Multilayer gas barrier films and bags

Abstract

1. A multilayer gas barrier film for containing a chemical solution, comprising: an inner film having a first surface in contact with the chemical solution and a second surface in contact with a first adhesive; an intermediate film having a third surface in contact with the first adhesive and a fourth surface in contact with the second adhesive; and an outer film having a fifth surface in contact with the second adhesive and a sixth surface, wherein the inner film comprises an olefin-based polymer having a glass transition temperature lower than 10°C and a melting point higher than 130°C; the intermediate film comprises a polymer having an ester bond and a glass transition temperature higher than 35°C and a melting point higher than 150°C, and the inorganic gas barrier material; and the outer film comprises a polymer having an amide bond.

Description

[Technical Field]

[0001] The present invention relates to a multilayer gas barrier film for containing a medicinal liquid, and further to a bag including the multilayer gas barrier film for containing a medicinal liquid. [Background technology]

[0002] Gas-barrier films and bags are required, for example, for the delivery of bicarbonate medicinal solutions, particularly dialysate for dialysis intended for the treatment of chronic renal failure using peritoneal dialysis, emergency dialysis, and hemodialysis. These purposes require, in particular, that such gas-barrier bags have a low tendency to permeate carbon dioxide. Furthermore, such gas-barrier bags may also be suitable for containing solutions and suspensions of enteral or parenteral nutritional formulas.

[0003] General-purpose barrier films and bags are known, for example, from German Patent Publication No. 102012018525. In this case, a polyester or polyamide film is coated with a ceramic coating, and then a polyolefin film is laminated to the coated surface, without any adhesive being used to join the two films. Films produced in this way have limited lamination strength and tear strength for multilayer films. In addition, it is quite difficult to produce a seam known as a peel seam, which is introduced into a multilayer bag to accommodate various solutions in one bag and pulled open to allow the solutions to mix within the bag before use.

[0004] European Patent Publication No. 0760283 describes a multilayer film comprising a polyester or polyamide matrix provided with an inorganic SiO2 layer and a second barrier layer made of PVC or a similar material. Adhesion of the barrier film to the inorganic SiO2 layer is said to be ensured by treating the inorganic layer with saline. While this type of multilayer film exhibits good water and oxygen barrier properties, it may not have sufficient mechanical stability to reliably store pharmaceutical solutions. Additionally, such films can be difficult to weld, resulting in low seam strength. Furthermore, depending on the layer order, these films exhibit insufficient values ​​for leachability of residual monomer compositions, such as caprolactam.

[0005] EP 0792846 describes so-called ormocers, composite systems that allow the coating of substrate films with organic-inorganic hybrid layers. However, the production of gas barrier films is very costly and inconvenient because it requires the use of a process known as a sol-gel process, which is incompatible with efficient production-scale film coating. Furthermore, it is difficult to impart suitable gas barrier properties, especially to carbon dioxide.

[0006] EP 1028994 describes a bilayer film comprising an oriented polyamide film coated with an inorganic silicon oxide layer. Such films may have limited residual monomer retention and little mechanical robustness. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] German publication number 102012018525 [Patent Document 2] European Publication No. 0760283 [Patent Document 3] European Patent No. 0792846 [Patent Document 4] European Patent No. 1028994 Summary of the Invention [Problem to be solved by the invention]

[0008] The object underlying the present invention is therefore to reduce the above-mentioned drawbacks of the prior art, in particular to ensure a mechanically stable film characterized by low permeability of residual monomers and other undesirable substances to the drug solution. A further object is to achieve a bag comprising the film of the present invention, which reduces the drawbacks of the prior art. [Means for solving the problem]

[0009] According to the present invention, the above objects are achieved by a multilayer gas barrier film for containing a chemical solution in accordance with a first aspect of the present invention, the multilayer gas barrier film comprising: an inner film having a first surface in contact with the chemical solution and a second surface in contact with a first adhesive; an intermediate film having a third surface in contact with the first adhesive and a fourth surface in contact with the second adhesive; and an outer film having a fifth surface in contact with the second adhesive and a sixth surface, wherein the inner film comprises an olefin-based polymer having a glass transition temperature lower than 10°C and a melting point higher than 130°C; the intermediate film comprises a polymer having an ester bond and a glass transition temperature higher than 35°C and a melting point higher than 150°C, and comprises an inorganic gas barrier material; and the outer film comprises a polymer having an amide bond.

