Hollow fiber membrane hemodialyzer with gradient aperture structure

Abstract

The invention is applicable to the technical field of hemodialyzers, and provides a hollow fiber membrane hemodialyzer with a gradient aperture structure, which comprises a shell, a hollow fiber membrane bundle packaged in the shell, an end cover and a sealing component, the hollow fiber membrane bundle is composed of a plurality of gradient aperture hollow fiber membranes; the hollow fiber membrane is of a two-way gradient aperture structure along the membrane thickness direction; a compact screening layer and a loose transition layer are sequentially arranged on the inner wall of the hollow fiber membrane; a loose diffusion layer and a compact protective layer are sequentially arranged on the outer side of the hollow fiber membrane; the pore diameter of the compact protective layer is not greater than 30nm; the porosity of the hollow fiber membrane is synchronously and progressively increased along with the aperture gradient, the porosity range is 40%-80%, the dialyzer has the characteristics of bidirectional gradient aperture optimization design, gradient functional coating protection, modular adaptation, special-shaped section synergy and the like, and the technical problems that an existing dialyzer is incomplete in toxin removal, insufficient in safety and the like are solved.

Description

A hollow fiber membrane hemodialyzer with a gradient pore size structure Technical Field

[0001] This invention relates to the field of hemodialysis technology, and more specifically, to a hollow fiber membrane hemodialysis device with a gradient pore size structure. Background Technology

[0002] Hemodialysis is a core treatment for end-stage renal disease patients to maintain their lives. Its core component is the hollow fiber membrane hemodialysis machine, which uses the sieving and diffusion effects of the membrane to exchange toxins in the blood with the dialysate, thus purifying the blood. Currently, hemodialysis machines on the market mainly suffer from the following technical defects.

[0003] First, the pore structure design is unreasonable: most existing hollow fiber membranes have a single pore size or a unidirectional gradient pore size structure, which makes it difficult to balance the clearance efficiency of small molecule toxins with the retention requirements of medium molecule toxins. This leads to the accumulation of medium molecule toxins such as β2-microglobulin, causing complications such as dialysis-related amyloidosis. At the same time, the poor matching between the membrane porosity and pore size distribution results in high mass transfer resistance, which affects dialysis efficiency.

[0004] Secondly, there are insufficient biocompatibility and safety: when blood comes into contact with the membrane surface, it can easily trigger a coagulation reaction, requiring the use of large amounts of anticoagulants and increasing the risk of bleeding; bacteria and impurities on the dialysate side can easily seep back into the blood through the membrane, leading to infectious complications; some membrane materials lack biomimetic design, which can easily trigger the body's immune rejection reaction.

[0005] Finally, it has a single function: it only relies on the pore size to remove toxins, and its purification effect on difficult-to-remove toxins such as protein-bound toxins is poor, which cannot meet the diverse blood purification needs of patients. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a hollow fiber membrane hemodialyzer with a gradient pore size structure, featuring bidirectional gradient pore size optimization design, gradient functional coating protection, modular adaptation, and enhanced efficiency of irregular cross-sections, thereby solving the technical problems of incomplete toxin removal and poor safety in existing dialyzers.

[0007] To achieve the above objectives, the present invention provides the following technical solution: a hollow fiber membrane hemodialysis device with a gradient pore size structure, comprising a shell, a hollow fiber membrane bundle encapsulated within the shell, end caps, and sealing components; the hollow fiber membrane bundle is composed of a plurality of hollow fiber membranes with gradient pore sizes; the hollow fiber membranes have a bidirectional gradient pore size structure along the membrane thickness direction; a dense screening layer and a loose transition layer are sequentially disposed on the inner wall of the hollow fiber membrane; a loose diffusion layer and a dense protective layer are sequentially disposed on the outer side of the hollow fiber membrane; the pore size of the dense screening layer is 20~100nm; the pore sizes of the loose transition layer and the loose diffusion layer gradually increase to 50~500nm along the membrane thickness direction; the pore size of the dense protective layer is not greater than 30nm; the porosity of the hollow fiber membrane increases synchronously with the pore size gradient, and the porosity ranges from 40% to 80%.

[0008] The present invention is further configured such that the gradient slope of the gradient aperture can be adjusted as needed. For patients with different toxin loads, the thickness of the dense screening layer is 1~5μm, and the gradient slope adjustment range is 0.05~0.2nm / μm. Among them, the gradient slope suitable for patients with medium molecular weight toxin accumulation is not less than 0.12nm / μm.

