METHOD FOR CONNECTING TWO SILICON HOSE SECTIONS AND PHARMACEUTICAL MEDIUM TRANSFER METHOD WITH SUCH A CONNECTION METHOD AND DEVICE FOR PERFORMING THE METHOD

Description

[0001] The present patent application claims priority from German patent application DE 10 2022 200 748.4, the contents of which are incorporated herein by reference.

[0002] The invention relates to a method for connecting two silicone tube sections. Furthermore, the invention relates to a pharmaceutical media transfer method for supplying a pharmaceutical medium from a source reservoir to a target reservoir using the connection method, a device for carrying out such a method, and the use of a liquid, UV-curing silicone material as an overmolding material in one of the aforementioned methods.

[0003] The connection of hose sections in connection with pharmaceutical or biomedical media transfer processes is known in the prior art in connection with hose materials made of thermoplastic elastomers. Such processes are known from EP 2 637 839 B1, EP 1 056 970 B1 and WO 2021 / 118780 A1, as well as from EP 3 060 292 B1 and EP 3 603 735 A1. EP 2 999 513 B1 discloses a device for a method for producing a sterile connection of hoses. US 2009 / 0 243 284 A1 discloses a fluid transfer assembly and the methods used therefor.One method comprises the steps of: positioning the facing end faces of the silicone hose sections to be connected in an overmolding mold such that the facing end faces are adjacent, and overmolding the adjacent end faces in the overmolding mold by filling an overmolding cavity of the mold with flowable silicone. DE 10 2019 202 513 A1 discloses a device for forming or overmolding plastic elements onto the surfaces of a semi-finished product.

[0004] Furthermore, US patent 2021 / 0 199 226 A1 discloses a method for providing a multi-lumen article, comprising: providing a first profile comprising at least one lumen, wherein the first end and a first lumen are present; providing a second profile comprising a second end and a second lumen, wherein at least the first profile, the second profile, or a combination thereof comprises a polymeric material; providing a surface activation treatment; treating at least the first end, the second end, or a combination thereof with the surface activation treatment;and direct contacting of the second end of the second profile with the first end of the first profile to join the first end and the second end at an interface of first end and second end and to provide a fluid conduit, wherein the first lumen has a fluid flow in a first path and the second lumen has a fluid flow in a path different from the first path.

[0005] US Patent 2016 / 0 200 038 A1 discloses a method for manufacturing a fluid management arrangement, comprising: coupling a first and a second silicone tubing section to a connector made of plastic material, which has at least one inlet and at least one outlet and an intermediate lumen, wherein the at least one inlet is connected to the first silicone tubing section at a first transition and the at least one outlet is connected to the second silicone tubing section at a second transition; inserting the connector into a cavity of a mold; injecting liquid silicone rubber into the mold cavity; and applying UV radiation to the liquid silicone rubber to cure the silicone.

[0006] It is an object of the present invention to further develop a method for connecting two silicone hose sections in such a way that it can be carried out safely, reproducibly and automatically with reasonable effort.

[0007] This problem is solved according to the invention by a connection method with the features specified in claim 1.

[0008] According to the invention, it has been found that overmolding adjacent contact surface areas of the silicone tubing sections to be connected with flowable silicone, which is subsequently cured, enables a reliable connection solution. Provided that appropriately sterilized silicone tubing sections are connected, a biocompatible and safe fluid connection is achieved between the connected silicone tubing sections.

[0009] The flowable silicone may be Liquid Silicone Rubber (LSR). It may be an LSR material type with a hardness between Shore A20 and Shore A70.

[0010] The silicone has sufficient flow properties to adequately fill the overmolding cavity. The viscosity of the flowable silicone can be adapted to a typical cavity size or shape.

[0011] A silicone hose section within the meaning of the present application is a hose section made of a material consisting predominantly of silicone. The adjacent contact surface areas of the silicone hose sections need not be in contact with each other over the entire circumference of the hose. However, this is preferred.

[0012] The curing of the flowable silicone is achieved through UV light irradiation, specifically in the UV-A wavelength range between 315 nm and 400 nm, particularly between 315 nm and 380 nm. Curing of the flowable silicone can also be achieved by irradiation with a different UV wavelength in the range between 100 nm and 315 nm, especially between 280 nm and 315 nm (UV-B). A broadband UV light source can be used, from which the specific UV wavelength range used can then be filtered out.

[0013] Another object of the invention is to improve the operational and handling safety of a pharmaceutical media transfer process for supplying a pharmaceutical medium from a source reservoir to a target reservoir.

