Enhanced biotreatment membranes for disposable biocontainers

Abstract

A multilayer polymer film comprising an inner biomaterial contacting layer and an outer layer comprising a polymer selected from the group consisting of polyester elastomer copolymers, polyethylene terephthalate (PET), nylon, polyethylene, polypropylene, thermoplastic elastomers, and copolymers and mixtures thereof, wherein the difference between the melting temperature of the inner contact layer and the melting temperature of the outer layer is 30-120 DEG C.

Description

Technical Field

[0001] The present invention relates to disposable, single-use polymeric containers for containing fluids and suitable for use in bioprocessing applications.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to U.S. Provisional Application No. 63 / 394,332 filed on August 2, 2022, the contents of which are incorporated herein in their entirety. Background Art

[0004] The disposable container for bioprocessing has been made of polymer film, and the volume range of the container that this polymer film is transformed into is 50 milliliters to up to 5000 liters.The typical conversion process from film to container utilizes multiple heat seals or welding technology to produce sealed containers.Such container can be used for many aspects of bioprocessing, and it comprises as bioreactor, buffer and culture medium storage container, mixing container, processing sampling container, and is used for final filling.Compare with the molded rigid container or the molded semi-rigid plastic container for stainless steel bioreactor of traditional stainless steel or glass container, this container, such container has a plurality of advantages.For example, disposable polymer container can be made into a plurality of required structures, and this is usually cheaper than other selections, and because of their disposable properties, the risk of cross contamination is lower, and the requirement of keeping sterility is lower. A variety of disposable containers have been described, for example, in U.S. Pat. Nos. 6,391,404, 8,043,680, 8,556,111, 8,722,164, 10,899,114, and 11,110,684; and U.S. Patent Application Nos. 20150360450, 20170175066, 20210107261, and 20210347156. However, lack of durability, including susceptibility to leakage, remains an obstacle to the use of such polymeric containers, especially for larger sized containers, and especially for three-dimensionally formed containers having a volume greater than about 100 liters. Summary of the invention

[0005] An overview of the disclosure is given to aid understanding, and those skilled in the art will appreciate that each of the various aspects and features of the disclosure may be advantageously used alone in some cases, or in combination with other aspects and features of the disclosure in other cases. The inclusion or exclusion of elements, components, or the like in this overview is not intended to limit the scope of the claimed subject matter.

[0006] In various aspects, the present disclosure provides a multilayer polymer film comprising an inner biomaterial contact layer and an outer layer, wherein the outer layer comprises a polymer selected from the group consisting of polyester elastomeric copolymers, polyethylene terephthalate (PET), nylon, polyethylene, polypropylene, thermoplastic elastomers, and copolymers and mixtures thereof, wherein the melting temperatures of the inner contact layer and the outer layer differ by 30-120°C.

[0007] In various aspects, the multilayer polymer film further comprises a gas barrier layer disposed between the inner biomaterial contact layer and the outer layer, a first tie layer disposed between the inner contact layer and the gas barrier layer, and a second tie layer disposed between the gas barrier layer and the outer layer. In various aspects, the gas barrier layer comprises one or more materials selected from the group consisting of ethylene vinyl alcohol (EVOH), polyvinylidene chloride (PVDC), liquid crystal polymer (LCP), and nylon 6. In various aspects, each tie layer comprises one or more materials selected from the group consisting of ethyl acrylate, ethacrylic acid, modified ethylene vinyl acetate, and polyethylene.

[0008] In various aspects, the outer layer comprises a mixture of at least two polymers selected from the group consisting of polyester elastomeric copolymers, polyethylene terephthalate (PET), nylon, polyethylene, polypropylene, thermoplastic elastomers. In various aspects, the outer layer comprises a mixture of at least two polyester elastomeric copolymers.

[0009] In various aspects, the inner biomaterial contact layer comprises low density polyethylene. In various aspects, the low density polyethylene is linear low density polyethylene or ultra low density polyethylene, or a mixture thereof. In various aspects, the polyethylene is maleic anhydride grafted polyethylene.

[0010] In various aspects, the melting temperatures of the inner biomaterial contact layer and the outer layer differ.

[0011] In various aspects, the film is an extruded polymer film. In various aspects, at least 5 layers of the film are coextruded to produce a single ply. In various aspects, the thickness of the single ply is 0.20-0.50 mm.

