Coating of hollow-fiber membranes in medical engineering iii

Abstract

The present invention relates to a method for coating a preferably porous and / or hydrophilic hollow-fiber membrane (1) with a coating material (B), the method comprising the steps of: providing the hollow-fiber membrane (1) that has a coating side to be coated and an oppositely facing secondary side; providing the coating material (B) and applying the coating material (B) to the coating side, or exclusively to the latter.

Description

[0001] Fresenius Medical Care Deutschland GmbH Description Coating of hollow fiber membranes in medical technology III The present invention relates to a method for coating a preferably porous and / or hydrophilic hollow fiber membrane with a coating material according to claim 1, a hollow fiber membrane according to claim 12, a dialyzer according to claim 13 and a device according to claim 14 or according to the respective preambles or generic terms of these claims. In ECLS (extracorporeal lung support), oxygen is supplied to the blood flowing extracorporeally in a gas exchange device depending on the blood flow rate (ECMO = extracorporeal membrane oxygenation) and / or CO2 is removed (ECCO2R = extracorporeal CO2 removal). The method represents an alternative and / or supplement to conventional mechanical ventilation that is advantageous for the patient in many respects.An object of the present invention is to provide a method for producing a hollow fiber membrane suitable for this treatment method. Furthermore, a membrane, in particular a hollow fiber membrane, a dialyzer and a device are to be specified. The object of the invention is achieved by means of the method for coating a preferably porous and / or hydrophilic hollow fiber membrane with a coating material having the features of claim 1, by means of the hollow fiber membrane with Fresenius Medical Care Deutschland GmbH the features of claim 12 and by means of the dialyzer with the features of claim 13. Furthermore, it is achieved by a device having the features of claim 14. According to the invention, a method for coating a preferably porous and / or hydrophilic hollow fiber membrane with a coating material is proposed.The method according to the invention comprises providing at least one hollow fiber membrane with a coating side to be coated and a secondary side opposite thereto, as well as providing the coating material. Furthermore, the method comprises applying the coating material to exactly one or at least one side of the hollow fiber membrane, namely the coating side, or only to this side, preferably not also to the secondary side. The coating material can be suitable and applied to reduce the passage of plasma through the pores of the hollow fiber membrane during later use of the hollow fiber membrane. When reference is made herein to a hollow fiber membrane, the statements made in this regard also apply in some embodiments to a plurality of hollow fiber membranes that mostly run parallel to one another, which, for example,bundled, for example in a common housing, for example the filter housing, as shown in section in Fig. 2B of US 10,583,458 B2. They can be coated simultaneously by means of the present invention. Fresenius Medical Care Deutschland GmbH If there are several hollow fibers, the coating side can correspond in each case to the side facing the inner lumen of the hollow fiber, the secondary side would be the outer surface of the hollow fibers, alternatively the entire space within the housing, which is formed or (co-)limited by the housing inner walls and the outer surfaces of the hollow fibers. In these embodiments, the volume adjacent to or surrounding the side of the hollow fiber membrane not to be coated, also called the secondary side, is preferably fluidically separated from an exterior of the housing or the dialyzer, e.g. by means of the housing.The housing can have fluid line connections as described herein, but can otherwise be fluidically separated. According to the invention, a hollow fiber membrane is proposed which has been coated by means of the method according to the invention. According to the invention, a dialyzer with a hollow fiber membrane according to the invention is proposed. In these or any other embodiments, the coating side can be the blood side. According to the invention, a device for coating a hollow fiber membrane is proposed, which is configured to carry out the method according to the invention. According to the invention, a control device is further proposed which is programmed as disclosed herein and which can be designed both as a control and a regulating device.Embodiments according to the invention can have some, some or all of the following features in any combination, provided that this is not recognizably technically impossible for a person skilled in the art. In all of the following statements, the use of the expression “can be” or “can have” etc. is to be understood as synonymous with “is preferably” or “preferably has” etc. and is intended to explain embodiments of the invention. Whenever numerical words are mentioned herein, a person skilled in the art will understand this as indicating a numerical lower limit. Unless this leads to a contradiction recognizable to a person skilled in the art, a person skilled in the art will therefore always read “at least one” or “at least one” when stating “a” or “an”. This understanding is also encompassed by the present invention, as is the interpretation that a numerical word such as “a” can alternatively be meant as “exactly one” wherever this is recognizably technically possible for a person skilled in the art.Both are encompassed by the present invention and apply to all numerical terms used herein. Whenever spatial information such as "top", "bottom", "left" or "right" is mentioned herein, the person skilled in the art will understand this to refer to the arrangement in the figures attached here and / or in the state of use. "Bottom" is closer to the center of the earth or the lower edge of the figure than "top". Fresenius Medical Care Deutschland GmbH Advantageous further developments of the present invention are each the subject of dependent claims and embodiments. Whenever an embodiment is mentioned herein, this represents an exemplary embodiment according to the invention, which is not to be understood as limiting.If it is disclosed herein that the subject matter according to the invention has one or more features in a specific embodiment, it is also disclosed herein that the subject matter according to the invention expressly does not have precisely this or these features in other, likewise inventive embodiments, e.g. in the sense of a disclaimer. For each embodiment mentioned herein, it therefore applies that the opposite embodiment, for example formulated as a negation, is also disclosed. If method steps are mentioned or disclosed herein, the device according to the invention is configured in some embodiments to carry out one, several or all of these method steps, in particular if these are automatically performable steps, in any combination, or corresponding devices, which are preferably based on the name of the respective method step (e.g.