[0014] This problem is solved according to the invention by a media transfer process with the features specified in claim 2. The advantages of the connection process according to the invention are particularly evident when used in a pharmaceutical media transfer process. Such a media transfer can take place throughout the entire production chain of a pharmaceutical manufacturing process, for example, during the manufacturing process from a batch preparation to a final filling process. The media transfer process can be used in pharmaceutical development steps from laboratory development through scale-up intermediate steps to mass production. An example of the pharmaceutical media transfer process is a pharmaceutical filling process, in particular the addition of a buffer solution for pH regulation in the target reservoir.A sterile container, a process reactor, or even a bag can be used as the target reservoir.

[0015] The pharmaceutical media transfer process also includes a sterilization step for the prong-side areas of the tubing sections produced during cutting. This sterilization of the prong-side areas is achieved using UV light irradiation. A UV-C wavelength in the range of 100 nm to 280 nm, particularly between 100 nm and 200 nm or between 200 nm and 280 nm, can be used.

[0016] A cutting method according to claim 3 has proven to be particularly suitable. The cutting can be carried out purely mechanically as a cold cut, i.e., without the effect of temperature. The cutting temperature can be less than 70°C, less than 60°C, less than 50°C, less than 40°C, and even less than 30°C. The cutting temperature is regularly greater than 10°C.

[0017] The advantages of a device according to claim 4 correspond to those already explained above with regard to the methods. A positioning device already known for positioning in connection with connecting TPE hose components can be used.

[0018] A mobile version according to claim 7 is particularly suitable for laboratory or clinical use. This mobile version can also be advantageously used in cleanroom or pre-production environments. The connection device can be designed to be mobile. The device performing the connection process can, in particular, be mobile. For this purpose, the device can have several casters mounted on a frame. In the mobile version, the device can also have a drive system, for example, via at least one electric motor. The connection device can have an independent power supply, i.e., it can be designed so that it does not rely on external power connections. The connection device can be designed for battery operation.

[0019] The connecting device can include a set of cutting units, for example, knives. The connecting device can include a set of interchangeable overmolding molds. The connecting device can include a reading unit for specifying a knife within the knife set and / or for specifying an overmolding mold within the overmolding mold set. This specification can be tailored to the hose sections to be connected. For the corresponding specification, the hoses for the hose sections to be connected can contain specification data, which can be encoded, for example, in the form of a QR code. The reading unit can then be designed as a QR code reader.

[0020] Using a connected silicone hose offers the advantages already discussed above. In particular, it can result in a robust and tear-resistant connection that simultaneously ensures reliable media or fluid flow.

[0021] The use of a UV-curing silicone material according to claim 10 has proven to be particularly suitable for the connection process.

[0022] The flowable silicone material can be a 1K or a 2K material.

[0023] A hardness range of the silicone material according to claim 11 has proven to be particularly suitable for producing a secure and at the same time stable connection.

[0024] Different UV wavelengths for curing on the one hand and sterilization on the other, according to claims 1, 4, and 10, have proven particularly suitable for process reliability and process speed. The UV curing wavelength can be a UV-A wavelength. The UV sterilization wavelength can be a UV-C wavelength.

[0025] Exemplary embodiments of the invention are explained in more detail below with reference to the drawing.

[0026] The only Figure 1 shows a flowchart of a process for connecting two silicone hose sections and a device for carrying out the process.

[0027] A method for connecting two silicone tube sections 1, 2 is used in a pharmaceutical media transfer process, particularly in a pharmaceutical drainage process, for supplying a pharmaceutical medium from a source reservoir 3 to a target reservoir 4. In principle, the connection method can also be used in other pharmaceutical, biological, medical technology, or other scientific or industrial processes.

[0028] The silicone hose sections 1 and 2 are hose sections made of a material that consists predominantly, i.e., more than 50% by weight, of silicone. This silicone material of the silicone hose sections 1 and 2 can also consist of more than 60%, 70%, 75%, 80%, 85%, 90%, 95%, or even 98% by weight of silicone.

[0029] The output reservoir 3 is connected to the silicone hose section 1 and the target reservoir 4 is connected to the silicone hose section 2, for example in fluid connection, especially for guiding a liquid medium.

[0030] The pharmaceutical filling process proceeds as follows: First, a pharmaceutical medium 5 is supplied to the output reservoir 3, including a silicone feed tube 6 connected to the output reservoir 3. Silicone tube section 1 is part of the silicone feed tube 6. Next, the target reservoir 4 is supplied, including a silicone discharge tube 7 connected to it. Silicone tube section 2 is part of the silicone discharge tube 7.

