DEVICE AND METHOD FOR THE APPLICATION OF A PHARMACEUTICAL FLUID

Description

[0001] The invention relates to a device for applying a pharmaceutical fluid comprising a hollow cylindrical body surrounding a channel extending through the body from a proximal end to a distal end, wherein an outer surface of the body has at least a partial external thread, and a connecting element arranged at the proximal end of the body, via which a proximal end of the channel can be reversibly connected to a reservoir for the pharmaceutical fluid in a fluid-conducting manner.

[0002] The invention relates in particular to a medical device for the temporary, local application of pharmaceutical fluids or other medical fluids over a period of hours to several months. The device according to the invention is primarily intended for the treatment of inflammatory joint diseases, such as activated osteoarthritis and rheumatoid arthritis. Background of the invention

[0003] Inflammatory joint diseases, such as activated osteoarthritis and rheumatoid arthritis, are widespread. These diseases are often associated with joint pain and, through a progressive inflammatory process, can cause increasing joint destruction, which can lead to impaired joint function or even a complete loss of joint function.

[0004] Besides systemic pharmacological therapy, which can have side effects for the patient and is less effective due to a comparatively low drug concentration at the site of inflammation, there is the possibility of influencing the inflammatory process through intra-articular injection of pharmaceutical fluids, particularly anti-inflammatory agents. Examples of such agents include dexamethasone phosphate, cyclosporine, sulfasalazine, and methotrexate.

[0005] A critical aspect of intra-articular injection is the significant risk of infection within the articular space. Furthermore, human joint capsules are equipped with nociceptors, making them highly sensitive to pain.

[0006] Bone screws with a central channel in the screw body and associated exit openings are known as cannulated and fenestrated screws. To date, these bone screws are primarily used in the spinal region as so-called cannulated and fenestrated pedicle screws. In this procedure, bone cement is injected through the screw channel into the usually osteoporotic vertebral body, forming a cement mantle that is predominantly coaxial with the longitudinal axis of the pedicle screw. The bone cement then hardens and forms an abutment for the pedicle screws. Numerous cannulated and fenestrated bone screws have been proposed. Examples include the patent applications DE 35 08 759 A1, DE 1994 9285 C2, DE 10 2011 112 890 B4, EP 1 210 019 B1, and EP 2 887 899 B1.

[0007] In addition, cannulated and fenestrated bone screws can also be used for the local application of pharmaceutical fluids, as described by way of example in patents and publications US 9,616,205 B2, US 10,357,298 B2, and US 2018 / 0014867 A1. US 2019 / 167326 discloses a bone screw that includes a check valve.

[0008] A disadvantage of the cannulated and fenestrated bone screws described so far is the ingrowth of tissue, especially connective tissue, into the discharge openings of the bone screws, which makes further application of pharmaceutical fluids via the fluid-conducting bone screw difficult or even completely prevents it.

[0009] A device that is protected against tissue ingrowth, particularly of connective tissue, is therefore desirable, allowing for the application of a pharmaceutical fluid over an extended period, such as several weeks or even months. Furthermore, the device should permit the local application of any pharmaceutical active ingredient in the form of pharmaceutical fluids, with the ability to change the composition and / or concentration of active ingredients in the pharmaceutical fluid at any time. It is also desirable that the concentration of the active ingredient in the pharmaceutical fluid, achieved directly at the implantation site of the device, can be adjusted externally. Tasks

[0010] One object of the present invention is to overcome at least some of the disadvantages arising from the prior art.

[0011] In particular, a device for the local application of pharmaceutical fluids, such as anti-inflammatory, cytostatic and glucocorticoid solutions, is to be provided, enabling the local and temporary delivery of the pharmaceutical fluid into the joint capsules of a patient, especially joint capsules of larger joints such as the knee joint.

[0012] The device should be designed to allow the repeated administration of pharmaceutical fluids of any and all varying compositions into a joint capsule from outside the patient's body, as needed, without the need to puncture the joint capsule. The device should also be suitable for the repeated delivery of the pharmaceutical fluid over extended periods, such as several weeks or months, without requiring removal and without clogging, particularly due to the deposition of endogenous tissue, especially endogenous proteins. Furthermore, synovial fluid should not leak from the joint capsule through the device. The device's design should prevent microorganisms from entering the intra-articular space.The device should be inexpensive to manufacture and ideally a hygienic, single-use, disposable product. The fluid output from the device should be externally controllable. Preferred embodiments of the invention

[0013] The features of the independent claims contribute to at least partially fulfilling at least one of the aforementioned tasks. The dependent claims provide preferred embodiments that contribute to at least partially fulfilling at least one of the tasks.

[0014] A first embodiment of the invention is a device for applying a pharmaceutical fluid comprising a hollow cylindrical body surrounding a channel extending through the body from a proximal end to a distal end, wherein an outer surface of the body has at least a partial external thread, a connecting element arranged at the proximal end of the body via which a proximal end of the channel can be reversibly connected to a reservoir for the pharmaceutical fluid, characterized by a check valve arranged in the channel which is designed to be fluid-impermeable towards the proximal end of the channel, and a sealing element arranged distal to the check valve in the channel which closes a distal end of the channel in a fluid-conducting manner and which has a gap.which, when pressure is applied to the pharmaceutical fluid from the direction of the proximal end of the channel, can be reversibly opened to allow fluid flow, so that the pharmaceutical fluid can be applied from the distal end of the channel.

