Multilayer gas barrier film and bag

Abstract

A multilayer gas barrier film for containing medical fluids comprises: an inner film having first and second surfaces, the first surface being in contact with the fluid and the second surface being in contact with a first adhesion agent; a middle film having third and fourth surfaces, the third surface being in contact with the first adhesion agent and the fourth surface being in contact with a second adhesion agent; an outer film having fifth and sixth surfaces, the fifth surface being in contact with the second adhesion agent; where the inner film comprises an olefinic polymer having a glass transition point of less than 10°C and a melting point of more than 130°C, the middle film contains a polymer with an ester bond that has a glass transition point of more than 35°C and a melting point of more than 150°C, and the middle film comprises an inorganic gas barrier material, and the outer film comprises a polymer with an amide bond.

Description

[0001] Multilayer gas barrier film and bags

[0002] Technical area

[0003] The invention relates to a multilayer gas-barrier film for containing medical fluids. The invention further relates to a bag for containing medical fluids, comprising a multilayer gas-barrier film.

[0004] background

[0005] Gas-barrier films and bags are required, for example, for the provision of bicarbonate-buffered medical fluids, particularly dialysis solutions for peritoneal, acute, and chronic renal failure treatment with hemodialysis. For this purpose, it is particularly important that such gas-barrier bags exhibit a low permeation tendency of carbon dioxide. Furthermore, such gas-barrier bags can also be suitable for containing enteral or parenteral nutritional solutions and suspensions.

[0006] Barrier films and bags of this type are known, for example, from DE102012018525A. In this case, a polyester or polyamide film is coated with a ceramic coating material, and the coated surface is then laminated with a polyolefin film, without using an adhesive to bond the two films. Films produced in this way are limited in their laminate strength and also in the tear resistance of the multilayer film. The production of so-called peel seams—i.e., seams that are introduced into the multilayer bag to contain different solutions in one bag and that are torn open before use, allowing the solutions to mix within the bag—is also difficult.

[0007] EP0760283A describes a multilayer film comprising a polyester or polyamide as the base material, which is provided with an inorganic SiO2 layer and which contains a second barrier layer made of PVC or a similar material. The adhesion of the barrier film to the inorganic SiO2 layer is intended to be ensured by a silane treatment of the inorganic layer. Such multilayer films exhibit good water and oxygen barrier properties, but may not be mechanically stable enough to safely store medical fluids. Such films are also difficult to weld, which may result in low weld seam strength. Depending on the layer sequence, these films also exhibit poor leachability values, for example, of residual monomer components such as caprolactam.

[0008] Further composite systems are described in EP0792846B, which involve coating a base film with a so-called ORMOCER, i.e., an organic-inorganic hybrid layer. However, such manufacturing processes for producing a gas-barrier film are very complex because they require a so-called sol-gel process, which precludes efficient coating of a film on a production scale. Furthermore, it is difficult to provide suitable gas-barrier properties, especially for carbon dioxide.

[0009] EP1028994B1 describes a two-layer film comprising an oriented polyamide film coated with an inorganic silicon oxide layer and a sealing layer. Such films exhibit limited retention of residual monomers and may be subject to low mechanical strength.

[0010] Object of the invention

[0011] The invention is therefore based on the object of reducing the disadvantages of the prior art. In particular, it is an object to ensure a mechanically stable film with low transfer of residual monomers and other undesirable substances to the medicinal fluid. Furthermore, it is an object to provide a bag comprising a film according to the invention that reduces the disadvantages of the prior art.

[0012] Summary of the invention

[0013] According to a first aspect of the invention, the object is achieved by providing a multi-layer gas barrier film for containing medical fluids, comprising an inner film having a first and a second surface, wherein the first surface is in contact with the fluid and the second surface is in contact with a first adhesive, a middle film having a third and a fourth surface, wherein the third surface is in contact with the first adhesive and the fourth surface is in contact with a second adhesive, an outer film having a fifth and a sixth surface, wherein the fifth surface is in contact with the second adhesive, wherein the inner film comprises an olefinic polymer having a glass transition point of less than 10°C and a melting point of more than 130°C,wherein the middle film comprises a polymer having an ester bond and a glass transition point above 35°C and a melting point above 150°C, and the middle film comprises an inorganic gas barrier material, and wherein the outer film comprises a polymer having an amide bond.

