Flexible heat sterilizable non-pvc multilayer film for medical packaging

Abstract

A flexible heat sterilizable multilayer film for medical packaging comprising a) a first polymeric layer (A) comprising an impact-modified polypropylene homopolymer; b) a second polymeric layer (B) comprising: B1) 60-85 wt% of a homogeneous composition (B1) having a melting temperature > 125°C, a density 945-960 kg / m 3 , which consists of B11) 65-85 wt% of an ethylene homopolymer and B12) 15-35 wt% of an ethylene / C4-C 12 alpha-olefin copolymer; B2) 11-30 wt% of a propylene terpolymer; B3) 4-15 wt% of a polyethylene elastomer (ethylene / C4-C 12 alpha-olefin copolymer); c) a central polymeric layer (C) comprising: C1) 61-80 wt% of a propylene terpolymer; C2) 15-25 wt% of a styrene block copolymer elastomer; C3) 5-19 wt% of a polyethylene elastomer.

Description

Technical Field

[0001] This invention relates to heat-sterilizable multilayer films comprising aliphatic polyolefins, methods for producing said films, and the use of said films in the preparation of medical packaging, as well as medical packaging containing said multilayer films. The multilayer film is sterilizable by hot steam and, when used as medical packaging, is characterized by a low likelihood of adsorption of drugs or medical solutions, a temperature-resistant outer layer, and sufficient adhesion between layers. Background Technology

[0002] For many years, multilayer films have had a wide range of applications, not only in the food industry but also in the medical / pharmaceutical industry, such as as primary or secondary packaging materials (overpackaging) for drugs in the form of solution bags, dry concentrates, and tablets.

[0003] Some multilayer films can be processed into flexible packaging, such as bags suitable for packaging and dispensing pharmaceutical solutions. Pharmaceutical solutions packaged in disposable flexible bags made of polyvinyl chloride (PVC) or non-PVC materials, such as infusion solutions for intravenous administration, are currently considered standard practice in the market.

[0004] Resilient PVC materials are harmful to health because they contain plasticizers that can be released again. Therefore, efforts are being made to replace PVC materials with non-PVC materials.

[0005] Flexible medical bags not only need to be able to collapse to ensure complete drainage, but also need to exhibit other performance standards such as transparency, be able to be steam sterilized at 121°C, have sufficient mechanical strength, especially under dynamic loads in the weld area, a good water vapor barrier, load capacity for standard pressure cuff applications such as pressure infusion, and, from a pharmaceutical perspective, have minimal impact on the contents of the bag.

[0006] It has been found that multilayer films with a polyolefin-based layered structure are advantageous for these needs.

[0007] DE-A 10361851 and WO 2020 / 127227 A1 describe a heat-sterilizable three-layer multilayer film for preparing medical bags, wherein the outer layer consists of a polypropylene homopolymer modified with an impact modifier, the middle layer consists of a polypropylene terpolymer modified with an impact modifier, and the inner layer consists of a polypropylene terpolymer and / or a polypropylene copolymer modified with an impact modifier. Suitable impact modifiers include styrene block copolymers (such as SEB) and ethylene / α-olefin copolymers. In the examples, the middle layer of the film consists of 75% by weight of PP terpolymer, 20% by weight of SEBS block copolymer, and 5% by weight of PE plastisol (ethylene / octene copolymer), and the inner layer consists of 85% or 75% by weight of PP terpolymer, 15% or 20% by weight of SEB block copolymer, and 0% or 5% by weight of PE plastisol.

[0008] DE 20320212 A1 describes a heat-sterilizable three-layer multilayer film for medical bags, prepared by a co-extrusion process. In the examples, the outer layer of the film consists of 97% by weight of polypropylene homopolymer and 3% by weight of SEBS block copolymer; the middle layer consists of 80% by weight of EXCELLEN (a heterogeneous copolymer of polypropylene and polyethylene) and 20% by weight of SEBS block copolymer; and the inner layer consists of 75% by weight of PP terpolymer, 20% by weight of SEBS block copolymer, and 5% by weight of PE plasmon.

[0009] KR-A 2010-0101332 discloses a multilayer film with excellent adhesion between its layers, which is prepared by co-extrusion of a polypropylene layer and a polyethylene layer, wherein the polypropylene layer is mixed with polyethylene (40%-50% by weight) or the polyethylene layer is mixed with polypropylene (20%-50% by weight).

[0010] EP-A 2231775 relates to a multilayer film for use as a medical solution container, preferably comprising an outer layer composed of a propylene homopolymer; a middle layer composed of 30%-70% by weight of a propylene-based polymer (such as a propylene-ethylene-butene terpolymer) and 30%-70% by weight of a thermoplastic elastomer (such as SEBS); and an inner layer composed of 50%-70% by weight of a propylene copolymer, 5%-20% by weight of polyethylene (such as HDPE), and 10%-45% by weight of a thermoplastic elastomer (such as SEBS).

[0011] EP-A 0229475 describes a multilayer film for medical containers, preferably a three-layer multilayer film comprising (a) a first (inner) heat-sealable layer, which is composed of a mixture of a propylene copolymer, preferably 40%-70% by weight, an ethylene-propylene copolymer or an ethylene-1-butene copolymer (preferably 5%-15% by weight), and an elastomer (e.g., an ethylene copolymer or a styrene block copolymer), preferably 5%-35% by weight; (b) a second (center) layer, composed of a mixture of (i) polyethylene (HDPE) (50%-90% by weight) and (ii) a modifier; and (c) a third (outer) layer, composed of a mixture of (i) polypropylene and (ii) a modifier.

[0012] JP-A 2007 / 245490 describes a heat-sterilizable multilayer film for use in medical bags, comprising a high-density (0.89-0.93 g / cm³) film. 3 The inner layer consists of a mixture of ethylene / α-olefin copolymer (preferably prepared by a metal catalyst) and HDPE (10%-40% by weight), and the outer layer consists of a propylene polymer.

[0013] US2012 / 0034404 A1 describes a multilayer film for medical packaging (e.g., bags), comprising: an outer layer preferably comprising a propylene homopolymer; a middle layer comprising 10%-60% by weight of a propylene copolymer and 40%-90% by weight of a thermoplastic elastomer; and an inner layer comprising 60%-80% by weight of a propylene copolymer, 10%-30% by weight of polyethylene, and 1%-10% by weight of a thermoplastic elastomer. The polyethylene is preferably a copolymer of ethylene and α-olefin with a melting temperature of 50°C-120°C (e.g., 60°C); preferably, the propylene copolymer is a propylene-ethylene-butene terpolymer. The thermoplastic elastomer used is preferably a hydrogenated styrene block copolymer.

[0014] There is still room for improvement in existing multilayer films, especially in terms of interlayer adhesion and the requirement for steam sterilization at 121°C. Summary of the Invention

[0015] Therefore, the objective of this invention is to provide a flexible, heat-sterilizable multilayer film for medical use, which has good adhesion and impact strength between layers, and is less likely to adsorb drugs or medical solutions on the surface (inner layer) facing the drug or medical solution, and can be processed into a medical container (e.g., a bag) by a simple method.

