Preparation Method of Biomedical Cycloolefin Copolymer Film

Abstract

The present invention discloses a preparation method of a bio-medical cycloolefin copolymer film. By finely regulating the polymerization reaction and the blending process, a film with good biocompatibility, low water vapor permeability, and high mechanical strength is obtained. First, norbornene is mixed with toluene and dried under nitrogen protection, and then polymerized with a catalyst and ethylene monomer to form a cycloolefin copolymer. The preparation of the modifier includes treating carbon fiber with titanate coupling agent and ultrasonically treating montmorillonite, and then mixing with a cationic starch solution. Finally, a 300-μm-thick film is prepared by co-blending and hot pressing through a co-rotating twin-screw extruder. Compared with the prior art, due to its excellent physical and biological properties, the film is suitable for the bio-medical field. The method has a simple process, high cost-effectiveness, and important application value and market prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of olefin coordination polymerization, and particularly to a method for preparing a biomedical cycloolefin copolymer film. Background Art

[0002] In the biomedical field, the demand for high-performance medical materials is increasing, especially in aspects such as artificial organs, drug delivery systems, tissue engineering, and regenerative medicine. These applications generally require materials to have good biocompatibility, excellent mechanical properties, stable chemical properties, and adjustable biodegradability.

[0003] As a new type of polymer material, cycloolefin copolymer has shown potential applications in the biomedical field due to its unique microstructure and adjustable physicochemical properties. However, traditional cycloolefin copolymers often need to be modified to enhance their performance in specific applications, such as improving their mechanical strength, water barrier properties, and cell affinity.

[0004] Currently, common modification methods include physical blending, chemical modification, and nanocomposite, etc. Physical blending is usually achieved by mixing the copolymer with various fillers, such as adding inorganic fillers or organic polymers. Chemical modification involves chemically modifying the copolymer molecular chain to introduce functional groups. Nanocomposite technology is to introduce nanomaterials such as carbon nanotubes, nanoclays, etc. into the copolymer matrix to expect to obtain a synergistic effect.

[0005] Although the above methods can improve the performance of cycloolefin copolymer to a certain extent, there are still some limitations, such as the dispersion problem of fillers, the biocompatibility problem of the modified material, and the complex preparation process, etc. Therefore, developing new modification strategies and preparation technologies to obtain biomedical cycloolefin copolymer films with better comprehensive performance has important scientific research and practical application value.

[0006] The present invention aims to provide a method for preparing a biomedical cycloolefin copolymer film. By using specific modifiers and advanced processing technologies, the problems existing in the prior art are solved, and a film material with a small water vapor transmission rate, a high relative cell proliferation rate, and excellent mechanical properties is prepared, which is suitable for a series of high-end biomedical applications.

[0007] Chinese Invention Patent Authorization CN105884971B discloses a chain olefin-cyclic olefin copolymer. By adjusting the content of cyclic olefin in the chain olefin-cyclic olefin copolymer and making the copolymer contain a two-unit group formed by direct bonding of two cyclic olefin structural units, the obtained copolymer can exhibit good properties in terms of tensile strength, elongation at break, processing performance, etc. The chain olefin-cyclic olefin copolymer of this invention can be used to manufacture polymer compositions. This chain olefin-cyclic olefin copolymer and this polymer composition can be used to manufacture optical components, packaging materials, electronic components, medical appliances, etc. However, the copolymer of this invention has a high water vapor transmission rate, which is not conducive to cell survival, and has poor tensile properties. Summary of the Invention

[0008] Aiming at the deficiencies existing in the prior art, the technical problem to be solved by this invention is: to provide a preparation method of a bio-medical cyclic olefin copolymer film with a small water vapor transmission rate, high cell survival, and strong tensile properties.

[0009] In order to achieve the above-mentioned invention purpose, this invention adopts the following technical scheme:

[0010] The preparation method of the bio-medical cyclic olefin copolymer film is as follows, by weight:

[0011] Step 1: Dilute 1000 - 3000 parts of norbornene with 8000 - 12000 parts of toluene under nitrogen protection, and dry at 100 - 120 °C for 1 - 3 hours to remove moisture, obtaining a pretreatment product;

[0012] Step 2: Add the pretreatment product prepared in Step 1 into 18000 - 22000 parts of toluene, add 100 - 300 parts of ligand, then add 18 - 22 parts of cocatalyst, at 30 - 50 °C, introduce ethylene gas to a certain pressure, add 8 - 12 parts of catalyst, start the reaction, and set the reaction time to 30 - 90 minutes;

[0013] Step 3: After the reaction ends, use a terminator and stir for 3 - 8 hours to ensure complete termination; remove unreacted monomers by suction filtration, and then dry in an oven to obtain a cyclic olefin copolymer;

[0014] Step 4: Use a co-rotating twin-screw extruder to melt-blend 80 - 120 parts of modifier and 800 - 1000 parts of the cyclic olefin copolymer prepared in Step 3; first perform the first extrusion to obtain a doped copolymer; then mix the doped copolymer with 800 - 1200 parts of the cyclic olefin copolymer prepared in Step 3, perform the second extrusion, and perform high-temperature vacuum melting treatment on the extruded particles in a vacuum drying oven; put the melted sample into a mold coated with a release agent and perform hot pressing on a flat vulcanizer to obtain a bio-medical cyclic olefin copolymer film.

[0015] The ligand is bis(3,5-dimethylphenyl)phosphine chloride.

[0016] The cocatalyst is methylaluminoxane.

[0017] The catalyst is one of rac-[Et(Ind)2]ZrCl2, rac-[Et(IndH4)2]ZrCl2, Cp2ZrCl2, (Ind)2ZrCl2.

[0018] The terminator is 2 - 4 wt% hydrochloric acid ethanol.

