Single-use bag for medicinal chemical manufacturing

Abstract

To provide a single-use bag for medicinal chemical manufacturing that is biodegradable, has a steam barrier, and is resistant to cell culture conditions.SOLUTION: The single-use bag for medicinal chemical manufacturing comprises a laminated film bag having a biodegradable polymer layer and an inorganic layer.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present disclosure relates to a single-use bag for pharmaceutical production.

Background Art

[0002] In pharmaceutical production, as containers used in various processes such as containers for liquid media for cell culture, containers for buffers for purification processes, storage containers for various solutions, and sampling containers for various solutions, single-use bags that do not require cleaning validation and can reduce the risk of contamination are widely used. The disposal of single-use bags used in pharmaceutical production is mainly carried out by landfill or incineration, and the problem of environmental impact has become prominent. Therefore, single-use bags for pharmaceutical production are required to have biodegradability to reduce the environmental impact.

[0003] So far, various materials have been proposed as biodegradable packaging materials. For example, Patent Document 1 describes a film having an inorganic vapor deposition film on at least one surface of a resin layer using a resin composition containing an aliphatic polyester-based resin. Patent Document 2 describes a laminated film in which an anchor layer and an inorganic layer are sequentially laminated on at least one side of a base film and the average linear expansion rate in thermomechanical analysis is in a specific range. Patent Document 3 describes a biodegradable film in which a base film containing a biodegradable resin layer having an oxygen permeability in a specific range and an inorganic vapor deposition film are laminated. Patent Document 4 describes a coextruded biaxially oriented aliphatic polyester-based roll film composed of at least three layers, at least one of the two outermost layers being an inorganic particle-containing layer, and the thickness of the inorganic particle-containing layer, the maximum particle diameter of the inorganic particles, and the average particle diameter of the inorganic particles satisfying a specific relationship and the static friction coefficient being in a specific range.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

[0005] Single-use bags for pharmaceutical manufacturing are required to have not only biodegradability but also water vapor barrier properties to prevent deterioration of the medicinal liquid inside. In addition, in the production of biopharmaceuticals, resistance under cell culture conditions may also be required. However, there has been no knowledge of single-use bags for pharmaceutical manufacturing that have both of the above properties. In view of the above circumstances, the present disclosure relates to a single-use bag for pharmaceutical production that has biodegradability, water vapor barrier properties, and resistance under cell culture conditions. [Means for solving the problem]

[0006] Means for solving the above problems include the following aspects. <1> A single-use bag for pharmaceutical production comprising a bag body made of a laminated film having a biodegradable polymer layer and an inorganic layer. <2> The inorganic layer comprises at least one layer selected from the group consisting of an aluminum layer and a silicon nitride layer; <1> A single-use bag for pharmaceutical manufacturing as described in . <3> The inorganic layer comprises at least one deposited layer selected from the group consisting of aluminum and silicon nitride; <1> or <2> A single-use bag for pharmaceutical manufacturing as described in . <4> The biodegradable polymer of the biodegradable polymer layer comprises an aliphatic polyester; <1> ~ <3> A single-use bag for pharmaceutical production according to any one of the preceding claims. <5> The single-use bag for pharmaceutical manufacturing according to <4>, wherein the aliphatic polyester contains at least one polyester selected from the group consisting of polybutylene succinate and polycaprolactone. <6> The single-use bag for pharmaceutical manufacturing according to any one of <1> to <5>, wherein the thickness of the inorganic layer is 0.05 μm to 1.5 μm. <7> The single-use bag for pharmaceutical manufacturing according to any one of <1> to <6>, wherein the thickness of the biodegradable polymer layer is 5 μm to 200 μm. <8> The single-use bag for pharmaceutical manufacturing according to any one of <1> to <7>, wherein the ratio of the thickness of the biodegradable polymer layer to the thickness of the inorganic layer is 3 to 4000. <9> The single-use bag for pharmaceutical manufacturing according to any one of <1> to <8>, wherein the laminated film has a two-layer structure of a biodegradable polymer layer and an inorganic layer. <10> The single-use bag for pharmaceutical manufacturing according to any one of <1> to <9>, wherein the laminated film does not have an anchor layer. <11> The water vapor transmission rate of the laminated film is 25 g / m 2 / 24 hours or less. The single-use bag for pharmaceutical manufacturing according to any one of <1> to <10>. <12> The reduction rate of the tensile strength of the laminated film measured at a tensile speed of 500 mm / min after standing for 72 hours under the conditions of 37 °C and 95% RH is 10% or less. The single-use bag for pharmaceutical manufacturing according to any one of <1> to <11>.

Advantages of the Invention

[0007] According to the present disclosure, there is provided a single-use bag for pharmaceutical manufacturing having biodegradability, water vapor barrier properties, and resistance under cell culture conditions.

