzle tube 23, so that the ring gap 31 encloses the nozzle tube 23. The cross-section of the ring gap 31 decreases in the axial direction.
[0048] If now a second fluid, particularly a suspension containing cells (cell suspension), flows through the outer nozzle 30, the second fluid is subject to a pre-acceleration adjacent to the distal end 25 of the instrument 10 due to the decreasing cross-section of the second conduit 14. Therefore, a pre-acceleration zone 18 is formed by the outer nozzle 30. Preferably, the acceleration is, however, less than the acceleration of the working fluid during passage through the first nozzle tube 23. In each case, the (average) output velocity of the cell suspension after passing through the nozzle (at the level of or adjacent to the first opening 12) is less than the Petition 870260077615, dated 04 / 08 / 2026, page 17 / 82 14 / 29 Average (average) exit velocity of the working jet at the first opening 12. In a particularly preferred embodiment, the ring-gap shaped external nozzle 30 for the cell suspension is sized so that the exit velocity of the nozzle (adjacent to the first opening 12) of the cell suspension is 50 to 90% of the exit velocity of the nozzle of the working jet (at the first opening 12) under the condition of predefined volume flow rates or mass flow rates of the working fluid as a first fluid, for example of 5-55 ml / min and particularly of 15-26 ml / min and of the cell suspension of 1-30 ml / min and particularly of 15-26 ml / min. This applies to the phase in which the emission of the cell suspension through the external nozzle 30 and the working fluid through the first opening 12 is carried out simultaneously to insert cells from the cell suspension via the working fluid into a channel in the tissue.For channel creation using a pilot jet of the working fluid, the exit velocity of the working jet nozzle can be even higher.
[0049] It is particularly advantageous if the ring gap 31 of the second conduit section 14 in the first opening 12 has an inner circumference U of at least 20 times the average diameter of the cells in the cell suspension and a radial gap width b at most ten times or event at most five times the average cell diameter, however, preferably at least four times the average cell diameter. Figure 3b shows a section along the section plane C3 that is drawn in Figure 3a. In Figure 3b, however, only the area of the section plane C3 around the center of the first opening 12 radially to the outer circumferential surface of the cylindrical section 29c of the flexible outer wall element 29 is shown. The inner circumference U of the ring gap 31 is equal to the outer circumference of the first nozzle tube 23. If the amount of the outer diameter of the first nozzle tube 23 is, for example, 0.25 mm and therefore the Petition 870260077615, dated 04 / 08 / 2026, p. 18 / 82 15 / 29 The inner circumference U of the ring gap is approximately 0.79 mm. The ring gap 31, for example, has a width b (radial gap width) of 0.1 mm, assuming a cell suspension with an average cell diameter of 25 micrometers. By doing this, on the one hand, the acceleration of the cell suspension is achieved as described above. On the other hand, tests have shown that by doing this, the ring gap 31 is sized large enough to allow sufficiently unobstructed passage of the cells if the cells used have an average diameter of 25 micrometers. The outer diameter of the working fluid jet (transport jet) at the outlet of the first opening 12 corresponds, in addition to twice the wall thickness of the nozzle tube 23, to the inner diameter of the ring gap 31 at the first opening 12.By forming the casing jet or casing flow 21 of the cell suspension, a casing jet or casing flow is created around the working fluid jet or working fluid flow 20 (compare Figure 1), in which the cells close to the working fluid flow 20 enter alongside the first opening 12, due to the radial dimension of the ring gap 31. By doing this, a particularly high accommodation of cells in the working fluid flow 20 can be ensured.
[0050] Between the rigid tube section of shaft 28 and the first conduit 11, a centering element 32 is provided, as is also evident in Figure 3c. The centering element 32 allows fluid passage through the second conduit 14, even though it is located in the second conduit 14. The centering element 32 provides a coaxial arrangement of the shaft tube 28 and the first conduit 11. The centering element 32 comprises one or more recesses or gaps 33 open in the axial direction, for example in the form of longitudinal grooves on the outer surface of the housing of the centering element 32. The cell suspension can pass through the recesses 33. You Petition 870260077615, dated 04 / 08 / 2026, p. 19 / 82 16 / 29 recesses 33 preferably comprise a uniform cross-section. Preferably, the recesses are regularly distributed around the circumference of the central element 32. The central element 32 finally provides a concentric arrangement of the first nozzle tube 23 for the working fluid 16 and the outer wall elastic element 29 for creating the jet or flow envelope 21. The central element 32 creates the concentric arrangement of the first nozzle tube 23 with the outer wall elastic element 29 indirectly through the shaft tube 28, as illustrated in the embodiment according to Figure 2.
