Asymmetric PMP hollow fiber membrane for blood oxygenation as well as preparation method and application of asymmetric PMP hollow fiber membrane

Abstract

The invention relates to the technical field of membrane materials, in particular to an asymmetric PMP hollow fiber membrane for blood oxygenation and a preparation method and application of the asymmetric PMP hollow fiber membrane. The PMP hollow fiber membrane comprises a main body, wherein the main body comprises a skin layer and a supporting layer; one side of the main body is an inner surface facing the inner cavity, and the other side of the main body is an outer surface; the side, away from the supporting layer, of the skin layer is an outer surface, and the side, away from the skin layer, of the supporting layer is an inner surface. The outer surface is a compact surface, and the thickness of the supporting layer is 68-118 microns; the ratio of the thickness of the supporting layer to the thickness of the PMP hollow fiber membrane is not less than 0.95; the helium flux of the PMP hollow fiber membrane is 1.5 ml / (cm < 2 > * min * bar)-3 ml / (cm < 2 > * min * bar); and the BET specific surface area of the PMP hollow fiber membrane is 30 m < 2 > / g-60 m < 2 > / g. The PMP hollow fiber membrane disclosed by the invention can have relatively high oxygen flux on the premise of having a relatively high separation ratio of carbon dioxide to oxygen, so that the PMP hollow fiber membrane has excellent oxygenation performance; and in addition, the high-toughness wire also has relatively high toughness and is not easy to break.

Description

Technical Field

[0001] The present invention relates to the technical field of membrane materials, and particularly relates to an asymmetric PMP hollow fiber membrane for blood oxygenation, a preparation method thereof, and an application thereof. Background Art

[0002] PMP (poly-4-methyl-1-pentene) is a high-performance thermoplastic polymer and is widely used in the manufacture of oxygenation membranes. When the PMP material comes into contact with blood, it exhibits good biocompatibility, reducing the risks of thrombosis formation and immune rejection reactions; it is stable to a variety of chemical substances, corrosion-resistant, and suitable for use in complex medical environments. The PMP membrane has excellent gas permeability performance, can efficiently perform the exchange of oxygen and carbon dioxide, and meets the high requirements of the oxygenator for gas transmission. Moreover, the PMP membrane has sufficient mechanical strength and durability to withstand the mechanical stress and pressure changes during the oxygenation process. Therefore, its unique physical and chemical properties make it an ideal material for oxygenators.

[0003] Extracorporeal membrane oxygenation (ECMO) is an advanced extracorporeal life support technology used to temporarily replace the cardiopulmonary function of patients and help patients through critical stages. ECMO draws the patient's venous blood out of the body through an extracorporeal circulation system, oxygenates and removes carbon dioxide through an artificial membrane lung, and then returns the blood to the body. In this way, ECMO can temporarily replace the cardiopulmonary function and provide sufficient oxygen for the patient and remove carbon dioxide. The artificial membrane lung is one of the core components of the ECMO system, which can replace the human lungs to discharge carbon dioxide, absorb oxygen, and perform effective gas exchange. When ECMO is operating, the blood is drawn from the vein, absorbs oxygen through the artificial membrane lung, discharges carbon dioxide, and the blood after gas exchange returns to the body, undertaking the gas exchange function of the human lungs and maintaining the normal physiological needs of the human body. Therefore, the main function of the artificial membrane lung is to achieve efficient oxygen and carbon dioxide exchange between the blood and the gas.

[0004] However, as the most widely used artificial membrane lung at present, the PMP hollow fiber membrane still has the problem of relatively insufficient oxygenation performance. Therefore, it is necessary to further improve the oxygenation performance of the PMP hollow fiber oxygenation membrane. Summary of the Invention

[0005] The object of the present invention is to overcome the above problems of the prior art, and provides an asymmetric PMP (poly-4-methyl-1-pentene) hollow fiber membrane for blood oxygenation, its preparation method and application. The asymmetric PMP hollow fiber membrane for blood oxygenation (hereinafter simply referred to as the hollow fiber membrane) of the present invention can have a high oxygen flux on the premise of having a high separation ratio of carbon dioxide to oxygen, so that the hollow fiber membrane has excellent oxygenation performance; in addition, the hollow fiber membrane also has high toughness.

[0006] To achieve the above object, the first aspect of the present invention provides an asymmetric PMP hollow fiber membrane for blood oxygenation, including a main body, the main body includes a skin layer and a support layer; one side of the main body is an inner surface facing the inner cavity, and the other side of the main body is an outer surface; the side of the skin layer facing away from the support layer is the outer surface, and the side of the support layer facing away from the skin layer is the inner surface; the outer surface has a dense surface, and the thickness of the support layer is 68 μm - 118 μm (such as 68 μm, 70 μm, 75 μm, 80 μm, 85 μm, 90 μm, 95 μm, 100 μm, 105 μm, 110 μm, 115 μm or 118 μm); the ratio of the thickness of the support layer to the thickness of the PMP hollow fiber membrane is not less than 0.95 (such as 0.95, 0.96, 0.97, 0.98, 0.99 or 0.995); the helium flux of the PMP hollow fiber membrane is 1.5 ml / (cm 2 ×min×bar) - 3 ml / (cm 2 ×min×bar) (such as 1.5, 2, 2.5 or 3 ml / (cm 2 ×min×bar)); the BET specific surface area of the PMP hollow fiber membrane is 30 m 2 / g - 60 m 2 / g (such as 30 m 2 / g, 40 m 2 / g, 50 m 2 / g or 60 m 2 / g).

[0007] In related technologies, in order to endow the oxygenation membrane with excellent oxygenation performance, it is generally desired that the PMP hollow fiber membrane has good gas selectivity (separation ratio of carbon dioxide to oxygen) and oxygen transport efficiency (oxygen flux). However, generally speaking, for example, according to the Roberson curve, when the hollow fiber membrane has a high separation ratio of carbon dioxide to oxygen, its oxygen flux is often too low to meet the actual requirements, which to a certain extent affects the oxygenation performance. Through research, it is found that gas diffusion in the hollow fiber membrane mainly involves two mechanisms: solution-diffusion and Knudsen diffusion. Among them, solution-diffusion is that the gas "dissolves" in the hollow fiber membrane and diffuses according to the concentration gradient; while Knudsen diffusion is the diffusion flow generated by the collision of gas molecules with the pore wall in a narrow space. In order to be able to improve the oxygen flux while ensuring a high separation ratio of carbon dioxide to oxygen, the inventors of the present invention conducted a large number of experiments and found that on the basis of a dense outer surface, by improving the pore structure of the support layer, the oxygen can diffuse reasonably in the support layer, thereby increasing the diffusion rate of oxygen in the support layer. Then, on the basis of realizing the rapid exchange of oxygen and carbon dioxide (with a high separation ratio), a high oxygen flux can also be ensured.

[0008] First, the hollow fiber membrane in the present invention includes a skin layer and a support layer. Among them, the skin layer has a dense outer surface, that is, there are almost no holes on the outer surface, so that when various gases (such as oxygen, carbon dioxide, etc.) pass through the outer surface, the gas exchange mainly relies on solution-diffusion. At this time, the hollow fiber membrane has a high separation ratio of carbon dioxide and oxygen. On the basis of the dense outer surface, we need to further improve the support layer to increase the oxygen flux of the hollow fiber membrane, as follows:

[0009] First, regulate the thickness of the support layer and the thickness ratio of the support layer in the hollow fiber membrane. Since the support layer is a region with relatively large internal pores in the hollow fiber membrane (there are almost no holes and very low porosity in the skin layer), the existence of internal pores is the basis for the gas to mainly diffuse through Knudsen diffusion. Therefore, in a suitable support layer structure, oxygen and carbon dioxide mainly diffuse through Knudsen diffusion. At this time, oxygen with a relatively small molecular weight diffuses faster than carbon dioxide. In order to increase the oxygen flux of the hollow fiber membrane, in the present invention, the thickness ratio of the support layer in the hollow fiber membrane accounts for a relatively large proportion, that is, 0.95 or more. Such a thickness ratio can not only ensure that the hollow fiber membrane has a high separation ratio of carbon dioxide to oxygen, but also increase the oxygen flux. In addition, on the basis of the relative proportion of the support layer, the absolute thickness of the support layer is also limited. In the present invention, the thickness of the support layer is 68 μm - 118 μm, which on the one hand enables the hollow fiber membrane to have a high oxygen flux and at the same time does not affect the practicality of the hollow fiber membrane (because when the thickness of the support layer and the overall thickness of the membrane are too low, the performance of the membrane such as tensile strength, pressure resistance strength, and plasma penetration time will be significantly reduced).

[0010] Second, the BET specific surface area of ​​the hollow fiber membrane is regulated. The specific surface area refers to the total area of ​​an object per unit mass, including the external surface area and the internal surface area. On the basis of the support layer having an appropriate absolute thickness and relative thickness, the present invention regulates the BET specific surface area of ​​the hollow fiber membrane to be 30 m 2 / g-60m 2 / g, the specific surface area is relatively high, but not too high. Our research and development found that the specific surface area within the above range means that the hollow fiber membrane has more surface area for gas exchange. That is, when gases such as oxygen and carbon dioxide are exchanged on the surface of the hollow fiber membrane, more sites can be provided to allow the gas to fully contact the membrane material, thereby improving the oxygen intake and carbon dioxide discharge efficiency, and enhancing the oxygenation performance of the oxygenation membrane. At the same time, the mass transfer process can also be optimized: a larger specific surface area can shorten the diffusion path of gas molecules in the membrane, making it easier for gas (especially oxygen) to be transferred from one side of the membrane to the other, speeding up the mass transfer rate, and thus increasing the amount of gas exchange per unit time of the oxygenation membrane, which is crucial to maintaining a good oxygenation effect. In addition, the specific surface area can also reflect the pore structure of the membrane (especially the membrane pore structure of the support layer) to a certain extent: the specific surface area is closely related to the pore structure of the membrane. Generally speaking, oxygenation membranes with suitable pore size and distribution have a larger specific surface area. The hollow fiber membrane of the present invention has a suitable specific surface area, which to a certain extent reflects that the membrane pores inside the support layer are relatively small and numerous, which is more conducive to the rapid permeation of oxygen through the support layer and improves the oxygen flux of the membrane. And our research found that the higher the specific surface area is, the better it is. On the contrary, too high a specific surface area will affect the gas exchange capacity, that is, the separation ratio of carbon dioxide to oxygen will be significantly reduced, which will in turn lead to a decrease in oxygenation capacity, and the mechanical properties of the membrane will also be significantly reduced. The regulation of the specific surface area in the present invention is selected based on the structure of the dense outer surface and a certain thickness of the support layer.

[0011] Third, regulate the helium flux of the hollow fiber membrane; in the oxygenation membrane technology of the prior art, technicians in this field are mainly concerned with oxygen and carbon dioxide, at most the gas flux of nitrogen and the corresponding separation ratio, but have hardly paid attention to the gas flux of helium. After continuous research, the present invention has found that when the outer surface is relatively dense, the support layer thickness is certain, and it has a high specific surface area, further regulating the helium flux will have a greater impact on the oxygenation performance of the hollow fiber membrane; this may be because helium is much smaller than gases such as oxygen and carbon dioxide in terms of molecular size and mass; therefore, the pore structure, pore size, various defects and other factors of the membrane will have a greater impact on the helium flux; therefore, in the present invention, the helium flux is used to characterize the pore structure and pore size of the membrane, and at the same time reflect the overall defect of the membrane to a certain extent; finally, after research, the helium flux of the membrane regulated in the present invention is 1.5ml / (cm2 ×min×bar)-3ml / (cm 2 ×min×bar), which means that the hollow fiber membrane of the present invention has a more open pore structure, further indicating that there are more pore structures in the support layer of the hollow fiber membrane, and the pore diameter of this pore structure is smaller, which is conducive to the rapid Knudsen diffusion of oxygen in the support layer. Finally, it is beneficial for the membrane to have a good oxygen flux on the basis of a high separation ratio.

[0012] Through a large number of studies, the present invention also finds that under certain conditions, the specific surface area of the membrane and the helium flux have a synergistic effect. On the one hand, it can improve the overall mass transfer performance of the membrane. As mentioned above, the larger the specific surface area of the membrane, the more channels and interfaces available for gas transmission. At the same time, when the helium flux is within a specific range, it indicates that oxygen and carbon dioxide can pass through the membrane more efficiently for exchange, and it helps to transport metabolic products such as carbon dioxide from the blood side to the gas phase side and expel them more quickly, so as to achieve more effective gas exchange and maintain the balance of gas components in the blood. Therefore, synergistically regulating the specific surface area of the membrane and the helium flux can effectively improve the oxygenation performance of the membrane, making it better meet the requirements of rapid blood oxygenation in medical applications such as ECMO. On the other hand, it can also improve the overall mechanical strength of the membrane. By synergistically regulating the specific surface area of the membrane and the helium flux, the pore structure of the membrane can be made more uniform and stable, which is beneficial to enhancing the tensile strength and flexibility of the membrane, thereby improving the durability of the membrane during use. In addition, synergistically controlling the two can indicate that the membrane has fewer defects, which is also beneficial to improving the mechanical strength of the membrane and reducing the risk of membrane rupture or damage.