Brief Description of the Drawings

[0008]

Figure 1

Figure 2

Mode for Carrying Out the Invention

[0009] Hereinafter, the mode for carrying out the embodiment of the present disclosure will be described in detail. However, the embodiments of the present disclosure are not limited to the following embodiments. In the following embodiments, the components (including element steps, etc.) are not essential unless otherwise specified. The same applies to numerical values and their ranges, which do not limit the embodiments of the present disclosure.

[0010] In the present disclosure, the term "step" includes not only a step independent of other steps but also a step that cannot be clearly distinguished from other steps as long as the purpose of the step is achieved. In the numerical range indicated by "~" in the present disclosure, the numerical values described before and after "~" are included as the minimum value and the maximum value, respectively. In the numerical ranges described step by step in the present disclosure, the upper limit value or the lower limit value described in one numerical range may be replaced with the upper limit value or the lower limit value of the numerical range described in other step-by-step descriptions. Also, in the numerical ranges described in the present disclosure, the upper limit value or the lower limit value of the numerical range may be replaced with the value shown in the examples. In the present disclosure, each component may contain a plurality of corresponding substances. When there are a plurality of substances corresponding to each component in the composition, the content rate or content of each component means the total content rate or content of the plurality of substances present in the composition, unless otherwise specified. In the present disclosure, a combination of two or more preferred embodiments is a more preferred embodiment. In the present disclosure, the term "layer" includes not only the case where it is formed over the entire region where the layer exists but also the case where it is formed only in a part of the region when observing the region where the layer exists.

[0011] <Single-Use Bag for Pharmaceutical Production> The single-use bag for pharmaceutical production of the present disclosure (hereinafter, also simply referred to as "the single-use bag of the present disclosure") includes a bag body made of a laminated film having a biodegradable polymer layer and an inorganic layer.

[0012] The single-use bag of the present disclosure is a single-use bag used in any manufacturing process of pharmaceuticals. For example, this bag can be used as a container for a liquid medium for cell culture, a buffer solution for a purification process, a storage container for various solutions, a sampling container for various solutions, a culture container, a mixer, or a container for liquid mixing, etc.

[0013] The "single-use bag" refers to a bag-shaped container assumed to be used only once, and is contrasted with a container that is repeatedly used after being washed. According to the single-use bag, processes such as washing, sterilization, and validation can be omitted. Also, the risk of contamination can be reduced.

[0014] "Biodegradable" means the property that a substance decomposes by biological activity. In the present disclosure, a biodegradable polymer is a polymer that undergoes composting for a maximum of 12 weeks by a disintegration test conforming to ISO 16929:2021 (corresponding to JIS K6952:2008), and finally the residue after sieving with a sieve having a mesh size of 2 mm is 10% by mass or less. Since the single-use bag for pharmaceutical production of the present disclosure has a biodegradable polymer layer, it is excellent in biodegradability. Specifically, the disintegration test is carried out as follows. The evaluation sample is fixed to a frame, and the temperature condition is set to less than 75°C for the first week, and then less than 65°C for the subsequent period, and at least 60°C for at least one week and at least 40°C for at least four consecutive weeks for the disintegration test. The period until the residue after sieving with a sieve having a mesh size of 2 mm becomes 10% by mass or less is preferably within 9 weeks, more preferably within 6 weeks, and even more preferably within 3 weeks.

[0015] The single-use bag of the present disclosure includes a bag body made of a laminated film having a biodegradable polymer layer and an inorganic layer. In a single-use bag for pharmaceutical manufacturing, in order to suppress deterioration or concentration change of the content liquid due to evaporation of the content liquid or intrusion of external vapor, it is preferable that the bag body has high water vapor barrier properties. In the single-use bag of the present disclosure, since a laminated film having an inorganic layer is used, it is considered to have excellent water vapor barrier properties. Further, in the production of biopharmaceuticals such as antibodies and vaccines, a single-use bag may be used for cell culture. The single-use bag of the present disclosure has also been found to be excellent in resistance and less likely to deteriorate in strength even under relatively high-temperature cell culture conditions (for example, 37°C).

[0016] [Bag body] The bag body used in the single-use bag of the present disclosure is a bag body made of a laminated film having a biodegradable polymer layer and an inorganic layer. The shape of the bag body is not particularly limited as long as it is a bag body (that is, a bag-shaped product made of a flexible material), and can be appropriately selected according to the use. Examples of the shape of the bag body include a bag shape such as a rectangle or any other shape (polygon, circle, ellipse, etc.), a polygonal prism shape such as a cylindrical shape or a cube, and a gusset bag. The bag body may be provided with an opening that serves as an outlet and / or an inlet for the contents. An additional member described later may be connected to the opening. The method for producing the bag body using the laminated film is not particularly limited, and two laminated films may be welded at the outer edge by heat pressing or the like to produce the bag body. Alternatively, two laminated films may be bonded together using an adhesive at the outer edge.

