Multilayer gas barrier film and pouch

Abstract

A multilayer gas barrier film for containing a medical fluid, comprising: an inner film having a first surface and a second surface, the first surface being in contact with the fluid and the second surface being in contact with a first adhesive; an intermediate film having a third surface and a fourth surface, the third surface being in contact with the first adhesive and the fourth surface being in contact with the second adhesive; and an outer film having a fifth surface and a sixth surface, the fifth surface being in contact with the second adhesive, where the inner film includes an olefin polymer having a glass transition point of less than 10 DEG C and a melting point of more than 130 DEG C, and the intermediate film includes a polymer having an ester bond and a glass transition point of more than 35 DEG C and a melting point of more than 150 DEG C, and the intermediate film includes an inorganic gas barrier material, and the outer film includes a polymer having an amide bond.

Description

Technical Field

[0001] The present invention relates to a multilayer gas barrier film for containing medical fluids. In addition, the present invention also relates to a bag for containing medical fluids, comprising the multilayer gas barrier film. Background Art

[0002] For example, when providing bicarbonate-buffered medical fluids, in particular for peritoneal dialysis, acute dialysis and dialysate for the treatment of chronic renal failure by hemodialysis, gas barrier films and gas barrier bags are required. For this reason, it is particularly required that such gas barrier bags have a low carbon dioxide permeation tendency. In addition, such gas barrier bags may also be suitable for accommodating enteral or parenteral nutrition solutions and suspensions.

[0003] For example, conventional gas barrier films and bags are known from DE 10 201 201 8 525 A. In this document, a polyester or polyamide film is coated with a ceramic coating material and the coated surface is subsequently laminated with a polyolefin film without any adhesive being used to bond the two films. The lamination strength of films produced in this way and the tear strength of multilayer films are limited. Furthermore, the production of seams known as tear seams, which are introduced into multilayer bags in order to accommodate different solutions in the bag and are pulled apart before the solutions are used to allow the solutions to mix in the bag, is more difficult.

[0004] EP0760283A describes a multilayer film comprising an inorganic SiO 2 The film comprises a polyester or polyamide substrate having a second barrier layer made of polyvinyl chloride (PVC) or a similar material. It is said that the inorganic layer is treated with salt water to ensure that the barrier film is in contact with the inorganic SiO 2 The multilayer films exhibit good water and oxygen barrier properties, but may not be mechanically stable enough to reliably store medical fluids. Furthermore, such films are difficult to weld and the resulting weld strength may be low. Depending on the layer sequence, these films also exhibit poor values ​​for the leachability of, for example, residual monomer components such as caprolactam.

[0005] EP0792846B describes a further composite system which provides for coating of the base film with so-called organic ceramics, i.e. organic-inorganic hybrid layers. However, such production processes are costly and inconvenient for producing gas barrier films, since they require the use of a process known as sol-gel, which is incompatible with efficient large-scale film coating production. Furthermore, it is difficult to provide suitable gas barrier properties, especially for carbon dioxide.

[0006] EP1028994B1 describes a two-layer membrane comprising an oriented polyamide membrane coated with an inorganic silicon oxide layer and a sealing layer. Such membranes have a limited ability to retain residual monomers and may have little mechanical robustness.

[0007] Purpose of the Invention

[0008] The object on which the present invention is based is therefore to reduce the disadvantages of the prior art. In particular, the object of the present invention is to ensure a membrane with stable mechanical properties, which has a low transfer of residual monomers and other undesirable substances to the medical fluid. Another object of the present invention is to provide a bag comprising the membrane according to the invention, which reduces the disadvantages of the prior art. Summary of the invention

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

[0010] Such medical fluids may be a solution, more specifically an aqueous solution, which may optionally include ionic and / or non-ionic water-soluble components; further, in particular, the medical fluid may include a carbonic acid component. Such multilayer films are also preferably used for medical fluids that react sensitively to the infiltration of atmospheric carbon dioxide into the fluid. In the case of containing carbonate or bicarbonate containing solutions, it is also desirable to minimize the loss of carbonate or bicarbonate ions in the solution.

