CN115400600B - A kind of hollow fiber composite membrane and its preparation method and application - Google Patents

Abstract

The invention provides a hollow fiber composite membrane, a preparation method and application thereof, wherein the preparation method of the hollow fiber composite membrane comprises the following steps: uniformly mixing the modified polyethersulfone mixture, the hydrophilic additive and the organic solvent to prepare a separation layer spinning solution; uniformly mixing the modified polyethersulfone mixture, the plasticizer, the pore-forming agent and the organic solvent to prepare a supporting layer spinning solution; forming an initial membrane by a coextrusion process of the separation layer spinning solution, the support layer spinning solution and the core solution, and solidifying and cleaning the initial membrane to obtain a hollow fiber composite membrane; the modified polyethersulfone mixture comprises polyethersulfone and/or end hydroxylated polyethersulfone. The invention solves the problems that the existing hollow fiber membrane is not easy to realize large-scale production, and the performance consistency is poor, so that the production cost of the hollow fiber membrane is increased.

Description

A kind of hollow fiber composite membrane and its preparation method and application

technical field

The invention relates to the technical field of blood purification materials, in particular to a hollow fiber composite membrane and its preparation method and application.

Background technique

Hemodialysis refers to the blood purification technology that uses the principles of diffusion, ultrafiltration and convection to remove harmful substances and excess water in the blood. It is one of the most commonly used renal replacement therapy methods and can also be used to treat drug overdose or poisoning. Hemofiltration is a medical technique that convectively removes excess water and uremic toxins from the body. Hemodiafiltration is a combination of hemodialysis and hemofiltration, offering the advantages of both modes of treatment, removing solutes by both diffusion and convection mechanisms.

Ultrafiltration membrane is the most important component to realize the above medical technology. The surface chemical composition and hydrophilic properties of ultrafiltration membranes have a great influence on the blood compatibility of the membranes. At present, the commonly used hemodialysis, hemofiltration and hemodiafiltration membranes include polysulfone (PSF) and polyethersulfone (PES). These two membrane materials have poor hydrophilicity, so blood compatibility is not satisfactory. . The commonly used improvement method is to add hydrophilic substances such as polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) for blending modification or coating modification on the membrane surface to make modified hemodialysis, hemofiltration Through and hemodiafiltration membrane, improve the hydrophilicity of the membrane material, and improve the blood compatibility of the membrane material.

However, adding hydrophilic substances such as polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) to blend and modify the membrane is convenient and easy to achieve large-scale production, but the separation layer and support layer of the membrane belong to the same formula system In terms of membrane structure control, it is difficult to adjust the formulations of the separation layer and support layer according to actual needs, that is, it is impossible to achieve differential control of the structure and performance of the separation layer and support layer through formulation regulation. Coating modification on the surface of the base film is a step-by-step film-making process, that is, the base film is prepared first, and then the second step is applied on the surface of the base film to form a film. Although this method can be modified according to actual needs, the base film and the coating layer Distributed preparation is carried out, but it is not easy to achieve large-scale production, and the performance consistency is poor, resulting in an increase in the production cost of the membrane.

In view of this, it is necessary to provide a method for preparing hollow fiber composite membranes that is easy to realize large-scale production, has good performance consistency, and can reduce production costs.

Contents of the invention

The invention aims to solve the problem that the existing hollow fiber membranes are not easy to realize large-scale production, and the performance consistency is poor, which leads to the increase of the production cost of the hollow fiber membranes.

In order to solve the above problems, the first aspect of the present invention provides a method for preparing a hollow fiber composite membrane, comprising the steps of:

uniformly mixing the modified polyethersulfone mixture, the hydrophilic additive and the organic solvent to prepare a separation layer spinning solution;

uniformly mixing the modified polyethersulfone mixture, plasticizer, porogen and organic solvent to prepare a spinning solution for the support layer;

The separation layer spinning solution, the supporting layer spinning solution and the core liquid are coextruded to form an initial membrane, and the initial membrane is solidified and cleaned to obtain a hollow fiber composite membrane;

Wherein, the modified polyethersulfone mixture includes polyethersulfone and/or hydroxylated polyethersulfone.

Further, the separation layer spinning solution is prepared by the following method:

Mix 15% to 35% of the modified polyethersulfone mixture, 25% to 40% of the hydrophilic additive and 45% to 60% of the organic solvent at 30°C to 80°C for 12h to 24h, and filter After degassing and vacuum degassing, a separation layer spinning solution was prepared.

Further, the hydrophilic additive is one or a combination of polyethylene glycol, cellulose acetate, polyvinyl alcohol and polymethyl methacrylate;

The organic solvent is one or a combination of triethyl phosphate, N-methylformamide, N,N-dimethylacetamide and N-methylpyrrolidone.

Further, the spinning solution for the support layer is prepared by the following method:

The mass percentage is 10% to 25% of the modified polyethersulfone mixture, 5% to 30% of the plasticizer, 15% to 40% of the porogen and 30% to 65% of the organic solvent at 30 ℃ to 80 Mixing at ℃ for 12h to 24h, after filtering and vacuum defoaming, the spinning solution for the support layer is prepared.