[0017] (Laminated film) The laminated film has a biodegradable polymer layer and an inorganic layer. FIG. 1 shows a schematic cross-sectional view of a laminated film in one embodiment. The laminated film 10 shown in FIG. 1 has a biodegradable polymer layer 12 and an inorganic layer 14 laminated on the biodegradable polymer layer 12. Note that the size of each layer shown is conceptual and is not limited to the embodiment of FIG. 1. Also, FIG. 1 shows an example of a laminated film having one layer each of a biodegradable polymer layer and an inorganic layer, but the laminated film is not limited to the embodiment of FIG. 1.

[0018] The laminated film may have only one biodegradable polymer layer or two or more biodegradable polymer layers. Also, the laminated film may have only one inorganic layer or two or more inorganic layers. The laminated film may adopt any laminated structure as long as at least one layer each of the biodegradable polymer layer and the inorganic layer is laminated. Typically, at least one of the outermost layers is a biodegradable polymer layer, which becomes the inner surface when a bag body is manufactured. For example, the laminated film may have a laminated structure shown in the following (a) to (g). In the following (a) to (g), the descriptions of "biodegradable polymer layer 1" and "biodegradable polymer layer 2" do not represent the types of the respective layers, but mean that each polymer layer is an independent polymer layer. Therefore, the type of each polymer layer is arbitrary and may be the same or different. Similarly, the descriptions of "inorganic layer 1" and "inorganic layer 2" do not represent the types of the respective layers, but mean that each inorganic layer is an independent inorganic layer. Therefore, the type of each inorganic layer is arbitrary and may be the same or different.

[0019] (a) Biodegradable polymer layer 1 / Inorganic layer 1 (b) Biodegradable polymer layer 1 / Biodegradable polymer layer 2 / Inorganic layer 1 (c) Biodegradable polymer layer 1 / Inorganic layer 1 / Inorganic layer 2 (d) Biodegradable polymer layer 1 / Biodegradable polymer layer 2 / Inorganic layer 1 / Inorganic layer 2 (e) Biodegradable polymer layer 1 / Inorganic layer 1 / Biodegradable polymer layer 1 (f) Biodegradable polymer layer 1 / Biodegradable polymer layer 2 / Inorganic layer 1 / Biodegradable polymer layer 1 (g) Biodegradable polymer layer 1 / Biodegradable polymer layer 2 / Inorganic layer 1 / Biodegradable polymer layer 1 / Biodegradable polymer layer 2

[0020] From the viewpoint of ease of production, it is preferable that the laminated film has a two-layer structure of a biodegradable polymer layer and an inorganic layer (that is, as in the above (a), it is composed of one layer of biodegradable polymer layer and one layer of inorganic layer).

[0021] An anchor layer may or may not be interposed between the layers of the laminated film. The anchor layer is a layer containing an anchor coating agent. Examples of the anchor coating agent include polyester resins, polyurethane resins, polyacrylic resins, polyvinyl alcohol resins, polyolefin resins, ethylene vinyl alcohol resins, vinyl-modified resins, oxazoline group-containing resins, carbodiimide group-containing resins, epoxy group-containing resins, isocyanate group-containing resins, alkoxyl group-containing resins, modified styrene resins, modified silicone resins, etc. The anchor coating agent may be used alone or in combination of two or more. For the formation of the anchor layer, in addition to the anchor coating agent, an appropriate solvent can be used. Examples of the solvent include organic solvents such as hydrocarbon solvents (cyclohexane, benzene, toluene, etc.), alcohol solvents (methyl alcohol, ethyl alcohol, isopropanol, etc.), ester solvents (ethyl acetate, etc.), ketone solvents (acetone, methyl ethyl ketone, etc.), amide solvents (dimethylformamide, etc.), and glycol solvents. The solvent may be used alone or in combination of two or more. From the viewpoint of preventing the components of the anchor layer from mixing into the contents when used as a single-use bag for pharmaceutical production, it is preferable that the laminated film does not have an anchor layer. When the laminated film has an anchor layer, it is necessary to verify as required that the eluates and residual solvents not recognized in pharmaceuticals from the inner layer of the laminated film are within the reference values (for example, meeting the regulations ICH-Q3C regarding residual solvents).

[0022] The thickness of the laminated film is not particularly limited, preferably 5.05 μm or more, more preferably 10.05 μm or more, and even more preferably 15.05 μm or more. The thickness of the laminated film is preferably 201.5 μm or less, more preferably 181.5 μm or less, and even more preferably 151.5 μm or less. From this perspective, the thickness of the laminated film is preferably 5.05 μm to 201.5 μm, more preferably 10.05 μm to 181.5 μm, and even more preferably 15.05 μm to 151.5 μm. In the present disclosure, the thickness of the laminated film represents the average thickness and is measured as follows. At a location where the laminated film is not adhered to other films or members (for example, the adhesion part of the laminated films for producing the bag body or other than the location where the laminated film is connected to other members), the average value of the thicknesses at five locations measured by a U-shaped steel plate micrometer (for example, manufactured by Mitutoyo Corporation, model number: PMU150 - 25MJ) is obtained.