[0013] In addition, due to the strong rigidity of the PMP material itself, during the process of weaving the membrane filaments into a membrane cloth and the subsequent installation and transportation of the membrane cloth, filament breakage is likely to occur. The present invention finds that by synergistically regulating the specific surface area, helium flux and support layer thickness, the toughness of the hollow fiber membrane is unexpectedly improved, its elongation at break is increased, and the probability of filament breakage is greatly reduced. This is probably because: as mentioned above, both the helium flux and the specific surface area can to a certain extent reflect the pore structure of the support layer. When both the helium flux and the specific surface area are within a specific range, it indicates to a certain extent that the number of pore structures in the support layer is large and the pore diameter is small. At this time, it is beneficial to improve the toughness of the membrane filaments, thereby improving the overall toughness of the membrane cloth. On this basis, further regulating the thickness of the support layer, when the thickness of the support layer is within a specific range, it can significantly reduce the resistance of gas diffusion in the membrane and ensure its mechanical strength; making its toughness match the thickness, which can improve its mechanical strength while ensuring the toughness of the membrane filaments, so that the membrane filaments are woven into a membrane cloth and the membrane cloth is not easily broken during subsequent installation and transportation.

[0014] In summary, by controlling the outer surface of the hollow fiber membrane to be dense, with a moderate support layer thickness and a relatively large thickness ratio, and having an appropriate helium flux and BET specific surface area, the hollow fiber membrane not only has a high carbon dioxide and oxygen separation ratio, but also improves the oxygen flux to a certain extent, enhances the oxygenation ability of the hollow fiber membrane, further meets the actual needs, and can basically be used as an "artificial lung" to provide arterial blood for human organs and enable human organs to still work normally. At the same time, it unexpectedly improves the toughness of the hollow fiber membrane.

[0015] In the present invention, the dense surface has the conventional meaning in the art, which means that the pore area ratio on the outer surface is not higher than 1% (i.e., less than or equal to 1%); the pore area ratio on the outer surface can be measured by conventional methods in the art. Specifically, a scanning electron microscope (SEM) is used. In the electron micrograph at a magnification of 10,000 times, at least 5 outer surfaces with an area preferably of 2 μm × 2 μm (the area can also be adjusted accordingly) are randomly selected, the pore area ratio is measured and calculated, and the average value is taken.

[0016] In the present invention, the hollow fiber membrane is integrally formed without going through the "composite" process. Therefore, by observing its main structure, it can be clearly seen that the hollow fiber membrane has a two-layer structure with completely different pore structures. Among them, the layer with a relatively high cross-sectional pore ratio is the support layer, and the layer with a relatively low cross-sectional pore ratio is the skin layer. The boundary between the skin layer and the support layer can be determined through the following steps:

[0017] First, use SEM to conduct a detailed morphological characterization of the part near the outer surface in the cross-section of the hollow fiber membrane from the inner surface to the outer surface. To clearly present the microscopic characteristics of the membrane structure, the magnification can be accurately set to 20,000 times (it can also be other multiples) to obtain a high-quality micrograph.

[0018] Second, on the obtained micrograph, carefully observe along the direction from the outer surface to the inner surface. The side of the pore that can be clearly identified by the naked eye and is close to the outer surface is used as the key interface, which is defined as interface P1. The area covered from the outer surface to interface P1 is the skin layer.

[0019] To more intuitively show the position of this interface, Figure 1The SEM micrograph of the cross-section of the hollow fiber membrane in one example of the present invention along the direction from the inner surface to the outer surface is given. In the figure, the interface pointed by the red arrow is the interface P1. It should be particularly noted that due to the influence of various factors during the preparation process of the hollow fiber membrane, the distance from the interface P1 to the outer surface is not fixed at different positions on its cross-section, which means that the shape of the interface P1 is not a simple circular arc curve, but may present a more complex geometric shape. That is, at the microscopic level, there are certain differences in the skin layer thickness at different positions and it is not equal everywhere.

[0020] Those skilled in the art should understand that in addition to the methods described above for determining the boundary between the skin layer and the support layer and obtaining relevant parameters, other suitable measurement means can also be adopted according to the actual situation to complete the same task. The measurement means introduced here is only for reference and aims to provide a feasible way for relevant research and applications.

[0021] In the present invention, when measuring the thickness of the support layer and the thickness of the PMP hollow fiber membrane, first, a scanning electron microscope can be used to comprehensively and carefully characterize the morphology of the membrane structure; to ensure the accuracy and representativeness of the measurement results, multiple measurement sites (preferably more than 5) should be selected on the membrane structure, and there should be a uniform and reasonable interval between each measurement site. For example, according to the actual size and performance requirements of the membrane, the site interval is preferably 1 - 5 μm (the specific value can be scientifically set according to the characteristics of the membrane and industry general standards to meet the measurement accuracy requirements in different application scenarios); after completing the site selection, for each site, computer software (such as Matlab, NIS-Elements, and NanoMeasurer, etc.) can be used for digital analysis and measurement. Through the image recognition and data analysis functions of the software, the thickness data corresponding to each site can be obtained. Manual measurement can also be adopted, with the help of professional measurement tools, and the data of each measurement site can be recorded according to the standard measurement process. After completing the measurement and calculation of multiple sites, statistical analysis is carried out on the series of thickness data obtained, and the arithmetic mean value is calculated to determine the thickness of the support layer and the PMP hollow fiber membrane; in addition, the overall thickness of the hollow fiber membrane can also be calculated by measuring the outer diameter and inner diameter of the membrane and using the formula (outer diameter - inner diameter) ÷ 2 to obtain the thickness data for each site respectively. Those skilled in the art can understand that in addition to the above methods, other suitable measurement means can also be used to obtain this parameter, and the measurement methods listed here are only for reference.

[0022] In the present invention, the BET specific surface area of the PMP hollow fiber membrane can be obtained by conventional testing methods in the art, such as the gas adsorption method.

[0023] As a further improvement of the present invention, the porosity of the PMP hollow fiber membrane is 40%-70% (for example, 40%, 50%, 60% or 70%); the cross-section of the support layer in the membrane thickness direction is a first cross-section, and there are several first holes on the first cross-section, and the pore size change gradient of the first holes on the first cross-section is 1.1 nm / 1 μm - 5.5 nm / 1 μm (for example, 1.1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5 or 5.5 nm / 1 μm); wherein, the pore size change gradient = (the SEM average pore size of the first holes in the area far from the skin layer - the SEM average pore size of the first holes in the area close to the skin layer) / the thickness of the support layer; the area close to the skin layer is the area formed within 5 μm from the boundary line between the skin layer and the support layer on the support layer; the area far from the skin layer is the area formed within 5 μm from the inner surface on the support layer.

[0024] Through research, it is found in the present invention that, on the premise of a dense outer surface, a moderate support layer thickness with a relatively large thickness ratio, and specific helium flux and BET specific surface area, by further regulating the overall porosity of the membrane and the pore size change gradient on the first cross-section, a multi-dimensional synergistic effect can be achieved, thereby further improving the gas transmission efficiency and mechanical stability of the hollow fiber membrane. The reason is as follows: when the porosity is 40%-70%, it indicates that on the basis of relatively small pore sizes in the support layer membrane pores, the number of membrane pores is relatively large. Such a structural design is conducive to reducing the diffusion path and resistance of gas molecules in the hollow fiber membrane, and providing a larger gas exchange surface area, thereby facilitating the improvement of gas transmission efficiency; and a suitable pore structure can provide better mechanical support, enhancing the pressure resistance and tensile resistance of the membrane.

[0025] The pore size change gradient indicates that in the support layer, in the direction from the outer surface to the inner surface, the pore size of the membrane pores gradually increases, and the increasing amplitude is relatively small, which further indicates that the pore sizes inside the support layer are relatively small and relatively uniform. Such a change gradient has the following advantages: First, it can enhance the molecular sieve effect of the hollow fiber membrane and improve its selectivity for gases; second, it can reduce the diffusion resistance of gases and increase the gas flux; third, such a change gradient is also conducive to optimizing the stress distribution. The smaller the pore size near the outer surface, the more conducive to improving the overall mechanical strength of the membrane; while the larger the pore size near the inner surface, the more conducive to reducing the overall brittleness; thus effectively avoiding the breakage and cracking of the membrane layer during the use of the hollow fiber membrane, and the membrane filaments are less likely to break, and various processing treatments can be carried out; finally, it also helps to achieve the transition from dissolution-diffusion to convection between the skin layer and the support layer, optimizing the gas transmission efficiency.

[0026] Moreover, the pore size change gradient has a synergistic effect with the helium flux and the specific surface area: on the one hand, when the helium flux of the hollow fiber membrane is within a specific range, by regulating the pore size change gradient, it is possible to further improve the oxygen flux while reducing the risk of plasma leakage. On the other hand, when the BET specific surface area of the hollow fiber membrane is within a specific range, by regulating the pore size change gradient, it is possible to further optimize the gas-blood contact area and diffusion path, improve the carbon dioxide clearance rate, and the oxygenation performance of the hollow fiber membrane.

[0027] Therefore, an appropriate porosity can provide more gas transmission channels, making it easier for oxygen to enter the blood and carbon dioxide to be removed; combined with an appropriate pore size change gradient, it is also beneficial to gas diffusion, enabling the gas to pass through the membrane material more quickly, thereby improving the gas transmission efficiency. At the same time, the regulation of the porosity and the pore size change gradient can make the microstructure of the hollow fiber membrane more reasonable and stable, enabling it to better withstand external pressure and tension, thereby improving the mechanical stability of the membrane and reducing the possibility of problems such as rupture and tearing during use.

[0028] In the present invention, the porosity of the PMP hollow fiber membrane can be measured by conventional methods in the art, and the present invention measures it by using the mercury intrusion method.

[0029] In the present invention, the specific positions of the near-cortex region and the far-cortex region are defined. The near-cortex region refers to the region formed within 5 μm from the boundary line between the cortex and the support layer on the support layer; the far-cortex region refers to the region formed within 5 μm from the inner surface on the support layer. The pore size change gradient refers to the ratio of the difference between the SEM average pore size of the first pores in the far-cortex region and the SEM average pore size of the first pores in the near-cortex region to the thickness of the support layer.

[0030] In the present invention, the aperture change gradient of the first hole on the first cross-section is obtained, for example, by the following method: First, use SEM to conduct a comprehensive and detailed morphological characterization of the first cross-section; to ensure the accuracy and representativeness of the measurement results, at least 5 mirror images with an area preferably of 2μm×2μm near the cortical region (there is a certain interval between the mirror images to ensure statistical scientificity) and mirror images far from the cortical region (there is a certain interval between the mirror images to ensure statistical scientificity) should be selected on the first cross-section respectively; Subsequently, use computer software (such as Matlab, NIS-Elements, etc.) or manual measurement to measure the SEM average aperture of the first hole on each mirror image (when the shape of the first hole is a regular circle, the aperture of the first hole refers to the diameter of the circle; when the shape of the first hole is an ellipse, the aperture of the first hole refers to half of the sum of the major axis and the minor axis; when the shape of the first hole is not a "regular circle", the longest line segment among the two-point line segments on the outer periphery of the hole can be used as the major axis, and then measure the longest line segment among the line segments connecting two points on the outer periphery of the hole that intersects perpendicularly with the major axis as the minor axis, and the aperture of the first hole is half of the sum of the major axis and the minor axis), conduct several tests (preferably more than 10 times, and the specific number of times depends on the situation), take the average value, so as to obtain the SEM average aperture of the first hole in different regions; Finally, calculate to obtain the aperture change gradient of the first hole on the first cross-section.

[0031] As a further improvement of the present invention, the SEM average aperture of the first hole on the near-cortical region is 100nm - 400nm (for example, 100nm, 200nm, 300nm or 400nm), and the pore density on the near-cortical region is 40 holes / 25μm 2 -180 holes / 25μm 2 (for example, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170 or 180 holes / 25μm 2 )。

[0032] The average SEM pore size and pore density of the first hole near the cortex can further reflect the membrane pore structure of the support layer, and further specifically explain that the pore size of the first hole in the support layer is small, and the number of holes is large, which increases the effective surface area of ​​the membrane and provides more gas exchange sites. At the same time, more holes mean that oxygen and carbon dioxide have more channels to pass through the membrane, which improves the gas exchange efficiency. In addition, the small pore size reduces the diffusion distance of gas molecules in the membrane, accelerates the gas exchange rate, and is conducive to the rapid penetration of oxygen into the cortex through the support layer, thereby improving the oxygen flux of the membrane. In addition, the area near the cortex has many and relatively small pores (the area near the cortex can be considered as the area with the smallest pore size in the support layer, and can also be considered as the "transition layer" between the support layer and the cortex). By regulating the gas diffusion path, a gradient diffusion network is formed to balance the gas permeation rate and selectivity, and at the same time, it has a certain optimization effect on the transmembrane pressure difference; in addition, it can also enhance the compressive strength of the outer surface, thereby improving the overall mechanical strength and long-term stability of the hollow fiber membrane and enhancing the pressure resistance. The porous structure with small pores forms more support points in the support layer, which improves the membrane's ability to resist pressure and is beneficial to improving the overall mechanical strength of the membrane. In addition, our research found that when the SEM average pore size and pore density of the first hole near the cortical area are not within a specific range, it will affect the gas exchange capacity, resulting in a significant decrease in the separation ratio of carbon dioxide and oxygen, which in turn leads to a decrease in oxygenation capacity, and the mechanical properties of the membrane will also be significantly reduced.