“Determining” as a method step and “device for determining” for the device, etc.) and which can also be part of the device(s) according to the invention or can be connected thereto in a signal connection, to be controlled accordingly. Fresenius Medical Care Deutschland GmbH When programmed or configured is mentioned herein, these terms can be interchangeable in some embodiments. The control device can initiate the execution of all or substantially all of the method steps. The method according to the invention can be carried out or initiated substantially or completely by the control device. It can be partially executed by the control device; in particular, those steps which do not require or involve human intervention and / or provision can be executed by the control device. The control device can serve as a pure control device or also as a regulating device.In some embodiments of the method according to the invention, the coating material is or comprises a bio- or blood-compatible plastic, preferably silicone. In some embodiments, the coating material is a mixture of a bio- or blood-compatible plastic, e.g. silicone, (preferably moisture-curing at room temperature) and a solvent or a solvent mixture, for example from the group of ethers or aliphatic hydrocarbons. In some embodiments, the coating material has a mixing ratio of 5 to 8:1 (solvent: bio- or blood-compatible plastic, e.g. silicone). Fresenius Medical Care Deutschland GmbH In some embodiments of the method, the at least one hollow fiber membrane is arranged in a housing, such as a filter housing. In some embodiments, the at least one hollow fiber membrane is arranged in the housing, or filter housing, of a dialyzer.In some embodiments, the method according to the invention further comprises a step in which the hollow fiber membrane is exposed to a vacuum and / or a negative pressure, wherein the vacuum and / or the negative pressure is generated by means of a vacuum source before and / or during the application of the coating material, or as a contributory factor or as the primary cause. This vacuum can be predetermined. It can be a negative pressure or a rough vacuum and can also be referred to as such. The vacuum is preferably between 200 hPa and 400 hPa, in particular it is 300 hPa. These values ​​are absolute or positive relative to 0 hPa (“true” vacuum). The pressure values ​​mentioned herein can refer to the first port for the dialysis fluid supply line, as further defined below.They are therefore optionally also present on the secondary side, since the hollow fiber membrane is permeable to air, which is why the same pressure is present on both sides of the hollow fiber membrane or in the entire housing surrounding the hollow fiber membrane or the internal volume of the housing. Fresenius Medical Care Deutschland GmbH When a vacuum is mentioned here, this can mean a negative pressure or a negative overpressure. The value mentioned for this can be an absolute pressure value, which relates to the zero pressure (vacuum) that prevails in the airless space of the universe, i.e. represents the difference to the ideal vacuum, alternatively a relative pressure, understood here as the difference between an absolute pressure and the respective (absolute) atmospheric pressure. In some embodiments, the hollow fiber membrane has a longitudinal direction with two ends opposite one another in the longitudinal direction, referred to herein as the first and second ends.the second end, wherein the coating material is brought into contact with the hollow fiber membrane at the first end for its application to the hollow fiber membrane in order to coat it. In some embodiments, the first end is or is placed further away from the vacuum source than the second end. In some embodiments of the method according to the invention, the housing has a plurality of connections and / or ports for supply or discharge lines. Although ports and connections can be identical in construction, for reasons of clarity, reference is made here to ports on the one hand and connections on the other. For example, the housing has a first connection for an incoming blood line, a second connection for an outgoing blood line, a first port for an incoming dialysis fluid supply line or incoming purge gas line, and a second port for an outgoing dialysate drain line or outgoing purge gas line.Fresenius Medical Care Deutschland GmbH connections therefore relate to the filling and emptying of the housing during use with blood after it has been connected to the corresponding lines, while ports relate to its filling and emptying with dialysis fluid or dialysate or purge gas. A purge gas, as used herein, can be a gas used for CO₂ elimination and oxygenation of the blood, for example 100% oxygen. Since the terms “dialysis fluid line” and “dialysate drain line” as used herein refer to the preferred design or use of a dialyzer, whenever at least one of these terms is used herein, this refers to an embodiment. Neither of these two terms is to be understood as limiting. What is disclosed herein in its context therefore also applies in some embodiments to an inlet line or a discharge line for purge gas.In some embodiments of the method, the housing is connected, in particular fluidically, to the vacuum source by means of one of its connections or ports, in particular by means of its first or second port. In some embodiments of the method, the housing is connected, in particular fluidically, to a source of the coating material by means of another of its connections or ports, in particular by means of its first or second connection. A line can be provided between the connections on the one hand and the vacuum source, the source of the coating material, a waste, a container, or the like, also referred to herein as the first or second line Fresenius Medical Care Deutschland GmbH. Such lines can also be provided between the ports on the one hand and the vacuum source or an opening to the environment. These connections to the sources, to the environment, etc.can preferably be or become opened or closed. Corresponding devices, which are in particular actuated automatically, for example effected by a control device as disclosed herein, can be provided and be part of the device according to the invention. The control device can be programmed accordingly. In some embodiments of the method according to the invention, the vacuum source has a nozzle. The latter can, for example, be provided between a pressure source, which can be part of the vacuum source, and the port of the housing connected to the vacuum source. The pressure