PP (polypropylene) hollow fiber oxygenation membrane as well as preparation method and application thereof

Abstract

The invention provides a PP (polypropylene) hollow fiber oxygenation membrane and a preparation method and application thereof, the oxygenation membrane is prepared by taking PP as a raw material, a plurality of first holes are formed in the outer surface of the oxygenation membrane, and the SEM (scanning electron microscope) average pore size of the first holes is not greater than 200nm; in the film thickness direction from the outer surface to the inner surface, the average aperture of the main body is firstly reduced and then increased, a small hole area with very small aperture exists in the film main body, the small hole area is close to the outer surface, and the nearest average distance from the small hole area to the outer surface is not greater than 5 microns; meanwhile, the whole oxygenation membrane has a proper uniform foaming point and porosity, the porosity is not lower than 25%, and the uniform foaming point of IPA is 0.7-0.99 MPa; therefore, the oxygenation membrane has excellent oxygenation performance and also has good plasma permeation time; the device is particularly suitable for blood oxygenation in cardiopulmonary surgery and / or organ transplantation; in addition, the invention also provides a preparation method of the hollow fiber membrane, and the preparation method is quick, effective, simple to operate and suitable for large-scale popularization.

Description

A PP hollow fiber oxygenation membrane, its preparation method and application Technical Field

[0001] This invention relates to the field of membrane materials technology, and more specifically to a PP hollow fiber oxygenation membrane, its preparation method, and its application. Background Technology

[0002] In many applications in the chemical, biological, or medical fields, there is a need to separate gaseous components from liquids or add these components to liquids. For these gas exchange processes, membranes are increasingly used as separation membranes between various liquids and fluids that adsorb or release gaseous components, separating gaseous components from or adding them to these liquids. The fluid can be a gas or a liquid containing or adsorbing the gaseous components to be exchanged. Using such membranes provides an exchange surface for gas exchange and, if necessary, avoids direct contact between the liquid and the fluid.

[0003] One important application of membrane-based gas exchange in the medical field is the oxygenator, also known as an artificial lung. These oxygenators, for example, are used in open-heart surgery to oxygenate and / or remove carbon dioxide from the blood. Typically, bundled hollow fiber membranes are used in these oxygenators; we refer to these hollow fiber membranes as oxygenation membranes. Venous blood flows through the external space surrounding the oxygenation membrane, while air, oxygen-enriched air, or even pure oxygen, is introduced into the cavity of the oxygenation membrane. Through this oxygenation membrane, oxygen can enter the blood, while carbon dioxide is transported from the blood into the cavity and expelled.

[0004] One of the most important indicators of oxygenation membranes is plasma permeation time. Ideally, the oxygenation membrane should exhibit good tolerance, meaning that its various properties (mechanical and oxygenation properties, etc.) should remain almost unchanged during prolonged contact with blood, thus ensuring a long service life to meet practical application requirements. To achieve a long plasma permeation time, researchers often aim for a sufficiently dense outer surface (with virtually no pores). However, in some special cases, researchers also desire a certain number of pores of a specific size on the outer surface, as illustrated in publication number CN11188894. Chinese Patent No. 6A (applied by Hangzhou Kebote Technology Co., Ltd.) - "An Asymmetric Hydrophobic Polyolefin Hollow Fiber Membrane and Its Preparation Method and Use" discloses a polyolefin hollow fiber membrane, including a support layer and a separation layer. The separation layer includes an outer surface containing a certain number of first pores of a certain pore size. The presence of the first pores facilitates the permeation of anesthetic gases such as sevoflurane into the patient's bloodstream through the hollow fiber membrane, reducing the amount of anesthetic used during surgery and avoiding secondary damage. At the same time, the hollow fiber membrane also has a long plasma permeation time (preferably greater than 48 hours).

[0005] With rapid economic development, some practical fields no longer require such long plasma permeation times (not necessarily greater than 48 hours), but higher oxygenation performance is needed. For example, in cardiopulmonary surgery and organ transplantation, oxygenation membranes need to have excellent oxygenation performance (but generally, improving oxygenation performance leads to a rapid decrease in the plasma permeation time of the membrane fibers) to achieve rapid exchange of oxygen and carbon dioxide in the blood, ensuring the normal operation of various organs and preventing secondary harm to patients during surgery. Therefore, how to prepare an oxygenation membrane with excellent oxygenation performance and a good plasma permeation time is currently one of the hot research topics. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a PP hollow fiber oxygenation membrane, its preparation method, and its application. The oxygenation membrane has pores on its outer surface and small pore regions with very small pore sizes within the membrane body, located near the outer surface. Simultaneously, the oxygenation membrane as a whole has suitable pore size and porosity, thereby achieving excellent oxygenation performance and good plasma permeation time.

[0007] To achieve the above objectives, the present invention provides the following technical solution: a PP hollow fiber oxygenation membrane, comprising a main body, one side of which is an inner surface facing the inner cavity, and the other side of which is an outer surface, wherein the main body has a non-directional tortuous pathway; the outer surface includes a plurality of first pores, wherein the SEM average pore size of the first pores is not greater than 200 nm;

[0008] In the film thickness direction from the outer surface to the inner surface, the average pore size of the body first decreases and then increases;

[0009] The main body includes a pore area, the nearest average distance from the pore area to the outer surface is less than the nearest average distance from the pore area to the inner surface, and the nearest average distance from the pore area to the outer surface is not greater than 5 μm; the porosity of the oxygenation membrane is not less than 25%, the uniform bubble point of IPA is 0.7-0.99 MPa, and the overall thickness is 30-80 μm.

[0010] The oxygenation membrane of this invention is made of PP (polypropylene). PP is a non-polar material that is easy to process, has low cost, and good chemical stability and biocompatibility. (The oxygenation mechanism of PP is very different from that of PMP, so the PP oxygenation membrane and PMP oxygenation membrane are not comparable and cannot be compared.) In order to make the oxygenation membrane of this invention have a higher oxygenation capacity and be able to quickly achieve gas exchange of oxygen and carbon dioxide, the oxygenation membrane first has a first pore of a certain size on its outer surface (the average SEM pore size of the first pore is no greater than 200 nm, because studies have found that when the pore size is greater than 200 nm, the plasma permeation time of the membrane fibers will decrease rapidly, which cannot meet practical requirements). The presence of the first pore is conducive to the rapid permeation of gases such as oxygen and carbon dioxide, which is completely different from a dense outer surface (there are almost no pores on the outer surface). (Although a dense outer surface can improve the tolerance of the membrane fibers, it also sacrifices some of the gas permeation rate, thereby reducing the oxygenation performance.) Furthermore, the uniform bubble point of the oxygenation membrane (IPA) is 0.7-0.99 MPa, indicating that the overall pore size of the oxygenation membrane is very small, while the porosity is 20%-60% (it can be 25%, 40%, 50% or even higher). This further indicates that the overall number of pores in the oxygenation membrane is relatively large. That is, although the overall pores of the membrane fibers are small, the number of pores is large. This structural design is more conducive to improving the oxygenation capacity of the PP oxygenation membrane. Furthermore, by controlling the thickness of the membrane fibers to 30-80 μm, the thickness is not too large, further ensuring the oxygenation capacity of the PP oxygenation membrane. In summary, the synergistic effect of pores on the outer and upper surfaces of the PP oxygenation membrane, with appropriate pore size, high porosity, and a certain thickness, ensures that the oxygenation membrane of this invention has excellent oxygenation capacity (of course, this is also inseparable from the unique pore size variation of this invention - first decreasing and then increasing in the thickness direction). This enables rapid exchange of oxygen and carbon dioxide in the blood, thereby ensuring the normal operation of various organs and ensuring that the surgery will not cause secondary harm to the patient.

[0011] As is known in the art, those skilled in the art generally expect the outer surface (regardless of whether it has pores; if the outer surface is dense, it's equivalent to the outer surface membrane pore size being 0) to be the region with the smallest pore size on the oxygenation membrane. This is because the outer surface of the oxygenation membrane is the area directly in contact with external blood; if its pore size is not the smallest, the oxygenation membrane's tolerance (i.e., plasma permeation time) will be very poor, failing to meet the needs of practical applications. However, continuous research has revealed that the pore size of the outer surface membrane of the oxygenation membrane does not necessarily have to be the smallest. In this invention, the pore size of the outer surface membrane is considered to be the smallest. Along the thickness direction of the membrane from the outer surface to the inner surface, the pore size of the oxygenation membrane generally decreases and then increases. This means there exists a region with very small pores within the main body of the oxygenation membrane, which we call the pore region (this region can be considered the area with the smallest pore size within the main body of the membrane). This pore region does not include the outer surface; it only needs to be located near the outer surface. Since blood is directly located on the outside of the oxygenation membrane, the distance between the pore region and the outer surface cannot be too far. The closest average distance from the pore region to the outer surface (the closest average distance refers to the average distance from the side of the pore region closest to the outer surface to the outer surface) needs to be small. With a thickness of 5 μm, the oxygenation membrane can significantly improve its oxygenation performance while maintaining a good plasma permeation time (unlike existing membrane fibers where plasma permeation time rapidly decreases once oxygenation performance is improved). Furthermore, the overall thickness of the oxygenation membrane also affects the plasma permeation time; therefore, the membrane fiber thickness cannot be too low. Research has shown that an overall thickness of 30-80 μm is optimal (excessive thickness negatively impacts the oxygenation capacity of the PP oxygenation membrane, significantly reducing it). This further enhances the plasma permeation capacity of the membrane fibers. Simultaneously, we also found that ultimately… Controlling the uniform bubble point of the IPA of the entire PP oxygenation membrane within 0.7-0.99 MPa is more conducive to ensuring the plasma permeation time of the oxygenation membrane. In summary, although the outer surface is not the region with the smallest pore size inside the oxygenation membrane in this invention, the presence of small pores near the outer surface of the PP oxygenation membrane, the overall thickness of the oxygenation membrane, and the uniform bubble point of the IPA still ensure that the oxygenation membrane has a good plasma permeation time, which is at least greater than 12 hours (some products may also be greater than 24 hours), and has high tolerance, which can meet the needs of practical applications.