[0014] Such a medicinal liquid can be a solution, in particular an aqueous solution, optionally comprising ionic and / or non-ionic water-soluble components; more particularly, the medicinal liquid can contain carbonate components. Such a multilayer film is also preferably used for medicinal liquids that are sensitive to the ingress of carbon dioxide from the atmosphere into the liquid. When containing carbonate or bicarbonate-containing solutions, it may also be desirable to minimize the loss of carbonate or bicarbonate ions from the solution.

[0015] Such a multilayer film exhibits good mechanical stability, ensuring the problem-free storage of medical fluids over extended periods. In particular, the bag can be handled under difficult conditions, for example in a hospital, without mechanical damage or, for example, tearing. Furthermore, it is ensured that residual monomers, which in particular contain polymers with an amide bond, cannot diffuse through the multilayer film to a critical extent and migrate into the medical fluid. Furthermore, it is guaranteed that the multilayer gas barrier film has a particularly low diffusion capacity for carbon dioxide. Because the inner surface comprises an olefinic polymer, the film is particularly easy to provide with a peel seam.A peel seam can then be created simply by welding a surface at a defined temperature, so that on the one hand the multilayer film can be processed into a multi-chamber bag containing different medical fluids, but on the other hand it is possible to break the peel seam before the medical fluids are used in the respective chambers and to enable different medical fluids to be mixed shortly before use. This is particularly desirable when medical fluids can be stored for a long time as separate solutions, but have only a limited shelf life once mixed. In addition, olefinic polymers are preferred for direct contact with medical fluids because they are particularly physiologically safe. Such multi-chamber bags are used in particular for containing medical dialysis solutions, and in particular for dialysis solutions for peritoneal dialysis.

[0016] In one embodiment, the multilayer gas barrier film is characterized in that the polymer with the amide bond has a glass transition point of 60 to 100°C in the dried state and / or a glass transition point of 20 to 60°C in the water-saturated state and a melting point greater than 200°C. Hygroscopic polyamides have proven particularly suitable for providing a multilayer gas barrier film, characterized in that the glass transition point decreases due to water absorption after extrusion of the film. The polyamide material must be sufficiently dried before processing into a film so that a residual moisture content of less than 0.1% remains.After processing into a multilayer gas barrier film and producing a bag for medical fluids, especially aqueous fluids, the polymer can absorb water up to saturation, resulting in a preferred mechanical property profile of flexibility and strength. Examples of such polyamides are polyamide 6 or polyamide 4,6 or 6,6. The glass transition point is determined using the DSC method, as stated in the further description. Particularly suitable polyamides have a melting point of less than 250°C. The polyamides are preferably aliphatic. A particularly preferred polyamide is polyamide 6 because it is widely and inexpensively available and has a particularly preferred property profile with regard to mechanical properties.

[0017] According to a further development of the invention, the multilayer gas barrier film is characterized in that the middle film with ester bond has an inorganic gas barrier layer on at least one surface of the polymer and that the third or fourth surface is formed by the inorganic layer.

[0018] Such films with ester bonds can be produced on an industrial scale; a corresponding manufacturing method is described in DE102012018525A. It is important that the inorganic gas barrier layer can be applied particularly well to the film with the ester bond, thus demonstrating good adhesion. The combination of the polymer with the ester bond, on the one hand, which has a particularly good diffusion barrier against carbon dioxide, and, on the other hand, the inorganic layer with its generally good barrier effect against all gases such as water vapor, oxygen, and carbon dioxide, is particularly important.

[0019] In a particular embodiment, the middle film of the multilayer gas-barrier film comprises inorganic SiOx particles. These particles are easily produced according to DE102012018525A and offer particularly good adhesion to the polymer with ester bonding while maintaining good gas-barrier properties.

[0020] In one embodiment of the invention, the multilayer gas-barrier film is characterized in that the middle film comprises a polyethylene terephthalate or a polyethylene naphthalate, or a mixture of both polymers. These polymers are highly mechanically resilient, easily extrudable into film, and exhibit particularly suitable properties regarding carbon dioxide diffusion. Polyethylene terephthalate is particularly preferred because it can provide good adhesion to the inorganic layer.

