WO2023142684A1 - 生物制药用一次性袋子的可降解薄膜及其应用 - Google Patents

生物制药用一次性袋子的可降解薄膜及其应用 Download PDF

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WO2023142684A1
WO2023142684A1 PCT/CN2022/136583 CN2022136583W WO2023142684A1 WO 2023142684 A1 WO2023142684 A1 WO 2023142684A1 CN 2022136583 W CN2022136583 W CN 2022136583W WO 2023142684 A1 WO2023142684 A1 WO 2023142684A1
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layer
adhesive layer
test conditions
thickness
under
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PCT/CN2022/136583
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English (en)
French (fr)
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王坤
秦孙星
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上海乐纯生物技术股份有限公司
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/36—Layered products comprising a layer of synthetic resin comprising polyesters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/06—Layered products comprising a layer of synthetic resin as the main or only constituent of a layer, which is next to another layer of the same or of a different material
    • B32B27/08—Layered products comprising a layer of synthetic resin as the main or only constituent of a layer, which is next to another layer of the same or of a different material of synthetic resin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/30—Layered products comprising a layer of synthetic resin comprising vinyl (co)polymers; comprising acrylic (co)polymers
    • B32B27/306—Layered products comprising a layer of synthetic resin comprising vinyl (co)polymers; comprising acrylic (co)polymers comprising vinyl acetate or vinyl alcohol (co)polymers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/32—Layered products comprising a layer of synthetic resin comprising polyolefins
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B7/00—Layered products characterised by the relation between layers; Layered products characterised by the relative orientation of features between layers, or by the relative values of a measurable parameter between layers, i.e. products comprising layers having different physical, chemical or physicochemical properties; Layered products characterised by the interconnection of layers
    • B32B7/04—Interconnection of layers
    • B32B7/12—Interconnection of layers using interposed adhesives or interposed materials with bonding properties
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D65/00—Wrappers or flexible covers; Packaging materials of special type or form
    • B65D65/38—Packaging materials of special type or form
    • B65D65/46—Applications of disintegrable, dissolvable or edible materials
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
    • C08J5/18—Manufacture of films or sheets
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2323/00—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers
    • C08J2323/02—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers not modified by chemical after treatment
    • C08J2323/04—Homopolymers or copolymers of ethene
    • C08J2323/08—Copolymers of ethene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
    • C08J2367/02—Polyesters derived from dicarboxylic acids and dihydroxy compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2403/00—Characterised by the use of starch, amylose or amylopectin or of their derivatives or degradation products
    • C08J2403/02—Starch; Degradation products thereof, e.g. dextrin
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2467/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
    • C08J2467/02—Polyesters derived from dicarboxylic acids and dihydroxy compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2467/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
    • C08J2467/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2497/00—Characterised by the use of lignin-containing materials
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02W—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO WASTEWATER TREATMENT OR WASTE MANAGEMENT
    • Y02W90/00—Enabling technologies or technologies with a potential or indirect contribution to greenhouse gas [GHG] emissions mitigation
    • Y02W90/10—Bio-packaging, e.g. packing containers made from renewable resources or bio-plastics

Definitions

  • the invention belongs to the field of new materials, and in particular relates to a degradable film for a disposable bag for biopharmaceuticals and an application thereof.
  • disposable bags mainly include liquid storage bags, liquid dispensing bags, cell reaction bags, etc.
  • bags that are potentially infectious after use they are usually sent to a designated place for incineration after high-pressure steam or dry heat sterilization; for bags that are not potentially infectious after use, they are usually incinerated or disposed of after sterilization. Sent to landfill for disposal.
  • the films used in biopharmaceutical bags are generally made of petroleum-based polymers, such as polyethylene, polypropylene, etc.
  • biodegradable materials are prepared from bio-based raw materials, which can be degraded into harmless substances in the natural environment, thereby reducing people's dependence on petroleum, and will not cause a net increase in CO 2 in the atmosphere.
  • the film needs to have excellent biocompatibility and will not have a significant impact on the active ingredients of the liquid medicine; the film needs to have excellent mechanical properties to ensure that the bag made is safe and firm during transportation and use, and will not occur Leakage; the film also needs to have excellent gas and water vapor barrier properties to ensure the controllability of the liquid environment in the biopharmaceutical process, and so on.
  • These requirements have posed challenges to the use of bio-based raw material resins, so as of now, there are no relevant research or reports on degradable films used in biopharmaceutical processes in the world.
  • the purpose of the present invention is to overcome the deficiencies of the prior art and provide a biodegradable film for a disposable bag for biopharmaceuticals and its application.
  • a first aspect of the present invention provides:
  • a biodegradable film for a disposable bag for biopharmaceuticals including a protective layer, a first adhesive layer, a high barrier layer, a second adhesive layer and a liquid contact layer in sequence from the outside to the inside, a total of 5 layers, wherein:
  • the protective layer is made of polybutylene adipate/terephthalate, polybutylene succinate and polyglycolic acid blend;
  • the first adhesive layer and the second adhesive layer are made of adhesive resin
  • the high barrier layer is made of fully biodegradable vinyl alcohol copolymer
  • the liquid contact layer is made of linear low density polyethylene modified with biodegradable filler.
  • the PBAT and PBS used in the protective layer have a melt index of 1.0-15.0 g/10 min under the test conditions of 190° C. and 2.16 kg, respectively.
  • the PBAT and PBS used in the protective layer have a melt index of 2.0-8.0 g/10 min under the test conditions of 190° C. and 2.16 Kg, respectively.
  • the melt index of the PGA under the test conditions of 250°C and 2.16Kg is 1.0-15.0g/10min.
  • the melt index of the PGA under the test conditions of 250°C and 2.16Kg is 2.0-8.0g/10min.
  • the melting index of the adhesive resin under the test conditions of 190° C. and 2.16 kg is 1.0 ⁇ 10.0 g/10 min.
  • the melting index of the adhesive resin under the test conditions of 190°C and 2.16Kg is 2.0-8.0g/10min.
  • the first adhesive layer and the second adhesive layer are made of fully biodegradable anhydride-modified adhesive resin.
  • the melt index of the fully biodegradable vinyl alcohol copolymer under the test conditions of 190° C. and 2.16 kg is 1.0-15.0 g/10 min.
  • the melt index of the fully biodegradable vinyl alcohol copolymer under the test conditions of 190°C and 2.16Kg is 2.0-8.0g/10min.
  • the biodegradable filler is a mixture of lignin and thermoplastic starch, and the mixing ratio of thermoplastic starch and lignin is 100:0 to 70:30.
  • the biodegradable filler is a mixture of lignin and thermoplastic starch, and the mixing ratio of thermoplastic starch and lignin is 100:0 to 75:25.
  • the weight ratio of the linear low density polyethylene to the biodegradable filler is 90:10 to 50:50.
  • the weight ratio of the linear low density polyethylene and the biodegradable filler is 70:30 to 50:50.