[0009] The present invention is further configured such that: the hollow fiber membrane is made of a composite modified material, the substrate being a blend of polysulfone polymer and polyvinylpyrrolidone, wherein the polysulfone polymer is one or more of polysulfone, polyethersulfone or polyethersulfone, and the proportion of polyvinylpyrrolidone is 5% to 15 wt%.

[0010] The present invention is further configured such that: the outer side of the loose transition layer is coated with a hydrophilic anticoagulant coating; the hydrophilic anticoagulant coating material is a heparinized derivative or a polyethylene glycol graft polymer, and the coating thickness is 0.1~1μm; the hollow fiber membrane interlayer is embedded with adsorbent nanoparticles; the adsorbent nanoparticles are one of activated carbon, zeolite molecular sieve or modified silica, with a particle size of 50~200nm, and the addition amount is 2%~8% of the substrate mass; the outer side of the dense protective layer is coated with an antibacterial coating; the antibacterial coating material is a quaternary ammonium salt compound or a chitosan derivative.

[0011] The present invention is further configured such that: a biomimetic material is mixed into the hollow fiber membrane substrate; the biomimetic material is one of collagen, hyaluronic acid or chitosan, and the addition amount is 3%~10wt%, which simulates the structure of the human kidney basement membrane and improves biocompatibility.

[0012] The present invention is further configured such that: the hollow fiber membrane is a smart responsive structure, and an environmentally responsive polymer is introduced into the substrate. The responsive polymer is a temperature-sensitive poly(N-isopropylacrylamide) or a pH-sensitive polymethacrylic acid. When the urea concentration in the blood is higher than 10 mmol / L, the membrane pore size can automatically expand by 10% to 20%.

[0013] The present invention is further configured such that: the two end caps are respectively connected to a blood inlet tube and a blood outlet tube; and the outer wall of the shell is sequentially connected to a dialysate inlet tube and a dialysate outlet tube.

[0014] The present invention is further configured such that the cross-section of the hollow fiber membrane is an irregular structure, selected from elliptical, trilobal, or pentlobal shapes. Compared with a circular cross-section, the contact area between blood and membrane is increased by 25% to 40%, and the blood flow resistance is reduced by 15% to 25%.

[0015] The advantages of this invention are: 1. This invention uses a bidirectional gradient pore size structure with synchronously increasing porosity design. The dense screening layer accurately traps useful proteins in the blood, while the loose transition layer and loose diffusion layer reduce mass transfer resistance, achieving a urea clearance rate of not less than 180 ml / min and a β2-microglobulin clearance rate of not less than 60 ml / min. The intermediate layer uses adsorption-type nanoparticles to target and remove protein-bound toxins. Combined with an intelligent responsive membrane structure (the pore size automatically expands when the urea concentration is too high), it adapts to different toxin load scenarios and solves the problem of single toxin removal in existing dialyzers.

[0016] 2. This invention reduces the risk of thrombosis and the dosage of anticoagulants by setting a hydrophilic anticoagulant coating on the blood side; the dense protective layer on the dialysate side and the antibacterial coating form a dual protection of "physical interception + antibacterial killing" to avoid reverse contamination; the biomimetic material mixed in the substrate simulates the structure of the human kidney basement membrane, reduces immune rejection, and comprehensively improves the safety of treatment. Attached Figure Description

[0017] Figure 1 is a schematic diagram of a hollow fiber membrane hemodialyzer with a gradient pore size structure according to the present invention.

[0018] Figure 2 is a cross-sectional view of the present invention from the right perspective of Figure 1.

[0019] Figure 3 is a cross-sectional view of the hollow fiber membrane of the present invention from a frontal perspective.

[0020] Figure 4 is a schematic diagram of the hollow fiber membrane with an elliptical cross-section in Embodiment 2 of the present invention.

[0021] Figure 5 is a schematic diagram of the hollow fiber membrane with a trilobal cross-section in Embodiment 2 of the present invention.

[0022] Figure 6 is a schematic diagram of the hollow fiber membrane with a five-lobed cross-section in Embodiment 2 of the present invention.

