Acites filter, ascites protein extraction system comprising ascites filter and ascites protein extraction method
By using hollow fiber membrane wires made of polysulfone resins and other polymer materials in ascites filters, and optimizing membrane pore distribution and rinsing design, the problems of low protein recovery and easy breakage of membrane wires in the prior art are solved, and efficient ascites protein recovery and safe filtration effects are achieved.
Patent Information
- Application Number
- CN202510186747.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-20
- Publication Date
- 2025-05-27
- Estimated Expiration
- 2045-02-20
AI Technical Summary
The existing ascites filters have low protein recovery, and the membrane wire filter pores are prone to breakage under backwashing pressure, resulting in high transmittance of harmful components and affecting the therapeutic effect.
A ascites filter was designed, in which the hollow fiber membrane filaments were made of a mixed material of polysulfone resin and other polymer materials, the membrane pore size was ≤0.285 μm, and the membrane pores with ≥0.25 μm accounted for ≥30% of the total area of the membrane pores. In addition, by expanding the diameter of the flushing liquid outlet to be 1.8-2.2 times the diameter of the flushing liquid inlet, the flushing efficiency is improved and the impact on the membrane wire is reduced.
It significantly improves the recovery rate of ascites protein by more than 90%, while reducing the transmittance of harmful components, enhancing the mechanical strength and compressive strength of the membrane wire, and improving the service life and safety of the filter.
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Figure CN120037780A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of ascites filtration, and particularly to an ascites filter, an ascites protein extraction system and method comprising the ascites filter. Background Art
[0002] In recent years, a treatment method using the Cellfree and Concentrated Ascites Reinfusion Therapy has been implemented for patients with liver cirrhosis and cancer. The process of ascites filtration and concentration is generally as follows: Ascites is extracted from the patient's abdominal cavity, filtered to remove cell components such as cancer cells and bacteria in the protein solution present in the ascites, and the preliminarily purified ascites is further processed through a concentration technique to remove excess water and retain useful components such as macromolecular substances like proteins. This process can significantly reduce the liquid volume while maintaining important protein components. Finally, the liquid after filtration and concentration treatment is reinjected into the patient's blood circulation system. This approach can help replenish the lost proteins, maintain blood volume, and relieve symptoms such as dyspnea and anorexia caused by a large amount of ascites.
[0003] During the filtration process of this therapy, due to the blockage of the filter pores of the hollow fiber membrane by substances such as cancer cells and bacteria, under the filtration operation pressure and flushing pressure, it is easy to cause the fragmentation of cancer cells, bacteria, etc. or the damage of the filter pores of the membrane filaments. A large amount of harmful components from the damage pass through the filter membrane and enter the concentrated solution, failing to achieve the effect of filtering out the causative substances. In this case, when the concentrated solution is reinjected intravenously, the patient will have side effects such as high fever, which instead consumes the patient's physical strength and energy.
[0004] Prior arts such as JP2023154449A, JP2023001798A, CN106794287B, CN106999855A, DE2611212C2, etc. disclose a similar filter. However, these filters still have some common deficiencies. The pore size of the membrane filaments used in these filters is too small, with a maximum not exceeding 0.2 μm. It is very difficult for the recovery rates of proteins and immunoproteins to exceed 85%. Moreover, such a pore size is not only easily blocked but also necessarily leads to an increase in the number of flushing times, subjecting the membrane filaments to more frequent impacts. For example, the protein transmittance of CN106794287B is only 80%. Although some technical solutions such as CN106999855A mention that the pore size of the membrane filaments is 0.010 μm - 10 μm, preferably 0.05 μm - 5 μm, such a wide pore size distribution makes the membrane filaments unsuitable for ascites filtration and easily leads to the recovery of harmful substances, posing a safety hazard to patients when reinfused intravenously. Summary of the Invention
[0005] (1) Technical problems to be solved
[0006] In view of the above-mentioned disadvantages and deficiencies of the prior art, the present invention provides an ascites filter, an ascites protein extraction system and method including the ascites filter, which can, to a certain extent, solve the technical problems of relatively low protein recovery rate in existing ascites and obvious deformation or damage of the pores of the membrane filaments under backwashing pressure, and further reduce the permeation rate of harmful components while increasing the ascites protein recovery rate.
[0007] (2) Technical solutions
[0008] In a first aspect, the present invention provides an ascites filter, which includes: a filtration chamber, in which a plurality of hollow fiber membrane filaments are installed, there is a spacing between the hollow fiber membrane filaments, and sealing materials are respectively provided at both ends of the hollow fiber membrane filaments, and the sealing materials seal the spacing between the hollow fiber membrane filaments and the spacing between the hollow fiber membrane filaments and the inner wall of the filtration chamber;
[0009] The filtration chamber includes a first end and a second end, a flushing liquid inlet is provided at the first end, and a filtrate outlet is provided at the second end; the two ends of the hollow fiber membrane filaments respectively form a spacing with the first end and the second end, and the spacing between the hollow fiber membrane filaments and the first end of the filtration chamber constitutes a flushing liquid inlet buffer zone, and the spacing between the hollow fiber membrane filaments and the second end of the filtration chamber constitutes a filtrate outlet buffer zone; an ascites inlet is provided on one side of the filtration chamber, and the ascites inlet communicates with the filtration chamber and corresponds to the middle between the two ends of the hollow fiber membrane filaments, and is at the end of the ascites inlet far from the filtrate outlet; a flushing liquid outlet is also provided on one side of the filtration chamber, and the flushing liquid outlet communicates with the filtration chamber and corresponds to the middle between the two ends of the hollow fiber membrane filaments, and the flushing liquid outlet is provided at the end far from the flushing liquid inlet;
[0010] Wherein, the hollow fiber membrane filaments comprise a mixed material of a first polymer material and a second polymer material, the first polymer material is a polysulfone resin, and the second polymer material is at least one selected from polyethylene, polypropylene, polyvinyl alcohol and polyacrylonitrile; wherein the mass ratio of the polysulfone resin is 55-65%; the pore diameter of the hollow fiber membrane filaments is d, d≤0.285μm, and the pores with a pore diameter above 0.25μm account for ≥30% of the total pore area of the membrane pores.
[0011] According to a preferred embodiment of the present invention, the mass ratio of the polysulfone resin in the hollow fiber membrane filaments is 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64% or 65%; and the ratio of the membrane pores with a pore diameter above 0.25 μm to the total area of the membrane pores does not exceed 50%, that is, the ratio of the membrane pores with a pore diameter above 0.25 μm to the total area of the membrane pores is 30-50%; more preferably, the ratio of the membrane pores with a pore diameter above 0.20 μm to the total area of the membrane pores is 40-65%. If the ratio of the membrane pores with a pore diameter above 0.20 μm or 0.25 μm is too high, it will affect the mechanical strength and anti-deformation ability of the hollow fiber membrane filaments, resulting in a decrease in its ability to resist filtration and washing pressure; therefore, preferably, the ratio of the membrane pores with a pore diameter above 0.25 μm to the total area of the membrane pores does not exceed 50%, and the ratio of the membrane pores with a pore diameter above 0.20 μm to the total area of the membrane pores is 40-65%.