[0015] In one embodiment of the device, the gap opens reversibly and fluid-conducting upon application of a pressure greater than 5 N / cm², preferably greater than 6 N / cm², and more preferably greater than 7 N / cm², so that the distal end of the channel is open and fluid-conducting. This embodiment is a second embodiment of the invention, which preferably depends on the first embodiment of the invention.

[0016] In the device, the check valve is a ball check valve comprising a ball and a return element.

[0017] In one embodiment of the device, the return element and the sealing element are formed as a single unit. This embodiment is a fourth embodiment of the invention, which preferably depends on the third embodiment of the invention.

[0018] In one embodiment of the device, a filter element is arranged in the channel. This embodiment is a fifth embodiment of the invention, which preferably depends on one of the preceding embodiments of the invention.

[0019] In one embodiment of the device, the filter element is arranged in the channel proximal to the check valve, i.e., closer to the proximal end of the channel than the check valve. This embodiment is a sixth embodiment of the invention, which preferably depends on the fifth embodiment of the invention.

[0020] In one embodiment of the device, the filter element is a microporous filter plate. This embodiment is a seventh embodiment of the invention, which preferably depends on the fifth or sixth embodiment of the invention.

[0021] In one embodiment of the device, the microporous filter plate has pores with an average pore diameter of less than 40 µm, preferably less than 5 µm, and more preferably less than 1 µm. This embodiment is an eighth embodiment of the invention, which preferably depends on the seventh embodiment of the invention.

[0022] In one embodiment of the device, a hollow cylindrical sleeve is arranged in the channel distal to the sealing element, i.e., closer to the distal end of the channel than the sealing element, in order to prevent the sealing element, and preferably also all other structural elements in the channel proximal to the sealing element, from being carried out of the distal end of the channel during the application of the pharmaceutical fluid. This embodiment is a ninth embodiment of the invention, which preferably depends on one of the preceding embodiments of the invention.

[0023] In one embodiment of the device, the proximal channel end is polygonal, in particular hexagonal, and the connecting element is equipped with a matching polygonal, in particular hexagonal, connecting element section to reversibly connect the connecting element to the proximal channel end in a fluid-conducting manner by inserting the connecting element section into the proximal channel end.

[0024] This embodiment is a tenth embodiment of the invention, which preferably depends on one of the preceding embodiments of the invention.

[0025] In one embodiment of the device, the polygonal, in particular hexagonal, proximal channel end has a greater axial extent than the polygonal, in particular hexagonal, connecting element section, so that after removal, in particular by cutting or sawing off, of a part, in particular a proximal part, of the proximal channel end, the connecting element can be reversibly and fluidly connected to a remaining part of the proximal channel end by inserting the connecting element section into the remaining proximal channel end. This embodiment is an eleventh embodiment of the invention, which preferably depends on the tenth embodiment of the invention.

[0026] In one embodiment of the device, the body comprises a metal, a polymer, or a metal and a polymer; in particular, the body consists of a metal, a polymer, or a metal and a polymer. This embodiment is a twelfth embodiment of the invention, which preferably depends on one of the preceding embodiments of the invention.

[0027] One object of the disclosure is a method for applying a pharmaceutical fluid by means of a device according to one of the first to twelfth embodiments of the invention comprising the following steps: a. Implanting the device; b. Fluid-conducting connection of the device to a reservoir for the pharmaceutical fluid; c. Building up a delivery pressure on the pharmaceutical fluid from the direction of the proximal channel end of greater than 5 N / cm²; d. Fluid-conducting opening of the gap in the sealing element by the action of the delivery pressure; e. Dispensing the pharmaceutical fluid from the fluid-conducting open gap; f. Fluid-conducting closing of the gap by reducing the delivery pressure to 5 N / cm² or less. General

[0028] In this description, range specifications also include values ​​referred to as limits. A specification of the type "in the range from X to Y" with respect to a quantity A therefore means that A can take the values ​​X, Y, and values ​​between X and Y. Similarly, a range limited on one side, such as "up to Y" for a quantity A, means that A can take the values ​​Y and less than Y.

[0029] Some of the described characteristics are linked to the term "essentially." The term "essentially" means that, under real-world conditions and manufacturing techniques, a mathematically exact interpretation of terms such as "superposition," "perpendicular," "diameter," or "parallelism" can never be exact, but only within certain manufacturing tolerances. For example, "essentially perpendicular axes" include an angle of 85 to 95 degrees to each other, and "essentially equal volumes" encompass a deviation of up to 5% by volume. A "device consisting essentially of plastic," for example, comprises a plastic content of ≥95% to ≤100% by weight. "An essentially complete filling of volume B," for example, encompasses a filling of ≥95% to ≤100% by volume of the total volume of B. Detailed description

[0030] A first object of the invention relates to a device for applying a pharmaceutical fluid, in particular for applying a pharmaceutical fluid into a joint capsule, comprising a hollow cylindrical body surrounding a channel extending through the body from a proximal end to a distal end of the body. wherein an outer surface of the body has at least a partial external thread, a connecting element arranged at the proximal end of the body, via which a proximal channel end of the channel can be reversibly connected to a reservoir for the pharmaceutical fluid, characterized by a check valve arranged in the channel which is designed to be fluid-impermeable in the direction of the proximal channel end, and a sealing element arranged distal to the check valve in the channel which closes a distal channel end of the channel in a fluid-conducting manner and in which, when pressure is applied to the pharmaceutical fluid from the direction of the proximal channel end, a gap can be reversibly opened in a fluid-conducting manner, so that the pharmaceutical fluid can be applied from the distal channel end.