[0012] Ultimately, we were pleasantly surprised to find that when the oxygenation membrane possesses the above characteristics, it has excellent oxygenation capacity, good plasma permeability (tolerance), and good practicality. It is particularly suitable for use in cardiopulmonary surgery and organ transplantation, completely replacing the function of the lungs and providing arterial blood to the organs.

[0013] The pore size and other characteristics of the first pore on the outer surface of the oxygenation membrane can be characterized by scanning electron microscopy (SEM) to reveal the membrane structure's morphology. Measurements can then be performed using computer software (such as Matlab or NIS-Elements) or manually, followed by corresponding calculations. During membrane fabrication, in the direction perpendicular to the membrane thickness (planar if the membrane is a flat sheet, and perpendicular to the radius if it's a hollow fiber membrane), the pore size and other characteristics are generally uniform and consistent. Therefore, the overall pore size on a given plane can be reflected by the pore size in a specific region. In actual measurement, the outer surface of the membrane can be characterized using a microscope to obtain a corresponding SEM image. Since the pore size on the outer surface is generally uniform, a specific area, such as 100 μm, can be selected. 2 (10μm x 10μm), 1μm 2 The area is 1μm x 1μm, and the specific area size depends on the actual situation. The pore size on this area is then measured using appropriate computer software or manually. Several tests are performed (preferably more than 10 times, the specific number depends on the situation), and the average value is taken to obtain the average SEM pore size of the first pore on the outer surface. Of course, those skilled in the art can also obtain the above parameters through other measurement methods. The above measurement methods are for reference only. The average SEM pore size of the second pore on the inner surface of the oxygenation membrane can also be obtained by referring to this method.

[0014] Since the oxygenated membrane of this invention is integrally formed without undergoing processes such as "composite bonding", by observing the main structure of the membrane (e.g., cross-sectional SEM image), it can be seen that the average pore size of the main body gradually changes with the thickness (without abrupt changes). Furthermore, in the membrane thickness direction from the outer surface to the inner surface, the membrane pore size first decreases and then increases. It should be noted that such pore size change is from the perspective of the membrane as a whole, rather than judging from just a specific location.

[0015] The non-directional tortuous pathways of the present invention refer to randomly oriented groove structures and / or discretely distributed pore structures, and each non-directional tortuous pathway is interconnected, which helps to ensure improved membrane fiber tolerance while also having a high gas mass transfer rate.

[0016] Since the pore size of the oxygenation membrane of this invention gradually decreases and then gradually increases with thickness (from the outer surface to the inner surface), there must exist a relatively dense pore region. The determination of this pore region is achieved by first characterizing the membrane cross-section using a scanning electron microscope to obtain a 10,000x magnification electron microscope image of the membrane cross-section; then, taking the outer surface as X0, ten baseline lines (straight lines) perpendicular to the membrane thickness direction are drawn at intervals of 0.5 μm and recorded as X1, X2…X8, X… 9 and X10, each baseline is 10 μm long; for example, taking X5 as an example, measure the pore size of the membrane located on this baseline (preferably more than 5 pores, the specific number depends on the situation), and then take the average value, which is △X5. Then, there must be at least one minimum value from △X1 to △X10, for example, △X5 is the minimum value; then, taking the position of X5 as Y0, draw 5 baselines (straight lines) perpendicular to the membrane thickness direction every 0.2 μm in the direction towards the inner and outer surfaces, and record them as Y. +1 -Y +5 Y -1 To Y -5 (Where the values ​​are +1 to +5 towards the outer surface and -1 to -5 towards the inner surface. However, depending on the actual situation of the SEM image, 6 baselines can be set towards the outer surface and only 4 towards the inner surface. The total number of baselines can also exceed 10, depending on the specific circumstances.) Each baseline is 10 μm long. Measure the pore diameter of the membrane pores located on this baseline (preferably 5 or more pores, the specific number depending on the situation), and then take the average value. Select several baselines whose difference from the average pore diameter of Y0 is no greater than 20% as qualified baselines. Finally, the qualified baseline closest to the outer surface and the qualified baseline closest to the inner surface are the small pore area (assuming the measured average pore diameter at Y0 is 200 nm, then any baseline with an average pore diameter no greater than 240 nm is a qualified baseline, such as Y3, Y2, Y1, Y...). -1 Y -2 These baselines are considered acceptable baselines. Therefore, the acceptable baseline closest to the outer surface is Y3, and the acceptable baseline closest to the inner surface is Y... -2 Therefore, the location of the small hole region can be considered as Y3-Y -2 (The thickness of the small hole area is the Y3 baseline and Y...) -2 The distance between the baselines), and the shortest average distance from the pore area to the outer surface is the distance between the outer surface and the Y3 baseline (the average distance is used because theoretically the membrane pore size cannot be absolutely uniform), and the shortest average distance from the pore area to the inner surface is the distance between the inner surface and the Y3 baseline. -2 The distance between baselines.

[0017] Bubble point is an important performance characteristic of membranes, and its level significantly affects the application range of the membrane. The testing methods for bubble point are well-known in the art; for example, the procedures for these tests are explained in detail in ASTM F316-70 and ANS / ASTM F316-70 (re-approved in 1976), which are incorporated herein by reference. The test solution used in this invention is IPA (isopropanol). The bubble point is divided into the bubble initiation point and the uniform bubble point. When the membrane fiber begins to bubble, the pressure at this point is recorded as the bubble initiation point. When the entire membrane fiber exhibits uniform bubble formation, the pressure at this point is recorded as the IPA uniform bubble point. The uniform bubble point reflects the overall pore size of the membrane; generally, a larger uniform bubble point indicates a smaller overall pore size. In this invention, the oxygenation membrane has a suitable IPA uniform bubble point, thus demonstrating that the oxygenation membrane has a suitable pore size.

[0018] The thickness of the oxygenated membrane of the present invention can be obtained by characterizing the morphology of the membrane structure using a scanning electron microscope, and then by measuring it using computer software (such as Matlab, NIS-Elements, etc.) or manually. Commonly used porosity testing methods include mercury intrusion porosimetry, density method and wet-dry membrane weighing method, etc. Of course, those skilled in the art can also obtain the above parameters by other measurement methods. The above measurement methods are for reference only.

[0019] As a further improvement of the present invention, the thickness of the pore region is 0.2-2 μm, and the ratio of the thickness of the pore region to the overall thickness of the membrane is 0.4%-5%.

[0020] Since the pore region can be considered the area with the smallest pore size within the membrane matrix, further research has revealed that both the absolute and relative thickness of the pore region affect the overall pore size (uniform bubble point size) and porosity of the membrane, thereby impacting the oxygenation performance and tolerance of the oxygenation membrane. When the absolute and relative thickness of the pore region is too large, it will reduce local porosity and affect the overall porosity, potentially increasing the resistance to gas (such as oxygen and carbon dioxide) flow and thus affecting oxygenation efficiency (even if the overall porosity of the membrane fibers remains relatively constant, excessively large pore thickness can still easily reduce oxygenation performance). Furthermore, it can also lead to excessively small overall pore size in the membrane fibers, which will also affect oxygenation performance. Excessive thickness of the pore area can hinder the effective exchange of oxygen and carbon dioxide. Furthermore, excessive thickness of the pore area can increase membrane rigidity, affecting its flexibility, significantly increasing processing difficulty, and reducing industrial applicability. Conversely, excessively small absolute and relative thicknesses of the pore area can lead to excessively large pore sizes in the membrane fibers, affecting their resilience and reducing plasma permeation time. In contrast, appropriately thick pore areas provide sufficient support (acting as a reinforcing layer), enhancing the membrane's pressure resistance and tensile strength. This also allows for a longer plasma permeation time and ensures effective oxygen and carbon dioxide exchange, meeting the needs of clinical applications.