[0012] The polysulfone resin component can enhance the compressive strength and toughness of the hollow fiber membrane filaments. However, although polysulfone (PSU) resin materials have good mechanical strength and chemical stability, they are strongly hydrophobic and not easily hydrophilic modified. And high hydrophobicity easily leads to high protein adsorption and cell adhesion, thus affecting the filtration efficiency and the service life of the membrane. In addition, the processability of the hollow fiber membrane made of all polysulfone resins is poor, and it is difficult to obtain a preset pore size distribution.
[0013] Preferably, the hollow fiber membrane filaments comprise a first polymer material and a second polymer material. The first polymer material is a polysulfone resin, and its mass ratio in the hollow fiber membrane filaments is 55-65%; the balance is the second polymer material, and the second polymer material is at least one of polyethylene, polypropylene, polyvinyl alcohol and polyacrylonitrile doped with 3-8 wt% PVP. Polyvinylpyrrolidone (PVP) has good biocompatibility and hydrophilicity, increases the hydrophilicity of the hollow fiber membrane, reduces the chance of cells adhering to the membrane surface, and thus reduces the cell transmittance. It can reduce the non-specific binding and adsorption of proteins to the membrane and improve the protein recovery rate.
[0014] Preferably, the surface of the hollow fiber membrane filaments is further subjected to a hydrophilic treatment. The methods of hydrophilic treatment include but are not limited to plasma, chemical grafting, or hydrophilic coating, etc. Among them, plasma treatment usually uses low-pressure plasma or atmospheric pressure plasma technology. This treatment can introduce polar groups (such as hydroxyl groups, carboxyl groups) on the membrane surface, thereby increasing the hydrophilicity of the membrane surface. Commonly used plasma treatment gases include oxygen, argon, nitrogen, carbon dioxide, etc. Different gases generate different active particles, and the effects on the modification of the membrane surface are also different. The treatment power can be set to 50W - 300W, and the treatment time is from several seconds to several minutes, usually operating in the range of dozens of pascals to hundreds of pascals. Chemical grafting can use acrylic monomers (such as acrylic acid, methacrylic acid) or PEG grafting. The hydrophilic coating can use natural polysaccharides such as chitosan, etc. The natural polysaccharide solution is coated on the membrane surface by dip coating method, and then cured by heating or cross-linking agent to form a stable hydrophilic layer. These measures can reduce the adsorption of proteins and the contamination of other biological components by the hollow fiber membrane.
[0015] Preferably, the membrane pore size is d ≤ 0.285μm, and the proportion of membrane pores with a pore size above 0.25μm is 30 - 50%. This allows some proteins and immune proteins to pass through the pores and be recovered, which is beneficial for both improving the protein recovery rate and the compressive strength of the hollow fiber membrane filaments. Membrane pores with a pore size above 0.25μm are larger pores. Such pore sizes can improve the recovery rate of ascites proteins, but when their proportion is too large, it may cause the compressive strength and toughness of the hollow fiber membrane filaments to deteriorate. During ascites filtration, under the operating pressure, the pore size of the hollow fiber membrane filaments further increases or even pores (merged pores) appear, resulting in harmful substances permeating into the protein recovery solution, which is unsafe.
[0016] According to a preferred embodiment of the present invention, the diameter of the flushing liquid outlet is D1, and the diameter of the flushing liquid inlet is D2, and D1 / D2 is 1.8 - 2.2. Preferably, D1 / D2 is 2. By increasing the diameter of the flushing liquid outlet to about 2 times the diameter of the flushing liquid inlet, this is beneficial for the backwashing of the filter. It can increase the pressure difference inside and outside the hollow fiber membrane under a lower operating pressure, produce a good flushing effect with a very small pressure, improve the flushing efficiency, and save time. As mentioned above, once pore deformation, pore rupture, or pore merging occurs, the safety of the ascites recovery product will decrease.
[0017] According to a preferred embodiment of the present invention, calculated based on the proportion of the total cross-section of the hollow fiber membrane filaments in the cross-section of the filtration chamber, the filling rate of the hollow fiber membrane filaments in the filtration chamber is 30 - 40%, more preferably 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, or 40%. The filling rate of the hollow fiber membrane filaments in the filtration chamber determines the membrane filtration area under a certain filtration chamber length.
[0018] According to a preferred embodiment of the present invention, the filtration chamber is a cylindrical filtration chamber with an inner diameter D3, where D3 = 4 - 4.5 cm, and the total specific surface area of the hollow fiber membrane filaments in the filtration chamber is 1.3 - 2.0 m²; when the filling rate of the hollow fiber membrane filaments in the filtration chamber is 30 - 40%, D1 / D3 at the flushing liquid outlet is 1 / 2 - 1 / 3. Herein, the total sum of the specific surface areas of the hollow fiber membrane filaments located in the filtration chamber refers to the membrane filtration area of the ascites filter. When the inner diameter of the filtration chamber is relatively small, the membrane filtration area can be satisfied by increasing the length of the hollow fiber membrane filaments in the filtration chamber. However, when the length of the hollow fiber membrane filaments is too large, the encapsulation difficulty is high, and the middle part of the hollow fiber membrane filaments becomes fragile and breaks. When the inner diameter of the filtration chamber is relatively large, the length of the hollow fiber membrane filaments must be shortened to meet the membrane filtration area. At this time, the filtration path becomes shorter and is prone to clogging.
[0019] According to a preferred embodiment of the present invention, in the filtration chamber, the hollow fiber membrane filaments are installed in an S shape or a C shape, thereby enabling the hollow fiber membrane filaments to have a certain degree of curvature. In the filtration chamber, the distance between the two ends of the hollow fiber membrane filaments is L1 (installation length), and the actual length of the hollow fiber membrane filaments is L2, where L2 / L1 is 1.05 - 1.3, preferably 1.1 - 1.2. Experiments have shown that when the membrane filaments have a certain degree of curvature, under filtration and backwashing conditions, the filtrate or backwashing water always acts on the surface of the membrane filaments at a certain non-vertical angle, which can not only improve the filtration efficiency but also reduce the damage to the membrane filaments caused by the filtration operation pressure and the backwashing pressure simultaneously.
[0020] According to a preferred embodiment of the present invention, the sealing material is a waterproof sealing adhesive, and the sealing adhesive is bonded to the outer surface of the ends of the hollow fiber membrane filaments to seal the gaps between the hollow fiber membrane filaments.
[0021] In a second aspect, the present invention provides an ascites protein extraction system including this ascites filter, which includes the above-mentioned ascites filter and a concentrator. Both the filter and the concentrator are horizontally arranged or installed. The filtration liquid outlet of the ascites filter is connected to the stock solution inlet of the concentrator by a pipeline. The concentrated liquid outlet of the concentrator is connected to a pump, and the concentrated liquid is introduced into a concentrated liquid collection device through the pump. A waste liquid outlet is also provided on one side of the concentrator, and the waste liquid outlet is connected to a negative pressure suction device; no pressurizing device is provided at the front end of the ascites filter.
[0022] Preferably, the concentrator is a hollow fiber membrane device, which includes a housing and a hollow fiber membrane bundle arranged inside the housing. One end of the housing is the stock solution inlet, which is connected to the filtration liquid outlet of the ascites filter. The other end of the housing is the concentrated liquid outlet, which is connected to a pump; the waste liquid outlet is provided on one side of the housing, the outer end of the waste liquid outlet is connected to the negative pressure suction device, and the inner end of the waste liquid outlet is communicated with the inside of the housing but not with the hollow channels of the hollow fiber membrane bundle.