source is described in more detail elsewhere. In some embodiments, the nozzle is a Venturi nozzle or a Laval nozzle or a similarly acting nozzle or has such a nozzle or a similarly acting nozzle.According to Wikipedia, a Venturi nozzle (also Venturi tube, developed by Giovanni Battista Venturi) usually consists of a smooth-walled piece of pipe with a constriction of the cross-section, for example by two cones facing each other, which preferably join at the point of their smallest diameter. A sampling tube is placed next to it at this point. When a fluid flows through a Venturi nozzle, the dynamic pressure (back pressure) is maximum and the hydrostatic pressure minimum at the narrowest point of the pipe. The velocity of the fluid increases in proportion to the cross-sections as it flows into the narrower part, because the same mass flows through the entire pipe per unit time (law of continuity). This causes the pressure in the sampling tube located in the narrower part to drop. This creates a differential pressure that can be used as a negative pressure or vacuum to suck in liquids or gases.In some embodiments, the nozzle is in fluid communication with the pressure source. In some embodiments, the pressure source is a source of a fluid, e.g., a gas or a liquid, prepared for dispensing the fluid under pressure. The fluid can, for example, be a compressed gas, in particular nitrogen or a mixture with nitrogen. In some embodiments, the method according to the invention further comprises a step in which, after the predetermined vacuum has been established, this or another vacuum is maintained for a predetermined period of time, optionally at least until the filter is completely filled with coating material, e.g., at least 20 seconds or at least 30 seconds. During this period, the coating material can flow into the hollow fiber membrane or into the housing, e.g., the filter housing, via a now opened fluid connection to the source, caused by the applied vacuum.In some embodiments, during this inflow or coating step, flow through the nozzle can be temporarily or permanently prevented and / or stopped. Fresenius Medical Care Deutschland GmbH However, since flow through the nozzle preferably continues during the inflow of the coating material, since according to the invention the housing does not have to be sealed from the environment during the inflow, which prevents vapors from escaping and satisfies safety requirements, the vacuum can also be "readjusted" by means of the nozzle until the end of the inflow process or maintained at the set value, which can prevent an otherwise observable drop in vacuum due to inflowing coating solution. This makes it possible to ensure constant process parameters for reproducible coating results.In some embodiments, the method according to the invention comprises a further step in which pressure is built up within the housing, for example either for a limited period of time or, with respect to this step, permanently. This can be done, for example, by means of the aforementioned or another pressure source or negative pressure source via one of the connections and / or ports, for example via the second connection for the outgoing blood line (connected, for example, to the second line), while one of the other connections and / or ports, for example the first connection for the incoming blood line (connected, for example, to the first line), is or becomes open. This allows excess coating material to be removed from the hollow fiber membrane and, for example, discarded. The pressure within the housing can be positive (overpressure) or negative (underpressure). In some embodiments, this step can be a blow-out.Fresenius Medical Care Deutschland GmbH In some embodiments, this step lasts, for example, two to six minutes, e.g., 4 minutes, at, for example, an overpressure of between 300 hPa and 600 hPa, preferably 500 hPa (0.5 bar). The overpressure describes the back pressure in front of the filter housing or the coated hollow fiber membrane. The purge gas can preferably be released from the filter housing with as little pressure as possible. In some embodiments, the method according to the invention comprises a further step in which pressure is built up within the housing. This takes place, for example, by means of the aforementioned or another pressure source via the connection opened in the previous step, wherein the connection which was connected to the pressure source in the previous step is now open, for example, to the atmosphere. This makes it possible to dry the coating material within the hollow fiber membrane.In some embodiments, this step lasts, e.g., ten to 15 minutes, e.g., 13 minutes, at, for example, an overpressure of between 300 hPa and 600 hPa, preferably 500 hPa (0.5 bar). The overpressure describes the dynamic pressure in front of the filter housing or the coated hollow-fiber membrane. The purge gas can preferably be released from the filter housing with as little pressure as possible. In some embodiments of the device according to the invention, it comprises a control device for controlling or regulating the method, e.g., as disclosed herein, in particular some or all of the steps described herein (in any combination), in particular those that do not require human intervention. In particular, the Fresenius Medical Care Deutschland GmbH control device can be configured for controlling or regulating the vacuum source, the generation of a negative or positive pressure, and the introduction of fluid, in particular a gas, in particular as described herein.It can be programmed to initiate the process automatically. If “automated” or “automatic” steps are mentioned here, this preferably includes the fact that a correspondingly programmed control device or a, for example, largely operator-free system can carry out those steps independently, i.e. without human intervention, without human intervention and / or without a human making a specific contribution to the implementation of the process. The initiation and thus ultimately implementation of these steps takes place through self-control and / or regulation of the control device or system, or is initiated thereby, i.e. for example without operator influence that would or could influence the process or a result thereof. An automatically initiated step can therefore be one that is triggered or initiated by the control device, in particular because it has been detected (e.g.based on sensor signals, based on reaching a program section, due to the occurrence of a predetermined point in time, because a previous step was completed, etc.) that the said step is now pending and its execution is therefore initiated or triggered by the control device. "Automated" or "automatic" is the opposite of "manual" in some embodiments, where "manual" is or includes the activation or initiation of steps by a human, e.g. by touching a switch, a touchscreen area