[0033] As a further improvement of the present invention, the SEM average pore size of the first hole in the region away from the cortex is 250nm-800nm ​​(for example, 250nm, 300nm, 400nm, 500nm, 600nm, 700nm or 800nm), and the pore density in the region away from the cortex is 30 / 25μm 2 -140 pieces / 25μm 2 (For example, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130 or 140 per 25 μm 2 ).

[0034] On the premise that the SEM average pore diameter and pore density of the first pores in the area near the skin layer are within a specific range, further regulating the SEM average pore diameter and pore density of the first pores in the area far from the skin layer can further illustrate that the overall pore diameter of the first pores in the support layer is small, but the pore diameter of the first pores in the area far from the skin layer is larger than that in the area near the skin layer (in the area far from the skin layer, the pore diameter of the first pores will be relatively larger; the area far from the skin layer can be considered the area with the largest inner membrane pores in the support layer), and the number of pores is large. Such a setting can optimize the stress distribution and can effectively absorb external pressure fluctuations to a certain extent, thereby avoiding stress concentration and the small pore area near the area near the skin layer; at the same time, within this pore diameter and pore density range, the pressure resistance of the inner surface of the hollow fiber membrane is also high. And such a setting can also form a pore diameter gradient with a small change gradient. Such a structure not only improves the overall toughness of the membrane and makes the membrane filaments not easy to break; it also further improves the gas selectivity of the hollow fiber membrane, is beneficial to reducing the diffusion resistance to gas, accelerates the gas diffusion rate, is beneficial to improving the overall permeability of the hollow fiber membrane, enables oxygen to enter the inside of the membrane filaments faster, and ensures faster removal of carbon dioxide. However, we also found that if the SEM average pore diameter and pore density of the first pores in the area far from the skin layer are both too large (for example, the SEM average pore diameter is greater than 800 nm, and the pore density is greater than 140 per 25 μm 2 ), it will cause too low pressure resistance of the inner surface, resulting in poor mechanical strength and toughness of the whole membrane, seriously affecting the practicality of the hollow fiber membrane. In addition, we found through research that when there are appropriate pore diameters and pore densities in the areas near the skin layer and far from the skin layer in the support layer acting together, it is more beneficial for the hollow fiber membrane to have appropriate helium flux and specific surface area, and at the same time have a higher porosity.

[0035] In the present invention, the pore density in the area near the skin layer and the pore density in the area far from the skin layer can be obtained by testing through conventional methods in the art. For example, SEM is used to perform morphological characterization on the areas near the skin layer and far from the skin layer of the hollow fiber membrane respectively to obtain corresponding SEM images. An area of 50 μm 2 (5 μm multiplied by 10 μm) can be selected (the specific area depends on the situation), and then the number of the first pores in this area is counted. After several tests (preferably more than 10 times, the specific number depends on the situation), the average value is taken to obtain the pore density of the first pores in different areas. It should be noted that when 1 / 2 or more of the area of the first pore is within the selected 50 μm 2 area, it is recorded as 1; when less than 1 / 2 of the area of the first pore is within the selected 50 μm 2 area, it is recorded as 0.

[0036] As a further improvement of the present invention, the support layer has support fibers for forming a porous structure; the average SEM width of the support fibers in the region close to the skin layer is 50 nm - 130 nm (for example, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm or 130 nm). The average SEM width of the support fibers in the region far from the skin layer is 70 nm - 150 nm (for example, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm or 150 nm), and the average SEM width of the support fibers in the region far from the skin layer is not less than the average SEM width of the support fibers in the region close to the skin layer.

[0037] As a further improvement of the present invention, the average SEM width of the support fibers in the region far from the skin layer is greater than the average SEM width of the support fibers in the region close to the skin layer.

[0038] It has been found through research that the average SEM width of the support fibers has a great influence on the mechanical strength of the hollow fiber membrane and the diffusion path of gases. When the average SEM width of the support fibers is too large (for example, the average width in the area close to the skin layer is greater than 130 nm, and the average width in the area far from the skin layer is greater than 150 nm), it is not conducive to gas diffusion and affects the gas movement speed. However, at this time, the support force for the membrane pores is strong, and the mechanical strength of the hollow fiber membrane is high. When the average SEM width of the support fibers is too small (for example, the average width in the area close to the skin layer is less than 50 nm, and the average width in the area far from the skin layer is less than 70 nm), the support force for the membrane pores is weak, resulting in insufficient mechanical strength of the hollow fiber membrane, increasing the difficulty of weaving the membrane filaments into a membrane cloth, and greatly reducing the practicality. Moreover, it is not sufficient to maintain normal gas diffusion, and the membrane pores are prone to collapse and deformation. In addition, by regulating the relationship between the average SEM width of the support fibers in the area far from the skin layer and the average SEM width of the support fibers in the area close to the skin layer, the overall mechanical strength and gas diffusion efficiency of the hollow fiber membrane can be further improved. The reason is as follows: First, as mentioned above, the larger the width of the support fibers, the stronger the support ability for the membrane, and the greater the overall mechanical strength of the membrane. Therefore, it is necessary to improve the support strength for the membrane in the area that is more affected by external stress (i.e., the area far from the skin layer). And the smaller the width of the support fibers, the better the flexibility of the membrane filaments. Therefore, it is necessary to improve the adaptability to the dynamic pressure fluctuation of blood flow in the area that is more affected by blood (i.e., the area close to the skin layer), and a relatively smaller support layer width is required. Second, the width of the support fibers can reflect the pore structure of the membrane to a certain extent. When the width of the support fibers is large, the pore diameter of the membrane is relatively large, which is suitable as the main channel for gas diffusion. Therefore, it is necessary to make the width of the support fibers in the area far from the skin layer larger, which is conducive to improving the gas exchange rate in the membrane, enabling oxygen to enter the interior of the membrane filaments faster, and enabling carbon dioxide to be removed as soon as possible. When the width of the support fibers is small, the pore diameter of the membrane is relatively small, which may be beneficial to further improving the separation ratio of carbon dioxide and oxygen of the hollow fiber membrane.

[0039] In the present invention, the average SEM width of the support fibers in the area close to the skin layer and the average SEM width of the support fibers in the area far from the skin layer can be obtained by testing through conventional methods in the art. For example, using SEM to perform morphological characterization on the areas close to the skin layer and far from the skin layer on the hollow fiber membrane respectively to obtain the corresponding SEM images. An area of 50 μm 2 (5 μm multiplied by 10 μm) (the specific area depends on the situation) can be selected, and then measured by using computer software (such as Matlab, NIS-Elements, etc.) or manually. Measure the width of the support fibers on this area, conduct several tests (preferably more than 10 times, the specific number depends on the situation), and take the average value to obtain the average SEM width of the support fibers in different areas.

[0040] As a further improvement of the present invention, within the support layer, the ratio of the SEM average width of the support fibers to the SEM average pore diameter of the first pores is the support coefficient Y; wherein, the support coefficient Y2 in the area far from the skin layer is 0.12 - 0.3 (for example, 0.12, 0.15, 0.2, 0.25 or 0.3).

[0041] The support coefficient Y2 has a great influence on the mechanical strength of the hollow fiber membrane, which is related to the pore stability in the area far from the skin layer and the pressure resistance of the inner surface of the membrane. When the support coefficient Y2 is too large (for example, greater than 0.3), the average pore diameter is relatively small compared to the average width, indicating that the overall mechanical strength of the hollow fiber membrane is good, but it will affect the gas permeation and is not conducive to the improvement of the oxygen flux; while when the support coefficient Y2 is too small (for example, less than 0.12), the average pore diameter is relatively large compared to the average width, which is not conducive to the structural stability and pressure resistance of the inner surface of the membrane. Therefore, by regulating Y2, the mechanical strength of the hollow fiber membrane can be further improved and it can have a higher oxygen flux.

[0042] As a further improvement of the present invention, the ratio of the support coefficient Y1 in the area close to the skin layer to the support coefficient Y2 in the area far from the skin layer is 1.01 - 2 (for example, 1.01, 1.05, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 or 2).

[0043] Within a certain range, Y1 needs to be larger than Y2. This is because the skin layer has a very low porosity, high mechanical strength and is relatively dense, and gas usually permeates in a dissolution-diffusion manner; while the support layer has a larger porosity, there are more gas flow paths, and its mechanical strength is lower than that of the skin layer, but it is convenient for gas permeation. Therefore, it is necessary to regulate the ratio of Y1 to Y2, which can provide a transition area for the conversion from the skin layer to the support layer. This transition area can not only achieve the gradient strengthening of mechanical properties, but also optimize the gas transmission efficiency, specifically as follows: First, the relatively dense structure (high support strength) can enhance the interfacial bonding force, prevent the separation of the skin layer and the support layer, and is conducive to improving the overall structural stability of the membrane; in addition, the blood is on the outer surface side of the hollow fiber membrane, so in order to further reduce the local stress concentration in the skin layer and increase the plasma penetration time, it is necessary to make the area close to the skin layer have a higher pressure resistance than the area far from the skin layer. Second, the area with low support strength is suitable as the main channel for gas diffusion. By regulating the ratio of Y1 to Y2, it helps to realize the conversion of the gas diffusion mode from the skin layer to the support layer, thereby optimizing the gas exchange efficiency and further improving the oxygenation performance.

[0044] As a further improvement of the present invention, a plurality of ventilation holes are provided on the inner surface; the average SEM pore diameter of the ventilation holes is 0.28 μm - 0.85 μm (for example, 0.28 μm, 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, 0.7 μm, 0.8 μm or 0.85 μm), and the hole area ratio of the ventilation holes on the inner surface is 5% - 25% (for example, 5%, 10%, 15%, 20% or 25%).

[0045] As a further improvement of the present invention, the ratio of the average SEM pore diameter of the ventilation holes to the average SEM pore diameter of the first holes on the area far from the cortex is 1.05 - 2.2 (for example, 1.05, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1 or 2.2).

[0046] The average SEM pore diameter of the ventilation holes on the inner surface can affect the rate of carbon dioxide and oxygen entering and leaving the membrane to a certain extent. Within a certain range, the larger the average SEM pore diameter, the faster oxygen can pass through the support layer to reach the cortex for exchange with blood, and the faster carbon dioxide can be discharged through the support layer, thereby increasing the oxygen entry speed and accelerating the carbon dioxide discharge speed, which is beneficial for the process of quickly supplying oxygen to patients and discharging carbon dioxide in emergency medical scenarios. At the same time, the hollow fiber membrane of the present invention also needs to have an appropriate number of ventilation holes on its inner surface, that is, the hole area ratio of the ventilation holes on the inner surface needs to be appropriate. Such a setting can cooperate with a specific average SEM pore diameter. On the premise of a specific average SEM pore diameter, further limiting the hole area ratio of the ventilation holes is more conducive to increasing the gas exchange surface area, thereby improving the gas exchange efficiency of the hollow fiber membrane; at the same time, it can also ensure the mechanical strength, durability and stability of the whole membrane. At the same time, when the specific average SEM pore diameter and hole area ratio are as above, the inner surface has higher pressure resistance and high industrial practicability. In addition, by limiting the ratio of the average SEM pore diameter of the ventilation holes to the average SEM pore diameter of the first holes on the area far from the cortex, the carbon dioxide and oxygen exchange rate can be further improved, making it easier for oxygen to enter the inside of the membrane filament and carbon dioxide to be discharged faster. This is because: the diffusion rate of gas is proportional to the partial pressure difference of the gas, the diffusion area and the solubility of the gas in the medium, and inversely proportional to the diffusion distance and the thickness of the medium. When the pore diameter ratio of the ventilation holes to the first holes on the area far from the cortex is within a certain range, the diffusion distance of the gas in the support layer is reduced. When oxygen diffuses from the outside of the membrane to the blood and carbon dioxide is discharged to the outside of the membrane, the larger ventilation hole diameter makes it easier for oxygen molecules to enter the blood and carbon dioxide molecules to be discharged outside the membrane, reducing the hindrance at the interface, thereby accelerating the diffusion speed of oxygen and carbon dioxide.

[0047] In the present invention, the SEM average pore diameter of the ventilation holes can be obtained by testing through conventional methods in the art. For example, using SEM to conduct a comprehensive and detailed morphological characterization of the inner surface of the hollow fiber membrane; to ensure the accuracy and representativeness of the measurement results, at least 5 mirror images with an area preferably of 2 μm × 2 μm need to be selected on the inner surface, and then measured using computer software (such as Matlab, NIS-Elements, etc.) or manually. Measure the SEM pore diameter of the ventilation holes on each mirror image (when the shape of the first hole is a regular circle, the pore diameter of the first hole refers to the diameter of the circle; when the shape of the first hole is an ellipse, the pore diameter of the first hole refers to half of the sum of the major axis and the minor axis; when the shape of the first hole is neither a "regular circle" nor an "ellipse", the longest line segment among the two-point line segments on the outer periphery of the hole can be used as the major axis, and then measure the longest line segment among the line segments connecting two points on the outer periphery of the hole that intersect perpendicularly with the major axis as the minor axis. The pore diameter of the first hole is half of the sum of the major axis and the minor axis). Conduct several tests (preferably more than 10 times, and the specific number depends on the situation), and take the average value to obtain the SEM average pore diameter of the ventilation holes.