[0016] This invention provides a heat-sterilizable multilayer film, comprising (and composed of):

[0017] a) A first polymer layer (A) comprising (consisting of) at least one modified by at least one, preferably an impact modifier, preferably a propylene homopolymer;

[0018] b) A second polymer layer (B), comprising (and consisting of):

[0019] B1) Based on (B), a homogeneous composition (=“composite material”) comprising 60%-85% by weight of (B), comprising:

[0020] B11) is based on (B1), a homopolymer of 65%-85% by weight of ethylene, and

[0021] B12) Based on (B1), at least one ethylene copolymer comprising 15%-35% by weight, preferably 20%-30% by weight, wherein the copolymer comprises at least one, preferably one having 4-12, more preferably 4-8, particularly preferably 4-6 carbon atoms, of an α-olefin as a comonomer, preferably selected from: 1-butene, 1-pentene, 1-hexene and 4-methyl-1-pentene, preferably 1-butene;

[0022] Furthermore, the melting temperature of composition (B1) is >125℃, and its density is 945-960 kg / m³. 3 ;

[0023] B2) Based on (B), at least one propylene terpolymer comprising 11%-30% by weight;

[0024] B3) Based on (B), at least one polyethylene elastomer in weight percentage of 4%-15%, wherein the elastomer is a copolymer of ethylene and at least one, preferably one, α-olefin having 4-12, preferably 7-12 carbon atoms;

[0025] c) A central polymer layer (C) located between the first polymer layer (A) and the second polymer layer (B), comprising (especially composing):

[0026] C1) is based on (C), comprising at least one propylene terpolymer in a weight percentage of 61%-80%, preferably 65%-80%;

[0027] C2) Based on (C), at least one styrene block copolymer elastomer comprising 15%-25% by weight;

[0028] C3) is based on (C), comprising 4%-14% by weight, preferably 4%-10% of at least one polyethylene elastomer, which is a copolymer of ethylene and at least one, preferably an α-olefin containing 4-12 carbon atoms.

[0029] In each case, the percentages expressed as a weight percentage add up to 100% of the weight. Detailed Implementation

[0030] In the context of this invention, the structural units of monomers in (co)polymers should be understood as structural units derived from monomers incorporated through polymerization.

[0031] The term "heat-sterilizable" means that the material can be sterilized at a high temperature, preferably by steam sterilization. Sterilization refers to the method of removing live microorganisms from materials and articles. The resulting state of the material and article is called "sterile." In the case of steam sterilization of filled or unfilled medical packaging, hot steam is used, and steam sterilization is usually carried out in an autoclave. This involves heating the medical packaging to 121°C at a pressure of 2 bar in steam, preferably for 20 minutes. The air inside the autoclave is completely replaced by steam.

[0032] The term "multilayer film" refers to a film formed by multiple co-extruded polymer layers of thermoplastic material bonded together in the form of a flowing web or sleeve.

[0033] The term "impact modifier" refers to polymeric materials, such as styrene block copolymer elastomers, polyethylene elastomers, and polypropylene elastomers, which, when mixed in the molten state, increase the impact strength of the polymer surrounding the impact modifier.

[0034] The term "impact strength" refers to the ability of a material to withstand dynamic loads. The Izod impact strength of plastics can be determined under specified conditions according to the standard DIN EN ISO 180:2013-08.

[0035] "Homogeneous composition" should be understood as a composition of substances (components) that are mixed together at the molecular level and together form a single phase.

[0036] "Melting temperature" (softening temperature, T) m It is usually determined by DSC (differential scanning calorimetry).

[0037] "Density" can be determined using a liquid specific gravity bottle according to DIN EN ISO 1183-1 (2019-09) - Method B.

[0038] First polymer layer (A)

[0039] By definition, the first polymer layer (A) of the multilayer film of the present invention is the polymer layer located on the outside of the packaging when the film is processed into packaging, preferably a bag. Therefore, when the film is further processed into packaging, it comes into direct contact with the surface of the welding tool, and thus a higher melting / softening temperature is preferably required, preferably above 125°C, particularly preferably 127°C-150°C, and very particularly preferably 130°C-145°C.

[0040] The first polymer layer (A) comprises at least one, preferably a polypropylene homopolymer, which is modified by at least one, preferably an impact modifier.

[0041] Preferably, the first polymer layer (A) is composed of at least one, more preferably one, polypropylene homopolymer modified by at least one, more preferably one impact modifier.

[0042] More preferably, the first polymer layer (A) comprises a polypropylene homopolymer modified by an impact modifier.

[0043] The first polymer layer (A) comprises (or consists of) at least one, preferably a polypropylene homopolymer (polypropylene), which is typically modified by at least one impact modifier at a weight percentage of 1%-30%, preferably 2%-20%, particularly preferably 2%-10%, especially 3%-5% to improve (low-temperature) impact strength.

[0044] The preparation of polypropylene homopolymers is known. Furthermore, polypropylene homopolymers can be purchased, for example, from LyondellBasell Corporation in the United States.

[0045] Preferably, the first polymer layer (A) comprises (or consists of) a polypropylene homopolymer modified with at least one impact modifier selected from styrene block copolymers, such as styrene-ethylene-butene-styrene block copolymer (SEBS), styrene-ethylene-propylene-styrene block copolymer (SEPS), styrene-ethylene-ethylene-propylene-styrene (SEEPS), styrene-isoprene-styrene block copolymer (SIS), and styrene-butadiene-styrene block copolymer (SBS), preferably SEBS and SEPS, especially SEBS; and / or selected from copolymers of ethylene with at least one α-olefin containing 4-12, preferably 4-8, carbon atoms, such as ethylene-butene copolymer and / or ethylene-octene copolymer.

[0046] Particularly preferably, the first polymer layer (A) comprises (or consists of) 90%-98%, particularly 95%-97% by weight of polypropylene homopolymer and 2%-10%, particularly 3%-5% by weight of styrene block copolymer and / or copolymer of ethylene with at least one α-olefin containing 4-12, preferably 4-8 carbon atoms.

[0047] In a preferred embodiment, the first polymer layer (A) comprises (or consists of) 95%-97% by weight of polypropylene homopolymer and 3%-5% by weight of styrene-ethylene / butene block copolymer.

[0048] The weight specified for the components of the first polymer layer (A) is based on the total weight of the first polymer layer (A).

[0049] Second polymer layer (B)

[0050] By definition, the second polymer layer (B) is the polymer layer located inside the packaging bag when the multilayer film of the present invention is processed into a package, preferably a bag. This polymer layer can tightly seal the package by heat sealing. The second polymer layer (B) of the film needs to be heat-sealed securely with itself and the properly inserted port elements at the lowest possible temperature and the shortest possible welding time, and can be heat-sterilized at temperatures above 121°C. Low welding temperatures are particularly important for minimizing structural stress on the film structure. Therefore, the melting / softening temperature of the second polymer layer (B) is generally above 121°C, preferably 122°C-135°C, particularly preferably 124°C-130°C, but in any case lower than the melting / softening temperature of the first polymer layer (A).

[0051] The second polymer layer (B) of the multilayer thin film according to the present invention comprises (or consists of) components B1), B2) and B3 in the following proportions (based on (B) in each case):

[0052] B1) 60%-85% by weight, preferably 65%-80% by weight, and particularly preferably 72%-78% by weight;

[0053] B2) 11%-30% by weight, preferably 15%-25% by weight, and particularly preferably 17%-22% by weight;

[0054] B3) 4%-15% by weight, preferably 4%-12% by weight, and particularly preferably 5%-10% by weight.

[0055] Component B1)

[0056] Component B1) is used to reduce the tendency of delamination between the second polymer layer (B) and the central polymer layer (C).

[0057] The homogeneous composition (=“composite material”) (B1) comprises:

[0058] B11) is based on (B1), a homopolymer of 65%-85% by weight of ethylene, and

[0059] B12) is based on (B1), comprising at least one of the following at a weight percentage of 15%-35%, preferably 20%-30%, preferably an ethylene copolymer containing at least one, preferably an α-olefin having 4-12, preferably 4-8, particularly preferably 4-6 carbon atoms, as a comonomer, very preferably selected from: 1-butene, 1-pentene, 1-hexene and 4-methyl-1-pentene, preferably 1-butene.

