A hollow fiber membrane and its preparation method

Abstract

The present invention relates to the field of membrane technology, and specifically provides a hollow fiber membrane and a preparation method thereof. The method of the present invention comprises: (1) co-extruding a spinning solution and a core liquid, spinning, curing and forming, to form a primary membrane; (2) washing and drying the primary membrane to obtain a hollow fiber membrane; the mass ratio of the spinning solution to the core liquid is (0.2-0.8):1; the spinning solution is composed of a polymer, alginate, an additive, an organic solvent and water; the core liquid is composed of an organic solvent, water and a ferrous salt, and the hollow fiber membrane is used for blood concentration. The prepared hollow fiber membrane is used for blood concentration. Compared with the prior art, the hollow fiber membrane of the present invention can not only improve hypoxemia after extracorporeal circulation heart surgery, but also has good anticoagulant properties.

Description

Technical Field

[0001] The present invention relates to the field of membrane technology, and more particularly to a hollow fiber membrane and a preparation method thereof. Background Art

[0002] Hemoconcentration is a treatment method that mainly treats patients through extracorporeal circulation. During extracorporeal circulation surgery, patients will have varying degrees of hemodilution (usually diluted with normal saline). Based on clinical needs, hollow fiber membranes are generally used to concentrate the blood at the end of the surgery to increase the patient's hematocrit. The main purpose of hemoconcentration is to remove low-molecular substances (urea, electrolytes, creatinine, metal ions, water, oxygen free radicals, inflammatory factors, etc.) dissolved in the plasma, or to increase the concentration of overly diluted blood, so as to reduce the patient's systemic inflammatory response, make the patient's postoperative hemodynamics more stable, and be more conducive to the recovery of important organs.

[0003] However, the hemoconcentration process can cause some complications, such as hypoxemia. This is because patients with valvular heart disease often have a long course of illness, recurrent heart failure, and poor cardiac function. Therefore, most preoperative patients have comorbidities such as hypertension, diabetes, and liver and kidney dysfunction, which lead to significant water retention and significant impairment of the functions of various vital organs. Reasonable hemodilution is routinely performed during extracorporeal circulation for hemoconcentration, but due to various factors, excessive dilution can occur, resulting in a decrease in hemoglobin concentration, a decrease in the blood's oxygen-carrying capacity, and hypoxemia. Although hemoconcentration can improve these conditions, the effect is not significant.

[0004] Chinese patent CN113069598B discloses a method for improving the anticoagulant properties of a hemodialysis device. This method bridges sodium alginate to the surface of the dialysis membrane filaments and uses sodium alginate to form a soluble chelate with calcium ions in the blood, thereby eliminating the coagulation effect of the calcium ions. This patent aims to improve the anticoagulant properties of the hemodialysis membrane.

[0005] Chinese patent CN104190271B discloses a polyethersulfone / alginate composite hollow fiber membrane and its preparation method. Specifically, the method fills the macropores of the polyethersulfone hollow fiber membrane with divalent alginate to form a sponge network structure. The high ion adsorption of the sponge network structure is used to adsorb anticoagulants, thereby avoiding in vitro coagulation during hemodialysis.

[0006] Currently, there are no papers or patents that specifically and in detail introduce and study the use of hollow fiber membranes for blood concentration to improve hypoxemia after blood concentration, especially for hypoxemia after extracorporeal circulation surgery. Summary of the Invention

[0007] In view of this, the object of the present invention is to provide a hollow fiber membrane and a preparation method thereof, wherein the hollow fiber membrane is applied to blood concentration, can not only improve hypoxemia occurring after extracorporeal circulation heart surgery, but also has good anticoagulant properties.

[0008] In order to achieve the above object, the present invention adopts the following technical solutions:

[0009] A method for preparing a hollow fiber membrane, comprising:

[0010] (1) The spinning solution and the core solution are co-extruded, and after spinning and solidification, a primary membrane is formed;

[0011] (2) washing and drying the primary membrane to obtain a hollow fiber membrane;

[0012] The mass ratio of the spinning solution to the core solution is (0.2-0.8):1;

[0013] The spinning solution consists of polymer, alginate, additives, organic solvent and water;

[0014] The core liquid consists of an organic solvent, water and ferrous salt;

[0015] The hollow fiber membrane is applied to blood concentration.