[0031] The device includes a check valve in the channel. A check valve is a component that allows the pharmaceutical fluid to flow in one direction while preventing flow in the opposite direction. The check valve according to the invention allows the pharmaceutical fluid to flow from the proximal end of the channel towards the distal end, while preventing flow from the distal end towards the proximal end. The check valve according to the invention is therefore designed to allow fluid flow towards the distal end of the channel and to be impermeable to fluid flow towards the proximal end.This allows a pharmaceutical fluid to be pumped and applied from a reservoir connected to the connecting element through the device and out of the distal end of the channel, while preventing the ingress of fluids, particularly fluids containing connective tissue, into the channel proximal to the check valve. This prevents, in particular, complete contamination and / or blockage of the device and the reservoir connected to the device by a fluid, such as blood, entering the distal end of the channel.

[0032] Distal to the check valve, i.e., closer to the distal end of the channel than the check valve, a sealing element is arranged within the channel. This element seals the distal end of the channel, allowing fluid to pass through, until a sufficiently high pressure is applied to the pharmaceutical fluid within the channel from the proximal end. This causes a gap in the sealing element to open, allowing fluid to pass through. If the pressure is insufficient, the gap remains sealed. With continued pressure, the pharmaceutical fluid can be applied from the channel to a desired location through the open gap. Once the pressure is released, the previously formed, open gap in the sealing element closes automatically within a few moments, for example, within fractions of a second, and the distal end of the channel is once again sealed by the sealing element.For this purpose, the sealing element is preferably made of an elastic material. The sealing element prevents the ingrowth of connective tissue and the ingress of blood into the device, which is why the device can remain functionally implanted in the patient's body for several days to months, allowing for repeated local application of a pharmaceutical fluid to the desired site. A further advantage of the device's design is that even if the distal end of the channel should become blocked, for example by connective tissue or clotted blood, this blockage would be cleared by pressurizing the device and subsequently dispensing the pharmaceutical fluid under pressure. The design and function of the device thus enable a "self-cleaning" of the blockage through its use.

[0033] The sealing element can have one or more gaps, which can have different shapes. Due to its simple manufacturing process, a single, elongated gap is preferred.

[0034] The device can be operated in at least two ways. In the first way, the pressure is applied in pulses, so that even the application of a small amount of pharmaceutical fluid, for example up to 2 milliliters, reduces the internal pressure generated by the pressure from the device to such an extent that the gap is closed again, allowing fluid to flow. In this case, the pressure only reaches the required threshold briefly, i.e., in pulses, to reversibly close the gap and allow fluid to flow. In the second way, the pharmaceutical fluid is continuously pressurized, so that it can be dispensed from the distal end of the channel as long as the pressure is maintained at the required threshold. This type of pressure application thus allows for the continuous application of a pharmaceutical fluid.

[0035] Should fluid containing connective tissue penetrate the distal end of the canal despite the sealing element, the check valve acts as a second barrier against the ingressing fluid. The sealing element and check valve thus work synergistically, effectively preventing contamination of the device. This allows the device to be implanted for a longer period compared to a device with only one barrier.

[0036] The check valve can have different designs. In one design, the check valve includes a check flap that allows the pharmaceutical fluid to flow through the channel only in one direction and closes the channel in a fluid-conducting manner in the opposite direction.

[0037] The device comprises a hollow cylindrical body. A hollow cylindrical body is understood to be a tubular structural element that surrounds a channel with an inner surface facing the channel and an outer surface facing away from the channel. The cross-section of the body can assume any desired shape. Due to the ease of manufacturing and the improved anchoring possibilities within a patient, the cross-section, and preferably also the cross-section of the channel, is essentially circular.

[0038] The canal runs from a proximal end of the body, through the body, to a distal end. A proximal end of the canal faces the proximal end of the body, and a distal end of the canal faces the distal end.

[0039] "Proximal" and "distal" merely serve to describe the spatially opposite ends of the device, the body, or other structural units of the device and do not allow any conclusions to be drawn about the orientation of the device implanted in a human body. "Distal to..." and "proximal to..." or similar formulations accordingly only express the spatial arrangement of two structural units of the device relative to each other.

[0040] The outer surface of the body has an external thread, at least in some sections. This external thread serves to anchor the device in tissue, particularly bone tissue of a patient, by screwing the device into a corresponding pre-drilled hole in the tissue, especially bone tissue. In one embodiment, the external thread extends over the entire axial length of the body, so that the body can be screwed into the corresponding hole along its entire length. The external thread can be arranged on the outer surface of a tube-like element that surrounds the body like a cuff. In a preferred embodiment, the outer surface of the body itself is formed as an external thread.

[0041] The device has a fluid-conducting connecting element at its proximal end, through which the proximal end of the channel can be reversibly connected to a reservoir for the pharmaceutical fluid. In one embodiment, the connecting element and the proximal end of the body are formed as a single unit. In further preferred embodiments, the connecting element and the distal end of the body are reversibly connected to each other in a fluid-conducting manner. The connecting element can be configured in various ways to connect the proximal end of the channel to a reservoir for a pharmaceutical fluid in a fluid-conducting manner. In one embodiment, the connecting element is shaped as a nozzle through which the proximal end of the channel can be connected to a reservoir by means of a hose.In another embodiment, the connecting element is formed as a thread which can be fluidly connected to a reservoir via a corresponding counterpart. In another embodiment, the connecting element forms a flange connection with a reservoir. In yet another embodiment, the connecting element forms a fluid-conducting connection with a reservoir via a hose coupling, whereby the connecting element can include either the coupling or the nipple of the hose coupling.