[0060] The homogeneous composition (B1) has a melting temperature >125°C, preferably 130°C-135°C, and a density of 945-960 kg / m³. 3 .

[0061] Ethylene copolymer (B12) contains no other comonomers except for α-olefins with 4-12 carbon atoms.

[0062] Based on (B12), the proportion of olefin comonomers is generally 25%-40% by weight, preferably 30%-37% by weight; based on (B12), the proportion of ethylene is correspondingly 60%-75% by weight, preferably 63%-70% by weight. In each case, the weight proportion is based on the structural units of the monomers incorporated into the ethylene copolymer (B12) through polymerization.

[0063] Preferably, component B1) is a homogeneous composition comprising:

[0064] B11) is based on (B1), a homopolymer of 70%-80% by mass of ethylene, and

[0065] B12) is based on (B1), comprising at least one, preferably an ethylene copolymer, in a mass percentage of 20%-30%, wherein the comonomer contains at least one, preferably an α-olefin, selected from: 1-butene, 1-pentene, 1-hexene and 4-methyl-1-pentene, preferably 1-butene.

[0066] Particularly preferably, component B1) is a homogeneous composition comprising:

[0067] B11) is based on (B1), a homopolymer of 70%-80% by mass of ethylene, and

[0068] B12) is based on (B1), and contains 20%-30% by weight of ethylene-1-butene copolymer.

[0069] In this embodiment, based on (B12), 1-butene accounts for 25%-40% by weight, preferably 30%-37% by weight.

[0070] The ethylene homopolymer (B11) used is typically high-density polyethylene (HDPE), preferably with a density of 950-970 kg / m³. 3 HDPE.

[0071] The preparation of HDPE is known to those skilled in the art.

[0072] In addition, HDPE is commercially available, for example, with a density of 950-970 kg / m³. 3 HDPE is available from Nipolon of Tosoh Co., Ltd. Obtained, or from Borealis HE2581-PH and Bormed HE7541-PH were obtained.

[0073] Ethylene copolymers (B12) are typically copolymerized from ethylene and α-olefin copolymers under a metallocene catalyst.

[0074] Suitable metallocene catalysts are organic compounds of transition metals having multiple ligands (the number of which corresponds to the valence of the transition metal) coordinated to the transition metal, wherein at least one ligand is a cyclopentadienyl radical. The transition metal is preferably selected from Zr, Ti, Hf, V, Nb, Tn, and Cr, preferably Zr or Hf, and very particularly preferably Zr.

[0075] Zr or Hf metallocene catalysts with two cyclopentadienyl radicals are preferred.

[0076] Special preference is given to metallocene catalysts bis(n-butylcyclopentadienyl)zirconium dichloride.

[0077] Ethylene copolymer (B12) was prepared using the aforementioned metallocene catalyst as an ionic complex. This ionic complex can be obtained by reacting the metallocene catalyst with organically modified alumina. The alumina used can be any commonly used clay material; sphagnum molybdenum, montmorillonite, and montmorillonite are preferred.

[0078] Organically modified alumina is obtained by reacting alumina with an aliphatic salt. Examples of such aliphatic salts include: N,N-dimethyldecylamine hydrochloride, N,N-dimethyldodecylamine hydrochloride, N,N-dimethyltetradecylamine hydrochloride, N,N-dimethylhexadecylamine hydrochloride, N,N-dimethyloctadecylamine hydrochloride, N,N-dimethyltimoethylenediamine hydrochloride, N,N-dimethyltimoethylenediamine hydrofluoride, N,N-dimethyltimoethylenediamine hydrobromide, and N,N-dimethyltimoethylenediamine hydroiodide; preferably, N,N-dimethyltimoethylenediamine hydrochloride.

[0079] Preferably, ethylene copolymer B12 can also be prepared by using an organoaluminum compound, preferably triisobutylaluminum, as a co-catalyst.

[0080] Ethylene copolymer (B12) can be prepared with a metallocene catalyst, for example by slurry method, solution method or in the gas phase.

[0081] For example, JP-A2019 / 111805 and JP-A2019 / 167430 describe methods for preparing ethylene α-olefin copolymers using such metallocene catalysts.

[0082] Ethylene copolymer B12 is a high-density ethylene copolymer. Preferably, the density of ethylene copolymer B12 is 945-960 kg / m³. 3 .

[0083] Component B2)

[0084] Component B2) is at least one, preferably a propylene terpolymer.

[0085] The term "terpolymer" refers to a copolymer made from three different monomers.

[0086] The term "propylene terpolymer" refers to a polypropylene molecular chain modified by two other comonomers during the polymerization process. Preferred other comonomers are ethylene and / or at least one C4-C copolymer. 12 α-olefins, preferably C4-C8 α-olefins, particularly preferably ethylene and a C4-C8 α-olefin, and very particularly preferably ethylene and 1-butene.

[0087] In each case, based on (B2), the proportion of ethylene is preferably 1%-4% by weight, and the proportion of at least one C4-C8 α-olefin, particularly 1-butene, is preferably 9%-12% by weight. In each case, the weight proportion is based on the structural units of the monomer incorporated into the terpolymer (B2) through polymerization.

[0088] A propylene terpolymer (B2) composed of structural units of propylene, ethylene and butene is particularly preferred.

[0089] The preparation of propylene terpolymers is known. Furthermore, suitable propylene terpolymers are commercially available, for example, from Borealis in Austria.

[0090] Component B3)

[0091] Component B3) is at least one, preferably one, polyethylene elastomer, which is a copolymer of ethylene and at least one, preferably one, α-olefin having 4-12, preferably 7-12, particularly preferably 8 carbon atoms.

[0092] The density of the ethylene / α-olefin copolymer B3 is preferably 600-950 kg / m³. 3 750-900 kg / m³ is particularly preferred. 3 .

[0093] Based on (B3), the structural units of the α-olefin incorporated by polymerization account for more than 8% by weight, preferably more than 10% by weight, and particularly 20%-30% by weight.

[0094] Preferably, component B3) is an ethylene-1-octene copolymer.

[0095] Suitable polyethylene elastomers are available for purchase, for example from Dow Chemical Company.

[0096] Preferably, the second polymer layer (B) according to the invention comprises (or consists of) a homogeneous composition (component B1) consisting of 70%-80% by weight of high-density polyethylene (B11) and 20%-30% by weight of ethylene-1-butene copolymer (B12); a propylene terpolymer (component B2) consisting of structural units of propylene, ethylene and butene (component B2); and an ethylene-1-octene copolymer (component B3).

[0097] Particularly preferably, the second polymer layer (B) according to the invention comprises (or is composed of): 65%-80%, preferably 72%-78% by weight, of a homogeneous composition (component B1) consisting of 70%-80% by weight of high-density polyethylene (B11) and 20%-30% by weight of ethylene-1-butene copolymer (B12); 15%-25%, preferably 17%-22% by weight of a terpolymer (component B2) consisting of structural units of propylene, ethylene and butene (component B2); and 4%-12%, preferably 5%-10% by weight of ethylene-1-octene copolymer (component B3).

[0098] The weights specified for components B1), B2), and B3) of the second polymer layer (B) are all based on the total weight of the second polymer layer (B).

[0099] Central polymer layer (C)

[0100] The central polymer layer (C) accounts for the largest proportion of the mass of the multilayer film (at least 50% by weight), preferably 60%-95% by weight, particularly preferably 70%-90% by weight, and very particularly preferably 75%-85% by weight of the entire multilayer film, in order to improve the impact strength of the overall structure.

[0101] The central polymer layer (C) of the multilayer thin film according to the invention comprises (or consists of) components C1), C2) and C3) in the following proportions (based on (C) in each case):

[0102] C1) 61%-80% by weight, preferably 65%-75% by weight;

[0103] C2) 15%-25% by weight, preferably 17%-22% by weight;

[0104] C3) weight percentage 5%-19%, preferably 8%-17%.