[0023] -Biodegradable polymer layer- The biodegradable polymer layer is a layer containing a biodegradable polymer. Examples of the biodegradable polymer include biodegradable polyesters, natural polymers, polyvinyl alcohol-based resins, and the like. The biodegradable polymer layer may contain one type or two or more types of biodegradable polymers. When the laminated film contains two or more biodegradable polymer layers, the biodegradable polymers contained in each biodegradable polymer layer may be the same or different from each other.

[0024] Examples of the biodegradable polyester include aliphatic polyesters, aromatic polyesters, and aliphatic aromatic polyesters. Examples of aliphatic polyesters include succinate-based polymers such as polyethylene succinate (PES), polybutylene succinate (PBS), and polybutylene succinate adipate (PBSA); polylactic acid (PLA)-based polymers such as polylactic acid and copolymers of lactic acid and other copolymer components (e.g., hydroxycarboxylic acids, aliphatic dicarboxylic acids, aliphatic diols, lactones, etc.); polybutylene adipate; polycaprolactone (PCL); polyglycolic acid; polydioxanone; polyhydroxypropionate, polyhydroxybutyrate (PHB), polyhydroxyvalerate, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and other polyhydroxyalkanoates. Among them, at least one selected from the group consisting of polybutylene succinate (PBS) and polycaprolactone (PCL) is preferred. Polybutylene succinate (PBS) and polycaprolactone (PCL) are particularly excellent in biodegradability and tend to be excellent in terms of resistance under cell culture conditions and gamma-ray resistance. Examples of aliphatic-aromatic polyesters include polybutylene adipate terephthalate (PBAT).

[0025] Examples of natural polymers include cellulose, cellulose acetate (CA), and thermoplastic starch (TPS).

[0026] Among them, from the viewpoint of more excellent biodegradability, biodegradable polyesters are preferred, and aliphatic polyesters are more preferred.

[0027] From the viewpoint of heat resistance, the melting point of the biodegradable polymer is preferably 37°C or higher, more preferably 40°C or higher, and even more preferably 50°C or higher. From the viewpoint of ease of processing and the like, the melting point of the biodegradable polymer is preferably 200°C or lower, more preferably 150°C or lower, and even more preferably 130°C or lower. From such viewpoints, the melting point of the biodegradable polymer is preferably 37°C to 200°C, more preferably 40°C to 150°C, and even more preferably 50°C to 130°C.

[0028] Single-use bags for pharmaceutical manufacturing are typically used after being sterilized. The sterilization treatment is performed, for example, by irradiation with radiation such as gamma rays. Although the biodegradability of the polymer may change when irradiated with gamma rays, the biodegradable polymer layer is preferably a polymer layer that satisfies the biodegradability criteria even after being irradiated with, for example, 50 kGy of gamma rays.

[0029] The biodegradable polymer layer may contain only the biodegradable polymer, or may contain other components in addition to the biodegradable polymer. Examples of other components include inorganic fillers and other additives. Examples of inorganic fillers include talc, calcium carbonate, silicon dioxide, titanium dioxide, mica, clay, and the like. Examples of other additives include plasticizers, heat stabilizers, antioxidants, ultraviolet absorbers, antistatic agents, and the like. Examples of plasticizers include aliphatic polycarboxylic acid esters, aliphatic polyhydric alcohol ester oxyacids esters, epoxy-based plasticizers, and the like. From the viewpoints of ease of manufacturing, reducing the elution of components into the contents, and obtaining excellent biodegradability, the content of the biodegradable polymer in the biodegradable polymer layer is preferably 50% by mass or more, more preferably 70% by mass or more, and even more preferably 90% by mass or more. The biodegradable polymer layer may contain only the biodegradable polymer.

[0030] The thickness of the biodegradable polymer layer is not particularly limited, and from the viewpoints of strength, gas barrier properties, and processability in production, it is preferably 5 μm or more, more preferably 10 μm or more, and even more preferably 15 μm or more. The thickness of the biodegradable polymer layer is preferably 200 μm or less, more preferably 180 μm or less, and even more preferably 150 μm or less. From such viewpoints, the thickness of the biodegradable polymer layer is preferably 5 μm to 200 μm, more preferably 10 μm to 180 μm, and even more preferably 15 μm to 150 μm. When the laminated film has two or more biodegradable polymer layers, the thickness of the biodegradable polymer layer represents the total thickness of the two or more biodegradable polymer layers. In the present disclosure, the thickness of the biodegradable polymer layer represents the average thickness and is measured as follows. At a location where the laminated film is not adhered to another film or member (for example, a bonding portion between laminated films for producing a bag body or a location other than a location where the laminated film is connected to another member), the average value of the thicknesses at five locations measured by a U-shaped steel plate micrometer (for example, manufactured by Mitutoyo Corporation, model number: PMU150-25MJ) is determined.