[0023] In the diagram: 1. Outer shell; 2. Hollow fiber membrane bundle; 3. End cap; 4. Hollow fiber membrane; 5. Dense screening layer; 6. Loose transition layer; 7. Loose diffusion layer; 8. Dense protective layer; 9. Antibacterial coating; 10. Hydrophilic anticoagulant coating; 11. Adsorbent nanoparticles; 12. Blood inlet tube; 13. Blood outlet tube; 14. Dialysis fluid inlet tube; 15. Dialysis fluid outlet tube. Detailed Implementation

[0024] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. The present invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0025] It should be noted that, unless otherwise specified, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0026] In this invention, unless otherwise stated, the directional terms such as "up" and "down" generally refer to the directions shown in the accompanying drawings, or to the vertical, perpendicular, or gravitational direction; similarly, for ease of understanding and description, "left" and "right" generally refer to the left and right shown in the accompanying drawings; "inner" and "outer" refer to the inner and outer contours of each component itself, but the above directional terms are not intended to limit this invention.

[0027] Example 1, please refer to Figures 1-3. The present invention provides the following technical solution: a hollow fiber membrane hemodialysis device with a gradient pore size structure, specifically including a shell 1, a hollow fiber membrane bundle 2 encapsulated in the shell 1, an end cap 3, and a sealing component; the hollow fiber membrane bundle 2 is composed of several gradient pore size hollow fiber membranes 4; the hollow fiber membranes 4 have a bidirectional gradient pore size structure along the membrane thickness direction; a dense screening layer 5 and a loose transition layer 6 are sequentially arranged on the inner wall of the hollow fiber membrane 4; a loose diffusion layer 7 and a dense protective layer 8 are sequentially arranged on the outer side of the hollow fiber membrane 4; the pore size of the dense screening layer 5 is 20~100nm; the pore sizes of the loose transition layer 6 and the loose diffusion layer 7 gradually increase to 50~500nm along the membrane thickness direction; the pore size of the dense protective layer 8 is not greater than 30nm; the porosity of the hollow fiber membrane 4 increases synchronously with the pore size gradient, and the porosity range is 40%~80%.

[0028] The dense screening layer 5 has a pore size of 50 nm and a thickness of 3 μm; the pore sizes of the loose transition layer 6 and the loose diffusion layer 7 gradually increase to 300 nm along the film thickness direction; the dense protective layer 8 has a pore size of 20 nm; the porosity of the hollow fiber membrane 4 increases synchronously with the pore size gradient, and the porosity is 60%.

[0029] The gradient slope of the gradient pore size can be adjusted as needed. For patients with different toxin loads, the thickness of the dense screening layer 5 is 1~5μm, and the gradient slope adjustment range is 0.05~0.2nm / μm. Among them, the gradient slope suitable for patients with medium molecular weight toxin accumulation is not less than 0.12nm / μm.

[0030] The gradient slope of the gradient pore size is adjusted to 0.15 nm / μm, which is suitable for patients with accumulation of medium molecular weight toxins (such as dialysis patients with β2-microglobulin concentration >30 mg / L).

[0031] The hollow fiber membrane 4 is made of composite modified material. The substrate is a blend of polysulfone polymer and polyvinylpyrrolidone, wherein the polysulfone polymer is one or more of polysulfone, polyethersulfone or polyethersulfone, and the polyvinylpyrrolidone accounts for 5% to 15 wt%.

[0032] Hollow fiber membrane 4 is made of composite modified material, with the substrate being a blend of polyethersulfone and polyvinylpyrrolidone, wherein the polyvinylpyrrolidone accounts for 10 wt%, which has both good mechanical strength and hydrophilicity.

[0033] The outer side of the loose transition layer 6 is coated with a hydrophilic anticoagulant coating 10; the hydrophilic anticoagulant coating 10 is made of heparinized derivatives or polyethylene glycol grafted polymers, and the coating thickness is 0.1~1μm; the middle layer of the hollow fiber membrane 4 is embedded with adsorbent nanoparticles 11; the adsorbent nanoparticles 11 are one of activated carbon, zeolite molecular sieves or modified silica, with a particle size of 50~200nm, and the addition amount is 2%~8% of the substrate mass; the outer side of the dense protective layer 8 is coated with an antibacterial coating 9; the antibacterial coating 9 is made of quaternary ammonium salt compounds or chitosan derivatives.

[0034] The loose transition layer 6 is coated with a polyethylene glycol grafted polymer hydrophilic anticoagulant coating 10 with a thickness of 0.5 μm to reduce the interfacial tension between blood and membrane surface and reduce platelet adhesion. The hollow fiber membrane 4 has activated carbon nanoparticles 11 with a particle size of 100 nm embedded in the middle layer, with an addition amount of 5% of the substrate mass, for adsorbing protein-bound toxins such as phenols and indoles in the blood. The dense protective layer 8 is coated with a quaternary ammonium salt antibacterial coating 9 to inhibit the adhesion and reproduction of common pathogenic bacteria such as Escherichia coli and Staphylococcus aureus in the dialysate.