[0012] In one aspect, a multilayer polymer film is provided, comprising an inner biomaterial contacting layer comprising about 70 wt. % low density polyethylene, an outer layer comprising about 5-10 wt. % polyester elastomeric copolymer or a mixture of polyester elastomeric copolymers, having a melt temperature of about 400-450°F, a gas barrier layer disposed between the inner biomaterial contacting layer and the outer layer, a first tie layer disposed between the inner contacting layer and the gas barrier layer, and a second tie layer disposed between the gas barrier layer and the outer layer, wherein the film has an oxygen transmission rate of less than about 0.5 cc / m at 70°F under conditions according to ASTM D-1307. 2 -day-atm, wherein the tear strength of the film is at least about 8 LbF under conditions according to ASTM D-1004, and wherein the melting temperatures of the inner contact layer and the outer layer differ by 100-120°C.

[0013] The disposable flexible film bag may also include an end seal having a strength characteristic of being able to withstand at least about 2 pounds per square inch (psi) for at least about 12 months without failure.

[0014] In various aspects, the present disclosure also provides a disposable flexible film bag, comprising a body defining an interior space, the body comprising at least one polymer sheet of the multilayer polymer film described herein. In various aspects, the body comprises at least 2-4 polymer sheets.

[0015] In various aspects, the bag further includes at least one port assembly extending through the opening in the bag and communicating with the interior space of the body.

[0016] In various aspects, the volume of the interior space of the body is 50-5000 liters.

[0017] In various aspects, the bag is sterile, optionally the bag is sterilized by gamma irradiation.

[0018] In various aspects, the bag is suitable for containing a fluid. In various aspects, the fluid comprises biological material, optionally wherein the biological material is a cell or virus and its products, the cell or virus products including protein products and nucleic acid products.

[0019] Other technical features will be apparent to those skilled in the art from the following drawings, embodiments and claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] With reference to the accompanying drawings (which are schematic and not intended to be drawn to scale), various non-limiting aspects of the present disclosure are described by way of example. The drawings are provided for illustrative purposes only, and the dimensions, positions, orders, and relative sizes reflected in the drawings may vary. In the drawings, identical or nearly identical or equivalent elements are generally represented by the same reference numerals, and similar elements are generally represented by similar reference numerals and redundant descriptions are omitted. For the purpose of clarity and brevity, not every element is labeled in each figure, nor is every element shown that does not require an illustration to enable a person of ordinary skill in the art to understand each aspect of the present disclosure.

[0021] Figure 1 is a schematic diagram of a multilayer polymer film according to one aspect of the present invention, showing the different layers.

[0022] Figure 2 is a schematic diagram of a disposable flexible container according to one aspect of the present invention.

[0023] Figure 3 is a schematic diagram of a disposable flexible container according to one aspect of the present invention.

[0024] Figure 4A is a photograph of a representative flexible container according to one aspect of the present invention which maintained its integrity for 17 months when inflated to 2 psi.

[0025] Figure 4B is a photograph of a representative flexible container according to one aspect of the present invention that has been subjected to burst testing. The illustrated bag burst at a pressure of 6 psi and failed away from the end seal. DETAILED DESCRIPTION

[0026] The present invention provides multilayer polymer films for constructing disposable containers for bioprocessing, and related containers and methods. The polymer films described herein have an enhanced film structure that provides an improved balance of strength, flexibility, and robustness when converted into disposable containers. For example, disposable flexible containers or disposable flexible bags made from the polymer films described herein exhibit excellent tensile yield, elongation, wear, tear, and outer layer hardness properties.

[0027] The multilayer polymer film described herein comprises an inner biomaterial contact layer and an outer layer, the outer layer comprising a polymer selected from the group consisting of polyester elastomer copolymers, polyethylene terephthalate (PET), nylon, polyethylene, polypropylene, thermoplastic elastomers, and copolymers and mixtures or blends thereof. The terms "mixture" and "blend" are used interchangeably herein. In various aspects, the outer layer partially functions as a thermal insulation layer. In various aspects, the outer layer comprises a polyester elastomer copolymer, which may also be referred to as a thermoplastic copolyester, or abbreviated as TPC or TPE. In various aspects, the outer layer comprises or is substantially composed of a blend of two polyester elastomer copolymers. In various aspects, the melting temperature of the outer layer is 300-450°F.

[0028] In various aspects, the multilayer polymer film further comprises a gas barrier layer disposed between the inner biomaterial contacting layer and the outer layer, a first tie layer disposed between the inner contacting layer and the gas barrier layer, and a second tie layer disposed between the gas barrier layer and the outer layer.

[0029] In various aspects, the multilayer polymeric film comprises 5 to 11 layers. In various aspects, at least 5 layers of the film are coextruded to produce a single ply.

[0030] In various aspects, the multilayer polymer film has a thickness of 0.20-0.50 millimeters (mm).