[0042] A reservoir is any container suitable for storing a pharmaceutical fluid. Examples of reservoirs include bags, syringes, pistons, balloons, canisters, and ampoules, with bags, balloons, and syringes being preferred.

[0043] The device according to the invention serves for the local application of a pharmaceutical fluid, in particular for the treatment of inflammatory joint diseases, such as activated osteoarthritis and rheumatoid arthritis, over a period of several days to several months. A pharmaceutical fluid contains at least one pharmaceutical active ingredient. For example, the pharmaceutical fluid is an aqueous or non-aqueous solution or suspension of pharmaceutical active ingredients.

[0044] In one embodiment, the pharmaceutical fluid consists of solutions containing at least one anti-inflammatory agent, cytostatic agent, and / or glucocorticoid. In another embodiment, the pharmaceutical fluids contain at least one disinfectant component.

[0045] Furthermore, pharmaceutical fluids also include gases, gas mixtures and solutions of gases in liquids, such as water.

[0046] The pressure applied to the pharmaceutical fluid required to form the fluid-conducting gap in the sealing element can depend on various factors, such as the material of the sealing element, the diameter of the sealing element and the length of the sealing element.

[0047] To ensure controlled application of the pharmaceutical fluid from the device, one embodiment of the device is characterized in that the gap only opens reversibly in a fluid-conducting manner in the sealing element when a pressure of at least 5 N / cm² is applied to the pharmaceutical fluid from the direction of the proximal channel end, so that the distal channel end is open and fluid-conducting. If the pressure does not reach this threshold, the gap, and thus the distal channel end, remains closed and fluid-conducting. This prevents the unintentional leakage of the pharmaceutical fluid from the device into the patient, which could pose health risks.A further advantage is that the penetration of fluids from the patient containing tissue, particularly connective tissue, through the distal end of the channel is not hindered without a correspondingly opposing pressure being exerted towards the proximal end of the channel. The penetration of these endogenous fluids could lead to contamination or blockage of the device. To ensure controlled application, even in small quantities, and without the risk of unintentional damage to the device, such as cracking in the body or the sealing element, it is preferred that the pressure required to open the gap for fluid flow does not exceed 150 N / cm².

[0048] The check valve can have different designs. In one embodiment, the check valve comprises a check flap that allows the pharmaceutical fluid to flow through the channel in only one direction, particularly towards the distal end of the channel, and closes the channel in a fluid-conducting manner in the opposite direction, particularly towards the proximal end of the channel. In another embodiment, the check valve is designed as a disc check valve.

[0049] One embodiment of the device is characterized in that the check valve is a ball check valve comprising a ball and a return element. In a ball check valve, a conduit is closed by a ball, which is held against the conduit by gravity or, as provided according to the invention, by a return element, in order to close it. A fluid that is conveyed through the conduit against the ball and the return element acting on the ball can, if the conveying pressure exceeds the pressure of the return element on the ball, open the ball check valve. From the opposite conveying direction, i.e., from the direction of the return element towards the conduit, the ball check valve remains closed by the ball.One advantage of a ball check valve is its simple, cost-effective design and low susceptibility to malfunctions.

[0050] The return element can be designed in various ways to press the ball against the fluid and to close the ball check valve in a fluid-conducting manner. In one embodiment, the return element comprises a spring, for example a coil spring or leaf spring, for example made of metal. In another embodiment, the return element comprises an elastic polymer element, in particular a tubular or leaf-spring-shaped polymer element.

[0051] The reset element can be a separate component or connected to other components of the device.

[0052] One embodiment of the device is characterized in that the return element and the sealing element are designed as a single unit. This reduces the number of components of the device, which simplifies its manufacture and also reduces its susceptibility to malfunctions. Since the sealing element is preferably made of an elastic material, the design of the end of the sealing element facing the check valve, in particular the ball of the ball check valve, as a return element—for example, as an elastic pipe section or as elastic leaf spring elements—allows for a simple and cost-effective design of the device.

[0053] To remove any microorganisms that may be present from the pharmaceutical fluid, one embodiment of the device is characterized by the fact that a filter element is arranged in the channel.

[0054] The filter element can be located at different points within the channel.

[0055] To prevent complete contamination of the device, for example by microorganisms, one embodiment of the device is characterized in that the filter element is arranged in the channel proximal to the check valve, i.e., closer to the proximal end of the channel than the check valve. In this embodiment, when the pharmaceutical fluid is conveyed through the channel from the direction of the proximal end, it first passes through the filter element, followed by the check valve, and finally the sealing element. Thus, when the pharmaceutical fluid is applied, it is filtered by the filter element before reaching the check valve and the sealing element.

[0056] The filter element can be designed in different ways. In one embodiment, the filter element comprises a nonwoven fabric, in particular a glass fiber nonwoven fabric. In another embodiment, the filter element comprises a fibrous material, in particular a polyester, metal, and / or cellulose fiber material. In yet another embodiment, the filter element comprises a wire mesh, in particular a stainless steel wire mesh.