  • the melt index of the linear low density polyethylene under the test conditions of 190°C and 2.16Kg is 1.0-10.0g/10min.
  • the linear low density polyethylene has a density of 2.0-8.0 g/10 min under the test conditions of 190° C. and 2.16 Kg.
  • the linear low density polyethylene has a density of 0.87-0.915 g/cm 3 .
  • the first adhesive layer and the second adhesive layer are made of fully biodegradable anhydride-modified adhesive resin.
  • the fully biodegradable vinyl alcohol copolymer is selected from Nichigo G-Polymer TM series resins.
  • the thickness of each layer is adjusted according to the specific application occasions.
  • the protective layer has a thickness of 10 ⁇ m-100 ⁇ m.
  • the thickness of the first adhesive layer is 10 ⁇ m ⁇ 50 ⁇ m.
  • the thickness of the high barrier layer is 5 ⁇ m-40 ⁇ m.
  • the thickness of the second adhesive layer is 10 ⁇ m ⁇ 50 ⁇ m.
  • the thickness of the liquid contact layer is 140 ⁇ m-500 ⁇ m.
  • the tensile strength of the degradable films is not lower than 18Mpa.
  • the elongation at break of the degradable film is not lower than 350%.
  • the water vapor transmission rate of the degradable films does not exceed 2.6 g/m 2 .day.
  • the oxygen transmission rate of the degradable films does not exceed 1.5 cm 3 /m 2 .day.bar.
  • the degradation rate of the degradable films under the GB/T 19277.1-2011 standard test is not less than 60%.
  • the tensile strength of the degradable film is not less than 18Mpa, the elongation at break is not less than 350%, the water vapor transmission rate is not more than 2.6g/m 2 .day, the oxygen transmission rate is not More than 1.5cm 3 /m 2 .day.bar.
  • the degradable films of some examples of the present invention have a high biodegradation rate, and simultaneously have excellent biocompatibility, strength, toughness and high barrier properties, and meet the stringent requirements of disposable bags for biopharmaceuticals.
  • the protective layer, the first adhesive layer, the high barrier layer, and the second adhesive layer are all made of completely biodegradable materials; the liquid contact layer is used because it will contact different liquids in the biopharmaceutical process.
  • the polyethylene material with extremely high solvent inertness is used as the main material, and a certain amount of thermoplastic starch/lignin is mixed in polyethylene to form a destructive biodegradable material.
  • the multi-layer structure and the material formula of each layer of the degradable film in the present invention are scientifically designed, so that it has excellent biodegradability under the premise of taking into account excellent mechanical properties, high barrier properties and biocompatibility / Compostability, the disposable bags made of it can be sterilized after use and can be directly buried for composting.
  • PBAT Polybutylene adipate/terephthalate
  • PBS polybutylene succinate
  • LLDPE Linear Low Density Polyethylene
  • TPS thermoplastic starch
  • a biodegradable film for disposable bags for biopharmaceuticals has a 5-layer structure, including a protective layer, a first adhesive layer, a high barrier layer, a second adhesive layer, and a liquid contact layer from the outside to the inside layer.
  • the outermost layer is the protective layer, which mainly plays the role of improving the film strength, scratch resistance, and protecting the film.
  • the middle layer is a high barrier layer, which mainly acts as a high barrier to gases such as oxygen and carbon dioxide.
  • the innermost layer is the liquid contact layer, which mainly plays the role of heat sealing, buffering and solvent inertness.
  • the first adhesive layer mainly plays the role of bonding the protective layer and the high barrier layer.
  • the second adhesive layer mainly plays the role of bonding the high barrier layer and the liquid contact layer.
  • the material of the protective layer is a blend of polybutylene adipate/terephthalate (PBAT), polybutylene succinate (PBS), and polyglycolic acid (PGA).
  • PBAT polybutylene adipate/terephthalate
  • PBS polybutylene succinate
  • PGA polyglycolic acid
  • PBAT has excellent biodegradability, ductility and impact resistance, and provides the flexibility of the protective layer.
  • PBS has excellent degradation performance, good biocompatibility and heat resistance, and excellent processing performance, which can significantly improve the processability of the protective layer.
  • PGA has good gas barrier properties, biocompatibility and degradability, and has extremely high mechanical strength, which can provide the required strength and high barrier properties to the protective layer.
  • the inventors found that the protective layer obtained by blending these three resins in a specific ratio will have excellent biodegradability, rigidity balance, and high barrier properties, meeting the stringent requirements of disposable bags for biopharmaceuticals .
  • the materials of the first adhesive layer and the second adhesive layer are all biodegradable anhydride modified adhesive resins.
  • the material of the high barrier layer is a fully biodegradable vinyl alcohol copolymer.
  • the material of the liquid contact layer is linear low density polyethylene (LLDPE) modified by biodegradable filler.
  • LLDPE linear low density polyethylene
  • the weight ratio of PBAT, PBS, and PGA in the protective layer is (40-70): (10-40): (5-30), preferably (50-60): (20-30): (15-25 ).
  • the PBAT in the protective layer has a melting index of 1.0-15.0 g/10 min, preferably 2.0-8.0 g/10 min under the test conditions of 190° C. and 2.16 Kg.
  • a suitable PBAT example with the trademark (more precisely, C1200) is sold by BASF Corporation.
  • the PBS in the protective layer has a melting index of 1.0-15.0g/10min, preferably 2.0-8.0g/10min under the test conditions of 190°C and 2.16Kg.
  • a suitable PBS is sold, for example, under the trademark BioPBS TM (more precisely, BioPBS TM FD92PM) by Mitsubishi Chemical Performance Polymers, Inc.
  • the PGA in the protective layer has a melting index of 1.0-15.0 g/10 min, preferably 2.0-8.0 g/10 min under the test conditions of 250° C. and 2.16 Kg.
  • a suitable PGA such as the trademark (more precisely, 100E35) is sold by KUREHA Corporation.
  • the melting index of the fully biodegradable anhydride-modified adhesive resin in the first adhesive layer and the second adhesive layer is 1.0-10.0 g/10min, preferably 2.0- 8.0g/10min.
  • a suitable binder resin is for example sold under the designation BTR8002P by Mitsubishi Chemical.
  • the melting index of the fully biodegradable vinyl alcohol copolymer in the high barrier layer is 1.0-15.0 g/10 min, preferably 2.0-8.0 g/10 min under the test conditions of 190° C. and 2.16 Kg.
  • Suitable vinyl alcohol copolymers are sold, for example, by Mitsubishi Chemical under the trademark Nichigo G-Polymer TM (more precisely, Nichigo G-Polymer TM OKS-8095P).
  • the biodegradable filler in the liquid contact layer is thermoplastic starch (TPS) alone or partially containing lignin, and the weight ratio of TPS to lignin is 100:0 to 70:30.
  • TPS thermoplastic starch
  • the LLDPE in the liquid contact layer has a density of 0.87-0.915g/cm 3 , and a melt index of 1.0-10.0g/10min, preferably 2.0-8.0g/10min under the test conditions of 190°C and 2.16Kg.