[0031] In various aspects, the inner biomaterial contact layer and the outer layer each have different melting temperatures, wherein the difference in melting temperature is not so great as to prevent coextrusion of the inner contact layer and the outer layer. In various aspects, the melting temperature difference between the inner biomaterial contact layer and the outer layer is 30-120° C. According to this aspect, the melting temperature difference between the inner contact layer and the outer layer provides a faster heat bonding cycle and eliminates the possibility of the contact layer being heat sealed to the outer layer, thereby providing an improved container manufacturing method.

[0032] The multilayer polymer films described herein can be produced by methods such as cast film coextrusion, blown film coextrusion, or extrusion lamination / adhesive. In various aspects, the multilayer polymer films described herein can be produced by methods including coextrusion of cast film to produce a single ply. In various aspects, a disposable container can be constructed using multiple plies of the film.

[0033] The multilayer polymer films described herein are stable to gamma radiation and are therefore sterilizable. In various aspects, a container comprising the multilayer polymer film described herein is sterilized.

[0034] In various aspects, the inner biomaterial contact layer is characterized by containing low levels of contaminating materials that are extractable or leached from the polymer surface. As used herein, the term "extractable" refers to compounds that migrate into the inner contact layer when exposed to a solvent, typically under conditions of time and temperature that exceed the limits of standard bioprocessing operating procedures. In contrast, the term "leachable" refers to compounds that migrate from the inner contact layer under standard operating conditions.

[0035] In various aspects, the outer layer of the multi-layer polymeric film has excellent abrasion resistance, puncture resistance, rupture resistance, and tear resistance as measured by industry standard tests.

[0036] In various aspects, the multilayer polymer film comprises an inner biomaterial contact layer; an outer layer comprising a polymer selected from the group consisting of polyester elastomer copolymers, polyethylene terephthalate (PET), nylon, polyethylene, polypropylene, thermoplastic elastomers, and copolymers and blends thereof; a gas barrier layer disposed between the inner biomaterial contact layer and the outer layer; a first tie layer disposed between the inner contact layer and the gas barrier layer; and a second tie layer disposed between the gas barrier layer and the outer layer. In various aspects, the outer layer comprises a blend of at least two polymers selected from the group consisting of polyester elastomer copolymers, polyethylene terephthalate (PET), nylon, polyethylene, polypropylene, thermoplastic elastomers, and the inner biomaterial contact layer comprises low density polyethylene.

[0037] In many aspects, the container composed of the multilayer polymer film of the present invention is in the form of a flexible film bag, which includes a disposable bag suitable for containing a fluid (the fluid includes a fluid containing one or more biological materials such as living cells). In many aspects, the container is in the form of a flexible film bag suitable for storing and / or processing biological materials, which includes a bioreactor used for culturing living cells (which can be animal, insect, plant or microbial cells (including, for example, yeast, bacteria and viruses)). In many aspects, the flexible film bag includes a main body, which forms an internal space and includes at least one polymer sheet of the multilayer polymer film described herein. In many aspects, the main body includes at least two, three or four polymer sheets. In many aspects, the flexible film bag also includes at least one port assembly, which extends through the opening in the bag and is connected to the internal space of the main body. In many aspects, the volume of the internal space of the main body is 50-5000 liters or 1000-5000 liters, or 2000-5000 liters.

[0038] The flexible film bags of the multi-layer polymer films described herein advantageously include high strength end seals such that the end seals can withstand at least about 2 pounds per square inch (psi) at room temperature humidity for at least 12-16 months without failure.

[0039] Polymer film as herein described can be transformed into disposable container, it is suitable for holding fluid, and allows fluid to be taken out from container and / or returned to container.In many aspects, container can be bioprocessing container, bioreactor, interception material container, mixing bag, or the like.Container as herein described can be produced by comprising film conversion, disposable container conversion, assembling, packaging and the method that is configured to final container.Standard heat sealing technology can be used, for example, constant temperature, heat pulse, RF welding and induction heating treatment.

[0040] The fluid solution to be contained and / or processed in the container may be any of a variety of fluid solutions in biology, medicine, biopharmaceuticals, biotechnology, and bioprocessing.

[0041] It should be understood that the present disclosure is not limited to the specific aspects described in the accompanying drawings, which depict illustrative aspects. All devices and systems and methods discussed herein are examples of devices and / or systems and / or methods implemented according to one or more principles of the present disclosure. Each example of an aspect is provided in an explanatory manner and is not the only way to implement these principles, but is merely an example. Therefore, references to elements or structures or features in the accompanying drawings must be understood as references to multiple examples of multiple aspects of the present disclosure, and should not be understood as limiting the present disclosure to the specific elements, specific structures or specific features shown. A person of ordinary skill in the art will think of other examples of ways to implement the disclosed principles after reading the present disclosure. In fact, it is obvious to those skilled in the art that various modifications and changes can be made to the present disclosure without departing from the scope or spirit of the present subject matter. For example, a feature shown or described as part of one aspect can be used together with another aspect to produce another aspect. Therefore, the present subject matter is intended to cover such modifications and changes that fall within the scope of the appended claims and their equivalents.