[0011] This multilayer film exhibits good mechanical stability, thereby ensuring trouble-free storage of medical fluids for a relatively long period of time. In particular, when the bag is handled under strict conditions, such as in a hospital, the bag will not be mechanically damaged or, for example, torn. In addition, it can be ensured that residual monomers present in polymers, especially those with amide bonds, will not diffuse in large quantities through the multilayer film and enter the medical fluid. In addition, it is ensured that the diffusivity of carbon dioxide through the multilayer gas barrier film is particularly low. Since the inner surface includes olefin polymers, it is particularly easy to set a tear seam on the film. The production of the tear seam can be simply completed by welding an area at a specific temperature, so that on the one hand, the multilayer film can be processed into a multi-chamber bag with different medical fluids, and on the other hand, the tear seam can be torn before using the medical fluids in each chamber, so that the mixing of different medical fluids can be achieved shortly before use. This is basically ideal when the medical fluid has a long storage life as a separate solution, but has only limited preservation characteristics after mixing. In addition, olefin polymers are physiologically harmless to a certain extent, so olefin polymers are preferably directly in contact with medical fluids. This multi-chamber bag is particularly used to accommodate medical dialysate, particularly dialysate for peritoneal dialysis.

[0012] In one embodiment, the multilayer gas barrier film is characterized in that the polymer having amide bonds has a glass transition point of 60 to 100°C in a dry state, and / or a glass transition point of 20 to 60°C in a water-saturated state, and a melting point greater than 200°C. Particularly suitable for providing a multilayer gas barrier film is a hygroscopic polyamide, characterized in that the glass transition point is lowered by absorbing water after film extrusion. Before processing into a film, the polyamide material must be fully dried to a residual moisture content of less than 0.1%. After processing into a multilayer gas barrier film and producing a bag for containing medical fluids, especially aqueous fluids, the polymer is able to absorb moisture until saturated, thereby obtaining ideal flexibility and strength mechanical properties. Examples of such polyamides include polyamide 6, polyamide 4.6 or 6.6. The glass transition point here is determined using a differential scanning calorimetry DSC method, as shown in the following description. Particularly suitable polyamides have a melting point below 250°C. The polyamide is preferably an aliphatic polyamide. A particularly preferred polyamide is polyamide 6, since it is widely available and inexpensive and has a particularly preferred property profile with regard to mechanical properties.

[0013] According to a refinement of the present 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 the third or fourth surface is formed of an inorganic layer.

[0014] Such films with ester bonds can be produced industrially: a corresponding production method is described in DE 10 2012 018 525 A. It is important that the inorganic gas barrier layer can be applied particularly effectively to the film with ester bonds, so that good adhesion strength is achieved. In this context, it is particularly important that the polymer with ester bonds has a particularly good diffusion barrier effect for carbon dioxide on the one hand, and that the inorganic layer generally has a good barrier effect for all gases such as water vapor, oxygen and carbon dioxide on the other hand.

[0015] In a particular embodiment, the middle film of the multilayer gas barrier film has SiOx inorganic layer particles. These particles can be easily produced according to DE102012018525A and provide particularly good adhesion strength on polymers with ester bonds and also have good gas barrier properties.

[0016] In one embodiment of the present invention, the multilayer gas barrier film is characterized in that the intermediate film comprises polyethylene terephthalate or polyethylene naphthalate or a mixture of these two polymers. These polymers have high mechanical robustness, are easy to extrude into films, and have particularly good performance in carbon dioxide diffusion. Polyethylene terephthalate is particularly preferred because it can provide good adhesion to the inorganic layer.

[0017] The multilayer gas barrier film is preferably characterized in that the multilayer film does not contain a silane coupling agent. Although such silane coupling agents can indeed be used to provide effective composite bonding between an inorganic layer and, for example, a polyolefin layer, such embodiments are expensive and inconvenient to develop and produce. For example, before reacting with the inorganic particles, the silane coupling agent must be hydrolyzed, a process that is costly and inconvenient, and also produces unwanted alcohols, such as methanol, which may be harmful, particularly if methanol enters the medical fluid. After the silane is hydrolyzed, the silanol also needs to be coupled with the inorganic particles, which is a relatively slow reaction. In addition, from a large number of silanes, the most suitable silane must first be selected, which depends on the different film layer sequences of the multilayer film, which is very expensive and inconvenient.