[0023] In a third aspect, the present invention provides a method for extracting ascites protein, which is implemented by the ascites protein extraction system described in the above solution, and includes the following steps:
[0024] S1. Horizontally place the ascites filter and concentrator on the operating platform;
[0025] S2. Place the normal saline bag at a height of 30 - 50 cm on the operating platform, so that the normal saline enters the filtration chamber from the ascites inlet of the filter under gravity and exits from the flushing liquid outlet, thereby completing the flushing of the inside of the filtration chamber and the outside of the hollow fiber membrane filaments; then, close the flushing liquid outlet, open the valve and the negative pressure suction device between the ascites filter and the concentrator, so that the normal saline enters from the ascites inlet of the filter under gravity and exits from the filtrate outlet, thereby completing the flushing of the inside of the hollow fiber membrane filaments of the ascites filter;
[0026] S3. Place the ascites bag at a height of 30 - 50 cm on the operating platform, open the valve between the ascites bag and the ascites filter, and at the same time open the negative pressure suction device and the pump connected to the concentrator; adjust the working pressure of the negative pressure suction device, adjust the pump speed to 10 - 30 mL / min, so that the filtration pressure of the filter is 30 KPa (225 mmHg) - 60 KPa (450 mmHg); at this time, the ascites enters the filtration chamber from the ascites inlet of the filter under gravity, the protein-containing filtrate is discharged from the filtrate outlet and enters the concentrator, and after entering the concentrator, it flows in the hollow channels of the hollow fiber membrane filament bundle of the concentrator, and the excess water and electrolytes are filtered to the outside of the hollow fiber membrane filament bundle and discharged from the waste liquid outlet under the operation of the negative pressure suction device; the protein-containing concentrated liquid remains inside the hollow fiber membrane filament bundle and is driven by the pump to enter the concentrated liquid collection device;
[0027] S4. When the outlet speed of the concentrated liquid drops to 50% of the initial speed, perform backwashing; the backwashing process is as follows:
[0028] S41. Close the valve between the ascites bag and the ascites inlet of the filter, and keep the filter connected to the concentrator; inject normal saline into the flushing liquid inlet (preferably inject 100 mL, manually push it in with a syringe), and push the protein-containing liquid inside the hollow fiber membrane filaments of the ascites filter into the concentrator for further concentration treatment through the normal saline;
[0029] S42. After the treatment is completed, turn off the pump and the negative pressure suction device, close the valve between the filter and the concentrator, open the valve between the ascites bag and the ascites inlet of the filter, inject normal saline into the flushing liquid inlet (preferably 200 mL, manually push it in with a syringe), and push the ascites that has entered the filtration chamber back into the ascites bag through the normal saline;
[0030] S43. Close the valve between the ascites bag and the ascites inlet of the filter, open the flushing liquid outlet, and inject normal saline into the flushing liquid inlet (preferably 50 mL, manually pushed in using a syringe). The normal saline permeates from the inside to the outside of the hollow fiber membrane filaments of the filter, flushing down the blockage on the outside of the hollow fiber membrane filaments. The operation of injecting normal saline is repeated 8 - 12 times, and the pressure of injecting normal saline does not exceed 66.6 KPa (500 mmHg).
[0031] S5. After the flushing is completed, close the flushing liquid outlet and the flushing liquid inlet, open the valve between the ascites bag and the filter, open the valve between the ascites filter and the concentrator, turn on the pump and the negative pressure suction device connected to the concentrator, and continue to extract ascites protein according to the method of S3.
[0032] (III) Beneficial effects
[0033] The technical effects of the present invention include, but are not limited to, the following points:
[0034] 1. By more reasonably designing the pore size of the hollow fiber membrane filaments of the filter, the membrane pore size of the hollow fiber membrane filaments ≤ 0.285 μm and the membrane pores with a membrane pore size above 0.25 μm account for ≥ 30% of the total membrane pore area; thus, the recovery rate of ascites protein is greatly improved, enabling the ascites protein recovery rate to exceed 90%, retaining more important protein components of the patient, and reducing the consumption of the patient's physical strength and energy during ascites dialysis; this protein recovery rate is greater than the prior art where the highest ascites protein recovery rate does not exceed 85%.
[0035] 2. When the pore size of the hollow fiber membrane filaments increases, the mechanical strength and the performance against the filtration operation pressure and the flushing pressure of the membrane filaments may be weakened. A certain proportion of polysulfone - based material is mixed into the material of the hollow fiber membrane filaments, making its incorporation amount reach 55 - 65%. The relatively high content of polysulfone resin strengthens the compressive strength and toughness of the filament membrane, enhancing the mechanical strength.
[0036] 3. The prior art has made improvements to the ascites filter in many aspects, including various optimization designs of the number of filter membrane filaments, the central pore size, the outer diameter of the membrane filaments, the setting density of the membrane filaments in the filtration chamber, the curvature of the membrane filaments, the filtration operation pressure, etc., but has not effectively solved the impact and damage of back - flushing on the membrane filaments, which easily causes obvious deformation or damage to the pore size of the filament membrane, reducing the quality of ascites filtration. In the present invention, by expanding the diameter of the flushing liquid outlet of the ascites filter to 1.8 - 2.2 times (preferably 2 times) the diameter of the flushing liquid inlet, a good flushing effect can be produced with a very small flushing pressure, improving the flushing efficiency. This is beneficial to reducing the impact of the flushing pressure on the hollow fiber membrane filaments, protecting the stability of the membrane pore size, and maintaining the accuracy and stability of the long - term retention parameters of the membrane filaments.
[0037] 4. In the ascites protein extraction system of the present invention, no pressurizing device is provided at the front end of the filter, which avoids the breakage (failure to achieve the filtering effect) of organisms such as cancer cells, bacteria, and red blood cells due to excessive pressure into fragments that cannot be intercepted by the filter, ensures the ascites protein extraction rate while reducing the residue of harmful substances, improves the transfusion safety of the recycled and concentrated protein solution of ascites, and reduces the side effects of transfusion.
[0038] 5. During the ascites protein extraction process, the ascites filter and concentrator are placed horizontally on the operation platform, so that the ascites filtration process mainly depends on the gravity flow into the filter, and the ascites flows naturally horizontally in the filter. This can prevent the upper end of the membrane filaments from deforming less but the lower end of the membrane filaments from being severely deformed due to greater pressure after the filter is placed vertically for a period of operation. The severely deformed membrane filaments and membrane filtration pores lose the ability to intercept harmful components, and the problem of inconsistent interception parameters at both ends of the membrane filaments is likely to cause some harmful substances with a relatively large specific gravity to tend to pass through the filter membrane from the lower end of the membrane filaments.
[0039] 6. The filtration pressure of the ascites protein extraction system is mainly adjusted by the negative pressure suction device at the rear connected to the concentrator, so that the filtration pressure of the ascites filter is 225 - 450 mmHg, preventing the problem of breakage of organisms such as cancer cells, bacteria, and red blood cells caused by pre-filter pressurization, and effectively protecting the hollow fiber membrane filaments of the ascites filter.