[0031] The pharmaceutical medium 5 is now displaced in a silicone feed tube section of the silicone feed tube 6, particularly towards the outlet reservoir 3, which in the Figure 1 The upper left indicates where the pharmaceutical medium 5 is displaced from a right half of the depicted section of the silicone supply tube 6 by means of a displacement mechanism 8. Figure 1The top left corner shows displacement step 9 of the filling process.

[0032] In a cutting step 10 (see Fig. 1 In the filling process (left center), the silicone feed tube section of the silicone feed tube 6 is then cut with a cutting unit 11 to create a sterile end face area 1a of the silicone feed tube section. In the same way, in a further cutting step 12, which is also in the Figure 1 The left center illustration shows a section of silicone drainage tube 7 being cut with the cutting unit 11 to create a sterile end face area 2a of the silicone drainage tube section. The cutting unit 11 can be an interchangeable blade.

[0033] The two cutting steps 10, 12 for cutting the hoses 6, 7 can be carried out simultaneously using the same cutting unit 11. For this purpose, the two hoses 6, 7 can be arranged parallel to each other.

[0034] The two hose sections, namely the silicone feed hose section on the one hand and the silicone discharge hose section on the other, represent the two silicone hose sections 1, 2 to be connected after cutting steps 10, 12.

[0035] The silicone feed hose section 6 and the silicone discharge hose section 7 are cut using the cutting unit 11 at a cutting temperature of less than 80°C. This temperature can be less than 70°C, less than 60°C, less than 50°C, less than 40°C, or less than 30°C. Cutting steps 10 and 12 are both cold cuts, performed purely mechanically, i.e., without applying heat to the silicone material of the silicone hose sections.

[0036] Sterilization of the two end face areas 1a, 2a can be carried out as part of the filling process using UV sterilization lighting of these end face areas 1a, 2a.

[0037] After cutting steps 10 and 12, the two silicone hose sections 1 and 2, with their end faces 1a and 2a facing each other, are positioned in an overmolding mold 13 such that the facing end faces 1a and 2a are in contact with each other. A positioning device, which is already known in the prior art, can be used to position the silicone hose sections 1 and 2 to be connected. Such a positioning device is described in the Figure 1 schematically indicated on the left center at 11a.

[0038] Now the adjacent end face areas 1a, 2a are overmolded in the overmolding mold 13 by filling an overmolding cavity 14 of the overmolding mold 13 with flowable silicone 15.

[0039] The flowable silicone can be a two-component (2K) material with components A and B, which are fed to the overmolding cavity 14 via separate feed / metering channels with metering units 16, 17. Alternatively, the flowable silicone can also be a one-component (1K) material. If the flowable silicone 15 is a one-component material, this single component contains a base polymer, a catalyst, and a crosslinker. If the flowable silicone 15 is a two-component material, one of the two components can contain a base polymer and a crosslinker, and the other component can contain a catalyst.

[0040] The dosing units 16, 17 represent a feeding device for the flowable silicone 15 as overmolding material.

[0041] A flowable, UV-curing silicone material in the form of flowable silicone 15 is used as an overmolding material in pharmaceutical filling processes, particularly in connection processes.

[0042] The Figure 1 The image at the bottom left shows an overmolding step 18 of the connecting process after the preceding positioning step, which is not shown in detail.

[0043] After overmolding 18, the flowable silicone is cured by irradiating it with a UV lamp 19 at a UV curing wavelength. The UV curing wavelength may differ from the UV sterilization wavelength. The cured silicone material resulting from the flowable silicone 15 can have a hardness in the Shore A range of 40 to 60.

[0044] Curing irradiation and sterilization irradiation can be performed in the same process step during the pharmaceutical filling process.

[0045] The irradiation time for curing or crosslinking of the flowable silicone 15 is in the range between 10 s and 120 s, for example between 60 s and 120 s. The crosslinking wavelength is in the UV-A range, i.e., in a wavelength range between 315 nm and 400 nm.

[0046] During sterilization, the irradiation duration ranges from 5 seconds to 1 minute, for example, from 10 seconds to 50 seconds or from 15 seconds to 45 seconds. The sterilization irradiation wavelength is in the UV-C range, i.e., in a wavelength range between 200 nm and 280 nm, for example, in a range between 240 nm and 260 nm.

[0047] Two different UV sources can be used for crosslinking irradiation on the one hand and for sterilization irradiation on the other. Alternatively, it is possible to use a single UV source, where appropriate filters are used to define the respective irradiation wavelengths for crosslinking / curing and sterilization.