[0021] As a further improvement of the present invention, the nearest average distance from the aperture region to the outer surface is 0.2-3 μm; the product of the SEM average aperture of the first hole and the nearest average distance from the aperture region to the outer surface is 10-300 nm*μm.

[0022] In this invention, the outer surface of the oxygenation membrane contains a first pore. The presence of this first pore helps improve oxygenation capacity, but it can easily affect the membrane's tolerance. The pore region, which can be considered the area with the smallest pore size within the membrane body, is relatively dense. When the closest average distance from the pore region to the outer surface is no greater than 5 μm, the oxygenation membrane can still maintain a good plasma permeation time and exhibit strong tolerance. Further research revealed that when the closest average distance from the pore region to the outer surface is 0.2-3 μm, it is more conducive to reducing plasma permeation, thereby prolonging the plasma permeation time and ensuring a high plasma permeation capacity of the membrane fibers. The permeation time also helps reduce the resistance to gas (such as oxygen and carbon dioxide) flow, improve oxygenation performance, and allow oxygen to enter the blood more easily and quickly through the membrane, while carbon dioxide is also more easily expelled from the blood. Simultaneously, it ensures good pressure resistance on the outer surface (the pore area provides appropriate support to the outer surface), guaranteeing the stability of the membrane during long-term use. Furthermore, further research has found that when the oxygenation membrane has a suitable pore area thickness and a suitable minimum distance between the pore area and the outer surface, the membrane fiber's tolerance is further increased, and the plasma permeation time of the membrane fiber can exceed 24 hours.

[0023] Furthermore, our research has revealed that, based on the specific oxygenation membrane structure of this invention, the closest distance from the pore area to the outer surface is inversely proportional to the average pore diameter of the first pore on the outer surface. Generally, if the average pore diameter of the first pore on the outer surface is larger, then the pore area should be closer to the outer surface; conversely, if the average pore diameter of the first pore on the outer surface is smaller, then the pore area should be slightly farther from the outer surface. The product of the SEM average pore diameter of the first pore and the closest average distance from the pore area to the outer surface is controlled to be 10-300 nm*μm. This is more conducive to the oxygenation membrane having excellent oxygenation performance and a high plasma permeation time, while also having good mechanical strength, thereby ensuring the stability of the membrane filament pore structure and size.

[0024] As a further improvement of the present invention, the SEM average pore size of the first hole is 20-100 nm; the pore area ratio of the outer surface is 0.1%-8%; the surface energy of the outer surface is 25-35 mN / m, and the roughness Ra is 10-80 μm.

[0025] The outer surface is the area of ​​the oxygenation membrane that directly contacts the external blood. Therefore, the characteristics of the outer surface will further affect the various properties of the oxygenation membrane. For example, studies have found that when the SEM average pore size of the first pore is 20-100 nm, it can not only increase the contact area between gas molecules and blood, thereby improving oxygen dissolution and carbon dioxide release, but also have a smaller impact on the membrane fiber tolerance (smaller change in plasma permeation time). At the same time, the pore area ratio (the ratio of the first pore area to the surface area) also affects the gas exchange efficiency of the oxygenation membrane. A higher pore area ratio means more gas exchange area, which can improve oxygenation efficiency. However, if the pore area ratio is too high, it may significantly reduce the plasma permeation time of the membrane fiber and may also reduce the mechanical strength of the membrane. The appropriate first pore size and the pore area ratio of the outer surface work synergistically to further improve the oxygenation performance of the oxygenation membrane, while having a smaller impact on the membrane fiber tolerance and ensuring the mechanical properties of the membrane fiber.

[0026] Furthermore, the oxygenation membrane of this invention is made of PP material, which has good biocompatibility. More specifically, the surface energy of the outer surface is preferably 25-35 mN / m. The surface of the oxygenation membrane affects its interaction with blood; higher surface energy may lead to increased adhesion between the membrane and blood, thereby increasing the risk of plasma leakage. By adjusting the surface energy, the blood compatibility of the membrane can be improved, reducing the possibility of thrombosis. At the same time, we also found that the roughness of the membrane fibers also affects oxygenation performance. This is because surface roughness affects the adsorption and desorption behavior of gas molecules on the membrane surface. Moderate roughness can increase the contact area between gas molecules and the membrane surface, improving gas exchange efficiency, but excessive roughness may lead to the deposition of blood components, affecting the long-term stability and performance of the oxygenation membrane.

[0027] The porosity of the outer surface can be determined by first characterizing the morphology of the outer surface using a scanning electron microscope, then measuring it using computer software (such as Matlab, NIS-Elements, etc.) or manually, and performing corresponding calculations; by selecting a certain area, for example, 1 μm 2 (1μm x 1μm) or 25μm 2 (5μm x 5μm), the specific area size depends on the actual situation. Then, use appropriate computer software or manual measurement to find the area of ​​all holes on this area, then calculate and sum them, and then divide by the corresponding area to obtain the porosity of the surface (measure multiple times, take the average, preferably more than 3 times); of course, those skilled in the art can also obtain the above parameters through other measurement methods, and the above measurement methods are for reference only; (the porosity of the inner surface of the oxygenation film can also be obtained by referring to this method).

[0028] The surface energy test method for the outer surface of the oxygen membrane is to test the hollow fiber membrane with a dyne pen. A 10cm long ink strip is brushed onto the hollow fiber membrane with the dyne pen, and it is observed whether more than 90% of the ink strip shrinks and forms ink droplets within 2 seconds until it stops shrinking and ink droplets appear. The surface energy of the ink tested in this way is the surface energy of the outer surface of the membrane. The roughness of the outer surface of the oxygen membrane of the present invention is measured and obtained using a Keyence 3D scanning microscope. The measurement is performed several times (preferably more than 5 times), and the average value is taken.

[0029] As a further improvement of the present invention, the first hole is a slit-like structure, the major axis of the first hole is consistent with the length direction of the oxygen membrane, the aperture direction of the first hole is consistent with the circumferential direction of the oxygen membrane, the ratio of the average major axis of the first hole to the average aperture of the first hole in SEM is 2-30:1, and the average major axis of the first hole in SEM is not greater than 1000nm.

[0030] The porosity of the oxygenation membrane is 25%-65%.

[0031] In this invention, the first pore can be a circular structure, but research has shown that some first pores are preferably slit-shaped pores (similar to a narrow slit shape), meaning the first pore has a major axis and a minor axis (the length of the major axis is greater than the length of the minor axis). The minor axis is considered to be the pore diameter of the first pore. A smaller minor axis (i.e., the pore diameter, the direction of which is basically consistent with the circumferential direction of the oxygenation membrane) ensures that the oxygenation membrane has a higher plasma permeation time; while a larger major axis (the direction of which is consistent with the length of the oxygenation membrane) may affect the gas exchange efficiency, affecting the gas flow path and speed, thereby improving the exchange efficiency of oxygen and carbon dioxide and enhancing the oxygenation effect; The size of the first pore can also affect the mechanical strength of the membrane fibers. However, if the long axis of the first pore is too large, it may reduce the membrane's pressure resistance and tensile strength, affecting its stability and durability. It can also affect the overall plasma permeation time of the membrane fibers, thus impacting its overall tolerance. Furthermore, having a suitable short axis (pore size) and a suitable ratio of long axis to pore size in the first pore can affect the membrane's surface energy and roughness. Changes in surface energy may affect the interaction between the membrane and blood, while changes in surface roughness may affect the adsorption and desorption behavior of gas molecules on the membrane surface. A first pore with a suitable shape (with a suitable long axis and pore size) and overall porosity can work together to maintain high oxygenation efficiency while also achieving a good plasma permeation time.

[0032] When the first pore is a slit-like pore, that is, when the first pore has both a major axis and an aperture, the SEM average major axis of the first pore can be obtained by first characterizing the morphology of the outer surface of the film using a scanning electron microscope, and then measuring it using computer software or manually, and performing corresponding calculations; by selecting a certain area, for example, 1 μm 2 (1μm x 1μm) or 25μm 2 (5μm x 5μm), the specific area size depends on the actual situation. Then, use appropriate computer software or manual measurement to determine the major diameter of the first hole on this area. Perform several tests (preferably more than 10 times, the specific number depends on the situation), and take the average value to obtain the SEM average major diameter of the first hole on the outer surface. Of course, those skilled in the art can also obtain the above parameters through other measurement methods. The above measurement methods are for reference only. (The SEM average major diameter of the second hole on the inner surface of the oxygenation membrane can also be obtained by referring to this method).

[0033] As a further improvement of the present invention, the ratio of the IPA bubbling point to the uniform bubbling point of the oxygenation membrane is 0.7-0.95:1; and / or, the product of the SEM average major axis of the first pore and the nearest average distance from the pore area to the outer surface is 50-900 nm*μm.