Further, the plasticizer is one or a combination of polyvinylpyrrolidone, polyethylene glycol, carboxymethylcellulose, hydroxyethylcellulose and polymethylmethacrylate;

The porogen is one or a combination of ethanol, ethylene glycol, isopropanol, ethylene glycol monomethyl ether, diethylene glycol, diethylene glycol and glycerol;

The organic solvent is one or a combination of triethyl phosphate, N-methylformamide, N,N-dimethylacetamide and N-methylpyrrolidone.

Further, the modified polyethersulfone mixture in the spinning solution of the separation layer includes polyethersulfone and hydroxylated polyethersulfone, or, the modified polyethersulfone mixture is hydroxylated polyethersulfone;

The modified polyethersulfone mixture in the spinning solution for the support layer includes polyethersulfone and hydroxylated polyethersulfone, or the modified polyethersulfone mixture is polyethersulfone.

Further, the initial film is prepared by the following method:

The separation layer spinning solution, the supporting layer spinning solution and the core liquid are simultaneously extruded from a three-hole annular spinneret to prepare an initial film, wherein the three-hole annular spinneret includes The core liquid channel, the separation layer solution channel and the support layer solution channel arranged in sequence from inside to outside, the core liquid is extruded from the core liquid channel, and the separation layer spinning solution is extruded from the separation layer solution channel, The support layer spinning solution is extruded from the support layer solution channel.

Further, the initial film is solidified by the following method:

The initial film is solidified sequentially through the air section and the coagulation bath, wherein the relative humidity of the air section is 30% to 90%, the temperature is 30°C to 50°C, and the residence time of the initial film in the air section is 0.5s to 1.5s; the coagulation bath is made by mixing water and a porogen, or the coagulation bath is made by mixing water and an organic solvent, and the liquid level of the coagulation bath is kept constant.

The second aspect of the present invention provides a hollow fiber composite membrane, which is prepared by the method for preparing a hollow fiber composite membrane according to any one of the first aspect.

The third aspect of the present invention provides an application of the hollow fiber composite membrane as described in the second aspect in hemodialysis.

The preparation method of the hollow fiber composite membrane described in the present invention uses a modified polyethersulfone mixture to prepare a separation layer spinning solution and a support layer spinning solution, and the modified polyethersulfone mixture includes polyethersulfone and/or terminal hydroxylation Polyethersulfone, hydroxyl-terminated polyethersulfone is a water-insoluble hydrophilic modified polyethersulfone, which can be blended with polyethersulfone to form a film, which can improve the hydrophilic performance of the hollow fiber composite membrane and improve the hollow fiber composite membrane. The blood compatibility of the membrane; in the process of film formation, the terminal hydroxyl groups in the hydroxyl-terminated polyethersulfone can form hydrogen bonds with hydrophilic substances (such as water-soluble PVP or PEG molecules, etc.), so that the hydrophilic substances are anchored in the hollow The surface of the fiber composite membrane can further improve the blood compatibility of the hollow fiber composite membrane, and the terminal hydroxyl groups in the hydroxyl-terminated polyethersulfone are connected to the hydrophilic substance through hydrogen bonds, so that the hydrophilic substance can be more firmly bound to the membrane. In terms of material, it is necessary to avoid falling off or dissolution of hydrophilic substances; and polyethersulfone has excellent mechanical properties, and using it as a supporting layer spinning solution is beneficial to improve the structural strength of the hollow fiber composite membrane; in addition, through separate regulation and separation The membrane-making formula of layer spinning solution and supporting layer spinning solution can prepare a hydrophilic separation layer, so that the surface of the separation layer and pores form a hydration layer to improve hydrophilicity, so as to improve the blood compatibility of the hollow fiber composite membrane, At the same time, the wall thickness of the separation layer can be adjusted to reduce the filtration resistance of the hollow fiber composite membrane, and the support layer can be prepared by adjusting the membrane formulation of the support layer spinning solution to prepare a porous layer to further reduce the filtration resistance of the hollow fiber composite membrane, and the separation layer The spinning solution and the supporting layer spinning solution use a similar structure of the main material, in the one-step film forming process, the interface molecules of the separation layer and the supporting layer can be entangled more firmly, and the bonding strength of the two is more stable.

In addition, the separation layer spinning solution, the supporting layer spinning solution and the core solution are co-extruded to prepare the hollow fiber composite membrane through the co-extrusion process, which can realize one-step film formation and facilitate large-scale production, and can be produced through the co-extrusion process. The membrane can not only combine the hydrophilic separation layer in direct contact with the blood with the support layer to improve the blood compatibility of the hollow fiber composite membrane, but also can separately control the membrane formulation of the separation layer and the support layer to optimize the hollow fiber composite membrane. The structure of the membrane improves the performance of the hollow fiber composite membrane.