[0019] The pressure is 0.9 - 1.5 atm.

[0020] The thickness of the biomedical cycloolefin copolymer film is 100 - 500 μm.

[0021] The preparation method of the modifier is as follows:

[0022] S1. Treat the carbon fiber with a titanate coupling agent. The mass concentration of the titanate coupling agent is controlled at 4 - 6%, and the dosage is 0.3 - 1% of the fiber mass. Treat at 60 - 80 °C for 5 - 10 hours, then fully defibrate and disperse, filter, and collect the solid to obtain the pretreated fiber.

[0023] S2. Use ultrasonic treatment on montmorillonite. Control the power at 500 - 1500 W and the time at 3 - 8 hours. Add cationic starch to water at 80 - 95 °C while keeping stirring to obtain a cationic starch solution with a mass concentration of 0.05 - 0.1%. Add the treated montmorillonite to the cationic starch solution for treatment for 5 - 15 h. The mass ratio of montmorillonite to the cationic starch solution is 1:3 - 5, and then rinse with water until clean to obtain the pretreated montmorillonite.

[0024] S3. Mix the pretreated fiber and the pretreated montmorillonite evenly to obtain the modifier.

[0025] The mass ratio of the pretreated fiber to the pretreated montmorillonite is 1:3 - 5.

[0026] In the preparation method of the biomedical cycloolefin copolymer film of the present invention, each substance has the following functions:

[0027] Norbornene, as one of the main monomers of the polymerization reaction, participates in forming the backbone of the cycloolefin copolymer.

[0028] Toluene, as a solvent, is used to dilute norbornene and provide a suitable reaction medium, and also plays a role in assisting heat transfer in the polymerization reaction.

[0029] Nitrogen is used to protect the polymerization reaction system to prevent oxidants and other impurities from affecting the polymerization reaction.

[0030] Bis(3,5-dimethylphenyl)phosphine chloride acts as a ligand in the polymerization reaction, combines with the catalyst, and affects the activity and selectivity of the catalyst.

[0031] Methylaluminoxane may act as a co-catalyst in the polymerization reaction to assist the main catalyst in its function.

[0032] Ethylene gas, as a comonomer in the polymerization reaction, participates in the polymerization reaction together with norbornene, affecting the chemical structure and physical properties of the copolymer.

[0033] rac-[Et(Ind)2]ZrCl2 acts as a catalyst for the polymerization reaction and promotes the polymerization of monomers.

[0034] Ethanol hydrochloride is used as a terminator to end the polymerization reaction and prevent excessive growth of the polymer molecular weight.

[0035] The modifier consists of pretreated fiber and pretreated montmorillonite, and is used to enhance the mechanical properties and biocompatibility of cyclic olefin copolymer.

[0036] Carbon fiber is used as a reinforcing material. After being treated with a titanate coupling agent, the bonding strength with the copolymer matrix is ​​increased, thereby improving the mechanical properties of the film.

[0037] Titanate coupling agent is used to treat carbon fiber and improve the compatibility of carbon fiber and copolymer matrix through chemical modification.

[0038] Montmorillonite is used as a filler, which increases the barrier properties of the film and reduces the water vapor permeability after being treated with ultrasound and modified with cationic starch.

[0039] Cationic starch is used to treat montmorillonite to provide cationic properties and enhance the interaction between montmorillonite and the copolymer matrix.

[0040] The synergistic effect of these substances makes the finally prepared cyclic olefin copolymer film have good biocompatibility, low water vapor permeability and excellent mechanical properties, and is suitable for use in the biomedical field.

[0041] Compared with the prior art, the present invention has the following beneficial effects:

[0042] 1) The cycloolefin copolymer film prepared by the present invention can significantly improve the tensile strength and mechanical stability of the cycloolefin copolymer film and improve the compatibility by using carbon fiber as a reinforcing material and treating the carbon fiber with a titanate coupling agent.

[0043] 2) The layered structure of montmorillonite and the modification effect of cationic starch used in the cycloolefin copolymer film prepared by the present invention may help to form an effective barrier layer, thereby reducing the water vapor permeability of the film and improving its performance as a packaging material.

[0044] 3) The cycloolefin copolymer film prepared by the present invention exhibits a relatively high relative cell proliferation rate, indicating that this material has a positive impact on cell growth and proliferation and is suitable for tissue engineering and regenerative medicine.

[0045] 4) The cycloolefin copolymer film prepared by the present invention has good comprehensive properties, making it applicable to a variety of biomedical applications and capable of providing high-performance solutions. Detailed implementation mode

[0046] Main sources of substances:

[0047] Cationic starch: Dongguan Dongmei Food Co., Ltd., model: 933.

[0048] Titanate coupling agent: Dongguan Dinghai Plastic Chemical Co., Ltd., product model: 201.

[0049] Aluminate coupling agent: Foshan Jingding Plastic Chemical Co., Ltd., single product item number: 20201016A.

[0050] Tris(trimethylsilyl) phosphate: Wuhan Kemike Biopharmaceutical Technology Co., Ltd., product model: TMSP.

[0051] Mica flakes: Lingshou County Xingzhou Mineral Products Processing Factory, model: 264.

[0052] Montmorillonite: Guangzhou Yifeng Chemical Technology Co., Ltd., model: TY-710C.

[0053] Kaolin: Guangdong Yongfeng Chemical Co., Ltd., item number: 012.

[0054] Poly(dimethyldiallylammonium chloride): Yixing Qingtai Purifying Agent Co., Ltd., model: CW-41.

[0055] Polyethyleneimine: Guangzhou Meigu Chemical Co., Ltd., model: PEI-M300.

[0056] Short aramid fiber: Haining Anjie Composite Materials Co., Ltd., length: 3 - 30 mm.