[0034] The bubble point of a membrane primarily reflects the maximum pore size within the membrane (when the pressure reaches this critical value, gas will overflow from the membrane pores, forming bubbles). If the bubble point is too small, it indicates that the maximum pore size inside the membrane is very large. This will affect the overall plasma permeation time of the membrane, increasing the risk of plasma permeation. Furthermore, it may indicate defects in certain areas of the membrane, affecting its mechanical properties. The ratio between the bubble point and the uniform bubble point further indicates the pore size distribution of the membrane. Pore size distribution affects the diffusion path of gas molecules, the mass transfer area, and the flow pattern within the pores (the transfer mechanism of gas molecules may differ in different pore sizes), thus significantly influencing the gas mass transfer rate and consequently affecting oxygenation performance. This invention features a suitable pore size distribution, ensuring appropriate porosity for the membrane fibers and relatively ideal mass transfer between oxygen and carbon dioxide, thereby facilitating carbon dioxide removal and allowing oxygen to more easily and quickly pass through the membrane into the bloodstream.

[0035] Based on the specific structure of the oxygenation membrane of this invention, when some of the first pores are slit-shaped pores, our research also found that the shortest distance from the pore area to the outer surface is inversely proportional to the average major diameter of the first pore on the outer surface. That is, the product of the SEM average major diameter of the first pore and the shortest average distance from the pore area to the outer surface also needs to be kept within a reasonable range (of course, this value will be larger than the product of the pore diameter of the first pore and the shortest average distance from the pore area to the outer surface). This is more conducive to the oxygenation membrane obtaining excellent oxygenation performance, while having less impact on the plasma permeation time and mechanical properties of the oxygenation membrane.

[0036] As a further improvement of the present invention, the inner surface includes a plurality of second holes, wherein the ratio of the average SEM diameter of the second holes to the average SEM diameter of the first holes is 2-20; and the pore area ratio of the inner surface is 1%-15%.

[0037] Generally, those skilled in the art desire a dense outer surface (to ensure plasma permeation time) and a large pore size on the inner surface (to ensure gas mass transfer rate, as the gas mass transfer rate affects oxygenation performance to some extent). This results in a high ratio of pore size between the inner and outer surfaces (often greater than 30 or even 50). However, in this invention, since a first pore of a certain size already exists on the outer surface, the pore size of the second pore on the inner surface does not need to be very large (it can be relatively smaller). That is, the ratio of the SEM average pore size of the second pore to the SEM average pore size of the first pore is relatively small (the ratio is 2-20, preferably 2.5-10). This inner and outer surface structure design is more conducive to effectively controlling the transport of oxygen and carbon dioxide in the membrane, achieving a better gas exchange balance; it also further improves the toughness of the membrane fibers, allowing the oxygenation membrane to simultaneously have higher internal and external burst pressures and high mechanical strength.

[0038] Meanwhile, the inner surface of the present invention also has a suitable number of second holes, that is, the inner surface has a suitable hole area ratio, which is slightly higher than that of the outer surface. This is beneficial to a larger gas exchange surface area, further improving the gas exchange efficiency of the oxygenation membrane; at the same time, it ensures the overall mechanical strength, durability and stability of the membrane fibers, and also has a high internal explosion pressure, making it highly practical for industrial use.

[0039] As a further improvement of the present invention, the second pore is a slit-like structure, the major axis of the second pore is consistent with the length direction of the oxygen membrane, the pore diameter direction of the second pore is consistent with the circumferential direction of the oxygen membrane, the ratio of the SEM average major axis of the second pore to the SEM average pore diameter of the second pore is 2-25:1; the SEM average major axis of the second pore is not greater than 2000 nm; and the porosity of the oxygen membrane is 30%-60%.

[0040] In this invention, the second pore can be a circular structure, but further research has found that some of the second pores are preferably slit-shaped pores (similar to an elliptical shape). That is, the second pore also has a major axis and a minor axis, with the length of the major axis being greater than the length of the minor axis. The minor axis is considered to be the pore size of the second pore (the direction of the major axis of the second pore is consistent with the length direction of the oxygenation membrane, and the direction of the pore size is consistent with the circumferential direction of the oxygenation membrane). The second pore has a suitable ratio of major to minor axis, which is more conducive to improving gas exchange efficiency, particularly the exchange efficiency of oxygen and carbon dioxide, thus improving the oxygenation effect. At the same time, it will further enhance the mechanical strength of the membrane fibers, because if the major axis of the second pore is too large, it may reduce the pressure resistance and tensile strength of the membrane, affecting the stability and durability of the membrane. The second pore with a suitable shape (with a suitable major axis and pore size) and the overall porosity can maintain high oxygenation efficiency while also having good mechanical strength.

[0041] As a further improvement of the present invention, the nearest average distance from the aperture region to the inner surface is 28-77 μm; the ratio of the SEM average pore diameter of the second hole to the nearest average distance from the aperture region to the inner surface is 5-30 nm / μm.

[0042] The pore region is the area with relatively small pore diameter within the membrane pores. Our research found that, in addition to controlling the distance to the outer surface, the closest distance from the pore region to the inner surface can also be further controlled. This is because the area between the pore region and the inner surface is the region with relatively large pores and a relatively large thickness within the membrane body. In this invention, the preferred average closest distance from the pore region to the inner surface is 28-77 μm. At this suitable distance, on the one hand, it is beneficial to improve mechanical support and increase the overall mechanical strength of the oxygenation membrane, enabling it to withstand the pressure and shear force generated by blood circulation; on the other hand, it maintains structural stability: it helps maintain the structural stability of the oxygenation membrane and prevents deformation or collapse during use; it also... Further optimization of gas exchange efficiency can provide more gas exchange area, thereby improving the gas exchange efficiency of the oxygenation membrane. Furthermore, we found that the distance from the pore area to the inner surface is related to the pore size of the second pore. Generally, we expect that a slightly larger pore size in the second pore results in a larger distance from the pore area to the inner surface. Our research suggests that the ratio of the SEM average pore size of the second pore to the nearest average distance from the pore area to the inner surface should be 5-30 nm / μm. This is more conducive to adjusting the pore size distribution of the oxygenation membrane. An appropriate pore size distribution helps improve gas exchange efficiency, tensile strength, and elongation at break; it also enhances the durability (lifespan) of the oxygenation membrane, allowing it to maintain excellent oxygenation performance during long-term use.

[0043] As a further improvement of the present invention, the plasma permeation time of the oxygenation membrane is not less than 12 hours; the O2 mass transfer rate of the oxygenation membrane is not less than 15 ml / (cm²). 2 *min*bar), CO2 mass transfer rate not less than 30ml / (cm²) 2 *min*bar);

[0044] At 1.6m 2 When oxygenation membranes process blood at a flow rate of 5 L / min, the blood oxygen saturation is not less than 99% and the oxygen partial pressure is not less than 150 mmHg.

[0045] The plasma permeation time of the PP oxygenation membrane of this invention is at least 12 hours, preferably at least 18 hours, and more preferably at least 24 hours, indicating that the oxygenation membrane has a long service life. During various cardiopulmonary surgeries and organ transplants, it is not necessary to replace the oxygenation membrane, ensuring the normal progress of the surgery and reducing the impact of external factors on the success of the surgery. The oxygenation membrane of this invention has a suitable oxygen and carbon dioxide mass transfer rate, allowing CO2 in the blood to be rapidly expelled and oxygen to quickly enter the blood, achieving ideal gas exchange without affecting the patient's physical and mental health, ensuring the smooth progress of the surgery. Furthermore, oxygenation performance testing shows that the oxygenation membrane has high oxygenation performance (oxygen saturation not less than 99%, preferably 100%; oxygen partial pressure not less than 150 mmHg, preferably not less than 200 mmHg, more preferably not less than 300 mmHg; the higher the oxygen partial pressure, the better the oxygenation performance), enabling the normal operation of various organs during surgery.

[0046] After mechanical strength testing, the PP oxide film of this invention has a tensile strength of not less than 300 CN and an elongation at break of not less than 600%, exhibiting excellent mechanical properties and high industrial practical value.

[0047] A second aspect of the present invention provides a method for preparing the PP hollow fiber oxygenation membrane as described above, the method comprising the following steps:

[0048] Step 1: Heat and plasticize PP, then dissolve it in a solvent system containing compound A and compound B, and mix it at a temperature of 195-230℃ to prepare a homogeneous casting solution; wherein compound A is a weak solvent for PP, and compound B is a non-solvent for PP; the solid content of PP in the casting solution is 30%-50%;

[0049] Step 2: Extrude the casting liquid under a die at a temperature of 175-190℃ to form a molded product with an inner and outer surface;

[0050] Step 3: Cool the molded part with a coolant to separate the phases. The cooling temperature is 5-20℃ and the cooling residence time is 20-75ms. The coolant is a solvent system containing compound A and compound C, where compound C is a strong solvent for PP and the mass fraction of compound C in the coolant is 10%-40%.

[0051] Step 4: Next, quench the molded product with quenching liquid at a temperature of 40-70℃ for 1-15 minutes. After quenching, a green film is obtained. The content of compound B in the quenching liquid is not less than 70%.

[0052] Step 5: Remove compounds A, B and C from the generated membrane to obtain the original membrane.

[0053] Step 6: Set the original film at high temperature to obtain a PP hollow fiber oxygen membrane.