[0031] As the biodegradable polymer layer, an available film may be used as it is, or a biodegradable polymer available as pellets or the like may be formed into a film and used. Examples of the forming method include a method of forming a biodegradable polymer or a composition containing a biodegradable polymer and other components used as necessary by extrusion molding, co-extrusion molding, blow molding, or the like.

[0032] -Inorganic layer- The inorganic layer is a layer of an inorganic substance and imparts water vapor barrier properties to the laminated film. Examples of the inorganic substances include simple substances such as aluminum, silicon, silver, indium, copper, chromium, nickel, titanium, etc.; compounds such as aluminum oxide, silicon oxide, titanium oxide, zinc oxide, aluminum nitride, silicon nitride, zinc sulfide, aluminum carbon oxide, aluminum oxynitride, silicon carbon oxide, silicon oxynitride, silicon carbon oxynitride, etc. The inorganic substances may be used alone or in combination of two or more. From the viewpoint of excellent water vapor barrier property, aluminum and silicon nitride are preferable as the inorganic substances. When the transparency of the laminated film is required, silicon nitride is particularly useful.

[0033] The method for forming the inorganic layer is not particularly limited, and a forming method capable of obtaining a desired thickness can be appropriately selected. From the viewpoint of easily forming a thin film with a desired thickness, vapor deposition is preferable. Examples of the vapor deposition include physical vapor deposition (PVD) and chemical vapor deposition (CVD). Examples of the physical vapor deposition include vacuum vapor deposition, sputtering, and ion plating. Two or more inorganic layers may be formed by combining different forming methods. From the viewpoint of adhesion, sputtering is preferable.

[0034] Among them, from the viewpoint of easily forming an inorganic layer with excellent water vapor barrier property, the inorganic layer is preferably at least one vapor deposition layer selected from the group consisting of aluminum and silicon nitride, and more preferably at least one vapor deposition layer selected from the group consisting of an aluminum vacuum vapor deposition layer and a silicon nitride sputtering layer.

[0035] The thickness of the inorganic layer is not particularly limited. From the viewpoint of obtaining better water vapor barrier properties, it is preferably 0.05 μm or more, more preferably 0.08 μm or more, and even more preferably 0.1 μm or more. From the viewpoints of ease of production and excellent followability, the thickness of the inorganic layer is preferably 1.5 μm or less, more preferably 1.3 μm or less, and even more preferably 1 μm or less. From such viewpoints, the thickness of the inorganic layer is preferably 0.05 μm to 1.5 μm, more preferably 0.08 μm to 1.3 μm, and even more preferably 0.1 μm to 1 μm. When the laminated film has two or more inorganic layers, the thickness of the inorganic layer represents the total thickness of two or more inorganic layers. When there is no special specification, the thickness of the inorganic layer is measured using a stylus surface roughness meter (for example, manufactured by Bruker Corporation, model number: Dektak) with a monitor piece at a location where the inorganic layer is not adhered to other films or members of the laminated film. When the thickness is not uniform, the thickness of the inorganic layer is taken as the average of the thicknesses measured at five locations. The thickness of the inorganic layer may also be measured by methods such as measuring the change in thickness with a micrometer, SEM cross-sectional analysis, and weight measurement.

[0036] When the inorganic layer is a vacuum deposition layer (for example, an aluminum vacuum deposition layer), the thickness of the inorganic layer is preferably 0.05 μm or more, more preferably 0.08 μm or more, and even more preferably 0.1 μm or more. From the viewpoints of ease of production and excellent followability, the thickness of the inorganic layer is preferably 1 μm or less, more preferably 0.7 μm or less, and even more preferably 0.5 μm or less. From such viewpoints, the thickness of the inorganic layer is preferably 0.05 μm to 1 μm, more preferably 0.08 μm to 0.7 μm, and even more preferably 0.1 μm to 0.5 μm. The thickness of the vacuum deposition layer is measured by light transmittance measurement at a location where it is not adhered to other films or members of the laminated film. When the thickness is not uniform, the thickness of the inorganic layer is taken as the average of the thicknesses measured at five locations. The thickness of the vacuum deposition layer may also be measured using a method of measuring the change in thickness with a micrometer, SEM cross-sectional analysis, weight measurement, or the like.