[0016] After the alginate in the spinning solution is mixed with the polymer, it can be evenly distributed in the polymer. During the co-extrusion process with the core liquid, the ferrous ions in the core liquid are exchanged with the inorganic ions in the spinning solution, and ferrous alginate is formed through chelation, forming a stable interpenetrating network structure that is evenly distributed on the inner surface and inside the pores of the hollow fiber membrane.

[0017] The method for preparing the hollow fiber membrane of the present invention preferably comprises: preparing the spinning solution according to a certain mass ratio of each component under nitrogen protection; and preparing the core solution according to a certain mass ratio of each component before co-extruding the spinning solution and the core solution.

[0018] In the present invention, the mass ratio of the spinning solution to the core solution is preferably (0.3-0.5):1;

[0019] The polymer is one or more of polysulfone, polyethersulfone, polyacrylonitrile, cellulose acetate, cellulose diacetate, polyimide, polymethyl methacrylate, and polyamide, preferably polysulfone or polyethersulfone;

[0020] The alginate is one or more of sodium alginate, zinc alginate, and magnesium alginate, preferably sodium alginate;

[0021] The ferrous salt is one or more of ferrous sulfate, ferrous nitrate, and ferrous chloride, preferably ferrous chloride;

[0022] The additive is one or more of polyvinyl pyrrolidone, polyethylene glycol, polypropylene glycol, polyvinyl alcohol, and polyethylene oxide, preferably polyvinyl pyrrolidone or polyethylene glycol;

[0023] The organic solvent is one or more of nitrogen-nitrogen dimethylacetamide, dimethyl sulfoxide, nitrogen-methyl pyrrolidone, tetrahydrofuran, and nitrogen-ethyl pyrrolidone, preferably nitrogen-nitrogen dimethylacetamide or dimethyl sulfoxide.

[0024] In the present invention, in the spinning solution, the mass ratio of polymer, alginate, additive, organic solvent and water is (1.0-2.5): (0.2-2.5): (0.2-1.0): (5.0-9.0): (0.2-2.0), preferably (1.0-2.5): (0.5-1.3): (0.5-0.8): (5.0-9.0): (0.5-1.0); in the core liquid, the mass ratio of organic solvent, water and ferrous salt is (2.0-9.0): (1.0-8.0): (0.5-5.0), preferably (6.0-8.0): (5.0-6.0): (0.5-3.0).

[0025] In one embodiment of the present invention, the mass ratio of polymer, alginate, additive, organic solvent and water in the spinning solution is 2.5:0.5:0.8:8.0:0.5; the mass ratio of organic solvent, water and ferrous salt in the core solution is 7.5:6.0:1.0;

[0026] In one embodiment of the present invention, the mass ratio of polymer, alginate, additive, organic solvent and water in the spinning solution is 1.0:0.5:0.5:5.0:0.6; the mass ratio of organic solvent, water and ferrous salt in the core solution is 6.0:5.5:0.5;

[0027] In one embodiment of the present invention, in the spinning solution, the mass ratio of polymer, alginate, additive, organic solvent and water is 1.6:1.3:0.8:9.0:0.6; in the core liquid, the mass ratio of organic solvent, water and ferrous salt is 7.0:5.5:2.5.

[0028] The method for preparing the spinning solution preferably includes: adding polymer, alginate, additives and water in an organic solvent in sequence under nitrogen protection, stirring at 30-100° C. for 6-24 hours, and preparing the spinning solution through sufficient mixing, dissolution, filtering and degassing, preferably with a mixing time of 20 hours.

[0029] The method for preparing the spinning solution comprises: mixing water and an organic solvent, adding ferrous salt thereto, and stirring at 40° C. to 80° C. for 5 to 24 hours to prepare a core solution, preferably mixing for 10 hours.

[0030] In the present invention, the spinning solution and the core solution are co-extruded through an annular spinneret;

[0031] During co-extrusion, the spinning solution enters the outer annular slit of the annular spinneret, and the core solution enters the inner hole of the annular spinneret.