[0040] 7. During the ascites protein extraction process, the flushing liquid inlet is flushed by manually injecting normal saline with a syringe. Compared with the traditional automated pressurized flushing equipment, the manual syringe push flushing can reduce the breakage rate of organisms such as cancer cells, bacteria, and red blood cells and membrane pores, greatly reduce the probability of harmful components entering the filtrate, and reduce the risk of side effects caused by the protein concentrate being transfused to patients. BRIEF DESCRIPTION OF THE DRAWINGS
[0041] Figure 1 It is a schematic diagram of the structure of the ascites filter of the present invention.
[0042] Figure 2 It is a schematic diagram of the ascites protein extraction system of the present invention. DETAILED DESCRIPTION OF THE INVENTION
[0043] In order to better explain the present invention for easy understanding, the present invention will be described in detail below with reference to the drawings through specific embodiments.
[0044] Such as Figure 1As shown in the figure, it is a schematic diagram of the ascites filter of the present invention. The ascites filter 100 includes a cylindrical filter chamber 2, and a number of hollow fiber filaments 11 are installed inside the filter chamber 2. A certain distance 5 is maintained between these hollow fiber filaments 11 (the hollow fiber filaments are not in close contact). Sealing materials 4 are provided at both ends of the hollow fiber filaments 11. These sealing materials 4 seal the distance between the hollow fiber filaments 11 and the distance between the hollow fiber filaments 11 and the inner wall of the filter chamber 2. The filter chamber 2 can be made of medical-grade polymer resin, preferably transparent polymer resin. The sealing material 4 is a waterproof sealing adhesive, and the sealing adhesive is bonded to the outer surface of the end of the hollow fiber filament 11 to seal the distance between the hollow fiber filaments 11, forming a waterproof sealing surface at both ends of the hollow fiber filament 11. The filter chamber 2 includes a first end and a second end, and top covers 1 are provided at both ends respectively. A flushing liquid inlet 9 is provided on the top cover 1 at the first end, and a filtered liquid outlet 8 is provided on the top cover at the second end. A certain distance is formed between both ends of the hollow fiber filament 11 and the top covers 1 at the first end and the second end respectively. The distance between the hollow fiber filament 11 and the first end of the filter chamber 2 constitutes a flushing liquid inlet buffer zone A, and the flushing liquid inlet buffer zone A is between the end sealing surface of the hollow fiber filament 11 and the top cover 1 at the first end. The distance between the hollow fiber filament 11 and the second end of the filter chamber 2 constitutes a filtered liquid outlet buffer zone B, and the filtered liquid outlet buffer zone B is between the end sealing surface of the hollow fiber filament 11 and the top cover 1 at the second end. The flushing liquid inlet buffer zone A is preferably 1 / 20 - 1 / 30 of the volume of the entire filter chamber 2, and the filtered liquid outlet buffer zone B is preferably 1 / 20 - 1 / 30 of the volume of the entire filter chamber 2. The volume ratios of the flushing liquid inlet buffer zone A and the filtered liquid outlet buffer zone B can keep an appropriate filtration pressure difference or flushing pressure difference inside the hollow fiber filament 11 in the filter chamber 2, improve the space utilization rate of the filter chamber 2, save the injection amount of the flushing liquid, and improve the recovery rate of ascites components. Both the flushing liquid inlet buffer zone A and the filtered liquid outlet buffer zone B are communicated with the internal channel 3 of the hollow fiber filament 11.
[0045] On one side of the filtration chamber 2, there is an ascites inlet 7. The ascites inlet 7 is in communication with the interior of the filtration chamber 2 and corresponds to the space between the two ends of the hollow fiber membrane filaments 11. The ascites inlet 7 is not directly in communication with the hollow channels of the hollow fiber membrane filaments 11. The ascites inlet 7 is provided at one end far from the filtrate outlet 8. On one side of the filtration chamber 2, there is also a flushing liquid outlet 10. The flushing liquid outlet 10 is in communication with the interior of the filtration chamber 2 and corresponds to the space between the two ends of the hollow fiber membrane filaments 11. The flushing liquid outlet 10 is not directly in communication with the hollow channels of the hollow fiber membrane filaments 11. The flushing liquid outlet 10 is provided at one end far from the flushing liquid inlet 9. Currently, the diameters of the flushing liquid inlet and the flushing liquid outlet of the hollow fiber membrane are basically equal. In the embodiment with an included angle of the present invention, the diameter D1 of the flushing liquid outlet 10 is 1.8 - 2.2 times the diameter D2 of the flushing liquid inlet 9 (D1 / D2 = 1.8 - 2.2), preferably 2 times. According to Bernoulli's equation, when the same amount of flushing liquid is used, by setting the diameter of the flushing liquid outlet 10 to be 2 times the diameter of the flushing liquid inlet, a larger pressure difference can be generated inside and outside the hollow fiber membrane filaments 11. This is beneficial for achieving a better flushing effect with less flushing liquid, improving the efficiency of back flushing, saving the back flushing time, and reducing the mechanical damage to the hollow fiber membrane filaments 11. The flushing liquid can enter the flushing liquid inlet buffer area A through the flushing liquid inlet 9, and after being distributed by the flushing liquid inlet buffer area A, it enters the internal channel 3 of the hollow fiber membrane filaments 11, and flushes the pollutants or blockages adhering to the outer wall of the hollow fiber membrane filaments 11 from the internal channel 3 of the hollow fiber membrane filaments 11 to the outside. The ascites sample enters the filtration chamber 2 through the ascites inlet 7 and is distributed in the space 5 between the hollow fiber membrane filaments 11. Proteins, moisture, etc. pass through the pores and enter the internal channel 3, come out from the internal channel 3, are collected in the filtrate outlet buffer area B, and then are discharged from the filtrate outlet 8.
[0046] Among them, the hollow fiber membrane filaments 11 are made of a mixed material of a first polymer material and a second polymer material through a method of casting a casting solution and phase inversion. The first polymer material is a polysulfone resin, and the mass of the polysulfone resin in the hollow fiber membrane filaments 11 accounts for 55-65%. The high content of the polysulfone resin can increase the mechanical strength and toughness of the hollow fiber membrane filaments 11. The second polymer material is at least one selected from polyethylene, polypropylene, polyvinyl alcohol, and polyacrylonitrile and contains 3-8 wt% of PVP incorporated therein. The pore diameter of the hollow fiber membrane filaments 11 is d, d≤0.285 μm. The pores with a pore diameter above 0.25 μm exceed 30-50% of the total pore area, and more preferably, the pores with a pore diameter above 0.20 μm account for 40-65% of the total pore area. For example, the pores with a pore diameter above 0.25 μm account for 30% of the total pore area, and the pores with a pore diameter above 0.20 μm account for 40%, 50%, or 60% of the total pore area. When the hollow fiber membrane filaments 11 meeting this condition are under an operating pressure of 500 mmHg or higher, the ascites protein recovery rate can stably reach over 90%, and it can well balance the mechanical strength and compressive strength of the hollow fiber membrane filaments, which is beneficial to maintaining the stability of the pore size, shape, and retention parameters of the hollow fiber membrane filaments and improving the reliability of the ascites protein recovery.
[0047] The ascites of patients may contain cancer cells, various bacteria, etc. Among them, the diameter of bacteria is 0.3-3 μm, the diameter of staphylococcus is 1 μm, the diameter of red blood cells is 2-3 μm, the diameter of platelets is 2-3 μm, the diameter of Escherichia coli is 1-2 μm, the diameter of yeast is 5 μm, the diameter of white blood cells is 6-30 μm, and the diameter of cancer cells is 10 μm. Therefore, when the pore diameter of the hollow fiber membrane filaments 11 is set below 0.285 μm, almost all useless or harmful components in the ascites can be filtered out, the dialysis efficiency can be improved, the blockage frequency of the fiber membrane can be reduced, and the recovery rate of ascites protein can be increased.