[0048] The crosslinking irradiation time can be longer than the sterilization irradiation time. Alternatively, the sterilization irradiation time can also be longer than the crosslinking irradiation time. Both irradiation times can also be the same.

[0049] The crosslinking / curing irradiation does not overlap with the sterilization irradiation duration. According to the invention, the sterilization irradiation takes place during the connection process before the crosslinking / curing irradiation.

[0050] The sterilization or curing irradiation is carried out via a control unit 20, controlled by temperature and / or time. A corresponding curing step 21 is included in the Figure 1 Shown in the upper right corner. Figure 1 The center shows a connection device 22 for carrying out the pharmaceutical filling process and in particular for carrying out the connection process.

[0051] The connecting device 22 includes the replaceable knife 11 and the overmolding mold 13. The connecting device 22 can have a magazine with several replaceable knives 11 or interchangeable blades, which can be used selectively and, in particular, automatically. For example, ten to one hundred cutting operations can be performed with one blade. The connecting device 22 can have a set of knives 11. The respective overmolding mold 13 can therefore be adapted to the hose sections 1, 2 to be connected.

[0052] The connecting device 22 can have a set of overmolding molds 13, in particular for receiving different outer diameters of silicone hose sections of the type of silicone hose sections 1, 2.

[0053] The overmolding mold 13 can be designed as an interchangeable overmolding mold. The connecting device 22 can have a mold magazine containing a plurality of such overmolding molds, in particular also with several selectable sizes of the overmolding cavity. Changing between the interchangeable overmolding molds can be automated. For example, 500 to 100,000, and in particular 10,000 to 25,000 overmolding operations can be performed per overmolding mold. The connecting device 22 can store between 3 and 12 overmolding mold sizes, which are specifically tailored to pharmaceutical standard sizes of the outer diameters of the silicone tube sections 1, 2.

[0054] The overmolding mold 13 can be received in a mold holder of the connecting device 22, which has a contour complementary to the contour of the received overmolding mold. This ensures, firstly, that the overmolding mold is secured against rotation in the mold holder and, secondly, that the overmolding mold is correctly oriented or positioned in the mold holder.

[0055] A signal connection can be established between the overmolding mold and the mold holder to ensure that the correct overmolding mold is used for the current connection task. This can be achieved, for example, by a multiple of contact pins on the mold holder, between which appropriate conductive connections are established via the overmolding mold when the correct pins are selected.

[0056] The overmolding mold 13 can be made of a polymer material, for example PMMA.

[0057] The operating time and number of use cycles of the respective indirect knife 11 can be specified and documented in the control unit 20, which also serves to control the knife 11.

[0058] The control unit 20 also serves to document the operation of the respective UV lamp, both for curing and for sterilization. Each connection process can be evaluated in the control unit 20.

[0059] In particular, radiation intensity, irradiation duration and temperature, especially of the flowable silicone 15 during the curing process or of the end face areas 1a, 2a during the sterilization process, can be specified and documented.

[0060] After successful connection, the pharmaceutical medium is dispensed from the output reservoir 3 via the now connected silicone tubing sections 1 and 2 to the target reservoir 4. The pharmaceutical medium is, for example, a buffer solution for pH regulation.

[0061] The connection device 22 can be mobile. The connection device 22 has a display / operating unit 23, which can be a touchscreen and is in signal communication with the control unit 20.

[0062] The connection device 22 can be designed to be mobile. The connection device 22 can be designed for battery operation 24 and / or for mains operation 25.

[0063] The connecting device 22 can have a reading unit 26 for specifying the respective knife 11 and / or for specifying the respective overmolding mold 13, which in the Figure 1The left center and left bottom sections are each shown schematically. The reading unit 26 can read a code on the respective knife 11 and / or on the respective overmolding mold 13, for example, a QR code. Alternatively or additionally, the reading unit 26 can read a corresponding code on at least one of the silicone tube sections 1, 2, which can also be a QR code.

[0064] A fully connected silicone tube 27 with the two connected, sterile end face areas 1a, 2a of the silicone tube sections 1, 2, which are connected to each other via an overmolding 28, is used for media supply in a pharmaceutical filling process.

Claims

1. Method for connecting two silicone tube sections (1, 2) with following steps: sterilizing the end face portions (1a, 2a) of the two silicone tube sections (1, 2) to be connected using a UV light irradiation with a UV sterilization wavelength; positioning the end face portions (1a, 2a) of the silicone tube sections (1, 2) to be connected that face each other in an overmolding mold (13) such that the end face portions (1a, 2a) facing each other abut each other; overmolding the end face portions (1a, 2a) abutting each other in the overmolding mold (13) by filling an overmolding cavity (14) of the overmolding mold (13) with flowable, UV curing silicone (15); curing (21) the flowable silicone (15) by UV light irradiation using a UV light irradiation with a UV curing wavelength; wherein the UV curing wavelength differs from the UV sterilization wavelength.