[0051] The selected elastic resilience of the elastic element, using a material with selected hardness and shape, can create an autonomous centering and adjustment effect of the convergent outer nozzle, particularly the ring gap 31, during the passage of the cellular suspension through the outer nozzle, as explained with reference to the embodiment according to Figure 1a and particularly based on Figure 1b. An asymmetry of the ring gap 31 that may remain, for example, due to manufacturing tolerances, is compensated by applying a force to the outer wall elastic element 29 during the application of the cellular suspension through the flow of the cellular suspension. By doing so, the outer wall element 29 is deflected so that a symmetrical ring gap 31 is created.The outer wall element 29 preferably consists of a non-toxic, biocompatible, short-term elastic material (up to 25 hours), for example, an elastomer such as silicon or a thermoplastic elastomer. The thickness of the outer wall elastic element 29 comprises, for example, 0.05 to 1 mm, preferably 0.1 to 0.4 mm. The hardness of the material is in the range of 3 Shore (A) to 70 Shore (A), preferably in the range of 20 Shore (A) to 55 Shore (A).
[0052] The elastic element of the outer wall 29 is surrounded by a cover 34 that is resistant to compression in the axial direction. The cover 34 Petition 870260077615, dated 04 / 08 / 2026, page 20 / 82 17 / 29 forms the distal end 25 of the instrument 10. The cap 34 comprises an opening 35 on the distal face of the cap 34. The opening 15 on the face of the elastic element of the outer wall 29 (which is the second opening 15 on the face of the second conduit 14) opposite the opening 35 of the cap 34 is displaced proximally along the axial direction A. The face of the cap 34 forms the distal end 25 of the instrument 10. The instrument 10 is configured with resistance to compression by means of the cap 34, such that a minimum distance between the distal opening 35 of the instrument 10 that can be pressed into the patient tissue and the first opening 12 and / or the second opening 15 is maintained, even if pressure is applied over the distal end 25 of the instrument 10 during the pressing of the instrument 10 against the tissue. The position of the first conduit 11 in relation to the cover 34 is also defined by the centering element 32.This has the advantage that, if instrument 10 is placed with a cap 34 on the tissue and a channel is opened in the tissue by a fluid impulse from the first conduit 11, the first opening 12 will remain above this created channel, so that a subsequent jet or flow of the first fluid 16 with ingredients of the second fluid 17 reliably reaches the channel.
[0053] Figure 4 shows portion B2 of Figure 2 in an enlarged manner. As particularly and exemplarily apparent in Figures 2 and 5, the first conduit 11 and the second conduit 14 are preferably guided adjacent to each other, particularly parallel to each other near the distal end 25 of the instrument 10. Subsequently, still in the axial direction A towards the distal end 25, the first conduit 11 and the second conduit 14 are preferably arranged coaxially. In the embodiment, the first conduit 11 and the second conduit 14 are arranged side by side on the head 24 and following a transition point 36 on the head 24 coaxially to each other. At the transition point 36, the arrangement changes from Petition 870260077615, dated 04 / 08 / 2026, p. 21 / 82 18 / 29 Parallel arrangement for coaxial by means of a commutator arrangement. The transition point 36 may also be located upstream, adjacent to the head 24, so that the first conduit 11 and the second conduit 14 are arranged adjacent to each other up to near the head 24, for example, twisted or parallel, and in the flow direction or in the axial direction A behind the transition point 36 towards the downstream distal end 25 and at the head 24 coaxially. Proximal or upstream of the transition point 36 or proximal to the head 24, the first adjacent and particularly parallel conduit 11 and the second conduit 14 can be joined by means of a sheathing hose 38. The sheathing hose 38 is exemplarily illustrated with lines around the first conduit 11 and the second conduit 14 in Figure 2. The sheathing hose 38 can, for example, extend (as illustrated) into or over the head 24.