[0057] Carbon fiber: Cangzhou Zhongli New Material Technology Co., Ltd., specification: 3 mm. Example 1:

[0058] The preparation method of the biomedical cycloolefin copolymer film is as follows:

[0059] Step 1: Dilute 2 kg of norbornene with 10 kg of toluene under nitrogen protection and dry it at 110°C for 2 hours to remove moisture, obtaining a pretreatment product;

[0060] Step 2: Add the pre-treated product prepared in Step 1 into 20 kg of toluene, add 0.2 kg of bis(3,5-dimethylphenyl)phosphine chloride, then add 20 g of methylaluminoxane. At 40 °C, introduce ethylene gas until the pressure reaches 1 atm, add 10 g of rac-[Et(Ind)2]ZrCl2, and start the reaction. The reaction time is set to 60 minutes;

[0061] Step 3: After the reaction is completed, use 3 wt% hydrochloric acid ethanol as the terminator and stir for 5 hours to ensure complete termination; remove the unreacted monomers by suction filtration, and then dry in an oven to obtain the cycloolefin copolymer;

[0062] Step 4: Use a co-rotating twin-screw extruder to melt-blend 100 g of the modifier and 900 g of the cycloolefin copolymer prepared in Step 3; first perform the first extrusion to obtain the doped copolymer; then mix the doped copolymer with 1 kg of the cycloolefin copolymer prepared in Step 3 and perform the second extrusion. Heat the extruded pellets under high-temperature vacuum melting in a vacuum drying oven; put the melted sample into a mold coated with a release agent and perform hot pressing on a flat vulcanizer to obtain the biomedical cycloolefin copolymer film with a thickness of 300 μm.

[0063] The preparation method of the modifier is as follows:

[0064] S1: Treat the carbon fiber with a titanate coupling agent. The mass concentration of the titanate coupling agent is controlled at 5%, and the dosage is 0.5% of the fiber mass. Treat at 70 °C for 8 hours, then fully defibrate and disperse, filter, and collect the solid to obtain the pre-treated fiber;

[0065] S2: Use ultrasonic treatment on montmorillonite with a power controlled at 1000 W for 5 hours. Add cationic starch into water at 90 °C while keeping stirring to obtain a 0.08% cationic starch solution by mass concentration. Add the treated montmorillonite into the cationic starch solution and treat for 10 h. The mass ratio of montmorillonite to the cationic starch solution is 1:4, and then rinse with water to obtain the pre-treated montmorillonite;

[0066] S3: Mix the pre-treated fiber and the pre-treated montmorillonite evenly according to the mass ratio of 1:4 to obtain the modifier. Example 2:

[0067] The preparation method of the biomedical cycloolefin copolymer film is as follows:

[0068] Step 1: Dilute 2 kg of norbornene with 10 kg of toluene under nitrogen protection and dry at 110 °C for 2 hours to remove moisture to obtain the pre-treated product;

[0069] Step 2: Add the pre-treated product prepared in Step 1 into 20 kg of toluene, add 0.2 kg of methyltriphenylphosphonium chloride, then add 20 g of methylaluminoxane. At 40 °C, introduce ethylene gas until the pressure reaches 1 atm, add 10 g of rac-[Et(Ind)2]ZrCl2, and start the reaction. The reaction time is set to 60 minutes;

[0070] Step 3: After the reaction is completed, use 3 wt% hydrochloric acid ethanol as the terminator and stir for 5 hours to ensure complete termination; remove the unreacted monomers by suction filtration, and then dry in an oven to obtain the cycloolefin copolymer;

[0071] Step 4: Use a co-rotating twin-screw extruder to melt-blend 100 g of the modifier and 900 g of the cycloolefin copolymer prepared in Step 3; first perform the first extrusion to obtain the doped copolymer; then mix the doped copolymer with 1 kg of the cycloolefin copolymer prepared in Step 3 and perform the second extrusion. Heat the extruded pellets under high-temperature vacuum melting in a vacuum drying oven; put the melted sample into a mold coated with a release agent and perform hot pressing on a flat vulcanizer to obtain the biomedical cycloolefin copolymer film with a thickness of 300 μm.

[0072] The preparation method of the modifier is the same as that in Example 1. Example 3:

[0073] The preparation method of the biomedical cycloolefin copolymer film is as follows:

[0074] Step 1: Dilute 2 kg of norbornene with 10 kg of toluene under nitrogen protection and dry at 110 °C for 2 hours to remove moisture to obtain the pre-treated product;

[0075] Step 2: Add the pre-treated product prepared in Step 1 into 20 kg of toluene, add 0.2 kg of 2,3,5-triiodobenzoic acid, then add 20 g of methylaluminoxane. At 40 °C, introduce ethylene gas until the pressure reaches 1 atm, add 10 g of rac-[Et(Ind)2]ZrCl2, and start the reaction. The reaction time is set to 60 minutes;

[0076] Step 3: After the reaction is completed, use 3 wt% hydrochloric acid ethanol as the terminator and stir for 5 hours to ensure complete termination; remove the unreacted monomers by suction filtration, and then dry in an oven to obtain the cycloolefin copolymer;

[0077] Step 4: Use a co-rotating twin-screw extruder to melt-blend 100 g of the modifier and 900 g of the cycloolefin copolymer prepared in Step 3; first perform the first extrusion to obtain a doped copolymer; then mix the doped copolymer with 1 kg of the cycloolefin copolymer prepared in Step 3 and perform the second extrusion, and subject the extruded pellets to high-temperature vacuum melting treatment in a vacuum drying oven; place the melted sample into a mold coated with a mold release agent and perform hot pressing on a flat vulcanizer to obtain a bio-medical cycloolefin copolymer film with a thickness of 300 μm.