Description of drawings

Fig. 1 is the flow chart of the preparation hollow fiber composite membrane provided by the embodiment of the present invention;

Fig. 2 is the structural representation of the three-hole annular spinneret provided by the embodiment of the present invention;

Fig. 3 is the cross-section electron micrograph of the hollow fiber composite membrane that the embodiment of the present invention 1 makes;

Fig. 4 is a cross-sectional electron micrograph of the separation layer of the hollow fiber membrane prepared in Example 1 of the present invention.

Explanation of reference signs:

200-core fluid channel; 210-separation layer solution channel; 220-support layer solution channel.

Detailed ways

In order to make the above objects, features and advantages of the present invention more comprehensible, specific embodiments of the present invention will be described in detail below in conjunction with the accompanying drawings.

It should be noted that, in the case of no conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other.

In addition, the meanings of the terms "comprising", "comprising", "containing" and "having" are non-limiting, that is, other steps and other components that do not affect the result can be added. Unless otherwise specified, materials, equipment, and reagents are commercially available.

In addition, although the present invention describes each step in the preparation such as step S100, step S200, step S300, etc., this description is only for the convenience of understanding, such as step S100, step S200, step S300, etc. does not mean Restrictions on the sequence of steps.

As shown in Figure 1, the embodiment of the present invention provides a method for preparing a hollow fiber composite membrane, comprising the following steps:

Step S100, uniformly mixing the modified polyethersulfone mixture, the hydrophilic additive and the organic solvent to prepare a separation layer spinning solution;

Step S200, uniformly mixing the modified polyethersulfone mixture, plasticizer, porogen and organic solvent to prepare a spinning solution for the support layer;

Step S300, the separation layer spinning solution, the supporting layer spinning solution and the core solution are co-extruded to form an initial membrane, and after the initial membrane is solidified and cleaned, a hollow fiber composite membrane is obtained;

Wherein, the modified polyethersulfone mixture includes polyethersulfone and/or hydroxylated polyethersulfone.

The preparation method of the hollow fiber composite membrane provided in this example uses a modified polyethersulfone mixture to prepare a separation layer spinning solution and a support layer spinning solution, and the modified polyethersulfone mixture includes polyethersulfone and/or terminal hydroxyl groups Polyethersulfone, hydroxyl-terminated polyethersulfone is a water-insoluble hydrophilic modified polyethersulfone, which can be blended with polyethersulfone to form a membrane, which can improve the hydrophilic performance of the hollow fiber composite membrane and improve the hollow fiber Blood compatibility of the composite membrane; during the film formation process, the terminal hydroxyl groups in the hydroxyl-terminated polyethersulfone can form hydrogen bonds with hydrophilic substances (such as water-soluble PVP or PEG molecules, etc.), so that the hydrophilic substances are anchored in the The surface of the hollow fiber composite membrane can further improve the blood compatibility of the hollow fiber composite membrane, and the terminal hydroxyl groups in the hydroxyl-terminated polyethersulfone are connected to the hydrophilic substance through hydrogen bonds, so that the hydrophilic substance can be more firmly bound to the component. On the membrane material, the phenomenon of falling off or dissolution of the hydrophilic material is avoided; and polyethersulfone has excellent mechanical properties, and it is beneficial to improve the structural strength of the hollow fiber composite membrane by using it as a supporting layer spinning solution; in addition, this embodiment In the process, the membrane-making formula of the separation layer spinning solution and the support layer spinning solution can be separately adjusted to prepare a hydrophilic separation layer, so that the surface and pores of the separation layer can form a hydration layer to improve hydrophilicity, so as to improve the hollow fiber composite membrane. Hemocompatibility, at the same time, the wall thickness of the separation layer can be adjusted to reduce the filtration resistance of the hollow fiber composite membrane, and the support layer can be prepared by adjusting the membrane formulation of the support layer spinning solution to prepare a porous layer to further reduce the filtration of the hollow fiber composite membrane. Resistance, and the separation layer spinning solution and the support layer spinning solution use the main material with similar structure. In the process of one-step film formation, the interface molecules of the separation layer and the support layer can be entangled more firmly, and the bonding strength of the two can be improved. more stable.

In addition, the separation layer spinning solution, the supporting layer spinning solution and the core solution are co-extruded to prepare the hollow fiber composite membrane through the co-extrusion process, which can realize one-step film formation and facilitate large-scale production, and can be produced through the co-extrusion process. The membrane can not only combine the hydrophilic separation layer in direct contact with the blood with the support layer to improve the blood compatibility of the hollow fiber composite membrane, but also can separately control the membrane formulation of the separation layer and the support layer to optimize the hollow fiber composite membrane. The structure of the membrane improves the performance of the hollow fiber composite membrane.

Specifically, in step S100, the following method can be used to prepare the separation layer spinning solution:

Mix 15% to 35% of the modified polyethersulfone mixture, 25% to 40% of the hydrophilic additive and 45% to 60% of the organic solvent at 30°C to 80°C for 12h to 24h until mixed Evenly, after filtering and vacuum defoaming for 10h to 12h, a clear and transparent spinning solution for the separation layer is obtained.