[0042] It should be understood that the present disclosure is described in different degrees of detail in this application. In some cases, details that are unnecessary for a person of ordinary skill in the art to understand the present disclosure, or details that make other details difficult to understand, may be omitted. The terms used herein are only for the purpose of describing specific aspects and are not intended to be limited to the scope of the appended claims. Unless otherwise defined, the technical terms used herein should be understood as commonly understood by a person of ordinary skill in the field to which the present disclosure belongs.

[0043] See also Figure 1, which shows a schematic diagram of the polymer film described herein (exploded cross-sectional view of the multiple layers and their arrangement relative to the outer side 102 and the fluid contact side 104 of the film). The gas barrier layer 110 is disposed between two tie layers 112a and 112b; and each tie layer is positioned to contact with a durable outer layer 106 forming the outer side of the film or a fluid contact layer 108 forming the interior of a flexible container made with the polymer film.

[0044] The outer layer 106 comprises a polymer selected from the following: polyester elastomer copolymers, polyethylene terephthalate (PET), nylon, polyethylene, polypropylene, thermoplastic elastomers and copolymers and mixtures thereof. In some aspects, the melting temperature of the polymer or polymer mixture forming the outer layer 106 is about 400-500° C. or about 400-450° C. In some aspects, the outer layer 106 comprises a mixture of at least two polymers selected from the following: polyester elastomer copolymers, polyethylene terephthalate (PET), nylon, polyethylene, polypropylene, thermoplastic elastomers. In various aspects, the outer layer comprises a polyester elastomer copolymer, or a mixture of at least two polyester elastomer copolymers. In various aspects, the outer layer comprises a mixture of two polyester elastomer copolymers. The polymer mixture can be, for example, a mixture of about 50 / 50wt%, a mixture of about 60 / 40wt%, or a mixture of about 70 / 30wt%.

[0045] The gas barrier layer 110 includes one or more materials selected from the group consisting of ethylene vinyl alcohol (EVOH), polyvinylidene chloride (PVDC), liquid crystal polymer (LCP), and nylon 6.

[0046] Each of the connecting layers 112a, 112b includes one or more materials selected from the group consisting of ethyl acrylate, ethyl acrylic acid, modified ethylene vinyl acetate, and polyethylene.

[0047] The inner layer 108 (also referred to as the fluid contact layer or the biomaterial contact layer) comprises low-density polyethylene. In various aspects, the low-density polyethylene is a linear low-density polyethylene or an ultra-low-density polyethylene, or a mixture thereof. In various aspects, the polyethylene is a maleic anhydride-grafted polyethylene.

[0048] As described above, one feature of the multilayer polymer films described herein is the difference in melting temperature between the inner layer 108 and the outer layer 106, which advantageously provides a faster heat bonding cycle during the manufacturing process and also prevents the inner layer 108 from being inadvertently heat sealed to the outer layer 106. In some aspects, the melting temperatures of the inner layer and the outer layer will differ by about 30-120° C., or about 50-120° C., or about 100-120° C. In some aspects, the melting temperatures of the inner layer and the outer layer will differ by at least 50° C., or at least 100° C.

[0049] In various aspects, the film is an extruded polymer film comprising Figure 1 The 5 layers shown are each coextruded to produce a single ply. In some aspects, the thickness of the single ply is 0.20-0.50 millimeters (mm). In some aspects, the thickness of the single 5-layer ply is 0.20 mm, 0.25 mm, 0.35 mm, 0.45 mm, or 0.5 mm.

[0050] In some aspects, the multilayer polymer films according to the present disclosure are characterized by certain material properties, including tear strength, oxygen transmission rate, abrasion resistance, puncture strength, and flex crack resistance, as determined according to American Society for Testing and Materials (ASTM) standards. For example, in some aspects, the film is characterized by a tear strength of about 7-9 pounds force (LbF) according to ASTM D-1004 Standard Test Method for Braves Tear of Plastic Film and Sheeting. In some aspects, the film is characterized by an oxygen transmission rate of 0.40-0.60 cubic centimeters per square meter (cc / m2) within 24 hours according to ASTM D-1307. 2 ), or less than 1cc / m 2 / day. In some aspects, the film is characterized by an abrasion resistance of at least 500 or at least 600 cycles before failure according to ASTM F-3300, a puncture strength of about 12-16 LbF according to ASTM F-1306, and / or a flex crack resistance of more than at least 800 or at least 900 cycles according to ASTM F-392. Preferably, the film is characterized by a combination of the above material properties, such as a combination of each of the tear strength, oxygen permeability, abrasion resistance, puncture strength and flex crack resistance as described above.