[0018] According to one embodiment, the multilayer gas barrier film is characterized in that the polymer of the outer film comprises polyamide 6. The multilayer gas barrier film is particularly preferably characterized in that the amount of caprolactam leaching measured by the method described in the description is less than 1 mg / l, preferably less than 0.1 mg / l. Depending on the raw materials, polyamides may contain a higher content of caprolactam in the form of residual monomer content, which is a disadvantage because this residual monomer content may be transferred to the medical fluid. This is particularly likely to occur if the bag for containing aqueous medical fluids is already made of a multilayer gas barrier film. By means of the arrangement according to the invention, it is possible to prevent caprolactam from being transferred to the medical fluid at an impermissibly high proportion.

[0019] According to one embodiment, the multilayer gas barrier film is characterized in that the inner film has a wall thickness of 100 to 250 μm, more particularly a wall thickness of 150 to 200 μm. The wall thickness range is mainly determined by the sufficient strength required for the inner film and the entire film, but the minimum and maximum wall thicknesses are also determined by the welding requirements generated when the film is processed into a bag for containing medical fluids. In particular, if high-strength welds and tear seams are to be present at the same time, as found during the research of the present invention, it is preferred to comply with a specific wall thickness range.

[0020] According to one embodiment, the multilayer gas barrier film is characterized in that the intermediate film has a wall thickness of 5 to 30 μm, more particularly 5 to 20 μm. In addition to providing sufficiently high strength, the polymer of the intermediate film also acts as a gas barrier to water vapor, oxygen and especially carbon dioxide. Careful selection of the wall thickness is essential for the target performance curve consisting of strength and diffusion barrier properties. If the intermediate film is coated with inorganic particles, the wall thickness specifications apply to the intermediate film after coating.

[0021] According to another embodiment, the multilayer gas barrier film is characterized in that the outer film has a wall thickness of 5 to 30 μm, more particularly 10 to 20 μm. The wall thickness range of the outer film must be carefully selected to ensure that the performance curve consisting of film flexibility and strength is sufficiently good.

[0022] In a preferred embodiment, the multilayer gas barrier film is characterized in that the sixth surface is in contact with the surrounding atmosphere. The film in the context of this embodiment is configured so that no additional layers are required to provide the overall performance profile.

[0023] According to an improved solution of the present invention, the multilayer gas barrier film is characterized in that the diffusion rate of carbon dioxide through the film is less than 20 cm 3 / m 2 *d*bar. In the experiments of the present invention it was found that a specific layer sequence, in particular the choice of polymer for the intermediate membrane using a polymer having ester bonds, is important for providing a membrane with low carbon dioxide diffusion. Low carbon dioxide diffusion is important for sufficient stability of the medical fluid, in particular if the medical fluid comprises a solution of solids and carbonate-containing substances.

[0024] According to a second aspect, the object of the present invention is achieved by providing a bag for containing medical fluids, the bag comprising a multilayer gas barrier film according to the first aspect of the present invention. Such a bag is formed, for example, by two film parts, and a weld is provided at the peripheral edge. It is preferred to use a flat film here. It may also be preferred to use a tubular film, especially when the hygienic requirements for the film are increased. The tubular film is particularly preferably produced using water cooling, especially if the film needs to have high transparency. Therefore, the bag according to the second aspect of the present invention is preferably characterized in that the bag includes a weld. In this case, for example, a certain degree of temperature is introduced into the film part in the peripheral edge area using a welding device, so that the inner film of the two film parts melts. By connecting the film parts, the molecules of the inner film polymer can be connected to each other, for example, by entanglement. The purpose here is to obtain such a weld strength to form a stable bag, so that the medical fluid can be reliably stored without the possibility of, for example, weld cracking.

[0025] Another embodiment of the second aspect of the invention is characterized in that the bag comprises a tear seam. The tear seam can be reliably produced, in particular when the welding is carried out in a similar manner to the strong welding of, for example, the surrounding bag edge, but the temperature and exposure time during welding are reduced to such an extent that the molecular entanglement is relatively weak, so that the weld produced is peelable. In particular, the coexistence of a strong seam and a tear seam is advantageous for the production of multi-chamber bags with the film of the invention. DETAILED DESCRIPTION

[0026] Example 1: Film production

[0027] 1. Production of polyolefin films:

[0028] The polyolefin film produced by the tube film extrusion process is a three-layer film with water cooling to achieve sufficient transparency. The outer layer uses a polypropylene homopolymer. The layer thickness is 15 microns. The middle layer consists of a polypropylene / thermoplastic elastomer TPE blend of 145 microns. The inner layer consists of another polypropylene / TPE blend with an increased TPE content. The TPE used is a styrene-ethylene-butylene-styrene block copolymer SEBS. The total thickness of the polyolefin film is 180 microns.