Limiting the dosage ratio of each component in the spinning solution of the separation layer within a certain range is conducive to improving the quality of the hollow fiber composite membrane, further improving the blood compatibility of the hollow fiber composite membrane, and is also beneficial to the separation layer. The wall thickness is adjusted to further reduce the filtration resistance of the hollow fiber composite membrane, which is beneficial to improve the efficiency of blood purification.

Wherein, the modified polyethersulfone mixture includes polyethersulfone and hydroxylated polyethersulfone, or the modified polyethersulfone mixture is hydroxylated polyethersulfone.

If the modified polyethersulfone mixture includes polyethersulfone and hydroxylated polyethersulfone, the polyethersulfone and hydroxylated polyethersulfone can be combined in any ratio, which is not further limited in this embodiment. For example: polyethersulfone and hydroxylated polyethersulfone can be mixed according to 25% polyethersulfone and 75% hydroxylated polyethersulfone.

The hydroxylated polyethersulfone in this example is purchased from the market, and the molecular structure of the hydroxylated polyethersulfone is as follows:

In this embodiment, the hydrophilic additive is one or a combination of polyethylene glycol, cellulose acetate, polyvinyl alcohol and polymethyl methacrylate, wherein the polyethylene glycol can be PEG200, PEG400, One or a combination of two of PEG600, PEG800 and PEG1000. The organic solvent is one or a combination of triethyl phosphate, N-methylformamide, N,N-dimethylacetamide and N-methylpyrrolidone. Compared with other types of hydrophilic additives and organic solvents in the prior art, the hydrophilicity and biocompatibility of the obtained hollow fiber composite membrane can be further improved when the above-mentioned types of hydrophilic additives and organic solvents are used.

When preparing the spinning solution, polyethersulfone, hydroxylated polyethersulfone and hydrophilic agent additives are dissolved in the organic solvent together to achieve blending. The advantages of blending and hydrogen bonding are conducive to the preparation of a good It is a hollow fiber composite membrane with blood compatibility, and it is also conducive to more firmly binding of hydrophilic substances to the modified polyethersulfone mixture.

Specifically, in step S200, the following method can be used to prepare the spinning solution for the support layer:

The mass percentage is 10% to 25% of the modified polyethersulfone mixture, 5% to 30% of the plasticizer, 15% to 40% of the porogen and 30% to 65% of the organic solvent at 30 ℃ to 80 ℃, stirring for 12h to 24h until the mixture is uniform, and after filtering and vacuum defoaming for 10h to 12h, a clear and transparent spinning solution for the support layer is obtained.

Limiting the dosage ratio of each component in the spinning solution of the support layer within a certain range is conducive to regulating the pore size of the support layer and preparing a support layer with a porous structure to further reduce the filtration resistance of the hollow fiber composite membrane. It is beneficial to improve the efficiency of blood purification.

Wherein, the modified polyethersulfone mixture includes polyethersulfone and hydroxylated polyethersulfone, or the modified polyethersulfone mixture is polyethersulfone.

It should be noted that if the separation layer spinning solution contains polyethersulfone and hydroxylated polyethersulfone, the supporting layer spinning solution can contain polyethersulfone and hydroxylated polyethersulfone at the same time, or only contain Polyethersulfone; if the separation layer spinning solution contains hydroxylated polyethersulfone, the supporting layer spinning solution can contain both polyethersulfone and hydroxylated polyethersulfone, or only polyethersulfone, as long as It can ensure that the modified polyethersulfone mixture in the spinning solution of the separation layer and the modified polyethersulfone mixture in the spinning solution of the support layer can contain polyethersulfone and hydroxylated polyethersulfone at the same time, ensuring that polyethersulfone and terminal hydroxyl Polyether sulfone is blended to form a membrane, which is beneficial to improve the hydrophilic performance of the hollow fiber composite membrane and improve the blood compatibility of the hollow fiber composite membrane.

If the modified polyethersulfone mixture includes polyethersulfone and hydroxylated polyethersulfone, the polyethersulfone and hydroxylated polyethersulfone can be combined in any ratio, which is not further limited in this embodiment. For example: polyethersulfone and hydroxylated polyethersulfone can be mixed according to 50% polyethersulfone and 50% hydroxylated polyethersulfone.

In this embodiment, the plasticizer is one or a combination of two of polyvinylpyrrolidone, polyethylene glycol, carboxymethyl cellulose, hydroxyethyl cellulose and polymethyl methacrylate, wherein polyethylene Pyrrolidone can be one or a combination of PVPK15, PVPK17, PVPK30 and PVPK60, and polyethylene glycol can be one or a combination of PEG8000, PEG10000 and PEG20000. The porogen is one or a combination of ethanol, ethylene glycol, isopropanol, ethylene glycol monomethyl ether, diethylene glycol, diethylene glycol and glycerol. The organic solvent is one or a combination of triethyl phosphate, N-methylformamide, N,N-dimethylacetamide and N-methylpyrrolidone. Compared with other types of plasticizers, porogens and organic solvents in the prior art, when using the above-mentioned plasticizers, porogens and organic solvents, the filtration resistance of the hollow fiber composite membrane obtained can be further improved, And further improve the bonding strength of the separation layer and the support layer.