[0010] This type of medicinal solution may optionally be a solution containing ionic and / or nonionic water-soluble components, more specifically, an aqueous solution, and may further include, in particular, a carbonate component. This type of multilayer film is also selectively used for medicinal solutions that are sensitive to the intrusion of atmospheric carbon dioxide into the solution. In situations involving the storage of carbonate- or bicarbonate-containing solutions, it may also be desirable to minimize the loss of carbonate or bicarbonate from the solution. This type of multilayer film exhibits good mechanical stability, thereby ensuring uninterrupted storage of the medicinal solution over a relatively long period of time. In particular, the bag can be handled under rigorous hospital conditions without mechanical damage, such as tearing. Furthermore, it is ensured that residual monomers, particularly those present in polymers with amide bonds, cannot diffuse through the multilayer film and enter the medicinal solution. Furthermore, it is ensured that the diffusion of carbon dioxide through the multilayer gas barrier film is particularly low. Because the inner surface comprises an olefin-based polymer, it is particularly easy to provide a peel seam in the film. The peel seam can be easily obtained by welding certain areas at a predetermined temperature. This peel seam allows the multilayer film to be processed into a multi-compartment bag containing multiple different medicinal solutions, and then, by breaking the peel seam, the medicinal solutions in each compartment can be used, allowing these different medicinal solutions to be mixed immediately before use. This is desirable when the medicinal solutions have a long shelf life as separate solutions but only a limited shelf life after mixing. Furthermore, olefin-based polymers are preferred for direct contact with medicinal solutions because they are physiologically harmless to a certain extent. This type of multi-compartment bag is particularly used to contain medical dialysis solutions, and in particular, peritoneal dialysis solutions. In one embodiment, the multilayer gas barrier film is characterized by a polymer containing amide bonds having a glass transition temperature of 60°C to 100°C in a dry state and / or 20°C to 60°C in a water-saturated state, and a melting point greater than 200°C. Hygroscopic polyamides, characterized by a glass transition temperature decrease upon water absorption after film extrusion, have emerged as particularly suitable for the realization of multilayer gas barrier films. These polyamide materials must be sufficiently dried to a residual moisture content of less than 0.1% before processing into a film. After processing into a multilayer gas barrier film and fabricating a bag for chemical solutions, particularly aqueous solutions, the polymer is able to absorb water until saturated, resulting in a favorable profile of mechanical properties: flexibility and strength. Examples of such polyamides are polyamide 6, polyamide 4.6, or polyamide 6.6. The glass transition temperature in this case can be determined using the DSC method described below. Particularly suitable polyamides have melting points below 250°C. These polyamides are preferably aliphatic. One particularly preferred polyamide is polyamide 6 because it is widely available, inexpensive, and has a particularly favorable property profile with respect to mechanical properties. According to one development of the invention, the multilayer gas barrier film is characterized in that the intermediate film having ester bonds has an inorganic gas barrier layer on at least one surface of the polymer, and that this inorganic layer forms the third or fourth surface.

[0011] This type of film having ester bonds can be produced on an industrial scale, and one corresponding production method is described in German Patent Publication No. 102012018525. In this case, it is important to be able to particularly effectively apply an inorganic gas barrier layer onto the film having ester bonds so that the adhesive strength is good. Particularly important in this situation is a combination of a polymer having ester bonds, which exhibits particularly good diffusion barrier properties against carbon dioxide, on the one hand, and an inorganic layer, which generally has a good barrier effect against all gases, such as water vapor, oxygen, and carbon dioxide, on the other hand.

[0012] In one particular embodiment, the intermediate film of the multilayer gas barrier film has an inorganic layer of SiO particles, which can be readily produced according to DE 102012018525 A1 and provide particularly good adhesive strength on polymers with ester bonds, combined with good gas barrier properties.

[0013] In one embodiment of the present invention, the multilayer gas barrier film is characterized in that the intermediate film comprises polyethylene terephthalate, polyethylene naphthalate, or a mixture of both polymers. These polymers have high mechanical robustness, can be easily extruded into films, and have particularly good properties with respect to carbon dioxide diffusion. Polyethylene terephthalate is particularly preferred because it can provide good adhesion to the inorganic layer.