[0054] The transition from parallel channel arrangement to concentric or conduit arrangement can be created, for example, by means of a commutator arrangement 37, as is exemplarily illustrated in Figure 3. It is clear that the first and second conduits 11, 14 illustrated separately adjacent to each other in Figures 2 and 4 can also be realized by a conduit body with and particularly parallel channels that are arranged adjacent to each other. The stress on the cells during passage through the channel in the area of the parallel channel arrangement is potentially lower than in the coaxial arrangement under the assumption of equal flow cross-sections, regardless of whether two individual conduits 11, 14 or two channels are provided in a conduit body.This occurs because the coaxial arrangement of the inner and outer conduit can be achieved by many centering elements in the ring space between the inner and outer conduit; this, however, would create increased shear forces on the central element - or the fixing of the coaxial arrangement could be omitted. Petition 870260077615, dated 04 / 08 / 2026, page 22 / 82 19 / 29 so that the inner conduit, particularly under bending or torsion, can abut the inside of the outer conduit. However, by arranging concentric channels in the area after the transition location 36, the aforementioned preferred configuration of an envelope-shaped lining of the fluid flow 20 of the cell suspension is achieved, where the fluid flow 20 is emitted from the first opening 12. It was recognized that, due to the short area between the transition location 36 and the distal end 25 of the instrument 10, in which the cell suspension due to the coaxial configuration flows through the cross-section of the ring, cell damage is minimized during passage of the second conduit 14 in the coaxial area. It was particularly demonstrated that in a length L of the coaxial area (from the transition location 36 to the first opening 12) less than or equal to 40 mm, no effect on cell vitality was recognized.The centering device by means of the centering element 32 which was explained with reference to Figure 3a may alternatively be omitted. For example, if in a location where the first conduit 11 is in any way disposed close to the head wall 24, as illustrated in Figure 4, the first conduit 11 may be fixed and particularly welded to the head wall 24 which may form the second conduit 14 downstream of the commutator arrangement 37 (which is downstream of the transition from the parallel arrangement of the first conduit 11 and the second conduit 14 to the coaxial arrangement).
[0055] Figure 5a schematically illustrates an embodiment of an application system 100 comprising an inventive instrument 10, for example, an inventive instrument 10 according to one of the embodiments explained above. The system 100 further comprises a supply device 101 with a control 102 for controlling the supply device 101. The supply device 101 comprises a source 103 for the first fluid 16 Petition 870260077615, dated 04 / 08 / 2026, page 23 / 82 20 / 29 and a source 104 for the second fluid 17.
[0056] The supply device 101 can be configured to supply a first fluid 16 which can be, for example, a liquid, particularly a suspension, a solution or similar. This liquid can also be referred to as the working fluid, because it serves in a first step to create a channel 105 in the tissue 106 in which the instrument 10 is placed, as illustrated in Figure 5b, and in a second step to introduce ingredients of the second fluid into the channel 105. In addition, the supply device 101 supplies a second fluid 17 comprising ingredients, which must be deposited into the channel 105 in the patient's tissue 106 by means of the instrument 10 or the system 100, respectively. The ingredients can be, for example, cells, cell components, pharmaceuticals, radioactive substances for labeling or treatment or similar. The supply device 101 is in fluid communication with the first conduit 11 and the second conduit 14.
[0057] The supply device 101 is configured by means of the control 102 to supply the first fluid 16 and the second fluid 17 in a sequence of supply intervals. The control 102 is preferably configured to control the application system 100 so that within an application time interval ΔtA, which is exemplarily illustrated in Figure 6, during a first working fluid supply interval ΔtAF1, the first fluid 16 is supplied so that it comprises a first intensity at the first opening 12, particularly a first velocity v1 to form the channel 105 in the tissue 106. During a second working fluid supply interval ΔtAF2, the control controls the application system 100 so that it comprises a reduced first intensity at the first opening 12, particularly a reduced first velocity v1r which is less than the first intensity or Petition 870260077615, dated 04 / 08 / 2026, p. 24 / 82 21 / 29 first velocity v1 respectively. Furthermore, control 102 is configured to control the application system 100 so that at least in phases during the second working fluid supply interval ΔtAF2 the second fluid 17 is supplied so that it comprises a second intensity or second velocity v2 that is lower than the first reduced intensity or first reduced velocity v1r. The output of the second fluid 17 near the first opening 12 in the reacceleration zone 19 in an active ingredient supply interval ΔtWF can be performed either during the first working fluid supply interval ΔtAF1 before the change in intensity or synchronously with the change in intensity at the first opening 12 or after the change in intensity. As already mentioned, the change in intensity is particularly the change in velocity at the first opening 12 in the axial direction A.The second intensity or desired second velocity v2 of the second fluid 17 at the level of the first opening 12 is obtained, among other things, because it flows through the cross-section of the ring of the second conduit 14 which tapers adjacent to the distal end. Upstream of the outer nozzle, the second fluid 17 flows at a lower velocity, which reduces the risk of damage to cells in the second fluid 17. The application time interval can be, for example, less than 1 second.