[0032] The inner diameter of the annular spinneret is 160-320 μm, preferably 300-320 μm, and the outer diameter is 260-420 μm, preferably 180-200 μm. In one embodiment of the present invention, the inner diameter of the annular spinneret is 320 μm and the outer diameter is 200 μm. In one embodiment of the present invention, the inner diameter of the annular spinneret is 300 μm and the outer diameter is 180 μm.

[0033] In the present invention, the spinning speed is 1 to 25 m / min, preferably 20 m / min; the spinning pressure is 0.1 to 0.5 MPa, preferably 0.2 MPa.

[0034] In the present invention, the solidification molding is carried out in a coagulation bath, which is composed of 20% to 100% water and 0 to 80% organic solvent, and the temperature of the coagulation bath is 40 to 80°C; the organic solvent in the coagulation bath is one or more of nitrogen-nitrogen dimethylacetamide, dimethyl sulfoxide, nitrogen-methyl pyrrolidone, tetrahydrofuran, and nitrogen-ethyl pyrrolidone.

[0035] In the present invention, the drying temperature is 70-150°C.

[0036] In the present invention, the nascent membrane is washed with water before being dried; the washing is carried out at 50-120°C.

[0037] The present invention also provides the above-mentioned hollow fiber membrane, which is prepared by the above-mentioned method.

[0038] The hollow fiber membrane of the present invention has a porous asymmetric structure and is applied to blood concentration. Ferrous alginate and polymer form a stable interpenetrating network structure, which is evenly distributed on the inner surface and inside the pores of the hollow fiber membrane.

[0039] In the present invention, the polymer is preferably polysulfone or polyethersulfone.

[0040] In the present invention, the average sidewall pore diameter of the hollow fiber membrane is 7 to 15 nm.

[0041] In the present invention, the hollow fiber membrane is a cylindrical hollow structure with an inner diameter of 160 to 320 μm and an outer diameter of 260 to 420 μm.

[0042] The protein retention rate of the hollow fiber membrane of the present invention is greater than 99.99%.

[0043] The beneficial effects of the present invention are as follows:

[0044] 1. Hollow fiber membranes can effectively supplement ferrous ions in the blood during blood concentration, participate in the synthesis of hemoglobin in the blood, increase the oxygen-carrying capacity of the blood, effectively relieve patients' postoperative hypoxemia, and effectively improve organ function after extracorporeal circulation heart surgery.

[0045] 2. Due to the polarity of alginate, ferrous alginate is evenly distributed on the inner surface and inside the pores of the hollow fiber membrane, which can improve the hydrophilicity of the hollow fiber membrane, further enhance the biocompatibility of the hollow fiber membrane, reduce complement activation, and prevent the phenomenon of pulmonary capillary embolism caused by leukocytes during complement activation, thereby effectively improving arterial oxygen partial pressure.

[0046] 3. The improved hydrophilicity of the hollow fiber membrane can also reduce the adhesion of blood cells and platelets on the surface of the hollow fiber membrane, effectively improving the anti-coagulant property of the hollow fiber membrane. The ferrous alginate formed by cross-linking avoids the unevenness and instability of physical dipping or spraying on the surface or inside of the hollow fiber. Therefore, its effect is not limited by the use time and has a long-term stable effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 is a cross-sectional scanning electron micrograph of a hollow fiber membrane (100 μm);

[0048] Figure 2 is a cross-sectional SEM image of a hollow fiber membrane (20 μm);

[0049] Figure 3 This is a scanning electron microscope image of the inner surface of the hollow fiber membrane;

[0050] Figure 4 This is a scanning electron microscope image of the outer surface of the hollow fiber membrane;

[0051] Figure 5 This is a graph showing the test results of the oxygen partial pressure in the blood after hemoconcentration;

[0052] Figure 6 This is the anticoagulation test result of the hollow fiber membrane. DETAILED DESCRIPTION

[0053] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0054] In order to further illustrate the present invention, the following examples are provided for detailed description. The raw materials used in the following examples of the present invention are all commercially available commodities.