[0048] The hole area ratio of the ventilation holes on the inner surface can be obtained by testing through conventional methods in the art. For example, first use SEM to characterize the inner surface of the hollow fiber membrane to obtain the corresponding SEM image, such as 100 μm 2 (10 μm multiplied by 10 μm) or 1 μm 2 (1 μm multiplied by 1 μm), and the specific area depends on the actual situation. Then use computer software or manually measure the total area of the ventilation holes on this area. Conduct several tests (preferably more than 10 times, and the specific number depends on the situation) to obtain the hole area ratio of the ventilation holes on the inner surface.

[0049] As a further improvement of the present invention, the inner surface has adjusting fibers for adjusting the surface roughness. The SEM average width of the adjusting fibers is greater than the SEM average width of the supporting fibers in the region away from the cortical region; and the SEM average width of the adjusting fibers is not less than 120 nm (such as 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm or 200 nm); the roughness of the inner surface is greater than the roughness of the outer surface.

[0050] The regulating fibers can be used to regulate the roughness of the inner surface. Therefore, their width also affects the oxygenation performance of the hollow fiber membrane. This is because during the use of the hollow fiber membrane, the removed carbon dioxide needs to be flushed away in a timely manner to maintain the carbon dioxide partial pressure difference across the membrane. Since the partial pressure difference driving carbon dioxide transport is inherently low, when carbon dioxide accumulates on the inner surface side, it will cause the partial pressure difference to further decrease, thereby affecting the transport of carbon dioxide. When the average SEM width of the regulating fibers is not less than 120 nm, it is beneficial to the removal of carbon dioxide on the inner surface side. The reasons are as follows: First, the rough surface increases the effective contact area, which has a positive impact on the removal of carbon dioxide; Second, the rough surface enhances the gas flow between gases, reduces the boundary layer thickness, and thus improves the efficiency of carbon dioxide removal. In addition, an appropriate width of the regulating fibers can also enhance the compressive resistance of the inner surface of the hollow fiber membrane.

[0051] In the present invention, the regulating fibers refer to the fibers protruding from the inner surface of the hollow fiber membrane. The average SEM width of the regulating fibers can be obtained by conventional methods in the art. For example, the inner surface of the hollow fiber membrane is characterized morphologically using SEM to obtain the corresponding SEM image. An area of 50 μm 2 (5 μm multiplied by 10 μm) (the specific area depends on the situation) can be selected, and then measured using computer software (such as Matlab, NIS-Elements, etc.) or manually. The widths of the regulating fibers in this area are measured, and several tests (preferably more than 10 times, the specific number depends on the situation) are carried out, and the average value is taken to obtain the average SEM width of the regulating fibers.

[0052] As a further improvement of the present invention, the ratio of the average SEM width of the regulating fibers to the average SEM pore diameter of the ventilation holes is the regulation coefficient Z, and the regulation coefficient Z is 0.3 - 0.8 (for example, 0.3, 0.4, 0.5, 0.6, 0.7, or 0.8); the pore size change gradient of the first holes on the first cross-section is 1.3 nm / μm - 3 nm / μm.

[0053] By regulating the regulation coefficient Z, the roughness of the inner surface can be further defined. As mentioned above, a certain roughness of the inner surface is beneficial to improving the efficiency of carbon dioxide removal. However, the roughness of the inner surface is not the greater the better. Because too large roughness may not only weaken the overall mechanical strength of the membrane, resulting in damage to the inner surface, but also be unfavorable for the removal of carbon dioxide. It may also lead to uneven gas distribution, resulting in too high or too low local gas concentration, which is also unfavorable for the removal of carbon dioxide. On this basis, further regulating the pore size change gradient of the first holes on the first cross-section and their synergistic regulation can further improve the oxygenation performance of the hollow fiber membrane.

[0054] As a further improvement of the present invention, the XRD crystallinity of the PMP hollow fiber membrane is 20%-55% (for example, 20%, 30%, 40%, 50% or 55%); the thickness of the skin layer is 0.2 μm-5 μm (for example, 0.2 μm, 0.5 μm, 1 μm, 2 μm, 3 μm, 4 μm or 5 μm); the separation ratio α(CO 2 / O 2 ) of the PMP hollow fiber membrane is not less than 1.8 (for example, 1.8, 2.1, 2.4, 2.6, 2.8 or 3).

[0055] In the present invention, the XRD crystallinity of the PMP hollow fiber membrane refers to obtaining the XRD diffraction pattern of the membrane by X-ray diffraction, and respectively calculating the diffraction peak area representing the crystal form and the sum of the diffraction peak area representing the crystal form and the diffraction peak area of the amorphous form. Through the diffraction peak area of the crystal form: the sum of the diffraction peak area of the crystal form and the diffraction peak area of the amorphous form, the XRD crystallinity value of the porous membrane is obtained. XRD crystallinity can reflect the proportion and order degree of the crystalline part in the membrane material. High crystallinity indicates a highly ordered internal structure of the membrane, and low crystallinity indicates a disordered internal structure of the membrane. When the XRD crystallinity of the hollow fiber membrane is in the range of 20%-55%, the chemical stability of the PMP material is relatively strong, and the stability of the membrane pores in the hollow fiber membrane is also relatively strong, indicating that the hollow fiber membrane can balance relatively high toughness and relatively high mechanical strength. In addition, since the diffusion rates of gases in the crystalline region and the non-crystalline region are different, therefore, the XRD crystallinity within a specific range indicates that the hollow fiber membrane has a relatively high separation ratio α(CO 2 / O 2 ). Since the skin layer is the region with the smallest pores inside the hollow fiber membrane, the thickness of the skin layer not only has a great influence on preventing blood cells and plasma proteins from infiltrating into the hollow fiber membrane, but also has a great influence on the oxygen flux of the hollow fiber membrane and the separation ratio of carbon dioxide to oxygen. When the thickness of the skin layer is too large (for example, greater than 5 μm), the time for carbon dioxide and oxygen to pass through the hollow fiber membrane by solution diffusion will be greatly increased, resulting in the inability of carbon dioxide to be discharged from the blood in time and the inability of oxygen to enter the blood in time, resulting in a significant decrease in oxygen flux, which will seriously affect its use; when the thickness of the skin layer is too small (for example, less than 0.2 μm), it will affect the degree of solution diffusion of gases. Although it is beneficial to the improvement of oxygen flux, the separation ratio of carbon dioxide to oxygen will decrease at this time; and the plasma penetration time of the membrane will be greatly shortened, affecting the service life. Controlling the separation ratio α(CO 2 / O 2 ) of the hollow fiber membrane can further ensure the rapid discharge of carbon dioxide. By synergistically controlling the XRD crystallinity, the thickness of the skin layer and the separation ratio α(CO 2 / O 2) It can further improve its oxygenation performance, enable the hollow fiber membrane to be used more reliably for a longer time, and has a longer plasma permeation time.

[0056] In the present invention, the XRD crystallinity of the PMP hollow fiber membrane can be obtained by testing with an X-ray diffractometer. The thickness of the skin layer can be obtained by testing with conventional methods in the art. For example: First, use SEM to perform high-resolution morphological characterization on the cross-sectional structure of the membrane to clearly present the microscopic structure of the skin layer and provide an accurate image basis for subsequent thickness measurement; then randomly select a measurement area along the direction perpendicular to the membrane thickness. Emphasize controlling the length of the measurement line in this direction ((it can be 10 μm or 5 μm, and the length of the measurement line can be flexibly determined according to the specific characteristics of the membrane and the measurement requirements); to ensure the independence and representativeness of the measurement data, a certain interval (preferably not less than 5 μm) needs to be maintained between each measurement area. This interval setting is related to the size and distribution of the membrane pores, which can effectively avoid data correlation caused by too small regional spacing, ensure that the measurement results meet statistical requirements, and more truly reflect the overall thickness characteristics of the skin layer; then for each selected measurement area, with the help of computer software (such as Matlab, NIS-Elements, etc.) or by manual measurement. To ensure the accuracy and reliability of the measurement results, each area is measured multiple times, and the number of measurements is preferably more than 10 times. The specific number of times can be reasonably adjusted according to the actual situation such as the uniformity of the membrane and the measurement accuracy requirements. Calculate the average value to obtain the thickness of the skin layer.

[0057] As a further improvement of the present invention, the PMP hollow fiber membrane is tested by the XRD method. The PMP hollow fiber membrane has a characteristic diffraction peak at a 2θ angle of 9° - 10° in the XRD diffraction pattern. The intensity of the characteristic diffraction peak accounts for 52% - 75% of the intensity of the overall crystalline diffraction peak (such as 52%, 55%, 60%, 65%, 70% or 75%), the full width at half maximum of the characteristic diffraction peak is 0.1° - 0.5° (such as 0.1°, 0.2°, 0.3°, 0.4° or 0.5°), and the crystal grains are not less than 250 Å; the PMP in the PMP hollow fiber membrane is in the tetragonal crystal system form.

[0058] Since PMP is a polymer with a relatively high degree of crystallinity and its molecular chain structure is relatively regular, it has a certain rigidity, but at the same time it is brittle. As a result, during the use of the oxygenation membrane, especially in some cases that require bending, stretching and other operations, cracks are likely to occur, and finally filament breakage occurs. Therefore, the PMP oxygenation membrane is prone to filament breakage, and it is necessary to further enhance the toughness of the PMP hollow fiber membrane. Through a large number of studies, it has been found that on the basis of a certain degree of crystallinity, further regulating the characteristic diffraction peaks of the XRD of the hollow fiber membrane can further improve its toughness. In the present invention, the hollow fiber membrane is tested by the XRD method to obtain its X-ray diffraction pattern. The contribution of the characteristic diffraction peak at the 2θ angle of 9°-10° is the largest in the overall pattern. Therefore, the characteristic diffraction peak at the 2θ angle of 9°-10° can be used to characterize the crystallization performance of the hollow fiber membrane. The full width at half maximum refers to the half-width of each diffraction peak in the XRD diffraction pattern, usually expressed in degrees or 2θ values. The full width at half maximum can be used to measure the change in lattice parameters in the crystal structure. Generally, the smaller the full width at half maximum of the diffraction peak, the more orderly the arrangement of atoms in the crystal and the fewer crystal defects; the larger the full width at half maximum, the more disorderly the arrangement of atoms in the crystal and the more crystal defects. Therefore, the full width at half maximum in the XRD pattern can be used to evaluate the quality and defect degree of the crystal. The full width at half maximum of the characteristic diffraction peak at the 2θ angle of 9°-10° in the present invention is within a suitable range, and the grain size is not less than 250 Å, which means that the arrangement of atoms in the crystal of the hollow fiber membrane of the present invention is more orderly and the crystal defects are fewer, which also means that the hollow fiber membrane has excellent toughness; at the same time, the more orderly the arrangement of atoms in the crystal and the fewer crystal defects, the better the mechanical strength and heat resistance of the whole membrane; in addition, the more orderly the arrangement of atoms in the crystal and the fewer crystal defects, it is beneficial to improve the plasma penetration time of the hollow fiber membrane, so that it can maintain good stability and mechanical strength for a long time. At the same time, further regulate PMP into a tetragonal crystal form. The PMP material with this structure performs better under mechanical stress and has more excellent heat resistance, which can further improve the mechanical strength and structural stability of the hollow fiber membrane.

[0059] As a further improvement of the present invention, the PMP hollow fiber membrane further satisfies one or more of the following characteristics: the tensile strength of the PMP hollow fiber membrane is not less than 80 cN, and the elongation at break is not less than 100%;

[0060] The plasma penetration time of the PMP hollow fiber membrane is not less than 48 hours, preferably not less than 96 hours;

[0061] At 1.6 m 2When the blood flow rate is 5 L / min and the blood is treated with the PMP hollow fiber membrane, the oxygen saturation of arterial blood is not less than 99%, the oxygen partial pressure is not less than 150 mmHg, the carbon dioxide partial pressure is not higher than 46 mmHg; and the end-tidal carbon dioxide concentration is not less than 29 mmHg.

[0062] The hollow fiber membrane of the present invention has obtained the following results through various performance tests: the tensile strength of the PMP hollow fiber membrane is not less than 80 cN, and the elongation at break is not less than 100%; this shows that the hollow fiber membrane of the present invention has good mechanical properties and high industrial practical value, and can fully meet the market demand. The plasma penetration time of the PMP hollow fiber membrane is not less than 48 hours, preferably not less than 96 hours. This shows that the hollow fiber membrane of the present invention is more reliable to use and has a long service life. At 1.6 m 2 When the blood flow rate is 5 L / min and the blood is treated with the PMP hollow fiber membrane, the oxygen saturation of arterial blood is not less than 99%, the oxygen partial pressure is not less than 150 mmHg, the carbon dioxide partial pressure is not higher than 46 mmHg; and the end-tidal carbon dioxide concentration is not less than 29 mmHg. This shows that the hollow fiber membrane of the present invention has appropriate oxygen and carbon dioxide mass transfer rates and a high separation ratio, so that carbon dioxide in the blood can be quickly discharged, and oxygen can enter the blood at an appropriate speed to achieve ideal gas exchange; and through the oxygenation performance test, the oxygenation membrane has high oxygenation performance, high oxygen saturation, and high oxygen partial pressure (the higher the oxygen partial pressure, the better the oxygenation performance), the carbon dioxide partial pressure in the blood is very low, and the end-tidal carbon dioxide partial pressure is very high, indicating that carbon dioxide can be completely discharged from the blood as quickly as possible, truly realizing extracorporeal membrane oxygenation and / or extracorporeal carbon dioxide removal, and realizing extracorporeal life support.