Specifically, in step S300, the following method can be used to prepare the initial film:

The separation layer spinning solution, the supporting layer spinning solution and the core liquid are simultaneously extruded from the three-hole annular spinneret to prepare the initial membrane, wherein the three-hole annular spinneret includes the core liquid sequentially arranged from the inside to the outside The channel, the separation layer solution channel and the support layer solution channel, the core liquid is extruded from the core liquid channel, the separation layer spinning solution is extruded from the separation layer solution channel, and the support layer spinning solution is extruded from the support layer solution channel.

Wherein, the structure of the three-hole annular spinneret is as shown in Figure 2, and the three-hole annular spinneret includes a core liquid channel 200, a separation layer solution channel 210 and a support layer solution channel 220 arranged in sequence from the inside to the outside, and the core liquid The channel 200 is a circular channel, the separation layer solution channel 210 and the support layer solution channel 220 are annular channels, and the core liquid, the separation layer spinning solution and the support layer spinning solution are arranged in sequence from the inside to the outside to form blood compatibility and mechanical properties. The initial film with better performance.

After the initial film is prepared, the initial film first passes through the air section, the relative humidity of the air section is 30% to 90%, the temperature is 30°C to 50°C, and the residence time of the initial film in the air section is 0.5s to 1.5s; After the stage, the initial membrane enters the coagulation bath for coagulation, the liquid level of the coagulation bath is kept constant, fully coagulated and formed in the coagulation bath, and the hollow fiber composite membrane is obtained.

In this embodiment, by passing the initial membrane first through the air section and then through the coagulation bath, it is beneficial to gradually increase the aperture of the inner wall of the hollow fiber composite membrane to the aperture of the outer wall of the hollow fiber composite membrane, and reduce the thickness of the inner wall of the hollow fiber composite membrane. Therefore, the resistance during the dialysis process of the hollow fiber composite membrane is reduced, and the efficiency of blood purification is improved.

In this embodiment, the core fluid can be prepared by mixing a porogen and an organic solvent, and the core fluid can also be prepared by mixing water and an organic solvent.

In order to further improve the hydrophilicity and biocompatibility of the obtained hollow fiber composite membrane, porogens include ethanol, ethylene glycol, isopropanol, ethylene glycol monomethyl ether, diethylene glycol, diethylene glycol One or a combination of diethylene glycol and glycerol; organic solvents include one of triethyl phosphate, N-methylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone one or a combination of two.

In this embodiment, the coagulation bath is prepared by mixing water and an organic solvent. Specifically, the coagulation bath is prepared by uniformly mixing 40% to 90% water and 10% to 60% organic solvent by mass percentage.

Alternatively, in this embodiment, the coagulation bath is prepared by mixing water and a porogen, specifically, the mass percentage is 30% to 80% of water and 20% to 70% of the porogen are uniformly mixed to obtain a coagulation bath .

In order to further improve the hydrophilicity and biocompatibility of the resulting hollow fiber composite membrane, organic solvents include triethyl phosphate, N-methylformamide, N,N-dimethylacetamide, N-methylpyrrolidone one or a combination of the two.

After fully coagulating in the coagulation bath, before preparing the hollow fiber composite membrane, it also includes washing the initial membrane after water washing and drying to obtain a hollow fiber composite membrane, wherein the water temperature during washing is 80 ° C to 100 °C, the drying temperature is 30 °C to 60 °C.

Chemical substances such as additives and solvents in the hollow fiber composite membrane can be removed by washing with water. The residual amount of these chemical substances has a great impact on blood compatibility, and the removal of water in the hollow fiber composite membrane by drying can eliminate internal stress and improve Dimensional stability of hollow fiber composite membranes.

It should be noted that the water used in this embodiment is all purified water or water for hemodialysis.

In order to further describe the present invention in detail, the present invention will be further described below in conjunction with specific examples. The experimental methods used in the examples of the present invention are conventional methods unless otherwise specified; the materials and reagents used in the examples of the present invention are purchased from the market unless otherwise specified. The hydroxylated polyethersulfone was purchased from SUMITOMO CHEMICAL, and the model number was Hydroxyl terminatedPES.

Example 1

This embodiment provides a method for preparing a hollow fiber composite membrane, comprising the following steps:

(1) Stir and mix 70wt% polyethersulfone and 30wt% hydroxyl-terminated polyethersulfone to obtain a modified polyethersulfone mixture; mix 18wt% modified polyethersulfone mixture, 40wt% hydrophilic additive PEG600, 52wt% organic solvent N,N-dimethylacetamide at 50°C, stirred for 24 hours until uniformly mixed, filtered and vacuum defoamed for 12 hours, to obtain a clear and transparent spinning solution for the separation layer;

The mass percent is 16% polyethersulfone, 8% plasticizer polyvinylpyrrolidone, 25% porogen ethylene glycol monomethyl ether and 51% organic solvent N,N-dimethylacetamide at 50 At ℃, stir for 24 hours until the mixture is uniform, and after filtering and vacuum defoaming for 12 hours, a clear and transparent spinning solution for the support layer is obtained;

Stir and mix 5wt% organic solvent N,N-dimethylacetamide and 95wt% water evenly to obtain core liquid;

Stir and mix 70wt% water and 30wt% organic solvent N,N-dimethylacetamide evenly to prepare a coagulation bath.