[0055] The hollow fiber membranes prepared in the examples and comparative examples were made into fiber bundles and encapsulated in a hemoconcentrator assembly to prepare a hemoconcentrator to facilitate subsequent performance testing (oxygen partial pressure test, anticoagulant test). The hemoconcentrator has three ports: a blood inlet, a blood outlet, and a filtrate port. The fiber bundle is 14 cm long and has an effective membrane area of ​​0.5 m 2 .

[0056] Example 1

[0057] Preparation of spinning solution: Under nitrogen protection, add 2.5 kg of polyethersulfone, 0.5 kg of magnesium alginate, 0.8 kg of polyvinylpyrrolidone and 0.5 kg of water to 8 kg of nitrogen-nitrogen dimethylacetamide, stir at 40±10°C for 20 hours, and prepare the spinning solution after sufficient mixing, dissolution, filtration and degassing.

[0058] Preparation of core liquid: add 12 kg of water to 15 kg of nitrogen-nitrogen dimethylacetamide and add 2 kg of ferrous nitrate to the solution, and stir at 50±10° C. for 10 hours to prepare the core liquid.

[0059] The spinning equipment was set at a spinning speed of 18 m / min and a spinning pressure of 0.2 MPa. The spinning solution and core solution were fed via a metering pump into a circular spinneret with an outer diameter of 320 μm and an inner diameter of 200 μm for co-extrusion. After an 80 cm dry spinning process, the spinneret was placed in a 40°C pure water coagulation bath to solidify and form a nascent membrane. The nascent membrane was then washed in a 50°C water bath and dried in a 70°C oven to produce a hollow fiber membrane for blood concentration.

[0060] Example 2

[0061] Preparation of spinning solution: Under nitrogen protection, add 1 kg of polysulfone, 0.5 kg of zinc alginate, 0.5 kg of polyvinylpyrrolidone and 0.6 kg of water to 5 kg of nitrogen-nitrogen dimethylacetamide, stir at 70±10°C for 20 hours, and prepare the spinning solution through sufficient mixing, dissolution, filtration and degassing.

[0062] Preparation of core liquid: add 11 kg of water and 1 kg of ferrous sulfate to 12 kg of nitrogen-nitrogen dimethylacetamide, and stir at 60±10° C. for 10 hours to prepare the core liquid.

[0063] The spinning equipment was set at a spinning speed of 25 m / min and a spinning pressure of 0.2 MPa. The spinning solution and core solution were fed via a metering pump into a circular spinneret with an outer diameter of 300 μm and an inner diameter of 180 μm for co-extrusion. After a 50 cm dry spinning process, the spinneret was placed in a coagulation bath consisting of 400 kg of dimethylacetamide and 100 kg of water at 60°C to solidify the resulting nascent membrane. The nascent membrane was then washed in a water bath at 80°C and dried in an oven at 120°C to produce a hollow fiber membrane for hemoconcentration.

[0064] Example 3

[0065] Preparation of spinning solution: Under nitrogen protection, 1.6 kg of polyethersulfone, 1.3 kg of sodium alginate, 0.8 kg of polyethylene glycol and 0.6 kg of water were added to 9 kg of dimethyl sulfoxide, and stirred at 90±10°C for 20 hours. The spinning solution was prepared by thorough mixing, dissolving, filtering and degassing.

[0066] Preparation of core liquid: add 11 kg of aqueous solution and 5 kg of ferrous chloride to 14 kg of dimethyl sulfoxide, and stir at 70±10° C. for 10 hours to prepare the core liquid.

[0067] The spinning equipment was set at a spinning speed of 20 m / min and a spinning pressure of 0.2 MPa. The spinning solution and core solution were fed via a metering pump into a circular spinneret with an outer diameter of 300 μm and an inner diameter of 180 μm for co-extrusion. After a 60 cm dry spinning process, the membrane was solidified in a coagulation bath consisting of 100 kg of dimethyl sulfoxide and 100 kg of water at 80°C to form a nascent membrane. The nascent membrane was then washed in a 120°C water bath and dried in a 150°C oven to produce a hollow fiber membrane for blood concentration.