[0078] The preparation method of the modifier is the same as that in Example 1. Example 4:

[0079] The preparation method of the bio-medical cycloolefin copolymer film is basically the same as that in Example 1, and the only difference lies in the different preparation methods of the modifier.

[0080] The preparation method of the modifier is as follows:

[0081] S1. Treat the chopped aramid fiber with a titanate coupling agent. The mass concentration of the titanate coupling agent is controlled at 5%, and the dosage is 0.5% of the fiber mass. Treat it at 70 °C for 8 hours, then fully defibrate and disperse it, filter, and collect the solid to obtain the pretreated fiber;

[0082] S2. Use ultrasonic treatment on montmorillonite, control the power at 1000 W and the time at 5 hours. Add cationic starch to water at 90 °C while keeping stirring to obtain a 0.08% cationic starch solution by mass concentration. Add the treated montmorillonite to the cationic starch solution and treat it for 10 h. The mass ratio of montmorillonite to the cationic starch solution is 1:4, and then rinse it with water until clean to obtain the pretreated montmorillonite;

[0083] S3. Mix the pretreated fiber and the pretreated montmorillonite evenly according to the mass ratio of 1:4 to obtain the modifier. Example 5:

[0084] The preparation method of the bio-medical cycloolefin copolymer film is basically the same as that in Example 1, and the only difference lies in the different preparation methods of the modifier.

[0085] The preparation method of the modifier is as follows:

[0086] S1. Treat the carbon fiber with an aluminate coupling agent. The mass concentration of the aluminate coupling agent is controlled at 5%, and the dosage is 0.5% of the fiber mass. Treat it at 70 °C for 8 hours, then fully defibrate and disperse it, filter, and collect the solid to obtain the pretreated fiber;

[0087] S2. Treat montmorillonite with ultrasound, control the power at 1000 W and the time at 5 hours. Add cationic starch to water at 90 °C while keeping stirring to obtain a cationic starch solution with a mass concentration of 0.08%. Add the treated montmorillonite to the cationic starch solution and treat for 10 h. The mass ratio of montmorillonite to the cationic starch solution is 1:4, and then rinse it with water until clean to obtain pretreated montmorillonite;

[0088] S3. Mix the pretreated fiber and the pretreated montmorillonite evenly according to the mass ratio of 1:4 to obtain a modifier. Example 6:

[0089] The preparation method of the bio-medical cycloolefin copolymer film is basically the same as that of Example 1, and the only difference lies in the preparation method of the modifier.

[0090] The preparation method of the said modifier is as follows:

[0091] S1. Treat carbon fiber with tris(trimethylsilyl) phosphate. Control the mass concentration of tris(trimethylsilyl) phosphate at 5% and the dosage at 0.5% of the fiber mass. Treat at 70 °C for 8 hours, then fully defibrate and disperse, filter, and collect the solid to obtain pretreated fiber;

[0092] S2. Treat montmorillonite with ultrasound, control the power at 1000 W and the time at 5 hours. Add cationic starch to water at 90 °C while keeping stirring to obtain a cationic starch solution with a mass concentration of 0.08%. Add the treated montmorillonite to the cationic starch solution and treat for 10 h. The mass ratio of montmorillonite to the cationic starch solution is 1:4, and then rinse it with water until clean to obtain pretreated montmorillonite;

[0093] S3. Mix the pretreated fiber and the pretreated montmorillonite evenly according to the mass ratio of 1:4 to obtain a modifier. Example 7:

[0094] The preparation method of the bio-medical cycloolefin copolymer film is basically the same as that of Example 1, and the only difference lies in the preparation method of the modifier.

[0095] The preparation method of the said modifier is as follows:

[0096] S1. Treat carbon fiber with titanate coupling agent. Control the mass concentration of titanate coupling agent at 5% and the dosage at 0.5% of the fiber mass. Treat at 70 °C for 8 hours, then fully defibrate and disperse, filter, and collect the solid to obtain pretreated fiber;

[0097] S2. Treat montmorillonite with ultrasound, control the power at 1000 W and the time at 5 hours. Add polyethyleneimine to water at 90 °C while keeping stirring to obtain a polyethyleneimine solution with a mass concentration of 0.08%. Add the treated montmorillonite to the polyethyleneimine solution and process for 10 h. The mass ratio of montmorillonite to the polyethyleneimine solution is 1:4, and then rinse with water until clean to obtain pretreated montmorillonite;

[0098] S3. Mix the pretreated fiber and the pretreated montmorillonite evenly according to a mass ratio of 1:4 to obtain a modifier. Example 8:

[0099] The preparation method of the bio-medical cycloolefin copolymer film is basically the same as that of Example 1, and the only difference lies in the preparation method of the modifier.

[0100] The preparation method of the said modifier is as follows:

[0101] S1. Treat carbon fiber with a titanate coupling agent, control the mass concentration of the titanate coupling agent at 5% and the dosage at 0.5% of the fiber mass, treat at 70 °C for 8 hours, then fully defibrate and disperse, filter, and collect the solid to obtain pretreated fiber;

[0102] S2. Treat montmorillonite with ultrasound, control the power at 1000 W and the time at 5 hours. Add polydimethyldiallylammonium chloride to water at 90 °C while keeping stirring to obtain a polydimethyldiallylammonium chloride solution with a mass concentration of 0.08%. Add the treated montmorillonite to the polydimethyldiallylammonium chloride solution and process for 10 h. The mass ratio of montmorillonite to the polydimethyldiallylammonium chloride solution is 1:4, and then rinse with water until clean to obtain pretreated montmorillonite;

[0103] S3. Mix the pretreated fiber and the pretreated montmorillonite evenly according to a mass ratio of 1:4 to obtain a modifier. Example 9:

[0104] The preparation method of the bio-medical cycloolefin copolymer film is basically the same as that of Example 1, and the only difference lies in the preparation method of the modifier.

