WO2022083067A1 - 一种具有梯度孔结构的聚(4-甲基-1-戊烯)中空纤维膜、制备方法及应用 - Google Patents

一种具有梯度孔结构的聚(4-甲基-1-戊烯)中空纤维膜、制备方法及应用 Download PDF

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WO2022083067A1
WO2022083067A1 PCT/CN2021/083475 CN2021083475W WO2022083067A1 WO 2022083067 A1 WO2022083067 A1 WO 2022083067A1 CN 2021083475 W CN2021083475 W CN 2021083475W WO 2022083067 A1 WO2022083067 A1 WO 2022083067A1
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methyl
pentene
poly
membrane
hollow fiber
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PCT/CN2021/083475
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French (fr)
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林亚凯
汪林
王晓琳
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清华大学
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/26—Polyalkenes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • B01D67/0002—Organic membrane manufacture
    • B01D67/0009—Organic membrane manufacture by phase separation, sol-gel transition, evaporation or solvent quenching
    • B01D67/0011—Casting solutions therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/08—Hollow fibre membranes

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  • the present application relates to a poly(4-methyl-1-pentene) hollow fiber membrane with a gradient pore structure, a preparation method and application thereof, in particular to the preparation of a poly(4-methyl-1-pentene) hollow fiber membrane with a gradient pore structure using a thermally induced phase separation method and a non-solvent phase separation integrated process Method for structured poly(4-methyl-1-pentene) hollow fiber membrane and hollow fiber membrane prepared by the method.
  • Extracorporeal Membrane Oxygenation (ECMO) system has the function of replacing human lungs to regulate the content of oxygen and carbon dioxide in the blood. It has become an important medical treatment in the treatment of acute respiratory diseases, waiting for lung transplantation and cardiovascular surgery. equipment.
  • ECMO consists of membrane oxygenator, blood pump, gas mixer, various pipelines and monitors.
  • Membrane oxygenator is the key place for gas-blood exchange and the core component of ECMO system. It requires the membrane to have good gas permeability and anti-blood infiltration during its work.
  • the membranes for ECMO are mainly polyolefin hollow fiber membranes, including polypropylene (Polypropene, PP) and poly(4-methyl-1-pentene, PMP).
  • the main processing method is thermally induced phase separation (Thermally induced phase separation). induced phase separation, TIPS) method.
  • the TIPS method was first proposed by Castro in US Patent No. 4,247,498 (1981), which can achieve a high-strength, high-porosity sponge microporous structure by adjusting the polymer concentration, diluent system and ratio, and has now become a polymer microporous structure. important means of membrane preparation.
  • Patents CN1301149C, CN1121896C, CN1136035C, CN1141169C, CN110538582A and CN110548411A describe in detail the method for preparing polyolefin hollow fiber membrane with asymmetric structure by TIPS method using polyolefin high temperature good solvent and non-solvent as diluent.
  • the melting temperature of poly(4-methyl-1-pentene) is close to the crystallization temperature, it is difficult to control the phase separation and crystallization behavior of poly(4-methyl-1-pentene) in the TIPS process.
  • the present application provides a preparation method of a poly(4-methyl-1-pentene) hollow fiber gradient pore membrane, which can avoid the use of toxic organic solvents and obtain poly(4-methyl-1-pentene) with better properties.
  • 4-methyl-1-pentene) hollow fiber gradient pore membrane 4-methyl-1-pentene
  • the preparation method of the poly(4-methyl-1-pentene) hollow fiber gradient pore membrane of the present application comprises the following steps:
  • Extrusion molding at 200-270° C., extrude the casting liquid described in step 1) into hollow fibers through an extruder at a speed of 20-100 m/min;
  • step 3 Phase separation and solidification: passing the hollow fiber described in step 2) through the air section at room temperature for 1-300ms, and then entering a cooling bath with a temperature of 0-50°C to solidify into a film;
  • step 5 Place the membrane after removing the diluent in step 4) in an oven to dry to obtain the poly(4-methyl-1-pentene) hollow fiber gradient pore membrane.
  • the above method firstly mixes the poly(4-methyl-1-pentene) with the diluent at a high temperature, and then extrudes it for one time.
  • the diluent yields hollow fiber membranes.
  • NIPS Nonsolvent induced phase separation
  • TIPS Nonsolvent induced phase separation
  • the behavior of TIPS and NIPS in the curing process can be further regulated, so as to realize the regulation and optimization of the gradient pore structure of poly(4-methyl-1-pentene) hollow fiber membranes.
  • the present application also provides poly(4-methyl-1-pentene) hollow fiber gradient pore membranes that can be prepared by the above method.
  • the present application also provides a poly(4-methyl-1-pentene) hollow fiber gradient pore membrane, wherein the gradient pores in the membrane are composed of a dense skin layer and the pore diameter gradually decreases from the center of the membrane to the surface of the membrane.
  • the transparent porous support layer is composed; the thickness of the dense skin layer is 0.05-5 ⁇ m, and the average pore size is less than 0.02 ⁇ m; the thickness of the porous support layer is 0.05-0.2 mm, and the average pore size is 0.02-5 ⁇ m.