[0029] The film is particularly suitable for making welds with different strengths. Thus the outer area of ​​the bag can be made particularly tear-resistant by strong welds, while at the same time a multi-chamber bag can be provided by providing an inner tear seam with low tear strength.

[0030] 2.PA film production:

[0031] The polyamide film made of polyamide 6 was produced as a cast film with biaxial stretching. The layer thickness was 15 μm.

[0032] 3. Production of PET / SiOx film:

[0033] A PET cast film or a biaxially stretched PET / PEN film with a thickness of 12 μm is used. The SiOx layer is applied by electron beam evaporation, and the thickness of the inorganic layer is about 50 nm. The production of this layer is described in more detail in DE 10 2012 018 525 A.

[0034] 4. Production of multi-layer films by lamination:

[0035] The outer layer of the polyolefin film - consisting of polypropylene - was moistened with a solvent-based polyurethane adhesive and initially dried in a heating tunnel. The PET-SiOx layer was laminated onto it in a roll laminator.

[0036] Next, another layer of polyurethane adhesive is applied and further preliminarily dried. The PA film is laminated onto this layer.

[0037] 5. Trimming:

[0038] The composite film after the lamination process is edge trimmed in a roll-to-slitter and then the film is cut into the required size.

[0039] Comparative Example 1: Film Production

[0040] The multilayer gas barrier film was manufactured as in Example 1 with the following differences:

[0041] The outer layer of the polyolefin film - consisting of polypropylene - is wetted with a solvent-based polyurethane adhesive and the layer is initially dried in a heating tunnel. The PA6 layer is laminated onto it in a roll laminator.

[0042] Then another layer of polyurethane adhesive is applied and further preliminary dried. The PET-SiOx film is laminated onto this layer. Here, the SiOx layer is in contact with the adhesive layer.

[0043] Comparative Example 2: Film Production

[0044] The polyolefin film and PET / SiOx film produced according to Example 1 were used. The outer layer of the polyolefin film - consisting of polypropylene - was wetted with a solvent-based polyurethane adhesive and preliminarily dried in a heating tunnel. The PET-SiOx layer was laminated to this film in a roll laminator.

[0045] Elution experiment

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

[0047] substance Numeric unit sodium 134 mmol / l calcium 1.25 mmol / l magnesium 0.5 mmol / l chlorine 103.5 mmol / l Bicarbonate 34 mmol / l D-Glucose 15 g / l pH 7.05 / aluminum* <10 μg / l

[0048] *The aluminum content is determined by the known ICP-mass spectrometry method.

[0049] The bags are produced from each film by firmly welding the edges. In the upper area, the filling tube is inserted and tightly welded, just like the bags that Fresenius Medical Care mass-produces under the name Sleep Safe Bica Vera 5000 ml.

[0050] A bag was produced in the same size as a commercially available bag. The bag was filled with 5 L of the above solution.

[0051] The bags were then subjected to a storage test at 40°C and relative humidity <25% for 3 months.

[0052] The concentration of caprolactam in the solution was analyzed by gas chromatography.

[0053] The conditions used for gas chromatography / mass spectrometry MS were as follows:

[0054] Table 1 Appropriate instrument settings, e.g.

[0055]

[0056] All samples, blank solutions and calibration solutions were extracted with chloroform and the corresponding chloroform solutions were then sent for analysis. The blank value must be determined to reduce the influence of any impurities and inaccuracies in the analysis. Using the corresponding calibration solutions, a calibration curve was generated by linear regression and the concentration of the sample solutions was determined. Under these conditions, the retention time of ε-caprolactam was approximately 6.3 minutes. The target ion used was the ion with a mass-to-charge ratio of 113.0 g / mol, and the verification ions used were the ions with a mass-to-charge ratio of 55.0 and 56.0 g / mol.