[0105] Component C1)

[0106] Component C1) is at least one, preferably a propylene terpolymer. The propylene terpolymer C1) is defined the same as component B2), therefore reference can be made to the relevant discussion of component B2).

[0107] Component C2)

[0108] Component C2) is at least one, preferably a styrene block copolymer (SBC) elastomer.

[0109] The term "styrene block copolymer elastomer" refers to a synthetic thermoplastic elastomer based on styrene block copolymers used for impact modification of polypropylene.

[0110] The at least one styrene block copolymer (SBC) elastomer (C2) is preferably selected from: styrene-ethylene-butene-styrene block copolymer (SEBS), styrene-ethylene-ethylene-propylene-styrene block copolymer (SEPS), styrene-ethylene-ethylene-propylene-styrene block copolymer (SEEPS), styrene-isoprene-styrene block copolymer (SIS), and styrene-butadiene-styrene block copolymer (SBS), with SEBS and SEPS being particularly preferred, especially SEBS.

[0111] Suitable styrene block copolymer (SBC) elastomers (C2) are commercially available, for example from Asahi Kasei in Japan.

[0112] The styrene block copolymer (SBC) elastomer can also be partially replaced by one or more thermoplastic olefin elastomers (TPE-O) (TPE-O accounts for no more than 45% by weight, preferably 20%-30% by weight).

[0113] Preferably, component C2) is a styrene block copolymer (SBC) elastomer that does not contain any proportion of thermoplastic olefin elastomer.

[0114] Component C3)

[0115] Component C3) is at least one, preferably a polyethylene elastomer, which is a copolymer of ethylene and an α-olefin containing 4-12, preferably 4-8, carbon atoms.

[0116] The density of the ethylene / α-olefin copolymer (C3) is preferably 440-860 kg / m³. 3 .

[0117] Based on (C3), the structural units of the α-olefin incorporated by polymerization account for more than 8% by weight, preferably more than 10% by weight, and particularly 20%-30% by weight.

[0118] Preferably, component C3) is an ethylene-1-butene copolymer, an ethylene-1-hexene copolymer, or an ethylene-1-octene copolymer, and particularly preferably an ethylene-1-octene copolymer.

[0119] Suitable polyethylene elastomers are commercially available, for example from Dow Chemical Company.

[0120] Preferably, the central polymer layer (C) according to the invention comprises (or is composed of): a propylene terpolymer (component C1) consisting of propylene, ethylene and butene structural units, a styrene-ethylene-butene-styrene block copolymer (SEBS) (component C2) and an ethylene-octene copolymer (component C3).

[0121] Particularly preferably, the central polymer layer (C) according to the invention contains (or consists of): 65%-80%, preferably 72%-78% by weight of a propylene terpolymer composed of propylene, ethylene and butene structural units (component C1); 17%-22%, preferably 19%-21% by weight of a styrene-ethylene-butene-styrene block copolymer (component C2); and 4%-10%, preferably 5%-8% by weight of an ethylene-octene copolymer (component C3).

[0122] Functional Layer (D)

[0123] The heat-sterilizable multilayer film according to the invention may further include an additional functional layer (D) as an outer layer, which is adjacent to the first polymer layer (A) on the outside of (A), that is, on the other side of (A) opposite to the side having the polymer layer (C).

[0124] The functional layer (D) preferably makes the heat-sterilizable multilayer film and the medical bags or film sleeves made therefrom airtight and / or waterproof.

[0125] Functional layer D) comprises (preferably consists of) at least one, preferably a material selected from: ethylene-vinyl alcohol copolymer, polyvinyl alcohol, polyamide, liquid crystal polymer (LCP), aromatic polyester, preferably polyester terephthalate, particularly preferably polyethylene terephthalate (PET), and silica (SiO2). x ), aluminum oxide (AlO) x ) and acrylate polymers

[0126] Preferably, the functional layer (D) is made of PET / SiO2. x composition.

[0127] The thickness of the functional layer (D) is preferably 5-25 μm, especially 10-20 μm.

[0128] Made of PET / SiO x The functional layer (D) significantly improves the gas barrier properties (e.g., oxygen barrier) of the heat-sterilizable multilayer film of the present invention, thus making the film also very suitable for the storage of oxygen-sensitive components.

[0129] According to the present invention, SiO x The PET functional layer (D) can reduce the oxygen barrier properties, or oxygen transmissibility (OTR), of heat-sterilizable multilayer films by 1000 times to an OTR value of <1cm. 3 / (m 2 × days)(ASTM F1927(23℃, 50% RH)).

[0130] Multilayer thin films

[0131] Preferably, the heat-sterilizable multilayer film according to the present invention is composed of polymer layers (A), (B) and (C).

[0132] In each polymer layer (A), (B), and (C), the multilayer film may contain conventional additives and / or processing aids in conventional amounts suitable for the intended use of the multilayer film.

[0133] The preferred additives are antioxidants and heat stabilizers (phosphoric acid and phenolic stabilizers, such as...). 168, Irgafos P-EPQ 1076 or Irganox 1010), and acid scavengers, such as Synthetic hydrotalcite (SHT) and magnesium oxide (MgO).

[0134] Preferably, the heat-sterilizable multilayer film composed of polymer layers (A), (B) and (C) according to the present invention contains at least one antioxidant, heat stabilizer and / or acid scavenger, the total amount of which is preferably <3000 ppm based on the entire multilayer film.

[0135] Preferably, polymer layers (A), (B), and (C) adhere to each other without the use of tackifiers; that is, the multilayer film of the present invention, composed of polymer layers (A), (B), and (C), preferably does not contain tackifiers. Furthermore, preferably, at least the second polymer layer (B) does not contain other additives and / or processing aids (e.g., modifiers or plasticizers, such as mineral oils), and very particularly preferably, polymer layers (A), (B), and (C) do not contain other additives and / or processing aids besides the aforementioned additives. Therefore, during sterilization and storage, the multilayer film of the present invention, as a packaging material, has little or no effect on pharmaceuticals or medical solutions.

[0136] In the case of the multilayer film of the present invention, which consists of polymer layers (A), (B), (C) and functional layer (D), the multilayer film generally contains tackifiers or pressure-sensitive adhesives in addition to the preferred additives described above.

[0137] The thickness of the first polymer layer (A) is generally 5%-15% of the total thickness of the multilayer film of the present invention by weight, preferably 7%-13% by weight, and particularly preferably 7.5%-10% by weight.

[0138] The thickness of the second polymer layer (B) is generally 5%-15% by weight of the total thickness of the multilayer film of the present invention, preferably 7%-13% by weight, and particularly preferably 7.5%-10% by weight.

[0139] The central polymer layer (C) accounts for the largest proportion of the multilayer film of the present invention (preferably at least 70% by weight of the total film thickness) and is used to improve the impact strength of the overall structure.

[0140] If a functional layer (D) is present, the thickness of the optional functional layer (D) is preferably 2.5%-12.5% ​​by weight of the total thickness of the multilayer film of the present invention, and particularly preferably 5%-10% by weight.

[0141] The total thickness of the multilayer thin film of the present invention is preferably 50-500 μm, particularly preferably 100-400 μm, and very particularly preferably 150-300 μm.

[0142] The total thickness of the multilayer film composed of polymer layers (A), (B) and (C) according to the present invention is preferably 50-500 μm, particularly preferably 100-400 μm, and very particularly preferably 150-300 μm.