[0037] When the inorganic layer is a sputter layer (for example, a silicon nitride sputter layer), the thickness of the inorganic layer is preferably 0.5 μm or more, more preferably 0.8 μm or more, and even more preferably 1.0 μm or more. From the viewpoint of ease of manufacture and excellent followability, the thickness of the inorganic layer is preferably 1.5 μm or less, more preferably 1.4 μm or less, and even more preferably 1.3 μm or less. From such a viewpoint, the thickness of the inorganic layer is preferably 0.5 μm to 1.5 μm, more preferably 0.8 μm to 1.4 μm, and even more preferably 1.0 μm to 1.3 μm. The thickness of the sputter layer is measured using a stylus surface roughness meter (for example, manufactured by Bruker Corporation, model number: Dektak) with a monitor piece at a location where it is not adhered to other films or members of the laminated film. When the thickness is not uniform, the thickness of the sputter layer is taken as the average of the thicknesses measured at five locations. The thickness of the sputter layer may also be measured using a method of measuring the change in thickness with a micrometer, SEM cross-sectional analysis, weight measurement, or the like.

[0038] In the laminated film, the ratio of the thickness of the biodegradable polymer layer to the thickness of the inorganic layer is preferably 3 to 4000, and more preferably 7 to 2250. When the laminated film has two or more biodegradable polymer layers and / or two or more inorganic layers, the above ratio represents the ratio of the total thickness of the biodegradable polymer layer to the total thickness of the inorganic layer. In one aspect, when the inorganic layer is a vacuum deposition layer (for example, an aluminum vacuum deposition layer), the above ratio is preferably 5 to 4000, and more preferably 14 to 2250. In one aspect, when the inorganic layer is a sputtered layer (for example, a silicon nitride sputtered layer), the above ratio is preferably from 3 to 400, more preferably from 7 to 225.

[0039] The lower the water vapor transmission rate of the laminated film, the more preferable. For example, the water vapor transmission rate of the laminated film is preferably 25 g / m 2 / 24 h or less, more preferably 5 g / m 2 / 24 h or less, still more preferably 1 g / m 2 / 24 h or less. The water vapor transmission rate of the laminated film is measured by a water vapor transmission rate test using an infrared sensor method in accordance with ASTM F1249 (corresponding to JIS K7129-2:2019). In the water vapor transmission rate test, a water vapor transmission rate tester (for example, manufactured by Mocon, model number: PEMATRAN W3 / 33) is used to permeate water vapor at 23°C and 90% RH through the laminated film, and the water vapor permeating through the laminated film and carried by dry nitrogen is detected by an infrared sensor to measure the water vapor transmission rate.

[0040] From the viewpoint of strength, the tensile strength of the laminated film is preferably 10 N / 15 mm or more, more preferably 15 N / 15 mm or more, and still more preferably 23 N / 15 mm or more. In the present disclosure, the tensile strength is measured using a tensile tester in accordance with JIS Z0238:1998 (for example, manufactured by IMADA, configuration: digital force gauge, model number ZTS-1000N, electric measurement stand, model number: MX2-1000N-L-V750) at a tensile speed of 500 mm / min.

[0041] The laminated film preferably has resistance under cell culture conditions. For example, the rate of decrease in the tensile strength of the laminated film measured at a tensile speed of 500 mm / min after standing for 72 hours under the conditions of 37°C and 95% RH is preferably 10% or less, more preferably 5% or less, and still more preferably 2% or less. The rate of decrease in the tensile strength is determined by the following formula. Rate of decrease in tensile strength (%) = ((Tensile strength before standing for 72 hours) - (Tensile strength after standing for 72 hours)) / (Tensile strength before standing for 72 hours) × 100

[0042] [Additional member] In addition to the bag body, the single-use bag of the present disclosure may have other members. For example, the single-use bag of the present disclosure may further have members such as a tube, a valve, a connector, a cap, a port, a clamp, and a joint. The additional member can be used, for example, to be connected to the opening of the bag body to serve as a moving path for the content or to control the movement.

[0043] Fig. 2 shows a schematic plan view of a single-use bag in one embodiment. The single-use bag 20 includes a bag body 22 made of a laminated film having a biodegradable polymer layer and an inorganic layer. The bag body 22 is formed by welding two laminated films at the outer periphery 24. Three ports 26 are attached to the bag body 22, and a tube 28 is inserted into each port. Desired members such as a clamp 30 and a coupling 32 can be attached to the tube 28. However, the single-use bag of the present disclosure is not limited to the mode shown in Fig. 2.

Example

[0044] Next, embodiments of the present disclosure will be specifically described by examples, but the embodiments of the present disclosure are not limited to these examples.

[0045] <Reference Example 1> Aliphatic polyester-based pellets (polybutylene succinate (manufactured by Mitsubishi Chemical Corporation, model number: Bio-PBS FD92PM, hereinafter PBS)) were used, and film forming by die extrusion molding was performed at an extrusion temperature of 170 °C, a take-up speed of 1.5 m / min, and a drying temperature of 80 °C to produce a film with a thickness of 100 μm. The thickness of the film was determined as the average value of the thicknesses at five locations measured by a U-shaped steel plate micrometer (manufactured by Mitutoyo Corporation, model number: PMU150-25MJ). The results are shown in Table 1.