2. Pharmaceutical media transfer method for supplying a pharmaceutical medium (5) from a source reservoir (3) to a target reservoir (4) with following steps: providing the pharmaceutical medium (5) in the source reservoir (3) including a silicone supply tube (6) being in media communication with the source reservoir (3); providing the target reservoir (4) including a silicone discharge tube (7) being in media communication with the target reservoir (4); displacing (9) the pharmaceutical medium (5) in a silicone supply tube section of the silicone supply tube (6); cutting (10) the silicone supply tube section of the silicone supply tube (6) for creating a sterile end face portion (1a) of the silicone supply tube section; cutting a silicone discharge tube section of the silicone discharge tube (7) for creating a sterile end face portion (2a) of the silicone discharge tube section; connecting the silicone supply tube section with the silicone discharge tube section with a method according to claim 1, wherein the silicone supply tube section on the one hand and the silicone discharge tube section on the other hand represent the two silicone tube sections to be connected by the method; transferring the pharmaceutical medium (5) from the source reservoir (3) to the target reservoir (4) via the connected tube sections (1, 2).

3. Pharmaceutical media transfer method according to claim 2, characterized in that the cutting (10) of the silicone supply tube section and / or the silicone discharge tube section is performed at a cutting temperature that is smaller than 80° C.

4. Apparatus (22) for connecting two silicone tube sections (1, 2) and for performing a method according to one of claims 1 to 3 with a UV source for sterilizing the end face portions (1a, 2a) of the two silicone tube sections (1, 2) to be connected using a UV light irradiation with a UV sterilization wavelength; with a cutting unit (11) for cutting at least one of the silicone tube sections (1, 2), with an overmolding mold (13) including a feeding device (16, 17) for the flowable silicone (15) as overmolding material, with a positioning device (11a) for positioning the silicone tube sections (1, 2) to be connected; and with a UV source for curing the flowable silicone (15) by UV light irradiation using a UV light irradiation with a UV curing wavelength; wherein the UV curing wavelength differs from the UV sterilization wavelength.

5. Apparatus according to claim 4, wherein the apparatus comprises a first UV source for sterilizing the end face portions (1a, 2a) of the two silicone tube sections (1, 2) to be connected using a UV light irradiation with a UV sterilization wavelength, and a second UV source for curing the flowable silicone (15) by means of UV light irradiation with a UV curing wavelength.

6. Apparatus according to claim 4, wherein the apparatus comprises a collective UV source which is configured such that the respective irradiation wavelengths for sterilizing the end face portions (1a, 2a) of the two silicone tube sections (1, 2) to be connected and for curing the flowable silicone (15) can be set via corresponding filters.

7. Apparatus according to any of claims 4 to 6, characterized by a mobile configuration for the laboratory use, the clinical use, the use in a clean room environment, or the use in a pre-series environment; wherein the apparatus is configured to be mobile and comprises several castors, which are mounted on a frame of the apparatus; wherein the apparatus in particular comprises a traction drive, especially an electric motor.

8. Apparatus according to any of claims 4 to 7, further comprising a set of blades (11); and a set of overmolding molds (13); wherein the tubes for the tube sections (1, 2) to be connected, namely the silicone supply tube (6) and the silicone discharge tube (7), have predefined data; wherein the apparatus further comprises a reading unit (26) for presetting a blade within the set of blades (11) and / or for presetting an overmolding mold within the set of overmolding molds (13), each adapted to the tube sections (1, 2) to be connected.

9. Apparatus according to claim 8, wherein the blades (11) of the set of blades (11) and the overmolding molds (13) of the set of overmolding molds (13) each have a code, in particular a QR code; wherein the predefined data of the tubes (6, 7) for the tube sections (1, 2) to be connected are in the form of codes, in particular QR codes; and wherein the reading unit (26) is configured as a code reader, in particular as a QR code reader.

10. Use of a liquid, UV curing silicone material (15) as overmolding material in a method according to one of the claims 1 to 3, which is configured such that a UV curing wavelength used in the curing of the silicone material differs from a UV sterilization wavelength used in a sterilization step of the silicone material..

11. Use according to claim 10, wherein the UV curing of the silicone material in cured state has a hardness in the range of Shore A40 to Shore A60.