  • a suitable LLDPE is sold, for example, by the DOW Chemical Company under the trademark Attane TM (more precisely, Attane TM 4404G).
  • the weight ratio of LLDPE and biodegradable filler in the liquid contact layer is 90:10 to 50:50.
  • the protective layer has a thickness of 10 ⁇ m-100 ⁇ m.
  • the thickness of the first adhesive layer is 10 ⁇ m-50 ⁇ m.
  • the thickness of the high barrier layer is 5 ⁇ m-40 ⁇ m.
  • the thickness of the second adhesive layer is 10 ⁇ m-50 ⁇ m.
  • the thickness of the liquid contact layer is 140 ⁇ m-500 ⁇ m.
  • the melt index of the PBAT used is about 4.0g/10min under the test conditions of 190°C and 2.16Kg, and the specific grade is C1200.
  • the PBS used has a melt index of about 4.0g/10min under the test conditions of 190°C and 2.16Kg, and the specific brand is BioPBS TM FD92PM.
  • the melt index of the PGA used is about 5.0g/10min under the test conditions of 250°C and 2.16Kg, and the specific grade is 100E35.
  • the melt index of the fully biodegradable adhesive resin used is about 3.0g/10min under the test conditions of 190°C and 2.16Kg, and the specific brand is BTR8002P.
  • the melt index of the fully biodegradable vinyl alcohol copolymer used is about 2.0g/10min under the test conditions of 190°C and 2.16Kg, and the specific brand is G-Polymer TM OKS-8095P.
  • the LLDPE used has a density of 0.902g/cm 3 , a melt index of about 4.0g/10min under the test conditions of 190°C and 2.16Kg, and the specific brand is Attane TM 4404G.
  • the preparation method of the degradable film used for the disposable bag of biopharmaceuticals may include multiple existing forms such as multi-layer co-extrusion casting, multi-layer co-extrusion blown film, extrusion compounding, extrusion lamination and the like.
  • multi-layer co-extrusion casting it mainly includes the following steps:
  • Step 1 Put various raw material particles into the corresponding suction channels of the multi-layer co-extrusion casting line, and automatically put them into the respective extruders in proportion through the precise metering system;
  • Step 2 Under the set extrusion temperature, the raw materials are melted and plasticized in their respective screws, and then layered and merged at the T-shaped die to cast a multi-layer film;
  • Step 3 After the cast multilayer film is cooled, rolled, cut and packaged, the finished biodegradable film can be obtained.
  • the protective layer uses a blend of PBAT, PBS, and PGA.
  • the weight ratio of PBAT, PBS, and PGA in the protective layer is 55:25:20; the set temperature of the screw used is 200-220-235-250°C;
  • Both the first adhesive layer and the second adhesive layer use 100% fully biodegradable tackifying resin, and the set temperature of the screw segments used is 190-210-230-230°C;
  • the high barrier layer uses 100% fully biodegradable vinyl alcohol copolymer, and the set temperature of the screw used is 190-210-230-230°C;
  • the liquid contact layer uses a blend of LLDPE and TPS, the weight ratio of LLDPE and TPS is 70:30, and the set temperature of the screw segment used is 190-210-230-230°C;
  • the thickness of the protective layer is 80 ⁇ m
  • the thickness of the first adhesive layer is 25 ⁇ m
  • the thickness of the high barrier layer is 20 ⁇ m
  • the thickness of the second adhesive layer is 25 ⁇ m
  • the thickness of the liquid contact layer is 170 ⁇ m
  • the total thickness is 320 ⁇ m.
  • the protective layer uses a blend of PBAT, PBS, and PGA, and the weight ratio of PBAT, PBS, and PGA in the protective layer is 50:30:20; the set temperature of the screw used is 200-220-235-250°C;
  • Both the first adhesive layer and the second adhesive layer use 100% fully biodegradable tackifying resin, and the set temperature of the screw segments used is 190-210-230-230°C;
  • the high barrier layer uses 100% fully biodegradable vinyl alcohol copolymer, and the set temperature of the screw used is 190-210-230-230°C;
  • the liquid contact layer uses a blend of LLDPE and TPS, the weight ratio of LLDPE and TPS in the liquid contact layer is 60:40, and the set temperature of the used screw segment is 190-210-230-230°C.
  • the thickness of the protective layer is 90 ⁇ m
  • the thickness of the first adhesive layer is 20 ⁇ m
  • the thickness of the high barrier layer is 25 ⁇ m
  • the thickness of the second adhesive layer is 20 ⁇ m
  • the thickness of the liquid contact layer is 170 ⁇ m
  • the total thickness is 325 ⁇ m.
  • the protective layer uses a blend of PBAT, PBS, and PGA.
  • the weight ratio of PBAT, PBS, and PGA in the protective layer is 60:25:15; the set temperature of the screw used is 200-220-235-250°C;
  • Both the first adhesive layer and the second adhesive layer use 100% fully biodegradable tackifying resin, and the set temperature of the screw segments used is 190-210-230-230°C;
  • the high barrier layer uses 100% fully biodegradable vinyl alcohol copolymer, and the set temperature of the screw used is 190-210-230-230°C;
  • the liquid contact layer uses a blend of LLDPE and TPS, and the weight ratio of LLDPE and TPS in the liquid contact layer is 50:50; the set temperature of the used screw segment is 190-210-230-230°C.
  • the thickness of the protective layer is 100 ⁇ m
  • the thickness of the first adhesive layer is 20 ⁇ m
  • the thickness of the high barrier layer is 25 ⁇ m
  • the thickness of the second adhesive layer is 20 ⁇ m
  • the thickness of the liquid contact layer is 155 ⁇ m
  • the total thickness is 320 ⁇ m.
  • the protective layer uses a blend of PBAT, PBS, and PGA, and the weight ratio of PBAT, PBS, and PGA in the protective layer is 55:30:15; the set temperature of the screw used is 200-220-235-250°C;
  • Both the first adhesive layer and the second adhesive layer use 100% fully biodegradable tackifying resin, and the set temperature of the screw segments used is 190-210-230-230°C;
  • the high barrier layer uses 100% fully biodegradable vinyl alcohol copolymer, and the set temperature of the screw used is 190-210-230-230°C;
  • the liquid contact layer uses LLDPE, TPS, a blend of lignin, LLDPE, TPS, the weight ratio of lignin is 60:28:12, and the set temperature of the screw segment used is 190-210-230-230°C.
  • the thickness of the protective layer is 90 ⁇ m
  • the thickness of the first adhesive layer is 25 ⁇ m
  • the thickness of the high barrier layer is 25 ⁇ m
  • the thickness of the second adhesive layer is 25 ⁇ m
  • the thickness of the liquid contact layer is 150 ⁇ m
  • the total thickness is 315 ⁇ m.
  • the protective layer uses a blend of PBAT, PBS, and PGA.