  • the present application also provides that the poly(4-methyl-1-pentene) hollow fiber gradient pore membrane prepared by the above method is applied to the process of extracorporeal membrane lung oxygenation.
  • the present application adopts the integrated process of TIPS method and NIPS method to prepare poly(4-methyl-1-pentene) hollow fiber membrane with gradient pore structure. Compared with the prior art, it has the following advantages:
  • a composite structure composed of a dense skin layer and a transparent sponge-like porous support layer whose pore size gradually decreases from the center of the membrane to the surface of the membrane is formed to obtain both high porosity.
  • the gradient pore structure of the thin and dense skin layer enhances the gas permeability, mechanical strength and blood infiltration resistance of poly(4-methyl-1-pentene) hollow fiber membranes;
  • Fig. 1 is the microporous structure of the main body of the support layer in the section of the poly(4-methyl-1-pentene) hollow fiber membrane in Example 1;
  • Fig. 2 is the dense surface of poly(4-methyl-1-pentene) hollow fiber membrane in Example 1;
  • FIG. 3 is the overall cross-sectional gradient pore structure of the poly(4-methyl-1-pentene) hollow fiber membrane in Example 1.
  • step 1) of the method of the present application poly(4-methyl-1-pentene) with a mass fraction of 20%-40% and a diluent with a mass fraction of 60%-80% are uniformly mixed as a casting liquid.
  • the mass fraction of poly(4-methyl-1-pentene) is preferably 25%-32%, and the mass fraction of the diluent is preferably 68%-75%.
  • the diluent is preferably composed of a high-temperature solvent of poly(4-methyl-1-pentene) and a high-temperature non-solvent, wherein the high-temperature solvent refers to a high temperature solvent that can interact with poly(4-methyl) in the temperature range of 200°C to 270°C. -1-pentene) to form a homogeneous solution and the homogeneous solution is phase-separated in the temperature range of 0-60 °C.
  • high temperature non-solvent means that it cannot form a homogeneous solution with poly(4-methyl-1-pentene) in the temperature range of 200°C-270°C and
  • a water-soluble solvent with a boiling point greater than 200° C. is preferably non-toxic or low-toxic, and its mass fraction is preferably 1%-60%, more preferably 1%-40%, further preferably 3%-20%.
  • the mass fractions are based on the diluent as a whole.
  • a homogeneous solution refers to a homogeneous solution, that is, there is no other insoluble phase in the solution, and its appearance is that the solution is clear and transparent.
  • the inability to form a homogeneous solution means that the components cannot be completely dissolved, there are at least two phases, and the appearance is layered or cloudy.
  • the poly(4-methyl-1-pentene) high temperature solvent is preferably tetradecanoic acid, hexadecanoic acid, oleic acid, octadecanoic acid, eicosic acid, methyl octadecanoate, glycerol triacetate, hexadecanoic acid Dibutyl acid, dioctyl adipate, triethyl citrate, tributyl phosphate, benzyl alcohol, 1-dodecanol, 1-tetradecanol, 1-hexadecanol, 1-octadecanol, One or one of 1-eicosanol, 1-docosanol, 1-tetracosanol, 1-docosanol, 1-dioctacosanol, 1-triacontol or its isomers more than one mixture.
  • the poly(4-methyl-1-pentene) high temperature non-solvent is preferably 1,2-propylene glycol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, One or more mixtures of polyethylene glycol and glycerol with a molecular weight of 200-1000.
  • step 2) of the method of the present application at 200-270° C., the casting liquid described in step 1) is extruded into hollow fibers through an extruder at a speed of 20-100 m/min.
  • the extruder can be, for example, a twin screw extruder.
  • the extrusion temperature may be further preferably 230-265°C.
  • the extrusion speed may be further preferably 60-80 m/min.
  • the extrusion temperature needs to ensure that the polymer and the diluent system can be completely melted and mixed evenly.
  • the extrusion speed affects the thickness and outer diameter of the film after forming. The faster the extrusion speed, the smaller the outer diameter of the film and the thinner the thickness.
  • step 3) of the method of the present application the hollow fiber in step 2) is passed through an air section at room temperature for 1-300 ms, and then enters a cooling bath with a temperature of 0-50° C., and then solidifies to form a film.
  • the air section temperature is preferably 15-25°C, eg 25°C.
  • the dwell time in the air section is further preferably 5-60 ms. The temperature and time of the air section affect the formation of the dense skin layer on the surface. The longer the air section, the thicker the dense skin layer.
  • the cooling bath is preferably water, or a mixture of ethanol or a high temperature non-solvent of poly(4-methyl-1-pentene) and water.
  • the cooling bath temperature is further preferably 0 to 30°C.
  • the residence time in the cooling bath is usually 0.1-10 s, preferably 1-5 s.
  • the cooling temperature and time affect the thermally induced phase separation process. The lower the temperature, the faster the cooling rate, the faster the phase separation rate, the lower the crystallinity of the polymer, and then the mechanical strength decreases, but the toughness increases. Adjusting the composition of the cooling bath can control the non-solvent-induced phase separation process, which in turn affects the distribution of the gradient pore structure in the membrane. The more intense the process, the thicker the membrane dense skin.