[0051] In a specific example of a multilayer polymer film according to the present disclosure, the material properties are shown in the following table.

[0052] Table 1: Material properties of representative multilayer polymer films

[0053]

[0054] A disposable flexible container consisting of at least one polymer sheet of a multilayer polymer film as described herein is also provided, which may also be referred to as a "film bag". The flexible container described herein includes a main body defining an internal space, the main body including at least one polymer sheet of a multilayer polymer film as described herein. In various aspects, the main body includes at least 2-4 polymer sheets. In some aspects, the main body is formed by two or four polymer sheets. In various aspects, the bag also includes at least one port extending through an opening in the bag and communicating with the internal space of the main body. In various aspects, the bag includes 2 to 4 ports. In various aspects, the volume of the internal space of the main body is 50-5000 liters or 100-5000 liters. In some aspects, the volume of the internal space of the main body is about 100 liters, about 250 liters, about 500 liters, about 750 liters, or about 1000 liters. In some aspects, the volume of the internal space of the main body is about 1000 liters, about 2000 liters, about 3000 liters, about 4000 liters, or about 5000 liters.

[0055] In various aspects, the bag is sterilized, such as by gamma irradiation.

[0056] In various aspects, the bag is suitable for containing a fluid, such as a fluid containing biological material including, for example, cells and / or cell products including viral particles and recombinant proteins or nucleic acids.

[0057] Figure 2 is a schematic diagram of a flexible container according to one aspect of the present invention. The container is shown in a two-dimensional view, which can also be considered a folded or collapsed view. The container is formed of four sheets of multilayer polymer film 202, which can be folded as shown for ease of packaging and assembly. Four ports 204 are also shown, which have associated conduits 206, clamps 210 and clamps 212, and associated fittings 208. The clamps 210 and clamps 212 can be, for example, clamps or sliding clamps.

[0058] Figure 3 is a schematic diagram of a flexible container according to an aspect of the present invention, showing four ports 304 in a three-dimensional view. Dimensions are in inches. The illustrated container has a volume of 50 liters, but the basic design is the same for containers of other volumes.

[0059] Figure 4A is a photograph of a representative flexible container made from a multilayer polymer film as described herein. The container was inflated with air to 2 psi at room temperature (approximately 70°F + / - 10°F) and monitored for a period of 17 months without loss of air.

[0060] Figure 4B is similar to Figure 4AA flexible container of the container described in was subjected to a burst test. In this test, the pressure was increased by 1 psi every 3 seconds. The bag shown in this article burst at 6 psi, which is much higher than the 2 psi pressure usually maintained to ensure the integrity of the bag. Importantly, this experiment showed that the failure point was at the end seal.

[0061] References to "one aspect", "on one hand", "some aspects", "other aspects" etc. in this specification indicate that one or more specific features, structures and / or characteristics according to the principles of the present disclosure may be included in conjunction with the aspect. However, such references do not necessarily mean that all aspects include multiple specific features, structures and / or characteristics, or that one aspect includes all features, structures and / or characteristics. Some aspects may include one or more such features, structures and / or characteristics and multiple combinations thereof. In addition, references to "one aspect", "on one hand", "some aspects", "other aspects" etc. in multiple places in the specification do not necessarily refer to the same aspect, nor are they independent or alternative aspects mutually exclusive with other aspects. When describing specific features, structures and / or characteristics in conjunction with an aspect, it should be understood that such features, structures and / or characteristics may also be used in conjunction with other aspects, unless clearly stated to the contrary. It should also be understood that such features, structures and / or characteristics may be used or exist alone, or in multiple combinations with each other to produce alternative aspects that are considered to be part of the present disclosure, because it is too troublesome to describe all the possible combinations and sub-combinations of features, structures and / or characteristics. In addition, various features, structures, and / or characteristics are described that may be exhibited by some aspects but not by other aspects. Similarly, various features, structures, and / or characteristics or requirements are described that may be features, structures, and / or characteristics or requirements of some aspects but may not be features, structures, and / or characteristics or requirements of other aspects. Therefore, the present disclosure is not limited to the aspects specifically described herein, and the examples of aspects disclosed herein are not intended to limit the broader aspects of the present disclosure.