  • the weight ratio of PBAT, PBS, and PGA in the protective layer is 65:20:15; the set temperature of the screw used is 200-220-235-250°C;
  • Both the first adhesive layer and the second adhesive layer use 100% fully biodegradable tackifying resin, and the set temperature of the screw segments used is 190-210-230-230°C;
  • the high barrier layer uses 100% fully biodegradable vinyl alcohol copolymer, and the set temperature of the screw used is 190-210-230-230°C;
  • the liquid contact layer uses LLDPE, TPS, a blend of lignin, LLDPE, TPS, the weight ratio of lignin is 60:30:10, and the set temperature of the used screw segment is 190-210-230-230°C.
  • the thickness of the protective layer is 100 ⁇ m
  • the thickness of the first adhesive layer is 25 ⁇ m
  • the thickness of the high barrier layer is 25 ⁇ m
  • the thickness of the second adhesive layer is 25 ⁇ m
  • the thickness of the liquid contact layer is 140 ⁇ m
  • the total thickness is 315 ⁇ m.
  • the protective layer uses a blend of PBAT and PBS, and the weight ratio of PBAT and PBS in the protective layer is 80:20; the set temperature of the screw used is 200-220-235-250°C;
  • Both the first adhesive layer and the second adhesive layer use 100% fully biodegradable tackifying resin, and the set temperature of the screw segments used is 190-210-230-230°C;
  • the high barrier layer uses 100% fully biodegradable vinyl alcohol copolymer, and the set temperature of the screw used is 190-210-230-230°C;
  • the liquid contact layer uses a blend of LLDPE and TPS, the weight ratio of LLDPE and TPS is 70:30, and the set temperature of the used screw segment is 190-210-230-230°C.
  • the thickness of the protective layer is 80 ⁇ m
  • the thickness of the first adhesive layer is 25 ⁇ m
  • the thickness of the high barrier layer is 20 ⁇ m
  • the thickness of the second adhesive layer is 25 ⁇ m
  • the thickness of the liquid contact layer is 170 ⁇ m
  • the total thickness is 320 ⁇ m.
  • the protective layer uses a blend of PBAT, PBS, and PGA.
  • the weight ratio of PBAT, PBS, and PGA in the protective layer is 30:30:40; the set temperature of the screw used is 200-220-235-250°C;
  • Both the first adhesive layer and the second adhesive layer use 100% fully biodegradable tackifying resin, and the set temperature of the screw segments used is 190-210-230-230°C;
  • the high barrier layer uses 100% fully biodegradable vinyl alcohol copolymer, and the set temperature of the screw used is 190-210-230-230°C;
  • the liquid contact layer uses a blend of LLDPE and TPS, the weight ratio of LLDPE and TPS in the liquid contact layer is 60:40, and the set temperature of the used screw segment is 190-210-230-230°C.
  • the thickness of the protective layer is 90 ⁇ m
  • the thickness of the first adhesive layer is 20 ⁇ m
  • the thickness of the high barrier layer is 25 ⁇ m
  • the thickness of the second adhesive layer is 20 ⁇ m
  • the thickness of the liquid contact layer is 170 ⁇ m
  • the total thickness is 325 ⁇ m.
  • the protective layer uses a blend of PBAT, PBS, and PGA, and the weight ratio of PBAT, PBS, and PGA in the protective layer is 90:5:5; the set temperature of the screw used is 200-220-235-250°C;
  • Both the first adhesive layer and the second adhesive layer use 100% fully biodegradable tackifying resin, and the set temperature of the screw segments used is 190-210-230-230°C;
  • the high barrier layer uses 100% fully biodegradable vinyl alcohol copolymer, and the set temperature of the screw used is 190-210-230-230°C;
  • the liquid contact layer uses LLDPE, TPS, a blend of lignin, LLDPE, TPS, the weight ratio of lignin is 60:30:10, and the set temperature of the used screw segment is 190-210-230-230°C.
  • the thickness of the protective layer is 100 ⁇ m
  • the thickness of the first adhesive layer is 25 ⁇ m
  • the thickness of the high barrier layer is 25 ⁇ m
  • the thickness of the second adhesive layer is 25 ⁇ m
  • the thickness of the liquid contact layer is 140 ⁇ m
  • the total thickness is 315 ⁇ m.
  • Performance tests were performed on the degradable films prepared in Examples 1 to 5 and Comparative Examples 1 to 3, mainly including degradable properties, mechanical properties, water vapor transmission properties, and oxygen transmission properties. The results are shown in the table below. Among them, the degradable performance is tested according to the GB/T 19277.1-2011 standard, the tensile strength and elongation at break are tested according to the ASTM D882 standard, the water vapor transmission performance is tested according to the ASTM F1249 standard, and the oxygen transmission performance is tested according to the ASTM D3985 standard. The results are shown in Table 1.
  • S represents an embodiment, such as S1 refers to embodiment 1
  • D represents a comparative example, such as D1 refers to comparative example 1.
  • the degradable films used in disposable bags for biopharmaceuticals prepared by the present invention (Example 1-5) have excellent biodegradable properties, mechanical properties, water vapor barrier properties and oxygen barrier properties, and have excellent market applications prospect.