[0143] Particularly preferably, the multilayer film according to the invention, composed of polymer layers (A), (B), and (C), is characterized in that the total thickness of the multilayer film is 50-500 μm, particularly preferably 100-400 μm, and in each case, based on the total thickness of the multilayer film, the thickness of the first polymer layer (A) is 5%-15% by weight, preferably 7%-13% by weight; the thickness of the second polymer layer (B) is 5%-15% by weight, preferably 7%-13% by weight; and the thickness of the central polymer layer (C) is 70%-85% by weight, preferably 74%-80% by weight; and in each case, the sum of the proportions of (A), (B), and (C) is equal to 100%.

[0144] Methods for preparing multilayer thin films

[0145] The present invention also provides a method for preparing the multilayer film of the present invention, wherein a first polymer layer (A), a central polymer layer (C), and a second polymer layer (B) are co-extruded.

[0146] Co-extrusion involves bringing together the molten plastic of polymer layers (A), (B), and (C) before they leave the extruder's die to form the multilayer film of the present invention.

[0147] In most cases, the extrusion process is a two-stage process. In the first step, the materials for the individual polymer layers are mixed and compacted in an extruder, preferably a parallel twin-screw extruder (compounder), a heated / cooled mixer, or a tablet press. The plastic melt of polymer layers (A), (B), and (C) is then brought together in another extruder, which may be directly coupled or spatially and temporally separated, and then exits through a die to form the multilayer film of the present invention.

[0148] Preferably, the multilayer film obtained according to the method of the present invention is subjected to water impact cooling.

[0149] Co-extrusion can produce the multilayer film of the present invention in the form of a planar film (planar film method, for example, when using a groove die) or a film sleeve (blown film method, for example, filling the interior of the film sleeve with (preferably sterile filtered) air), in the case of a film sleeve, the exterior is composed of a first polymer layer (A) and the interior is composed of a second polymer layer (B).

[0150] In a further method step, an optional functional layer (D) may be applied, for example, by thermal lamination or preferably by lamination, to the multilayer film obtained by the method of the present invention.

[0151] According to a specific embodiment of the method for preparing the laminated multilayer thin film sleeve of the present invention, the method of the present invention includes the following steps:

[0152] (a') A membrane sleeve made of the multilayer film of the present invention is prepared by co-extruding a first polymer layer (A), a central polymer layer (C), and a second polymer layer (B), wherein the membrane sleeve is filled with air, preferably sterile filtered air;

[0153] (b') Optionally, the membrane sleeve obtained in step (a') of the method is cooled;

[0154] (c') The optional cooling membrane sleeve is coated with a pressure-sensitive adhesive layer on at least one side (first polymer layer (A));

[0155] (d') Optionally, the membrane sleeve coated with the pressure-sensitive adhesive layer is dried;

[0156] (e') At least one side of the membrane sleeve coated with a pressure-sensitive adhesive layer (first polymer layer (A)) and the functional layer (D), particularly SiO x / PET functional layers are laminated;

[0157] (f') Optionally, the laminated film sleeve is dried and cured.

[0158] According to the above-described embodiment of the method of the present invention, the two parallel inner sides of the film sleeve (= the second polymer layer (B)) are preferably directly adhered to each other on top after the melt extrusion or co-extrusion of the film sleeve, so that the outer surface of the film sleeve (the first polymer layer (A)) can be coated when the inside of the film sleeve is closed. The closed interior, which is inflated when the resulting film sleeve is subsequently used, is therefore substantially free of particles.

[0159] Preferably, in the above-described embodiments of the method according to the invention, the interior of the membrane sheath is filled with sterile filtered air, thereby maintaining a low particulate content in the laminated multilayer membrane sheath and making it particularly suitable for medical use.

[0160] Particularly preferred is the preparation of low-particle laminated multilayer film sleeves by carrying out the above-described method of the present invention in a cleanroom.

[0161] In the above embodiments of the method according to the invention, it is preferred to use a tackifier that allows complete curing at room temperature for about 2 weeks, preferably 1 week. Curing can also be achieved more quickly at high temperatures in a heated chamber, preferably 30°C or higher, and in most cases 40°C-60°C.

[0162] Suitable tackifiers (pressure-sensitive adhesives, adhesives, or laminating adhesives) include, for example, isocyanates, polyurethanes, poly(ethyl acrylate / methacrylate), pure acrylate copolymers, vinyl ester / acrylate copolymers, or inorganic-organic hybrid polymers.

[0163] The preferred tackifier is a two-component system, which can be solvent-based or solvent-free, silane-based or silane-free, and can be selectively used with other "catalysts" to accelerate curing.

[0164] Suitable solvent-based two-component systems include, for example, polyurethane adhesives, including commercially available systems such as...

[0165] -Dow's ADCOTE TM 675A+ADCOTE TM 675C co-reactants;

[0166] -Dow's ADCOTE 811A + ADCOTE 811B co-reactants;

[0167] - Dow's ADCOTE E735A-75+ADCOTE TM E735C2 co-reactant;

[0168] -MORCHEM's PS241AE+CS-97 co-reactant;

[0169] - Henkel's Loctite Liofol LA2798 + Henkel's Loctite Liofol LA7371;

[0170] - Henkel's Loctite HY 4070 2K blended adhesive.

[0171] The above system can be used selectively with a "catalyst", including those such as Dow's 9L10 (polyisocyanate), 9L200, and F Adcote 40-3E, which are commercially available.

[0172] Suitable solvent-free two-component systems are, for example, polyurethane adhesives, including commercially available systems such as...

[0173] - Dow's Mor-Free TM L 75-720 adhesive + CR 88-720 or CR 88-721 or MOR-FREE TM C79S co-reactants;

[0174] - Dow's Mor-Free TM 203A Adhesive + MOR-FREE TM 200C co-reactants;

[0175] - Dow's Mor-Free TM L705 Adhesive + MOR-FREE TM C 79 or MOR-FREE TM C-102 co-reactant.

[0176] In addition, the tackifier used can be a single-component system, which can be solvent-based or solvent-free, silane-based or silane-free, and can be selectively used with other "catalysts" to accelerate curing.

[0177] Suitable solvent-free single-component systems are, for example, Dow's MOR-FREE. TM ELM 415A (polyurethane adhesive) or WB film lamination adhesive FP NDC 375224 is commercially available.

[0178] Particularly preferably, the selected adhesive should meet the requirements of pharmacopoeia restrictions, such as regarding migration properties, and preferably be free of organic solvents.

[0179] Depending on the processing method or the desired coating, an adhesive layer can be applied to one or both sides of the film sleeve prepared by a co-extrusion process. This can be achieved by methods such as spraying or blade coating. An aqueous solution of the relevant adhesive is also applicable.

[0180] After the adhesive layer is applied, the resulting film sleeve can be selectively dried. For example, if water is used to apply the adhesive, drying can be achieved through the evaporation of the water.

[0181] The thickness of the pressure-sensitive adhesive layer is preferably 3-10 μm.

[0182] The present invention also provides the use of the multilayer film of the present invention in the preparation of medical packaging, preferably medical bags.

[0183] The present invention also provides the use of the medical packaging of the present invention as a container for at least one drug.

[0184] The medical packaging according to the invention is particularly suitable as a container for at least one drug. The combination of the polypropylene outer and middle layers (polymer layers (a) and (c)) with the polyethylene inner layer (polymer layer (B)) means that good processability can be guaranteed for all commonly used bag sealing machines, while the possibility of the polyethylene inner layer adsorbing active pharmaceutical ingredients is extremely low.

[0185] In a preferred embodiment, the packaging according to the invention is subdivided into multiple chambers, thereby allowing it to be used simultaneously as a container for multiple drugs. This is necessary, for example, for drug combinations that must be administered together but are unstable over a long period; or for solid drugs administered in solution or suspension form but unstable in solution or suspension over a long period. The components of the final dosage form can be stored individually in separate chambers and mixed together shortly before administration by opening the dividers.