[0063] The second aspect of the present invention provides a preparation method of the asymmetric PMP hollow fiber membrane for blood oxygenation described in the first aspect of the present invention.

[0064] The preparation method includes the following steps:

[0065] Step 1: Heat and plasticize PMP, and then dissolve it in a first solvent system containing compound A and compound C for kneading to obtain a homogeneous casting solution; the solid content (mass content) of PMP in the casting solution is 30%-49% (for example, 30%, 35%, 40%, 45% or 49%); wherein, compound A is a strong solvent for PMP, and compound C is a non-solvent for PMP; the mass content of compound C in the first solvent system is 5%-30% (for example, 5%, 10%, 15%, 20%, 25% or 30%);

[0066] Step 2: Extrude the casting solution under the die head to form a molded product with an inner surface and an outer surface; wherein, the inner core liquid is a second solvent system containing Compound A and Compound B; Compound B is a poor solvent for PMP, and the mass content of Compound B in the second solvent system is 5%-20% (such as 5%, 10%, 15% or 20%); the temperature of the inner core liquid is 60°C - 140°C lower than the extrusion temperature (such as 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, 120°C, 130°C or 140°C);

[0067] Step 3: Perform preliminary phase separation on the molded product in the air section, wherein the temperature of the air section is 10°C - 80°C (such as 10°C, 20°C, 30°C, 40°C, 50°C, 60°C, 70°C or 80°C), and the length of the air section is 5 mm - 50 mm (such as 5 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm, 35 mm, 40 mm, 45 mm or 50 mm);

[0068] Step 4: Cool and phase-separate the preliminarily phase-separated molded product with coolant Compound C to obtain a green film; wherein the cooling temperature is 3°C - 40°C (such as 3°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C or 40°C), and the distance of the cooling phase separation is 1 m - 10 m (such as 1 m, 2 m, 3 m, 4 m, 5 m, 6 m, 7 m, 8 m, 9 m or 10 m);

[0069] Step 5: Remove Compound A, Compound B, and Compound C from the green film to obtain a raw film;

[0070] Step 6: Dry and shape the raw film to obtain the asymmetric PMP hollow fiber membrane.

[0071] In the present invention, Compound A used in the first solvent system in Step 1 and Compound A used in the second solvent system in Step 2 can be the same substance or different substances. Similarly, Compound C used in Step 4 and Compound C used in the first solvent system in Step 1 can be the same substance or different substances.

[0072] In the present invention, "removing Compound A, Compound B, and Compound C from the green film" in Step 5 refers to removing Compound A and Compound C in the first solvent system in Step 1, Compound A and Compound B in the second solvent system in Step 2, and Compound C in Step 4.

[0073] As a further improvement of the present invention, the compound A includes one or more of dioctyl adipate, di-n-octyl phthalate, bis(2-ethylhexyl) adipate, and diisooctyl phthalate; the compound B includes one or more of N,N-bis(2-hydroxyethyl) cetylamine, methyl-12-hydroxystearic acid, paraffin oil, dibutyl sebacate, dibutyl phthalate, diethyl phthalate, and oleic acid amide; the compound C includes one or more of mineral oil, palm oil, dimethyl phthalate, dimethyl carbonate, and glyceryl triacetate.

[0074] As a further improvement of the present invention, the temperature of the kneading in step one is 210°C - 270°C (for example, 210°C, 220°C, 230°C, 240°C, 250°C, 260°C, or 270°C), and the temperature of the extrusion in step two is 220°C - 250°C (for example, 220°C, 230°C, 240°C, or 250°C).

[0075] As a further improvement of the present invention, the cooling temperature in step four is 10°C - 50°C lower than the temperature of the air section in step three (for example, 10°C, 20°C, 30°C, 40°C, or 50°C).

[0076] As a further improvement of the present invention, the cooling temperature in step four is 60°C - 120°C lower than the temperature of the inner core liquid in step two (for example, 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, or 120°C).

[0077] As a further improvement of the present invention, the removal of compound A, compound B, and compound C from the green film in step five specifically refers to extracting the green film with an extraction liquid at a temperature of 60°C - 80°C for 4h - 8h; wherein, the extraction liquid is one or more of isopropanol, ethanol, and acetone.

[0078] As a further improvement of the present invention, the temperature of the extrusion is 5°C - 25°C lower than the temperature of the kneading (for example, 5°C, 10°C, 15°C, 20°C, or 25°C).

[0079] As a further improvement of the present invention, in step six, the drying and shaping includes heat drying and heat setting. Specifically, the original film is first subjected to heat drying treatment. The temperature of the heat drying is 40°C - 60°C (such as 40°C, 45°C, 50°C, 55°C or 60°C), and the time of the heat drying is 60 min - 120 min (such as 60 min, 70 min, 80 min, 90 min, 100 min, 110 min or 120 min). Then, the original film after the heat drying treatment is subjected to heat setting treatment. The temperature of the heat setting is 80°C - 120°C higher than the temperature of the heat drying (such as 80°C, 90°C, 100°C, 110°C or 120°C), and the time of the heat setting is 5 s - 20 s (such as 5 s, 10 s, 15 s or 20 s).

[0080] The present invention prepares a hollow fiber membrane by the thermally induced phase separation method. The first step is to heat and plasticize PMP, and then dissolve it into a specific solvent system (a combination of a strong solvent and a non-solvent of PMP), and carry out kneading at a temperature of 210°C - 270°C and a kneading pressure of 2 MPa - 5 MPa, so that PMP is uniformly dispersed in the first solvent system. On the one hand, it is convenient to form a uniform casting solution, and on the other hand, it can combine with the subsequent corresponding phase separation process, so as to facilitate obtaining a hollow fiber membrane with better integrity and uniformity. The present invention adopts a first solvent system of "strong solvent + non-solvent", and the content of the strong solvent in the first solvent system is greater than that of the non-solvent, which is more conducive to the uniform dispersion of PMP in the solvent system, and further ensures the integrity of the membrane filaments and the uniformity of the membrane pores. In addition, a certain amount of non-solvent needs to be added to the first solvent system of the present invention, which can produce a synergistic effect with the higher PMP solid content and the subsequent specific phase separation process, ensuring that the overall phase separation speed of the hollow fiber membrane is relatively fast, and no large pores will be generated in the support layer, and the outer surface is relatively dense. And we have found that the appropriate PMP solid content in the casting solution is 30% - 49%, preferably 35% - 45%; this is conducive to rapid phase separation, so that the membrane as a whole has a smaller pore size, and the skin layer basically has no pores and has a dense outer surface, which is not only conducive to improving the separation ratio of carbon dioxide and oxygen, but also ensures the plasma penetration time, and also has a good porosity. If the solid content is too low (for example, less than 30%), it is not easy to form small pores, and even it is easy to cause pores with a certain pore size in the skin layer, especially on the outer surface; while if the solid content is too high (for example, greater than 49%), the film-making difficulty will be greatly increased, and at the same time the porosity will be significantly reduced, resulting in poor toughness of the whole membrane. It can be understood that antioxidants, nucleating agents, fillers and other additives can also be added to the casting solution according to actual needs.

[0081] In the present invention, a strong solvent for PMP means that at 1 atmosphere (101.325 kPa), PMP with a solid content of 25% can be completely dissolved at a temperature of T1, where T1 ≤ the melting point of PMP at 1 atmosphere + 30°C; that is, a strong solvent for PMP means that PMP with a solid content of 25% can be completely dissolved in this solvent when the temperature is within 30°C above its melting point (when the temperature is within Tm + 30°C). A weak solvent for PMP means that at 1 atmosphere (101.325 kPa), PMP with a solid content of 25% can be completely dissolved at a temperature of T2, where the melting point of PMP at 1 atmosphere + 30°C < T2 ≤ the melting point of PMP at 1 atmosphere + 50°C; that is, a weak solvent for PMP means that PMP with a solid content of 25% can be completely dissolved in this solvent when the temperature is within 50°C above its melting point (when the temperature is within Tm + 30°C to Tm + 50°C).

[0082] A non - solvent for PMP means that at 1 atmosphere (101.325 kPa), PMP with a solid content of 25% can be completely dissolved at a temperature of T3, where T3 > the melting point of PMP at 1 atmosphere + 50°C; that is, a non - solvent for PMP means that PMP with a solid content of 25% can be completely dissolved in this solvent only when the temperature exceeds 50°C above its melting point (when the temperature exceeds Tm + 50°C).

[0083] In the second step, the casting solution is extruded under the die head to form a molded article having an inner surface and an outer surface; this molded article is a hollow fiber membrane; the casting solution is extruded through the middle cavity of the hollow fiber die head, and the middle cavity serves as the inner core, playing a role in forming and stabilizing the hollow fiber membrane cavity. During the extrusion process, the extruded hollow fiber membrane (molded article) has a surface facing the cavity, i.e., the inner surface, and a surface opposite to the cavity, i.e., the outer surface, which is separated from the inner surface by the hollow fiber membrane wall. In the prior art, an inert gas (such as nitrogen, argon, etc.) is generally selected as the inner core. However, as one of the innovative points of the present invention, the inner core used during the extrusion of the hollow fiber membrane of the present invention is in liquid form. Through extensive research, the inventors of the present invention have found that one of the key factors for preparing a support layer with small and numerous pores lies in the selection of the inner core liquid. When the solubility of the inner core liquid in PMP is slightly stronger than that of the casting solution system, the inner surface of the prepared membrane filaments can have slightly larger pores, but not too large; and in the direction extending from the inner surface to the outer surface, the pore size of the holes in the support layer changes less, and the overall pore size of the support layer is small and numerous. The reasons are as follows: First, a strong solvent for PMP can effectively dissolve the PMP material, while a weak solvent for PMP plays a role in regulating the dissolution rate and degree. Through the cooperation of the two, the solubility of the inner core liquid system can be precisely controlled. When the solubility of the inner core liquid system is slightly stronger than that of the casting solution system, the inner core liquid can moderately penetrate into the casting solution, thereby forming a slightly larger pore structure on the inner surface of the membrane filaments, but not overly penetrate, thus avoiding overly large pore sizes. And the solubility of the inner core liquid system directly affects the pore structure on the inner surface of the membrane filaments. The inner core liquid with slightly stronger solubility will form larger pores on the inner surface of the membrane filaments, and these pores serve as the starting points of the support layer, further affecting the pore size distribution of the support layer. By selecting a suitable core liquid system, a moderate pore structure can be formed on the inner surface, laying a foundation for the subsequent formation of the support layer. Second, during the subsequent phase inversion process, the interaction between the inner core liquid and the casting solution leads to the exchange of solvents and non-solvents, thereby forming a pore structure. When the solubility of the inner core liquid system is slightly stronger, the exchange rate of the solvent is moderate, and small and numerous holes can be formed in the support layer. And by adjusting the solubility of the inner core liquid, the pore size of the support layer can change less in the thickness direction. This is because moderate solubility can ensure that the solvent exchange occurs uniformly throughout the membrane thickness, thus avoiding excessive increase or decrease of the pore size in a certain area. Third, the inner core liquid with slightly stronger solubility can form a moderate pore structure on the inner surface of the membrane filaments, and these pores serve as the starting points of the support layer, further forming small and numerous holes through the phase inversion process. This structure not only improves the mechanical strength of the support layer but also increases the channels for gas transmission, thereby improving the oxygen flux of the hollow fiber membrane.

[0084] More preferably, the temperature of the inner core liquid is 50°C - 120°C lower than the extrusion temperature. Such a setting can not only further optimize the pore structure of the hollow fiber membrane, but also improve the mechanical strength of the support layer, and it is less likely for the membrane filaments to break. This is because: during the membrane formation process by the phase inversion method, temperature is a key factor affecting the exchange rate of the solvent and the non-solvent. When the temperature of the inner core liquid is lower than the extrusion temperature, after the inner core liquid contacts the casting solution, it will accelerate the diffusion of the solvent in the casting solution into the inner core liquid, and at the same time, the non-solvent diffuses into the casting solution. This rapid mass transfer process will promote phase separation and form a more porous structure with smaller and more uniform pores. And the low temperature can slow down the movement of polymer chains, making the phase separation process more controllable, thus avoiding the problems of too large holes or uneven distribution, and helping to form smaller and more evenly distributed holes, especially in the support layer. In addition, when the temperature of the inner core liquid is relatively low, the casting solution will quickly cool after contacting the inner core liquid, resulting in the rapid curing of PMP. This rapid curing process helps to form a denser skin layer and a small and porous support layer, thereby improving the mechanical strength of the membrane. Under low temperature conditions, due to the restricted movement of polymer chains, the defects (such as large holes or cracks) caused by chain segment relaxation or rearrangement are reduced, thus improving the integrity and durability of the membrane.