[0048] Among them, the mass ratio of the polysulfone resin in the hollow fiber membrane filaments 11 is 55%, 56%, 57%, 58%, 59%, 60%, 62%, or 65%. Although the higher the proportion of pores with a pore diameter of 0.25 μm - 0.285 μm, the higher the theoretical ascites protein recovery rate, once the proportion of pores with a pore diameter above 0.25 μm is too high, the mechanical strength and anti-deformation ability of the hollow fiber membrane filaments 11 are weakened, resulting in a decrease in its ability to resist filtration and flushing pressure. Therefore, the proportion of pores with a pore diameter above 0.25 μm in the filter membrane of the hollow fiber membrane filaments 11 does not exceed 50% of the total pore area.
[0049] Since polysulfone is a hydrophobic material, an excessive proportion of it will make the hydrophobicity of the hollow fiber membrane filaments 11 too strong. To further improve the hydrophilicity of the hollow fiber membrane filaments 11, after the hollow fiber membrane filaments 11 are prepared, plasma treatment, chemical grafting, hydrophilic coating or other methods can be used to introduce polar groups on the surface of the hollow fiber membrane filaments 11, thereby improving their hydrophilicity. The improvement of hydrophilicity is beneficial to protein filtration and reduces the fouling of cancer cells on the hollow fiber membrane filaments. The hydrophilic membrane surface has a high hydration capacity and good wettability, which can reduce the non-specific adsorption of proteins on its surface and is more conducive to improving the protein recovery rate and filtration efficiency. Plasma treatment, chemical grafting, hydrophilic coating or other treatments are common methods to improve the hydrophilicity of the hollow fiber membrane filaments 11.
[0050] The filling rate of the hollow fiber membrane filaments 11 in the filtration chamber 2 is 30 - 40%. The filling rate is calculated as the ratio of the total cross-sectional area of all the hollow fiber membrane filaments 11 in the filtration chamber 2 to the internal cross-sectional area of the filtration chamber 2. The filtration chamber 2 is a cylindrical filtration chamber. If the inner diameter of the filtration chamber 2 is defined as D3 and the flushing liquid outlet is D1, when the filling rate of the hollow fiber membrane filaments in the filtration chamber is 30 - 40%, D1 / D3 is 1 / 2 - 1 / 3. In a preferred embodiment of the filter 100, the total specific surface area of the hollow fiber membrane filaments 11 in the filtration chamber 2 is 1.3 - 2.0 m². The total specific surface area is actually the membrane filtration area of the filter 100. Among them, the filling rate of the hollow fiber membrane filaments 11 in the filtration chamber 2 can be 31%, 33%, 35%, 36%, 37%, 38% or 40%. Generally, the length of the filtration chamber 2 is set to 40 - 60 cm, the inner diameter D3 is 4 - 4.5 cm, and the flushing liquid outlet D1 can be set to 1.5 - 2.25 cm. The ratio of the flushing liquid outlet D1 to the inner diameter D3 of the filtration chamber 2 takes into account the strength of the structure of the filtration chamber 2 (if the proportion of D1 is too large, the filtration chamber 2 becomes fragile; the smaller the proportion of D1, the greater the internal pressure of the filtration chamber 2) and the appropriate filtration pressure and flushing pressure of the filtration chamber 2. The larger the membrane filtration area, the faster the filtration speed. However, when the volume of the filtration chamber is determined, it means that the filling rate of the hollow fiber membrane filaments 11 is larger, the distance between the membrane filaments is reduced, more normal saline is required for backwashing, and a larger operating pressure is required for filtration, which is not conducive to the stability of the pore structure and retention parameters of the membrane filaments; while increasing the volume of the filtration chamber easily leads to protein loss in the ascites.
[0051] Such as Figure 1As shown, in the filtration chamber 2, the hollow fiber membrane filaments 11 are not installed in a straight state, but are installed in an S shape or a C shape in the filtration chamber 2, thereby enabling the hollow fiber membrane filaments 11 to have a certain degree of curvature. Under backwashing or filtration pressure, the hollow fiber membrane filaments 11 exhibit a certain S-shaped swinging state. Specifically, assuming the distance between the two ends of the hollow fiber membrane filament 11 is L1 (i.e., the interval length inside the filtration chamber 2), and the actual length of the hollow fiber membrane filament is L2, then L2 / L1 is 1.05 - 1.3, preferably 1.1 - 1.2. Experiments have shown that when the hollow fiber membrane filaments 11 have a certain degree of curvature, under filtration and backwashing conditions, the substance molecules and water molecules in the filtrate or backwash water always act on the surface of the membrane filaments at a certain non-perpendicular angle, which can not only improve the filtration efficiency but also reduce the mechanical damage of the filtration operation pressure and backwashing pressure on the hollow fiber membrane filaments 11 at the same time.
[0052] The casting solution for preparing the above-mentioned hollow fiber membrane filaments 11 is: 20 - 22.5% of the second polymer material, 27.5 - 37.2% of the polysulfone resin, 2 - 10% of the pore-forming agent, and the balance is the solvent; the second polymer material is at least one selected from polyethylene, polypropylene, polyvinyl alcohol, and polyacrylonitrile and doped with 3 - 8 wt% of PVP. First, prepare the casting solution of the hollow fiber membrane filaments. After filtration and degassing, the casting solution is extruded from a spinneret composed of two concentric tubes, passed through a dry spinning process of 20 - 80 cm, and solidified in an aqueous solution with a solvent mass content of 40 - 50% and a temperature of 5°C - 40°C to obtain the nascent filaments. Then, after four or more passes of biaxial stretching and moderate retraction, four to six passes of water washing, and pore retention treatment with a pore retention agent with a mass percentage concentration of 20 - 30%, the hollow fiber membrane is obtained. Among them, the pore-forming agent is one or more of lithium chloride or sodium nitrite; the solvent is dimethyl sulfoxide, dimethylformamide, dimethylacetamide, or N-methylpyrrolidone; the pore retention agent for the pore retention treatment is selected from one or more of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, isopentanol, ethylene glycol, and glycerol. The preparation method of the hollow fiber membrane filaments 11 can be prepared according to the prior art. After the hollow fiber membrane filaments 11 are prepared and formed, if the hydrophilicity is poor, polar groups can be introduced on the surface of the hollow fiber membrane filaments 11 by means of plasma, chemical grafting, or coating to improve the hydrophilicity.