[0057] One embodiment of the device is characterized in that the filter element comprises a microporous filter plate, in particular that the filter element is a microporous filter plate.

[0058] The microporous filter plate can have pores with varying average pore diameters. An average pore diameter is defined as the arithmetic mean of the pore diameters of the pores in the filter plate.

[0059] One embodiment of the device is characterized in that the microporous filter plate has pores with an average pore diameter of less than 40 µm, preferably less than 5 µm, and more preferably less than 1 µm. This allows for good purification of the pharmaceutical fluid. To ensure smooth flow of the pharmaceutical fluid through the device despite the good filtration performance, it is preferred that the average pore diameter is not less than 0.05 µm.

[0060] To prevent the sealing element from being carried out of the distal end of the channel during the application of a pharmaceutical fluid using the device, the sealing element can be secured in the channel in various ways. In one embodiment, the sealing element is fixed within the channel using an adhesive.

[0061] One embodiment of the device is characterized in that a hollow cylindrical sleeve is arranged in the channel distal to the sealing element, i.e., closer to the distal end of the channel than the sealing element, in order to prevent the sealing element from being carried out of the distal end of the channel during the application of the pharmaceutical fluid. To fix the hollow cylindrical sleeve itself in the channel, it can interact with the inner surface of the body by means of a tongue-and-groove connection, forming a positive and / or force-fit connection, thus preventing it from being carried out.

[0062] The connecting element and the hollow cylindrical body can be joined in various ways to create a fluid-conducting connection between the connecting element and the proximal end of the channel. In one embodiment, the connecting element and the body are formed as a single unit.

[0063] In other embodiments, the connecting element and the body are connected to each other by means of an adhesive connection, a bayonet connection or a threaded connection.

[0064] One embodiment of the device is characterized in that the proximal channel end is polygonal, in particular hexagonal, and the connecting element is equipped with a polygonal, in particular hexagonal, connecting element section in order to reversibly connect the connecting element to the proximal channel end in a fluid-conducting manner by inserting the connecting element section into the proximal channel end.

[0065] Insertion, i.e., sliding the connecting element section into the proximal end of the channel, provides a secure, simple, and cost-effective method for attaching the connecting element to the proximal channel end. After insertion, the proximal channel end and the connecting element section engage in a form-fit and / or force-fit connection, but can also be separated again by pulling on the connecting element if necessary. This process can be repeated as often as required. To ensure a secure, fluid-conducting connection between the two components, the connecting element and the proximal channel end preferably have the same number of edges and matching edge dimensions, allowing them to be slid together like a lock and key.One advantage of this design is that it prevents unwanted axial rotation of the two components relative to each other, and the device can be connected to a reservoir for a pharmaceutical fluid in a desired orientation. Another advantage is that the polygonal design of the proximal channel end allows the device to be screwed into a suitably prepared borehole in the patient's bone tissue using a matching polygonal tool, particularly a wrench.

[0066] In order to allow the polygonal connecting element section to be fully inserted into the proximal channel end, it is preferred that the polygonal proximal channel end has at least the same axial extent as the polygonal connecting element section.

[0067] One embodiment of the device is characterized in that the polygonal proximal channel end has a larger axial extent than the polygonal connecting element section, so that after removing part of the proximal channel end, in particular by sawing or cutting, the connecting element can be fluidly connected to a remaining part of the proximal channel end by inserting the connecting element section into the remaining proximal channel end.

[0068] The device can be implanted into a patient's bone tissue in various ways. To ensure maximum joint mobility and thus the most natural, pain-free movement possible, it is preferable to embed the device as completely as possible within the bone tissue. Depending on the patient's size and the thickness of the existing bone tissue, it may be necessary to shorten the device to achieve the most complete embedding.

[0069] If the axial extent, i.e. the length, of the polygonal proximal channel end is greater than the axial extent of the polygonal connecting element section, the proximal channel end can be shortened, for example by cutting or sawing, whereby after shortening the proximal channel end the connecting element section can still be fully inserted into the proximal channel end in order to connect the connecting element fluidly to the channel.

[0070] In one embodiment of the device, the body comprises a metal, a polymer, or a metal and a polymer; in particular, the body consists of a metal, a polymer, or a metal and a polymer. Examples of polymers include polyamides, polyesters, polyketones, polymethacrylates, and their copolymers. Examples of metals include pure metals such as aluminum and titanium, or metal alloys such as stainless steels, in particular stainless steel 1.4404, or titanium alloys such as TiAl6V4.

[0071] To ensure proper and targeted application at the desired location within a patient, one embodiment of the device is characterized in that at least a portion of the device, in particular the hollow cylindrical body of the device, has a radiopaque material. The radiopaque material allows the correct positioning of the device within the patient to be visualized using X-ray imaging techniques. Examples of radiopaque materials include barium sulfate, zirconium dioxide, and calcium carbonate.

[0072] Another subject of the disclosure relates to a method for applying a pharmaceutical fluid using a device according to one of the preceding embodiments, comprising the following steps: a. Implanting the device; b. Fluid-conducting connection of the device to a reservoir for the pharmaceutical fluid; c. Building up a delivery pressure on the pharmaceutical fluid from the direction of the proximal channel end of greater than 5 N / cm²; d. Fluid-conducting opening of the gap in the sealing element by the action of the delivery pressure; e. Dispensing the pharmaceutical fluid from the fluid-conducting open gap; f. Fluid-conducting closing of the gap by reducing the delivery pressure to 5 N / cm² or less.