[0105] The preparation method of the said modifier is as follows:

[0106] S1. Treat carbon fiber with a titanate coupling agent, control the mass concentration of the titanate coupling agent at 5% and the dosage at 0.5% of the fiber mass, treat at 70 °C for 8 hours, then fully defibrate and disperse, filter, and collect the solid to obtain pretreated fiber;

[0107] S2. Treat kaolin with ultrasound, control the power at 1000 W and the time at 5 hours. Add cationic starch into water at 90 °C while keeping stirring to obtain a cationic starch solution with a mass concentration of 0.08%. Add the treated kaolin into the cationic starch solution and treat for 10 h. The mass ratio of kaolin to the cationic starch solution is 1:4, and then rinse it with water until clean to obtain pretreated kaolin.

[0108] S3. Mix the pretreated fiber and pretreated kaolin evenly according to the mass ratio of 1:4 to obtain a modifier. Example 10:

[0109] The preparation method of the bio-medical cycloolefin copolymer film is basically the same as that in Example 1, and the only difference lies in the preparation method of the modifier.

[0110] The preparation method of the said modifier is as follows:

[0111] S1. Treat carbon fiber with a titanate coupling agent, control the mass concentration of the titanate coupling agent at 5% and the dosage at 0.5% of the fiber mass, treat at 70 °C for 8 hours, then fully defibrate and disperse, filter, and collect the solid to obtain pretreated fiber.

[0112] S2. Treat mica flakes with ultrasound, control the power at 1000 W and the time at 5 hours. Add cationic starch into water at 90 °C while keeping stirring to obtain a cationic starch solution with a mass concentration of 0.08%. Add the treated mica flakes into the cationic starch solution and treat for 10 h. The mass ratio of mica flakes to the cationic starch solution is 1:4, and then rinse it with water until clean to obtain pretreated mica flakes.

[0113] S3. Mix the pretreated fiber and pretreated mica flakes evenly according to the mass ratio of 1:4 to obtain a modifier.

[0114] Comparative Example 1

[0115] The preparation method of the bio-medical cycloolefin copolymer film is as follows:

[0116] Step 1. Dilute 2 kg of norbornene with 10 kg of toluene under nitrogen protection and dry at 110 °C for 2 hours to remove moisture to obtain a pretreated product.

[0117] Step 2. Add the pretreated product prepared in Step 1 into 20 kg of toluene, add 0.2 kg of bis(3,5-dimethylphenyl)phosphine chloride, then add 20 g of methylaluminoxane. At 40 °C, introduce ethylene gas to a pressure of 1 atm, add 10 g of rac-[Et(Ind)2]ZrCl2, start the reaction, and set the reaction time to 60 minutes.

[0118] Step 3: After the reaction is completed, use 3wt% hydrochloric acid ethanol as a terminator and stir for 5 hours to ensure complete termination; remove the unreacted monomers by suction filtration, and then dry them in an oven to obtain a cycloolefin copolymer;

[0119] Step 4: Use a co-rotating twin-screw extruder to melt-blend 20 g of carbon fiber, 80 g of montmorillonite, and 900 g of the cycloolefin copolymer prepared in Step 3; first perform the first extrusion to obtain a doped copolymer; then mix the doped copolymer with 1 kg of the cycloolefin copolymer prepared in Step 3 and perform the second extrusion. Subject the extruded pellets to high-temperature vacuum melting treatment in a vacuum drying oven; place the melted sample in a mold coated with a release agent and perform hot pressing on a flat vulcanizer to obtain a bio-medical cycloolefin copolymer film with a thickness of 300 μm.

[0120] Comparative Example 2

[0121] The preparation method of the bio-medical cycloolefin copolymer film is as follows:

[0122] Step 1: Dilute 2 kg of norbornene with 10 kg of toluene under nitrogen protection and dry at 110°C for 2 hours to remove moisture to obtain a pretreatment product;

[0123] Step 2: Add the pretreatment product prepared in Step 1 to 20 kg of toluene, add 0.2 kg of bis(3,5-dimethylphenyl)phosphine chloride, then add 20 g of methylaluminoxane, at 40°C, introduce ethylene gas to a pressure of 1 atm, add 10 g of rac-[Et(Ind)2]ZrCl2, start the reaction, and set the reaction time to 60 minutes;

[0124] Step 3: After the reaction is completed, use 3wt% hydrochloric acid ethanol as a terminator and stir for 5 hours to ensure complete termination; remove the unreacted monomers by suction filtration, and then dry them in an oven to obtain a cycloolefin copolymer;

[0125] Step 4: Use a co-rotating twin-screw extruder to melt-blend 20 g of chopped aramid fiber, 80 g of montmorillonite, and 900 g of the cycloolefin copolymer prepared in Step 3; first perform the first extrusion to obtain a doped copolymer; then mix the doped copolymer with 1 kg of the cycloolefin copolymer prepared in Step 3 and perform the second extrusion. Subject the extruded pellets to high-temperature vacuum melting treatment in a vacuum drying oven; place the melted sample in a mold coated with a release agent and perform hot pressing on a flat vulcanizer to obtain a bio-medical cycloolefin copolymer film with a thickness of 300 μm.