[0054] As a further improvement of the present invention, the isotacticity of the PP is greater than 95%, and the weight-average molecular weight is 300,000-800,000; the mass fraction of compound A in the solvent system of step one is 60%-80%.

[0055] As a further improvement of the present invention, compound A is at least one of dioctyl phthalate, paraffin oil, dibutyl sebate, dibutyl phthalate and diisooctyl phthalate;

[0056] Compound B is at least one of diethyl phthalate, glyceryl triacetate, castor oil and dioctyl adipate, glyceryl diacetate, glycerol and polyethylene glycol 200;

[0057] Compound C is at least one of soybean oil, N,N-bis(2-hydroxyethyl) tallow amine, palm seed oil, sesame oil, peanut oil, sunflower seed oil, and corn oil.

[0058] As a further improvement of the present invention, before cooling and separating the molded article in step three, the molded article is first subjected to preliminary phase separation. The specific steps of preliminary phase separation are to perform preliminary phase separation on the molded article in an air section; the length of the air section is 1-5 meters, and the temperature of the air section is 70-130℃; and / or, in step four, the quenching liquid is a solvent system of compound A and compound B, and the mass fraction of compound B in the solvent system is 75%-90%.

[0059] As a further improvement of the present invention, the removal of compounds A, B and C from the biofilm in step five specifically refers to extracting the biofilm with an extraction solution at a temperature of 60-80°C for 4-12 hours; wherein the extraction solution is any one of isopropanol, ethanol and acetone; and / or, the high-temperature setting of the original membrane in step six specifically refers to placing the original membrane at a temperature of 90-120°C for high-temperature setting for 30-60 minutes.

[0060] This invention prepares PP (polypropylene) hollow fiber oxygenated membranes via a thermally induced phase separation method. The first step in membrane preparation is to heat and plasticize the PP, then dissolve it in a solvent system containing compounds A and B. The mixture is then kneaded at 195-230°C to uniformly disperse the PP in the solvent system of compounds A and B, facilitating the formation of a homogeneous solution and thus obtaining hollow fiber membranes with good integrity and uniformity. As one of the innovative aspects of this invention, a suitable casting solution formulation has been discovered, in which the solvent system includes compounds A and B. Unlike traditional solvent systems, this invention uses a weak solvent + non-solvent combination. The combination of compounds, wherein compound A is a weak solvent for PP and compound B is a non-solvent for PP; in this invention, a strong solvent refers to a polymer with a solid content of 25% that can be completely dissolved in the solvent at a temperature 30°C above the polymer melting point; a weak solvent refers to a polymer with a solid content of 25% that can be completely dissolved in the solvent at a temperature 50°C above the polymer melting point; and a non-solvent refers to a polymer with a solid content of 5% that can be completely dissolved in the solvent at a temperature 50°C above the polymer melting point; more preferably, compound A is at least one of dioctyl phthalate, paraffin oil, dibutyl sebate, dibutyl phthalate, and diisooctyl phthalate; and compound B is diethyl phthalate or glycerotriacetic acid. The solvent system comprises at least one of esters, castor oil and dioctyl adipate, glyceryl diacetate, glycerol and polyethylene glycol 200; that is, the solvent system of the present invention is a "weak-weak" solvent system (no strong solvent), thereby, combined with the subsequent corresponding phase separation process, forming the membrane pore structure (with small pore regions) and corresponding pore size (with suitable bubble point) and porosity (high porosity) characteristics required for the oxygenated membrane of the present invention; preferably, the mass fraction of compound A in the solvent system is 60%-80%, that is, in the solvent system, the content of weak solvent is greater than the content of non-solvent, which is more conducive to the uniform dispersion of PP in the solvent system, further ensuring the integrity of membrane fibers and the uniformity of membrane pores; while P The solid content of polypropylene (PP) needs to be relatively high, ranging from 30% to 50%, to ensure a small overall pore size in the membrane, guaranteeing plasma permeation time, while also maintaining high porosity. (Too low a solid content makes it difficult to form small pore regions; too high a solid content greatly increases the difficulty of membrane fabrication and significantly reduces porosity). Preferably, isotactic PP is selected, with an isotacticity greater than 95% and a weight-average molecular weight of 300,000 to 800,000. Choosing a suitable PP is more conducive to obtaining ideal pore structure and porosity, and also helps the resulting membrane exhibit excellent mechanical properties. Of course, if necessary, other substances such as antioxidants, nucleating agents, fillers, and similar substances can also be used as additives.

[0061] The second step involves forming a molded product with inner and outer surfaces in a die at a temperature higher than the critical delamination temperature using a casting solution; this molded product is a hollow fiber membrane. The casting solution is extruded through the central cavity of the hollow fiber die, which serves as the inner core, forming and stabilizing the hollow fiber membrane cavity. During extrusion, the inner core is heated to essentially the same temperature as the polymer solution. The extruded hollow fiber membrane has a surface facing the cavity, i.e., the inner surface, and a surface opposite the cavity, i.e., the outer surface, which is separated from the inner surface by the hollow fiber membrane wall. In this invention, the inner core used during hollow fiber membrane extrusion is in gaseous form, preferably nitrogen, argon, or other inert gases, thereby ensuring that the pressure inside the hollow fiber membrane cavity remains balanced with the external pressure, thus stabilizing the hollow fiber membrane cavity.

[0062] The third step is to cool and separate the molded product using a coolant. When solidifying the molded product through phase separation, the selection of the type of coolant, the cooling temperature, and the duration of the cooling residence time are crucial, as these factors determine whether an oxygenated membrane with ideal structure and performance can be obtained. As one of the innovations of this invention, in existing technologies, the coolant is either a non-solvent or the same solvent system as the casting solution. However, in this invention, to ensure that the outer surface of the final oxygenated membrane has a first pore of a certain diameter, and to simultaneously produce an ideal membrane structure (where the average pore size of the main body first decreases and then increases in the film thickness direction from the outer surface to the inner surface), after repeated research, a solvent system of compounds A and C was selected for the coolant (different from the solvent system in the casting solution; the coolant in this invention is a medium-strong solvent system). Compound C is a strong solvent for PP (preferably soybean oil, N,N-bis(2-hydroxy) The presence of at least one of the following: (ethyl) tallow amine, palm seed oil, sesame oil, peanut oil, sunflower seed oil, and corn oil. A small amount of strong solvent in the coolant is beneficial for the formation of ideal pore size and number of primary pores on the outer surface. Simultaneously, the strong solvent compound C must be present in small amounts; otherwise, the overall pore size of the membrane may be too large, which is detrimental to plasma permeation time. To ensure that the overall pore size of the membrane remains small and has high tolerance, under the action of a suitable formulation, the cooling temperature is controlled at 5-20℃, the cooling residence time is 20-75ms, and a suitable coolant system works together to ensure that the overall pore size of the oxygenation membrane is small and has a high plasma permeation time. Furthermore, we were pleasantly surprised to find that in addition to ensuring small pore size, it also ensures a relatively large number of pores (i.e., the overall membrane still has high porosity). This ensures that the oxygenation membrane has high oxygenation performance and rapidly achieves the exchange of oxygen and carbon dioxide.

[0063] Preferably, before cooling and separating the molded product in step three, preliminary phase separation can be performed on the molded product. The purpose of preliminary phase separation is to create the "prototype" of pores on the outer surface of the membrane. With proper preliminary phase separation and cooling phase separation working together, it is beneficial to obtain an ideal outer surface, that is, the outer surface has a suitable number of first pores with suitable pore size, and the outer surface has a suitable roughness, and the pore size of the first pores is relatively uniform. However, it should be noted that the preliminary phase separation must be extremely short, otherwise it is easy to create large pores on the outer surface, which will affect the plasma permeation time of the membrane fibers.

[0064] The fourth step is to quench the molded product with a quenching liquid at a temperature of 40-70℃ for 1-15 minutes, after which a green film is obtained. The content of non-solvent compound B in the quenching liquid is not less than 70% (preferably, the quenching liquid is a solvent system of compound A and compound B, with compound B comprising 75%-90% by mass). In this invention, a suitable quenching process is beneficial for fixing the pore structure: quenching can rapidly solidify the polymer phase formed during phase separation, preventing structural changes during subsequent processing or use; it also improves the uniformity of the film, further contributing to the formation of a uniform pore structure and film thickness, which is crucial for the consistency and reliability of the oxygenated film; furthermore, it minimizes stress and defects in the film, thereby improving the various mechanical properties of the film.

[0065] The fifth step is to remove compounds A, B, and C from the biofilm to obtain the original membrane. This process removes as many solvents (strong and weak) and non-solvents as possible to minimize residues, prevent the introduction of other impurities, ensure the biocompatibility of the PP oxygen membrane, and minimize secondary harm to patients. Preferably, isopropanol, ethanol, or acetone is used as the extraction solvent, and extraction is performed at 60-80℃ for 4-12 hours to ensure the removal of solvents (strong and weak) and non-solvents from the membrane as possible, reducing internal stress and defects, thereby improving membrane uniformity and mechanical properties.