[0068] Comparative Example 1

[0069] Preparation of spinning solution: Under nitrogen protection, add 1.5 kg of polyethersulfone and 0.5 kg of polyvinylpyrrolidone to 8 kg of nitrogen-nitrogen dimethylacetamide, stir at 75±5°C for 12 hours, and then prepare the spinning solution through sufficient mixing, dissolution, filtration and degassing.

[0070] Preparation of core liquid: add 20 kg of water to 20 kg of nitrogen-nitrogen dimethylacetamide, stir and mix at 50±5° C. for 10 hours to prepare the core liquid.

[0071] The spinning equipment was set at a spinning speed of 20 m / min and a spinning pressure of 0.2 MPa. The spinning solution and core solution were pumped into a circular spinneret with an outer diameter of 300 μm and an inner diameter of 180 μm via a metering pump for co-extrusion. After an 80 cm dry spinning process, the spinneret was placed in a coagulation bath consisting of 200 kg of dimethylacetamide and 100 kg of water at 50°C to solidify the nascent membrane. The nascent membrane was then washed in a 60°C water bath and dried in a 100°C oven to produce a hollow fiber membrane for blood concentration.

[0072] Comparative Example 2

[0073] Preparation of spinning solution: Under nitrogen protection, add 1.5 kg of polyethersulfone, 0.5 kg of sodium alginate, 0.8 kg of polyvinylpyrrolidone and 0.5 kg of water to 8 kg of nitrogen-nitrogen dimethylacetamide, stir at 80±5°C for 20 hours, and prepare the spinning solution after sufficient mixing, dissolution, filtration and degassing.

[0074] Preparation of core liquid: add 20 kg of water to 20 kg of nitrogen-nitrogen dimethylacetamide, stir and mix at 50±5° C. for 10 hours to prepare the core liquid.

[0075] The spinning equipment was set at a spinning speed of 20 m / min and a spinning pressure of 0.2 MPa. The spinning solution and core solution were pumped into a circular spinneret with an outer diameter of 280 μm and an inner diameter of 160 μm via a metering pump for co-extrusion. After a 50 cm dry spinning process, the spinneret was placed in a coagulation bath consisting of 150 kg of dimethylacetamide and 100 kg of water at 40°C to solidify the resulting nascent membrane. The nascent membrane was then washed in a water bath at 80°C and oven-dried at 110°C to produce a hollow fiber membrane for hemoconcentration.

[0076] Comparative Example 3

[0077] Preparation of spinning solution: Under nitrogen protection, 1.6 kg of polyethersulfone, 1.3 kg of sodium alginate, 0.8 kg of polyethylene glycol and 0.6 kg of water were added to 9 kg of dimethyl sulfoxide, and stirred at 90±10°C for 20 hours. The spinning solution was prepared by thorough mixing, dissolving, filtering and degassing.

[0078] Preparation of core liquid: Add 11 kg of aqueous solution and 5 kg of magnesium chloride to 14 kg of dimethyl sulfoxide, and stir at 70±10° C. for 10 hours to prepare the core liquid.

[0079] The spinning equipment was set at a spinning speed of 20 m / min and a spinning pressure of 0.2 MPa. The spinning solution and core solution were fed via a metering pump into a circular spinneret with an outer diameter of 300 μm and an inner diameter of 180 μm for co-extrusion. After a 60 cm dry spinning process, the membrane was solidified in a coagulation bath consisting of 100 kg of dimethyl sulfoxide and 100 kg of water at 80°C to form a nascent membrane. The nascent membrane was then washed in a 120°C water bath and dried in a 150°C oven to produce a hollow fiber membrane for blood concentration.

[0080] Test example

[0081] The hemoconcentrators assembled with the hollow fiber membranes prepared in the comparative examples and examples were subjected to the following relevant tests:

[0082] 1) Scanning electron microscope test

[0083] The cross section, inner surface and outer surface of the hollow fiber membrane were observed at different magnifications using Hitachi TM4000 to obtain the inner and outer diameters of the hollow fiber membrane and the pore sizes of the inner and outer sidewalls.