[0058] The inventive application system 100 or the inventive instrument 10 can be used during operation, for example, as follows:
[0059] In order to minimize cell stress during the application process and still achieve sufficient cell penetration depth, the application process is preferably carried out in at least two stages, as already explained. In a first stage, channel 105 is prepared in tissue 106. For this, in a first working fluid supply interval ΔtAF1 (see Figure 7), it is Petition 870260077615, dated 04 / 08 / 2026, page 25 / 82 22 / 29 creates a high-intensity working pilot jet, particularly with a high nozzle exit velocity v1. This working pilot jet 20 consists of a working fluid 16, whose components are unacceptable against mechanical stress, particularly shear stress. Such liquids comprise, for example, physiological saline solution, a cell culture medium, a wetting or gel-type coating medium for the cells of the second fluid to increase mechanical protection and / or slippage capacity, or a mixture of one or more of these fluids or liquids. The channel 105 is created in the tissue 106 by means of the working pilot jet 20, wherein the working pilot jet 20 displaces and / or mechanically destroys the tissue components along the channel to be created.In the second phase of the second working fluid supply interval ΔtAF2, the intensity of the working pilot jet 20 is reduced, particularly the velocity at the first opening until the first reduced velocity v1r (see Figure 7). In doing so, the composition of the first fluid 16 can also be altered, particularly by adding substances or by changing the working fluid. Preferably, the composition of the first fluid outlet from the first opening 12 is similar in the first and second phases. While reducing the intensity, particularly the velocity of the working pilot jet 20, the jet outlet from the cell suspension casing 21 from the second opening 15 is initiated.As illustrated in the lower part of the diagram in Figure 7, the start can occur before the reduction in the working jet intensity during the first working fluid supply interval (this is shown in dashed lines at the bottom of Figure 7), synchronously with the reduction, or after the reduction (this is shown at the bottom of Figure 7 with solid lines). The second fluid 17 may comprise a wetting or gel-type coating medium in addition to the cells in suspension. During the creation of channel 105 by means of the pilot jet, the... Petition 870260077615, dated 04 / 08 / 2026, page 26 / 82 23 / 29 second conduit 14 is preferably filled with cell suspension up to within the head area 24, in which the first conduit 11 and the second conduit 14 extend coaxially. Preferably, the second conduit 14 is almost completely filled with cell suspension up to a level (measured in the axial direction) of the first opening 12, in order to facilitate a supply of cell suspension into the created channel substantially without delay. This is also a result of the inventive provision of two separate conduits 11, 14 for the first and second fluid and a combination of the first fluid and the second fluid only in the reacceleration zone 19 at the distal end 25 of the instrument 10.
[0060] If the cell suspension exits through the outer nozzle and passes the first opening 12 towards the distal end, it envelops the working jet 20 that exits centrally from the first opening 12 of the inner nozzle formed by the nozzle tube 23 in a manner similar to an envelope, preferably symmetrically. The autonomous centering of the elastic section of the outer wall 22 or of the outer wall element 29 can support or facilitate the cell suspension enveloping the working jet 20 in a manner similar to an envelope, preferably symmetrically. By doing so, a uniform loading of the surface of the working jet 20 with the cells is achieved simultaneously by the uniform flow velocity of the second fluid 17. This results in a low comparability of cell interaction with each other, which facilitates low cell stress.By means of instrument 10, the working fluid 16 and the cell suspension are emitted so that the jet of working fluid downstream of the first opening 12 sucks the cell suspension 17 which surrounds the working jet 20 in a manner similar to a radially inward casing towards the working jet 20. This goes back to the Bernoulli effect, which also applies to a jet pump and is contrary to the simple mixing of two jets. Petition 870260077615, dated 04 / 08 / 2026, page 27 / 82 24 / 29 fluid by overlapping. If the working fluid 16 and the cell suspension 17 come into contact with each other, distal to the nozzle tube 23 (particularly as described above by a suction of the jet from the casing 21 by the working jet 20), the cells are received by, transported and accelerated by the working jet until the velocity of the cells matches the velocity of the working jet 20. The small acceleration of the cell suspension 17 in the pre-acceleration zone 18 in the outer nozzle has the advantage that the cells are subject to only a small shear stress on the radial interior and on the radially external wall surfaces of the outer nozzle that limit the channel in the second conduit 14. But, on the other hand, the relative velocity between the cells and the working fluid 20 at the initial contact of the first and second fluids 16, 17 in the re-acceleration zone 19 is less than the flow velocity of the working fluid 16.The difference in velocity between the two liquids 16, 17 in this area, where these fluids first come into contact, does in fact lead to the creation of shear stress on the cells; however, overall, a small cellular stress is achieved and therefore a high cell survival rate during injection into channel 105 in tissue 106.