[0073] The device can be implanted in the patient in various ways. In a preferred embodiment, implantation is achieved by screwing the device into a pre-drilled hole in the patient's bone tissue. The implantation preferably takes place in close proximity to a joint capsule so that pharmaceutical fluid applied via the device can reach the corresponding joint space. To prevent complications and potential joint infections, the device is preferably implanted in such a way that the joint capsule is not perforated. For example, to treat a knee joint, the device can be inserted into a hole in the distal femur, with the hole ending in the intercondylar space. To ensure secure fixation of the device in the bone tissue, the diameter of the hole is selected so that the device can be screwed into the hole with virtually no gap.

[0074] The length of the drill hole can be determined radiographically (X-ray), so that the device can be shortened before implantation if necessary.

[0075] Preferably, the device is screwed into the borehole to such an extent that the proximal end of the body terminates just below, for example 1 mm below, the corresponding joint surface. This ensures a largely normal range of motion of the corresponding joint.

[0076] Following implantation, the device is connected to a reservoir for the pharmaceutical fluid via a fluid-conducting connection. This connection can be implemented in various ways, with the preferred method being to connect the device and the reservoir using a flexible tube. For example, an adapter, particularly a Luer fitting with a cap, can be used to connect the tube to the reservoir. This allows pharmaceutical fluids to be introduced into the intra-articular space to be treated as needed, using a simple syringe.

[0077] To prevent contamination with microorganisms, it is preferable to equip the hose with a sterile filter.

[0078] To apply the pharmaceutical fluid from the device, particularly from the distal end of the channel, a delivery pressure is applied to the pharmaceutical fluid, acting from the proximal end of the channel towards the distal end. This delivery pressure forces the pharmaceutical fluid from the reservoir into the proximal end of the device's channel, through the check valve and the sealing element, and ultimately out of the distal end. To ensure the fluid passes through the check valve and, in particular, the sealing element, a delivery pressure of at least 5 N / cm² is applied to the pharmaceutical fluid. This delivery pressure is sufficient to reversibly open the gap in the sealing element, allowing the pharmaceutical fluid to flow out of the device, especially from the distal end of the channel.

[0079] The delivery pressure on the pharmaceutical fluid to create the fluid-conducting open gap in the sealing element can be applied in various ways. In one embodiment, the delivery pressure is applied by means of a separate pump, for example a peristaltic pump, which acts on a hose used as a fluid-conducting connection between the device and the reservoir. In another embodiment, the reservoir for the pharmaceutical fluid is a syringe, and the delivery pressure on the pharmaceutical fluid is applied by means of a syringe plunger belonging to the syringe.

[0080] If the delivery pressure is reduced to 5 N / cm² or less, the gap in the sealing element closes automatically within a few moments, for example within one second or less, and the application of the pharmaceutical fluid is stopped.

[0081] The features disclosed for the device are also disclosed for the method and vice versa. Figures

[0082] The invention is further illustrated below by means of figures. The invention is not limited to the figures. They show

[0083] Fig. 1 a schematic longitudinal section of a device for applying a pharmaceutical fluid, Fig. 2 the device made of Figure 1 in a perspective side view of a partial schematic longitudinal section of a, Fig. 3 the device made of the Figure 1 and 2 with conveyed pharmaceutical fluid, Fig. 4 the device from the Figures 1 to 3 When applying the pharmaceutical fluid, Fig. 5, the device from the Figures 1 to 4 , fluid-conductingly connected to a reservoir for a pharmaceutical fluid, and Fig. 6 a method for applying a pharmaceutical fluid. Description of the characters

[0084] Figure 1 shows a schematic longitudinal section of an exemplary embodiment of a device 100 for applying a pharmaceutical fluid (in Figure 1 (not shown). The device 100 comprises a hollow cylindrical body 200 with a proximal body end 210 and a distal body end 220 axially opposite the proximal body end 210. An outer surface of the body 200 is formed as an external thread 230. In the embodiment of the device 100 shown, the external thread 230 extends over almost the entire length of the device 100. In other embodiments of the device 100 not shown, the external thread 230 does not extend over almost the entire length, but, for example, only over 50% of the total length of the device 100. The external thread 230 serves to screw the device 100 into a drilled hole in the bone of a patient.

[0085] A fluid-conducting channel 250 extends axially through the hollow cylindrical body 200, the channel 250 extending from a proximal channel end 260 facing the proximal body end 210 through the entire body 200 to a distal channel end 270 facing the distal body end 220. The proximal channel end 260 is fluidly connected to a connecting element 300, via which the device 100 is connected to a reservoir for a pharmaceutical fluid (both not shown in [reference]). Figure 1) is fluid-conducting. To connect the connecting element 300 fluid-conductingly to the proximal channel end 260, the connecting element 300 has a connecting element section 310 which is inserted into the proximal channel end 260. In the illustrated embodiment, the connecting element 300 is shaped as a nozzle, so that a reservoir for a pharmaceutical fluid can be fluid-conductingly connected to the device 100 by means of a hose 610 (only formed in sections).