[0046] <Reference Example 2> Aliphatic polyester pellets (polycaprolactone (manufactured by Ingevity, model number: Capa6500, hereinafter referred to as PCL)) were used, and film forming was performed by die extrusion molding at an extrusion temperature of 140 °C, a take-up speed of 1.5 m / min, and a drying temperature of 80 °C to produce a film with a thickness of approximately 100 μm. The thickness of the film was determined as the average value of the thicknesses at five locations measured by a U-shaped steel plate micrometer (manufactured by Mitutoyo Corporation, model number: PMU150-25MJ). The results are shown in Table 1.

[0047] <Example 1> Aluminum was vacuum-deposited on the same PBS film as in Reference Example 1 to form a deposition layer with a thickness of approximately 0.1 μm, and a laminated film was produced. The thickness of the laminated film was determined as the average value of the thicknesses at five locations measured by a U-shaped steel plate micrometer (manufactured by Mitutoyo Corporation, model number: PMU150-25MJ). The results are shown in Table 1.

[0048] <Example 2> Si3N4 was sputter-treated on the same PBS film as in Reference Example 1 to form a sputter layer with a thickness of approximately 1 μm, and a laminated film was produced. The thickness of the laminated film was determined as the average value of the thicknesses at five locations measured by a U-shaped steel plate micrometer (manufactured by Mitutoyo Corporation, model number: PMU150-25MJ). The results are shown in Table 1.

[0049] <Example 3> Aluminum was vacuum-deposited on the same PCL film as in Reference Example 2 to form a deposition layer with a thickness of approximately 0.1 μm, and a laminated film was produced. The thickness of the laminated film was determined as the average value of the thicknesses at five locations measured by a U-shaped steel plate micrometer (manufactured by Mitutoyo Corporation, model number: PMU150-25MJ). The results are shown in Table 1.

[0050] <Example 4> The same PCL film as in Reference Example 2 was sputter-treated with Si3N4 to form a sputter layer of about 1 μm, and a laminated film was produced. The thickness of the laminated film was determined as the average value of the thicknesses at five locations measured using a U-shaped steel plate micrometer (manufactured by Mitutoyo Corporation, model number: PMU150-25MJ). The results are shown in Table 1.

[0051] 〔Water vapor transmission rate〕 Using the infrared sensor method in accordance with ASTM F1249 (corresponding to JIS K7129-2:2019), the water vapor transmission rate tests of the films of Reference Examples 1 and 2 and Examples 1 to 4 were carried out. In the water vapor transmission rate test, a water vapor transmission rate tester (manufactured by Mocon, model number: PEMATRAN W3 / 33) was used to permeate water vapor at 23°C and 90% RH through the film, and the water vapor permeating through the film and carried by dry nitrogen was detected by an infrared sensor to measure the water vapor transmission rate. The results are shown in Table 1.

[0052] 〔Biodegradability〕 The films of Reference Example 1 and Reference Example 2 were irradiated with gamma rays of about 50 kGy. Then, a disintegration test in accordance with ISO 16929:2021 (corresponding to JIS K6952:2008) was carried out. Specifically, the evaluation samples were fixed to a frame, and the temperature condition was set to less than 75°C for the first week, and then to less than 65°C, and at least 60°C for at least one week and at least 40°C for at least four consecutive weeks for the disintegration test. The time until the aliphatic polyester-based film completely disintegrated was measured. The results are shown in Table 1.

[0053] 〔Melting point〕 The films of Reference Example 1 and Reference Example 2 were irradiated with gamma rays of about 50 kGy. Then, a high-sensitivity differential scanning calorimeter (manufactured by Hitachi High-Tech Science Corporation, model number: X-DSC7000) was used to evaluate the melting point of the film by differential scanning calorimetry (DSC). The results are shown in Table 1.

[0054] 〔Tensile strength〕 The films of Reference Examples 1 and 2 and Examples 1 to 4 were heat-treated at 37°C and 95% RH for 72 hours assuming cell culture conditions. Then, a tensile testing machine conforming to JIS Z0238:1998 (manufactured by IMADA, configuration: digital force gauge, model number ZTS-1000N, electric measurement stand, model number: MX2-1000N-L-V750) was used to measure the tensile strength of the film at a tensile speed of 500 mm / min, and the change in film strength was evaluated. The measured tensile strengths are shown in Table 1.

[0055] Note that the laminated films produced in Examples 1 to 4 have the configuration shown in FIG. 1, that is, a configuration consisting of a biodegradable film and an inorganic layer, each of one layer. However, the configuration in FIG. 1 is conceptual, and the thickness and ratio of each layer shown do not accurately reflect the thickness of the laminated films produced in each example.