[0186] A method for preparing the medical packaging, preferably a bag, of the present invention includes the following steps:

[0187] a) Provide at least one heat-sterilizable multilayer film according to the invention;

[0188] b) Optionally, one or more port elements and / or flexible tubes may be provided;

[0189] c) A medical package, preferably a bag, is formed from at least one heat-sterilizable multilayer film, such that a second polymer layer (B) forms the medical package, preferably the inner surface of the bag, while a first polymer layer (A) forms the medical package, preferably the outer surface of the bag.

[0190] d) Optionally, the port element and / or flexible tube are located between the inner surfaces of the medical packaging, preferably at the contour of the bag;

[0191] e) Make the inner surfaces contact each other and make the inner surfaces contact the port elements and / or flexible tubes between the inner surfaces optionally located at the outline of the medical packaging, preferably the bag;

[0192] f) Heat-seal the inner surfaces to each other and heat-seal the inner surfaces to the port elements and / or flexible tubes that are optionally located at the outline of the medical packaging, preferably the bag.

[0193] In step a), the multilayer thin film of the present invention is preferably provided in the form of a planar film or a tubular film. Depending on the form of the provided film, the remainder of the method may vary in specific details. The obtained low-particle film sheath can be combined with a functional layer (D), such as SiO2, through other method steps. x / PET functional layers are laminated.

[0194] In the use of medical packaging according to the invention, a bag is preferred, and after the multilayer film of the invention is provided, additional elements such as port elements and / or flexible tubes may optionally be provided in step b) of the method. Providing these elements is useful, for example, if the medical packaging according to the invention is used, the bag is preferably used as a fixing component of a medical device or attached to a medical device. Omitting step b) may be useful, for example, if the medical packaging is used, the bag is preferably used only for storing medicine and is damaged to remove the medicine, for example, by tearing or puncturing with a cannula.

[0195] In step c), the provided multilayer film of the present invention is made into a medical package, preferably a bag. If a tubular film is provided in step a), the forming of the medical package, preferably a bag, may, for example, consist only of cutting the tubular film to the desired length, since the second polymer layer (B) has formed the inner surface of the tubular film and the first polymer layer (A) has formed the outer surface of the tubular film. If a planar film is provided in step a), the medical package, preferably a bag, may be formed from a single multilayer film as in step c), for example by cutting the film sheet into a mirror-symmetrical shape and folding it downward along the mirror axis, such that the edges of the film overlap each other uniformly, with the second polymer layer (B) located inside. Alternatively, the medical package, preferably a bag, of the present invention may be formed from two planar films, for example by cutting the two planar films into mirror-symmetrical shapes and stacking them uniformly on top of each other, with the second polymer layer (B) located inside. Rectangular shapes are particularly suitable for cutting because of minimal material loss and the simplest processing. However, other shapes are also possible; for example, medical packages, preferably bags, can be produced with aesthetically pleasing shapes that appeal to children and distract them from actual drug administration.

[0196] Depending on whether additional elements such as port elements and / or flexible tubes are provided in step b), in step d), the elements are positioned between the inner surfaces of the formed medical packaging, preferably the bag, along its contour. In the case of tubular films, this means inserting the additional elements into the openings of the tubular film. Here, the elements are located only on two opposite sides of the medical packaging, preferably the bag. In the case of planar films, the insertion of the additional elements means that they are uniformly stacked between the edges of one or more planar films in step c). Here, the elements can be located at any point along the edges, but are most preferably placed on two opposite edges.

[0197] In step e), the inner surfaces of the formed medical package, preferably the bag, come into contact with each other and with additional elements between the inner surfaces, optionally located at the contour of the bag, so that the inner surfaces can be sealed together by heat and optionally mechanical pressure provided in step f). For heat sealing, the temperature is preferably above the melting / softening point of the second polymer layer (B), but below the melting / softening point of the first polymer layer (A). This makes it possible to ensure that the second polymer layer (B) melts at the contour of the medical package, preferably the bag, thereby permanently and fluidly sealing together, while the first polymer layer (A) retains its shape, thus maintaining the stability of the medical package, preferably the bag.

[0198] An important criterion for using the multilayer film according to the present invention as the primary packaging material for medical solutions is its barrier function to prevent liquid loss. Such liquid loss will cause changes in the concentration of the active ingredient in the solution, and the liquid loss must not exceed a specific value. Liquid loss during storage determines the shelf life of the product. The formulation of the multilayer film of the present invention is selected to provide good moisture barrier properties and good impact strength.

[0199] The multilayer film according to the present invention is characterized by being heat-sterilizable, impact-resistant, and flexible (plasticizer-free), and can even be reliably heat-sealed to port elements by continuous heat welding methods, without the need for tackifiers, having good adhesion between layers, and having little or no effect on medical solutions or drugs.

[0200] Multilayer thin films with an additional functional layer (D) according to the present invention, particularly SiO x The PET functional layer has significantly improved gas barrier properties, which makes it possible to store oxygen-sensitive components.

[0201] The invention will now be described in more detail based on embodiments, and the implementation methods are therefore not limited.

[0202] Example 1

[0203] First polymer layer (A):

[0204] - 97% by weight is from Lyondell Basell Corp., USA. HP525J / Polypropylene homopolymer;

[0205] -3% by weight from Asahi Kasei, Japan H1062 / styrene-ethylene / butene block copolymer.

[0206] The formulation is mixed in a molten state in a separate compounding step and then granulated for further use.

[0207] Second polymer layer (B):

[0208] B1) 75% by weight of Tosoh FY-13 from Tosoh Corp., Japan / / Composition consisting of ethylene homopolymer (70%-80% by weight) and ethylene-1-butene copolymer (20%-30% by weight) / Density: 950 kg / m³ 3 T m 128℃;

[0209] B2) 20% by weight from Borealis, Austria TD109CF / propylene terpolymer;

[0210] B3) 5% by weight from Dow Chemical Company, USA 8003 / Ethylene-Octene Polyolefin Elastomer.

[0211] The formulation is mixed in a molten state in a separate compounding step and then granulated for further use.

[0212] Central polymer layer (C):

[0213] -70% by weight from Borealis, Austria TD109CF / propylene terpolymer;

[0214] -20% by weight from Asahi Kasei, Japan H1062 / styrene-ethylene / butene block copolymer;

[0215] -10% by weight from Dow Chemical Company, USA 8003 / Ethylene-Octene Polyolefin Elastomer.

[0216] The formulation is mixed in a molten state in a separate compounding step and then granulated for further use.

[0217] The melt of the granular compounds of the first polymer layer (A), the central polymer layer (C), and the second polymer layer (B) is co-extruded on a blown film production line and cooled with water using polypropylene with conventional process parameters to obtain a multi-layer film sleeve in the form of a film sleeve, the inside of which is filled with sterile filtered air.

[0218] The total thickness of the film is 200 μm, of which the thickness of the first polymer layer (A) and the second polymer layer (B) is 15 μm each, and the thickness of the central polymer layer (C) is 170 μm.

[0219] The resulting film can be sterilized with hot steam and permanently heat-sealed using welding tools set to 125°C.

[0220] Example 2

[0221] The membrane sleeve prepared according to Example 1 is further provided with SiO on both sides. x / The functional layer (D) is composed of PET (Techbarrier T from Mitsubishi) with a layer thickness of 15 μm on each side.

[0222] First, a two-component adhesive (Dow's ADCOTE 811A+ADCOTE 811B co-reactant and Dow catalyst 9L10, available from Dow Chemical Company) is coated on both sides of the flat membrane sleeve. Then, the adhesive-coated membrane sleeve and the functional layer are laminated on both sides.