  • step 4) of the method of the present application the film in step 3) is immersed in the extractant to remove the diluent in the film.
  • the extractant is preferably selected from at least one of water, methanol, ethanol, propanol, n-butanol and isobutanol.
  • step 5) of the method of the present application the membrane from which the diluent is removed in step 4) is dried in an oven to obtain the poly(4-methyl-1-pentene) hollow fiber gradient pore membrane.
  • the drying temperature may be 30-70°C, more preferably 50-70°C.
  • the thickness of the dense skin layer of the poly(4-methyl-1-pentene) hollow fiber gradient pore membrane of the present application is 0.05-5 ⁇ m, preferably 0.1-0.5 ⁇ m, and the average pore size is less than 0.02 ⁇ m, preferably 0.0005-0.005 ⁇ m; porous;
  • the thickness of the support layer is 0.05-0.2 mm, preferably 0.05-0.15 mm, and the average pore diameter is 0.02-5 ⁇ m, preferably 0.05-1 ⁇ m.
  • the preparation method of poly(4-methyl-1-pentene) hollow fiber gradient pore membrane is carried out by the following steps:
  • casting liquid 25% of poly(4-methyl-1-pentene), 70% of dibutyl adipate and 5% of propylene glycol are mixed uniformly as casting liquid;
  • Extrusion molding extruding the casting liquid described in step 1) into a hollow fiber shape at a speed of 80 m/min through a twin-screw extruder at 250°C;
  • step 3 Phase separation and solidification: the hollow fiber described in step 2) is cooled in a water bath with a temperature of 30°C for 2s after passing through an air section of 25°C for 10ms, and the poly(4-methyl-1-pentene)/diluted The thermal-induced phase separation and the non-solvent-induced phase separation process occur simultaneously in the agent system, and then solidify to form a film;
  • step 3 Extraction and removal of diluent: the film in step 3) is immersed in ethanol to remove the diluent in the film;
  • Example 1 The mass fraction of poly(4-methyl-1-pentene) in the casting solution prepared in step 1) of Example 1 was increased to 30%, and the mass fraction of dibutyl adipate and propylene glycol were decreased to 65.3% and 4.7%, respectively , other conditions remain unchanged.
  • Example 2 The temperature of the twin-screw extruder in step 2) of Example 1 was lowered to 230° C., and other conditions remained unchanged.
  • step 2) of Example 1 the extrusion speed of the filaments was reduced to 40 m/min, and other conditions remained unchanged.
  • Step 3) in Example 1) the air passage time during the phase separation and curing was increased to 50ms, and other conditions remained unchanged.
  • Example 1 The temperature of the water bath in step 3) of Example 1 was reduced to 0° C. during phase separation and curing, and other conditions remained unchanged.
  • Example 1 The cooling bath in step 3) of Example 1 was changed to an aqueous ethanol solution with a mass fraction of 50%, and the temperature of the cooling bath was set to 0°C, and other conditions remained unchanged.
  • step 5 During drying in step 5) of Example 1, the temperature was increased to 70°C, and other conditions remained unchanged.
  • step 1) in the preparation of the casting solution dibutyl adipate was replaced with behenicol with a mass fraction of 68%, and propylene glycol was replaced with triethylene glycol with a mass fraction of 7%, and other conditions remained unchanged.
  • step 1) of Example 1 in the preparation of the casting solution, dibutyl adipate was replaced with palmitic acid with a mass fraction of 72%, and propylene glycol was replaced with polyethylene glycol 600 with a mass fraction of 3%, and other conditions remained unchanged.
  • the method of the comparative example is basically the same as that of Example 1, the difference is that: in step 1) preparing the casting solution, the formula is changed to poly(4-methyl-1-pentene) with a mass fraction of 25% and a mass fraction of 75%. % dioctyl phthalate was mixed uniformly as the casting liquid, and other conditions remained unchanged.
  • FIG. 1 shows the microporous structure of the main body of the support layer in the cross section of the poly(4-methyl-1-pentene) hollow fiber membrane in Example 1.
  • FIG. 2 shows the dense surface of the poly(4-methyl-1-pentene) hollow fiber membrane in Example 1.
  • FIG. Fig. 3 shows the overall cross-section of the poly(4-methyl-1-pentene) hollow fiber membrane in Example 1. It can be clearly seen from Fig. 3 that the membrane has a gradient pore structure, and the dense skin layer and porous There are clear boundaries between the support layers.
  • the structural properties and properties of the hollow fiber membranes prepared in the above examples and comparative examples were characterized, and the results obtained are shown in Table 1. Among them, the microstructure of the film, the thickness of the dense skin layer and the thickness of the support layer were directly observed and measured by scanning electron microscope multiple times, and the thickness of the dense skin layer and the thickness of the support layer were the arithmetic mean of the thickness values measured by multiple sampling, respectively. The number of samples in this experiment is 5.
  • the average pore size of the membrane support layer was obtained by analyzing the pore size of the membrane support layer with a pore size analyzer (Bestode BSD-PBL) at 25°C.
  • the pore size of the dense skin of the membrane was analyzed by Positron Annihilation Lifetime Spectrometer (PALS EG&G).