[0062] It should be understood that common features in the drawings are identified by common reference numerals, and for the sake of brevity and convenience and without limitation, the description of common features is generally not repeated. For the purpose of clarity, not all components with the same reference numeral are numbered. In addition, a group of similar elements can be represented by numbers and letters, and generally only numbers (excluding letters associated with each similar element) can be used to refer to one or such elements or such elements as a group. It should be understood that in the following description, certain features in one figure can be used in different figures and are not necessarily individually labeled when appearing in different figures.

[0063] The various features, aspects or the like of the disposable containers or treatments described herein can be used independently or in combination. It should be understood that the containers and / or systems disclosed herein can be implemented in many different forms and should not be construed as being limited to the aspects shown in the drawings, such as described herein. On the contrary, providing these aspects enables the disclosure to convey certain aspects of the containers and / or treatment systems formed according to the various principles of the disclosure to those skilled in the art.

[0064] It should be understood that, as described herein, "aspects" (such as those shown in the accompanying drawings) may refer to illustrative representations of environments or articles or components in which the disclosed concepts or features may be provided or implemented, or to representations of ways in which only concepts or features may be provided or implemented. However, such illustrative aspects will be understood as examples (unless otherwise specified), and other ways of implementing the described concepts or features (such as those that can be understood by a person of ordinary skill in the art when learning the concepts or features from this disclosure) are within the scope of this disclosure. In addition, it should be understood that although multiple drawings may jointly show one or more aspects of multiple concepts or features in a single aspect of an environment, article or component incorporating such concepts or features, such concepts or features should be understood (unless otherwise specified) to be independent and separate from each other, and to be shown together for convenience, and are not intended to be limited to co-existence or co-use. For example, a feature shown or described as part of an aspect may be used alone, or used together with one or more other features to produce yet another aspect. Therefore, the subject matter is intended to cover such modifications and variations that fall within the scope of the appended claims and their equivalents.

[0065] In view of the above, it should be understood that the multiple aspects shown in the drawings have multiple separated and independent features, each feature has at least a unique benefit alone, which is desirable for the container, system and related methods of the present disclosure, but not critical. Therefore, in order to achieve at least some desired features and / or benefits described herein, multiple individual features described herein do not need to exist. Only one of multiple features can exist in a container or system formed according to the various principles of the present disclosure. Alternatively, one or more features described with reference to an aspect can be combined with one or more features of any other aspect provided herein. That is, any feature described herein can be mixed and matched to produce a hybrid design, and such a hybrid design is within the scope of the present disclosure. In addition, throughout the present disclosure, reference numerals are used to indicate general elements or general features of the disclosed aspects. The same reference numerals can be used to indicate multiple elements or features that are not identical in form, shape, structure, etc. but provide similar functions or benefits. Additional reference numerals (such as letters, relative to numbers) can be used to distinguish similar elements or features from each other.

[0066] In the context of the present invention, the phrases "at least one", "one or more", and "and / or" as used herein are open expressions that are both conjunctive and disjunctive in operation. The terms "one", "an", "the", "first", "second", etc., do not exclude a plurality. For example, the term "one" or "an" entity as used herein refers to one or more of that entity. Therefore, the terms "one" (or "one"), "one or more", and "at least one" can be used interchangeably herein. All directional references (e.g., proximal, distal, upper, lower, upward, downward, left, right, lateral, longitudinal, front, rear, top, bottom, above, below, vertical, horizontal, radial, axial, clockwise, counterclockwise, and / or the like) are used only for identification purposes to help the reader understand the present disclosure, and / or to distinguish areas of associated elements from each other, and do not limit the associated elements, particularly with respect to the position, orientation, or use of the present disclosure. Unless otherwise specified, connection references (e.g., attached, coupled, connected, and joined) are to be construed broadly and may include intermediate members between a collection of elements and relative movement between elements. Thus, connection references do not necessarily infer that two elements are directly connected and in fixed relation to each other. Identification references (e.g., primary, secondary, first, second, third, fourth, etc.) are not intended to indicate importance or priority, but are used to distinguish one feature from another.

[0067] The term "about" when used to refer to a particular value or range of values ​​includes values ​​within ±10% of the indicated value, including the value itself.

[0068] Unless otherwise stated, all percentages, parts, ratios, etc., are by weight. In addition, when the quantity, concentration or other values ​​or parameters of a list as a range, a preferred range or a preferred upper limit and a preferred lower limit are given, this should be understood as specifically disclosing all ranges formed by any logarithmic value of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether these ranges are disclosed separately. Unless otherwise stated, the numerical ranges listed herein are intended to include their endpoints, and all integers and fractions within the range. This does not mean that the scope of the present invention is limited to the specific values ​​listed when defining the range. When a component is expressed as being present in a range starting from 0, this component is an optional component (that is, it may exist or not). When the component is present, the optional component may be at least 0.1% by weight of a composition or copolymer, unless a lower amount is specified.