[0223] The resulting film can be sterilized with hot steam and permanently heat-sealed using welding tools adjusted to 125°C.

[0224] Example 3 (Comparative example, according to Example 1 of DE10361851A1))

[0225] First polymer layer (A):

[0226] - 97% by weight is from Lyondell Basell Corp., USA. HP525J / Polypropylene homopolymer;

[0227] -3% by weight from Asahi Kasei, Japan H1062 / styrene-ethylene / butene block copolymer.

[0228] The formulation is mixed in a molten state in a separate compounding step and then granulated for further use.

[0229] Second polymer layer (B):

[0230] -85% by weight from Borealis, Austria TD109CF / propylene terpolymer;

[0231] -15% by weight from Asahi Kasei, Japan H1062 / styrene-ethylene / butene block copolymer.

[0232] The formulation is mixed in a molten state in a separate compounding step and then granulated for further use.

[0233] Central polymer layer (C):

[0234] -75% by weight from Borealis, Austria TD109CF / polypropylene terpolymer;

[0235] -20% by weight from Asahi Kasei, Japan H1062 / styrene-ethylene / butene block copolymer;

[0236] -5% by weight from Dow Chemical Company, USA 8003 / Ethylene-Octene Polyolefin Elastomer.

[0237] The formulation is mixed in a melt state in a separate compounding step and then granulated for further use.

[0238] Co-extrusion was performed on a blown film production line, and polypropylene with conventional process parameters was water-cooled to obtain a multilayer film in the form of a film sleeve.

[0239] The film has a total thickness of 200 μm, with the first polymer layer (A) and the second polymer layer (B) each having a thickness of 15 μm, and the central polymer layer (C) having a thickness of 170 μm. The resulting film can be sterilized with hot steam and can be permanently heat-sealed using welding tools adjusted to a temperature of 125°C.

[0240] Example 4 (Comparative example, not based on the present invention)

[0241] First polymer layer (A):

[0242] - 97% by weight is from Lyondell Basell Corp., USA. HP525J / Polypropylene homopolymer;

[0243] -3% by weight from Asahi Kasei, Japan H1062 / styrene-ethylene / butene block copolymer.

[0244] The formulation is mixed in a molten state in a separate compounding step and then granulated for further use.

[0245] Second polymer layer (B):

[0246] -75% by weight from Borealis, Austria LE6600-PH / Low-density polyethylene (LDPE);

[0247] - 20% by weight from Borealis, Austria TD109CF / propylene terpolymer;

[0248] -5% by weight from Dow Chemical Company, USA 8003 / Ethylene-Octene Polyolefin Elastomer.

[0249] The formulation is mixed in a molten state in a separate compounding step and then granulated for further use.

[0250] Central polymer layer (C):

[0251] -70% by weight from Borealis, Austria TD109CF / propylene terpolymer;

[0252] -20% by weight from Asahi Kasei, Japan H1062 / styrene-ethylene / butene block copolymer;

[0253] -10% by weight from Dow Chemical Company, USA 8003 / Ethylene-Octene Polyolefin Elastomer.

[0254] The formulation is mixed in a molten state in a separate compounding step and then granulated for further use.

[0255] The particulate compounds of polymer layers (A), (B) and (C) are co-extruded on a blown film production line and water-cooled with polypropylene using conventional process parameters to obtain a multilayer film in the form of a film sleeve.

[0256] The total thickness of the film is 200 μm, of which the thickness of the first polymer layer (A) and the second polymer layer (B) is 15 μm each, and the thickness of the central polymer layer (C) is 170 μm.

[0257] Welding strength tests of the films in Examples 1-4

[0258] 1.(a) A heat-sealed sample was made by using a film sealing device (IST Med from Kopp) to form two overlapping films (20 x 15 cm each); the welded area (film edge) was about 15 mm.

[0259] Welding parameters: pressure 2-3 bar, time 1-2 seconds, gap: 320 μm.

[0260] (b) Then, a 15x80mm wide test strip with heat-sealed edges is pierced (=unsterilized sample).

[0261] 2. The obtained test strips, including the heat-sealed edges, were steam-sterilized at 121°C (WEBECO Model A 35 autoclave, 2 bar, 20 minutes) (= steam-sterilized sample). Film adhesion was prevented by pre-opening the non-heat-sealed area of ​​the test strip and placing paper in the middle.

[0262] 3. The weld strength is determined by clamping the cooled test strip, including the heat-sealed edge, in a tensile testing machine (Zwick iLine 500N from Zwick) and pulling the test strip at a speed of 400 mm / min.

[0263] The results of the welding assessment are reported in N / 15mm.

[0264] The weld strength of the multilayer film should be greater than 25 N / 15 mm, preferably greater than 30 N / 15 mm. If the weld strength of the multilayer film is 10-20 N / 15 mm, it indicates that it has a peelable weld.

[0265] Figure 1 The welding curves of the unsterilized samples in Examples 1-4 are shown. The x-axis represents the welding temperature [°C], and the y-axis represents the tensile strength [N / 15mm].

[0266] Figure 2 The welding curves of the samples sterilized by hot steam in Examples 1-4 are shown. The x-axis represents the welding temperature [°C]; the y-axis represents the tensile strength [N / 15mm].

[0267] In the figure, each embodiment is represented by lines with different structures.

[0268] result:

[0269] (a) Unsterilized sample

[0270] Welding curves of the films in Examples 1, 3 and 4 (see) Figure 1 The weld strength at approximately 130°C is >30 N / 15 mm; Example 2 contains PET / SiO x The functional layer film can be heat-sealed at a temperature rise of approximately 5°C (weld strength > 30 N / 15 mm), which is not a problem because of the PET / SiO film. x The functional layer gives the film higher temperature resistance.

[0271] (b) Samples sterilized by heat steam

[0272] Welding curves of the films in Examples 1, 2 and 3 (see) Figure 2The weld profile of the unsterilized sample was similar, exhibiting a weld strength >30 N / 15 mm at approximately 130°C or 135°C; the film of Example 4 (with the second polymer layer based on LDPE) did not show the required weld strength after steam sterilization. It was clear that the weld seams had separated or “peeled”, or delaminated. If the film of Example 4 were used as medical bags, these bags would open during or upon removal from autoclave sterilization.

[0273] PE materials such as LDPE or HDPE are incompatible with polypropylene, meaning that in the case of multilayer films with a PP interlayer, the inner layer can easily separate from the interlayer. Furthermore, the melting temperature of LDPE raw material is between 110℃ and 115℃, meaning the raw material melts during hot steam sterilization, thus weakening the weld.

[0274] Due to the specific combination of the second polymer layer (inner layer) B), which is a combination of polyethylene composition B1), PP terpolymer B2) and polyethylene elastomer B3 (as a tackifier), the multilayer film of the present invention according to Examples 1 and 2 shows the advantage that the inner layer B) cannot be easily separated from the central layer C; in addition, the composite material B1) used does not melt during hot steam sterilization, thus maintaining sufficiently high weld strength.

[0275] Compared to the prior art multilayer film in Example 3 (with an inner layer B composed of an impact-modified propylene terpolymer), the multilayer films of Examples 1 and 2 according to the present invention, due to the use of a polyethylene composition B1 for their inner layer B, exhibit very good impact strength even without the addition of impact modifiers, and they also possess considerable weld strength and suitability for steam sterilization. Furthermore, the multilayer films according to the present invention, compared to the multilayer films according to Example 3, also have the advantage of less adhesion of the active ingredients to the PE-containing inner layer, i.e., a higher so-called "recovery value".