[0035] Bionic materials are mixed into the hollow fiber membrane substrate 4; the bionic materials are one of collagen, hyaluronic acid or chitosan, and the addition amount is 3%~10wt%, which simulates the structure of the human kidney basement membrane to improve biocompatibility.

[0036] 5wt% of collagen biomimetic material is mixed into the hollow fiber membrane (4) substrate to simulate the chemical composition and structure of the human kidney basement membrane, reduce the immunogenicity of the membrane and improve biocompatibility.

[0037] Hollow fiber membrane 4 has a smart responsive structure. An environmentally responsive polymer is introduced into the substrate. The responsive polymer is temperature-sensitive poly(N-isopropylacrylamide) or pH-sensitive polymethacrylic acid. When the urea concentration in the blood is higher than 10 mmol / L, the membrane pore size can automatically expand by 10% to 20%.

[0038] The hollow fiber membrane 4 has a smart responsive structure. Temperature-sensitive poly(N-isopropylacrylamide) is introduced into the substrate. When the urea concentration in the blood is higher than 10 mmol / L, the pore size of the loose transition layer 6 and loose diffusion layer 7 of the membrane automatically increases by 15%, thereby improving the mass transfer efficiency under high toxic load.

[0039] The two end caps 3 are respectively connected to a blood inlet tube 12 and a blood outlet tube 13; the outer wall of the shell 1 is sequentially connected to a dialysate inlet tube 14 and a dialysate outlet tube 15.

[0040] Blood and dialysate flow in a countercurrent manner to maximize the concentration gradient and improve toxin removal efficiency.

[0041] The working principle of this embodiment is as follows: During treatment, the patient's blood enters the hollow fiber membrane bundle 2 inside the dialyzer housing 1 through the blood inlet tube 12. The blood flows in the inner cavity of the hollow fiber membrane 4. The dialysate enters the chamber between the housing 1 and the hollow fiber membrane bundle 2 through the dialysate inlet tube 14, flowing in the opposite direction to the blood. Small molecule toxins such as urea and creatinine in the blood are sieved by the dense screening layer 5 and diffused into the dialysate through the loose transition layer 6 and the loose diffusion layer 7. Medium molecule toxins such as β2-microglobulin are efficiently removed under the synergistic effect of gradient pore size and high porosity. Protein-bound toxins are adsorbed by activated carbon nanoparticles 11 in the intermediate layer. When the urea concentration in the blood is too high, the intelligent responsive polymer automatically expands the membrane pore size, increasing the toxin removal rate. The hydrophilic anticoagulant coating 10 reduces thrombus formation, the antibacterial coating 9 and the dense protective layer 8 prevent reverse contamination on the dialysate side, and the collagen biomimetic material improves biocompatibility, ultimately achieving safe and efficient blood purification.

[0042] Example 2, please refer to Figures 4-6. This example 2 is an improvement on Example 1. Specifically, the cross-section of the hollow fiber membrane 4 is an irregular structure, selected from elliptical, trilobal, or pentlobal shapes. Compared with a circular cross-section, the contact area between blood and membrane is increased by 25% to 40%, and the blood flow resistance is reduced by 15% to 25%.

[0043] The other technical parameters of this second embodiment are the same as those of the first embodiment, and it is suitable for dialysis patients with high blood viscosity and poor vascular conditions (such as end-stage renal disease patients with diabetic vascular complications).

[0044] The working principle of this embodiment two is consistent with the core purification principle of embodiment one, the difference being the design of the trilobal cross-section: compared with the circular cross-section, the trilobal structure increases the contact area between the blood and the inner wall of the hollow fiber membrane 4, allowing toxins in the blood to come into more full contact with the membrane surface and be removed through the membrane structure; at the same time, the flow channel design of the trilobal cross-section is more in line with the flow characteristics of blood, reducing turbulence and eddies, lowering blood flow resistance, and keeping the blood chamber pressure drop below 60 mmHg (lower than the 80 mmHg upper limit of traditional circular cross-section dialyzers), avoiding vascular damage caused by excessive pressure, improving patient treatment comfort, and is especially suitable for patients with poor vascular conditions and who cannot tolerate high-pressure dialysis (the cross-sections of elliptical and pentagonal shapes are different from those of trilobal shapes, and will not be described in detail here).