[0061] The present invention further improves cell survival due to the alteration adjacent to the distal end of the instrument 10 of the channels extending close to each other, particularly parallel, to the channels extending coaxially from the first and second conduits 11, 14.Also, due to following an approach with the invention for external mixing, in which the instrument 10 receives the first fluid 16 and the cell comprising a second fluid 17 through the conduits 11, 14 and the addition of the cell suspension 17 or cells in the working jet 20 is carried out only after passing through the first nozzle tube 23, a high survival rate of the cells is improved. A. Petition 870260077615, dated 04 / 08 / 2026, page 28 / 82 25 / 29 second nozzle formed by the outer surface of the nozzle tube 23 and the inner surface of the outer wall section 22 or by the outer wall element 29, as illustrated in figures 1 or 2, provides a specific low shear flow configuration and is therefore conducive to a high cell survival rate by the continuous tapering of at least the inner diameter of the outer wall elastic element 29.
[0062] The transport of the cell suspension 17 or of the cell ingredients by the working jet 20 is facilitated if the distal end of the first nozzle tube 23 is diverted from the distal end of the outer wall elastic element 29, as exemplified in figures 1 and 2. The re-acceleration zone 19 in which mixing occurs is thus enclosed in axial sections from the outer wall elastic element 29, more precisely from the cylindrical section 29c. The shape of the outer wall element 29 and the arrangement of the outer wall element 29 and the nozzle tube 23 have the advantage that the jet from the shell 21, particularly due to section 29c, is constantly brought closer to the nozzle tube 23 and finally to the central working jet 20 and, in fact, preferably substantially so that the shell jet 21 and the working jet 20 have predominantly the same directional components.The distal end of the nozzle tube 23, which forms the first opening 12, can be displaced backward relative to the distal end of the elastic outer wall section 29, which forms the second opening 15, for example, by 0.5 to 3 mm. In a particularly preferred embodiment, the nozzle tube 23 is moved back 1 mm. Due to this displacement of the first opening 12 on the distal face 13 of the first conduit, from the distal end 25 of the instrument 10, a minimum length of the reacceleration zone 19, in which the reception of the ingredients of the second fluid 17 to the first fluid 16 also occurs, is defined within the instrument 10. The reacceleration zone 19. Petition 870260077615, dated 04 / 08 / 2026, page 29 / 82 26 / 29 is also mostly free if the distal end 25 of instrument 10 is pressed into tissue 106.
[0063] If the distal end 25 of the instrument 10 is pressed lightly on the tissue surface, it can be achieved that the position of the distal end 25 of the instrument 10 and particularly of the first nozzle tube 23 is not altered during the creation of the channel 105 and the application of the cells. For this purpose, the exemplary embodiment of the instrument 10 according to Figure 2 comprises a cap 34 of a material that is resistant to compression in the axial direction A and resistant to bending, wherein the cap 34 prevents the tissue from reaching and deforming the elastic element of the outer wall 29 when the instrument is placed in the tissue.
[0064] An application process comprises a needle-free creation of an injection channel 105 in the tissue 106 in a target area by means of instrument 10 and the injection of a cell suspension at a predefined dosage into the channel 105. The application process may further comprise the subsequent sealing of the injection channel 105, for example, by means of a sealing medium additively mixed with the working fluid jet 20 subsequently to add the cell suspension 17 through the second conduit 14 to the working fluid jet 20. The added sealing medium may have a higher viscosity than the cell suspension. The sealing medium may be similar to a gel.