[0069] The terms "comprises," "comprising," "includes," "including," "has," "having," or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.

[0070] The term "consisting essentially of" when used in reference to the multilayer polymer film compositions described herein means that essentially only one or more polymers in the composition are the recited one or more polymers. As used herein, the term "essentially" means present in an amount greater than 95 wt % or greater than 99 wt %, based on the total weight of the polymer composition. The term does not exclude the presence of conventional additives or polymer carriers, as long as such polymer carriers are present only in small amounts (in amounts less than 5 wt % or less than 1 wt %). Any such small amounts of additional polymeric materials do not alter the basic and novel properties of the multilayer polymer film compositions described herein.

[0071] As used herein, the term "copolymer" refers to a polymer comprising copolymerized units resulting from the copolymerization of two or more comonomers, and the "copolymer" may be described with reference to the constituent comonomers or with reference to the amounts of constituent comonomers, e.g., "a copolymer comprising ethylene and 15 weight percent methyl acrylate." A description of a copolymer with reference to the constituent comonomers of the copolymer or the amounts of constituent comonomers refers to a copolymer containing copolymerized units of the specified comonomer (when a comonomer is specified, in the specified amount). Polymers having more than two monomers (e.g., terpolymers) are also included within the term "copolymer" as used herein. A dimer consists essentially of two copolymerized comonomers and a terpolymer consists essentially of three copolymerized comonomers. With respect to the copolymerized comonomers, the term "consisting essentially of" allows for the presence of small amounts (i.e., not more than 0.5 weight percent) of unrecited copolymerized units, which may be derived, for example, from impurities present in more common feedstocks or from the decomposition of the comonomers during the polymerization process.

[0072] Unless otherwise stated, all percentages, parts, ratios, etc., are by weight. In addition, when the quantity, concentration or other values ​​or parameters of a list as a range, a preferred range or a preferred upper limit and a preferred lower limit are given, this should be understood as specifically disclosing all ranges formed by any logarithmic value of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether these ranges are disclosed separately. Unless otherwise stated, the numerical ranges listed herein are intended to include their endpoints, and all integers and fractions within the range. This does not mean that the scope of the present invention is limited to the specific values ​​listed when defining the range. When a component is expressed as being present in the range from 0, this component is an optional component (that is, it may exist or not). When the component exists, the optional component can be at least 0.1% by weight of a composition or copolymer, unless a lower amount is specified.

[0073] The above discussion has a wide range of applications, and the above discussion is proposed for the purpose of illustration and description, and is not intended to limit the present disclosure to one form or multiple forms disclosed herein. It should be understood that, without departing from the concept, spirit and scope of the present disclosure, multiple additions, modifications and replacements can be made to the multiple aspects disclosed herein. In particular, it will be clear to those skilled in the art that, without departing from the concept, spirit or scope or features of the present disclosure, the principles of the present disclosure can be implemented in other forms, structures, arrangements, proportions and by other elements, materials and components. For example, in order to streamline the purpose of the present disclosure, the multiple features of the present disclosure are combined together in one or more aspects or configurations. However, it should be understood that the multiple features of some aspects or configurations of the present disclosure can be combined in alternative aspects or configurations. Although the present disclosure is presented according to multiple aspects, it should be understood that in order to realize at least some desired features and / or benefits of the present theme or to realize such individual features, the multiple individual features of the present theme do not need to exist in full. Those skilled in the art will appreciate that, without departing from the principles or spirit or scope of the present disclosure, the present disclosure can be used with many modifications or changes in the structure, arrangement, proportion, material, assembly, etc. used in the practice of the present disclosure, which are particularly suitable for specific environments and operating requirements. For example, an element shown as being formed as a whole can be composed of multiple parts, or an element shown as multiple parts can be formed as a whole, the operation of the element can be reversed or otherwise changed, and the size or size of the element can be changed. Similarly, although operations or behaviors or steps are described in a particular order, this should not be understood as requiring such a particular order, or that all operations or behaviors or steps must be performed to achieve the desired results. In addition, other embodiments are also within the scope of the following claims. Therefore, the aspects of the present disclosure are considered to be illustrative and not restrictive in all aspects, and the scope of the subject matter claimed is indicated by the attached claims, and is not limited to the previous description or the multiple specific aspects or arrangements described or illustrated herein. In view of the foregoing, the unique features of any aspect can be used, and these unique features can be claimed alone or in combination with the features of this aspect or any other aspect, and the scope of the subject matter is indicated by the attached claims, and is not limited to the previous description.