[0021] The multilayer gas barrier film is preferably characterized in that the multilayer film does not contain a silane coupling agent. While such a silane coupling agent makes it possible to provide good bonding between the inorganic layer and, for example, a polyolefin layer, such embodiments are particularly complex to develop and manufacture. Silane coupling agents, for example, must be laboriously hydrolyzed before reacting with the inorganic particle, producing undesirable alcohols, such as methanol, which can be disadvantageous, particularly when transferred into medical fluids. After silane hydrolysis, the silanol must still couple to the inorganic particle, which represents a comparatively slow reaction. Furthermore, the most suitable silane must first be selected from a large number of available silanes, which is very complex depending on the film sequence of the multilayer film.According to one embodiment, the multilayer gas barrier film is characterized in that the polymer of the outer film comprises polyamide 6. Particularly preferably, the multilayer gas barrier film has a caprolactam leaching rate, determined according to the method specified in the description, of less than 1 mg / l, preferably less than 0.1 mg / l. Depending on the raw material, polyamide may have an elevated caprolactam content as a residual monomer, which is disadvantageous because this residual monomer content can migrate into the medicinal liquid. This can occur in particular if a bag for containing aqueous medicinal liquids has been produced from the multilayer gas barrier film. However, the arrangement according to the invention can prevent an unacceptably high proportion of caprolactam from migrating into the medicinal liquid.

[0022] According to one embodiment, a multilayer gas barrier film can be characterized in that the inner film has a wall thickness of 100 to 250 μm, in particular of 150 to 200 μm. The wall thickness range essentially results from the need for sufficient strength of the inner film and the overall film; however, the minimum and maximum wall thickness are also determined by the need for welding, which arises when the film is to be processed into a bag for containing medical liquids. In particular, if a high-strength weld seam and a peel seam are required at the same time, adherence to certain wall thickness ranges is preferred, as has been shown in the course of the work on the invention.

[0023] According to one embodiment, a multilayer gas barrier film can be characterized in that the middle film has a wall thickness of 5 to 30 μm, in particular 5 to 20 μm. In addition to providing sufficiently high strength, the polymer of the middle film also acts as a gas barrier for the gases water vapor, oxygen, and in particular carbon dioxide. Careful selection of the wall thickness is crucial for the desired property profile of strength and diffusion barrier. If the middle film is coated with inorganic particles, the wall thickness specified applies to the coated middle film. According to a further embodiment, the multilayer gas barrier film is characterized in that the outer film has a wall thickness of 5 to 30 μm, in particular 10 to 20 μm.The wall thickness range of the outer film must be carefully selected to ensure a sufficient property profile of the film's flexibility and strength.

[0024] In a preferred embodiment, the multilayer gas barrier film is characterized in that the sixth surface is in contact with the surrounding atmosphere. In this embodiment, the film is designed such that no additional layer is required to provide the overall property profile.

[0025] According to a further development of the invention, the multilayer gas barrier film is characterized in that the diffusion of carbon dioxide through the film is less than 20 cm 3 / m 2* d * bar. Experiments conducted for this invention have shown that the specific layer sequence, particularly the selection of the polymer for the middle film using a polymer with an ester bond, is important for providing a film with low carbon dioxide diffusivity. Especially when the medical fluid contains solids and solutions with carbonate-containing substances, the low carbon dioxide diffusivity is important for sufficient stability of the medical fluid.

[0026] According to a second aspect, the object of the invention is achieved by providing a bag for containing medical liquids, comprising a multi-layer gas barrier film according to the first aspect of the invention. Such a bag is formed, for example, from two film sections, wherein the peripheral edges are provided with a weld seam. Flat films can preferably be used for this purpose. The use of tubular films can also be preferred, in particular if increased hygiene requirements are placed on the film. Tubular films are particularly preferably produced using water cooling, in particular if the films are to have a high degree of transparency. The bag according to the second aspect of the invention is thus preferably characterized in that the bag comprises a weld seam.Using a welding device, for example, in the peripheral edge area, sufficient heat is introduced into the film sections to melt the inner film of both film sections. By joining the film sections, the molecules of the polymer of the inner film can be bonded together, for example, by entangling. The goal is to achieve a weld seam strength sufficient to create a stable bag that allows for the safe storage of the medicinal liquid without, for example, the weld seam being able to tear.

[0027] A further embodiment of the second aspect of the invention is characterized in that the bag comprises a peelable seam. Peelable seams can be produced particularly reliably when the welding is carried out in a similar way to the permanent welding of, for example, the peripheral edge of the bag, but the temperature and exposure time during the welding are reduced to such an extent that a comparatively weak entanglement of the molecules occurs, so that the resulting weld seam is peelable. The juxtaposition of permanent and peelable seams is particularly advantageous for the production of a multi-chamber bag using a film according to the invention.