Claims

1. A heat-sterilizable multilayer film, characterized in that, include: a) A first polymer layer (A) comprising at least one polypropylene homopolymer modified with at least one impact modifier; b) The second polymer layer (B) comprises: B1) Based on (B), a homogeneous composition (B1) comprising 60%-85% by weight, comprising: B11) is based on (B1), a homopolymer of 65%-85% by weight of ethylene, and B12) is based on (B1), comprising 15%-35% by weight of at least one ethylene copolymer, wherein the ethylene copolymer contains at least one α-olefin having 4-12 carbon atoms as a comonomer. The melting temperature of composition (B1) was >125°C, as determined by DSC. The density of composition (B1) was 945-960 kg / m³, as determined by Method B of DIN EN ISO 1183-1:2019-09. 3 ; B2) Based on (B), at least one propylene terpolymer comprising 11%-30% by weight; B3) Based on (B), 4%-15% by weight of at least one polyethylene elastomer, wherein the elastomer is a copolymer of ethylene and at least one α-olefin having 4-12 carbon atoms; c) A central polymer layer (C) located between the first polymer layer (A) and the second polymer layer (B), comprising: C1) Based on (C), at least one propylene terpolymer comprising 61%-80% by weight; C2) Based on (C), at least one styrene block copolymer elastomer comprising 15%-25% by weight; C3) is based on (C), comprising 5%-19% by weight of at least one polyethylene elastomer, which is a copolymer of ethylene and at least one α-olefin containing 4-12 carbon atoms.

2. The heat-sterilizable multilayer film according to claim 1, characterized in that, The homogeneous composition (B1) comprises: B11) weight percentage 70%-80%, and B12) weight percentage 20%-30%.

3. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The ethylene copolymer (B12) is copolymerized from ethylene and at least one α-olefin copolymer under a metallocene catalyst.

4. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The ethylene homopolymer B11 used is high-density polyethylene (HDPE).

5. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, Ethylene copolymer (B12) contains 25%-40% by weight of at least one α-olefin comonomer.

6. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, Ethylene copolymer (B12) contains at least one comonomer of an α-olefin, selected from: 1-butene, 1-pentene, 1-hexene and 4-methyl-1-pentene.

7. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, Components B2) and / or C1) are propylene, ethylene, and / or C4-C 16 terpolymers of α-olefins.

8. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, Component B3) is a copolymer of ethylene and an α-olefin having 7-12 carbon atoms.

9. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The second polymer layer (B) comprises: B1) 65%-80% by weight; B2) 15%-25% by weight; B3) 4%-12% by weight.

10. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The central polymer layer (C) comprises: C1) weight percentage 65%-75%; C2) weight percentage 17%-22%; C3) weight percentage: 8%-17%.

11. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The styrene block copolymer (SBC) elastomer (C2) is selected from: styrene-ethylene-butene-styrene block copolymer (SEBS), styrene-ethylene-propylene-styrene block copolymer (SEPS), styrene-ethylene-ethylene-propylene-styrene block copolymer (SEEPS), styrene-isoprene-styrene block copolymer (SIS), and styrene-butadiene-styrene block copolymer (SBS).

12. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The polyethylene elastomer (C3) is an ethylene-butene copolymer and / or an ethylene-octene copolymer.

13. A method for preparing the multilayer thin film of claim 1, characterized in that, The first polymer layer (A), the central polymer layer (C), and the second polymer layer (B) are co-extruded.

14. The heat-sterilizable multilayer film according to claim 1, characterized in that, It includes an additional functional layer (D) adjacent to the first polymer layer (A).

15. A method for preparing a laminated multilayer film sleeve made of the multilayer film of claim 14, characterized in that, Includes the following steps: (a') Prepare a membrane sleeve made of a multilayer thin film obtained by the method of claim 13, wherein the interior of the membrane sleeve is filled with air; (c') Coat the membrane sleeve with a pressure-sensitive adhesive layer on at least one side of the membrane sleeve; (e') Laminating at least one side of the film sleeve coated with a pressure-sensitive adhesive layer to the functional layer (D).

16. The application of the multilayer film of claim 1 or 14 in the preparation of medical packaging.

17. A method for preparing medical packaging made of a multilayer film according to any one of claims 1 or 14, characterized in that, Includes the following steps: a) Provide at least one multilayer thin film prepared by the method according to claim 13 or 15; c) A medical package is formed from at least one or more layers of film, such that a second polymer layer (B) forms the inner surface of the medical package and a first polymer layer (A) forms the outer surface of the medical package; e) Bring the inner surfaces into contact with each other and into contact with the outline of the medical packaging; f) Heat seal the inner surfaces together and heat seal the inner surfaces to the outline of the medical packaging.

18. The heat-sterilizable multilayer film according to claim 1, characterized in that, include: B12) is based on (B1), comprising 20%-30% by weight of at least one ethylene copolymer, wherein the ethylene copolymer contains at least one α-olefin having 4-12 carbon atoms as a comonomer.

19. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The ethylene homopolymer B11 used has a density of 950-970 kg / m³. 3 HDPE.

20. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, Ethylene copolymer (B12) contains 30%-37% by weight of at least one α-olefin comonomer.

21. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The ethylene copolymer (B12) contains at least 1-butene as a comonomer.

22. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, Components B2) and / or C1) are terpolymers of propylene, ethylene and butene.

23. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The second polymer layer (B) comprises: B1) Weight percentage 72%-78%; B2) Weight percentage 17%-22%; B3) 5%-10% by weight.

24. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The styrene block copolymer (SBC) elastomer (C2) is selected from SEBS and SEPS.

25. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The styrene block copolymer (SBC) elastomer (C2) is SEBS.

26. The heat-sterilizable multilayer film according to claim 1 or 2, characterized in that, The polyethylene elastomer (C3) is an ethylene-octene copolymer.

27. A method for preparing a laminated multilayer film sleeve made of the multilayer film of claim 15, characterized in that, The membrane sleeve prepared in step (a') is filled with sterile filtered air.

28. A method for preparing a laminated multilayer film sleeve made of the multilayer film of claim 15, characterized in that, In step (c'), a pressure-sensitive adhesive layer is coated on the first polymer layer (A) of the membrane sleeve. In step (e'), the first polymer layer (A) of the membrane sleeve coated with the pressure-sensitive adhesive layer is laminated with the functional layer (D).

29. The use of the multilayer film of claim 1 or 14 in the preparation of medical bags.

30. The method according to claim 17, characterized in that, The medical packaging is a bag.

31. A method for preparing a laminated multilayer film sleeve made of the multilayer film of claim 15, characterized in that, It also includes the following steps: (b') Cool the membrane sleeve obtained in step (a') of the method.

32. A method for preparing a laminated multilayer film sleeve made of the multilayer film of claim 15, characterized in that, It also includes the following steps: (d') Dry the film sleeve coated with pressure-sensitive adhesive layer.

33. A method for preparing a laminated multilayer film sleeve made of the multilayer film of claim 15, characterized in that, It also includes the following steps: (f') Dry and cure the laminated film sleeve.

34. A method for preparing medical packaging made of a multilayer film according to any one of claims 1 or 14, characterized in that, Includes the following steps: a) Provide at least one multilayer thin film prepared by the method according to claim 13 or 15; b) Provide one or more port elements and / or flexible tubing; c) A medical package is formed from at least one or more layers of film, such that a second polymer layer (B) forms the inner surface of the medical package and a first polymer layer (A) forms the outer surface of the medical package; d) Position the port element and / or flexible tube between the inner surfaces of the outline of the medical packaging; e) Make the inner surfaces contact each other and make the inner surfaces contact the port elements and / or flexible tubes located between the inner surfaces at the outline of the medical packaging; f) Heat-seal the inner surfaces to each other and heat-seal the port elements and / or flexible tubes between the inner surfaces and the inner surfaces located at the contour of the medical packaging.

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