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Abstract

本发明属于新材料领域，公开了生物制药用一次性袋子的可降解薄膜及其应用。该薄膜由外到内依次包括保护层、第一粘合层、高阻隔层、第二粘合层和液体接触层共计5层。本发明一些实例的可降解薄膜，生物降解速度高，同时兼具优异的生物相容性、强度，韧性和高阻隔性，满足生物制药用一次性袋子的苛刻要求；通过大量使用完全生物降解材料，同时优化组成，使其在兼顾优良力学性能、高阻隔性和生物相容性的前提下，具有优异的生物可降解性/堆肥性，用其做成的一次性袋子在使用后经灭菌可直接进行掩埋堆肥处理。

Description

生物制药用一次性袋子的可降解薄膜及其应用 技术领域
本发明属于新材料领域，具体涉及生物制药用一次性袋子的可降解薄膜及其应用。
背景技术
近几年来，仿制药市场在国内快速发展，国内制药企业纷纷进军生物制药市场。在生物制药领域，产品的快速研发是至关重要的。传统的不锈钢系统已经不能支持不同批次产品的快速研发与转换。而一次性产品能够很好地解决上述问题，正逐渐成为生物制药行业用于研发新药物的首选方案。目前，全球生物制药一次性耗材整体市场规模在1000亿元左右，而中国市场占到150亿元，年均增速约20％。
一次性袋子作为生物制药企业的重要耗材，主要包括储液袋，配液袋，细胞反应袋等等。对于使用过后有潜在感染性的袋子，通常会在高压蒸汽或干热灭菌后，送至指定地点焚烧处理；而对于使用过后无潜在感染性的袋子，通常会在灭菌后，焚烧处理或送至垃圾填埋场掩埋处理。然而，塑料废弃物在焚烧时会产生大量有害气体和烟雾，会加剧空气污染和温室效应。另外，生物制药用袋子所使用的薄膜一般由石油基聚合物制备，例如聚乙烯，聚丙烯等，将这些材料掩埋在土壤中很难降解，数十年后依旧会有残留，这对土壤有很大危害，还会通过食物链进一步威胁到人类的生命健康安全。因此，开发一种生物可降解一次性袋子势在必行。大部分生物可降解材料是由生物基原材料制备，在自然环境中可以降解成无害物质，从而可以减少人们对于石油的依赖，不会造成大气中CO 2净增加。
2020年，我国政府提出力争在2030年前实现碳达峰，2060年前实现碳中和的目标。生物可降解材料的广泛推广和使用，对于早日实现这一目标有 积极推动作用。作为一次性袋子关键原材料的薄膜，技术开发难度很高，国内制膜企业没有相关经验，导致目前国内一次性耗材制造企业所用薄膜几乎95％以上来自于进口。然而，薄膜对综合性能的要求较为苛刻，所以这些进口薄膜几乎全部由成熟的石油基树脂制造，对生物基树脂的尝试很少。例如，薄膜需要有优秀的生物相容性，不会对药液的有效成分产生明显影响；薄膜需要有优异的力学性能，保证制成的袋体在运输及使用过程中安全牢固，不会发生泄露；薄膜还需要有出色的气体和水蒸气阻隔性，保证生物制药过程中药液环境的可控性，等等。这些要求都对生物基原材料树脂的使用提出了挑战，所以截至目前全球也没有关于用于生物制药过程的可降解薄膜的相关研究或报道。
发明内容
本发明的目的在于克服现有技术的不足，提供一种生物制药用一次性袋子的可降解薄膜及其应用。
本发明所采取的技术方案是：
本发明的第一个方面，提供：
一种生物制药用一次性袋子的可降解薄膜，由外到内依次包括保护层、第一粘合层、高阻隔层、第二粘合层和液体接触层共计5层，其中：
所述保护层由聚己二酸/对苯二甲酸丁二酯、聚丁二酸丁二醇酯和聚乙醇酸共混物制成；
所述第一粘合层和所述第二粘合层由粘合树脂制成；
所述高阻隔层由全生物降解型乙烯醇共聚物制成；
所述液体接触层由生物可降解填料改性的线性低密度聚乙烯制成。
在一些可降解薄膜的实例中，所述保护层使用的PBAT和PBS在190℃，2.16Kg测试条件下的熔融指数分别为1.0～15.0g/10min。
进一步的，在一些可降解薄膜的实例中，所述保护层使用的PBAT和PBS在190℃，2.16Kg测试条件下的熔融指数分别为2.0～8.0g/10min。
在一些可降解薄膜的实例中，所述PGA在250℃，2.16Kg测试条件下的 熔融指数为1.0～15.0g/10min。
进一步的，在一些可降解薄膜的实例中，所述PGA在250℃，2.16Kg测试条件下的熔融指数为2.0～8.0g/10min。
在一些可降解薄膜的实例中，所述粘合树脂在190℃，2.16Kg测试条件下的熔融指数为1.0～10.0g/10min。
进一步的，在一些可降解薄膜的实例中，所述粘合树脂在190℃，2.16Kg测试条件下的熔融指数为2.0～8.0g/10min。
在一些可降解薄膜的实例中，所述第一粘合层和所述第二粘合层由全生物降解型的酸酐改性粘合树脂制成。
在一些可降解薄膜的实例中，所述全生物降解型乙烯醇共聚物在190℃，2.16Kg测试条件下的熔融指数为1.0～15.0g/10min。
进一步的，在一些可降解薄膜的实例中，所述全生物降解型乙烯醇共聚物在190℃，2.16Kg测试条件下的熔融指数为2.0～8.0g/10min。
在一些可降解薄膜的实例中，所述生物可降解填料为木质素和热塑性淀粉的混合物，热塑性淀粉和木质素的混合比为100：0至70：30。
进一步的，在一些可降解薄膜的实例中，所述生物可降解填料为木质素和热塑性淀粉的混合物，热塑性淀粉和木质素的混合比为100：0至75：25。
在一些可降解薄膜的实例中，所述液体接触层中，线性低密度聚乙烯和生物可降解填料的重量份比为90：10至50：50。
进一步的，在一些可降解薄膜的实例中，所述液体接触层中，线性低密度聚乙烯和生物可降解填料的重量份比为70：30至50：50。
在一些可降解薄膜的实例中，所述线性低密度聚乙烯在190℃，2.16Kg测试条件下的熔融指数为1.0～10.0g/10min。
进一步的，在一些可降解薄膜的实例中，所述线性低密度聚乙烯的密度在190℃，2.16Kg测试条件下的熔融指数为2.0～8.0g/10min。
在一些可降解薄膜的实例中，所述线性低密度聚乙烯的密度为0.87～0.915g/cm 3。
在一些可降解薄膜的实例中，所述保护层中，聚己二酸/对苯二甲酸丁二 酯、聚丁二酸丁二醇酯和聚乙醇酸的重量比为PBAT：PBS：PGA＝(40～70)：(10～40)：(5～30)。
在一些可降解薄膜的实例中，所述保护层中，聚己二酸/对苯二甲酸丁二酯、聚丁二酸丁二醇酯和聚乙醇酸的重量比为PBAT：PBS：PGA＝(50～65)：(20～30)：(15～25)。
在一些可降解薄膜的实例中，所述第一粘合层和所述第二粘合层由全生物降解型的酸酐改性粘合树脂制成。
在一些可降解薄膜的实例中，所述全生物降解型乙烯醇共聚物选自Nichigo G-Polymer TM系列树脂。
各层的厚度，根据具体的应用场合不同而进行相应的调整。
在一些可降解薄膜的实例中，所述保护层的厚度为10μm～100μm。
在一些可降解薄膜的实例中，所述第一粘合层的厚度为10μm～50μm。
在一些可降解薄膜的实例中，所述高阻隔层的厚度为5μm～40μm。
在一些可降解薄膜的实例中，所述第二粘合层的厚度为10μm～50μm。