  • the 22 Na radioactive source was used as the positron source, and the BaF 2 scintillator detector was used to detect the ⁇ -rays released by the positron annihilation.
  • the membrane is fixed in the positron source and detector, and the free volume radius of the dense skin is calculated by measuring the annihilation lifetime of positrons in the dense skin, which is the average pore size of the dense skin.
  • the tensile strength at break and elongation at break of the film were measured by using a material universal testing machine (SHIMADZU AGS-J) to stretch the film at a speed of 250 mm/min at about 25°C until it broke.
  • a material universal testing machine SHIMADZU AGS-J
  • Oxygen and carbon dioxide flux (F) measurement of membrane encapsulate the prepared membrane in a membrane module, connect the oxygen or carbon dioxide gas source to the inner side of the membrane and apply 0.5bar pressure (P) at about 25°C, and connect to the outer side of the membrane
  • the gas flow meter detects the gas volume (V) permeated per unit time (t), and calculates the gas permeability by the following formula according to the effective area (A) of the membrane:
  • Membrane plasma leakage time determination This test is carried out with reference to the method proposed in US Patent US6497752-B1, the prepared membrane is packaged in a membrane module and filled with phosphate buffered saline (PBS) solution in the shell side of the module and kept at constant temperature 37 °C, in the tube side of the membrane module, nitrogen is introduced for purging, and the outlet of the purging gas is connected to a drying tube equipped with anhydrous copper sulfate. The time elapsed from the beginning of discoloration of anhydrous copper sulfate in the drying tube was defined as the plasma leakage time.
  • PBS phosphate buffered saline
  • the poly(4-methyl-1-pentene) hollow fiber membrane prepared by the method of the present application has better mechanical properties and plasma permeability resistance.
  • the membrane structure and performance can be regulated by adjusting the film-forming formula and film-making process.