[0085] In order to obtain an oxygenation membrane with a dense outer surface, a support layer thickness within a specific range, and a specific helium flux and a relatively high specific surface area, it is also necessary to coordinately control Step 3 and Step 4. As one of the creative aspects of the present invention, Step 3 is to perform preliminary phase separation in the air section. Under the synergistic action of the appropriate preliminary phase separation in the present invention and the cooling phase separation in Step 4, on the one hand, it is beneficial to obtain an ideal outer surface, that is, a dense surface (almost no defects such as scratches on the outer surface), on the other hand, an ideal support layer structure is obtained, and in addition, it has a suitable crystallization situation.

[0086] Step 3 is to perform preliminary phase separation in the air section, and the presence of the air section will affect the kinetic process of phase separation. Phase separation generally involves the exchange of the solvent and the non-solvent; and the preliminary phase separation in the air section will start to adjust the diffusion rate of the solvent and the non-solvent before entering the cooling bath, thereby affecting the formation of the pore structure, and then further affecting the pore size and quantity of the membrane; preferably, compared with the cooling phase separation, the temperature of the air section in the preliminary phase separation is relatively high and the path is relatively short, which is more conducive to the gradient adjustment of the diffusion rate of the solvent and the non-solvent. At the same time, the relatively high temperature will accelerate the solvent volatilization, induce the local concentration increase of the polymer, trigger the initial phase separation, and may form a certain amount of "pore nuclei", which is more conducive to the precise control of the inner surface pore size (in cooperation with the core liquid), and at the same time optimize the phase separation process, make the pore size distribution of the support layer relatively uniform, with a large number of holes and the pore size changing appropriately with the thickness, improving the toughness and gas transmission efficiency of the membrane.

[0087] The fourth step is to cool and phase-separate the formed product after the preliminary phase separation with the coolant compound C to obtain a green film. When phase-separating and curing the formed product, the selection of several factors such as the type of coolant, the cooling temperature, and the distance of cooling phase separation is extremely crucial. These factors determine whether a hollow fiber membrane with an ideal structure and performance can ultimately be obtained. Based on Steps 1 to 3, the coolant of the present invention is a non-solvent compound C. Compound C includes one or more of mineral oil, palm oil, dimethyl phthalate, dimethyl carbonate, and glyceryl triacetate. Such a selection helps the overall rapid phase separation of the membrane, and at the same time further regulates the temperature and distance in the cooling phase separation. With the synergistic effect of a suitable coolant, a lower cooling temperature, and a certain distance of cooling phase separation, the overall phase separation speed of the membrane is relatively fast. Based on the pre-phase separation effect in the air section, the pore size distribution is finely regulated, which is more conducive to forming a structure with small and numerous pores in the support layer. Finally, the obtained hollow fiber membrane has a suitable helium flux and specific surface area. Of course, the corresponding pre-phase separation process and cooling phase separation process are both based on a suitable casting solution and a suitable core liquid. In addition, in Steps 3 and 4, the running speed of the formed product is 30 m / min - 100 m / min. By regulating the running speed of the membrane filaments, the thickness of the skin layer and the crystallization situation of the whole membrane can be further controlled.

[0088] The fifth step is to remove Compound A, Compound B, and Compound C from the green film to obtain a raw membrane. The purpose is to remove Compound A, Compound B, and Compound C as much as possible and reduce the residue of substances, so as to ensure the biocompatibility of the hollow fiber membrane and minimize the secondary harm to patients. In the removal step, at least one of isopropanol, ethanol, and acetone is selected as the extraction liquid, and the temperature is 60°C - 80°C, and the time is 4 h - 8 h; this can ensure that Compound A, Compound B, and Compound C in the membrane are removed as much as possible, reduce the internal stress and defects in the membrane, and thus improve the uniformity and mechanical properties of the membrane.

[0089] The sixth step is to dry and shape the original membrane. Drying and shaping is a process of treating the hollow fiber membrane at a certain temperature to improve its dimensional stability (stabilizing the pore structure and pore size) and physical properties. During the drying and shaping process, the molecular chains of the membrane material in the hollow fiber membrane may rearrange, thus affecting the structure and uniformity of the skin layer. Appropriate drying and shaping conditions can improve the physical properties and dimensional stability of the membrane material, while inappropriate drying and shaping conditions may cause local overheating or excessive shrinkage of the membrane material, thus affecting the uniformity of the skin layer; and it is easy to cause the overall toughness of the membrane to become poor, prone to filament breakage, and not practical. In the present invention, a special drying and shaping process is adopted according to the corresponding membrane structure - first drying at a lower temperature for a longer time, and then heat setting at a higher temperature for a very short time; preferably, the temperature of the heat drying is controlled at 40°C - 60°C, and the time is 60 min - 120 min; while the temperature of the heat setting is 80°C - 120°C higher than the temperature of the heat drying, and the time is 5 s - 20 s. The temperature of the heat drying is much lower than the temperature of the heat setting, and the time of the heat drying is much longer than the time of the heat setting. Such a setting can perform long-term heat drying at a lower temperature, which helps to gradually remove the extraction liquid and possibly remaining Compound A, Compound B, and Compound C, while reducing the structural defects caused by rapid drying; and performing short-term heat setting at a higher temperature helps to fix the structure of the membrane filaments and avoid excessive heat treatment resulting in too large a pore structure. Through the synergistic effect of the two, the structure and performance of the hollow fiber membrane can be effectively controlled to improve its oxygenation performance, while maintaining good toughness of the membrane filaments. It should be noted that in Steps Five and Six, there is no need to perform stretching treatment on the membrane filaments, because after the stretching treatment, the membrane filaments will instead shrink, affecting their service life.

[0090] The third aspect of the present invention provides an application of an asymmetric PMP hollow fiber membrane, and the asymmetric PMP hollow fiber membrane is used for extracorporeal membrane oxygenation and / or extracorporeal carbon dioxide removal. The asymmetric PMP hollow fiber membrane includes the asymmetric PMP hollow fiber membrane for blood oxygenation described in the first aspect of the present invention and / or the asymmetric PMP hollow fiber membrane for blood oxygenation prepared by the preparation method described in the second aspect of the present invention.

[0091] Through the above technical solutions, the present invention has at least the following advantages compared with the prior art:

[0092] (1) The hollow fiber membrane of the present invention can have both a high carbon dioxide to oxygen separation ratio and an oxygen flux, and has excellent oxygenation performance;

[0093] (2) The hollow fiber membrane of the present invention has high toughness and is not prone to filament breakage.

[0094] The endpoints and any values in the ranges disclosed herein are not limited to the exact ranges or values. These ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoint values of each range, between the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein. Description of the Drawings

[0095] Figure 1 Shown is a scanning electron microscope (SEM) schematic diagram of a cross-section of a hollow fiber membrane in the direction from the outer surface to the inner surface in an example of the present invention.

[0096] Figure 2 Shown is a scanning electron microscope (SEM) schematic diagram of the outer surface of the hollow fiber membrane prepared in Example 1, where the magnification is 20000×.

[0097] Figure 3 Shown is a scanning electron microscope (SEM) schematic diagram of the overall cross-section of the hollow fiber membrane prepared in Example 1, where the magnification is 1300×.

[0098] Figure 4 Shown is a scanning electron microscope (SEM) schematic diagram of the area near the skin layer in the support layer of the hollow fiber membrane prepared in Example 1, where the magnification is 10000×.

[0099] Figure 5 Shown is a scanning electron microscope (SEM) schematic diagram of the area far from the skin layer in the support layer of the hollow fiber membrane prepared in Example 1, where the magnification is 20000×.

[0100] Figure 6 Shown is a scanning electron microscope (SEM) schematic diagram of the inner surface of the hollow fiber membrane prepared in Example 2, where the magnification is 10000×.

[0101] Figure 7 Shown is a scanning electron microscope (SEM) schematic diagram of the inner surface of the hollow fiber membrane prepared in Example 3, where the magnification is 10000×.

[0102] Figure 8 Shown is a schematic diagram of the device for testing the oxygenation performance of the hollow fiber membrane. Detailed Description of the Invention

[0103] The present invention will be described in detail below through examples. The examples described in the present invention are only a part of the examples of the present invention, rather than all of the examples. All other examples obtained by those of ordinary skill in the art based on the examples in the present invention without making creative efforts fall within the scope of protection of the present invention.

[0104] In the following examples, unless otherwise specified, the materials used are commercially available analytical pure grade.

[0105] The following examples are used to illustrate the asymmetric PMP hollow fiber membrane of the present invention.

[0106] Example 1 The asymmetric PMP hollow fiber membrane was prepared according to the following method:

[0107] Step 1: Heat and plasticize PMP, and then dissolve it in a first solvent system containing compound A (dioctyl adipate) and compound C (palm oil) for kneading to obtain a homogeneous casting solution. Among them, the kneading temperature is 245 °C, the kneading pressure is 3 MPa, the solid content (mass content) of PMP in the casting solution is 40%; the mass content of compound C in the first solvent system is 18%;

[0108] Step 2: Extrude the casting solution under the die head to form a molded product with an inner surface and an outer surface; among them, the extrusion temperature is 235 °C (the extrusion temperature is 10 °C lower than the kneading temperature); the core liquid is a second solvent system containing compound A (dioctyl adipate) and compound B (dibutyl phthalate); the mass content of compound B in the second solvent system is 12%; the temperature of the core liquid is 135 °C (the temperature of the core liquid is 100 °C lower than the extrusion temperature);

[0109] Step 3: Perform preliminary phase separation on the molded product in the air section, where the temperature of the air section is 45 °C and the length of the air section is 30 mm;

[0110] Step 4: Cool and phase-separate the preliminarily phase-separated molded product with coolant compound C (palm oil) to obtain a green film; among them, the cooling temperature is 18 °C (the cooling temperature is 27 °C lower than the temperature of the air section in Step 3 and 117 °C lower than the temperature of the core liquid in Step 2), and the distance of cooling and phase separation is 5 m;

[0111] Step 5: Extract the green film with an extractant (isopropyl alcohol) at a temperature of 70 °C for 6 h; thereby removing compound A, compound B, and compound C from the green film to obtain a raw film;

[0112] Step 6: Dry and shape the raw film to obtain an asymmetric PMP hollow fiber membrane; among them, the drying and shaping include heat drying and heat setting. First, perform heat drying treatment on the raw film, the heat drying temperature is 50 °C, and the heat drying time is 90 min; then perform heat setting treatment on the raw film after heat drying treatment, the heat setting temperature is 100 °C higher than the heat drying temperature, and the heat setting time is 12 s.

[0113] Example 2 The hollow fiber membrane was prepared according to the following method:

[0114] Step 1: Heat and plasticize PMP, and then dissolve it in a first solvent system containing Compound A (bis(2-ethylhexyl) adipate) and Compound C (glycerol triacetate) for kneading to obtain a homogeneous casting solution. Among them, the kneading temperature is 260 °C, the kneading pressure is 2 MPa, and the solid content (mass content) of PMP in the casting solution is 45%; the mass content of Compound C in the first solvent system is 25%.

[0115] Step 2: Extrude the casting solution under the die to form a molded product with an inner surface and an outer surface; among them, the extrusion temperature is 240 °C (the extrusion temperature is 20 °C lower than the kneading temperature); the core liquid is a second solvent system containing Compound A (bis(2-ethylhexyl) adipate) and Compound B (methyl-12-hydroxystearic acid); the mass content of Compound B in the second solvent system is 18%; the temperature of the core liquid is 120 °C (the temperature of the core liquid is 120 °C lower than the extrusion temperature).

[0116] Step 3: Conduct preliminary phase separation on the molded product in the air section. Among them, the temperature of the air section is 30 °C, and the length of the air section is 10 mm.

[0117] Step 4: Cool and phase-separate the preliminarily phase-separated molded product with coolant Compound C (glycerol triacetate) to obtain a green film; among them, the cooling temperature is 10 °C (the cooling temperature is 20 °C lower than the temperature in the air section in Step 3 and 110 °C lower than the temperature of the core liquid in Step 2), and the distance of cooling and phase separation is 2 m.

[0118] Step 5: Extract the green film with an extractant (ethanol) at a temperature of 60 °C for 8 h; thereby removing Compound A, Compound B, and Compound C from the green film to obtain a raw film, and obtain a raw film.

[0119] Step 6: Dry and shape the raw film to obtain an asymmetric PMP hollow fiber membrane; among them, the drying and shaping include heat drying and heat setting. First, conduct heat drying treatment on the raw film. The heat drying temperature is 45 °C, and the heat drying time is 120 min; then conduct heat setting treatment on the raw film after heat drying treatment. The heat setting temperature is 85 °C higher than the heat drying temperature, and the heat setting time is 20 s.

[0120] Example 3 prepares a hollow fiber membrane according to the following method:

[0121] Step 1: Heat and plasticize PMP, and then dissolve it in a first solvent system containing Compound A (diisooctyl phthalate) and Compound C (dimethyl carbonate) for kneading to obtain a homogeneous casting solution. Among them, the kneading temperature is 225 °C, the kneading pressure is 4 MPa, and the solid content (mass content) of PMP in the casting solution is 35%; the mass content of Compound C in the first solvent system is 10%.