[0086] A check valve 400 in the form of a ball check valve, comprising a ball 410 and a return element 420 in the form of four elastic, leaf-spring-shaped elements, is arranged in channel 250 (only three of the elements are shown; the fourth is located outside the plane of the drawing). The return element 420 exerts a force on the ball 410, causing it to close the check valve 400, allowing fluid to pass through. The check valve 400 is arranged such that a fluid coming from the direction of the proximal channel end 260 can displace the ball 410 against the force of the return element 420 toward the distal channel end 270, thus opening the check valve 400, allowing fluid to pass through. In the opposite direction, i.e. from the distal end of the canal 270 towards the proximal end of the canal 260, the check valve 400 remains fluid-conducting and cannot be opened without damage.

[0087] Distal to the check valve 400, a sealing element 500 comprising a fluid-conducting sealed gap 510 is arranged within the channel 250. In the illustrated embodiment of the device 100, the return element 420 and the sealing element 500 are designed as a single unit.

[0088] To protect the sealing element 500, and thus also the check valve 500, against unintentional discharge from the channel 250 during the application of a pharmaceutical fluid, a sleeve 360 ​​is arranged distal to the sealing element 500, which is fixed to the body 200 in the channel 250 via a spring-groove connection 365.

[0089] Proximal to the check valve 400, a filter element 350 in the form of a microporous filter plate is arranged in the channel 250 to clean a pharmaceutical fluid conveyed through the device 100 of microorganisms.

[0090] As a counterpart to the sleeve 260, the channel 250 has a channel constriction 255, so that the filter element 350, the check valve 400 and the sealing element 500 are fixed between sleeve 360 ​​and channel constriction 255.

[0091] Figure 2 The device shows 100 from Figure 1 in a perspective side view of a partial schematic longitudinal section. For the design and arrangement of the individual structural features, refer to the explanations regarding Figure 1 referred. In the Figure 2 From the perspective shown of the device 100, it can be seen that the connecting element section 310 and the proximal channel end 260 are designed in a polygonal, in particular hexagonal, shape, so that the connecting element section 310 can be inserted reversibly and in a rotationally secure manner into the proximal channel end 260.

[0092] The polygonal proximal channel end 260 has a greater axial extent than the polygonal connecting element section 310. This allows the proximal channel end 260 to be shortened, for example by sawing or cutting it off, and the connecting element section 310 to be fluid-conductingly connected to the remaining portion of the proximal channel end 260 after shortening. The device 100, thus shortened in its overall length, can therefore also be implanted in bone tissue that would have had insufficient thickness before shortening.

[0093] Figure 3 The device shows 100 from the Figure 1 and 2A pharmaceutical fluid 650 is introduced into the proximal end of the channel 260 via the tube 610. The pharmaceutical fluid 650 fills the channel 260 from the proximal end 260 to the ball 410. To convey the pharmaceutical fluid 650 further towards the distal end of the channel 270, a delivery pressure must be built up on the pharmaceutical fluid 650, which overcomes at least the force of the return element 420 acting on the ball 40 and thus opens the check valve 400 to allow fluid flow.

[0094] Figure 4 The device shows 100 from the Figures 1 to 3, wherein a sufficiently high delivery pressure 660 (symbolized by an arrow) is exerted on the pharmaceutical fluid 650 from the direction of the proximal channel end 260 to displace the ball 410 against the restoring force of the restoring element 420 towards the distal channel end 270. In doing so, the restoring element 420 is reversibly deformed and the check valve 400 is opened to allow fluid flow. Furthermore, the delivery pressure 660 is sufficiently high to also reversibly open the gap 510 of the sealing element 500 to allow fluid flow. This allows the pharmaceutical fluid 650 to be applied from the distal end of the channel 270. If the delivery pressure 660 is reduced so that the gap 510, the check valve 400 or the gap 510 and the check valve 400 reversibly close again in a fluid-conducting manner, the application of the pharmaceutical fluid 650 stops within a few moments, for example within one second or less.

[0095] Figure 5The device shows 100 from the Figures 1 to 4 The device 100 is fluidly connected to a reservoir 600 for a pharmaceutical fluid 650 in the form of a syringe. The device 100 is fluidly connected to the reservoir 600 via a hose 610 and an adapter 620 in the form of a Luer connection. By actuating the syringe, a delivery pressure 660 can be built up on the pharmaceutical fluid 650, and this fluid can then be applied by the device 100 to a desired location.

[0096] Figure 6Figure 1 shows a flowchart of a method for applying a pharmaceutical fluid 650 using the device 100, comprising steps 710 to 760. The device 100 comprises the hollow cylindrical body 200, which surrounds the channel 250 extending through the body 200 from the proximal end 210 to the distal end 220, wherein the outer surface of the body 200 has at least a portion of the external thread 230, the connecting element 300 arranged at the proximal end 210 being reversibly connectable via the proximal end 260 of the channel 250 to a reservoir 600 for the pharmaceutical fluid 650, wherein the check valve 400 arranged in the channel 250, which is designed to be fluid-impermeable towards the proximal end 260 of the channel 250, and the check valve 400 located distally in the channel 250 Sealing element 500 arranged for the non-return valve 400,which closes the distal end of the channel 270 of the channel 250 in a fluid-conducting manner and, when pressure 660 is applied to the pharmaceutical fluid 650 from the direction of the proximal end of the channel 260, the gap 510 can be reversibly opened in a fluid-conducting manner, so that the pharmaceutical fluid (650) can be applied from the distal end of the channel (270).