[0084] Specific test steps:

[0085] Attach the hollow fiber membrane to the sample stage with conductive adhesive and spray-coat it with gold. Start the scanning electron microscope, pump the vacuum to 0.01 MPa, and maintain it until the shooting button is permanently illuminated, then click the shooting button. Set the voltage value and adjust the brightness and contrast until a brighter image appears. Then, coarsely adjust the focus to display a clearer image. After finding the sample to be observed at low magnification and obtaining a clearer image, increase the magnification to a magnification greater than the desired shooting magnification, place the cursor on the focus fine-tuning, and slowly scroll the wheel until the image is clear. Then adjust the magnification to the desired shooting magnification, adjust the brightness and contrast, and click Photo to capture and save.

[0086] Figure 1 、 Figure 2 The cross-sectional scanning electron micrograph of the hollow fiber membrane shows that the inner diameter of the prepared hollow fiber membrane for blood concentration is about 200 μm and the outer diameter is about 280 μm. Figure 3 This is a scanning electron microscope image of the inner surface of the hollow fiber membrane. Figure 4 This is a scanning electron microscope image of the outer surface of the hollow fiber membrane. Figure 3 、 4 It can be seen that the pore size distribution of the side wall of the hollow fiber membrane is 7 to 15 nm.

[0087] 2) Oxygen partial pressure test

[0088] Measuring oxygen partial pressure (POP) can reveal the degree of hypoxia in the body and whether hypoxemia is present. If the POP in the blood is less than 80 mmHg, hypoxemia may be present. If it's between 60 and 80 mmHg, it's considered mild hypoxia; between 45 and 60 mmHg, it's considered moderate hypoxia; and if it's less than 45 mmHg, it's considered severe hypoxia.

[0089] Specific test steps:

[0090] Connect the tubing and hemoconcentrator, connect the hemoconcentrator blood inlet to the pump, start the pump, adjust the flow rate to 100 ml / min, and purge bubbles from the hemoconcentrator and tubing with a standard simulant solution. Run the pump for 15 minutes. Blood was drawn from several healthy albino guinea pigs of the same breed and size. The blood was diluted 1.2-fold with normal saline and then passed through the hemoconcentrator inlet into the hollow fiber membrane for hemoconcentration. The concentrated blood was then returned to the albino guinea pigs. Blood was drawn from mice 0, 8, 16, 24, and 48 hours after the blood was returned to the albino guinea pigs. The oxygen partial pressure in the blood was measured using a PO2 electrode (composed of a platinum cathode and a silver chloride anode). Five experiments were conducted using each of the hollow fiber membranes prepared in the comparative examples and examples, using five albino guinea pigs. The oxygen partial pressure in the blood was measured and the average value was plotted.

[0091] Figure 5 Figure 1 shows a graph of oxygen partial pressure in the blood of albino guinea pigs after hemoconcentration, and Table 1 shows the oxygen partial pressure data for albino guinea pigs after hemoconcentration. As can be seen, compared with the hollow fiber membrane without ferrous alginate (prepared in Comparative Example 2), the oxygen partial pressure in the blood of the albino guinea pigs drawn at the same time after the blood was passed through the hollow fiber membrane containing ferrous alginate and then reinfused back into the albino guinea pigs was significantly increased. This demonstrates the effectiveness of ferrous alginate in improving hypoxemia in patients after hemoconcentration.

[0092] Table 1 Test data of oxygen partial pressure in the blood of albino guinea pigs after a certain period of time after blood concentration

[0093]

[0094] 3) Anticoagulant test

[0095] The anticoagulant test can reflect the anticoagulant properties of hollow fiber membranes. The longer the blood coagulation time in the hollow fiber membrane, the stronger the membrane's anticoagulant effect. A related literature (Study on the Anticoagulant Properties of Ti-Ta-O Coatings, Chen Junying et al., High Technology Communications, November 2000) describes a test method using absorbance to characterize anticoagulant properties. The present invention also draws on this test method to perform anticoagulant testing.