在一些可降解薄膜的实例中，所述液体接触层的厚度为140μm～500μm。
为满足生物制药用一次性袋子要求，对薄膜的力学性能进行相应的调整。
在一些可降解薄膜的实例中，所述可降解薄膜的拉伸强度不低于18Mpa。
在一些可降解薄膜的实例中，所述可降解薄膜的断裂伸长率不低于350％。
在一些可降解薄膜的实例中，所述可降解薄膜的水汽透过量不超过2.6g/m 2.day。
在一些可降解薄膜的实例中，所述可降解薄膜的氧气透过量不超过1.5cm 3/m 2.day.bar。
在一些可降解薄膜的实例中，所述可降解薄膜的GB/T 19277.1-2011标准测试下的降解率不低于60％。
在一些可降解薄膜的实例中，所述可降解薄膜的拉伸强度不低于18Mpa、断裂伸长率不低于350％、水汽透过量不超过2.6g/m 2.day、氧气透过量不超过1.5cm 3/m 2.day.bar。
本发明的有益效果是：
本发明一些实例的可降解薄膜，生物降解速度高，同时兼具优异的生物相容性、强度，韧性和高阻隔性，满足生物制药用一次性袋子的苛刻要求。
本发明一些实例的可降解薄膜，保护层、第一粘合层、高阻隔层、第二粘合层全部由完全生物降解材料构成；液体接触层因为要接触生物制药过程中的不同液体，使用溶剂惰性极高的聚乙烯材料作为主材，并在聚乙烯中混合一定量的热塑性淀粉/木质素，构成破坏性生物降解材料。本发明中的可降解薄膜的多层结构及每一层的材料配方均经过科学设计，使其在兼顾优良力学性能、高阻隔性和生物相容性的前提下，具有优异的生物可降解性/堆肥性，用其做成的一次性袋子在使用后经灭菌可直接进行掩埋堆肥处理。
具体实施方式
本发明中，使用的缩写含义如下：
PBAT：聚己二酸/对苯二甲酸丁二酯
PBS：聚丁二酸丁二醇酯
PGA：聚乙醇酸
LLDPE：线性低密度聚乙烯
TPS：热塑性淀粉。
一种用于生物制药用一次性袋子的可降解薄膜，所述薄膜有5层结构，由外到内依次包括保护层，第一粘合层，高阻隔层，第二粘合层，液体接触层。
最外层是保护层，主要起到提高薄膜强度，耐刮擦，保护薄膜的作用。中间层是高阻隔层，主要起到对氧气、二氧化碳等气体的高阻隔作用。最内层是液体接触层，主要起到热封，缓冲和溶剂惰性的作用。第一粘合层，主要起到将保护层和高阻隔层粘合起来的作用。第二粘合层，主要起到将高阻隔层和液体接触层粘合起来的作用。
所述保护层的材料为聚己二酸/对苯二甲酸丁二酯(PBAT)，聚丁二酸丁二醇酯(PBS)，聚乙醇酸(PGA)的共混物。其中，PBAT具有优异的生物降解性、延展性和抗冲击性能，提供保护层的柔韧性。PBS降解性能优异， 具有良好的生物相容性和耐热性，并且加工性能出色，能明显改善保护层的可加工性。PGA具有良好的气体阻隔性、生物相容性和可降解性，而且机械强度极高，能够给保护层提供所需的强度和高阻隔性。发明人研究发现，把这三种树脂按照特定比例进行共混得到的保护层，将拥有极佳的生物降解性，刚韧平衡性，以及高阻隔性，满足生物制药用一次性袋子的苛刻要求。
所述第一粘合层和第二粘合层的材料均为全生物降解型的酸酐改性粘合树脂。
所述高阻隔层的材料为全生物降解型乙烯醇共聚物。
所述液体接触层的材料为生物可降解填料改性的线性低密度聚乙烯(LLDPE)。
所述保护层中PBAT，PBS，PGA的重量份比为(40～70)：(10～40)：(5～30)，优选(50～60)：(20～30)：(15～25)。
所述保护层中的PBAT在190℃，2.16Kg测试条件下的熔融指数为1.0～15.0g/10min，优选2.0～8.0g/10min。合适的PBAT例如以商标
Figure PCTCN2022136583-appb-000001
(更确切地，
Figure PCTCN2022136583-appb-000002
C1200)由BASF Corporation出售。
所述保护层中的PBS在190℃，2.16Kg测试条件下的熔融指数为1.0～15.0g/10min，优选2.0～8.0g/10min。合适的PBS例如以商标BioPBS TM(更确切地，BioPBS TMFD92PM)由Mitsubishi Chemical Performance Polymers,Inc.出售。
所述保护层中的PGA在250℃，2.16Kg测试条件下的熔融指数为1.0～15.0g/10min，优选2.0～8.0g/10min。合适的PGA例如以商标
Figure PCTCN2022136583-appb-000003
(更确切地，
Figure PCTCN2022136583-appb-000004
100E35)由KUREHA Corporation出售。
所述第一粘合层和第二粘合层中的全生物降解型的酸酐改性粘合树脂在190℃，2.16Kg测试条件下的熔融指数均为1.0～10.0g/10min，优选2.0～8.0g/10min。合适的粘合树脂例如牌号BTR8002P，由Mitsubishi Chemical出售。
所述高阻隔层中的全生物降解型乙烯醇共聚物在190℃，2.16Kg测试条件下的熔融指数为1.0～15.0g/10min，优选2.0～8.0g/10min。合适的乙烯醇共聚物例如以商标Nichigo G-Polymer TM(更确切地，Nichigo G-Polymer TM OKS-8095P)由Mitsubishi Chemical出售。
所述液体接触层中的生物可降解填料为单独或者包含部分木质素的热塑性淀粉(TPS)，TPS和木质素的重量份比为100：0至70：30。
所述液体接触层中的LLDPE的密度为0.87～0.915g/cm 3，在190℃，2.16Kg测试条件下的熔融指数为1.0～10.0g/10min，优选2.0～8.0g/10min。合适的LLDPE例如以商标Attane TM(更确切地，Attane TM4404G)由DOW Chemical Company出售。
所述液体接触层的LLDPE和生物可降解填料的重量份比为90：10至50：50。
所述保护层的厚度为10μm-100μm。
所述第一粘合层的厚度为10μm-50μm。
所述高阻隔层的厚度为5μm-40μm。
所述第二粘合层的厚度为10μm-50μm。
所述液体接触层的厚度为140μm-500μm。
为使本发明实施例的目的、技术方案和优点更加清楚，下面将结合本发明实施例，对本发明实施例的技术方案进行清楚、完整地描述。但是应当理解，这些描述只是为进一步说明本发明的特征和优点，而不是对本发明权利要求的限制。
如无特别说明，以下实例中：
所使用的PBAT在190℃，2.16Kg测试条件下的熔融指数约为4.0g/10min，具体牌号为
Figure PCTCN2022136583-appb-000005
C1200。
所使用的PBS在190℃，2.16Kg测试条件下的熔融指数约为4.0g/10min，具体牌号为BioPBS TMFD92PM。
所使用的PGA在250℃，2.16Kg测试条件下的熔融指数约为5.0g/10min，具体牌号为
Figure PCTCN2022136583-appb-000006