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Abstract

本发明提供了利用热致相分离与非溶剂致相分离法耦合以制备出具有梯度孔结构的聚(4-甲基-1-戊烯)中空纤维膜的方法，包括：首先将聚(4-甲基-1-戊烯)与稀释剂高温混匀，通过挤出一次成型，经空气段后进入冷却浴冷却发生热致相分离与非溶剂相分离，最后萃取出稀释剂得到中空纤维膜。本发明方法制备的中空纤维膜具有提高的安全性，并且易于调控聚(4-甲基-1-戊烯)-稀释剂体系中热致相分离与非溶剂致相分离过程，从而获得具有更好力学强度、气体渗透性及耐血浆浸润性的聚(4-甲基-1-戊烯)膜。本发明还提供聚(4-甲基-1-戊烯)中空纤维膜及其用于人工膜肺领域的用途。

Description

一种具有梯度孔结构的聚(4-甲基-1-戊烯)中空纤维膜、制备方法及应用
本申请要求于2020年10月21日提交中国专利局、申请号为202011130843.5、申请名称为“一种具有梯度孔结构的聚(4-甲基-1戊烯)中空纤维膜及其制备方法”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本申请涉及一种具有梯度孔结构的聚(4-甲基-1-戊烯)中空纤维膜、制备方法及应用，具体涉及采用热致相分离法与非溶剂相分离集成工艺制备具有梯度孔结构的聚(4-甲基-1-戊烯)中空纤维膜的方法及通过该方法制备的中空纤维膜。
背景技术
体外膜肺氧合(Extracorporeal Membrane Oxygenation，ECMO)系统，具有替代人体肺脏调节血液内氧气与二氧化碳含量的功能，现已成为治疗急性呼吸疾病、等待肺移植阶段及心血管手术等过程中的重要医疗设备。ECMO由膜式氧合器、血泵、气体混合器及各种管路及监视器构成。膜式氧合器是气血交换的关键场所，是ECMO系统的核心部件，其在工作中要求膜需具有良好的气体渗透性能及抗血液浸润性。
目前ECMO用膜主要是聚烯烃中空纤维膜，包括聚丙烯(Polypropene,PP)与聚(4-甲基-1-戊烯)(Polymethylpentene，PMP)，其主要加工方法为热致相分离(Thermally induced phase separation,TIPS)法。TIPS法首先由Castro在美国专利US4247498(1981)中提出，可通过调节聚合物浓度、稀释剂体系及配比以实现高强度、高孔隙率的海绵体微孔结构，现已成为聚合物微孔膜的重要制备手段。专利CN1301149C、CN1121896C、CN1136035C、CN1141169C、CN110538582A及CN110548411A中详细地描述了采用聚烯烃高温良溶剂与非溶剂作为稀释剂，通过TIPS法制备具有非对称结构的聚烯烃中空纤维膜的 方法。但由于聚(4-甲基-1-戊烯)的熔融温度与结晶温度相近，导致聚(4-甲基-1-戊烯)在TIPS过程中的相分离与结晶行为调控难度大，以至于很难实现高性能聚(4-甲基-1-戊烯)中空纤维膜的连续化稳定生产，目前仅有3M一家能够提供满足ECMO用的聚(4-甲基-1-戊烯)中空纤维膜产品。此外，在上述部分专利描述中，涉及多种对环境或人体有毒性的有机溶剂，这将极大影响聚(4-甲基-1-戊烯)中空纤维膜的安全性。
发明内容
针对以上问题，本申请提供一种聚(4-甲基-1-戊烯)中空纤维梯度孔膜的制备方法，所述方法可避免使用有毒的有机溶剂并可获得具有更好性能的聚(4-甲基-1-戊烯)中空纤维梯度孔膜。
本申请的聚(4-甲基-1-戊烯)中空纤维梯度孔膜的制备方法包括如下步骤：
1)制备铸膜液：将质量分数为20％-40％的聚(4-甲基-1-戊烯)、质量分数为60％-80％的稀释剂混合均匀作为铸膜液；
2)挤出成型：在200-270℃下，将步骤1)所述铸膜液通过挤出机以20-100m/min的速度挤出成中空纤维；
3)相分离与固化：将步骤2)所述中空纤维经过室温空气段1-300ms，随后进入温度为0-50℃的冷却浴中，固化成膜；
4)萃取除稀释剂：将步骤3)中的膜浸入萃取剂中，脱除膜中的稀释剂；
5)将步骤4)中脱除稀释剂后的膜置于烘箱中烘干获得所述的聚(4-甲基-1-戊烯)中空纤维梯度孔膜。
上述方法首先将聚(4-甲基-1-戊烯)与稀释剂高温混匀，通过挤出一次成型，经空气段后冷却浴冷却发生热致相分离与非溶剂相分离，最后萃取出稀释剂得到中空纤维膜。通过选用水溶性的稀释剂，在冷却固化过程中诱使聚(4-甲基-1-戊烯)中空纤维表层与主体层分别发生NIPS(非溶剂致相分离，Nonsolvent induced phase separation)与TIPS过程，继而形成梯度孔结构。
在本申请的方法中，通过调节稀释剂中聚(4-甲基-1-戊烯)高温溶剂与高温非溶剂的种类与配比、挤出温度、空气段时间、冷却浴温度及冷却时间等条件，能够进一步实现对固化过程中TIPS与NIPS行为的调控，从而实现对聚(4-甲基-1-戊烯)中空纤维膜梯度孔结构的调控与优化。
本申请还提供可通过上述方法制得的聚(4-甲基-1-戊烯)中空纤维梯度孔膜。