[0066] Finally, the original membrane is high-temperature set to obtain a PP hollow fiber oxygenated membrane. The PP oxygenated membrane after high-temperature setting has good mechanical strength (high tensile strength and elongation at break), thus meeting the needs of actual industrial production. Preferably, the high-temperature setting of this invention specifically refers to setting at a temperature of 90-120℃ for 30-60 minutes to further fix the pore structure formed in the oxygenated membrane during the production process, ensuring the consistency (uniformity) of the pore structure and thickness of the oxygenated membrane, and further guaranteeing the overall performance of the membrane. The final PP oxygenated membrane has excellent oxygenation performance and also has a good plasma permeation time.

[0067] As a further improvement of the present invention, an application of a PP hollow fiber oxygenation membrane is provided, wherein the oxygenation membrane is used for blood oxygenation in cardiopulmonary surgery and / or organ transplantation.

[0068] In cardiopulmonary surgery, oxygenation membranes can provide temporary cardiopulmonary support, ensuring oxygen supply and carbon dioxide removal in the patient's body and maintaining stable vital signs. In organ transplantation, oxygenation membranes can be used to maintain donor organs by providing stable blood circulation and oxygen supply, protecting organs from ischemia and reperfusion injury, while also helping to improve graft quality, reduce post-transplant complications, and improve patient survival rate and quality of life. The oxygenation membrane of this invention has excellent oxygenation performance, can rapidly increase blood oxygen partial pressure and blood oxygen saturation, and also has a good plasma penetration time, making it particularly suitable for use in cardiopulmonary surgery and / or organ transplantation.

[0069] The beneficial effects of this invention are as follows: The PP hollow fiber oxygenation membrane provided by this invention has pores on its outer surface and a small pore region with a very small pore size within the membrane body, located near the outer surface. Simultaneously, the oxygenation membrane as a whole has suitable and uniform bubble point and porosity, thereby achieving excellent oxygenation performance and good plasma permeation time, making it particularly suitable for blood oxygenation in cardiopulmonary surgery and / or organ transplantation. Furthermore, this invention also provides a method for preparing this oxygenation membrane, which is rapid, effective, simple to operate, and suitable for large-scale promotion. Attached Figure Description

[0070] Figure 1 is a scanning electron microscope (SEM) schematic diagram of the cross-section of the PP oxygen membrane prepared in Example 1 near the outer surface, where the magnification is 5000×.

[0071] Figure 2 is a scanning electron microscope (SEM) schematic diagram of the cross-section of the PP oxygen membrane prepared in Example 1 near the inner surface, where the magnification is 5000×.

[0072] Figure 3 is a scanning electron microscope (SEM) schematic diagram of the outer surface of the PP oxygen membrane prepared in Example 1, where the magnification is 20000×.

[0073] Figure 4 is a scanning electron microscope (SEM) schematic diagram of the inner surface of the PP oxygen membrane prepared in Example 1, where the magnification is 20000×.

[0074] Figure 5 is a schematic diagram of the testing device for oxygen saturation and oxygen partial pressure in the oxygenation membrane. Detailed Implementation

[0075] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments.

[0076] Example 1: A method for preparing a PP hollow fiber oxygen membrane, comprising the following steps:

[0077] Step 1: Heat and plasticize PP, then dissolve it in a solvent system containing compound A and compound B, and mix it at a temperature of 210°C to prepare a homogeneous casting solution.

[0078] Compound A is a weak solvent for PP, and compound B is a non-solvent for PP; compound A is dioctyl phthalate; compound B is glyceryl triacetate; the mass fraction of compound A in the solvent system is 70%;

[0079] The solid content of PP in the casting solution is 40%; the isotacticity of the PP is greater than 95%, and the weight-average molecular weight is 500,000.

[0080] Step 2: The casting liquid is extruded under a die at a temperature of 185℃ to form a molded product with an inner surface and an outer surface;

[0081] Step 3: First, perform preliminary phase separation on the molded product. The molded product is placed in an air section with a length of 3 meters and a temperature of 100℃. Next, cool the molded product for further phase separation using a coolant at a temperature of 12℃ and a residence time of 40ms. The coolant is a solvent system containing compound A and compound C, where compound C is a strong solvent for PP and is soybean oil; compound A is dioctyl phthalate; the mass fraction of compound C in the coolant is 25%.

[0082] Step 4: Next, quench the molded product with a quenching solution at a temperature of 55℃ for 8 minutes. After quenching, a green film is obtained. The quenching solution is a solvent system of compound A and compound B. Compound A is dioctyl phthalate, and compound B is triglyceride. The mass fraction of compound B in the solvent system is 80%. Step 5: Extract the green film with isopropanol at a temperature of 70℃ for 8 hours to remove compounds A, B, and C from the green film and obtain the original film.

[0083] Step 6: Place the original film at a temperature of 110℃ for high-temperature setting for 50 minutes to obtain a PP hollow fiber oxygenated film.

[0084] Example 2: A method for preparing a PP hollow fiber oxygen membrane, comprising the following steps:

[0085] Step 1: Heat and plasticize PP, then dissolve it in a solvent system containing compound A and compound B, and mix it at a temperature of 220°C to prepare a homogeneous casting solution.

[0086] Compound A is a weak solvent for PP, and compound B is a non-solvent for PP; compound A is paraffin oil; compound B is diethyl phthalate; the mass fraction of compound A in the solvent system is 65%;

[0087] The solid content of PP in the casting solution is 45%; the isotacticity of the PP is greater than 95%, and the weight-average molecular weight is 650,000.

[0088] Step 2: The casting liquid is extruded through a die at a temperature of 190℃ to form a molded product with an inner and outer surface;

[0089] Step 3: First, perform preliminary phase separation on the molded product. The molded product is placed in an air section with a length of 2 meters and a temperature of 90°C. Next, cool the molded product for further phase separation using a coolant at a temperature of 8°C and a residence time of 25 ms. The coolant is a solvent system comprising compound A and compound C, where compound C is a strong solvent for PP and is N,N-bis(2-hydroxyethyl) tallow amine; compound A is paraffin oil; the mass fraction of compound C in the coolant is 15%.

[0090] Step 4: Next, quench the molded product with quenching liquid at a temperature of 50°C for 15 minutes. After quenching, a green film is obtained. The quenching liquid is a solvent system of compound A and compound B. Compound A is paraffin oil and compound B is diethyl phthalate. The mass fraction of compound B in the solvent system is 80%.

[0091] Step 5: Extract the raw membrane with isopropanol at 70℃ for 12 hours to remove compounds A, B and C from the raw membrane and obtain the original membrane;

[0092] Step 6: Place the original film at a temperature of 100℃ for high-temperature setting for 60 minutes to obtain a PP hollow fiber oxygenated film.

[0093] Example 3: A method for preparing a PP hollow fiber oxygen membrane, comprising the following steps:

[0094] Step 1: Heat and plasticize PP, then dissolve it in a solvent system containing compound A and compound B, and mix it at a temperature of 205°C to prepare a homogeneous casting solution.

[0095] Compound A is a weak solvent for PP, and compound B is a non-solvent for PP; compound A is dibutyl sebate; compound B is castor oil; the mass fraction of compound A in the solvent system is 75%;

[0096] The solid content of PP in the casting solution is 35%; the isotacticity of the PP is greater than 95%, and the weight-average molecular weight is 550,000.

[0097] Step 2: The casting liquid is extruded through a die at a temperature of 180℃ to form a molded product with an inner and outer surface;

[0098] Step 3: First, perform preliminary phase separation on the molded product. The molded product is placed in an air section with a length of 4 meters and a temperature of 110℃. Next, cool the molded product with a coolant for further phase separation. The cooling temperature is 16℃, and the cooling residence time is 55ms. The coolant is a solvent system containing compound A and compound C, where compound C is a strong solvent for PP and is palm seed oil; compound A is dibutyl sebate; the mass fraction of compound C in the coolant is 30%.

[0099] Step 4: Next, quench the molded product with quenching liquid at a temperature of 60℃ for 10 minutes. After quenching, a green film is obtained. The quenching liquid is a solvent system of compound A and compound B. Compound A is dibutyl sebate and compound B is castor oil. The mass fraction of compound B in the solvent system is 85%.

[0100] Step 5: Extract the raw membrane with ethanol at 60℃ for 6 hours to remove compounds A, B and C from the raw membrane and obtain the original membrane;

[0101] Step 6: Place the original film at a temperature of 105℃ for high-temperature setting for 45 minutes to obtain a PP hollow fiber oxygenated film.

[0102] Example 4: A method for preparing a PP hollow fiber oxygen membrane, comprising the following steps:

[0103] Step 1: Heat and plasticize PP, then dissolve it in a solvent system containing compound A and compound B, and mix it at a temperature of 200°C to prepare a homogeneous casting solution.

[0104] Compound A is a weak solvent for PP, and compound B is a non-solvent for PP; compound A is dibutyl phthalate; compound B is glyceryl diacetate; the mass fraction of compound A in the solvent system is 80%;

[0105] The solid content of PP in the casting solution is 40%; the isotacticity of the PP is greater than 95%, and the weight-average molecular weight is 450,000.