[0045] Obviously, the embodiments described above are merely some, not all, embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort should fall within the scope of protection of the present invention.

[0046] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0047] It should be noted that the terms "first," "second," etc., used in the specification, claims, and accompanying drawings of this application are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments of this application described herein can be implemented in sequences other than those illustrated or described herein.

[0048] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

[0049] 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 hollow fiber membrane hemodialysis device with a gradient pore size structure, comprising a shell (1), a hollow fiber membrane bundle (2) encapsulated within the shell (1), an end cap (3), and a sealing component; characterized in that: The hollow fiber membrane bundle (2) is composed of several hollow fiber membranes (4) with gradient pore sizes; the hollow fiber membrane (4) has a bidirectional gradient pore size structure along the membrane thickness direction; a dense screening layer (5) and a loose transition layer (6) are sequentially arranged on the inner wall of the hollow fiber membrane (4); a loose diffusion layer (7) and a dense protective layer (8) are sequentially arranged on the outer side of the hollow fiber membrane (4); the pore size of the dense screening layer (5) is 20~100nm; the pore size of the loose transition layer (6) and the loose diffusion layer (7) gradually increases to 50~500nm along the membrane thickness direction; the pore size of the dense protective layer (8) is not greater than 30nm; the porosity of the hollow fiber membrane (4) increases synchronously with the pore size gradient, and the porosity range is 40%~80%.

2. The hollow fiber membrane hemodialyzer with a gradient pore size structure according to claim 1, characterized in that: The gradient slope of the gradient aperture can be adjusted as needed. For patients with different toxin loads, the thickness of the dense screening layer (5) is 1~5μm, and the gradient slope adjustment range is 0.05~0.2nm / μm. The gradient slope suitable for patients with medium molecular weight toxin accumulation is not less than 0.12nm / μm.

3. A hollow fiber membrane hemodialyzer with a gradient pore size structure according to claim 2, characterized in that: The hollow fiber membrane (4) is made of a composite modified material. The substrate is a blend of polysulfone polymer and polyvinylpyrrolidone, wherein the polysulfone polymer is one or more of polysulfone, polyethersulfone or polyethersulfone, and the polyvinylpyrrolidone accounts for 5% to 15 wt%.

4. A hollow fiber membrane hemodialyzer with a gradient pore size structure according to claim 3, characterized in that: The loose transition layer (6) is coated with a hydrophilic anticoagulant coating (10) on the outside; the hydrophilic anticoagulant coating (10) is made of heparinized derivatives or polyethylene glycol grafted polymers, and the coating thickness is 0.1~1μm; the hollow fiber membrane (4) has an adsorption nanoparticle (11) embedded in the middle layer; the adsorption nanoparticle (11) is one of activated carbon, zeolite molecular sieve or modified silica, with a particle size of 50~200nm, and the amount added is 2%~8% of the substrate mass; the dense protective layer (8) is coated with an antibacterial coating (9) on the outside; the antibacterial coating (9) is made of quaternary ammonium salt compounds or chitosan derivatives.

5. A hollow fiber membrane hemodialyzer with a gradient pore size structure according to claim 4, characterized in that: The hollow fiber membrane (4) substrate is mixed with biomimetic materials; the biomimetic materials are one of collagen, hyaluronic acid or chitosan, and the amount added is 3%~10wt%, which simulates the structure of the human kidney basement membrane to improve biocompatibility.

6. A hollow fiber membrane hemodialyzer with a gradient pore size structure according to claim 5, characterized in that: The hollow fiber membrane (4) has a smart responsive structure. An environmentally responsive polymer is introduced into the substrate. The responsive polymer is temperature-sensitive poly(N-isopropylacrylamide) or pH-sensitive polymethacrylic acid. When the urea concentration in the blood is higher than 10 mmol / L, the membrane pore size can automatically expand by 10% to 20%.

7. A hollow fiber membrane hemodialyzer with a gradient pore size structure according to claim 6, characterized in that: The two end caps (3) are respectively connected to a blood inlet tube (12) and a blood outlet tube (13); the outer wall of the shell (1) is connected to a dialysate inlet tube (14) and a dialysate outlet tube (15).

8. A hollow fiber membrane hemodialyzer with a gradient pore size structure according to claim 7, characterized in that: The hollow fiber membrane (4) has an irregular cross-section, selected from elliptical, trilobal or pentlobal shapes. Compared with a circular cross-section, the contact area between blood and membrane is increased by 25% to 40%, and the blood flow resistance is reduced by 15% to 25%.

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