[0057] result

[0058]

[0059] Gas barrier properties:

[0060] The carbon dioxide permeability is measured at 23°C and 0% relative humidity using a DIN 53380-4 test instrument on membrane sections previously sterilized in steam at 120°C for 20 minutes. All membranes have a carbon dioxide permeability of less than 20 cm 3 / m 2 *d*bar permeability and is therefore suitable for containing solutions containing bicarbonate. Mechanical properties:

[0061] Tensile tests were carried out in each case according to DIN EN ISO 527-Part 3, test specimen type 2 with a width of 15 mm. The specimens were removed from the film with a corresponding punch. The measurements were carried out at 23°C and an atmospheric humidity of 40-60%. The test speed was 1 mm per minute. Determination of the elastic modulus - the target values ​​for the elastic modulus in the production direction and in the direction orthogonal thereto were in each case 350 MPa or more. The results are as follows:

[0062] sample Reach or exceed target value Example 1 conform to Comparative Example 1 conform to Comparative Example 2 Not Compliant

[0063] In addition, the bags were drop tested using mass-produced bag packaging of the product "Sleep Safe BicaVera 5000ml" from Fresenius Medical Care. The packaging was fixed at a height of 60 cm and then dropped flat onto a solid substrate from a predetermined height. Ten samples were used per example and the percentage of defects (leaks) was determined. Before the experiment, each sample was individually brought to a temperature of 5°C. The experiment was carried out at room temperature within less than 2 minutes after being taken out of the conditioning chamber.

[0064] In Comparative Example 2, 80% of the experiments showed leakage after the drop test, while in Example 1 and Comparative Example 1, no leakage occurred at a drop height of 60 cm.

[0065] Compared with the prior art, this exemplary embodiment excels in mechanical robustness and has extremely low elution values ​​of residual monomers, so the embodiment according to the present invention is particularly suitable for containing medical fluids, more specifically dialysate, and more specifically dialysate for peritoneal dialysis.

Claims

1. A multilayer gas barrier film for containing medical fluids, comprising: an inner membrane having a first surface and a second surface, the first surface being in contact with the fluid and the second surface being in contact with a first adhesive; an intermediate film having a third surface and a fourth surface, the third surface being in contact with the first adhesive and the fourth surface being in contact with the second adhesive; An outer film having a fifth surface and a sixth surface, the fifth surface being in contact with a second adhesive, wherein the inner film comprises an olefin polymer having a glass transition point 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 point higher than 35°C and a melting point higher than 150°C, and the intermediate film comprises an inorganic gas barrier material, and the outer film comprises a polymer having an amide bond.

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

3. The multilayer gas barrier film according to any one of the preceding claims, characterized in that The melting point of the polymer having an amide bond has a melting point lower than 250°C.

4. The multilayer gas barrier film according to any one of the preceding claims, characterized in that The polymer having amide bonds is an aliphatic polyamide.

5. The multilayer gas barrier film according to claim 1, characterized in that The intermediate film having an ester bond has an inorganic gas barrier layer on at least one surface of the polymer, and the third surface or the fourth surface is formed of an inorganic layer.

6. The multilayer gas barrier film according to claim 5, characterized in that The inorganic layer includes SiOx particles.

7. The multilayer gas barrier film according to any one of claims 1 to 6, characterized in that The intermediate film comprises polyethylene terephthalate or polyethylene naphthalate.

8. The multilayer gas barrier film according to any one of the preceding claims, characterized in that The multilayer film does not include a silane coupling agent.

9. The multilayer gas barrier film according to any one of the preceding claims, characterized in that The polymer of the outer membrane comprises polyamide 6.

10. The multilayer gas barrier film according to claim 9, characterized in that The amount of caprolactam leached out measured by the method described in the specification is less than 1 mg / l, preferably less than 0.1 mg / l.

11. The multilayer gas barrier film according to any one of the preceding claims, characterized in that The inner membrane has a wall thickness of 100 μm to 250 μm.

12. The multilayer gas barrier film according to any one of the preceding claims, characterized in that The intermediate film has a wall thickness of 5 μm to 30 μm.

13. The multilayer gas barrier film according to any one of the preceding claims, characterized in that The outer membrane has a wall thickness of 5 μm to 30 μm.

14. The multilayer gas barrier film according to any one of the preceding claims, characterized in that The sixth surface is in contact with the surrounding atmosphere.

15. The multilayer gas barrier film according to any one of the preceding claims, characterized in that The diffusion rate of carbon dioxide through the membrane is less than 20 cm 3 / m 2 *d*bar.

16. A bag for containing medical fluids comprising the multilayer gas barrier film according to any one of the preceding claims.

17. The bag according to claim 16, characterized in that The bag includes a weld.

18. The bag according to claim 16 or 17, characterized in that The bag includes a tear seam.

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