or the like, the Fresenius Medical Care Deutschland GmbH execution of predetermined gestures, usually with their hands, their voice, a body movement, and / or by means of their presence, e.g. in front of a camera, in front of a motion sensor, etc. If at least one of the steps, for example the first step of a method, is initiated or triggered by a human.influenced, or if human intervention, for example an input, is necessary during the process, then the process can be referred to as a “semi-automatic” process, provided that the remaining process steps continue to run without human intervention, as explained above. In some embodiments, the dialyzer according to the invention is designed for use in dialysis, hemodialysis, hemofiltration or hemodiafiltration, in particular for acute or chronic renal replacement therapy or for continuous renal replacement therapy (CKRT). In some embodiments, no pump is used to pump the coating material or to circulate the coating material to introduce the coating material into or onto the hollow fiber membrane, i.e. the coating material is not pumped into the hollow fiber membrane for the purpose of coating.In certain embodiments, the vacuum contributes more to the introduction of the coating material into or onto the hollow fiber membrane than a pump, should a pump be used to pump the coating material, i.e. the Fresenius Medical Care Deutschland GmbH coating material is sucked into the hollow fiber membrane for the purpose of coating rather than pumped in. In some embodiments, the device does not have a piston or filter piston arranged in or on the hollow fiber membrane, e.g. downstream thereof, in particular no piston or filter piston connected to a vacuum source, especially not if it is arranged between the vacuum source and the hollow fiber membrane. In some embodiments, no pump is provided between the source of coating material and the hollow fiber membrane.Coating material moving out of the source and into the hollow fiber membrane is not pumped here or thereto in these embodiments. In some embodiments, the hollow fiber membrane is held vertically or perpendicularly for introducing the coating material into or onto it, e.g. by means of a device or holder of the apparatus. In some embodiments, the hollow fiber membrane consists of polysulfone, polyvinylpyrrolidone or a mixture thereof, or comprises at least one of these materials or the mixture, in particular before its coating. In some embodiments, the hollow fiber membrane is designed as in DE 10034 098 C2, the relevant disclosure of which is hereby incorporated by reference in its entirety. Fresenius Medical Care Deutschland GmbH Some or all embodiments of the invention can have one, several or all of the advantages mentioned above and / or below.In recent years, CO2 removal from the blood has increasingly come into focus, not least due to the COVID-19 pandemic and the ever-increasing prevalence of COPD. When using a hollow-fiber membrane coated according to the invention in an ultra-low-flow procedure, the blood flow can be, for example, less than 1000 ml / min or even less than 500 ml / min, but is not limited to this. This means that treatment can be "minimally invasive" compared to standard treatment (low-flow ECMO), as it can be performed using a smaller catheter for vascular access than in ECMO, such as the one used for dialysis (e.g., the Shaldon catheter (11-13.5 Fr).The field of application of the present invention can therefore be, in particular, the treatment of patients with chronic obstructive pulmonary disease (COPD), including those suffering from an acute exacerbation, i.e., a significant worsening of their disease. The present invention and its advantages can thus benefit a large number of patients. State-of-the-art gas exchangers can be used to treat these patients. Gas exchangers are typically produced in much smaller quantities than dialyzers. Their production therefore has only a low degree of automation. For this reason, gas exchangers are comparatively expensive to manufacture.One advantage of the present invention can therefore be that the coating process can be automated, i.e. in particular without human intervention. This can help save time and costs. A further advantage can be that a large number of coated dialyzers according to the invention can be produced, since several modules can be coated simultaneously using the present invention. Since this can accelerate the production of dialyzers suitable for gas exchange, this can also help save time and costs. While the vacuum is being built up on the coating side of the hollow fiber membrane, the air located there is displaced via the membrane towards the secondary side.If outflow from the secondary side out of the housing were prevented, defects could occur in the coating of the hollow fiber membrane, which could be dangerous for a patient during subsequent treatment using the coated hollow fiber membrane. With the present invention, this can be advantageously prevented or at least reduced. This can contribute to increased patient safety. A further advantage of the present invention can be that solvent from the coating material, which filters over the hollow fiber membrane towards the secondary side during coating of the coating side and evaporates there or already beforehand, can escape from the housing. This avoids solvent residues that would otherwise remain in the dialyzer or filter housing.This can also contribute to increasing patient safety and optimizing the quality of the Fresenius Medical Care Deutschland GmbH coating. Using a Laval or Venturi nozzle to generate a vacuum allows gases, especially flammable ones, to be extracted directly. This advantageously allows applicable explosion protection regulations to be met with little effort. The advantages of using a vacuum for coating are that the coating process is quick and clean, and in some embodiments, less coating solution is required. Furthermore, the design of the device used as a coating device can be comparatively simpler. Furthermore, the pressure conditions can be better reproduced, and the coating can therefore be applied more evenly.In order to comply with applicable safety regulations during the manufacture of the coated dialyzer, the resulting solvent vapors must be able to escape passively or be actively extracted. Since the interior of the housing never needs to be completely sealed with the inventive solution, these safety regulations can be easily complied with. The use of a nozzle, e.g., a Laval nozzle, is therefore advantageous for the invention. It allows the creation of a vacuum, for which, however, the housing or the interior of the housing does not have to be completely sealed. By means of the present invention, coating using a constant or otherwise adjusted vacuum can ensure that the pressure of the coating solution on the membrane remains stable throughout the entire