[0065] In order to guarantee the high efficiency of a substance introduced into a patient's tissue, for example, in order to guarantee high integrity of cells introduced into a patient's tissue, according to the invention an instrument 10 with a first conduit 11 for emitting a first fluid 16 from a first opening 12 of the first conduit 11 in an axial direction A in a reacceleration zone 19 and with a second conduit 14 for channeling of Petition 870260077615, dated 04 / 08 / 2026, page 30 / 82 27 / 29 A second fluid 17 in the reacceleration zone 19 in the axial direction A is provided so that the components of the active ingredient, for example, cells, of the second fluid 17 are reaccelerated in the axial direction as a result of the flow in the reacceleration zone 19 through the first fluid 16 entering the reacceleration zone 19. A coaxial configuration of the first and second conduits 11, 14 is preferred, since by doing so, around the first opening 12 an envelope jet 21 of the second fluid 17 can be created flowing downstream in the axial direction around the central working jet 20. In addition, a head 24 for an inventive instrument 10 and an application system 100 with an inventive instrument 10 is provided. In exemplary embodiments, not illustrated, of the instrument, the instrument may comprise multiple second conduits, i.e., at least two second conduits.With multiple secondary conduits, similar or different secondary fluids can be channeled into the reacceleration zone in an alternating manner and / or at least during phases simultaneously. By doing so, ingredients of the secondary fluids can be reaccelerated in the axial direction due to the flow into the reacceleration zone by the first fluid that enters the reacceleration zone in the axial direction. For example, the secondary fluids can be different substances or can comprise different substances, for example, different active ingredients. Alternatively or additionally, embodiments of the inventive instrument may further comprise multiple primary conduits, for example, at least two primary conduits that are configured to emit similar or different primary fluids into the reacceleration zone in order to reaccelerate one or more secondary fluids. List of reference signs: first conduit instrument Petition 870260077615, dated 04 / 08 / 2026, page 31 / 82 28 / 29 12 first opening 13 face 14 second conduit 15 second opening 16 first fluid 17 second fluid 18 pre-acceleration zone 19 re-acceleration zone 20 working flow / carrier flow 21 casing flow 22 outer wall section 23 nozzle tube 24 head 25 distal end of instrument 26 conduit sections 27 outer wall of first conduit / inner wall of second conduit 28 shaft tube section 29 Outer wall element 29a Cylindrical section 29b Tapered section 29c Additional cylindrical section 30 outer nozzle 31 Ring gap 32 Centering element 33 recess / clearance 34 cap 35 opening 36 transition location 37 Switch arrangement Petition 870260077615, dated 04 / 08 / 2026, page 32 / 82 29 / 29 38 coating hose 100 application system 101 dispensing device 102 control 103 source 104 source 105 channel 106 fabric P arrow A axial direction U inner circumference b Gap width B1, B2, B3 sections C1, C2, C3 cross-sectional areas L length AtA application time intervals AtAF1 first working fluid dispensing interval AtAF2 second working fluid dispensing interval AtWF active ingredient dispensing interval v1 first speed v1r reduced first speed v2 second speed Petition 870260077615, dated 04 / 08 / 2026, page 33 / 82
Claims
1 / 5 CLAIMS 1. An instrument (10) for needle-free injection of a medicinal fluid, characterized in that it has a first conduit (11) for emitting a first fluid (16) from a first opening (12) of the first conduit (11) in an axial direction (A) into a reacceleration zone (19), having a second conduit (14) for channeling a second fluid (17) into the reacceleration zone (19) in the axial direction (A) such that ingredients of the second fluid (17) due to flow in the reacceleration zone (19) are reaccelerated in the axial direction (A) by a first fluid (16) entering the reacceleration zone, wherein the instrument (10) is configured to emit the first fluid (16) out of the first opening (12) with a velocity in the reacceleration zone (19), while this velocity is greater than the velocity of the second fluid (17) in the axial direction. (A) near the first opening (12), where the first conduit (11) is laid in a second conduit (14),The first conduit (11) and the second conduit (14) are arranged coaxially with respect to each other, the first conduit (11) and the second conduit (14) are configured to be traversed by the first fluid (16) and the second fluid (17), respectively, in the axial direction A, the first opening (12) is arranged upstream of the second opening (15), a pre-acceleration zone (18) is formed by a conical internal cross-section of the second conduit (14) towards the second opening (15), and an acceleration zone (19) is arranged downstream of the first opening (12), where the ingredients of the second fluid (17) Petition 870260077615, dated 04 / 08 / 2026, page 34 / 82 2 / 5 are received in the carrier flow (20) of the first fluid (16).