[0053] As Figure 2As shown in the figure, it is a schematic diagram of the ascites protein extraction system of the present invention. The ascites protein extraction system includes an ascites filter 100 and a concentrator 200. Both the ascites filter 100 and the concentrator 200 are horizontally arranged or installed, that is, the ascites filter 100 and the concentrator 200 are horizontally placed and fixed on a certain operating platform or horizontally installed and fixed in combination using a bracket. A physiological saline bag / ascites bag 101 is provided at the front end of the ascites filter 200. The physiological saline bag / ascites bag 101 is connected to the ascites inlet 7 of the ascites filter 100 by a pipeline 102, and a valve 121 is provided on the pipeline 102. The filtrate outlet 8 of the ascites filter 100 is connected to the stock solution inlet 201 of the concentrator 200 by a pipeline 103, and a valve 131 is provided on the pipeline 103. The concentrated solution outlet 202 of the concentrator 200 is connected to a pump 206. A valve 261 is provided between the concentrated solution outlet 202 and the pump 206. The pump 206 is connected to a concentrated solution collection device 204 by a pipeline 207, and a valve 271 is provided on the pipeline 207. On one side of the housing of the concentrator 200, there is also a waste liquid outlet 205. The waste liquid outlet 205 is connected to a negative pressure suction device 208, and a valve 251 is provided in the connection relationship between the waste liquid outlet 205 and the negative pressure suction device 208. The negative pressure suction device 208 also includes a waste liquid storage tank. No pressurizing device is provided at the front end of the ascites filter 200. A valve 108 is provided at the flushing liquid inlet 9 of the ascites filter 100, and the flushing liquid inlet 9 can be connected to a hand-pushed syringe. The flushing liquid outlet 10 of the ascites filter 100 is connected to a flushing liquid recovery device 105 by a pipeline 104, and a valve 141 is provided on the pipeline 104.
[0054] The concentrator 200 is also a hollow fiber membrane device, including a housing and a hollow fiber membrane bundle provided inside the housing. One end of the housing is the stock solution inlet 201, and the stock solution inlet 201 is connected to the filtrate outlet 8 of the ascites filter 100. The other end of the housing is the concentrated solution outlet 202, and the concentrated solution outlet 202 is connected to the pump 206. A waste liquid outlet 205 is provided on one side of the housing. The outer end of the waste liquid outlet 205 is connected to the negative pressure suction device 208, and the inner end of the waste liquid outlet 205 is communicated with the internal cavity of the housing but not with the hollow channels of the hollow fiber membrane bundle of the concentrator 200. A flushing liquid inlet 209 is also provided on one side of the concentrator 200. However, since the concentrator 200 is only used to concentrate the protein-rich liquid filtered and collected by the ascites filter 100, remove excess water and part of the inorganic salts (electrolytes), and reduce the volume of the recovered protein-containing liquid, the concentrator 200 is not easily blocked. Therefore, the concentrator 200 does not need to be flushed within one ascites protein extraction cycle. It should be noted that the ascites to be treated is an ex vivo material drawn from the patient's body, and the system of the present invention is not directly connected to the human body.
[0055] The following describes the invention solution and technical effects in combination with specific embodiments of the present invention.
[0056] Example 1
[0057] The design parameters of the ascites filter 100 in this example are as follows: Material composition of the hollow fiber membrane filaments 11 (mass percentage, dry membrane filaments): polysulfone PSU 55%, polypropylene 41.4%, PVP 3.6%. The membrane pore size is ≤0.285 μm, and the membrane pores with a size ≥0.25 μm account for 30% of the total membrane pore area, among which the membrane pores with a size ≥0.20 μm account for 42% of the total membrane pore area. The diameter of the flushing liquid outlet 10 is 2.2 cm, and the diameter of the flushing liquid inlet 9 is 1.1 cm. The inner diameter of the filtration chamber 2 is 4.4 cm, the filling rate of the hollow fiber membrane filaments is 35%, and the membrane filtration area is 1.4 ㎡. The installation length of the hollow fiber membrane filaments 11 is 30 cm, and the actual length of the hollow fiber membrane filaments 11 is 33 cm. The number of the hollow fiber membrane filaments 11 filled in the filtration chamber is 7800.
[0058] Example 2
[0059] The design parameters of the ascites filter 100 in this example are as follows: Material composition of the hollow fiber membrane filaments 11 (mass percentage, dry membrane filaments): polysulfone PSU 60%, polypropylene 36.8%, PVP 3.2%. After the hollow fiber membrane filaments are made, they are subjected to hydrophilic treatment using plasma. The membrane pore size is ≤0.285 μm, and the membrane pores with a size ≥0.25 μm account for 30% of the total membrane pore area, among which the membrane pores with a size ≥0.20 μm account for 50% of the total membrane pore area. The diameter of the flushing liquid outlet 10 is 2.2 cm, and the diameter of the flushing liquid inlet 9 is 1.1 cm. The inner diameter of the filtration chamber 2 is 4.4 cm, the filling rate of the hollow fiber membrane filaments is 35%, and the membrane filtration area is 1.4 ㎡. The installation length of the hollow fiber membrane filaments 11 is 30 cm, and the actual length of the hollow fiber membrane filaments 11 is 33 cm. The number of the hollow fiber membrane filaments 11 filled in the filtration chamber is 7800.
[0060] Example 3
[0061] The design parameters of the ascites filter 100 in this example are as follows: Material composition of the hollow fiber membrane filaments (mass percentage, dry membrane filaments): polysulfone PSU 65%, polyethylene 32.2%, PVP 2.8%. After the hollow fiber membrane filaments are made, they are subjected to hydrophilic treatment using plasma. The membrane pore size is ≤0.285 μm, and the membrane pores with a size ≥0.25 μm account for 40% of the total membrane pore area, among which the membrane pores with a size ≥0.20 μm account for 65% of the total membrane pore area. The diameter of the flushing liquid outlet 10 is 2.2 cm, and the diameter of the flushing liquid inlet 9 is 1.1 cm. The inner diameter of the filtration chamber 2 is 4.4 cm, the filling rate of the hollow fiber membrane filaments is 40%, and the membrane filtration area is 1.6 ㎡. The installation length of the hollow fiber membrane filaments 11 is 30 cm, and the actual length of the hollow fiber membrane filaments 11 is 33 cm. The number of the hollow fiber membrane filaments 11 filled in the filtration chamber is 8914.
[0062] To test the extraction effect of the above-mentioned ascites filter 100 on ascites protein, a simulated ascites sample was prepared using bovine blood containing blood cell components next. The preparation method is as follows: Take 5 L of bovine blood, add 50,000 units of anticoagulant sodium heparin, and then centrifuge it to obtain the solutions of the plasma layer, red blood cell layer, and buffy coat layer respectively, and recover them separately. Then, mix the plasma layer with normal saline and add proteins to make simulated transudative ascites (hepatic ascites, non-cancerous ascites) of various concentrations. Then, add white blood cells and red blood cells to the buffy coat layer, and then mix it with plasma to make simulated exudative ascites (cancerous ascites) of various concentrations. According to the above method, 3 kinds of simulated transudative ascites and 3 kinds of simulated exudative ascites samples as shown in Table 1 were prepared.
[0063] Table 1: Composition of simulated transudative ascites samples and simulated exudative ascites samples
[0064]
[0065]
[0066] Adopt Figure 2 the system shown to recover and extract ascites protein. The operation process is as follows:
[0067] (1) Horizontally place the ascites filter 100 and the concentrator 200 on an operation platform. The concentrator 200 is a conventional ultrafiltration (UF) membrane (pore size 1 - 5 nm), with a filtration chamber length of 30 cm and a membrane area of 1.5 ㎡. The ascites filter 100 is the filter of Examples 1 - 3.
[0068] (2) Place the normal saline bag 101 at a height of 40 cm on the operation platform, so that the normal saline enters the filtration chamber 2 of the filter 100 from the ascites inlet 7 of the filter 100 under gravity, and then the normal saline comes out from the flushing liquid outlet 10, thus completing the flushing of the inside of the filtration chamber 2 and the outside of the hollow fiber membrane filaments 11. 1000 mL of normal saline is used for this flushing.