[0014] The multilayer gas barrier film is preferably characterized by the absence of a silane bonding agent. While such a silane bonding agent can certainly provide effective composite adhesion between an inorganic layer and, for example, a polyolefin layer, this type of embodiment is particularly costly and inconvenient to develop and manufacture. For example, the silane bonding agent must be hydrolyzed in a costly and inconvenient process before reacting with the inorganic particles, which produces undesirable alcohols, such as methanol, that can be harmful, especially if introduced into chemical solutions. Following silane hydrolysis, silanols must also be bonded to the inorganic particles, a process that exhibits a relatively slow reaction rate. Furthermore, an optimal silane must first be selected from a large selection of silanes, which can be very costly and inconvenient depending on the film sequence of the multilayer film.

[0015] According to one embodiment, the multilayer gas barrier film is characterized in that the polymer of the outer film comprises polyamide 6. Particularly preferred, the multilayer gas barrier film has a caprolactam leaching amount of less than 1 mg / L, preferably less than 0.1 mg / L, as determined by the method described herein. Depending on the raw materials, polyamides may have a high caprolactam content in the form of residual monomer content, which is disadvantageous because it can migrate into the chemical solution. This can occur, in particular, when the multilayer gas barrier film is used to make a bag for containing an aqueous chemical solution. The arrangement according to the present invention can prevent the possibility of unacceptably high caprolactam content migrating into the chemical solution.

[0016] One embodiment of the multilayer gas barrier film can be characterized by an inner film having a wall thickness of 100 μm to 250 μm, more specifically, 100 μm to 200 μm. This wall thickness range is primarily dictated by the need for sufficient strength of the inner film and the overall film, but the minimum and maximum wall thicknesses are also determined by the need for welding when the film is to be processed into a bag for containing medical solutions. As was discovered as part of the research leading to the present invention, it is preferable to adhere to a specific wall thickness range, particularly when high-strength welded seams and peel seams are to be present.

[0017] A multilayer gas barrier film according to one embodiment can be characterized by an intermediate film having a wall thickness of 5 μm to 30 μm, more specifically 5 μm to 20 μm. In addition to providing sufficient strength, the polymer of the intermediate film provides a gas barrier function to gases such as water vapor, oxygen, and especially carbon dioxide. Careful selection of the wall thickness is important to achieve the desired property profile of strength and diffusion barrier. If the intermediate film is coated with inorganic particles, this wall thickness specification applies to the coated intermediate film.

[0018] According to a further embodiment, the multilayer gas barrier film is characterized in that the outer film has a wall thickness of 5 μm to 30 μm, more particularly 10 μm to 20 μm. The wall thickness range of the outer film must be carefully selected, as it is necessary to ensure an adequate property profile consisting of flexibility and strength of the film.

[0019] In one preferred embodiment, the multilayer gas barrier film is characterized by a sixth surface in contact with the ambient atmosphere, and the film in this embodiment is configured such that no additional layers are required to provide the overall property profile.

[0020] According to one embodiment of the present invention, the multilayer gas barrier film has a carbon dioxide diffusion rate of 20 cm 3 / m 2 *d*bar. In connection with experiments related to the present invention, it has been found that the selection of a specific layer order, particularly the polymer of the intermediate film using a polymer with an ester bond, is important for achieving a film with low carbon dioxide diffusivity. In particular, when the drug solution contains a solid and a solution with a carbonate-containing substance, low carbon dioxide diffusivity is important for sufficient stability of the drug solution.

[0021] According to a second aspect, the object of the present invention is achieved by realizing a bag for containing a medicinal liquid, comprising a multilayer gas barrier film according to the first aspect of the present invention. Such a bag may be formed, for example, from two film sections and provided with a peripheral welded seam. Alternatively, a flat film may be used. The use of a tubular film may be preferred, particularly when high hygiene requirements are imposed on the film. A tubular film may be produced, particularly when high transparency is required, using water cooling. Thus, the bag according to the second aspect of the present invention is preferably characterized in that the bag comprises a welded seam. In this case, a temperature is introduced into these film sections, for example, in the peripheral region using a welding device, to such an extent that the inner film of both film sections melts. By joining these film sections, the polymer molecules of the inner film can be bonded to each other, for example, by intertwining. The aim here is to achieve a welded seam strength such that a stable bag is formed, leading to reliable storage of medical liquids, for example, without the possibility of the welded seam opening.