[0126] Comparative Example 3

[0127] The preparation method of the bio-medical cycloolefin copolymer film is as follows:

[0128] Step 1: Dilute 2 kg of norbornene with 10 kg of toluene under nitrogen protection, and dry it at 110 °C for 2 hours to remove moisture, obtaining a pretreated product;

[0129] Step 2: Add the pretreated product prepared in Step 1 to 20 kg of toluene, add 0.2 kg of bis(3,5-dimethylphenyl)phosphine chloride, then add 20 g of methylaluminoxane. At 40 °C, introduce ethylene gas to a pressure of 1 atm, add 10 g of rac-[Et(Ind)2]ZrCl2, and start the reaction. The reaction time is set to 60 minutes;

[0130] Step 3: After the reaction is completed, use 3 wt% hydrochloric acid ethanol as a terminator and stir for 5 hours to ensure complete termination; Remove the unreacted monomers by suction filtration, and then dry them in a drying oven to obtain a cycloolefin copolymer;

[0131] Step 4: Use a co-rotating twin-screw extruder to melt-blend 20 g of carbon fiber, 80 g of kaolin, and 900 g of the cycloolefin copolymer prepared in Step 3; First, perform the first extrusion to obtain a doped copolymer; Then mix the doped copolymer with 1 kg of the cycloolefin copolymer prepared in Step 3 and perform the second extrusion. Subject the extruded pellets to high-temperature vacuum melting treatment in a vacuum drying oven; Place the melted sample in a mold coated with a mold release agent and perform hot pressing on a flat vulcanizer to obtain a bio-medical cycloolefin copolymer film with a thickness of 300 μm.

[0132] Comparative Example 4

[0133] The preparation method of the bio-medical cycloolefin copolymer film is as follows:

[0134] Step 1: Dilute 2 kg of norbornene with 10 kg of toluene under nitrogen protection, and dry it at 110 °C for 2 hours to remove moisture, obtaining a pretreated product;

[0135] Step 2: Add the pretreated product prepared in Step 1 to 20 kg of toluene, add 0.2 kg of bis(3,5-dimethylphenyl)phosphine chloride, then add 20 g of methylaluminoxane. At 40 °C, introduce ethylene gas to a pressure of 1 atm, add 10 g of rac-[Et(Ind)2]ZrCl2, and start the reaction. The reaction time is set to 60 minutes;

[0136] Step 3: After the reaction is completed, use 3 wt% hydrochloric acid ethanol as a terminator and stir for 5 hours to ensure complete termination; Remove the unreacted monomers by suction filtration, and then dry them in a drying oven to obtain a cycloolefin copolymer;

[0137] Step 4: Use a co-rotating twin-screw extruder to melt-blend 20 g of carbon fiber, 80 g of mica flakes, and 900 g of the cycloolefin copolymer prepared in Step 3; first perform the first extrusion to obtain a doped copolymer; then mix the doped copolymer with 1 kg of the cycloolefin copolymer prepared in Step 3 and perform the second extrusion. Subject the extruded pellets to high-temperature vacuum melting treatment in a vacuum drying oven; place the melted sample into a mold coated with a release agent and perform hot pressing on a flat vulcanizer to obtain a bio-medical cycloolefin copolymer film with a thickness of 300 μm.

[0138] Comparative Example 5

[0139] The preparation method of the bio-medical cycloolefin copolymer film is as follows:

[0140] Step 1: Dilute 2 kg of norbornene with 10 kg of toluene under nitrogen protection and dry at 110 °C for 2 hours to remove moisture to obtain a pretreated product;

[0141] Step 2: Add the pretreated product prepared in Step 1 to 20 kg of toluene, add 0.2 kg of bis(3,5-dimethylphenyl)phosphine chloride, then add 20 g of methylaluminoxane. At 40 °C, introduce ethylene gas to a pressure of 1 atm, add 10 g of rac-[Et(Ind)2]ZrCl2, start the reaction, and set the reaction time to 60 minutes;

[0142] Step 3: After the reaction, use 3 wt% hydrochloric acid ethanol as a terminator and stir for 5 hours to ensure complete termination; remove the unreacted monomers by suction filtration, and then dry in a drying oven to obtain a cycloolefin copolymer;

[0143] Step 4: Use a co-rotating twin-screw extruder to melt-blend 900 g of the cycloolefin copolymer prepared in Step 3; first perform the first extrusion to obtain a copolymer; then mix the copolymer with 1 kg of the cycloolefin copolymer prepared in Step 3 and perform the second extrusion. Subject the extruded pellets to high-temperature vacuum melting treatment in a vacuum drying oven; place the melted sample into a mold coated with a release agent and perform hot pressing on a flat vulcanizer to obtain a bio-medical cycloolefin copolymer film with a thickness of 300 μm.

[0144] Test Example 1

[0145] Water vapor transmission rate test

[0146] The barrier properties of the biomedical cycloolefin copolymer films obtained in Examples 1-10 and Comparative Examples 1-5 of the present invention were measured, and the water vapor transmission rate was used to characterize the barrier properties of the materials. Referring to the weight gain method in GB / T 1037-2021 "Determination of Water Vapor Transmission Properties of Plastic Films and Sheets - Cup Method for Weight Gain and Weight Loss", the water vapor transmission rate was tested. The test temperature was 38 °C, the humidity was 90% RH, the preheating time was 2 h, the rotation interval was 10 min, and 3 parallels were set for each group. The lower the value of the water vapor transmission rate, the better the water resistance.

[0147] The test results are shown in Table 1.

[0148] Table 1

[0149] Experimental Scheme Water Vapor Transmission Rate g / (m²·d) Example 1 0.35 Example 2 0.69 Example 3 0.71 Example 4 0.37 Example 5 0.45 Example 6 0.48 Example 7 0.46 Example 8 0.51 Example 9 0.72 Example 10 0.83 Comparative Example 1 0.73 Comparative Example 2 0.73 Comparative Example 3 0.77 Comparative Example 4 0.83 Comparative Example 5 1.85

[0150] Test Example 2

[0151] Cell relative proliferation rate test

[0152] The cytocompatibility of the biomedical cycloolefin copolymer film was evaluated. The specific experimental steps are as follows:

[0153] 1. The prepared cycloolefin copolymer film samples (including Examples 1 to 10 and Comparative Examples 1 to 5) were cut into small segments about 0.5 cm long.