100E35。
所使用的全生物降解型粘合树脂在190℃，2.16Kg测试条件下的熔融指数约为3.0g/10min，具体牌号为BTR8002P。
所使用的全生物降解型乙烯醇共聚物在190℃，2.16Kg测试条件下的熔融 指数约为2.0g/10min，具体牌号为G-Polymer TMOKS-8095P。
所使用的LLDPE密度为0.902g/cm 3，在190℃，2.16Kg测试条件下的熔融指数约为4.0g/10min，具体牌号为Attane TM4404G。
用于生物制药用一次性袋子的可降解薄膜的制备方法，可以包括多层共挤流延，多层共挤吹膜，挤出复合，挤出贴合等多种现有形式。以多层共挤流延为例，主要包括以下步骤：
步骤一：将各种原材料颗粒，分别加入多层共挤流延线所对应的各自吸料通道内，经精确计量系统，按比例自动投入到各自挤出机中；
步骤二：在设定挤出温度下，原材料在各自螺杆内熔融塑化，然后在T型模头处分层汇合，进而流延出多层膜；
步骤三：流延出的多层膜经过冷却，收卷，分切，包装后，可以得到可降解薄膜成品。
实施例1
保护层使用PBAT，PBS，PGA的共混物，保护层中PBAT，PBS，PGA的重量份比为55：25：20；所用螺杆分段设定温度为200-220-235-250℃；
第一粘合层和第二粘合层均使用100％全生物降解型增粘树脂，所用螺杆分段设定温度均为190-210-230-230℃；
高阻隔层使用100％全生物降解型乙烯醇共聚物，所用螺杆分段设定温度为190-210-230-230℃；
液体接触层使用LLDPE和TPS的共混物，LLDPE和TPS的重量份比为70：30，所用螺杆分段设定温度为190-210-230-230℃；
保护层的厚度为80μm，第一粘合层的厚度为25μm，高阻隔层的厚度为20μm，第二粘合层的厚度为25μm，液体接触层的厚度为170μm，总厚度为320μm。
实施例2
保护层使用PBAT，PBS，PGA的共混物，保护层中PBAT，PBS，PGA的重量份比为50：30：20；所用螺杆分段设定温度为200-220-235-250℃；
第一粘合层和第二粘合层均使用100％全生物降解型增粘树脂，所用螺杆 分段设定温度均为190-210-230-230℃；
高阻隔层使用100％全生物降解型乙烯醇共聚物，所用螺杆分段设定温度为190-210-230-230℃；
液体接触层使用LLDPE和TPS的共混物，液体接触层中LLDPE和TPS的重量份比为60：40，所用螺杆分段设定温度为190-210-230-230℃。
保护层的厚度为90μm，第一粘合层的厚度为20μm，高阻隔层的厚度为25μm，第二粘合层的厚度为20μm，液体接触层的厚度为170μm，总厚度为325μm。
实施例3
保护层使用PBAT，PBS，PGA的共混物，保护层中PBAT，PBS，PGA的重量份比为60：25：15；所用螺杆分段设定温度为200-220-235-250℃；
第一粘合层和第二粘合层均使用100％全生物降解型增粘树脂，所用螺杆分段设定温度均为190-210-230-230℃；
高阻隔层使用100％全生物降解型乙烯醇共聚物，所用螺杆分段设定温度为190-210-230-230℃；
液体接触层使用LLDPE和TPS的共混物，液体接触层中LLDPE和TPS的重量份比为50：50；所用螺杆分段设定温度为190-210-230-230℃。
保护层的厚度为100μm，第一粘合层的厚度为20μm，高阻隔层的厚度为25μm，第二粘合层的厚度为20μm，液体接触层的厚度为155μm，总厚度为320μm。
实施例4
保护层使用PBAT，PBS，PGA的共混物，保护层中PBAT，PBS，PGA的重量份比为55：30：15；所用螺杆分段设定温度为200-220-235-250℃；
第一粘合层和第二粘合层均使用100％全生物降解型增粘树脂，所用螺杆分段设定温度均为190-210-230-230℃；
高阻隔层使用100％全生物降解型乙烯醇共聚物，所用螺杆分段设定温度为190-210-230-230℃；
液体接触层使用LLDPE，TPS，木质素的共混物，LLDPE，TPS，木质素 的重量份比为60：28：12，所用螺杆分段设定温度为190-210-230-230℃。
保护层的厚度为90μm，第一粘合层的厚度为25μm，高阻隔层的厚度为25μm，第二粘合层的厚度为25μm，液体接触层的厚度为150μm，总厚度为315μm。
实施例5
保护层使用PBAT，PBS，PGA的共混物，保护层中PBAT，PBS，PGA的重量份比为65：20：15；所用螺杆分段设定温度为200-220-235-250℃；
第一粘合层和第二粘合层均使用100％全生物降解型增粘树脂，所用螺杆分段设定温度均为190-210-230-230℃；
高阻隔层使用100％全生物降解型乙烯醇共聚物，所用螺杆分段设定温度为190-210-230-230℃；
液体接触层使用LLDPE，TPS，木质素的共混物，LLDPE，TPS，木质素的重量份比为60：30：10，所用螺杆分段设定温度为190-210-230-230℃。
保护层的厚度为100μm，第一粘合层的厚度为25μm，高阻隔层的厚度为25μm，第二粘合层的厚度为25μm，液体接触层的厚度为140μm，总厚度为315μm。
对比例1
保护层使用PBAT，PBS的共混物，保护层中PBAT和PBS的重量份比为80：20；所用螺杆分段设定温度为200-220-235-250℃；
第一粘合层和第二粘合层均使用100％全生物降解型增粘树脂，所用螺杆分段设定温度均为190-210-230-230℃；
高阻隔层使用100％全生物降解型乙烯醇共聚物，所用螺杆分段设定温度为190-210-230-230℃；
液体接触层使用LLDPE和TPS的共混物，LLDPE和TPS的重量份比为70：30，所用螺杆分段设定温度为190-210-230-230℃。
保护层的厚度为80μm，第一粘合层的厚度为25μm，高阻隔层的厚度为20μm，第二粘合层的厚度为25μm，液体接触层的厚度为170μm，总厚度为320μm。
对比例2
保护层使用PBAT，PBS，PGA的共混物，保护层中PBAT，PBS，PGA的重量份比为30：30：40；所用螺杆分段设定温度为200-220-235-250℃；
第一粘合层和第二粘合层均使用100％全生物降解型增粘树脂，所用螺杆分段设定温度均为190-210-230-230℃；
高阻隔层使用100％全生物降解型乙烯醇共聚物，所用螺杆分段设定温度为190-210-230-230℃；
液体接触层使用LLDPE和TPS的共混物，液体接触层中LLDPE和TPS的重量份比为60：40，所用螺杆分段设定温度为190-210-230-230℃。
保护层的厚度为90μm，第一粘合层的厚度为20μm，高阻隔层的厚度为25μm，第二粘合层的厚度为20μm，液体接触层的厚度为170μm，总厚度为325μm。
对比例3
保护层使用PBAT，PBS，PGA的共混物，保护层中PBAT，PBS，PGA的重量份比为90：5：5；所用螺杆分段设定温度为200-220-235-250℃；