本申请还提供一种聚(4-甲基-1-戊烯)中空纤维梯度孔膜，其中，所述膜中的梯度孔由致密皮层和孔径在由膜中心到膜表面逐渐变小的通透多孔支撑层组成；致密皮层厚度为0.05-5μm，平均孔径小于0.02μm；多孔支撑层厚度为0.05-0.2mm，平均孔径为0.02-5μm。
本申请还提供上述方法制得的聚(4-甲基-1-戊烯)中空纤维梯度孔膜应用于体外膜肺氧合过程。
本申请采用TIPS法与NIPS法集成工艺制备具有梯度孔结构的聚(4-甲基-1-戊烯)中空纤维膜，与现有技术相比，有以下优势：
1.通过选用聚(4-甲基-1-戊烯)高温溶剂与非溶剂的混合体系，扩大了TIPS法制备聚(4-甲基-1-戊烯)的稀释剂筛选范围；
2.通过选用水溶性的非溶剂，诱使聚(4-甲基-1-戊烯)在固化成膜过程中同时发生TIPS与NIPS过程，增加膜结构与性能的可控因素，改善成膜过程中的工艺稳定性及可控性；
3.通过表层NIPS成膜与主体TIPS成膜相结合的方式，形成由致密皮层和孔径由膜中心到膜表面逐渐变小的通透海绵状多孔支撑层构成的复合结构，获得兼具高孔隙率与薄致密皮层的梯度孔结构，增强聚(4-甲基-1-戊烯)中空纤维膜的气体渗透率、力学强度与耐血液浸润性；
4.通过选用无毒或低毒性的稀释剂体系，提高了通过本方法制备的聚(4-甲基-1-戊烯)中空纤维膜产品的安全性。
附图说明
图1为实施例1中聚(4-甲基-1-戊烯)中空纤维膜的断面中支撑层主体的微孔结构；
图2为实施例1中聚(4-甲基-1-戊烯)中空纤维膜的致密表面；
图3为实施例1中聚(4-甲基-1-戊烯)中空纤维膜的整体断面梯度孔结构。
具体实施方式
本申请方法的步骤1)中，将质量分数为20％-40％的聚(4-甲基-1-戊烯)、 质量分数为60％-80％的稀释剂混合均匀作为铸膜液。通过调节聚合物与稀释剂的比例，可调节所制备膜的结构、实现对膜主体孔隙率的调控。聚(4-甲基-1-戊烯)的质量分数优选为25％-32％，稀释剂的质量分数优选为68％-75％。
所述的稀释剂优选由聚(4-甲基-1-戊烯)的高温溶剂与高温非溶剂组成，其中高温溶剂指在200℃-270℃的温度范围内可与聚(4-甲基-1-戊烯)形成均匀溶液且该均匀溶液在0-60℃的温度范围内发生分相的沸点大于200℃的溶剂，优选其无毒或低毒性，优选其质量分数为40％-99％，更优选60％-99％，进一步优选80％-97％；高温非溶剂指在200℃-270℃的温度范围内与聚(4-甲基-1-戊烯)不能形成均匀溶液且沸点大于200℃的具有水溶性的溶剂，优选其无毒或低毒性，优选其质量分数为1％-60％，更优选1％-40％，进一步优选3％-20％。所述质量分数基于稀释剂整体计。通过调节高温溶剂与非溶剂的组成，可影响到相分离成膜过程中铸膜液体系成核、聚结、分相与结晶过程，继而实现对膜孔径及形貌的调控。
本申请中，均匀溶液指的是均相溶液，即溶液中不存在不溶的其它相，其外观表现为溶液澄清透明。不能形成均匀溶液指的是各组分不能完全相溶，存在至少两相，其外观表现为分层或者浑浊。
所述聚(4-甲基-1-戊烯)高温溶剂优选为十四酸、十六酸、油酸、十八酸、二十酸、十八酸甲酯、三乙酸甘油酯、己二酸二丁酯、己二酸二辛酯、柠檬酸三乙酯、磷酸三丁酯、苯甲醇、1-十二醇、1-十四醇、1-十六醇、1-十八醇、1-二十醇、1-二十二醇、1-二十四醇、1-二十六醇、1-二十八醇、1-三十醇或其异构体中的一种或一种以上的混合物。
所述的聚(4-甲基-1-戊烯)高温非溶剂优选1,2-丙二醇、乙二醇、一缩二乙二醇、二缩三乙二醇、三缩四乙二醇、分子量为200-1000的聚乙二醇、丙三醇中的一种或一种以上的混合物。
本申请方法的步骤2)中，在200-270℃下，将步骤1)所述铸膜液通过挤出机以20-100m/min的速度挤出成中空纤维。所述挤出机例如可为双螺杆挤出机。挤出温度可进一步优选为230-265℃。挤出速度可进一步优选为60-80m/min。挤出温度需要保证聚合物与稀释剂体系能够完全熔融并混合均匀，挤出速度影响膜成型后厚度与外径，挤出速度越快，膜外径越小、厚度越薄。
本申请方法的步骤3)中，将步骤2)所述中空纤维经过室温空气段1-300ms，随后进入温度为0-50℃的冷却浴中，继而固化成膜。空气段温度优选15-25℃，例如25℃。在空气段停留的时间进一步优选为5-60ms。空气段的温度与时间影响其表面致密皮层的形成，空气段越长，致密皮层越厚。
冷却浴优选为水，或者乙醇或聚(4-甲基-1-戊烯)的高温非溶剂与水的混合物。冷却浴温度进一步优选为0-30℃。在冷却浴中停留的时间通常为0.1-10s，优选为1-5s。冷却温度与时间影响热致相分离过程，温度越低，冷却速度越快，相分离速度越快，聚合物结晶度越低，继而力学强度下降，但韧性提高。调节冷却浴组成可调控非溶剂致相分离过程，继而影响到膜中梯度孔结构的分布，其中聚(4-甲基-1-戊烯)高温非溶剂的比例越高，非溶剂致相分离过程越剧烈，膜致密皮层越厚。
本申请方法的步骤4)中，将步骤3)中的膜浸入萃取剂中，脱除膜中的稀释剂。所述的萃取剂优选选自水、甲醇、乙醇、丙醇、正丁醇和异丁醇中的至少一种。
本申请方法的步骤5)中，将步骤4)中脱除稀释剂后的膜置于烘箱中烘干获得所述的聚(4-甲基-1-戊烯)中空纤维梯度孔膜。烘干温度可为30-70℃，进一步优选为50-70℃。