[0097] In step 710, the device 100 is implanted, in particular into bone tissue of a patient in close proximity to a joint, for example into a condyle of a corresponding bone.

[0098] In step 720, the device 100 is fluidly connected to a reservoir 600 for the pharmaceutical fluid 650. This can be done, for example, via a tube 610. The fluid-conducting connection 720 can take place before or after implantation in step 710, with after implantation being preferred.

[0099] In step 730, a delivery pressure 660 of at least 5 N / cm² is applied to the pharmaceutical fluid 650 from the direction of the proximal channel end 260. This delivery pressure 660 is sufficient to open the check valve 400 and the sealing element 500, in particular the gap 510 in the sealing element 500, allowing fluid to flow. If the delivery pressure 660 is less than 5 N / cm², at least the gap 510 in the sealing element 500 remains closed, and the pharmaceutical fluid 650 is not discharged from the device 100, in particular from the distal channel end 270 of the device 100. This limit value for the delivery pressure 660 ensures that there is no unintentional and uncontrolled application of the pharmaceutical fluid 650 from the device 100, which could have negative consequences for the patient.

[0100] In step 750, in conjunction with the fluid-conducting opening of the gap 510, the pharmaceutical fluid 650 is dispensed from it. The dispensing of the pharmaceutical fluid 650 continues as long as the delivery pressure 660 is above the limit value of 5 N / cm² or until the pharmaceutical fluid 650 has been completely dispensed.

[0101] In step 760, the delivery pressure 660 is reduced below the limit of 5 N / cm 2<, which causes at least the gap 510 to close again automatically in a fluid-conducting manner and the application of the pharmaceutical fluid 650 to be terminated.

[0102] The 700 procedure can be performed any number of times. Reference sign

[0103] 100 Device 200 Hollow cylindrical body 210 Proximal body end 220 Distal body end 230 External thread 250 Channel 255 Channel constriction 260 Proximal channel end 270 Distal channel end 300 Connecting element 310 Connecting element section 350 Filter element 360 Sleeve 365 Spring-and-groove connection 400 Check valve 410 Ball 420 Return element 500 Sealing element 510 Gap 600 Reservoir 610 Hose 620 Adapter 650 Pharmaceutical fluid 660 Pressurization 700 Method for applying a pharmaceutical fluid 710 Implanting 720 Fluid-conducting connection 730 Building up a delivery pressure 740 Fluid-conducting opening 750 Dispensing 760 fluid-conducting closure

Claims

1. A device (100) for applying a pharmaceutical fluid (650) into a joint capsule, comprising a hollow cylindrical body (200) which surrounds a channel (250) extending through the body (200) from a proximal body end (210) to a distal body end (220) of the body (200), an outer surface of the body (200) at least partially comprising an external thread (230), a connecting element (300) which is arranged at the proximal body end (210) and via which a proximal channel end (260) of the channel (250) can be reversibly connected to a reservoir (600) for the pharmaceutical fluid (650) in a fluid-conducting manner, and a check valve (400) which is arranged in the channel (250) and is designed to be fluid-impermeable in the direction of the proximal channel end (260), characterized by a sealing element (500) which is arranged distally from the check valve (400) in the channel (250), closes a distal channel end (270) of the channel (250) in a fluid-conducting manner and comprises a gap (510) which can be reversibly opened in a fluid-conducting manner when pressure (660) is applied to the pharmaceutical fluid (650) from the direction of the proximal channel end (260), so that the pharmaceutical fluid (650) can be applied from the distal channel end (270) and the check valve (400) being a ball check valve comprising a ball (410) and a return element (420).

2. The device (100) according to claim 1, wherein the gap (510), when subjected to a pressure (660) greater than 5 N / cm2, reversibly opens in a fluid-conducting manner.

3. The device (100) according to claim 1 or 2, wherein the return element (420) and the sealing element (500) are designed as a single unit.

4. The device (100) according to any of the preceding claims, wherein a filter element (350) is arranged in the channel (250).

5. The device (100) according to claim 4, wherein the filter element (350) is arranged in the channel (250) proximally to the check valve (400).

6. The device (100) according to claim 4 or 5, wherein the filter element (350) is a microporous filter plate.

7. The device (100) according to claim 6, wherein the microporous filter plate comprises pores with an average pore diameter of less than 40 µm.

8. The device (100) according to any of the preceding claims, wherein a hollow cylindrical sleeve (360) is arranged in the channel (250) distally from the sealing element (500) in order to prevent the sealing element (500) from being discharged from the distal channel end (270) when the pharmaceutical fluid (650) is applied.

9. The device (100) according to any of the preceding claims, wherein the proximal channel end (260) is polygonal and the connecting element (300) is equipped with a polygonal connecting element portion (310) in order to reversibly connect the connecting element (300) to the proximal channel end (210) in a fluid-conducting manner by inserting the connecting element portion (310) into the proximal channel end (260).

10. The device (100) according to claim 9, wherein the polygonal proximal channel end (260) has a greater axial extent than the polygonal connecting element portion (310), so that after removing part of the proximal channel end (260), in particular by sawing or cutting it off, the connecting element (300) can be connected in a fluid-conducting manner to a part of the proximal channel end (260) remaining on the device (100) by inserting the connecting element portion (310) into the remaining proximal channel end (260).

11. The device (100) according to any of the preceding claims, wherein the body (200) comprises a metal and / or a polymer.