[0069] (3) Then, close the flushing liquid outlet 10, open the valve 131 between the ascites filter 100 and the concentrator 200 and the negative pressure suction device 208, so that the normal saline enters from the ascites inlet 7 of the ascites filter 100 and comes out from the filtrate outlet 8 under gravity, and is sucked out from the waste liquid outlet 205 through the negative pressure suction device 208, thus completing the flushing of the hollow channels of the hollow fiber membrane filaments 11 of the ascites filter 100. 1000 mL of normal saline is used for this flushing.
[0070] (4) Place the prepared simulated ascites sample in the ascites bag 101. Hang the ascites bag 101 at a height of 40 cm on the operation platform. Open the valve 121 between the ascites bag 101 and the ascites filter 100. At the same time, turn on the negative pressure suction device 208 and the pump 206 connected to the concentrator 200. Adjust the working pressure of the negative pressure suction device 208 and adjust the speed of the concentrated liquid output of the pump 206 to 10 - 30 mL / min, so that the filtration pressure of the ascites filter 100 is 30 - 50 KPa. At this time, the ascites in the ascites bag 101 flows horizontally from the ascites inlet 7 of the ascites filter 100 into the filtration chamber 2 under gravity, and permeates and filters from the outside of the hollow fiber membrane filaments 11 into the hollow channels inside the hollow fiber membrane filaments 11. Among them, the filtrate containing protein permeates into the inside of the hollow fiber membrane filaments 11, is discharged from the filtrate outlet 8 and enters the concentrator 200. After entering the concentrator 200, it flows in the hollow channels of the hollow fiber membrane filament bundle in the concentrator. The excess water and electrolytes are filtered to the outside of the hollow fiber membrane filament bundle and discharged from the waste liquid outlet 205 under the operation of the negative pressure suction device 208, while the protein-containing concentrated liquid continues to remain in the hollow channels inside the hollow fiber membrane filament bundle 11 of the concentrator 200 and is collected into the concentrated liquid collection device 204 under the drive of the pump 206 to achieve the filtration and concentration of the simulated ascites.
[0071] (5) When the liquid output speed of the concentrated liquid outlet 202 drops to 50% of the initial set speed, it indicates that the hollow fiber membrane filaments of the ascites filter 100 are fouled and need to be backwashed. The backwashing process is as follows:
[0072] ① Close the valve 121 between the ascites bag 101 and the ascites inlet 7 of the filter 100, and keep the ascites filter 100 connected to the concentrator 200. Manually push a syringe to inject 100 mL of physiological saline into the flushing liquid inlet 9 of the ascites filter 100. Use the injected physiological saline to push the protein-containing liquid inside the hollow fiber membrane filaments 11 of the ascites filter 100 into the concentrator 200 for further concentration to remove excess water, electrolytes, etc., and collect the concentrated protein solution.
[0073] ② After the previous step is completed, turn off the pump 206 and the negative pressure suction device 208, close the valve 131 between the ascites filter 100 and the concentrator 200, open the valve 121 between the ascites bag 101 and the ascites inlet 7 of the filter 100, and manually push a syringe to inject 200 mL of physiological saline into the flushing liquid inlet 9. Use the physiological saline to backflush the ascites that has entered the filtration chamber 2, and return it to the ascites bag 101 through the ascites inlet 7 and the pipeline 102 to avoid waste.
[0074] ③After the previous step is completed, close the valve 121 between the ascites bag 101 and the ascites inlet 7 of the filter, open the flushing liquid outlet 10 and the valve 141, and inject normal saline into the flushing liquid inlet 9 by hand-pushing a syringe for flushing. Each injection of normal saline is 50 mL, and the operation is repeated 10 times. The normal saline penetrates from the inside to the outside of the hollow fiber membrane filaments 11 of the ascites filter 100 to wash down the pollutants adhering to the outer wall or pores of the hollow fiber membrane filaments 11 and send them into the flushing liquid recovery device 105. Among them, the pressure of each injection of normal saline is about 60 KPa.
[0075] (6) After completing the above flushing process, close the flushing liquid outlet 10 and the flushing liquid inlet 9 of the ascites filter 100, open the valve 121 between the ascites bag 101 and the ascites filter 100, open the valve 131 between the ascites filter 100 and the concentrator 200, and turn on the pump 206 and the negative pressure suction device 208 connected to the concentrator 200 to continue the extraction of ascites protein.
[0076] After processing the above 6 kinds of simulated ascites samples through the Figure 2 system shown, the ascites protein extraction rate and the blockage situation are recorded in Table 2.
[0077] Table 2: Treatment situation of ascites samples using the ascites protein extraction system of the present invention
[0078]
[0079] Note: The filtration time does not include the backwashing time.
[0080] From the test results in Table 2, it can be seen that the ascites protein extraction system and the ascites filter of the present invention can achieve a protein recovery rate of more than 90% for different simulated ascites samples, and the protein recovery rate for most simulated ascites samples can exceed 90%.
[0081] Next, prepare 10 L of simulated transudative ascites sample 2# and 10 L of simulated exudative ascites sample 5#, each adding 500 Staphylococcus per liter as bacterial interferents; perform ascites protein concentration and recovery under the same conditions as in Table 2; among them, the system needs to perform 1 backwashing during the filtration process of the transudative ascites sample 2#, and the system needs to perform 2 backwashings during the filtration process of the simulated exudative ascites sample 5#; record the cumulative protein recovery amount and the number of Staphylococcus filtered out within the first 2 minutes of the first filtration and within the first 2 minutes of re-filtration after each backwashing, and the statistical results are shown in Table 3.
[0082] Table 3: Filtration effect of the ascites filter after the first filtration and backwashing
[0083]
[0084] As can be seen from the test results in Table 3, the ascites protein filtration and concentration system of the present invention still has a stable protein recovery rate and the function of removing harmful substances after multiple rounds of backwashing; the hollow fiber membrane of the ascites filter is not prone to enlargement of the pore size after backwashing, and the interception accuracy can be maintained for a long time, and bacteria such as Staphylococcus aureus and Escherichia coli can be effectively filtered out. This proves that the hollow fiber membrane filaments 11 of the ascites filter 100 prepared by the present invention have good mechanical strength and toughness, and after multiple pressure operations such as backwashing, they can maintain a stable filtration pore size and accurate interception performance.
[0085] In summary, the ascites filter of the present invention has both high ascites protein recovery rate, good mechanical strength, toughness and anti-flushing deformation performance.
[0086] Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements, or in the case where the technical features in the above embodiments do not conflict with each other, can be combined in the manner described in the embodiments, and these modifications, replacements or combinations do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention.