(2) Extrude the separation layer spinning solution, the support layer spinning solution and the core liquid from the three-hole annular spinneret at the same time, and the three-hole annular spinneret includes core liquid passages, separation layers, The solution channel and the support layer solution channel, the core liquid is extruded from the core liquid channel, the separation layer spinning solution is extruded from the separation layer solution channel, and the support layer spinning solution is extruded from the support layer solution channel to prepare the initial membrane.

(3) Make the initial film first pass through the air section, the temperature and humidity of the air section remain constant, the relative humidity of the air section is 60%, the temperature is 40°C, and the initial film's residence time in the air section is 1s, after passing through the air section, The pre-separated initial film enters the coagulation bath for coagulation. The liquid level of the coagulation bath remains constant. The pre-separated initial film is fully solidified in the coagulation bath and then enters the cleaning water tank. The temperature of the cleaning water tank is 90 ° C. After cleaning , and the cleaned initial membrane enters a circulating hot air drying oven and is dried at 45° C. to obtain a hollow fiber composite membrane.

The cross-sectional electron micrograph of the hollow fiber composite membrane prepared in this example is shown in FIG. 3 , and the cross-sectional electron micrograph of the separation layer of the hollow fiber composite membrane prepared in this example is shown in FIG. 4 . As can be seen from Figures 3 to 4, the interface between the separation layer and the support layer of the hollow fiber composite membrane prepared in this example is relatively firm, which is conducive to improving the mechanical strength of the hollow fiber composite membrane, and the support layer is porous Structure, the wall thickness of the separation layer is small, which is beneficial to reduce the filtration resistance of the hollow fiber composite membrane and improve the efficiency of blood purification.

Example 2

This example provides a preparation method of a hollow fiber composite membrane, the preparation method of the hollow fiber composite membrane in this example is basically the same as that of Example 1, the difference is that the separation layer spinning solution and the support layer spinning The proportioning ratio of each component in the solution is different, specifically:

Stir and mix 20wt% polyethersulfone and 80wt% hydroxyl-terminated polyethersulfone to obtain a modified polyethersulfone mixture; mix 18wt% modified polyethersulfone mixture, 35wt% hydrophilic additive PEG600, 57wt% % organic solvent N, N-dimethylacetamide at 50°C, stirred for 24 hours until uniformly mixed, filtered and vacuum defoamed for 12 hours, to obtain a clear and transparent spinning solution for the separation layer;

The mass percent is 16% polyethersulfone, 8% plasticizer polyvinylpyrrolidone, 28% porogen glycerol and 48% organic solvent N,N-dimethylacetamide at 50°C, stirring After 24 hours until the mixture is uniform, after filtration and vacuum defoaming for 12 hours, a clear and transparent spinning solution for the support layer is obtained.

Example 3

This example provides a preparation method of a hollow fiber composite membrane, the preparation method of the hollow fiber composite membrane in this example is basically the same as that of Example 1, the difference is that the separation layer spinning solution and the support layer spinning The proportioning ratio of each component in the solution is different, specifically:

The modified polyethersulfone mixture is only hydroxyl-terminated polyethersulfone; 18wt% of the modified polyethersulfone mixture, 35wt% of the hydrophilic additive PEG600, 57wt% of the organic solvent N,N-dimethylacetamide at 50 At ℃, stir for 24 hours until the mixture is uniform, and filter and vacuum defoam for 12 hours to obtain a clear and transparent spinning solution for the separation layer;

The mass percent is 15% polyethersulfone, 10% plasticizer polyvinylpyrrolidone, 27% porogen glycerol and 48% organic solvent N,N-dimethylacetamide at 50°C, stirring After 24 hours until the mixture is uniform, after filtration and vacuum defoaming for 12 hours, a clear and transparent spinning solution for the support layer is obtained.

Example 4

This example provides a preparation method of a hollow fiber composite membrane, the preparation method of the hollow fiber composite membrane in this example is basically the same as that of Example 1, the difference is that the separation layer spinning solution and the support layer spinning The proportioning ratio of each component in the solution is different, specifically:

Stir and mix 20wt% polyethersulfone and 80wt% hydroxyl-terminated polyethersulfone to obtain a modified polyethersulfone mixture; mix 18wt% modified polyethersulfone mixture, 35wt% hydrophilic additive PEG400, 57wt% % organic solvent N, N-dimethylacetamide at 50°C, stirred for 24 hours until uniformly mixed, filtered and vacuum defoamed for 12 hours, to obtain a clear and transparent spinning solution for the separation layer;

The mass percentage is 8% polyethersulfone, 8% hydroxyl-terminated polyethersulfone, 9% plasticizer polyvinylpyrrolidone, 25% porogen ethylene glycol monomethyl ether and 50% organic solvent N, N-dimethylacetamide was stirred at 50° C. for 24 hours until uniformly mixed. After filtering and vacuum defoaming for 12 hours, a clear and transparent spinning solution for the support layer was obtained.