2. Instrument (10), according to claim 1, including a pre-acceleration zone (18) of the second conduit (14) upstream of the re-acceleration zone (19), characterized in that the instrument is configured to pre-accelerate the second fluid (17) in the axial direction (A) in the pre-acceleration zone (18), and in that a first opening (12) is disposed in the re-acceleration zone (19) such that the outlet of the first fluid (16) from the first opening (12) re-accelerates the second pre-accelerated fluid (17) in the axial direction (A).
3. Instrument (10), according to claim 2, characterized in that the pre-acceleration zone (18) is formed by a section of the nozzle of the second conduit (14) in which the internal cross-section tapers in the flow direction.
4. Instrument (10), according to claim 3, characterized in that the internal cross-section of the nozzle section continuously tapers in at least one subsection of the nozzle section.
5. Instrument (10), according to any of the preceding claims, characterized in that the second conduit (14) concentrically encircles the first conduit (11) at the first opening (12) in order to create a ring-shaped envelope flow (21) of the second fluid (17) around the first fluid (16) exiting the first opening (12).
6. Instrument (10), according to any of the preceding claims, characterized in that the second conduit (14) is configured to radially approach the casing flow (21) to the first conduit (11) so that the working flow (20) exiting the first opening (12) sucks ingredients from the casing flow (21) to the working flow (20).
7. Instrument (10), according to any of the preceding claims, characterized in that the outer wall of the second conduit (14) is elastic in a section (22) around the first opening (12).
8. Instrument (10), according to claim 7, characterized in that section (22) is formed by an elastic element (29) that forms the outer wall of the second conduit (14).
9. Instrument (10), according to claim 8, characterized in that the elastic element (29) is upstream connected with a section of the tube (28) of the second conduit (14), and in that radially between the section of the tube (28) and the first conduit (11) a centering device (32) is effective.
10. Instrument (10), according to claim 9, characterized in that the section of the tube (28) of the second conduit (14) surrounds a section of the tube (26) of the first conduit (11), wherein the centering device (32) is arranged radially between the section of the tube (28) of the second conduit (14) and the section of the tube (26) of the first conduit (11) in order to concentrically align the section of the tube (26) of the first conduit (11) with the section of the tube (28) of the second conduit (14).
11. Instrument (10), according to any of the preceding claims, characterized in that the second conduit (14) terminates downstream of the first opening (12) and / or upstream of a distal opening (35) of the instrument (10).
12. Instrument (10), according to any of the preceding claims, characterized in that the instrument (10) is configured to channel the first fluid (16) and the second fluid (17) adjacent to each other in the conduit sections of the first and second conduit (11, 14) arranged adjacent to each other until they reach a transition location (36) near the distal end (25) of the instrument (10) and to channel the first fluid (16) and the second fluid (17) in the coaxial conduit sections of the first and second conduit (11, 14) after the transition location (36) to the distal end (25).
13. Instrument (10), according to any of the preceding claims, characterized in that the pre-acceleration zone (18) and / or the re-acceleration zone (19) are arranged in a head (24) of the instrument.
14. Instrument head (24), characterized in that it is for an instrument (10), as defined in claim 13.
15. Application system (100), characterized in that it comprises: an instrument (10), as defined in any of the preceding claims, a supply device (101) that is in fluid connection with the first conduit (11) and the second conduit (14) and that is configured to supply the first fluid (16) and the second fluid (17) in a sequence of supply intervals (ΔtAF1, ΔtAF2, ΔtWF).
16. Application system (100), according to claim 15, characterized in that the supply device (101) comprises a control (102) that controls the application system (100) such that within an application time interval (ΔtA) during a first working fluid supply interval (ΔtAF1) the first fluid (16) is supplied so as to comprise a first velocity (v1) at the first opening (12) for creating a channel (105) in the tissue (106), during a second working fluid supply interval (ΔtAF2) the first fluid (16) is supplied so as to comprise a reduced first velocity (v1r) at the first opening (12) which is less than the first velocity (v1) and at least during the phases during the second working fluid supply interval. Petition 870260077615, dated 04 / 08 / 2026, p.37 / 82 5 / 5 (ΔtAF2) the second fluid (17) is supplied so that it comprises a second velocity (v2) at the first opening (12) which is less than the first reduced velocity (v1r). Petition 870260077615, dated 04 / 08 / 2026, page 38 / 82.