[0028] Detailed description of an embodiment

[0029] Example 1: Production of the film

[0030] 1 . Production of a polyolefin film:

[0031] A polyolefin film is produced as a three-layer film by tubular extrusion, with water cooling used to achieve sufficient transparency. It has an outer layer made of PP homopolymer. The layer thickness is 15 μm. The middle layer consists of a 145 μm PP / TPE blend. The inner layer consists of another PP / TPE blend with an increased TPE content. SEBS is used as the TPE. The total thickness of the polyolefin film is 180 μm. The film is particularly suitable for the production of weld seams of varying strength. For example, the outer layer of a bag can be made particularly tear-resistant through intensive welding, while a multi-chamber bag can be created by providing an inner peel seam with low tear strength.

[0032] 2. Production of a PA film

[0033] A polyamide film made of polyamide 6 is produced as a cast film with biaxial orientation. The layer thickness is 15 μm.

[0034] 3. Production of a PET / SiOx film.

[0035] A cast film made of PET with a layer thickness of 12 pm or biaxially oriented PET / PEN is used. The SiOx layer is applied by electron beam evaporation, with the inorganic layer thickness being approximately 50 nm. The production of the layer is described in more detail in DE102012018525A.

[0036] 4. Production of the multilayer film by lamination

[0037] The outer layer of the polyolefin film—consisting of polypropylene—is coated with a solvent-based polyurethane adhesive, and the layer is pre-dried in a heating tunnel. The PET(SiO)x layer is then laminated onto it in a roll laminator.

[0038] Next, another layer of polyurethane adhesive is applied and allowed to dry again. The PA film is then laminated onto this.

[0039] 5. Trimming

[0040] After the lamination process, the composite film is subjected to a finishing of the edges in a roll cutter or the film is cut to size.

[0041] Comparative example 1 : Production of the film

[0042] The multilayer gas barrier film is manufactured as in Example 1, with the following difference: The outer layer of the polyolefin film—consisting of polypropylene—is coated with a solvent-based polyurethane adhesive, and the layer is pre-dried in a heating tunnel. The PA6 layer is then laminated onto this layer in a roll laminator. A further layer of polyurethane adhesive is then applied, followed by another drying process. The PET-SiOx film is then laminated onto this layer. This brings the SiOx layer into contact with the adhesive layer.

[0043] Comparative example 2: Production of the film

[0044] A polyolefin film and a PET / SiOx film are used, as described in Example 1. The outer layer of the polyolefin film, consisting of polypropylene, is coated with a solvent-based polyurethane adhesive, and the layer is pre-dried in a heating tunnel. The PET(SiO)x layer is then laminated onto this layer in a roll laminator.

[0045] Elution experiment

[0046] A solution suitable for peritoneal dialysis is prepared. The concentrations are as follows:

[0047] *The aluminum content is determined using the well-known measurement method of ICP mass spectroscopy. A bag is made from the respective film by firmly sealing the edges. A filling tube is inserted into the upper section and sealed tightly, as is the case with the bags available as standard under the name sleep safe BicaVera 5000 ml from Fresenius Medical Care.

[0048] A bag is prepared in the appropriate dimensions, as determined from the commercially available bag. This bag is filled with 5 liters of the above-mentioned solution.

[0049] This bag is then stored at 40°C and < 25% relative humidity for 3 months.

[0050] The solution is analyzed for the concentration of caprolactam using gas chromatography.

[0051] The conditions for gas chromatography / MS are as follows:

[0052] Table 1 Appropriate instrument settings, eg

[0053] All samples, blank solutions, and calibration solutions are extracted in chloroform, and the respective chloroform solutions are then subjected to analysis. The blank value must be determined to minimize the influence of any impurities and inaccuracies in the analysis. A calibration curve is constructed using linear regression with the respective calibration solutions, allowing the concentrations of the sample solutions to be determined. The retention time of s-caprolactam under these conditions is approximately 6.3 minutes. The target ion is the ion with a mass of 113.0 g / mol, and the check ions are ions with ionic masses of 55.0 and 56.0 g / mol.