[0154] 2. These small film segments were thoroughly sterilized by ultraviolet light irradiation.

[0155] 3. The sterilized small film segments were placed in a 48-well cell culture plate, and the same number of HMS cells (105 cells) were added to each well.

[0156] 4. The cell culture plate was then placed in a cell culture incubator for 24 hours of culture.

[0157] 5. The evaluation of cell viability was performed using a CCK-8 cell viability kit (provided by Tiangen Co., China). In the experiment, the total cell viability level was measured by the optical density (OD value) at a wavelength of 450 nm.

[0158] 6. As a control experiment, the same number of cells were cultured without the film scaffold to compare and evaluate the effect of the film samples on cell viability.

[0159] 7. By calculating the cell relative proliferation rate (RGR), the proliferation of cells on the film samples was quantitatively analyzed. The calculation formula of RGR is: RGR(%) = (OD value of the sample well / OD value of the control group) × 100%.

[0160] The purpose of this experiment is to evaluate the biocompatibility of cycloolefin copolymer films with HMS cells through cell viability tests, so as to provide experimental basis for the application of this material in the biomedical field. By comparing the relative cell proliferation rates of different samples, the ability to support cell growth can be inferred, which is crucial for the design and optimization of biomedical materials.

[0161] The test results are shown in Table 2.

[0162] Table 2

[0163] Experimental Scheme Relative Growth Rate of Cells RGR(%) Example 1 97.4 Example 2 96.3 Example 3 95.5 Example 4 96.9 Example 5 94.6 Example 6 96.1 Example 7 95.6 Example 8 95.1 Example 9 96.1 Example 10 97.3 Comparative Example 1 93.1 Comparative Example 2 92.5 Comparative Example 3 92.6 Comparative Example 4 93.0 Comparative Example 5 89.4

[0164] Test Example 3

[0165] Tensile strength tests were respectively carried out on the biomedical cycloolefin copolymer films obtained in Examples 1 to 10 and Comparative Examples 1 to 5 of the present invention. Among them, the tensile strength was measured according to GB / T 1040.3-2006 "Plastics - Determination of tensile properties - Part 3: Test conditions for films and sheets", the test speed was 100 mm / min, the specimen size was 150 mm × 15 mm, and the test temperature was 23 °C.

[0166] The test results are shown in Table 3.

[0167] Table 3

[0168] Experimental Scheme Tensile Strength (MPa) Example 1 92.4 Example 2 86.3 Example 3 84.5 Example 4 84.1 Example 5 92.1 Example 6 90.5 Example 7 92.2 Example 8 91.9 Example 9 91.5 Example 10 90.1 Comparative Example 1 86.3 Comparative Example 2 85.2 Comparative Example 3 85.9 Comparative Example 4 84.1 Comparative Example 5 76.6

[0169] It can be seen from Test Examples 1 to 3 that the biomedical cycloolefin copolymer film obtained in Example 1 of the present invention has a small water vapor transmission rate, a high relative cell proliferation rate, and a large tensile strength.

[0170] In Examples 1 to 3 of the present invention, by changing the ligands in the polymerization reaction, significant effects can be exerted on the properties of the cycloolefin copolymer film. Specifically, in Example 1, bis(3,5-dimethylphenyl)phosphine chloride was used; in Example 2, methyltriphenylphosphonium chloride was used; and in Example 3, 2,3,5-triiodobenzoic acid was used. These different ligands affected the activity, selectivity of the polymerization reaction, and the microstructure of the polymer, thereby changing the physical and chemical properties of the film, such as water vapor transmission rate, relative cell proliferation rate, and tensile strength. Both bis(3,5-dimethylphenyl)phosphine chloride and methyltriphenylphosphonium chloride are phosphine ligands, but they have different electron densities and steric hindrances. This may affect the electronic environment of the metal catalyst, and further affect the activity of the polymerization reaction and the growth rate of the polymer chain. Different ligands may produce different steric effects around the catalyst active center, which will affect the stereoselectivity of the polymerization reaction, thereby affecting the molecular weight distribution and microstructure of the polymer. Bis(3,5-dimethylphenyl)phosphine chloride in Example 1 may promote a more uniform growth of the polymer chain, resulting in a narrower molecular weight distribution and a higher regularity of the polymer chain, which helps to improve the tensile strength of the film and reduce the water vapor transmission rate. The ligand in Example 1 may promote the formation of specific functional groups on the polymer chain, and these functional groups may be more conducive to cell attachment and proliferation, thereby increasing the relative cell proliferation rate.

[0171] In Example 1 and Example 4 of the present invention, the main difference lies in the different types of reinforcing fibers used in the modifier: carbon fibers were used in Example 1, while chopped aramid fibers were used in Example 4. Carbon fibers and aramid fibers have different surface chemical properties and roughness, which may affect their adhesion strength with the resin, thereby affecting the mechanical properties of the film. Carbon fibers are well-known for their excellent mechanical strength and stiffness, while aramid fibers also have high strength and modulus, but their stress-strain behaviors may be different. These differences may affect the tensile strength of the copolymer film. The surface energy and chemical functional groups of carbon fibers and aramid fibers are different, which may affect their compatibility and dispersibility with the cycloolefin copolymer resin, thereby affecting the microstructure and macroscopic properties of the film. Carbon fibers have extremely high thermal stability, while aramid fibers may exhibit different thermal behaviors at high temperatures. This may affect the thermal stability and crystallization behavior of the film during the melt blending and hot pressing processes. The low water absorption of carbon fibers may help reduce the water vapor transmission.