[0074] Although the foregoing invention has been described in detail by way of illustration and example for the purpose of clear understanding, it will be appreciated by those skilled in the art that certain changes and modifications may be implemented within the scope of the appended claims. In addition, each reference provided herein is incorporated in its entirety by reference, just as each reference is incorporated individually by reference. In the event of a conflict between the present application and the references provided herein, the present application shall prevail.

Claims

1. A multilayer polymer film comprising an inner biomaterial contact layer and an outer layer, wherein the outer layer comprises a polymer selected from the group consisting of polyester elastomeric copolymers, polyethylene terephthalate (PET), nylon, polyethylene, polypropylene, thermoplastic elastomers and copolymers and mixtures thereof, wherein the melting temperatures of the inner contact layer and the outer layer differ by 30-120°C.

2. The multilayer polymer film of claim 1 , further comprising a gas barrier layer disposed between the inner biomaterial contact layer and the outer layer, a first tie layer disposed between the inner contact layer and the gas barrier layer, and a second tie layer disposed between the gas barrier layer and the outer layer.

3. The multilayer polymer film according to claim 1 or 2, wherein the outer layer comprises a mixture of at least two polymers selected from the group consisting of polyester elastomeric copolymers, polyethylene terephthalate (PET), nylon, polyethylene, polypropylene, thermoplastic elastomers.

4. The multilayer polymer film of claim 3, wherein the outer layer comprises a mixture of at least two polyester elastomeric copolymers.

5. The multilayer polymer film of any one of claims 1 to 4, wherein the inner biomaterial contact layer comprises low density polyethylene.

6. The multilayer polymer film of claim 5, wherein the low density polyethylene is a linear low density polyethylene or an ultra low density polyethylene, or a mixture thereof.

7. The multilayer polymer film according to any one of claims 2 to 6, wherein the gas barrier layer comprises one or more materials selected from the group consisting of ethylene vinyl alcohol (EVOH), polyvinylidene chloride (PVDC), liquid crystal polymer (LCP) and nylon 6.

8. The multilayer polymer film of any one of claims 2 to 7, wherein the tie layer comprises one or more materials selected from the group consisting of ethyl acrylate, ethacrylic acid, modified ethylene vinyl acetate, and polyethylene.

9. The multilayer polymer film of claim 8, wherein the polyethylene is maleic anhydride grafted polyethylene.

10. The multilayer polymer film according to any one of claims 1 to 9, wherein the film is an extruded polymer film.

11. The multilayer polymer film of claim 10, wherein at least 5 layers of the film are coextruded to produce a single ply.

12. The multilayer polymer film according to claim 11, wherein the thickness of the individual plies is 0.20-0.50 mm.

13. The multilayer polymer film of any one of claims 1 to 12, wherein the inner biomaterial contact layer and the outer layer have different melting temperatures.

14. A multilayer polymer film comprising an inner biomaterial contact layer comprising about 70% by weight low density polyethylene, an outer layer comprising about 5-10 wt. % of a polyester elastomeric copolymer or a mixture of polyester elastomeric copolymers having a melt temperature of about 400-450° F., a gas barrier layer disposed between the inner biomaterial contacting layer and the outer layer, a first tie layer disposed between the inner contact layer and the gas barrier layer, and a second tie layer disposed between the gas barrier layer and the outer layer, wherein the film has an oxygen transmission rate of less than about 0.5 cc / m at 70°F under conditions according to ASTM D-1307 2 -day-atm, wherein the film has a tear strength of at least about 8 LbF under conditions according to ASTM D-1004, The melting temperatures of the inner contact layer and the outer layer differ by 100-120°C.

15. A disposable flexible film bag comprising a body defining an interior space, said body comprising at least one polymer sheet of the multilayer polymer film according to any one of claims 1 to 14, wherein said bag is suitable for containing a fluid.

16. The disposable flexible film bag according to claim 15, wherein the body comprises at least 2-4 polymer sheets of a multi-layer polymer film.

17. The disposable flexible film bag of claim 15, comprising end seals having a strength characteristic of being able to withstand at least about 2 pounds per square inch (psi) for at least about 12 months without failure.

18. The disposable flexible film bag according to claim 15 or 16, wherein: The bag also includes at least one port assembly extending through the opening in the bag and communicating with the interior space of the body.

19. The disposable flexible film bag according to any one of claims 15-16 or 18, wherein the volume of the inner space of the main body is 50-5000 liters.

20. The disposable flexible film bag according to any one of claims 15-16 or 18-19, wherein the bag is sterile.

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