本申请的聚(4-甲基-1-戊烯)中空纤维梯度孔膜的致密皮层厚度为0.05-5μm，优选为0.1-0.5μm，平均孔径小于0.02μm，优选为0.0005-0.005μm；多孔支撑层厚度为0.05-0.2mm，优选为0.05-0.15mm，平均孔径为0.02-5μm，优选为0.05-1μm。
下面结合具体实施例对本申请作详细的说明，但本申请并不限于以下实施例所作的描述。
实施例1
聚(4-甲基-1-戊烯)中空纤维梯度孔膜的制备方法通过如下步骤进行：
1)制备铸膜液：将质量分数为25％的聚(4-甲基-1-戊烯)、质量分数为70％的己二酸二丁酯及质量分数为5％的丙二醇混合均匀作为铸膜液；
2)挤出成型：将步骤1)所述铸膜液通过250℃的双螺杆挤出机以80m/min的速度挤出成中空纤维状；
3)相分离与固化：将步骤2)所述中空纤维在经过10ms的25℃的空气段后进入温度为30℃的水浴中冷却2s，聚(4-甲基-1-戊烯)/稀释剂体系同时发生热致相分离与非溶剂致相分离过程，继而固化成膜；
4)萃取除稀释剂：将步骤3)中的膜浸入乙醇中，脱除膜中的稀释剂；
5)烘干：将步骤4)中脱除稀释剂后的膜置于50℃烘箱中烘干获得聚(4-甲基-1-戊烯)中空纤维梯度孔膜。
实施例2
将实施例1步骤1)制备铸膜液中聚(4-甲基-1-戊烯)质量分数提高至30％，己二酸二丁酯与丙二醇的质量分数分别降低至65.3％与4.7％，其他条件不变。
实施例3
将实施例1步骤1)制备铸膜液中己二酸二丁酯替换为磷酸三丁酯，质量分数降低至45％，丙二醇质量分数增加至30％，其他条件不变。
实施例4
将实施例1步骤2)挤出成型中双螺杆挤出机温度降低至230℃，其他条件不变。
实施例5
将实施例1步骤2)挤出成型中膜丝挤出速度降低至40m/min，其他条件不变。
实施例6
将实施例1步骤3)相分离与固化中经过空气段时间增加至50ms，其他条件不变。
实施例7
将实施例1步骤3)相分离与固化中水浴温度降低至0℃，其他条件不变。
实施例8
将实施例1步骤3)相分离与固化中冷却浴改变为质量分数50％的乙醇水溶液，冷却浴温度设置为0℃，其他条件不变。
实施例9
将实施例1步骤5)烘干中，温度提高至70℃，其他条件不变。
实施例10
将实施例1步骤3)相分离与固化中冷却浴冷却时间增加至6s，其他条件不变。
实施例11
将实施例1步骤1)制备铸膜液中己二酸二丁酯替换为质量分数68％的二十二醇，丙二醇更换为质量分数7％的二缩三乙二醇，其他条件不变。
实施例12
将实施例1步骤1)制备铸膜液中己二酸二丁酯替换为质量分数72％的棕榈酸，丙二醇更换为质量分数3％的聚乙二醇600，其他条件不变。
对比例1
对比例与实施例1的方法基本相同，区别在于：在步骤1)制备铸膜液中将配方更改为质量分数为25％的聚(4-甲基-1-戊烯)与质量分数为75％的邻苯二甲酸二辛酯混合均匀作为铸膜液，其他条件不变。
图1示出了实施例1中聚(4-甲基-1-戊烯)中空纤维膜的断面中支撑层主体的微孔结构。图2示出了实施例1中聚(4-甲基-1-戊烯)中空纤维膜的致密表面。图3示出了实施例1中聚(4-甲基-1-戊烯)中空纤维膜的整体断面，由图3可以清楚地看出所述膜具有梯度孔结构，并且在致密皮层和多孔支撑层之间有清晰的边界。
效果评价
对上述各实施例和对比例所制备的中空纤维膜进行结构性质及性能的表征，所得结果见表1。其中膜的微观结构、致密皮层厚度与支撑层的厚度利用扫描电子显微镜多次取样直接观察测得，并且致密皮层厚度与支撑层的厚度分别是通过多次取样测得厚度值的算术平均值，本文的实验中取样次数为5。
膜支撑层平均孔径是在25℃，通过孔径分析仪(贝士德BSD-PBL)对膜支撑层孔径进行分析而获得。
膜致密皮层孔径通过正电子湮灭寿命谱仪(PALS EG&G)进行了分析，以 22Na放射源作为正电子源，以BaF 2闪烁体探测器探测正电子湮没释放的γ射线。将膜固定在正电子源与探测器中，通过测定正电子在致密皮层中的湮灭寿命计算出致密皮层的自由体积半径，即为致密皮层的平均孔径大小。
膜的断裂拉伸强度及断裂伸长率利用材料万能试验机(SHIMADZU AGS-J)在25℃左右以250mm/min的速度均速拉伸膜直至断裂测得。
膜的氧气及二氧化碳通量(F)测量：将制备的膜封装在膜组件中，在25℃左右，将氧气或二氧化碳气源与膜内侧相连并施加0.5bar压力(P)，在膜外侧连接气体流量计，检测单位时间(t)透过的气体体积(V)，根据膜的有效面积(A)，通过如下公式计算气体渗透率：
Figure PCTCN2021083475-appb-000001
膜的血浆渗漏时间测定：该测试参考美国专利US6497752-B1中建议的方法进行，将制备的膜封装在膜组件中并在组件的壳程中灌满磷酸缓冲盐(PBS)溶液并恒温37℃，在膜组件的管程中通入氮气进行吹扫，吹扫气出口接入装有无水硫酸铜的干燥管。将干燥管中无水硫酸铜开始变色经过的时间定义为血浆渗漏时间。
表1 各示例所得聚(4-甲基-1-戊烯)中空纤维梯度孔膜的结构、性质及性能表征结果