process. This can represent a further advantage for Fresenius Medical Care Deutschland GmbH.In this case, the vacuum can advantageously be maintained in a simple manner. All advantages achievable with the methods according to the invention can also be achieved without impairment with the devices according to the invention in certain embodiments of the invention, and vice versa. The present invention is described below purely by way of example with reference to the attached figures. In them, identical reference numerals designate identical or similar components. The following applies: Fig. 1 shows the sequence of an inventive method for coating a preferably porous and / or hydrophilic hollow fiber membrane with a coating material in an exemplary embodiment; Fig. 2 shows an exemplary hollow membrane which can be coated by carrying out the inventive method and using a device according to the invention; Fig.3 shows an exemplary arrangement for carrying out the method according to the invention in one embodiment using a device according to the invention in an exemplary embodiment during a method step; Fresenius Medical Care Deutschland GmbH Fig. 4 shows the exemplary arrangement of Fig. 3 during a further method step; Fig. 5 shows the exemplary arrangement of Fig. 3 during a further method step; Fig. 6 shows the exemplary arrangement of Fig. 3 during a further method step; and Figs. 7a to 7f show various embodiments of the method according to the invention, which differ in particular in their flow directions during the various method steps. Fig. 1 shows the sequence of the method according to the invention for coating a preferably porous and / or hydrophilic hollow fiber membrane 1 with a coating material B in an exemplary embodiment.Reference is made here to the reference numerals of the device 100 and components in the following figures. Method step M1 represents providing the hollow fiber membrane 1. The hollow fiber membrane 1 can be arranged in a housing, such as a filter housing 50, for example of a dialyzer, for example as shown in the following figures by Fresenius Medical Care Deutschland GmbH. The housing has a plurality of connections and / or ports for discharge or supply lines, in the example of the following figures, a first connection 51 for an incoming blood line, a second connection 53 for an outgoing blood line, a first port 55 for an incoming dialysis fluid supply line, and a second port 57 for an outgoing dialysate drain line. Method step M1 further represents providing the coating material B.The coating material B can be or comprise a solution, preferably a silicone solution. The application of the coating material B to exactly one or at least one side of the hollow fiber membrane 1, which serves as the coating side, and the preparation and post-processing for this are represented in the following method steps M2 to M5. It should be noted that the terms "side" and "end" of the hollow fiber membrane 1 have different meanings here, as explained herein, and are therefore not equivalent. The volume adjacent to the secondary side of the hollow fiber membrane 1 that is not to be coated is preferably separated from the exterior of a housing, e.g., the filter housing 50, or a dialyzer. In the optional method step M2, which can also be referred to as the "evacuation step," a vacuum or a predetermined negative pressure is applied to one of the ports (55 or 57), and thus in the housing, e.g.,the Fresenius Medical Care Deutschland GmbH filter housing 50, a negative pressure is generated. This process step M2 is described in more detail in Fig. 3. In process step M3, which can also be referred to as the “coating step” or “coating,” coating material B is sucked into the filter housing 50 from a source 200 for the coating material B due to the vacuum or negative pressure in the filter housing 50, and the coating side of the hollow fiber membrane 1 is thus coated. This process step M3 is described in more detail in Fig. 4. In the optional process step M4, which can also be referred to as the “removal step” or “blowing out,” excess coating material B is expelled from the hollow fiber membrane 1 by building up pressure or overpressure in the filter housing 50, and can be discarded or collected for reuse. This process step M4 is described in more detail in Fig. 5.In the optional process step M5, which can also be referred to as the "drying step" or "drying", the coating material B is dried by flowing gas, e.g. air, under excess pressure through the filter housing 50 and the hollow fiber membrane 1 arranged therein. This process step M5 is described in more detail in Fig. 6. The advantage here is that the applicable safety regulations, which must be met during the manufacture of the coated dialyzer, can be met simply by the fact that the interior of the housing never has to be completely closed off if this is not desired. The use of a nozzle, e.g. a Laval nozzle, as explained below, allows a vacuum to be created inside the housing without having to close it completely. Fig.2 shows an exemplary arrangement for carrying out the method according to the invention in one embodiment using a device 100 according to the invention, which is only partially shown here. At least one, preferably porous and / or hydrophilic, hollow-fiber membrane 1 is arranged in a housing 50, in this case a filter housing. It has a longitudinal direction L with two ends 10, 20 opposite one another in the longitudinal direction L. The hollow-fiber membrane 1 is optionally fluidically connected at its first end 10 to a first line 80 and at its second end 20 to a second line 90. The first line 80, or the first end 10, is fluidically connected to a source 200 for a coating material B, which can be or comprise silicone or a silicone solution. The hollow-fiber membrane 1 has a coating side 30 and a secondary side 40.By means of the present invention, the coating material B finds its way along the coating side 30 and through the filter housing 50 towards the second end 20, remaining fully or partially adhered as a coating to the coating side 30 of the hollow fiber membrane 1. This path is indicated by black arrows. Reference is made to the explanations for the following figures at Fresenius Medical Care Deutschland GmbH. In the example of Fig. 2, the housing 50 further comprises a first connection 51, a second connection 53, a first port 55, and a second port 57, through which gas, in particular solvent-enriched or saturated air, e.g., can flow out or be discharged passively or actively into the atmosphere. This is illustrated in Fig. 2 by small black circles. See also the explanations regarding overpressure in Fig. 5 and Fig. 6.In a very simplified schematic, a control device 101 for carrying out the method and / or for controlling and / or regulating the device 100 is shown above it. This can be or include controlling or regulating the generation of the