[0056]

Table 1

[0057] As a result of the evaluation of the water vapor transmission rate, in the case of using either the PBS or PCL film as the polymer layer, the water vapor transmission rate was lower in the laminated film having an inorganic layer than in the film without an inorganic layer. Therefore, it was shown that the laminated films produced in Examples 1 to 4 are excellent in water vapor barrier properties.

[0058] As a result of the evaluation of biodegradability after gamma-ray irradiation, complete disintegration was confirmed after about 6 weeks in the PBS film of Reference Example 1 and after about 3 weeks in the PCL film of Reference Example 2, and it was shown that both are biodegradable. Since the PBS film and the PCL film are biodegradable, and aluminum and Si3N4 are hydrolyzable and decomposed by the moisture in the soil, it is considered that the laminated films of Examples 1 to 4 having an aluminum vacuum deposition layer or a Si3N4 sputter layer are also biodegradable in the same way.

[0059] As a result of the evaluation of the melting point after gamma-ray irradiation, the PBS film of Reference Example 1 and the PCL film of Reference Example 2 had melting points of 87°C and 53°C, respectively, and it was confirmed that they could be suitably used for the production of biopharmaceuticals under culture conditions of, for example, 37°C. From this, it is considered that the laminated films of Examples 1 to 4 can also be suitably used for the production of biopharmaceuticals.

[0060] As a result of the evaluation of the tensile strength, in all of the evaluation samples of Reference Examples 1 and 2 and Examples 1 to 4, the tensile strength was at the same level before and after heat treatment. Therefore, it was shown that the films did not deteriorate even after heating at 37°C for 72 hours, and the laminated films of Examples 1 to 4 can be suitably used for the production of biopharmaceuticals.

[0061] From the above results, it was shown that the laminated films produced in Examples 1 to 4 have biodegradability, water vapor barrier properties, and resistance under cell culture conditions, and are suitable for single-use bags for pharmaceutical production.

[0062] <Production of Single-Use Bag> Using the laminated film obtained as described above, a single-use bag shown in the schematic diagram of Figure 2 can be produced as follows. First, a hole is made at the welding location of the port of one laminated film, the welding surface of the port is aligned with the welding surface of the laminated film, the port is inserted into the hole of the laminated film, and welded. Subsequently, the welding surface of the laminated film with the port welded is aligned with the welding surface of another laminated film, and the outer periphery is welded. Then, a tube of an appropriate size is inserted into the port and fixed with a fastening tool such as a cable tie. Desired members such as a clamp, connector, coupling, and needleless valve are attached to the tube.

Explanation of Reference Numerals

[0063] 10 Laminated film 12 Biodegradable polymer layer 14 Inorganic layer 20 Single-use bag 22 Bag body 24 Outer periphery 26 Port 28 tubes 30 clamps 32 couplings

Claims

1. A single-use bag for pharmaceutical manufacturing, comprising a bag body of a laminated film having a biodegradable polymer layer and an inorganic layer.

2. The single-use bag for pharmaceutical manufacturing according to Claim 1, wherein the inorganic layer includes at least one layer selected from the group consisting of an aluminum layer and a silicon nitride layer.

3. The single-use bag for pharmaceutical manufacturing according to Claim 1, wherein the inorganic layer includes at least one vapor deposition layer selected from the group consisting of aluminum and silicon nitride.

4. The single-use bag for pharmaceutical manufacturing according to Claim 1, wherein the biodegradable polymer of the biodegradable polymer layer includes an aliphatic polyester.

5. The single-use bag for pharmaceutical manufacturing according to Claim 4, wherein the aliphatic polyester includes at least one polyester selected from the group consisting of polybutylene succinate and polycaprolactone.

6. The single-use bag for pharmaceutical manufacturing according to Claim 1, wherein the thickness of the inorganic layer is 0.05 μm to 1.5 μm.

7. The single-use bag for pharmaceutical manufacturing according to Claim 1, wherein the thickness of the biodegradable polymer layer is 5 μm to 200 μm.

8. The single-use bag for pharmaceutical manufacturing according to Claim 1, wherein the ratio of the thickness of the biodegradable polymer layer to the thickness of the inorganic layer is 3 to 4000.

9. The single-use bag for pharmaceutical manufacturing according to Claim 1, wherein the laminated film has a two-layer structure of the biodegradable polymer layer and the inorganic layer.

10. The single-use bag for pharmaceutical manufacturing according to Claim 1, wherein the laminated film does not have an anchor layer.

11. The water vapor transmission rate of the laminated film is 25 g / m ２ / 24 hours or less, and the single-use bag for pharmaceutical production according to any one of claims 1 to 9.

12. The single-use bag for pharmaceutical manufacturing according to any one of Claims 1 to 9, wherein the reduction rate of the tensile strength of the laminated film measured at a tensile speed of 500 mm / min after standing still for 72 hours under the conditions of 37°C and 95% RH is 10% or less.

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