The performance of the hollow fiber composite membranes of Examples 1 to 4 is tested, and the blood compatibility of the hollow fiber composite membranes is mainly characterized by inner surface contact angle, recalcification time, and hemolysis rate, wherein the smaller the inner surface contact angle , indicating that the surface hydrophilicity of the hollow fiber composite membrane is better; the longer the recalcification time, the lower the hemolysis rate, indicating the better blood compatibility. The specific test method is as follows:

1. Inner surface contact angle test

Lay the hollow fiber composite membrane sample flat on the loading platform, level the baseline, then drop about 5 μL of deionized water on the surface of the membrane, adjust the rotation measuring instrument, and read the contact angle. Three parallel samples were measured for each hollow fiber composite membrane, 7 test points were taken on each sample, and the average value of the test results was taken.

2. Recalcification time (PRT) test

(1) Take 5mL bovine whole blood, centrifuge (2000g, about 4411r/min, 10min), and take the supernatant to obtain platelet-poor plasma (PPP);

(2) Put the hollow fiber composite membrane into a 24-well cell culture plate, label, and drop 0.1mL of the above PPP onto the surface of the membrane in a constant temperature water bath at 37°C for one minute;

(3) Add 0.1 mL of 0.025 mol/L CaCl 2 solution preheated to 37°C dropwise on the surface of the membrane, stop timing when the first fibrin filament appears, and record the recalcification time.

3. Hemolysis rate (HR) test

(1) Wash the hollow fiber composite membrane with deionized water for 10 minutes, and then wash the membrane with 0.9% NaCl solution for 10 minutes;

(2) Soak the membrane in a NaCl solution with a mass fraction of 0.9% at a temperature of 37° C. for 30 minutes;

(3) Add 200 μL of bovine whole blood to NaCl solution with membrane, NaCl solution without membrane and pure water respectively, and keep the temperature at 37°C for 1 hour;

(4) Centrifuge the above sample (800g, about 2790r/min, 10min), take the supernatant, and measure the absorbance at 545nm with a UV spectrophotometer. The NaCl aqueous solution of 0.9wt% is a negative control, and deionized water is a positive control, and the hemolysis rate is calculated by the following formula (1):

HR=(AS-AN)/(AP-AN)×100% formula (1)

In the formula: AS—absorbance of sample; AN—absorbance of negative control; AP—absorbance of positive control.

The hollow fiber composite membrane prepared above is applied to the separation of plasma components to remove pathogenic substances in the blood (pathogenic substances depend on the type of disease) to realize an application of the present invention, such as severe autoimmune diseases (SAID), using double plasma exchange therapy, directly removes immune complexes, immunoglobulins, complement and other pathogenic factors in the plasma, and restores the patient's cellular immune function and reticuloendothelial cell phagocytosis, and blocks the occurrence and development of SAID in time link, can achieve the purpose of relieving the disease.

The hollow fiber composite membranes prepared in Examples 1 to 4 were processed to obtain a hollow fiber plasma component separator with an effective membrane area of 1.0 m ² . Plasma is fresh anticoagulated bovine blood, bovine plasma at 37°C

Control the plasma inlet flow rate to 100ml/min, the filtrate flow rate to 25ml/min, the waste plasma flow rate to 5-10ml/min, and the processing time to 3h. Membrane performance was evaluated by determining the concentration of each protein in solution and in pre-filtered plasma.

Clearance rate (%)=(1-concentration in filtrate/concentration in stock solution)×100%

The hemolysis rate of the hollow fiber composite membrane was tested, and the immunoglobulin clearance performance test was performed on the plasma component separator made of the hollow fiber composite membrane. The test results are shown in Table 1.

Table 1

It can be seen from Table 1 that compared with Example 1, the inner surface contact angles of the hollow fiber composite membranes in Examples 2 to 4 all have a relatively large decrease, indicating that the middle end of the separation layer of the hollow fiber composite membrane The content of hydroxyl polyether sulfone increases, which is conducive to improving the hydrophilic performance of the membrane inner surface; Calcium time, the hemolysis rate of the hollow fiber composite membrane in embodiment 2 to embodiment 4 is all lower than the hemolysis rate of the hollow fiber composite membrane in embodiment 1, illustrates that with the separation layer of the hollow fiber composite membrane, the terminal hydroxyl polyether The content of sulfone increases, the rate of hemolysis decreases, and the recalcification time increases, which is beneficial to improve the blood compatibility of the hollow fiber composite membrane. Both the separation layer and the support layer of the hollow fiber composite membrane of Example 4 contain hydroxyl-terminated polyethersulfone and polyethersulfone, and in the hollow fiber composite membranes of Examples 2 and 3, only the separation layer contains hydroxyl-terminated polyethersulfone. Compared with polyethersulfone, ethersulfone is beneficial to further improve the blood compatibility of the entire membrane section.