vacuum, the introduction of the coating material B, the supply or discharge of gas, or controlling and / or regulating a nozzle 105 (not shown here, see the following figures), in particular as described herein. Optionally, pressure measuring sensors or other measuring means can be provided which can measure and transmit prevailing pressures, e.g. in the housing, in the lines, at the ports or connections, or components fluidically connected thereto. They can be used as pressure monitors. In the event of "incorrect" pressures, e.g. too high or too low, each compared by means of the control device 101 with e.g.a threshold or limit value, the control device 101 can abort the method or individual steps thereof or prevent them from starting at all. Fresenius Medical Care Deutschland GmbH Fig. 3 shows an exemplary arrangement for carrying out the method according to the invention in one embodiment using a device 100 according to the invention in a first exemplary embodiment during the optional method step M2, the evacuation step, which here is optionally carried out before the method step M3. A joint implementation of the activities from M2 and M3 is also encompassed by the present invention. At least one, preferably porous and / or hydrophilic, hollow fiber membrane 1 is arranged in a filter housing 50. It has a longitudinal direction L with two ends 10, 20 opposite one another in the longitudinal direction L.The hollow fiber membrane 1 is already fluidically connected to a source 200 for coating material B during process step M2, or only later, at its first end 10, or by means of this, or at another location, here exemplarily via the first connection 51 and the first line 80. The lines 80 and 90 each have a clamp 85, 95, which are closed. At the start of the coating process, the clamp 85 in or on the line 80 is opened. The hollow fiber membrane 1 is optionally fluidically connected to a second line 90 via the second connection 53. The connections 51 and 53 are preferably fluidically connected to one another, e.g., via the lumen of the hollow fiber membrane 1 formed on the coating side.By means of the vacuum source 103 (which can be a negative pressure source), a vacuum (alternatively: a negative pressure) is applied to one of the ports (here, port 55). The other port (here, port 57) is closed, in the example in Fig. 3, by means of a closure cap. Ports 55 and port 57 can be fluidically connected to one another, e.g., via the interior of the housing to which the secondary side is adjacent. Since the first line 80 and the second line 90 are also closed by means of hose clamps, a negative pressure is generated in the housing, here the filter housing 50, which, for example, is in the range between 200 hPa and 400 hPa (absolute values). Alternatively or in addition to the closable lines 80, 90 or their blocking, plugs, closure caps or the like can be provided in order to close the first and second connections 51 and 53, respectively, from the atmosphere.Further alternatively, the lines 80, 90, connections 51, 53 and / or ports 55, 57 can be closed and / or opened by controllable valves or the like. A corresponding control device can be provided, for example that designated by reference numeral 101 in Fig. 2 or Fig. 3. These embodiments are each likewise encompassed by the present invention. The vacuum source 103 can have a Laval or Venturi nozzle 105 for generating the vacuum. The Laval or Venturi nozzle 105 optionally has a silencer 111 or is connected thereto. In a very simplified schematic, the control device 101 for carrying out the method and / or for controlling and / or regulating the device 100 is arranged next to the latter. It can control or regulate the vacuum source, the generation of a negative or positive pressure, and the introduction of fluid, Fresenius Medical Care Deutschland GmbH in particular a gas, in particular as described herein.Fig. 4 shows the exemplary arrangement for carrying out the method according to the invention of Fig. 3 during method step M3, the coating step. Reference is made to the explanations for the preceding figures. The coating material B flows into the filter housing 50 through the first line 80 by means of the applied negative pressure (see Fig. 3), which is represented in Fig. 4 by a block arrow and the level of the coating material B in the source 200 for the coating material B, which has decreased compared to Fig. 3. If the vacuum is generated by means of a Laval or Venturi nozzle 105, as shown by way of example in Fig. 4, there is preferably a fluidic connection to the environment during the inflow of the coating material B, whereby solvent vapors that may be released during coating can flow out passively, i.e. outside the housing or the hollow fiber membrane 1, or can be actively sucked away.Since all usable solvents are flammable, it is advantageously possible by means of the present invention to comply with applicable explosion protection regulations, for example, with little effort, which is particularly useful in industrial production. The coating material B can alternatively flow in via the second line 90 and the second connection 53 (see Fig. 7c and Fig. 7d), or further alternatively via both Fresenius Medical Care Deutschland GmbH lines 80, 90 and both connections 51, 53 (see Fig. 7e and Fig. 7f). Both are also encompassed by the present invention. During the inflow of the coating material B, a vacuum preferably remains applied on the secondary side. The hollow fiber membrane 1 filled with coating material B is, for example, vacuumed from the secondary side for some time T1, preferably an additional 30 seconds to five minutes (in the example of Fig.4 via the first port 55) and then ventilated by switching off the Laval or Venturi nozzle 105. Fig. 5 shows the exemplary arrangement for carrying out the method according to the invention of Fig. 3 during the optional method step M4, the removal step or during blowing out. Reference is made to the explanations for the preceding figures. In the example of Fig. 5, the removal of the excess coating material B from the hollow fiber membrane 1 takes place with the aid of a pressurized fluid or gas, herein, if a gas, also referred to as compressed gas. The removal takes place here, for example, via the second line 90, i.e. via the second connection 53 in the direction of the first connection 51. In other embodiments, the removal of the excess coating material B from the hollow fiber membrane 1 can take place in the opposite direction, i.e. from connection 51 in the direction of the second connection 53 (see Fig. 7a, Fig. 7d and Fig. 7e).This is also encompassed by the present invention. Fresenius Medical Care Deutschland GmbH Preferably, and also for safety reasons, a non-flammable fluid such as gaseous nitrogen is used, although other liquids or gases, e.g. room air, are also suitable. The pressure is preferably in a range between (preferably above) 0 hPa (0 bar) and 1000 hPa (1 bar). During this process, the ports 55 and 57 of the secondary side of the hollow fiber membrane 1 are closed. In the example in Fig. 5, this is done by means of closure caps. The means listed above for closing the connections 51 or 53 can also be used analogously for closing the ports 55 or 57. This is also encompassed by the present invention, as are other closure means. Method step M4 preferably lasts 30 seconds to five minutes (T2).Any excess pressure that may arise on the secondary side can preferably be reduced simultaneously with switching off the pressure source 107 for inflowing compressed gas to remove the coating solution via the secondary side, i.e. one of the or both ports 55 or 57 (not shown in Fig. 5). The corresponding port can then be closed again. Fig. 6 shows the exemplary arrangement for carrying out the method according to the invention of Fig. 3 during the optional method step M5, the drying step. Reference is made to the explanations for the preceding figures. Fresenius Medical Care Deutschland GmbH After the excess coating material B has been removed, the coated hollow fiber membrane 1 is dried. The drying of the hollow fiber membrane 1 takes place in the example of Fig.6, again optionally with the aid of pressurized gas via the first line 80 from the first connection 51 in the direction of the second connection 53. In other embodiments, the drying of the coating material B within the hollow fiber membrane 1 can take place in the opposite direction, i.e. from the second connection 53 in the direction of the first connection 51 (see Fig. 7a, Fig. 7d and Fig. 7e). This is also encompassed by the present invention. Preferably, also for safety reasons, a non-flammable fluid or gas such as nitrogen is also used in this method step M5. The pressure is preferably in a range between 0 hPa (0 bar), or above this, and 1000 hPa (1 bar). During this process, the ports 55 and 57 of the secondary side of the hollow fiber membrane 1 are closed, in the example in Fig. 6 optionally by means of closure caps.Reference is made to the explanations regarding closure means herein to avoid repetition. Process step M5 preferably lasts five to 50 minutes (T3). In this process step M5, an overpressure can also arise on the secondary side, which can preferably be reduced analogously to the procedure in process step M4. Fresenius Medical Care Deutschland GmbH Fig. 7a to Fig. 7f show various embodiments of the process according to the invention, which differ in particular in their flow directions within the various process steps. The flow directions are indicated by block arrows and designated by the respectively associated process steps M3 (coating step, coating), M4 (removal step; blowing out) or M5 (drying step; drying). Reference is made to the reference numerals and embodiments of the preceding figures. Fig. 7a to Fig.7f each show an arrangement analogous to the preceding figures. A hollow fiber membrane 1 is arranged in a housing 50. The first connection 51 with the first line 80 and the second connection 53 with the second line 90 can be seen. These reference numerals have only been used in Fig. 7a for reasons of clarity. The ports, the vacuum source and the associated lines have also been omitted from Figs. 7a to 7f for this reason. Fig. 7a shows that the method step M3, coating, in this embodiment takes place through the first line 80 via the first connection 51 into the hollow fiber membrane 1. The method step M4, blowing out of the hollow fiber membrane 1, takes place via the second connection 53 and through the second line 90, for example in the direction of a waste container (not shown in Fig. 7a).Fresenius Medical Care Deutschland GmbH Process step M5, drying, is then carried out again by means of a flow in the direction of the first connection 51 and via the first line 80 out of the housing, for example into the environment. Fig. 7b shows the arrangement of Fig. 3 to Fig. 6, i.e. process step M3, coating, is carried out through the first line 80 via the first connection 51 into the hollow fiber membrane 1 (see Fig. 4). Process step M4, blowing out, is carried out from the hollow fiber membrane 1, also via the first connection 51 and through the first line 80, for example in the direction of a waste container (see Fig. 5). Process step M5, drying, is carried out by means of a flow in the direction of the second connection 53 and via the second line 90 out of the housing into the environment (see Fig. 6).7c shows that during process step M3, coating, coating material B is introduced into the hollow fiber membrane 1 by means of the second line 90 via the second connection 53. In such an embodiment, gravity can also be used advantageously in addition to the vacuum. Process step M4, blowing out, takes place out of the hollow fiber membrane 1 via the first connection 51 and through the first line 80, for example in the direction of a waste container. Fresenius Medical Care Deutschland GmbH Process step M5, drying, then takes place again by means of a flow in the direction of the second connection 53 and via the second line 90, for example out into the environment. Fig. 7d shows that process step M3, coating, can take place through the second line 90 via the second connection 53 into the hollow fiber membrane 1.In such an embodiment, in addition to the vacuum, gravity also advantageously assists in the introduction of the coating material B. The process step M4, blowing out, takes place by means of a flow out of the hollow fiber membrane 1, also via the second connection 53 and through the second line 90, for example in the direction of a waste container. The process step M5, drying, takes place by means of a flow in the direction of the first connection 51, via the first line 80, for example into the environment. Fig. 7e shows that the process step M3, coating, can take place both through the first line 80 via the first connection 51 and through the second line 90 via the second connection 53 into the hollow fiber membrane 1.Process step M4, blowing out, takes place from the hollow fiber membrane 1 via the second connection 53 and through the second line 90, for example, in the direction of a waste container. Fresenius Medical Care Deutschland GmbH. Process step M5, drying, then takes place again in the direction of the second connection 53 and via the second line 90. Fig. 7f shows that process step M3, coating, can take place both through the first line 80 via the first connection 51 and through the second line 90 via the second connection 53 into the hollow fiber membrane 1. Process step M4, blowing out, takes place from the hollow fiber membrane 1 via the first connection 51 and through the first line 80, for example, in the direction of a waste container. Process step M5, drying, takes place in the direction of the second connection 53 and via the second line 90.