[0054] Results:

[0055] Gas barrier properties:

[0056] CO2 permeability is measured on a film section that has previously been sterilized at 120°C in steam for 20 minutes using a test device according to DIN 53380-4 at 23°C and 0% relative humidity. All films exhibit a permeability of less than 20 cm. 3 / m 2 *d*bar and are therefore suitable for containing bicarbonate-containing solutions. Mechanical properties:

[0057] A tensile test is conducted in accordance with DIN EN ISO 527-Part 3, Type 2 specimen with a width of 15 mm. The specimens are removed from the film using a suitable punch. The measurement is carried out at 23°C and 40-60% humidity. The test speed is 1 mm per minute. The elastic modulus is determined, with the target value for the elastic modulus in the direction of production and orthogonal to it being 350 MPa or higher. The results are as follows:

[0058] Additionally, a drop test is conducted on a bag described above, using standard packaging for the bag, such as the sleep safe BicaVera 5000 ml product. The packaging is fixed at a height of 60 cm and then dropped flat onto a solid surface from the predetermined height. Ten samples are used per sample, and the percentage of defects (leaks) is determined. Each sample is brought to a temperature of 5°C prior to the test. The test itself is conducted at room temperature within less than 2 minutes of removal from the temperature chamber.

[0059] In Comparative Example 2, leakage occurred in 80% of the tests after the drop test. In Example 1 and Comparative Example 1, no leakage occurred at a drop height of 60 cm.

[0060] Compared to the prior art, the embodiment shows excellent mechanical strength combined with extremely low elution values ​​for residual monomers, so that embodiments according to the invention are particularly suitable for containing medical fluids, in particular dialysis fluids, furthermore in particular dialysis fluids for peritoneal dialysis.

Claims

A multilayer gas barrier film for containing medical fluids, comprising an inner film having a first and a second surface, the first surface being in contact with the fluid and the second surface being in contact with a first adhesive, a middle film having a third and a fourth surface, the third surface being in contact with the first adhesive and the fourth surface being in contact with a second adhesive, an outer film having a fifth and a sixth surface, the fifth surface being in contact with the second adhesive, the inner film comprising an olefinic polymer having a glass transition point of less than 10°C and a melting point of over 130°C, the middle film comprising a polymer having an ester bond and a glass transition point of over 35°C and a melting point of over 150°C,and the middle film comprises an inorganic gas barrier material, and wherein the outer film comprises a polymer with an amide bond. The multilayer gas barrier film according to claim 1, characterized in that the polymer with the amide bond has a glass transition point of 60 to 100°C in the dried state and a glass transition point of 20 to 60°C in the water-saturated state, and a melting point greater than 200°C. The multilayer gas barrier film according to any one of the preceding claims, characterized in that the melting point of the polymer with the amide bond has a melting point of less than 250°C. Multilayer gas barrier film according to one of the preceding claims, characterized in that the polymer with an amide bond is an aliphatic polyamide. Multilayer gas barrier film according to claim 1, characterized in that the middle film with an ester bond has an inorganic gas barrier layer on at least one surface of the polymer, and that the third or fourth surface is formed by the inorganic layer. Multilayer gas barrier film according to claim 5, characterized in that the inorganic layer comprises particles of SiOx. Multilayer gas barrier film according to claims 1 to 6, characterized in that the middle film comprises a polyethylene terephthalate or a polyethylene naphthalate. Multilayer gas barrier film according to one of the preceding claims, characterized in that the multilayer film does not contain a silane coupling agent.Multilayer gas barrier film according to one of the preceding claims, wherein the polymer of the outer film comprises polyamide 6. Multilayer gas barrier film according to claim 9, characterized in that the leaching of caprolactam, determined according to the method specified in the description, is less than 1 mg / l, preferably less than 0.1 mg / l. Multilayer gas barrier film according to one of the preceding claims, characterized in that the inner film has a wall thickness of 100 μm to 250 μm. Multilayer gas barrier film according to one of the preceding claims, characterized in that the middle film has a wall thickness of 5 μm to 30 μm. Multilayer gas barrier film according to one of the preceding claims, characterized in that the outer film has a wall thickness of 5 μm to 30 μm. Multilayer gas barrier film according to one of the preceding claims, wherein the sixth surface is in contact with the surrounding atmosphere. Multilayer gas barrier film according to one of the preceding claims, characterized in that the diffusion of carbon dioxide through the film is less than 20 cm 3 / m 2 * d * bar. A bag for containing medical fluids, comprising a multilayer gas barrier film according to any one of the preceding claims. A bag according to claim 16, characterized in that the bag comprises a weld seam. A bag according to claim 16 or 17, characterized in that the bag comprises a peel seam.

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