[0096] Specific steps:

[0097] Connect the tubing and hemoconcentrator, start the blood inlet pump, adjust the blood flow rate to 100 ml / min, empty the air bubbles in the hemoconcentrator and tubing with a standard simulant, and run for 15 minutes. Next, connect bovine blood to the inlet tubing and set the pump flow rate to 50 ml / min. After the bovine blood fills the entire hollow fiber membrane in the hemoconcentrator, let it rest for 10, 20, 30, 40, and 50 minutes, and then place it in 200 ml of distilled water. Uncoagulated blood cells will undergo hemolysis, and free hemoglobin will be evenly distributed in the distilled water. The concentration of hemoglobin dissolved in water is characterized by measuring the absorbance α of the solution (wavelength 540 nm) using an ultraviolet spectrophotometer. At the same time point, the greater the absorbance α, the higher the hemoglobin concentration in the solution and the weaker the blood's coagulability on the inner surface of the hollow fiber membrane. The longer the clotting time, the stronger the anticoagulant effect of the hollow fiber membrane. Figure 6 is the anticoagulant test curve of the prepared hollow fiber membrane, and Table 2 is the anticoagulant test data of the hollow fiber membrane. It can be seen that compared with the hollow fiber membrane without ferrous alginate (prepared in Comparative Example 2), the anticoagulant property of the hollow fiber membrane containing a certain amount of ferrous alginate has been significantly improved.

[0098] Table 2 Anticoagulant test data of hollow fiber membrane

[0099]

[0100] 4) Hemofiltration rate test

[0101] The hemofiltration rate (HFR) reflects the hollow fiber membrane's ability to remove water. A higher HFR indicates a stronger ability to remove water, which in turn helps alleviate systemic inflammatory responses.

[0102] Specific steps:

[0103] Connect the pipeline and blood concentrator, connect the blood inlet of the blood concentrator to the pump, set the pump speed to 100ml / min, turn on the pump and use 500ml of normal saline to pre-fill the membrane bundle in the plasma component separator, remove bubbles and moisten the membrane. After running for 15 minutes, connect the bovine blood and allow the bovine blood to flow through each hollow fiber membrane bundle. Run for five minutes to completely discharge the normal saline. Stop the pump and reset the pump speed to 200ml / min. Adjust the blood pump flow (QF1) on the filtrate passage and the pressure control device at the outlet of the plasma component separator so that the transmembrane pressure (TMP) value falls between 100mmHg. After the pressure stabilizes for 5 minutes, read the values ​​of each pressure gauge, collect the filtrate with a measuring cylinder, time for 1 minute, and read the liquid volume. Calculate the blood filtration rate (UFR) using the following formula:

[0104]

[0105] 5) Albumin screening coefficient test

[0106] During the hemoconcentration process, some albumin is lost. The greater the albumin loss, the higher the patient's risk of hypoalbuminemia. The albumin sieving coefficient (ASC) reflects the amount of high-molecular-weight albumin that passes through the hollow fiber membrane. A lower ASC indicates a lower degree of albumin loss.

[0107] Specific steps:

[0108] Connect the pipeline and the hemoconcentrator, connect the blood inlet of the hemoconcentrator to the pump, turn on the pump, adjust the flow rate to 100ml / min, empty the bubbles in the hemoconcentrator and the pipeline with a standard simulated liquid, and run for 15 minutes. Then connect the inlet pipeline to bovine plasma, set the pump flow rate to 200ml / min, and control the filtrate flow rate QF at 80ml / min. Run under this condition for 20 minutes, and take 20ml of the hemoconcentrator filtrate, hemoconcentrator outlet liquid, and hemoconcentrator inlet liquid as the test liquid. Take 1ml of the above test liquid and do two sets of parallel control experiments. Add the reagent and shake well. Then use ultraviolet spectrophotometry to determine the albumin concentration (CF) in the hemoconcentrator filtrate, the albumin concentration (CBO) in the hemoconcentrator outlet liquid, and the albumin concentration (CBI) in the hemoconcentrator inlet liquid. Then calculate the albumin screening coefficient S by the following formula:

[0109]

[0110] 6) Interleukin-6 screening coefficient test

[0111] Interleukin-6, a small molecule inflammatory factor, is a polypeptide substance primarily expressed in inflammatory responses. Higher levels indicate more severe inflammation. Its screening coefficient reflects the hollow fiber membrane's ability to remove small molecule inflammatory factors. A higher interleukin-6 screening coefficient indicates a stronger hollow fiber membrane's ability to remove small molecule inflammatory factors, and thus a greater ability to prevent inflammatory responses in patients.