The hollow fiber composite membranes in Examples 1 to 4 can be used in plasma component separators to remove various pathogenic factors such as immunoglobulins, complements, immune complexes, and macromolecular lipoproteins in the blood, and the molecular mass Smaller albumin can be infiltrated back into the patient's body through the membrane pores, thus achieving the purpose of removing harmful components in the blood and treating diseases. Adopt the hollow fiber composite membrane in embodiment 1 to embodiment 4 to carry out the scavenging performance test of immunoglobulin, the test result surface, the hollow fiber composite membrane prepared in embodiment 1 to embodiment 4 all shows good to immunoglobulin Clearance performance, wherein the hollow fiber composite membrane prepared in Example 2 has the most outstanding clearance performance for IgG, IgM, and IgA three kinds of immunoglobulins.

In order to further describe the present invention in detail, the present invention will be further described below in conjunction with specific examples. The experimental methods used in the examples of the present invention are conventional methods unless otherwise specified; the materials and reagents used in the examples of the present invention are purchased from the market unless otherwise specified.

Claims (7)

1. The preparation method of the hollow fiber composite membrane is characterized by comprising the following steps:

uniformly mixing a modified polyethersulfone mixture, a hydrophilic additive and an organic solvent to prepare a separation layer spinning solution, wherein the hydrophilic additive is one or a combination of two of polyethylene glycol, cellulose acetate, polyvinyl alcohol and polymethyl methacrylate;

uniformly mixing a modified polyethersulfone mixture, a plasticizer, a pore-forming agent and an organic solvent to prepare a supporting layer spinning solution, wherein the plasticizer is one or two of polyvinylpyrrolidone, polyethylene glycol, carboxymethyl cellulose, hydroxyethyl cellulose and polymethyl methacrylate, and the pore-forming agent is one or two of ethanol, ethylene glycol, isopropanol, ethylene glycol monomethyl ether, diethylene glycol and glycerol;

the separation layer spinning solution, the support layer spinning solution and the core solution form an initial membrane through a coextrusion process, and the initial membrane is solidified and cleaned to obtain a hollow fiber composite membrane;

wherein the modified polyethersulfone mixture in the spinning solution of the separation layer comprises polyethersulfone and hydroxyl-terminated polyethersulfone, or the modified polyethersulfone mixture in the spinning solution of the separation layer is hydroxyl-terminated polyethersulfone;

the modified polyethersulfone mixture in the supporting layer spinning solution comprises polyethersulfone and hydroxyl-terminated polyethersulfone, or the modified polyethersulfone mixture in the supporting layer spinning solution is polyethersulfone.

2. The method for preparing a hollow fiber composite membrane according to claim 1, wherein the spinning solution for the separation layer is prepared by the following method:

mixing 15-35% of modified polyethersulfone mixture, 25-40% of hydrophilic additive and 45-60% of organic solvent at 30-80 ℃ for 12-24 hours, filtering and vacuum defoaming to obtain the spinning solution.

3. The method for preparing a hollow fiber composite membrane according to claim 1, wherein the support layer spinning solution is prepared by the following method:

10 to 25 mass percent of modified polyethersulfone mixture, 5 to 30 mass percent of plasticizer, 15 to 40 mass percent of pore-forming agent and 30 to 65 mass percent of organic solvent are mixed for 12 to 24 hours at 30 to 80 ℃, and the spinning solution of the support layer is prepared after filtration and vacuum deaeration.

4. The method for producing a hollow fiber composite membrane according to claim 1, wherein,

the organic solvent is one or the combination of two of triethyl phosphate, N-methyl formamide, N-dimethyl acetamide and N-methyl pyrrolidone.

5. The method for preparing a hollow fiber composite membrane according to claim 1, wherein the initial membrane is prepared by the following method:

and extruding the separation layer spinning solution, the support layer spinning solution and the core solution from a three-hole annular spinneret simultaneously to prepare an initial membrane, wherein the three-hole annular spinneret comprises a core solution channel, a separation layer solution channel and a support layer solution channel which are sequentially arranged from inside to outside, the core solution is extruded from the core solution channel, the separation layer spinning solution is extruded from the separation layer solution channel, and the support layer spinning solution is extruded from the support layer solution channel.

6. The method for producing a hollow fiber composite membrane according to claim 1, wherein the initial membrane is coagulated by:

the initial film is sequentially solidified through an air section and a coagulating bath, wherein the relative humidity of the air section is 30-90%, the temperature is 30-50 ℃, and the residence time of the initial film in the air section is 0.5-1.5 s; the coagulating bath is prepared by mixing water and a pore-forming agent, or the coagulating bath is prepared by mixing water and an organic solvent, and the liquid level of the coagulating bath is kept constant.

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