[0106] Step 2: The casting liquid is extruded through a die at a temperature of 175°C to form a molded product with an inner and outer surface;

[0107] Step 3: First, perform preliminary phase separation on the molded product. The molded product is placed in an air section with a length of 5 meters and a temperature of 120°C. Next, cool the molded product with a coolant at a temperature of 20°C for a cooling residence time of 70 ms. The coolant is a solvent system containing compound A and compound C, where compound C is a strong solvent for PP and is sesame oil; compound A is dibutyl phthalate; the mass fraction of compound C in the coolant is 35%.

[0108] Step 4: Next, quench the molded product with a quenching solution at a temperature of 65℃ for 5 minutes. After quenching, a green film is obtained. The quenching solution is a solvent system of compound A and compound B. Compound A is dibutyl phthalate, and compound B is glycerol diacetate. The mass fraction of compound B in the solvent system is 85%. Step 5: Extract the green film with acetone at a temperature of 75℃ for 10 hours to remove compounds A, B, and C from the green film and obtain the original film.

[0109] Step 6: Place the original film at a temperature of 120℃ for high-temperature setting for 40 minutes to obtain a PP hollow fiber oxygenated film.

[0110] Structural and performance tests were performed on the samples.

[0111] 1. Structural characterization: The morphology of the main membrane structure of each sample was characterized using a scanning electron microscope (Hitachi S-5500), and the required data were obtained; the specific results are shown in the table below:

[0112] Table 1 - External Surface Characteristics:

[0113]

[0114] Meanwhile, surface energy tests showed that the surface energy of the PP oxygenated films prepared in Examples 1-4 was 25-35 mN / m, indicating suitable surface energy.

[0115] Table 2 - Characteristics of the small hole area

[0116]

[0117] Table 3 - Overall characteristics of oxygenation membrane

[0118]

[0119]

[0120] Table 4 - Internal Surface Characteristics

[0121]

[0122] As can be seen from Tables 1 to 4, Examples 1-4 all have ideal membrane structures.

[0123] Comparative Example 1

[0124] The procedure was carried out in accordance with Example 1, except that preliminary phase separation was not performed in step three when preparing the PP oxygenated membrane. In addition, when the molded product was cooled and phase separated with a coolant, the coolant was replaced with a solvent system containing compound A and compound B, wherein compound A is dioctyl phthalate and compound B is glyceryl triacetate, and the mass fraction of compound B in the coolant is 25%; the other conditions remain unchanged.

[0125] In the final PP hollow fiber oxygenated membrane, the outer surface of the membrane is dense, meaning there are no first pores. At the same time, the membrane pores gradually increase in the thickness direction from the outer surface to the inner surface, meaning there are no so-called small pore areas.

[0126] Comparative Example 2

[0127] The procedure was carried out in accordance with Example 1, except that preliminary phase separation was not performed in step three when preparing the PP oxygenated membrane. Instead, when cooling the molded product for phase separation with a coolant, the cooling temperature was set to 25°C and the cooling residence time was set to 90 ms. The coolant was a solvent system comprising compound A and compound C, where compound C is a strong solvent for PP and is soybean oil; compound A is dioctyl phthalate; the mass fraction of compound C in the coolant was set to 45%; all other conditions remained unchanged.

[0128] In the final PP hollow fiber oxygenated membrane, the outer surface of the oxygenated membrane has a first pore, but the SEM average pore size of the first pore is too large, about 307 nm. At the same time, there is a small pore region in the thickness direction from the outer surface to the inner surface, but the nearest average distance from the small pore region to the outer surface is greater than 5 μm, which is 5.8 μm.

[0129] Comparative Example 3

[0130] The procedure was carried out in accordance with Example 1, except that in step 1, the solvent system consisted only of compound A, which is a weak solvent for PP and is dioctyl phthalate; the solid content of PP in the casting solution was 20%; no preliminary phase separation was performed in step 3; and all other conditions remained unchanged.

[0131] In the final PP hollow fiber oxygen membrane, the uniform bubble point of the IPA in the oxygen membrane is 0.51 MPa. The bubble point is too small, which indicates that the overall pore size of the oxygen membrane is too large.

[0132] Comparative Example 4

[0133] The procedure was carried out in accordance with Example 1, except that the solid content of PP in the casting solution in step one was 60%; the isotacticity of the PP was 80%; no preliminary phase separation was performed in step three, and the cooling temperature during cooling phase separation was 3°C and the cooling residence time was 10ms, while the other conditions remained unchanged.

[0134] In the final PP hollow fiber oxygenated membrane, the uniform bubble point of IPA was 1.08 MPa, which was too high, indicating that the overall pore size of the oxygenated membrane was too small; at the same time, the overall porosity was only 12%, which was too low, indicating that the number of membrane pores was too small.

[0135] Example 5

[0136] The procedure was carried out in accordance with Example 1, except that the mass fraction of compound A in the solvent system in step one was 85%; the isotacticity of the PP was 90% and the weight-average molecular weight was 200,000; and no preliminary phase separation was performed in step three, while the other conditions remained unchanged; in the final PP hollow fiber oxygenated membrane, the thickness of the pore region in the oxygenated membrane was less than 0.2 μm, about 0.1 μm, and the overall membrane thickness was 50 μm, with the ratio of the pore region thickness to the overall membrane thickness being 0.1 / 50 = 0.2%; compared with Example 1, Example 5 showed lower tolerance and a shorter plasma permeation time.

[0137] Example 6

[0138] The process was carried out in accordance with Example 1, except that the mass fraction of compound A in the solvent system in step one was 50%; the isotacticity of the PP was 90%; no preliminary phase separation was performed in step three; and in step six, the high-temperature setting temperature was 130°C and the setting time was 20 minutes; all other conditions remained unchanged. In the final PP hollow fiber oxygenated membrane, the thickness of the pore region was greater than 2 μm, approximately 3 μm, and the overall membrane thickness was 50 μm. The ratio of the pore region thickness to the overall membrane thickness was 3 / 50 = 6%. Compared to Example 1, the oxygenation performance of Example 6 was lower.

[0139] Example 7

[0140] The procedure was carried out in accordance with Example 1, except that in step one, the mass fraction of compound A in the solvent system was 90%; in step three, no preliminary phase separation was performed; in step four, the quenching liquid was a solvent system of compound A and compound B, with the mass fraction of compound B in the solvent system being 70%; and the other conditions remained unchanged.

[0141] In the final PP hollow fiber oxygenated membrane, the SEM average pore size of the first pore on the outer surface of the oxygenated membrane is 120 nm; and the closest average distance from the pore area to the outer surface is 3.3 μm (the pore area is slightly far from the outer surface); compared with Example 1, Example 7 has lower tolerance and shorter plasma permeation time.

[0142] Example 8

[0143] The procedure was carried out in accordance with Example 1, except that in step one, the mass fraction of compound A in the solvent system was 55%; in step three, no preliminary phase separation was performed; in step four, the quenching liquid was a solvent system of compound A and compound B, and the mass fraction of compound B in the solvent system was 95%; all other conditions remained unchanged.

[0144] In the final PP hollow fiber oxygenated membrane, the SEM average pore size of the first pore on the outer surface of the oxygenated membrane is 18 nm; and the closest average distance from the pore area to the outer surface is 0.15 μm (the pore area is slightly closer to the outer surface); compared with Example 1, the oxygenation performance of Example 8 is weaker.

[0145] II: Performance Testing

[0146] 1. Gas mass transfer rate tests were conducted on the PP oxygen membranes prepared in Examples 1 to 8. The testing method was as follows: Under conditions of 25°C, 1 bar pressure, and a membrane sample area of ​​0.1 square meters, one side of the membrane sample was subjected to the test gas (oxygen, carbon dioxide, anesthetic gas); the test gas was supplied into the inner cavity of the hollow fiber membrane; the volumetric flow rate of the gas permeating through the membrane wall was measured using a flow meter (KOFLOC / 4800, Japan); the test was performed three times from inside the membrane to outside, and three times from outside the membrane to inside, and the average value was taken. This average value is the gas mass transfer rate of the membrane. Gas mass transfer rate unit: ml / (cm²) 2 *min*bar)

[0147] 2. To determine the plasma leakage time of the sample, a phospholipid solution (1.5g lecithin dissolved in 500ml physiological saline solution) at 37℃ was used at a rate of 6L / (min*m). 2 A pressure of 1.0 bar is applied to the surface of the membrane sample. Air is then allowed to flow along the other side of the membrane sample, and the air that has flowed through the membrane sample passes through a cold trap. The weight of the liquid that accumulates in the cold trap is measured as a function of time. The time at which a significant increase in weight occurs, i.e., the time at which the liquid first significantly accumulates in the cold trap, is defined as the plasma leakage time.