[0022] A further embodiment of the second aspect of the invention is characterized in that the bag comprises a peel seam. Peel seams can be produced reliably, in particular, when the welding is carried out in a manner similar to, for example, a strong welding of the bag periphery, but the temperature and exposure time during welding are reduced to such an extent that there is only a relatively weak entanglement of the molecules and therefore the welded seam is peelable. The presence of strong seams and peel seams alongside each other is particularly beneficial for the production of multi-compartment bags using the film of the invention. DETAILED DESCRIPTION OF THE INVENTION

[0023] [Example] Example 1: Film Preparation 1. Preparation of Polyolefin Film The polyolefin film was produced as a three-layer film by tube extrusion, with water cooling to ensure sufficient transparency. The outer layer was a PP homopolymer. The layer thickness was 15 μm. The middle layer consisted of a 145 μm PP / TPE blend. The inner layer consisted of a further PP / TPE blend with an increased TPE content. The TPE used was SEBS. The total thickness of the polyolefin film was 180 μm. This film is particularly suitable for producing welded seams with various strengths. Thus, a multi-chamber bag can be realized by providing an inner pulley system with a low tear strength, while the outer area of ​​the bag can be made particularly tear-resistant by high-strength welding.

[0024] 2. Preparation of PA Film The polyamide film made from polyamide 6 was produced as a cast film by biaxial stretching. The layer thickness was 15 μm.

[0025] 3. Preparation of PET / SiOx Film Biaxially stretched cast films of PET or PET / PEN with a layer thickness of 12 μm were used. The SiOx layer was deposited by electron beam evaporation, and the inorganic layer had a thickness of around 50 nm. The preparation of this layer is described in more detail in German Patent Publication No. 102012018525.

[0026] 4. Fabrication of multilayer films by lamination An outer layer of polyolefin film (composed of polypropylene) was wetted with a solvent-based polyurethane adhesive and this layer was subjected to primary drying in a heated tunnel. A PET-SiOx layer was laminated onto this layer using a roller laminator. This laminate was followed by the addition of an additional layer of polyurethane adhesive and further primary drying. A PA film was laminated onto this layer.

[0027] 5. Trimming After the lamination process, the composite film was edge-trimmed in a roll cutter and cut to size.

[0028] Comparative Example 1: Film Preparation A multilayer gas barrier film was prepared similarly to Example 1, with the following exceptions: An outer layer of polyolefin film (composed of polypropylene) was wetted with a solvent-based polyurethane adhesive, and this layer was subjected to primary drying in a heated tunnel. A PA6 layer was laminated to this layer using a roller laminator. This stack was followed by the addition of an additional layer of polyurethane adhesive and further primary drying. A PET-SiOx film was laminated onto this layer. In this case, the SiOx layer was in contact with the adhesive layer.

[0029] Comparative Example 2: Film Preparation The polyolefin film and PET / SiOx film described in Example 1 were used. The outer layer of the polyolefin film (composed of polypropylene) was wetted with a solvent-based polyurethane adhesive and pre-dried in a heating tunnel. A PET-SiOx layer was laminated onto this film in a roller laminator.

[0030] Dissolution experiment Solutions deemed suitable for performing peritoneal dialysis were prepared with the following concentrations: TIFF2025533128000001.tif52143 *Aluminum content was determined by the known method of ICP-mass spectrometry. Bags were made from each of the above films by edge film welding. A filling tube was inserted into the upper region and tightly welded, as in the case of the mass-produced bag available from Fresenius Medical Care under the name "sleep safe BicaVera 5000ml".

[0031] A bag was made with the same dimensions as a commercially available bag and filled with 5 liters of the above solution.

[0032] The bags were then storage tested at 40°C and <25% relative humidity for 3 months.

[0033] The solution was analyzed by gas chromatography for the concentration of dissolved caprolactam.

[0034] The conditions for gas chromatography / MS were as follows: Table 1. Examples of appropriate instrument settings TIFF2025533128000002.tif130143 For all samples, the blank and calibration solutions were extracted into chloroform, and then each chloroform solution was analyzed. A blank value was determined to reduce the influence of any impurities and analytical inaccuracies. Using each calibration solution, a calibration curve was constructed by linear regression, which allowed the concentration of the sample solution to be determined. The retention time of ε-caprolactam under these conditions was around 6.3 minutes. The target ion used was an ion with a mass of 113.0 g / mol, and the verification ions used were ions with masses of 55.0 g / mol and 56.0 g / mol.

[0035] result TIFF2025533128000003.tif31141

[0036] Gas barrier properties: CO2 permeability is measured at 23°C and 0% relative humidity using a DIN 53380-4 test meter on film sections previously sterilized in steam at 120°C for 20 minutes. All films are sterilized in a 20cm 3 / m 2 It had a permeability below *d*bar and was therefore suitable for containing hydrogen carbonate-containing solutions.