[0122] Step 2: Extrude the casting solution under the die head to form a molded product with an inner surface and an outer surface; wherein, the extrusion temperature is 220 °C (the extrusion temperature is 5 °C lower than the mixing temperature); the inner core liquid is a second solvent system containing compound A (diisooctyl phthalate) and compound B (dibutyl sebacate); the mass content of compound B in the second solvent system is 6%; the temperature of the inner core liquid is 140 °C (the temperature of the inner core liquid is 80 °C lower than the extrusion temperature);

[0123] Step 3: Conduct preliminary phase separation on the molded product in the air section, wherein, the temperature of the air section is 60 °C and the length of the air section is 45 mm;

[0124] Step 4: Cool and phase-separate the molded product after preliminary phase separation with coolant compound C (dimethyl carbonate) to obtain a green film; wherein, the cooling temperature is 30 °C (the cooling temperature is 30 °C lower than the temperature in the air section in Step 3 and 110 °C lower than the temperature of the inner core liquid in Step 2), and the distance for cooling and phase separation is 8 m;

[0125] Step 5: Extract the green film with an extraction liquid (acetone) at a temperature of 80 °C for 4 h; thereby removing compound A, compound B, and compound C from the green film to obtain a raw film;

[0126] Step 6: Dry and shape the raw film to obtain an asymmetric PMP hollow fiber membrane; wherein, the drying and shaping include heat drying and heat setting. First, conduct heat drying treatment on the raw film, the heat drying temperature is 60 °C, and the heat drying time is 65 min; then conduct heat setting treatment on the raw film after heat drying treatment, the heat setting temperature is 110 °C higher than the heat drying temperature, and the heat setting time is 6 s.

[0127] Test Example I

[0128] (1) Structure test

[0129] Conduct structural characterization on the asymmetric PMP hollow fiber membranes prepared in Examples 1-3, and use a scanning electron microscope (Hitachi S-5500) to characterize the morphology of the membrane main structure of each example sample; then obtain the required data; and obtain corresponding data through other tests; the specific results are shown in Tables 1-5, wherein the roughness of the inner surface in Examples 1-3 is greater than that of the outer surface.

[0130] Among them, Figure 2 The schematic diagram of the scanning electron microscope (SEM) of the outer surface of the hollow fiber membrane prepared in Example 1 is shown. Figure 3 The schematic diagram of the scanning electron microscope (SEM) of the overall cross-section of the hollow fiber membrane prepared in Example 1 is shown. Figure 4The figure shows a scanning electron microscope (SEM) schematic diagram of the region near the skin layer in the support layer of the hollow fiber membrane prepared in Example 1. Figure 5 The figure shows a scanning electron microscope (SEM) schematic diagram of the region far from the skin layer in the support layer of the hollow fiber membrane prepared in Example 1. Figure 6 The figure shows a scanning electron microscope (SEM) schematic diagram of the inner surface of the hollow fiber membrane prepared in Example 2. Figure 7 The figure shows a scanning electron microscope (SEM) schematic diagram of the inner surface of the hollow fiber membrane prepared in Example 3.

[0131] (2) Performance testing

[0132] The asymmetric PMP hollow fiber membranes prepared in Examples 1-3 were tested for helium gas flux and the separation ratio of carbon dioxide to oxygen. The specific testing method is as follows:

[0133] Under the conditions of a temperature of 25 °C, a pressure of 1 bar, and a hollow fiber membrane sample area of 0.1 m 2 , one side of the sample was exposed to the gas to be tested (helium, oxygen, and carbon dioxide); the gas to be tested was fed into the inner cavity of the sample, and the volumetric flow rate of the gas passing through the sample membrane wall was measured using a flow meter (KOFLOC / 4800, Japan); it was tested 3 times from inside the membrane to outside the membrane and also 3 times from outside the membrane to inside the membrane, and then the average value was taken. Among them, the average value of the helium test is the helium flux, with the unit of ml / (cm 2 ×min×bar), and the ratio of the gas flux of carbon dioxide to the gas flux of oxygen is the separation ratio α(CO 2 / O 2 ), and the specific results are shown in Table 5.

[0134] (3) XRD testing

[0135] The asymmetric PMP hollow fiber membranes prepared in Examples 1-3 were subjected to XRD testing. The results showed that the hollow fiber membranes prepared in Examples 1-3 had characteristic diffraction peaks at a 2θ angle of 9°-10° in the XRD diffraction pattern, and the crystal grains of this characteristic diffraction peak were not less than 250 Å; and the PMP was in a tetragonal crystal system form. The remaining results are shown in Table 6.

[0136] Table 1 Outer surface and skin layer related characteristics

[0137] Outer surface topography Cortex thickness Example 1 Dense surface 1.5μm Example 2 Dense surface 2.9μm Example 3 Dense surface 0.8μm

[0138] Table 2 Support layer related characteristics

[0139]

[0140]

[0141] Table 3 Related characteristics of the support layer

[0142]

[0143] Table 4 Related characteristics of the inner surface

[0144]

[0145] Table 5 Overall characteristics of the membrane

[0146]

[0147] Table 6 Related characteristics of XRD

[0148] Characteristic diffraction peak position Intensity ratio of characteristic diffraction peak Full width at half maximum Example 1 9.5° 64％ 0.3° Example 2 9.4° 58％ 0.4° Example 3 9.6° 71％ 0.2°

[0149] The asymmetric PMP hollow fiber membranes prepared in Examples 1-3 all have an ideal pore structure. The outer surface is dense, the overall membrane has more pores, and the support layer has smaller and uniformly distributed pore diameters, with a suitable helium flux and excellent specific surface area. They have excellent oxygenation performance and a long plasma permeation time, can work efficiently for a long time, and can truly be used as an "artificial lung" to provide arterial blood for human organs and enable human organs to still work normally. They are suitable for various extracorporeal life supports (including cardiac surgery, cardiopulmonary transplantation bridging, emergency cardiopulmonary resuscitation, acute respiratory distress syndrome, cardiopulmonary organ transplantation, multiple organ failure, and congenital heart disease in children).

[0150] Comparative Example 1

[0151] It was carried out with reference to Example 1, except that during the preparation of the hollow fiber membrane, the cooling temperature in Step 4 was 50 °C and the cooling demixing distance was 14 m; the other conditions remained unchanged;

[0152] In the finally prepared hollow fiber membrane, the outer surface is not dense, that is, there are a certain number of holes with a certain pore diameter; this will lead to a significant reduction in the oxygenation performance of the hollow fiber membrane; at the same time, the tolerance is poor and the plasma permeation time is too short.

[0153] Comparative Example 2

[0154] It was carried out with reference to Example 1, except that during the preparation of the hollow fiber membrane, the solid content of PMP in the casting solution in Step 1 was relatively high, being 55%, and the length of the air section in Step 3 was too short, only being 2 mm; the other conditions remained unchanged;

[0155] In the finally prepared hollow fiber membrane, the helium flux is less than 1.5 ml / (cm 2 ×min×bar), the oxygenation performance of the hollow fiber membrane is insufficient, and the toughness is poor.

[0156] Comparative Example 3

[0157] It was carried out with reference to Example 1, except that when preparing the hollow fiber membrane, the solid content of PMP in the casting solution in Step 1 was relatively low, only 23%, and the length of the air section in Step 3 was too long, 65 mm; other conditions remained unchanged;

[0158] In the finally prepared hollow fiber membrane, the helium flux was greater than 3 ml / (cm 2 ×min×bar), the oxygenation performance of the hollow fiber membrane was insufficient, and the plasma penetration time was short, less than 48 hours.

[0159] Comparative Example 4

[0160] It was carried out with reference to Example 1, except that when preparing the hollow fiber membrane, the first solvent system was only Compound A, and in Step 2, the core liquid was not used but replaced with nitrogen;

[0161] In the finally prepared hollow fiber membrane, the BET specific surface area was less than 30 m 2 / g, and the oxygenation performance of the hollow fiber membrane was insufficient.

[0162] Comparative Example 5

[0163] It was carried out with reference to Example 1, except that when preparing the hollow fiber membrane, the first solvent system was Compound B (dibutyl phthalate) and Compound C, and the mass content of Compound C in the first solvent system was 3%, and the second solvent system was only Compound B;

[0164] In the finally prepared hollow fiber membrane, the BET specific surface area was greater than 60 m 2 / g, the toughness of the hollow fiber membrane was insufficient, and it was very easy to break the filaments; and the oxygenation performance was also poor.

[0165] By comparing Example 1 with Comparative Examples 1-5, it can be seen that the hollow fiber membrane of the present invention, based on regulating that the outer surface of the membrane is dense, the thickness of the support layer, and the proportion of the thickness of the support layer in the membrane, further regulates the synergistic effect of having a suitable helium flux and a relatively high BET specific surface area, greatly improving the oxygenation ability of the hollow fiber membrane (the improvement of oxygenation performance is the result of the combined action of each feature of the membrane, and none of them can be missing), shortening the gap with the human lung, and truly being able to be used as an "artificial lung" to provide arterial blood for human organs and enable human organs to still work normally.

[0166] Example 4 group

[0167] This group of examples was used to verify the influence brought about by the change of "porosity and the pore size change gradient of the first holes on the first cross-section".

[0168] This group of examples was carried out with reference to Example 1, and the different steps are specifically as follows:

[0169] Example 4a, in step one, the mixing temperature is 210 °C, and the solid content of PMP in the casting solution is 30%; in step two, the extrusion temperature is 220 °C (the extrusion temperature is 10 °C higher than the mixing temperature, i.e., -10 °C lower), and the temperature of the inner core liquid is 158 °C (the temperature of the inner core liquid is 62 °C lower than the extrusion temperature); in step three, the temperature of the air section is 40 °C; in step four, the cooling temperature is 35 °C (the cooling temperature is 5 °C lower than the temperature of the air section in step three and 123 °C lower than the temperature of the inner core liquid in step two), and the cooling phase separation distance is 10 m;

[0170] In the finally prepared hollow fiber membrane, the porosity is 72%, and the pore size change gradient of the first holes on the first cross-section is 5.8 nm / 1 μm;

[0171] Example 4b, in step one, the mixing temperature is 250 °C, and the solid content of PMP in the casting solution is 49%; in step two, the extrusion temperature is 220 °C (the extrusion temperature is 30 °C lower than the mixing temperature), and the temperature of the inner core liquid is 150 °C (the temperature of the inner core liquid is 70 °C lower than the extrusion temperature); in step three, the temperature of the air section is 55 °C; in step four, the cooling temperature is 3 °C (the cooling temperature is 52 °C lower than the temperature of the air section in step three and 147 °C lower than the temperature of the inner core liquid in step two), and the cooling phase separation distance is 2 m;

[0172] In the finally prepared hollow fiber membrane, the porosity is 38%, and the pore size change gradient of the first holes on the first cross-section is 0.8 nm / 1 μm.

[0173] Example 5 group

[0174] This group of examples is used to verify the influence brought by the change of "the SEM average pore size and pore density of the first holes in the region near the skin layer and far from the skin layer".

[0175] This group of examples is carried out with reference to Example 1, and the different steps are specifically as follows:

[0176] Example 5a, in step one, the mixing temperature is 272 °C; in step two, the extrusion temperature is 251 °C (the extrusion temperature is 21 °C lower than the mixing temperature), and the temperature of the inner core liquid is 126 °C (the temperature of the inner core liquid is 125 °C lower than the extrusion temperature); in step three, the temperature of the air section is 60 °C; in step four, the cooling temperature is 5 °C (the cooling temperature is 55 °C lower than the temperature of the air section in step three and 121 °C lower than the temperature of the inner core liquid in step two);

[0177] In the finally prepared hollow fiber membrane, the SEM average pore size of the first holes in the region near the skin layer is 93 nm, and the pore density in the region near the skin layer is 35 holes / 25 μm 2 ;

[0178] Example 5b, the mixing temperature in Step 1 is 209°C; in Step 2, the extrusion temperature is 215°C (the extrusion temperature is 6°C higher than the mixing temperature, i.e., -6°C lower); the temperature of the inner core liquid is 90°C (the temperature of the inner core liquid is 125°C lower than the extrusion temperature); in Step 3, the temperature of the air section is 40°C; in Step 4, the cooling temperature is 32°C (the cooling temperature is 8°C lower than the temperature of the air section in Step 3 and 58°C lower than the temperature of the inner core liquid in Step 2);

[0179] In the finally prepared hollow fiber membrane, the average SEM pore diameter of the first pores in the area far from the skin layer is 812 nm, and the pore density in the area far from the skin layer is 25 pores / 25 μm 2 。

[0180] Example 6

[0181] To verify the influence brought by the change of "the average SEM width of the support fibers in the area close to the skin layer and in the area far from the skin layer".

[0182] It is carried out with reference to Example 1, and the different steps are specifically as follows:

[0183] In Step 1, the solid content of PMP in the casting solution is 47%; in Step 5, the temperature of the extraction liquid is 50°C; in Step 6, the heat drying temperature is 35°C, and the heat drying time is 50 min; the heat setting temperature is 75°C higher than the heat drying temperature, and the heat setting time is 3 s;

[0184] In the finally prepared hollow fiber membrane, the average SEM width of the support fibers in the area close to the skin layer is 48 nm, and the average SEM width of the support fibers in the area far from the skin layer is 65 nm.