Figure PCTCN2021083475-appb-000002
Figure PCTCN2021083475-appb-000003
通过表1中实施例1-12与对比例1的数据对比，可发现采用本申请方法制备的聚(4-甲基-1-戊烯)中空纤维膜拥有更优的力学性能与耐血浆渗漏性；且可通过调节成膜配方与制膜工艺实现对膜结构与性能的调控。

Claims (19)

  1. 一种聚(4-甲基-1-戊烯)中空纤维梯度孔膜的制备方法，其中，包括如下步骤：
    1)制备铸膜液：将质量分数为20％-40％的聚(4-甲基-1-戊烯)、质量分数为60％-80％的稀释剂混合均匀作为铸膜液；
    2)挤出成型：在200-270℃下，将步骤1)所述铸膜液通过挤出机以20-100m/min的速度挤出成中空纤维；
    3)相分离与固化：将步骤2)所述中空纤维经过室温空气段1-300ms，随后进入温度为0-50℃的冷却浴中，固化成膜；
    4)萃取除稀释剂：将步骤3)中的膜浸入萃取剂中，脱除膜中的稀释剂；
    5)将步骤4)中脱除稀释剂后的膜置于烘箱中烘干获得所述的聚(4-甲基-1-戊烯)中空纤维梯度孔膜。
  2. 根据权利要求1所述的制备方法，其中，所述的稀释剂由聚(4-甲基-1-戊烯)的高温溶剂与高温非溶剂组成，其中高温溶剂质量分数为40％-99％，高温非溶剂质量分数为1％-60％，高温溶剂为在200℃-270℃的温度范围内可与聚(4-甲基-1-戊烯)形成均匀溶液且该均匀溶液在0-60℃的温度范围内发生分相的沸点大于200℃的溶剂，高温非溶剂为在200℃-270℃的温度范围内与聚(4-甲基-1-戊烯)不能形成均匀溶液且沸点大于200℃的具有水溶性的溶剂，所述质量分数基于稀释剂整体计。
  3. 根据权利要求2所述的制备方法，其中，所述高温溶剂为十四酸、十六酸、油酸、十八酸、二十酸、十八酸甲酯、三乙酸甘油酯、己二酸二丁酯、己二酸二辛酯、柠檬酸三乙酯、磷酸三丁酯、苯甲醇、1-十二醇、1-十四醇、1-十六醇、1-十八醇、1-二十醇、1-二十二醇、1-二十四醇、1-二十六醇、1-二十八醇、1-三十醇或其异构体中的一种或一种以上的混合物。
  4. 根据权利要求2所述的制备方法，其中，所述高温非溶剂为1,2-丙二醇、乙二醇、一缩二乙二醇、二缩三乙二醇、三缩四乙二醇、聚乙二醇200、聚乙二醇400、聚乙二醇600、聚乙二醇800、聚乙二醇1000、丙三醇中的一种或一种以上的混合物。
  5. 根据权利要求1-4任一项所述的制备方法，其中，所述的冷却浴包括水。
  6. 根据权利要求5所述的制备方法，其中，所述冷却浴还包括聚(4-甲基-1-戊烯)的高温非溶剂或乙醇中的至少一种。
  7. 根据权利要求1-6任一项所述的制备方法，其中，所述的萃取剂选自水、甲醇、乙醇、丙醇、正丁醇和异丁醇中的至少一种。
  8. 根据权利要求1-7任一项所述的制备方法，其中，在所述铸膜液中，所述聚(4-甲基-1-戊烯)的质量分数为25％-32％，所述稀释剂的质量分数为68％-75％。
  9. 根据权利要求2所述的制备方法，其中，在所述稀释剂中，所述高温溶剂的质量分数为60％-99％，所述高温非溶剂的质量分数为1％-40％。
  10. 根据权利要求1-9任一项所述的制备方法，其中，所述中空纤维经过室温空气段的时间为5-60ms。
  11. 根据权利要求1-10任一项所述的制备方法，其中，所述中空纤维在冷却浴中的停留时间为0.1-10s。
  12. 根据权利要求1-11任一项所述的制备方法，其中，步骤5)中的烘干温度为30-70℃。
  13. 一种根据权利要求1-12任一项所述的方法所制备的聚(4-甲基-1-戊烯)中空纤维梯度孔膜。
  14. 根据权利要求13所述的中空纤维梯度孔膜，其中，所述膜中的梯度孔由致密皮层和孔径在由膜中心到膜表面的方向上逐渐变小的通透多孔支撑层组成；
    其中，所述致密皮层的厚度为0.05-5μm，所述多孔支撑层的厚度为0.05-0.2mm。
  15. 根据权利要求14所述的中空纤维梯度孔膜，其中，所述致密皮层的厚度为0.1-0.5μm，所述多孔支撑层的厚度为0.05-0.15mm。
  16. 根据权利要求14或15所述的中空纤维梯度孔膜，其中，所述致密皮层的平均孔径小于0.02μm，所述多孔支撑层的平均孔径为0.02-5μm。
  17. 根据权利要求14-16任一项所述的中空纤维梯度孔膜，其中，所述致密皮层的平均孔径为0.0005-0.005μm，所述多孔支撑层的平均孔径为0.05-1μm。
  18. 根据权利要求1-12任一项所述的方法所制备的聚(4-甲基-1-戊烯)中 空纤维梯度孔膜应用于体外膜肺氧合过程。
  19. 一种聚(4-甲基-1-戊烯)中空纤维梯度孔膜，其中，所述膜中的梯度孔由致密皮层和孔径在由膜中心到膜表面的方向上逐渐变小的通透多孔支撑层组成；致密皮层厚度为0.05-5μm，平均孔径小于0.02μm；多孔支撑层厚度为0.05-0.2mm，平均孔径为0.02-5μm。
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