[0037] Mechanical properties: Tensile tests were carried out in each case according to DIN EN ISO 527-Part 3, type 2 specimens with a width of 15 mm. Samples were removed from the films using a corresponding punch. Measurements were carried out at 23°C and an atmospheric humidity of 40-60%. The test speed was 1 mm per minute. The elastic modulus was determined; the target values ​​for the elastic modulus in the direction of production and transverse to it were in each case 350 MPa or higher. The results were as follows: TIFF2025533128000004.tif26141

[0038] Additionally, a drop test was carried out on the bags described above using mass-produced packages of bags from the product "Sleep Safe BicaVera 5000ml". The packages were fixed at a height of 60 cm and then dropped horizontally onto a solid substrate from a predetermined height. Ten samples per example were used to determine the percentage of defects (leaks) that occurred. Prior to the experiment, the samples were allowed to cool to 5°C. The experiment itself was carried out less than two minutes after removal from the conditioning chamber.

[0039] In the case of Comparative Example 2, leakage occurred after the drop test in 80% of the experiments, and in the cases of Example 1 and Comparative Example 1, there was no leakage after a drop height of 60 cm.

[0040] Compared to the prior art, the illustrative embodiments exhibit outstanding mechanical robustness combined with extremely low elution values ​​for residual monomers, making the embodiments according to the invention particularly suitable for containing medicinal fluids, more particularly dialysis fluids, and even more particularly dialysis fluids for peritoneal dialysis.

Claims

1. 1. A multi-layer gas barrier film for containing a chemical solution, comprising: an inner film having a first surface in contact with the medicament and a second surface in contact with the first adhesive; an intermediate film having a third surface in contact with the first adhesive and a fourth surface in contact with the second adhesive; an outer film having a fifth surface in contact with the second adhesive and a sixth surface; 1. A multilayer gas barrier film, wherein the inner film comprises an olefin-based polymer having a glass transition temperature below 10°C and a melting point above 130°C, the intermediate film comprises a polymer having an ester bond, a glass transition temperature above 35°C and a melting point above 150°C, and also comprises an inorganic gas barrier material, and the outer film comprises a polymer having an amide bond.

2. 2. The multilayer gas barrier film of claim 1, wherein the polymer having the amide bond has a glass transition temperature of 60°C to 100°C in a dry state and 20°C to 60°C in a water-saturated state, and a melting point higher than 200°C.

3. 3. The multilayer gas barrier film according to claim 1, wherein the polymer having the amide bond has a melting point lower than 250°C.

4. 4. The multilayer gas barrier film according to claim 1, wherein the polymer having an amide bond is an aliphatic polyamide.

5. 2. The multilayer gas barrier film of claim 1, wherein the intermediate film having ester bonds has an inorganic gas barrier layer on at least one surface of the polymer, and the third and fourth surfaces are formed by the inorganic layer.

6. 6. The multilayer gas barrier film of claim 5, wherein the inorganic layer comprises particles of SiOx.

7. 7. The multilayer gas barrier film of claim 1, wherein the intermediate film comprises polyethylene terephthalate or polyethylene naphthalate.

8. 8. The multilayer gas barrier film of claim 1, wherein the multilayer film does not contain a silane coupling agent.

9. 9. The multilayer gas barrier film of claim 1, wherein the polymer of the outer film comprises polyamide 6.

10. 10. The multilayer gas barrier film of claim 9, wherein the amount of caprolactam leached is less than 1 mg / l, preferably less than 0.1 mg / l, as determined by the method set forth in the specification.

11. 11. The multilayer gas barrier film of claim 1, wherein the inner film has a wall thickness of from 100 μm to 250 μm.

12. 12. The multilayer gas barrier film of claim 1, wherein the intermediate film has a wall thickness of from 5 μm to 30 μm.

13. 13. The multilayer gas barrier film of claim 1, wherein the outer film has a wall thickness of from 5 μm to 30 μm.

14. 14. The multilayer gas barrier film of claim 1, wherein the sixth surface is in contact with the ambient atmosphere.

15. The diffusion of carbon dioxide through the film was 20 cm 3 / m 2 15. The multilayer gas barrier film of claim 1, wherein the gas barrier strength is less than *d*bar.

16. A bag for containing a chemical solution, comprising the multilayer gas barrier film according to any one of claims 1 to 15.

17. 17. The bag of claim 16, wherein the bag comprises a welded seam.

18. 18. The bag of claim 16 or 17, wherein the bag comprises a peel seam.

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