[0002] Fresenius Medical Care Deutschland GmbH List of reference symbols 1 Hollow fiber membrane 10 First end 20 Second end 30 Coating side 40 Secondary side 50 Filter housing 51 First connection for an incoming blood line or first line 53 Second connection for an outgoing blood line or second line 55 First port for an incoming dialysis fluid inlet line 57 Second port for an outgoing dialysate outlet line 80 First line, assigned to the first end or the first connection 85 First hose clamp on the first line 90 Second line, assigned to the second end or the second connection 95 Second hose clamp on the second line 100 Device 101 Control device 103 Vacuum source 105 Laval nozzle, Venturi nozzle 107 Pressure source for fluid under pressure, e.g.Compressed gas 109 Waste 111 Silencer Fresenius Medical Care Deutschland GmbH 200 Source of coating material B Coating material L Longitudinal direction M1 to M5 Process steps p1, p2 Gas pressure, vacuum or negative pressure T1, T2, T3 Time periods.

Claims

Fresenius Medical Care Deutschland GmbH Claims 1. A method for coating a preferably porous and / or hydrophilic hollow fiber membrane (1) with a coating material (B), comprising the steps (M1): - providing the hollow fiber membrane (1) with a coating side to be coated and a secondary side opposite thereto; - providing the coating material (B); and - applying the coating material (B) to the coating side of the hollow fiber membrane (1) or only to this. Wherein the coating material (B) is or comprises a solution, preferably a silicone solution, and where the hollow fiber membrane (1) is arranged in a housing, such as a filter housing (50), and where the method further comprises the step (M2): - exposing the hollow fiber membrane (1) to a vacuum and / or a negative pressure generated by a vacuum source (103) before and / or during the application of the coating material (B) and / or in addition thereto. 2.Method according to claim 1, wherein the housing has a plurality of connections and / or ports for supply or discharge lines, for example a first connection (51) for a supplying blood line, a second connection (53) for a draining blood line. Fresenius Medical Care Deutschland GmbH a first port (55) for a supply dialysis fluid supply line or a supply purge gas line and a second port (57) for a discharge dialysate drain line or a discharge purge gas line.

3. Method according to claim 2, wherein the housing is connected to the vacuum source (103) by means of one of its connections or ports, in particular by means of its first or second port (55, 57), and is connected to a source (200) for the coating material (B) by means of another of its connections or ports, in particular by means of its first or second connection (51, 53).

4. Method according to claim 3, wherein the vacuum source (103) has a nozzle.

5. Method according to claim 4, wherein the nozzle is or has a Venturi nozzle (105) or a Laval nozzle.

6. Method according to claim 5, wherein the nozzle is connected to a pressure source (107) for a fluid under pressure, e.g.Compressed gas, in particular nitrogen or a mixture with nitrogen, is in fluid communication.

7. Method according to one of the preceding claims, wherein in a step (M3), after the predetermined vacuum has been established, a vacuum is maintained for a predetermined period of time (T1), in particular at least 20 s or at least 30 s, during which a fluid connection to the source (200) for the coating material (B) is opened, so that coating material (B) can enter the hollow fiber membrane (1). Fresenius Medical Care Deutschland GmbH or into the housing, for example the filter housing (50).

8. The method according to claim 7, wherein during step (M3), temporarily or permanently, flow through the nozzle is or is prevented and / or terminated.

9. The method according to any one of claims 2 to 8, wherein in a step (M4) pressure is built up within the housing, e.g. by means of the pressure source (107), via one of the connections and / or ports, for example via the second connection (53) for the outgoing blood line, while one of the other connections and / or ports, for example the first connection (51) for the incoming blood line, is or is opened.

10. The method according to claim 9, wherein in a step (M5) pressure is built up within the housing, e.g. B. by means of the pressure source (107), via the first connection (51) opened in step (M4) with the second connection (53) now open, which was connected to the pressure source (107) in step (M4).

11. The method according to any one of the preceding claims, wherein the vacuum and / or the negative pressure is preferably between 200 hPa and 400 hPa, in particular 300 hPa.

12. A hollow-fiber membrane (1) coated by the method according to any one of the preceding claims.

13. A dialyzer comprising a hollow-fiber membrane (1) according to claim 12. Fresenius Medical Care Deutschland GmbH 14. Device (100) for coating a hollow fiber membrane (1), configured to carry out the method according to one of claims 1 to 11.

15. Device (100) according to claim 14, comprising a control device (101) for controlling or regulating the method, in particular any or all of the steps M2 to M5, individually or in any combination.

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