第一粘合层和第二粘合层均使用100％全生物降解型增粘树脂，所用螺杆分段设定温度均为190-210-230-230℃；
高阻隔层使用100％全生物降解型乙烯醇共聚物，所用螺杆分段设定温度为190-210-230-230℃；
液体接触层使用LLDPE，TPS，木质素的共混物，LLDPE，TPS，木质素的重量份比为60：30：10，所用螺杆分段设定温度为190-210-230-230℃。
保护层的厚度为100μm，第一粘合层的厚度为25μm，高阻隔层的厚度为25μm，第二粘合层的厚度为25μm，液体接触层的厚度为140μm，总厚度为315μm。
对实施例1至5和对比例1至3制备出的可降解薄膜进行性能测试，主要包括可降解性能、力学性能、水汽透过性能、氧气透过性能，结果如下表所示。其中，可降解性能按照GB/T 19277.1-2011标准测试，拉伸强度和断裂伸长率按照ASTM D882标准测试，水汽透过性能按照ASTM F1249标准测 试，氧气透过性能按照ASTM D3985标准测试。结果如表1所示。
表1
测试性能 S1 S2 S3 S4 S5 D1 D2 D3
降解率(％) 66％ 69％ 73％ 70％ 68％ 66％ 67％ 68％
拉伸强度(MPa) 18.6 20.4 19.4 19.8 18.9 14.1 25.2 15.2
断裂伸长率(％) 405％ 366％ 372％ 385％ 392％ 465％ 206％ 488％
水汽透过量(g/m 2.day) 1.8 1.6 2.0 2.2 2.5 3.0 1.9 2.6
氧气透过量(cm 3/m 2.day.bar) 0.6 0.5 0.5 0.6 1.2 2.9 0.4 2.2
注：S表示实施例，如S1指实施例1；D表示对比例，如D1指对比例1。
由表1的数据可知：
1)本发明制备的用于生物制药用一次性袋子的可降解薄膜(实施例1～5)拥有优异的生物可降解性能、力学性能、水汽阻隔性能和氧气阻隔性能，具有极好的市场应用前景。
2)对比例1中的保护层由于不含PGA刚性材料，导致薄膜的拉伸强度明显降低，制成的袋体有发生漏液的可能性；而且不含PGA也导致膜材整体气体阻隔性能下降，不适合应用。
3)对比例2中的保护层由于PGA含量太高40％，导致膜材偏硬，并且断裂伸长率只有200％左右，制成的袋体较容易发生褶皱形变而漏液，不适合应用。
4)对比例3中PBAT占的比例太高90％，保护层刚性不足而导致拉伸强度降低，不适合应用。
以上是对本发明所作的进一步详细说明，不可视为对本发明的具体实施的局限。对于本发明所属技术领域的普通技术人员来说，在不脱离本发明构思的简单推演或替换，都在本发明的保护范围之内。

Claims (9)

  1. 一种生物制药用一次性袋子的可降解薄膜，其特征在于：由外到内依次包括保护层、第一粘合层、高阻隔层、第二粘合层和液体接触层共计5层，其中：
    所述保护层由聚己二酸/对苯二甲酸丁二酯、聚丁二酸丁二醇酯和聚乙醇酸共混物制成，聚己二酸/对苯二甲酸丁二酯、聚丁二酸丁二醇酯和聚乙醇酸的重量比为PBAT：PBS：PGA＝(40～70)：(10～40)：(5～30)，所述保护层使用的PBAT和PBS在190℃，2.16Kg测试条件下的熔融指数分别为1.0～15.0g/10min，所述PGA在250℃，2.16Kg测试条件下的熔融指数为1.0～15.0g/10min；
    所述第一粘合层和所述第二粘合层由粘合树脂制成；
    所述高阻隔层由全生物降解型乙烯醇共聚物制成；
    所述液体接触层由生物可降解填料改性的线性低密度聚乙烯制成，线性低密度聚乙烯和生物可降解填料的重量份比为90：10至50：50，所述线性低密度聚乙烯在190℃，2.16Kg测试条件下的熔融指数为1.0～10.0g/10min，所述线性低密度聚乙烯的密度为0.87～0.915g/cm 3。
  2. 根据权利要求1所述的可降解薄膜，其特征在于：
    所述粘合树脂在190℃，2.16Kg测试条件下的熔融指数为1.0～10.0g/10min；和/或
    所述全生物降解型乙烯醇共聚物在190℃，2.16Kg测试条件下的熔融指数为1.0～15.0g/10min；和/或
    所述生物可降解填料为木质素和热塑性淀粉的混合物，热塑性淀粉和木质素的混合比为100：0至70：30。
  3. 根据权利要求2所述的可降解薄膜，其特征在于：
    所述保护层使用的PBAT和PBS在190℃，2.16Kg测试条件下的熔融指数分别为2.0～8.0g/10min；和/或
    所述PGA在250℃，2.16Kg测试条件下的熔融指数为2.0～8.0g/10min；和/或
    所述粘合树脂在190℃，2.16Kg测试条件下的熔融指数为2.0～8.0g/10min；和/或
    所述全生物降解型乙烯醇共聚物在190℃，2.16Kg测试条件下的熔融指数为2.0～8.0g/10min；和/或
    所述生物可降解填料为木质素和热塑性淀粉的混合物，热塑性淀粉和木质素的混合比为100：0至75：25；和/或
    所述液体接触层中，线性低密度聚乙烯和生物可降解填料的重量份比为70：30至50：50；和/或
    所述线性低密度聚乙烯的密度在190℃，2.16Kg测试条件下的熔融指数为2.0～8.0g/10min。
  4. 根据权利要求1～3任一项所述的可降解薄膜，其特征在于：所述第一粘合层和所述第二粘合层由全生物降解型的酸酐改性粘合树脂制成。
  5. 根据权利要求1～3任一项所述的可降解薄膜，其特征在于：所述全生物降解型乙烯醇共聚物选自NichigoG-Polymer TM系列树脂。
  6. 根据权利要求1～3任一项所述的可降解薄膜，其特征在于：所述保护层的厚度为10μm～100μm；和/或
    所述第一粘合层的厚度为10μm～50μm；和/或
    所述高阻隔层的厚度为5μm～40μm；和/或
    所述第二粘合层的厚度为10μm～50μm；和/或
    所述液体接触层的厚度为140μm～500μm。
  7. 根据权利要求1所述的可降解薄膜，其特征在于：所述保护层中，聚己二酸/对苯二甲酸丁二酯、聚丁二酸丁二醇酯和聚乙醇酸的重量比为PBAT：PBS：PGA＝(50～65)：(20～30)：(15～25)。
  8. 根据权利要求1～3任一项所述的可降解薄膜，其特征在于：所述可降解薄膜的
    拉伸强度不低于18Mpa；和/或
    断裂伸长率不低于350％；和/或
    水汽透过量不超过2.6g/m 2.day；和/或
    氧气透过量不超过1.5cm 3/m 2.day.bar；和/或
    GB/T 19277.1-2011标准测试下的降解率不低于60％。
  9. 一种生物制药用一次性袋子，其包括权利要求1～8任一项所述的可降解薄膜。
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