[0172] In Example 1 of the present invention, compared with Examples 5 to 6, by changing the type of coupling agent used for the surface treatment of carbon fiber, changes in the properties of the cycloolefin copolymer film can be observed. These coupling agents include titanate coupling agent, aluminate coupling agent, and tris(trimethylsilyl) phosphate. Different coupling agents have different steric structures. Aluminate and tris(trimethylsilyl) phosphate may have a greater steric hindrance relative to titanate, which may affect their dispersibility and compatibility in the copolymer matrix. The carbon fiber treated with titanate coupling agent may form a more effective barrier layer in the copolymer matrix, reducing the water vapor transmission rate. The titanate coupling agent may provide more suitable surface characteristics, promoting cell attachment and proliferation, thereby increasing the relative cell proliferation rate. Tris(trimethylsilyl) phosphate has a high hydrophobicity, which may be unfavorable for cell attachment, while the hydrophilicity of the titanate coupling agent may be more suitable for biomedical materials.

[0173] In Examples 1, 7, and 8 of the present invention, by changing the type of cationic polymer used for treating montmorillonite in the modifier, differences in the water vapor transmission rate, relative cell proliferation rate, tensile strength, etc. of the cycloolefin copolymer film can be observed. Polyethyleneimine and polydimethyldiallylammonium chloride have more linear molecular structures, while cationic starch has a branched structure. This structural difference may affect the dispersibility and compatibility of the polymer in the copolymer matrix. Cationic starch may provide more suitable surface characteristics, promoting cell attachment and proliferation, thereby increasing the relative cell proliferation rate. As a natural polymer, cationic starch may have better biocompatibility, contributing to improving the biomedical properties of the film.

[0174] In Examples 1, 9, and 10, by changing the type of clay mineral (montmorillonite, kaolin, mica flakes) used in the modifier, differences in the water vapor transmission rate, relative cell proliferation rate, tensile strength, etc. of the cycloolefin copolymer film can be observed. Montmorillonite, kaolin, and mica flakes have different interlayer structures and interlayer spacings. Montmorillonite usually has a more suitable interlayer charge and interlayer spacing, which may result in better intercalation ability and reinforcement effect. Due to its layered structure, montmorillonite may provide a better reinforcement effect, thereby increasing the tensile strength of the film. The interlayer structure of montmorillonite may more effectively block water vapor, thereby reducing the water vapor transmission rate of the film.

Claims

1. A method for preparing a biomedical cycloolefin copolymer film, characterized in that: The method is as follows, in parts by weight: Step 1, diluting 1000-3000 parts of norbornene with 8000-12000 parts of toluene under nitrogen protection, and drying at 100-120° C. for 1-3 hours to remove moisture to obtain a pretreated product; Step 2, adding the pretreated product prepared in step 1 to 18000-22000 parts of toluene, adding 100-300 parts of ligand, and then adding 18-22 parts of co-catalyst, at 30-50° C., introducing ethylene gas to a certain pressure, adding 8-12 parts of catalyst, starting the reaction, and setting the reaction time to 30-90 minutes; Step 3: After the reaction is completed, a terminator is used and stirred for 3 to 8 hours to ensure sufficient termination; unreacted monomers are removed by suction filtration, and then dried in a drying oven to obtain a cycloolefin copolymer; Step 4, using a co-rotating twin-screw extruder to melt-blend 80-120 parts of the modifier and 800-1000 parts of the cycloolefin copolymer prepared in step 3; firstly, perform a first extrusion to obtain a doped copolymer; then mix the doped copolymer with 800-1200 parts of the cycloolefin copolymer prepared in step 3, perform a second extrusion, and perform a high-temperature vacuum melting treatment on the extruded particles in a vacuum drying oven; put the melted sample into a mold coated with a release agent, and perform hot pressing on a flat vulcanizer to obtain a biomedical cycloolefin copolymer film; The ligand is bis(3,5-dimethylphenyl)phosphine chloride; The preparation method of the modifier is as follows: S1. Treat the carbon fiber with a titanate coupling agent, wherein the mass concentration of the titanate coupling agent is controlled at 4-6%, the dosage is 0.3-1% of the fiber mass, and the treatment is carried out at 60-80°C for 5-10 hours, and then the carbon fiber is fully dispersed, filtered, and the solid is collected to obtain a pretreated fiber; S2, using ultrasound to treat montmorillonite, the power is controlled at 500~1500W, the time is 3~8 hours, the cationic starch is added to 80~95℃ water, and stirring is maintained at the same time, to obtain a cationic starch solution with a mass concentration of 0.05~0.1%, and the treated montmorillonite is added to the cationic starch solution for treatment for 5~15h, the mass ratio of montmorillonite to cationic starch solution is 1:3~5, and then rinsed with water to obtain pretreated montmorillonite; S3, mixing the pretreated fiber and the pretreated montmorillonite uniformly to obtain a modifier; The mass ratio of the pretreated fiber to the pretreated montmorillonite is 1:3-5.

2. The method for preparing the biomedical cycloolefin copolymer film according to claim 1, characterized in that: The co-catalyst is methylaluminoxane.

3. The method for preparing the biomedical cycloolefin copolymer film according to claim 1, characterized in that: The catalyst is one of rac-[Et(Ind)2]ZrCl2, rac-[Et(IndH4)2]ZrCl2, Cp2ZrCl2, and (Ind)2ZrCl2.

4. The method for preparing the biomedical cycloolefin copolymer film according to claim 1, characterized in that: The terminator is 2-4 wt% ethanol hydrochloride.

5. The method for preparing the biomedical cycloolefin copolymer film according to claim 1, characterized in that: The pressure is 0.9~1.5atm.

6. The method for preparing the biomedical cycloolefin copolymer film according to claim 1, characterized in that: The biomedical cycloolefin copolymer film has a thickness of 100-500 μm.

7. A biomedical cyclic olefin copolymer film, characterized in that: The method is described in any one of claims 1 to 6.