[0148] 3. Based on the ISO-7199 standard, at 1.6m 2 Under oxygenation membrane treatment of blood at a flow rate of 5 L / min, the oxygen saturation and partial pressure of oxygen in blood (arterial blood) were measured using a blood gas analyzer (unit: mmHg), as shown in Figure 5.

[0149] Sample O2 mass transfer rate CO2 mass transfer rate Plasma osmosis time Oxygen saturation Oxygen partial pressure Example 1 2 9 4 3 > 24 hours 100% 30 9 Example 2 2 0 3 5 > 24 hours 100% 30 4 Example 3 3 7 5 1 > 24 hours 100% 31 2 Example 4 4 ​​3 5 8 > 24 hours 100% 31 7 Example 5 2 3 3 7 > 12 hours 100% 25 7 Example 6 1 5 3 0 > 24 hours 100% 16 3 Example 7 2 1 3 5 > 18 hours 100% 23 1 Example 8 1 7 3 2 > 24 hours 100% 18 2 Comparative Example 1 9 18 / 98% 10 8 Comparative Example 2 / / 1.5 hours / / Comparative Example 3 / / 3 hours / / Comparative Example 4 4 ​​12 / 97% 92 surface

[0150] After testing, the plasma permeation time of the PP oxygenation membranes prepared in Examples 1-8 was all over 12 hours, which shows that the PP oxygenation membranes prepared by the present invention have good tolerance and a suitable service life; at the same time, they have excellent oxygenation performance and can quickly achieve rapid exchange of oxygen and carbon dioxide.

[0151] 4. Tensile strength and elongation at break test: Each sample was stretched at a uniform speed (50 mm / min, 30 mm distance between upper and lower clamps) using a tensile testing machine at room temperature until it broke. The tensile strength and elongation at break were measured. This was repeated 3 times, and the average value was taken. This average value is the final tensile strength and elongation at break value of the film. The PP oxygen film prepared in Examples 1-8 of this invention has a tensile strength of not less than 300 cN and an elongation at break of not less than 600%, which has excellent mechanical properties and high industrial practical value.

[0152] The above description is merely a preferred embodiment of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principles of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A PP hollow fiber oxygenation membrane, comprising a main body, wherein 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, characterized in that: The main body has non-directional tortuous pathways; the outer surface contains a plurality of first pores, the SEM average pore size of the first pores being no greater than 200 nm; in the film thickness direction from the outer surface to the inner surface, the average pore size of the main body first decreases and then increases; the main body includes a pore region, the nearest average distance from the pore region to the outer surface is less than the nearest average distance from the pore region to the inner surface, and the nearest average distance from the pore region to the outer surface is no greater than 5 μm; the porosity of the oxygenation membrane is no less than 25%, the uniform bubble point of IPA is 0.7-0.99 MPa, and the overall thickness is 30-80 μm.

2. The PP hollow fiber oxygenation membrane according to claim 1, characterized in that: The thickness of the pore region is 0.2-2 μm, and the ratio of the thickness of the pore region to the overall thickness of the membrane is 0.4%-5%.

3. The PP hollow fiber oxygenation membrane according to claim 1, characterized in that: The nearest average distance from the pore area to the outer surface is 0.2-3 μm; the product of the SEM average pore diameter of the first hole and the nearest average distance from the pore area to the outer surface is 10-300 nm*μm.

4. The PP hollow fiber oxygenation membrane according to claim 1, characterized in that: The average SEM pore size of the first hole is 20-100 nm; the pore area ratio of the outer surface is 0.1%-8%; the surface energy of the outer surface is 25-35 mN / m, and the roughness Ra is 10-80 μm.

5. The PP hollow fiber oxygenation membrane according to claim 1, characterized in that: The first pore is a slit-like structure. The major axis of the first pore is aligned with the length of the oxygen membrane, and the pore diameter is aligned with the circumferential direction of the oxygen membrane. The ratio of the average major axis of the first pore to the average pore diameter in SEM is 2-30:

1. The average major axis of the first pore in SEM is no greater than 1000 nm. The porosity of the oxygen membrane is 25%-65%.

6. The PP hollow fiber oxygenation membrane according to claim 1, characterized in that: The ratio of the IPA bubbling point to the uniform bubbling point of the oxygenation membrane is 0.7-0.95:1; and / or, the product of the SEM average major axis of the first pore and the nearest average distance from the pore area to the outer surface is 50-900 nm*μm.

7. The PP hollow fiber oxygenation membrane according to claim 1, characterized in that: The inner surface includes a plurality of second holes, the ratio of the average SEM diameter of the second holes to the average SEM diameter of the first holes being 2-20; the pore area ratio of the inner surface is 1%-15%.

8. A PP hollow fiber oxygenation membrane according to claim 7, characterized in that: The second pore is a slit-like structure. The major axis of the second pore is aligned with the length of the oxygen membrane, and the pore diameter is aligned with the circumferential direction of the oxygen membrane. The ratio of the average major axis of the second pore to the average pore diameter in SEM is 2-25:

1. The average major axis of the second pore in SEM is no greater than 2000 nm. The porosity of the oxygen membrane is 30%-60%.

9. A PP hollow fiber oxygenation membrane according to claim 7, characterized in that: The nearest average distance from the pore area to the inner surface is 28-77 μm; the ratio of the SEM average pore diameter of the second hole to the nearest average distance from the pore area to the inner surface is 5-30 nm / μm.

10. A PP hollow fiber oxygenation membrane according to claim 1, characterized in that: The plasma permeation time of the oxygenation membrane is not less than 12 hours; the O2 mass transfer rate of the oxygenation membrane is not less than 15 ml / (cm²). 2 *min*bar), CO2 mass transfer rate not less than 30ml / (cm²) 2 *min*bar); at 1.6m 2 When oxygenation membranes process blood at a flow rate of 5 L / min, the blood oxygen saturation is not less than 99% and the oxygen partial pressure is not less than 150 mmHg.

11. A method for preparing a PP hollow fiber oxygen membrane according to any one of claims 1-10, characterized in that: The process includes the following steps: Step 1: Heating and plasticizing PP, then dissolving it in a solvent system containing compound A and compound B, and mixing at a temperature of 195-230℃ to prepare a homogeneous casting solution; wherein compound A is a weak solvent for PP, and compound B is a non-solvent for PP; the solid content of PP in the casting solution is 30%-50%; Step 2: Extruding the casting solution under a die at a temperature of 175-190℃ to form a molded product with an inner and outer surface; Step 3: Cooling and separating the molded product with a coolant at a temperature of 5-20℃, and stopping the cooling process. The residence time is 20-75ms; the coolant is a solvent system including compound A and compound C, wherein compound C is a strong solvent for PP, and the mass fraction of compound C in the coolant is 10%-40%; Step 4: The molded product is then quenched with quenching liquid at a temperature of 40-70℃ for 1-15min, and a green film is obtained after quenching; wherein the content of compound B in the quenching liquid is not less than 70%; Step 5: Compound A, compound B and compound C are removed from the green film to obtain the original film; Step 6: The original film is high-temperature set to obtain a PP hollow fiber oxygenated film.

12. The method for preparing a PP hollow fiber oxygen membrane according to claim 11, characterized in that: The isotacticity of the PP is greater than 95%, and the weight-average molecular weight is 300,000-800,000; the mass fraction of compound A in the solvent system of step one is 60%-80%.

13. The method for preparing a PP hollow fiber oxygen membrane according to claim 11, characterized in that: Compound A is at least one of dioctyl phthalate, paraffin oil, dibutyl sebate, dibutyl phthalate, and diisooctyl phthalate; Compound B is at least one of diethyl phthalate, glyceryl triacetate, castor oil, dioctyl adipate, glyceryl diacetate, glycerol, and polyethylene glycol 200; Compound C is at least one of soybean oil, N,N-bis(2-hydroxyethyl) tallow amine, palm seed oil, sesame oil, peanut oil, sunflower seed oil, and corn oil.

14. The method for preparing a PP hollow fiber oxygen membrane according to claim 11, characterized in that: Before cooling and separating the molded product in step three, a preliminary phase separation is performed on the molded product. The specific steps for the preliminary phase separation are as follows: the molded product is subjected to preliminary phase separation in an air section; the length of the air section is 1-5 meters, and the temperature of the air section is 70-130℃; and / or, in step four, the quenching liquid is a solvent system of compound A and compound B, and the mass fraction of compound B in the solvent system is 75%-90%.

15. The method for preparing a PP hollow fiber oxygen membrane according to claim 11, characterized in that: In step five, removing compounds A, B, and C from the raw membrane specifically refers to extracting the raw membrane with an extraction solution at a temperature of 60-80℃ for 4-12 hours; wherein the extraction solution is any one of isopropanol, ethanol, and acetone; and / or, in step six, high-temperature setting of the original membrane specifically refers to placing the original membrane at a temperature of 90-120℃ for high-temperature setting for 30-60 minutes.

16. The application of a PP hollow fiber oxygenation membrane according to any one of claims 1-10, characterized in that: The oxygenation membrane is used for blood oxygenation in cardiopulmonary surgery and / or organ transplantation.

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