Claims
1. An ascites filter, characterized in that: include: A filter chamber, in which a plurality of hollow fiber membranes are installed, with a spacing between the hollow fiber membranes, and sealing materials are respectively provided at both ends of the hollow fiber membranes, and the sealing materials seal the spacing between the hollow fiber membranes and the spacing between the hollow fiber membranes and the inner wall of the filter chamber; The filter chamber includes a first end and a second end, the first end is provided with a flushing liquid inlet, and the second end is provided with a filtrate outlet; the two ends of the hollow fiber membrane respectively form a gap with the first end and the second end, the gap between the hollow fiber membrane and the first end of the filter chamber constitutes a flushing liquid inlet buffer zone, and the gap between the hollow fiber membrane and the second end of the filter chamber constitutes a filtrate outlet buffer zone; an ascites inlet is provided on one side of the filter chamber, the ascites inlet is connected to the filter chamber and corresponds to between the two ends of the hollow fiber membrane, and the ascites inlet is far away from one end of the filtrate outlet; a flushing liquid outlet is also provided on one side of the filter chamber, the flushing liquid outlet is connected to the filter chamber and corresponds to between the two ends of the hollow fiber membrane, and the flushing liquid outlet is arranged at one end far away from the flushing liquid inlet; The mass proportion of the polysulfone resin in the hollow fiber membrane is 55-65%; the membrane pore size of the hollow fiber membrane is d, d≤0.285μm, and the membrane pores with a pore size of more than 0.25μm account for ≥30% of the total membrane pore area.
2. The ascites filter according to claim 1, characterized in that: The hollow fiber membrane comprises a first polymer material and a second polymer material, wherein the first polymer material is a polysulfone resin, which accounts for 55-65% by mass in the hollow fiber membrane; the remainder is a second polymer material, and the second polymer material is at least one of polyethylene, polypropylene, polyvinyl alcohol and polyacrylonitrile doped with 3-8wt% PVP.
3. The ascites filter according to claim 1, characterized in that: In the hollow fiber membrane, the membrane pores with a pore size of more than 0.25 μm account for no more than 50% of the total membrane pore area; preferably, the membrane pores with a pore size of more than 0.20 μm account for 40-65% of the total membrane pore area.
4. The ascites filter according to claim 1, characterized in that: The diameter of the flushing liquid outlet is D1, the diameter of the flushing liquid inlet is D2, and D1 / D2 is 1.8-2.
2.
5. The ascites filter according to claim 1 or 4, characterized in that: Calculated based on the ratio of the total cross-section of the hollow fiber membrane to the cross-section of the filter cavity, the filling rate of the hollow fiber membrane in the filter cavity is 30-40%.
6. The ascites filter according to claim 4, characterized in that: The filter cavity is a cylindrical filter cavity with an inner diameter of D3, D3 = 4-4.5 cm, and the total specific surface area of the hollow fiber membrane in the filter cavity is 1.3-2.0 m2; when the filling rate of the hollow fiber membrane in the filter cavity is 30-40%, D1 / D3 is 1 / 2-1 / 3.
7. The ascites filter according to claim 1, characterized in that: In the filter cavity, the distance between the two ends of the hollow fiber membrane is L1, the actual length of the hollow fiber membrane is L2, and L2 / L1 is 1.05-1.
3.
8. The ascites filter according to claim 1, characterized in that: The sealing material is a waterproof sealing adhesive, which is bonded to the outer surface of the end of the hollow fiber membrane and is used to seal the gaps between the hollow fiber membranes.
9. A system for extracting ascites protein, characterized in that: It includes the ascites filter and concentrator according to any one of claims 1 to 8, the filter and the concentrator are both arranged or installed horizontally, the filtrate outlet of the ascites filter is connected to the raw liquid inlet of the concentrator by a pipeline, the concentrated liquid outlet of the concentrator is connected to a pump, and the concentrated liquid is introduced into a concentrated liquid collecting device through the pump, and a waste liquid outlet is also provided on one side of the concentrator, and the waste liquid outlet is connected to a negative pressure suction device; no pressurizing device is arranged at the front end of the ascites filter.
10. The ascites protein extraction system according to claim 9, characterized in that: The concentrator is a hollow fiber membrane device, which includes a shell and a hollow fiber membrane bundle arranged inside the shell, one end of the shell is a raw liquid inlet, which is connected to the filtrate outlet of the ascites filter, and the other end of the shell is a concentrated liquid outlet, which is connected to a pump; the waste liquid outlet is arranged on one side of the shell, the outer end of the waste liquid outlet is connected to the negative pressure suction device, and the inner end of the waste liquid outlet is connected to the inside of the shell but not to the hollow channel of the hollow fiber membrane bundle.
11. A method for extracting ascites protein, which is achieved by the ascites protein extraction system according to claims 9-10, characterized in that: The extraction method comprises the following steps: S1. Place the ascites filter and concentrator horizontally on the operating platform; S2, placing a bag of physiological saline at a height of 30-50 cm on the operating platform, allowing the physiological saline to enter the filter cavity from the ascites inlet of the filter under gravity and exit from the rinsing liquid outlet, thereby completing the rinsing of the inside of the filter cavity and the outside of the hollow fiber membrane; then, closing the rinsing liquid outlet, opening the valve and negative pressure suction device between the ascites filter and the concentrator, allowing the physiological saline to enter from the ascites inlet of the filter under gravity and exit from the filtrate outlet, thereby completing the rinsing of the inside of the hollow fiber membrane of the ascites filter; S3. Place the ascites bag at a height of 30-50 cm on the operating platform, open the valves of the ascites bag and the ascites filter, and simultaneously open the negative pressure suction device and pump connected to the concentrator; adjust the working pressure of the negative pressure suction device and the pump speed to 10-30 mL / min, so that the filtration pressure of the filter is 225-450 mmHg; Ascites enters the filter cavity from the ascites inlet of the filter under gravity, and the protein-containing filtrate is discharged from the filtrate outlet and enters the concentrator. After entering the concentrator, it flows in the hollow channel of the hollow fiber membrane bundle of the concentrator, and the excess water and dielectric are filtered to the outside of the hollow fiber membrane bundle and discharged from the waste liquid outlet under the operation of the negative pressure suction device; The protein-containing concentrate remains inside the hollow channel of the hollow fiber membrane bundle and enters the concentrate collection device under the drive of the pump; S4. When the outlet velocity of the concentrated liquid drops to 50% of the initial velocity, backwashing is performed; the backwashing process is as follows: S41, closing the valve between the ascites bag and the ascites inlet of the filter, keeping the filter connected to the concentrator; injecting physiological saline into the flushing liquid inlet, and pushing the protein-containing liquid inside the hollow fiber membrane of the ascites filter into the concentrator through the physiological saline to continue the concentration process; S42, after the treatment is completed, turn off the pump and the negative pressure suction device, close the valve between the filter and the concentrator, open the valve between the ascites bag and the ascites inlet of the filter, inject normal saline into the flushing fluid inlet, and push the ascites that has entered the filter cavity back to the ascites bag through the normal saline; S43, close the valve between the ascites bag and the ascites inlet of the filter, open the flushing liquid outlet, and inject normal saline into the flushing liquid inlet. The normal saline penetrates from the inside of the hollow fiber membrane of the filter to the outside to flush out the blockage on the outside of the hollow fiber membrane. Repeat the operation of injecting normal saline 8-12 times, and the pressure of the injected normal saline does not exceed 500 mmHg. S5. After the flushing is completed, close the flushing liquid outlet and the flushing liquid inlet, open the valve between the ascites bag and the filter, open the valve between the ascites filter and the concentrator, turn on the pump and negative pressure suction device connected to the concentrator, and continue to extract ascites protein according to the method of S3.
12. The method for extracting ascites protein according to claim 11, characterized in that: The operation of injecting normal saline from the flushing fluid inlet is manual injection using a syringe.
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