[0112] Specific steps:

[0113] Connect the tubing and hemoconcentrator, start the blood inlet pump, adjust the blood flow rate to 100 ml / min, and use a standard simulant to evacuate bubbles from the hemoconcentrator and tubing. Run for 15 minutes. Dissolve 10 g of interleukin-6 in 500 ml of bovine plasma and stir evenly. Then connect the inlet tubing to the bovine plasma, set the pump flow rate to 200 ml / min, and control the filtrate flow rate QF at 80 ml / min. Run under these conditions for 15 minutes. Take 20 ml each of the hemoconcentrator filtrate, hemoconcentrator outlet, and hemoconcentrator inlet as test solutions. Take 2 ml of each of these test solutions for two parallel control experiments. Add the reagent and shake well. Then, determine the interleukin-6 concentration (CF) in the hemoconcentrator filtrate, the interleukin-6 concentration (CBO) in the hemoconcentrator outlet, and the interleukin-6 concentration (CBI) in the hemoconcentrator inlet by ultraviolet spectrophotometry. Then, the interleukin-6 screening coefficient S is calculated using the above formula for calculating the albumin screening coefficient.

[0114] Table 3 is the blood filtration rate, albumin screening coefficient, interleukin-6 screening coefficient test results of the hollow fiber membrane. It can be seen that the hollow fiber membrane with ferric alginate in the embodiment has a higher blood filtration rate and interleukin-6 screening coefficient than the hollow fiber membrane without ferric alginate in the comparative example. Therefore, the presence of ferrous alginate can significantly improve the hollow fiber membrane's ability to remove water from the blood and its ability to remove small molecule inflammatory factors, and the albumin screening coefficient remains at a low level.

[0115] Table 3 Other relevant performance test results of hollow fiber membrane

[0116]

[0117] The above description of the disclosed embodiments will enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is to be construed in the widest manner consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a hollow fiber membrane, characterized in that: include: (1) The spinning solution and the core solution are co-extruded, and after spinning and solidification, a primary membrane is formed; (2) washing and drying the primary membrane to obtain a hollow fiber membrane; The mass ratio of the spinning solution to the core solution is (0.2-0.8):1; The spinning solution consists of polymer, alginate, additives, organic solvent and water; The core liquid consists of an organic solvent, water and ferrous salt; The hollow fiber membrane is used for blood concentration; In the spinning solution, the mass ratio of polymer, alginate, additive, organic solvent and water is (1.0-2.5):(0.2-2.5):(0.2-1.0):(5.0-9.0):(0.2-2.0); In the core liquid, the mass ratio of the organic solvent, water and ferrous salt is (2.0-9.0):(1.0-8.0):(0.5-5.0).

2. The method for preparing a hollow fiber membrane according to claim 1, wherein: The polymer is one or more of polysulfone, polyethersulfone, polyacrylonitrile, cellulose acetate, cellulose diacetate, polyimide, polymethyl methacrylate, and polyamide.

3. The method for preparing a hollow fiber membrane according to claim 1, wherein: The alginate is one or more of sodium alginate, zinc alginate and magnesium alginate.

4. The method for preparing a hollow fiber membrane according to claim 1, wherein: The ferrous salt is one or more of ferrous sulfate, ferrous nitrate and ferrous chloride.

5. The method for preparing a hollow fiber membrane according to claim 1, wherein: The additive is one or more of polyvinyl pyrrolidone, polyethylene glycol, polypropylene glycol, polyvinyl alcohol, and polyethylene oxide.

6. The method for preparing a hollow fiber membrane according to claim 1, wherein: The organic solvent is one or more of nitrogen-nitrogen dimethylacetamide, dimethyl sulfoxide, nitrogen-methyl pyrrolidone, tetrahydrofuran, and nitrogen-ethyl pyrrolidone.

7. A hollow fiber membrane produced by the method for producing a hollow fiber membrane according to any one of claims 1 to 6.

8. The hollow fiber membrane according to claim 7, characterized in that The average sidewall pore diameter of the hollow fiber membrane is 7 to 15 nm.

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