[0185] Example 7

[0186] To verify the influence brought by the change of "the ratio Y1 / Y2 of the support coefficient Y1 in the area close to the skin layer to the support coefficient Y2 in the area far from the skin layer".

[0187] It is carried out with reference to Example 1, and the different steps are specifically as follows:

[0188] In Step 1, the solid content of PMP in the casting solution is 32%; in Step 5, the temperature of the extraction liquid is 90°C; in Step 6, the heat drying temperature is 65°C, and the heat drying time is 130 min; the heat setting temperature is 121°C higher than the heat drying temperature, and the heat setting time is 60 s;

[0189] In the finally obtained hollow fiber membrane, the average SEM width of the support fibers in the area close to the skin layer is 70 nm, and the average SEM width of the support fibers in the area far from the skin layer is 150 nm; Y1 is 0.266, Y2 is 0.308, and Y1 / Y2 is 0.86.

[0190] Test Example II

[0191] (1) Tensile strength and elongation at break test

[0192] The hollow fiber membranes prepared in the examples were used as specimens for the tensile strength and elongation at break tests. The specific test methods are as follows:

[0193] At room temperature (25 °C), each specimen was uniformly stretched with a tensile machine (tensile speed: 50 mm / min, distance between the upper and lower clamps: 30 mm) until the specimen broke. Thus, the tensile strength and elongation at break were measured, repeated 3 times, and the average value was taken. The results showed that the tensile strength of all examples of the present invention was not less than 80 cN, the elongation at break was not less than 100%, and the elongation at break of the hollow fiber membranes in Examples 1-3 was not less than 150%. This indicates that the hollow fiber membranes of the present invention have excellent mechanical properties and high industrial practical value. Further, the burst pressure tests were carried out on the hollow fiber membranes prepared in Examples 1-3, and it was found that the internal burst pressure of the oxygenation membranes was not less than 2.5 bar (from outside to inside), and the external burst pressure was not less than 4 bar (from inside to outside), further indicating that the oxygenation membranes have good mechanical strength.

[0194] (2) Plasma permeation time test

[0195] The hollow fiber membranes prepared in the examples were used as specimens for the plasma permeation time test. The specific test methods are as follows:

[0196] Let a phospholipid solution at 37 °C (1.5 g of lecithin dissolved in 500 ml of physiological saline solution) flow through the surface of the specimen at a rate of 6 L / (min×m 2 ) and a pressure of 1.0 bar. Let air flow along the other side of the specimen, and the air flowing through the specimen passes through a cold trap. The weight of the liquid accumulated in the cold trap was measured as a function of time. When a significant increase in weight occurred, that is, the time when the liquid first significantly accumulated in the cold trap was defined as the plasma leakage time, and the results were recorded in Table 7.

[0197] (3) Oxygen saturation test

[0198] The hollow fiber membranes prepared in the examples and comparative examples were used as specimens for oxygen saturation, oxygen partial pressure, carbon dioxide partial pressure, and end-tidal carbon dioxide concentration tests. The specific test methods are as follows:

[0199] Based on the ISO-7199 standard, at 1.6 m 2While the blood sample is being processed at a flow rate of 5 L / min, use a blood gas analyzer to measure the oxygen saturation, partial pressure of oxygen, and partial pressure of carbon dioxide in the blood (arterial blood), and measure the end-tidal carbon dioxide concentration. The schematic diagram of the test device is as shown in Figure 8 and record the results in Table 7.

[0200] Table 7

[0201]

[0202] Note: " / " in Table 7 indicates not tested.

[0203] It can be seen from Table 7 that the hollow fiber membrane of the present invention has excellent oxygenation performance compared with the comparative example; and the hollow fiber membrane of the present invention has a longer plasma penetration time.

[0204] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited thereto. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention, including any other suitable combination of each technical feature. These simple modifications and combinations should also be regarded as the content disclosed by the present invention and fall within the protection scope of the present invention.

Claims

1. An asymmetric PMP hollow fiber membrane for blood oxygenation, characterized in that: It comprises a main body, wherein the main body comprises a skin layer and a support layer; one side of the main body is an inner surface facing the inner cavity, and the other side of the main body is an outer surface; the side of the skin layer facing away from the support layer is the outer surface, and the side of the support layer facing away from the skin layer is the inner surface; The outer surface has a dense surface, The thickness of the support layer is 68 μm-118 μm; the ratio of the thickness of the support layer to the thickness of the PMP hollow fiber membrane is not less than 0.95; The helium flux of the PMP hollow fiber membrane is 1.5 ml / (cm 2 ×min×bar)-3ml / (cm 2 ×min×bar); The BET specific surface area of ​​the PMP hollow fiber membrane is 30 m 2 / g-60m 2 / g.

2. The asymmetric PMP hollow fiber membrane for blood oxygenation according to claim 1, characterized in that: The porosity of the PMP hollow fiber membrane is 40%-70%; The cross section of the support layer along the film thickness direction is a first cross section, the first cross section has a plurality of first holes, and the pore size variation gradient of the first holes on the first cross section is 1.1 nm / 1 μm-5.5 nm / 1 μm; Among them, the pore size change gradient = (SEM average pore size of the first hole on the area away from the cortex - SEM average pore size of the first hole on the area close to the cortex) / thickness of the supporting layer; the area close to the cortex is an area on the supporting layer formed within 5 μm from the boundary between the cortex and the supporting layer; the area away from the cortex is an area on the supporting layer formed within 5 μm from the inner surface.

3. The asymmetric PMP hollow fiber membrane for blood oxygenation according to claim 2, characterized in that: The average pore size of the first hole near the cortex region is 100nm-400nm by SEM, and the pore density near the cortex region is 40 / 25μm 2 -180 pieces / 25μm 2 ; And / or, the average pore size of the first hole in the region away from the cortex is 250nm-800nm ​​by SEM, and the pore density in the region away from the cortex is 30 / 25μm 2 -140 pieces / 25μm 2 .

4. The asymmetric PMP hollow fiber membrane for blood oxygenation according to claim 2, characterized in that: The support layer has support fibers for forming a porous structure; The SEM average width of the supporting fibers in the region near the cortex is 50 nm to 130 nm; And / or, the SEM average width of the supporting fibers in the region away from the cortex is 70nm-150nm, and the SEM average width of the supporting fibers in the region away from the cortex is not less than the SEM average width of the supporting fibers in the region close to the cortex.

5. The asymmetric PMP hollow fiber membrane for blood oxygenation according to claim 4, characterized in that: In the support layer, the ratio between the SEM average width of the support fibers and the SEM average pore size of the first holes is the support coefficient Y; wherein the support coefficient Y2 away from the cortex region is 0.12-0.3; And / or, the ratio of the support coefficient Y1 close to the cortical area to the support coefficient Y2 far from the cortical area is 1.01-2.

6. The asymmetric PMP hollow fiber membrane for blood oxygenation according to claim 2, characterized in that: The inner surface is provided with a plurality of vents; the SEM average pore size of the vents is 0.28 μm-0.85 μm, and the hole area rate of the vents on the inner surface is 5%-25%; And / or, the ratio of the SEM average pore size of the ventilation holes to the SEM average pore size of the first holes in the area away from the cortex is 1.05-2.

2.

7. The asymmetric PMP hollow fiber membrane for blood oxygenation according to claim 2, characterized in that: The inner surface has adjustment fibers for adjusting the surface roughness, the SEM average width of the adjustment fibers is greater than the SEM average width of the supporting fibers in the area away from the cortex; and the SEM average width of the adjustment fibers is not less than 120nm; the roughness of the inner surface is greater than the roughness of the outer surface.

8. The asymmetric PMP hollow fiber membrane for blood oxygenation according to claim 7, characterized in that: The ratio of the SEM average width of the regulating fiber to the SEM average pore size of the vent is the regulation coefficient Z, and the regulation coefficient Z is 0.3-0.8; The pore size variation gradient of the first hole on the first cross section is 1.3 nm / μm-3 nm / μm.

9. The asymmetric PMP hollow fiber membrane for blood oxygenation according to claim 1, characterized in that: The XRD crystallinity of the PMP hollow fiber membrane is 20%-55%; the thickness of the skin layer is 0.2μm-5μm; the separation ratio α (CO2 / O2) of carbon dioxide and oxygen of the PMP hollow fiber membrane is not less than 1.

8.

10. The asymmetric PMP hollow fiber membrane for blood oxygenation according to claim 1, characterized in that: The PMP hollow fiber membrane was tested by XRD method. The PMP hollow fiber membrane has a characteristic diffraction peak at a 2θ angle of 9°-10° in the XRD diffraction spectrum, the intensity of the characteristic diffraction peak accounts for 52%-75% of the overall crystal diffraction peak intensity, the half-peak width of the characteristic diffraction peak is 0.1°-0.5°, and the grain size is not less than 250 angstroms; the PMP in the PMP hollow fiber membrane is in a tetragonal crystal morphology.

11. The asymmetric PMP hollow fiber membrane for blood oxygenation according to claim 1, characterized in that: The PMP hollow fiber membrane also meets one or more of the following characteristics: The tensile strength of the PMP hollow fiber membrane is not less than 80 cN, and the elongation at break is not less than 100%; The plasma permeation time of the PMP hollow fiber membrane is not less than 48 hours, preferably not less than 96 hours; At 1.6m 2 When the PMP hollow fiber membrane processes blood at a flow rate of 5L / min, the oxygen saturation of arterial blood is not less than 99%, the oxygen partial pressure is not less than 150mmHg, the carbon dioxide partial pressure is not higher than 46mmHg; and the end-tidal carbon dioxide concentration is not less than 29mmHg.

12. A method for preparing an asymmetric PMP hollow fiber membrane for blood oxygenation according to any one of claims 1 to 11, characterized in that: The following steps are involved: Step 1: heating and plasticizing PMP, and then dissolving it into a first solvent system containing compound A and compound C for mixing to obtain a homogeneous casting solution; the solid content of PMP in the casting solution is 30%-49%; Wherein, the compound A is a strong solvent for PMP, and the compound C is a non-solvent for PMP; the mass content of the compound C in the first solvent system is 5%-30%; Step 2: Extruding the casting liquid under a die head to form a molded product having an inner surface and an outer surface; wherein the inner core liquid is a second solvent system comprising compound A and compound B; the compound B is a weak solvent for PMP, and the mass content of the compound B in the second solvent system is 5%-20%; the temperature of the inner core liquid is 60°C-140°C lower than the extrusion temperature; Step 3: performing preliminary phase separation on the molded product in an air section; wherein the temperature of the air section is 10° C.-80° C., and the length of the air section is 5 mm-50 mm; Step 4: Cooling and separating the molded product after the preliminary phase separation with a coolant compound C to obtain a green film; wherein the cooling temperature is 3°C-40°C, and the cooling and phase separation distance is 1m-10m; Step 5: removing the compound A, the compound B and the compound C from the raw film to obtain an original film; Step 6: Dry and shape the original membrane to obtain the asymmetric PMP hollow fiber membrane.

13. The preparation method according to claim 12, characterized in that: The compound A comprises one or more of dioctyl adipate, di-n-octyl phthalate, di(2-ethylhexyl) adipate and di-isooctyl phthalate; The compound B includes one or more of N,N-bis-2-hydroxyethyl hexadecylamine, methyl-12-hydroxystearic acid, paraffin oil, dibutyl sebacate, dibutyl phthalate, diethyl phthalate and oleamide; The compound C comprises one or more of mineral oil, palm oil, dimethyl phthalate, dimethyl carbonate and triacetin.

14. The preparation method according to claim 12, characterized in that: The mixing temperature in step 1 is 210°C-270°C, and the extrusion temperature in step 2 is 220°C-250°C; And / or, the cooling temperature in step 4 is 10°C-50°C lower than the air section temperature in step 3; And / or, the cooling temperature in step 4 is 60°C-120°C lower than the temperature of the inner core liquid in step 2.

15. The preparation method according to claim 12, characterized in that: The step of removing compound A, compound B and compound C from the green film in step 5 specifically refers to extracting the green film with an extracting liquid at a temperature of 60° C. to 80° C. for 4 h to 8 h; wherein the extracting liquid is one or more of isopropanol, ethanol and acetone; And / or, the extrusion temperature is 5°C-25°C lower than the mixing temperature.

16. The preparation method according to claim 12, characterized in that: In step 6, the drying and shaping includes heat drying and heat shaping, specifically, the original film is first subjected to heat drying treatment, the heat drying temperature is 40°C-60°C, and the heat drying time is 60min-120min; Then, the original film after the heat drying treatment is subjected to heat setting treatment, wherein the heat setting temperature is 80° C.-120° C. higher than the heat drying temperature, and the heat setting time is 5s-20s.

17. An application of an asymmetric PMP hollow fiber membrane, characterized in that: The asymmetric PMP hollow fiber membrane is used for extracorporeal membrane oxygenation and / or extracorporeal carbon dioxide removal, and the asymmetric PMP hollow fiber membrane comprises the asymmetric PMP hollow fiber membrane for blood oxygenation described in any one of claims 1-11 and / or the asymmetric PMP hollow fiber membrane for blood oxygenation prepared by the preparation method described in any one of claims 12-16.

Images